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Discovery of HIV variant shows virus can evolve to be more severe — and contagious

Melody Schreiber

A colorized electron microscope image from the National Institute of Allergy and Infectious Diseases shows a single human immunodeficiency virus budding from a human immune cell. AP hide caption

A colorized electron microscope image from the National Institute of Allergy and Infectious Diseases shows a single human immunodeficiency virus budding from a human immune cell.

A variant of HIV that is faster at progressing to serious illness and more contagious than other versions of the virus has been circulating in the Netherlands for decades, researchers have found.

The findings, which were published in the journal Science on Thursday, demonstrate how HIV can mutate to create more severe disease and more rapid transmission.

"Even after 100 years of HIV infecting humans, it still has the capacity to evolve and change," says Joel Wertheim , associate professor of medicine at the University of California, San Diego, who was not involved in the study but wrote a perspective about the research findings, also published in Science on Thursday.

Fact check: The theory that SARS-CoV-2 is becoming milder

The study serves as a reminder — in the age of COVID variants — that viruses don't always weaken over time. "We should never underestimate the potential for viral evolution," Wertheim says. "Let this study stand in stark contrast to the claim that all viruses will inevitably evolve to be benign."

A contagious new discovery

The discovery of the HIV variant was sparked by a curious set of samples.

In late 2018, Chris Wymant , the lead author of the study and senior researcher at the Big Data Institute at University of Oxford, noticed something interesting in a database for a project called BEEHIVE , which collects HIV samples from Uganda and several countries in Europe to help scientists understand how the virus is evolving.

There was a recent cluster of 17 samples that showed a lot of unusual mutations, he says — and 15 of the samples came from the Netherlands.

Wymant and his co-authors wanted to know more, so they dived into another Dutch study with more data. They discovered a total of 109 people who had this particular variant and never knew it, dating all the way back to 1992. The variant probably emerged in the late '80s, Wymant says, picking up steam around 2000 and then eventually slowing down around 2010.

People with this variant have a viral load that is three to four times higher than usual for those with HIV. This characteristic means the virus progresses into serious illness twice as fast — and also makes it more contagious, says Wymant.

History Repeats Itself: COVID-19 Vaccine Inequities Echo HIV Crisis

The good news: Existing medications work very well to treat even very virulent variants like this one, cutting down on transmission and reducing the chance of developing severe illness, he says.

"Nobody should be alarmed," Wymant says. "It responds exactly as well to treatment as HIV normally does."

There's no need to develop special treatments for this variant, he adds. It shows no signs at all of resisting medications, as some HIV variants do. But because the variant moves quickly, people need to receive medicine as fast as possible.

How to slow down the variant

This research was "nicely done" and "well-designed," says Adeeba Kamarulzaman , president of the International AIDS Society and professor of medicine at the University of Malaya, who did not work on the study.

It also helps answer a pressing question in the field of HIV research, she notes. Previously, researchers wondered whether people get sicker or are more contagious because of how their immune systems respond to the virus. The study found that individual responses are part of it but not all. It can also happen if a virus evolves to cause more severe illness and readier transmission.

Kamarulzaman warns that a mutation like this could happen in other places. If a number of HIV patients in a particular area have this kind of variant but isn't taking medication, "you are going to have a lot more people with advanced disease a lot more quickly," she says.

To prevent this from happening, she says, "early tests or frequent testing and immediate initiation of treatment is the way to go." The goal isn't to identify a specific variant but rather to diagnose new cases of HIV so that treatment may start as soon as possible. But some countries still struggle to do that, and they need more support, she adds.

Ambitious Plan To Stem HIV/AIDS Epidemic Meets None Of Its Goals

That's how this variant eventually slowed down in the Netherlands before researchers even identified it.

"The public health intervention that's been rolled out and expanded in the Netherlands over the last decade or so — improving access to treatments, getting people tested as soon as possible, getting them onto treatment as soon as possible — has helped reduce the numbers of this variant, even though we didn't know that it existed," Wymant says.

Rapid treatment also helps slow viral evolution, so variants like these are less likely to emerge.

"This doesn't mean we need to change strategy," Wertheim says. "It just means we need to do more of what we're already doing."

Melody Schreiber (@m_scribe) is a journalist and the editor of What We Didn't Expect: Personal Stories About Premature Birth .

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Journey from victim to a victor—a case study of people living with HIV and AIDS

As kushwaha.

* Associate Professor, Department of Community Medicine, AFMC, Pune – 40

Minaxi Kumkar

† Medico-Social Worker, Department of Community Medicine, AFMC, Pune – 40

Introduction

It will take a concerted and sustained effort globally to achieve UNAIDS' (United Nations Programme on HIV/AIDS) vision of zero discrimination, zero new human immunodeficiency virus (HIV) infections, and zero acquired immunodeficiency syndrome (AIDS)-related deaths. 1 Unequal treatment and increased vulnerability make women hapless victims of HIV/AIDS. Nearly 40% of HIV-positive people in India are women, according to United Nations Development Programme (UNDP). The UNDP states that nearly 80% of HIV infections among women in 2005 were the outcome of women contracting the disease from their husbands. 2 Gender plays a key role in the complex interplay between HIV-related stigma, moral judgement, shame, and blame. Women, whether married or single, divorced or widowed, sex workers or seasonal migrants or adolescent girls, are most susceptible to the negative impacts of HIV and AIDS. Further, women are biologically more prone to HIV infection than men in terms of any single act of unprotected sex with an infected partner. Gender disparities in terms of access to education, resources, income, political power, coupled with incidences of sexual violence, coercion, social dislocation in conflict situations like war etc. or owing to migration for work, serve to increase the risk of HIV infection to women through unprotected sexual intercourse.

For India, women account for about 39% of all infections despite the fact that > 90% of them are in monogamous relationships. It is estimated that about 30 million men in India buy sex on a regular basis while the social and cultural limits placed on women's sexuality imply that a majority of women abstain from sex before marriage and postmarriage remain monogamous. Predictably, the inequality that characterises the social and economic spheres of society is often mirrored in sexual interactions, creating an unequal balance of power in sexual relations. As a result, majority of women have little or no control over the circumstances in which and with whom sexual intercourse takes place. 3

There exists an inextricable link between human rights, gender, and HIV and AIDS. Men encounter more opportunities, owing to their indulgent and risky behaviour, to contract and transmit HIV. The right to make safer and informed decisions is still not seen as the prerogative of women and girls. Social restrictions also contribute to lesser healthcare for women, girls, and children. Women risk violence, abandonment, neglect of health and material needs, destitution, and community ostracism.

Violations of rights may worsen the impact of HIV, increase vulnerability, and hinder positive responses to the epidemic. 4 A rights-based approach to HIV requires enabling, empowerment, and protecting people living with HIV so that they can live and thrive with dignity. Today, the majority of countries (89%) explicitly acknowledge human rights in their national AIDS strategies, with 92% of countries reporting that they have programmes in place to reduce HIV-related stigma and discrimination. 1

The greater involvement of people living with HIV and AIDS (GIPA) principle encourages the active involvement of people living with AIDS in policy-making, and in the development and implementation of programmes. Activities such as training and supporting people living with HIV as public speakers, educators, and counsellors have helped to reduce stigmatisation.

There is an urgent need to strengthen the response towards HIV among women. Rather than placing the onus of prevention on women, programmes must address the gender issues related to HIV and AIDS, at the socio-cultural and structural level. National AIDS Control Organisation III (NACP III) plan document reflects an understanding of such issues.

A case study is a research method common in social science. It is based on an in-depth investigation of a single individual, group, or event. Case study methods involve an in-depth, longitudinal (over a long period of time) examination of a single instance or event, a case.

This case study is about Anamika (name changed), a 35-year-old female who is an empowered HIV-positive and presently works as Community Co-ordinator at an anti-retroviral treatment (ART) centre. Her transformation from a victim of social stigma and discrimination due to her HIV-positive status to her present role has been possible due to her determination and social support she received from our medico-social workers. This case is being presented as a case study which shows the potential of effective social rehabilitation and exploring utilisation of HIV-positives as a resource in our fight against this medico-social epidemic of HIV/AIDS. A case report on process involved in rehabilitation of HIV-positive children was reported in 2006 by Verma et al. 5

Medico-Social History

Anamika was born on 9 January 1975 as the youngest of three siblings to parents who belonged to rural Maharashtra. She lost her father in an accident during her infancy. The family including her mother blamed her (‘you have heralded misfortune on the family’) as being an unlucky omen for the family. She moved with her mother to her maternal grandparents where they lived in a joint family. She was neglected, ridiculed, and rebuked by her cousins who were always jealous and critical of her. She was made to do all household chores and even worked at fields. Once at 8–9 years of age she was sexually abused by a male working for the family in the fields. Despite these traumatic and unpleasant experiences in childhood she continued her education and successfully completed her matriculation in 1990. She always dreamt of becoming a working women, who would be financially independent and show to the society that she is capable of better things in life. She believed that one is the master of one's destiny. She took science subjects in her higher secondary school against wishes of her family as she wanted to become self-reliant. She passed her senior school successfully in 1992 while rest of her classmates in the village had failed. Despite her resistance and unwillingness, her education was curtailed as she was forced to marry a farm worker in June 1994 at the tender age of 19 years. She was not lucky to enjoy marital bliss as her husband used to dislike her for not being so good looking. She knew of the extramarital exposures of her husband but she could not do much about it. Her husband used to tell her of his ‘enjoyment’ (sexual contacts) whenever he visited Pune city. After few months after marriage she started keeping unwell and she was advised HIV test by the doctor. Both Anamika and her husband were tested and found to be HIV-positive. She was devastated as she was an innocent victim of this deadly disease. They did not disclose their status to their family and friends for fear of stigma and social discrimination. Despite HIV infection she decided to go for pregnancy for two reasons. Firstly, there was a social and family pressure to produce a child to prove her fertility. Secondly, she was not very aware of the vertical transmission of infection from mother to foetus. During her first childbirth in January 1996, she went to a hospital where there was no doctor available and she was later transferred to another hospital where she delivered a neonate who died within 30 minutes of birth. During this delivery, she did not disclose her status to the hospital staff for fear of being turned out. During her second pregnancy she was fully aware that there was a possibility of children being HIV-positive. She however, always believed that children will not be affected as she had unshakable faith in God. She delivered in the vehicle while being transported to a hospital in March 1997. The child was negative for HIV. She became pregnant for the third time in September 1998. Later in 1998, her husband started keeping unwell and was being treated with unknown medications and the family and society had come to know of their status. He got some treatment from medicine brought from Cochin and also at Pune. She is not sure if he ever received anti-retroviral therapy (ART). Her husband died on 9 June 1999 despite treatment after a downhill course. She used to be cursed by her in-laws (‘you have killed my son; he has got the disease because of you’). Three weeks later she delivered a female child. During delivery she had been kept in a separate room in the hospital with another HIV-positive lady by the hospital staff. She was not exhibited any ART during these pregnancies. Her second daughter received nevirapine at birth. Her in-laws tried to get the second child eliminated. Fortunately, both children were born negative for HIV. She was now a widow who was HIV-positive with two daughters left to fend for herself with no social support from family and society. She was discriminated by the family and the neighbourhood. People used to cover their face while passing by their house; she was not permitted to enter kitchen and household of in-laws and was kept separately. Nobody interacted with her and she was not invited to attend any social function. The children from the village were not permitted to mingle with her children. She had a flour mill which had to be closed since people did not patronise it. During this phase of her life she felt like committing suicide and thought she should rather jump into her husband's pyre. She however did not do so because she thought about her two daughters. She decided to fight against her circumstances as she felt she was innocent victim of HIV and there was no fault on her side. She developed a defiant attitude to the discrimination she faced and wanted to prove to the world that she is capable of handling her circumstances and would not surrender without fighting it out. She decided that she will prove to others that she can overcome her difficulties with her determination. She was supported by her mother and brother. Her in-laws grabbed her savings and money obtained from selling flour mill. She was finding it difficult to make her ends meet. She even worked as farm labourer to earn her livelihood besides stitching clothes. She had received a sewing machine with the help of NMP+ (Network of HIV-positive people of Maharashtra) with whom she had registered. The children were admitted to the village primary school. She states that there was no discrimination against her children at school.

In 2006, during our routine visit to her village where rural health training centre of Armed Forces Medical College (AFMC) is located, she came in contact with our medico-social worker when her daughter needed surgery for chronic suppurative otitis media (CSOM). She was helped through Prayas Club (medico-social initiative of medical students) of AFMC for this treatment by arranging for her transport, accommodation, petty expenses, and food. She was then followed-up regularly. In 2007, being a widow she was befriended by a farm labourer from Punjab who was a migrant who came for work at her village with harvest machine and they developed sexual contact and she became pregnant. She was promised that he will marry her despite her seropositive status. She thought that she would get some companionship and support and would be more secure in the hostile world. She then consulted medico-social workers of our department. She was advised to undergo abortion and discontinue her relationship as there was a chance for her being left high and dry after sexual exploitation by a migrant labourer. She was then counselled to get herself examined and enrol herself at the ART centre for follow-up. She expressed her desire to work and earn her livelihood. It was thought that economic independence would help her to fight out her social circumstances. Under Maharashtra State AIDS Control Society (MSACS) initiative ART centre in AFMC was started in March 2009. There was a post for people living with HIV and AIDS (PLHA) as Community Care Co-ordinator which was to be filled. Medico-social worker spoke to the officer-in-charge of ART centre and suggested that there was a PLHA who could be the right candidate for the job. Anamika had the requisite education, motivation, communication skill, and positive outlook, besides she had also participated in conference, seminar as PLHA spokesperson. She was thus interviewed, selected, and appointed as Community Care Co-ordinator. Since then, she has now become an advocate, spokesperson, counsellor, HIV worker, and a volunteer. She believes that she has been able to realise her dream of becoming a ‘working woman’ only because she came to Pune for her disease follow-up. She believes that HIV has come to her as a blessing in disguise. Her two children have been rehabilitated by putting them into a hostel run by a nongovernmental organisation working for the welfare of children. She regularly visits them. She has maintained good health and has not required ART so far for last 16 years that she has been positive. She attributes her maintained health to her positive and optimistic attitude towards life, tenacity to fight, not surrendering to challenges. She has sound spiritual health and unshakable faith in god. She has good health seeking behaviour and has access to good healthcare system. She consumes balanced vegetarian diet. She also takes supplements like iron, calcium, multivitamin, and vitamin C. She is also consuming some ayurvedic natural herb extracts like tulsi, ginger, mint, adulsa, belpatra, prajakta flower, and jaggery. She gets her medical follow-up done regularly.

She is an empowered HIV-positive now working for HIV-positives. She feels empowered as she is now aware about the disease and has opportunity to work with professional people for the welfare of HIV-positives. She feels that this disease has given her an opportunity to serve people who are distressed and discriminated. She helps new PLHAs by motivating them with her personal example. She is a role model for PLHAs registered at our ART centre. She is now economically independent. She feels this disease can be fought and won over if one has determination and gets the requisite social support. Her all relatives now call her for social functions and she is re-integrated into the society. She is now respected for her courage and conviction and she is no longer discriminated in the society. She says now even her in-laws have now started behaving with her appropriately. She has been given her share in the property, which was earlier denied to her by her in-laws. She is leading a life with dignity and pride as a PLHA. She now says that ‘I am proud to be a HIV-positive person’.

Inspiration

Anamika, a lady from a rural background with a traumatic childhood gets infected with HIV from her husband. She is faced with the challenge of looking after herself and her two daughters. She has not only faced the death of her husband, social discrimination, and poverty but emerged stronger with her faith, determination, and resolve. She has been able to overcome her trials and tribulations due to her education, positive outlook, social support, and access to quality healthcare. She is now a role model for PLHAs. She is helping people with HIV infection to cope with their problems and able to give them a lot of hope and optimism by her personal example. This case study highlights the fact that a well rehabilitated HIV-positive person with social support and timely guidance can not only lead a healthy and positive life but also contribute significantly to the society. A great difference can be made to the life of a HIV-positive by small efforts from the society. The case portrays journey of a victim of HIV to a victor who is positive not only for HIV but also in life.

Conflicts of Interest

None identified.

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• High-Impact Prevention
• Case Studies
• National Center for HIV, Viral Hepatitis, STD, and Tuberculosis Prevention

HIV Screening and Testing

What to know.

HIV testing and screening are important first steps in diagnosing infection. Diagnosing HIV infection early is cost-effective and saves the public money on direct medical costs. Expanding HIV testing saves lives and prevents others from getting infected.

The benefits of HIV screening and testing

In 2015, approximately 39,000 persons received a new HIV (human immunodeficiency virus) infection diagnosis. HIV testing is the vital first step for HIV care and effective prevention. These persons had been living undiagnosed with HIV but now know their status and have the opportunity to receive life-saving treatment.

HIV diagnosis also greatly reduces the risk of transmitting the virus to others. Persons without HIV learn about effective tools for reducing their risk of getting infected.

Cost-effectiveness of HIV screening and testing

Initial studies reported voluntary HIV screening to be cost-effective in health care settings where undiagnosed HIV infection is less than ≥0.1% 1 2 . It was also reported to be more cost-effective than many established screening programs for chronic disease (e.g., hypertension, colon cancer, and breast cancer). 2 3 Treatment costs are lowered as well because treatment can begin before severe immunologic compromise occurs.

A more recent study reported HIV testing in clinical settings is cost-saving. This study focused on a model with consistent, standardized methods of evaluating the costs and effects of established and emerging HIV prevention strategies. 4

The unit cost of testing was adjusted by the positivity rate of persons tested (0.6%). This was based on reports of HIV testing from CDC-funded sites to find a cost per new diagnosis. It found that the cost per case of HIV prevented by testing in a clinical setting was less than the lifetime treatment cost per HIV case.

Effectiveness of expanded testing in the United States

CDC-funded testing programs in the U.S. are substantial. They led to approximately one-third of all new HIV diagnoses in 2013.

From 2007 to 2010, CDC-funded Expanded Testing Initiative sites provided more than 2.8 million HIV tests. These tests resulted in approximately 18,000 new HIV diagnoses and saved $1.2 billion in direct medical costs. 4 For every $1.00 spent on HIV testing, CDC saved the general public $2.00 on direct medical costs.

As more people receive an HIV infection diagnosis, the percentage of people who are unaware of their infection decreases. In 2006, 19% of persons with HIV were unaware of their infection. In 2014, this decreased to 15%. 5 Some of the biggest improvements were among young gay and bisexual males between the ages of 13-24. 6 This group was previously at the highest risk of HIV infection.

• Walensky RP, Weinstein MC, Kimmel AD, et al. Routine human immunodeficiency virus testing: an economic evaluation of current guidelines. Am J Med 2005;118:292–300.
• Paltiel AD, Weinstein MC, Kimmel AD, et al. Expanded screening for HIV in the United States—an analysis of cost-effectiveness. N Engl J Med 2005;352:586–95.
• Sanders GD, Bayoumi AM, Sundaram V, et al. Cost-effectiveness of screening for HIV in the era of highly active antiretroviral therapy. N Engl J Med 2005;352:570–85.
• Lin F, Farnham PG, Shrestha RK, Mermin J, Sansom SL. Cost effectiveness of HIV prevention interventions in the U.S. Am J Prev Med 2016; 50:699–708.
• Satcher Johnson A, Song R, Hall HI. State-level estimates of HIV incidence, prevalence, and undiagnosed infections [Abstract 899]. Presented at the Conference on Retroviruses and Opportunistic Infections, Seattle, Washington, February 13–16, 2017.
• Singh S, Song R, Satcher Johnson A, McCray E, Hall HI. HIV incidence, prevalence and undiagnosed infections in men who have sex with men [Abstract 30]. Presented at the Conference on Retroviruses and Opportunistic Infections, Seattle, Washington, February 13–16, 2017.
• Krueger A, Dietz P, Van Handel M, Belcher L, Johnson AS. Estimates of CDC-funded and national HIV diagnoses: a comparison by demographic and HIV-related factors. AIDS Behav 2016;20:2961–5.

High-Impact Prevention is a cost-effective, proven, scalable public health approach that prevents new infections, saves life-years, and reduces disparities.

In a 1st, HIV vaccine triggers rare and elusive antibodies in humans

Scientists have taken a big step toward making an effective HIV vaccine.

An HIV vaccine is one step closer to reality following a human trial that produced rare and elusive antibodies, a new study reports. 

Many hurdles stand in the way of an effective HIV vaccine. The virus is a master of evasion, dodging the immune system by coating itself in sugars that resemble those made by the body, said Dr. Barton Haynes , a leader of the recent trial and director of the Duke Human Vaccine Institute. The virus also mutates rapidly, changing its form so that the immune system struggles to make antibodies that can grab hold of it.

A major goal in HIV vaccine development is triggering the production of broadly neutralizing antibodies, which latch onto parts of the virus's outer coating, or envelope, that are very similar between different HIV strains. This makes the antibodies protective against a wide variety of strains, regardless of how they mutate.

The challenge is that "these antibodies, naturally during infection, are very rare to find," said Thomas Hope , a professor of cell and developmental biology who studies HIV at Northwestern University Feinberg School of Medicine. "It takes a couple years of real infection to make these antibodies," said Hope, who was not involved in the new study but has collaborated with some of its authors in the past.

Related: We could end the AIDS epidemic in less than a decade. Here's how.

Vaccines typically work by eliciting a similar immune reaction to what's seen during a real infection. But in the case of HIV, vaccine developers have to dramatically expedite the process, calling forth antibodies in weeks that would usually take years to show up. 

Now, in a study published Friday (May 17) in the journal Cell , scientists have demonstrated that this feat is possible in humans.

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"We're gathering proof of concept that a vaccine could be made — can be made," Haynes told Live Science. "We're having to coax the immune system, to guide the immune system in a way we've never had to do."

In the trial, the researchers targeted a protein embedded in HIV's envelope — specifically, part of the protein called the membrane proximal external region (MPER). The coveted antibodies that target MPER bind to both the backbone of this protein and to the fatty membrane it's embedded within. 

"These are very unusual because they bind two things at once," Haynes said, and this makes the antibodies oddly shaped. To make antibodies of the right shape, immune cells must pick up genetic mutations over time, following exposure to a pathogen. But for reasons not fully understood, the mutations required to make antibodies against MPER and similar targets happen only very rarely . 

The idea behind the new vaccine is to make these mutations more probable by exposing the immune system to a series of reaction-triggering substances. These substances, or immunogens, contain short snippets of protein and bubbles of fat. "What we're learning to do is design immunogens that can select for these rare mutations very efficiently," Haynes said. 

This strategy has been demonstrated in various animal models and early human studies that aimed for targets other than MPER. These previous studies successfully coaxed immune cells to make precursors to the final, desired antibodies — but the new trial represents the first time that the end-goal antibodies have been achieved in people.

"This supports the whole concept," Hope told Live Science. "Many worry if this is possible," so the new study lends credence to this iterative HIV vaccination strategy. 

— How are people cured of HIV? Here's everything you need to know

— New trial hints at a possible HIV cure approach: Wake up latent virus hiding in the body, then kill it

— Kids under 5 with HIV are dying at high rates. Here's why.  

The trial included 20 HIV-negative volunteers. Fifteen received two vaccine doses, spaced two months apart, while the remaining five got a third dose four months after their second. Tests showed that two doses of vaccine triggered a robust response from immune cells and kicked off the production of broadly neutralizing antibodies. The team further confirmed the presence of these antibodies in the three-dose group by closely analyzing their immune cells.

The original goal of the trial was for everyone to get four doses, but it was paused after one participant given three doses had a serious allergic reaction to a vaccine ingredient called polyethylene glycol (PEG). PEG helps to stabilize certain types of vaccines in the body, but rarely, patients can have a reaction to it . The researchers have now reformulated the vaccine without PEG and will soon test the new version.

This is just one step toward making an effective HIV vaccine, Haynes emphasized. The ideal vaccine would induce four different types of broadly neutralizing antibodies — that is, anti-MPER antibodies plus three more kinds. This would help prevent HIV from escaping the vaccine's protection. In addition, the antibodies need to be made in high quantities and hang around in the body for a long time.

"It's a decent starting point and it can be built upon and combined with other people's work," Hope said of the recent trial. He added that he hopes this vaccine strategy pans out, given the potential it has shown so far. Hope has been studying HIV since the late 1980s. 

"I would really like to see the end of this virus," he said. "It'll lose eventually, but I'd like to see it losing."

Ever wonder why some people build muscle more easily than others or why freckles come out in the sun ? Send us your questions about how the human body works to [email protected] with the subject line "Health Desk Q," and you may see your question answered on the website!

Nicoletta Lanese is the health channel editor at Live Science and was previously a news editor and staff writer at the site. She holds a graduate certificate in science communication from UC Santa Cruz and degrees in neuroscience and dance from the University of Florida. Her work has appeared in The Scientist, Science News, the Mercury News, Mongabay and Stanford Medicine Magazine, among other outlets. Based in NYC, she also remains heavily involved in dance and performs in local choreographers' work.

New trial hints at a possible HIV cure approach: Wake up latent virus hiding in the body, then kill it

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• Published: 24 November 2021

A study of awareness on HIV/AIDS among adolescents: A Longitudinal Study on UDAYA data

• Shobhit Srivastava   ORCID: orcid.org/0000-0002-7138-4916 1 ,
• Shekhar Chauhan   ORCID: orcid.org/0000-0002-6926-7649 2 ,
• Ratna Patel   ORCID: orcid.org/0000-0002-5371-7369 3 &
• Pradeep Kumar   ORCID: orcid.org/0000-0003-4259-820X 1  

Scientific Reports volume  11 , Article number:  22841 ( 2021 ) Cite this article

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Acquired Immunodeficiency Syndrome caused by Human Immunodeficiency Virus (HIV) poses a severe challenge to healthcare and is a significant public health issue worldwide. This study intends to examine the change in the awareness level of HIV among adolescents. Furthermore, this study examined the factors associated with the change in awareness level on HIV-related information among adolescents over the period. Data used for this study were drawn from Understanding the lives of adolescents and young adults, a longitudinal survey on adolescents aged 10–19 in Bihar and Uttar Pradesh. The present study utilized a sample of 4421 and 7587 unmarried adolescent boys and girls, respectively aged 10–19 years in wave-1 and wave-2. Descriptive analysis and t-test and proportion test were done to observe changes in certain selected variables from wave-1 (2015–2016) to wave-2 (2018–2019). Moreover, random effect regression analysis was used to estimate the association of change in HIV awareness among unmarried adolescents with household and individual factors. The percentage of adolescent boys who had awareness regarding HIV increased from 38.6% in wave-1 to 59.9% in wave-2. Among adolescent girls, the percentage increased from 30.2 to 39.1% between wave-1 & wave-2. With the increase in age and years of schooling, the HIV awareness increased among adolescent boys ([Coef: 0.05; p  < 0.01] and [Coef: 0.04; p  < 0.01]) and girls ([Coef: 0.03; p  < 0.01] and [Coef: 0.04; p  < 0.01]), respectively. The adolescent boys [Coef: 0.06; p  < 0.05] and girls [Coef: 0.03; p  < 0.05] who had any mass media exposure were more likely to have an awareness of HIV. Adolescent boys' paid work status was inversely associated with HIV awareness [Coef: − 0.01; p  < 0.10]. Use of internet among adolescent boys [Coef: 0.18; p  < 0.01] and girls [Coef: 0.14; p  < 0.01] was positively associated with HIV awareness with reference to their counterparts. There is a need to intensify efforts in ensuring that information regarding HIV should reach vulnerable sub-groups, as outlined in this study. It is important to mobilize the available resources to target the less educated and poor adolescents, focusing on rural adolescents.

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Introduction.

Acquired Immunodeficiency Syndrome (AIDS) caused by Human Immunodeficiency Virus (HIV) poses a severe challenge to healthcare and is a significant public health issue worldwide. So far, HIV has claimed almost 33 million lives; however, off lately, increasing access to HIV prevention, diagnosis, treatment, and care has enabled people living with HIV to lead a long and healthy life 1 . By the end of 2019, an estimated 38 million people were living with HIV 1 . More so, new infections fell by 39 percent, and HIV-related deaths fell by almost 51 percent between 2000 and 2019 1 . Despite all the positive news related to HIV, the success story is not the same everywhere; HIV varies between region, country, and population, where not everyone is able to access HIV testing and treatment and care 1 . HIV/AIDS holds back economic growth by destroying human capital by predominantly affecting adolescents and young adults 2 .

There are nearly 1.2 billion adolescents (10–19 years) worldwide, which constitute 18 percent of the world’s population, and in some countries, adolescents make up as much as one-fourth of the population 3 . In India, adolescents comprise more than one-fifth (21.8%) of the total population 4 . Despite a decline projection for the adolescent population in India 5 , there is a critical need to hold adolescents as adolescence is characterized as a period when peer victimization/pressure on psychosocial development is noteworthy 6 . Peer victimization/pressure is further linked to risky sexual behaviours among adolescents 7 , 8 . A higher proportion of low literacy in the Indian population leads to a low level of awareness of HIV/AIDS 9 . Furthermore, the awareness of HIV among adolescents is quite alarming 10 , 11 , 12 .

Unfortunately, there is a shortage of evidence on what predicts awareness of HIV among adolescents. Almost all the research in India is based on beliefs, attitudes, and awareness of HIV among adolescents 2 , 12 . However, few other studies worldwide have examined mass media as a strong predictor of HIV awareness among adolescents 13 . Mass media is an effective channel to increase an individuals’ knowledge about sexual health and improve understanding of facilities related to HIV prevention 14 , 15 . Various studies have outlined other factors associated with the increasing awareness of HIV among adolescents, including; age 16 , 17 , 18 , occupation 18 , education 16 , 17 , 18 , 19 , sex 16 , place of residence 16 , marital status 16 , and household wealth index 16 .

Several community-based studies have examined awareness of HIV among Indian adolescents 2 , 10 , 12 , 20 , 21 , 22 . However, studies investigating awareness of HIV among adolescents in a larger sample size remained elusive to date, courtesy of the unavailability of relevant data. Furthermore, no study in India had ever examined awareness of HIV among adolescents utilizing information on longitudinal data. To the author’s best knowledge, this is the first study in the Indian context with a large sample size that examines awareness of HIV among adolescents and combines information from a longitudinal survey. Therefore, this study intends to examine the change in the awareness level of HIV among adolescents. Furthermore, this study examined the factors associated with a change in awareness level on HIV-related information among adolescents over the period.

Data and methods

Data used for this study were drawn from Understanding the lives of adolescents and young adults (UDAYA), a longitudinal survey on adolescents aged 10–19 in Bihar and Uttar Pradesh 23 . The first wave was conducted in 2015–2016, and the follow-up survey was conducted after three years in 2018–2019 23 . The survey provides the estimates for state and the sample of unmarried boys and girls aged 10–19 and married girls aged 15–19. The study adopted a systematic, multi-stage stratified sampling design to draw sample areas independently for rural and urban areas. 150 primary sampling units (PSUs)—villages in rural areas and census wards in urban areas—were selected in each state, using the 2011 census list of villages and wards as the sampling frame. In each primary sampling unit (PSU), households to be interviewed were selected by systematic sampling. More details about the study design and sampling procedure have been published elsewhere 23 . Written consent was obtained from the respondents in both waves. In wave 1 (2015–2016), 20,594 adolescents were interviewed using the structured questionnaire with a response rate of 92%.

Moreover, in wave 2 (2018–2019), the study interviewed the participants who were successfully interviewed in 2015–2016 and who consented to be re-interviewed 23 . Of the 20,594 eligible for the re-interview, the survey re-interviewed 4567 boys and 12,251 girls (married and unmarried). After excluding the respondents who gave an inconsistent response to age and education at the follow-up survey (3%), the final follow-up sample covered 4428 boys and 11,864 girls with the follow-up rate of 74% for boys and 81% for girls. The effective sample size for the present study was 4421 unmarried adolescent boys aged 10–19 years in wave-1 and wave-2. Additionally, 7587 unmarried adolescent girls aged 10–19 years were interviewed in wave-1 and wave-2 23 . The cases whose follow-up was lost were excluded from the sample to strongly balance the dataset and set it for longitudinal analysis using xtset command in STATA 15. The survey questionnaire is available at https://dataverse.harvard.edu/file.xhtml?fileId=4163718&version=2.0 & https://dataverse.harvard.edu/file.xhtml?fileId=4163720&version=2.0 .

Outcome variable

HIV awareness was the outcome variable for this study, which is dichotomous. The question was asked to the adolescents ‘Have you heard of HIV/AIDS?’ The response was recorded as yes and no.

Exposure variables

The predictors for this study were selected based on previous literature. These were age (10–19 years at wave 1, continuous variable), schooling (continuous), any mass media exposure (no and yes), paid work in the last 12 months (no and yes), internet use (no and yes), wealth index (poorest, poorer, middle, richer, and richest), religion (Hindu and Non-Hindu), caste (Scheduled Caste/Scheduled Tribe, Other Backward Class, and others), place of residence (urban and rural), and states (Uttar Pradesh and Bihar).

Exposure to mass media (how often they read newspapers, listened to the radio, and watched television; responses on the frequencies were: almost every day, at least once a week, at least once a month, rarely or not at all; adolescents were considered to have any exposure to mass media if they had exposure to any of these sources and as having no exposure if they responded with ‘not at all’ for all three sources of media) 24 . Household wealth index based on ownership of selected durable goods and amenities with possible scores ranging from 0 to 57; households were then divided into quintiles, with the first quintile representing households of the poorest wealth status and the fifth quintile representing households with the wealthiest status 25 .

Statistical analysis

Descriptive analysis was done to observe the characteristics of unmarried adolescent boys and girls at wave-1 (2015–2016). In addition, the changes in certain selected variables were observed from wave-1 (2015–2016) to wave-2 (2018–2019), and the significance was tested using t-test and proportion test 26 , 27 . Moreover, random effect regression analysis 28 , 29 was used to estimate the association of change in HIV awareness among unmarried adolescents with household factors and individual factors. The random effect model has a specific benefit for the present paper's analysis: its ability to estimate the effect of any variable that does not vary within clusters, which holds for household variables, e.g., wealth status, which is assumed to be constant for wave-1 and wave-2 30 .

Table 1 represents the socio-economic profile of adolescent boys and girls. The estimates are from the baseline dataset, and it was assumed that none of the household characteristics changed over time among adolescent boys and girls.

Figure  1 represents the change in HIV awareness among adolescent boys and girls. The percentage of adolescent boys who had awareness regarding HIV increased from 38.6% in wave-1 to 59.9% in wave-2. Among adolescent girls, the percentage increased from 30.2% in wave-1 to 39.1% in wave-2.

The percenate of HIV awareness among adolescent boys and girls, wave-1 (2015–2016) and wave-2 (2018–2019).

Table 2 represents the summary statistics for explanatory variables used in the analysis of UDAYA wave-1 and wave-2. The exposure to mass media is almost universal for adolescent boys, while for adolescent girls, it increases to 93% in wave-2 from 89.8% in wave-1. About 35.3% of adolescent boys were engaged in paid work during wave-1, whereas in wave-II, the share dropped to 33.5%, while in the case of adolescent girls, the estimates are almost unchanged. In wave-1, about 27.8% of adolescent boys were using the internet, while in wave-2, there is a steep increase of nearly 46.2%. Similarly, in adolescent girls, the use of the internet increased from 7.6% in wave-1 to 39.3% in wave-2.

Table 3 represents the estimates from random effects for awareness of HIV among adolescent boys and girls. It was found that with the increases in age and years of schooling the HIV awareness increased among adolescent boys ([Coef: 0.05; p  < 0.01] and [Coef: 0.04; p  < 0.01]) and girls ([Coef: 0.03; p  < 0.01] and [Coef: 0.04; p  < 0.01]), respectively. The adolescent boys [Coef: 0.06; p  < 0.05] and girls [Coef: 0.03; p  < 0.05] who had any mass media exposure were more likely to have an awareness of HIV in comparison to those who had no exposure to mass media. Adolescent boys' paid work status was inversely associated with HIV awareness about adolescent boys who did not do paid work [Coef: − 0.01; p  < 0.10]. Use of the internet among adolescent boys [Coef: 0.18; p  < 0.01] and girls [Coef: 0.14; p  < 0.01] was positively associated with HIV awareness in reference to their counterparts.

The awareness regarding HIV increases with the increase in household wealth index among both adolescent boys and girls. The adolescent girls from the non-Hindu household had a lower likelihood to be aware of HIV in reference to adolescent girls from Hindu households [Coef: − 0.09; p  < 0.01]. Adolescent girls from non-SC/ST households had a higher likelihood of being aware of HIV in reference to adolescent girls from other caste households [Coef: 0.04; p  < 0.01]. Adolescent boys [Coef: − 0.03; p  < 0.01] and girls [Coef: − 0.09; p  < 0.01] from a rural place of residence had a lower likelihood to be aware about HIV in reference to those from the urban place of residence. Adolescent boys [Coef: 0.04; p  < 0.01] and girls [Coef: 0.02; p  < 0.01] from Bihar had a higher likelihood to be aware about HIV in reference to those from Uttar Pradesh.

This is the first study of its kind to address awareness of HIV among adolescents utilizing longitudinal data in two indian states. Our study demonstrated that the awareness of HIV has increased over the period; however, it was more prominent among adolescent boys than in adolescent girls. Overall, the knowledge on HIV was relatively low, even during wave-II. Almost three-fifths (59.9%) of the boys and two-fifths (39.1%) of the girls were aware of HIV. The prevalence of awareness on HIV among adolescents in this study was lower than almost all of the community-based studies conducted in India 10 , 11 , 22 . A study conducted in slums in Delhi has found almost similar prevalence (40% compared to 39.1% during wave-II in this study) of awareness of HIV among adolescent girls 31 . The difference in prevalence could be attributed to the difference in methodology, study population, and study area.

The study found that the awareness of HIV among adolescent boys has increased from 38.6 percent in wave-I to 59.9 percent in wave-II; similarly, only 30.2 percent of the girls had an awareness of HIV during wave-I, which had increased to 39.1 percent. Several previous studies corroborated the finding and noticed a higher prevalence of awareness on HIV among adolescent boys than in adolescent girls 16 , 32 , 33 , 34 . However, a study conducted in a different setting noticed a higher awareness among girls than in boys 35 . Also, a study in the Indian context failed to notice any statistical differences in HIV knowledge between boys and girls 18 . Gender seems to be one of the significant determinants of comprehensive knowledge of HIV among adolescents. There is a wide gap in educational attainment among male and female adolescents, which could be attributed to lower awareness of HIV among girls in this study. Higher peer victimization among adolescent boys could be another reason for higher awareness of HIV among them 36 . Also, cultural double standards placed on males and females that encourage males to discuss HIV/AIDS and related sexual matters more openly and discourage or even restrict females from discussing sexual-related issues could be another pertinent factor of higher awareness among male adolescents 33 . Behavioural interventions among girls could be an effective way to improving knowledge HIV related information, as seen in previous study 37 . Furthermore, strengthening school-community accountability for girls' education would augment school retention among girls and deliver HIV awareness to girls 38 .

Similar to other studies 2 , 10 , 17 , 18 , 39 , 40 , 41 , age was another significant determinant observed in this study. Increasing age could be attributed to higher education which could explain better awareness with increasing age. As in other studies 18 , 39 , 41 , 42 , 43 , 44 , 45 , 46 , education was noted as a significant driver of awareness of HIV among adolescents in this study. Higher education might be associated with increased probability of mass media and internet exposure leading to higher awareness of HIV among adolescents. A study noted that school is one of the important factors in raising the awareness of HIV among adolescents, which could be linked to higher awareness among those with higher education 47 , 48 . Also, schooling provides adolescents an opportunity to improve their social capital, leading to increased awareness of HIV.

Following previous studies 18 , 40 , 46 , the current study also outlines a higher awareness among urban adolescents than their rural counterparts. One plausible reason for lower awareness among adolescents in rural areas could be limited access to HIV prevention information 16 . Moreover, rural–urban differences in awareness of HIV could also be due to differences in schooling, exposure to mass media, and wealth 44 , 45 . The household's wealth status was also noted as a significant predictor of awareness of HIV among adolescents. Corroborating with previous findings 16 , 33 , 42 , 49 , this study reported a higher awareness among adolescents from richer households than their counterparts from poor households. This could be because wealthier families can afford mass-media items like televisions and radios for their children, which, in turn, improves awareness of HIV among adolescents 33 .

Exposure to mass media and internet access were also significant predictors of higher awareness of HIV among adolescents. This finding agrees with several previous research, and almost all the research found a positive relationship between mass-media exposure and awareness of HIV among adolescents 10 . Mass media addresses such topics more openly and in a way that could attract adolescents’ attention is the plausible reason for higher awareness of HIV among those having access to mass media and the internet 33 . Improving mass media and internet usage, specifically among rural and uneducated masses, would bring required changes. Integrating sexual education into school curricula would be an important means of imparting awareness on HIV among adolescents; however, this is debatable as to which standard to include the required sexual education in the Indian schooling system. Glick (2009) thinks that the syllabus on sexual education might be included during secondary schooling 44 . Another study in the Indian context confirms the need for sex education for adolescents 50 , 51 .

Limitations and strengths of the study

The study has several limitations. At first, the awareness of HIV was measured with one question only. Given that no study has examined awareness of HIV among adolescents using longitudinal data, this limitation is not a concern. Second, the study findings cannot be generalized to the whole Indian population as the study was conducted in only two states of India. However, the two states selected in this study (Uttar Pradesh and Bihar) constitute almost one-fourth of India’s total population. Thirdly, the estimates were provided separately for boys and girls and could not be presented combined. However, the data is designed to provide estimates separately for girls and boys. The data had information on unmarried boys and girls and married girls; however, data did not collect information on married boys. Fourthly, the study estimates might have been affected by the recall bias. Since HIV is a sensitive topic, the possibility of respondents modifying their responses could not be ruled out. Hawthorne effect, respondents, modifying aspect of their behaviour in response, has a role to play in HIV related study 52 . Despite several limitations, the study has specific strengths too. This is the first study examining awareness of HIV among adolescent boys and girls utilizing longitudinal data. The study was conducted with a large sample size as several previous studies were conducted in a community setting with a minimal sample size 10 , 12 , 18 , 20 , 53 .

The study noted a higher awareness among adolescent boys than in adolescent girls. Specific predictors of high awareness were also noted in the study, including; higher age, higher education, exposure to mass media, internet use, household wealth, and urban residence. Based on the study findings, this study has specific suggestions to improve awareness of HIV among adolescents. There is a need to intensify efforts in ensuring that information regarding HIV should reach vulnerable sub-groups as outlined in this study. It is important to mobilize the available resources to target the less educated and poor adolescents, focusing on rural adolescents. Investment in education will help, but it would be a long-term solution; therefore, public information campaigns could be more useful in the short term.

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This paper was written using data collected as part of Population Council’s UDAYA study, which is funded by the Bill and Melinda Gates Foundation and the David and Lucile Packard Foundation. No additional funds were received for the preparation of the paper.

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Srivastava, S., Chauhan, S., Patel, R. et al. A study of awareness on HIV/AIDS among adolescents: A Longitudinal Study on UDAYA data. Sci Rep 11 , 22841 (2021). https://doi.org/10.1038/s41598-021-02090-9

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A trial HIV vaccine triggered elusive and essential antibodies in humans

Finding points the way toward a successful vaccine that elicits broadly neutralizing antibodies.

An HIV vaccine candidate developed at the Duke Human Vaccine Institute triggered low levels of an elusive type of broadly neutralizing HIV antibodies among a small group of people enrolled in a 2019 clinical trial.

The finding, reported May 17 in the journal Cell , not only provides proof that a vaccine can elicit these antibodies to fight diverse strains of HIV, but that it can also initiate the process within weeks, setting in motion an essential immune response.

The vaccine candidate targets an area on the HIV-1 outer envelope called the membrane proximal external region (MPER), which remains stable even as the virus mutates. Antibodies against this stable region in the HIV outer coat can block infection by many different circulating strains of HIV.

"This work is a major step forward as it shows the feasibility of inducing antibodies with immunizations that neutralize the most difficult strains of HIV," said senior author Barton F. Haynes, M.D., director of the Duke Human Vaccine Institute (DHVI). "Our next steps are to induce more potent neutralizing antibodies against other sites on HIV to prevent virus escape. We are not there yet, but the way forward is now much clearer."

The research team analyzed data from a phase 1 clinical trial of a vaccine candidate developed by Haynes and S. Munir Alam, Ph.D., at DHVI.

Twenty healthy, HIV-negative people enrolled in the trial. Fifteen participants received two of four planned doses of the investigational vaccine, and five received three doses.

After just two immunizations, the vaccine had a 95% serum response rate and a 100% blood CD4+ T-cell response rate -- two key measurements that demonstrated strong immune activation. Most of the serum responses mapped to the portion of the virus targeted by the vaccine.

Importantly, broadly neutralizing antibodies were induced after just two doses.

The trial was halted when one participant experienced a non-life-threatening allergic reaction, similar to rare incidents reported with COVID-19 vaccinations. The team investigated the cause of the event, which was likely from an additive.

"To get a broadly neutralizing antibody, a series of events needs to happen, and it typically takes several years post-infection," said lead author Wilton Williams, Ph.D., associate professor in Duke's Department of Surgery and member of DHVI. "The challenge has always been to recreate the necessary events in a shorter space of time using a vaccine. It was very exciting to see that, with this vaccine molecule, we could actually get neutralizing antibodies to emerge within weeks."

Other features of the vaccine were also promising, most notably how the crucial immune cells remained in a state of development that allowed them to continue acquiring mutations, so they could evolve along with the ever-changing virus.

The researchers said there is more work to be done to create a more robust response, and to target more regions of the virus envelope. A successful HIV vaccine will likely have at least three components, all aimed at distinct regions of the virus.

"Ultimately, we will need to hit all the sites on the envelope that are vulnerable so that the virus cannot escape," Haynes said. "But this study demonstrates that broadly neutralizing antibodies can indeed be induced in humans by vaccination. Now that we know that induction is possible, we can replicate what we have done here with immunogens that target the other vulnerable sites on the virus envelope."

In addition to Haynes and Williams, study authors include S. Munir Alam, Gilad Ofek, Nathaniel Erdmann, David Montefiori, Michael S. Seaman, Kshitij Wagh, Bette Korber, Robert J. Edwards, Katayoun Mansouri, Amanda Eaton, Derek W. Cain, Mitchell Martin, Robert Parks, Maggie Barr, Andrew Foulger, Kara Anasti, Parth Patel, Salam Sammour, Ruth J. Parsons, Xiao Huang, Jared Lindenberger, Susan Fetics, Katarzyna Janowska, Aurelie Niyongabo, Benjamin M. Janus, Anagh Astavans, Christopher B. Fox, Ipsita Mohanty, Tyler Evangelous, Yue Chen, Madison Berry, Helene Kirshner, Elizabeth Van Itallie, Kevin Saunders, Kevin Wiehe, Kristen W. Cohen, M. Juliana McElrath, Lawrence Corey, Priyamvada Acharya, Stephen R. Walsh, and Lindsey R. Baden.

• HIV and AIDS
• Infectious Diseases
• Bird Flu Research
• Microbes and More
• Antiretroviral drug
• Flu vaccine
• MMR vaccine

Story Source:

Materials provided by Duke University Medical Center . Note: Content may be edited for style and length.

Journal Reference :

• Wilton B. Williams, S. Munir Alam, Gilad Ofek, Nathaniel Erdmann, David C. Montefiori, Michael S. Seaman, Kshitij Wagh, Bette Korber, Robert J. Edwards, Katayoun Mansouri, Amanda Eaton, Derek W. Cain, Mitchell Martin, JongIn Hwang, Aria Arus-Altuz, Xiaozhi Lu, Fangping Cai, Nolan Jamieson, Robert Parks, Maggie Barr, Andrew Foulger, Kara Anasti, Parth Patel, Salam Sammour, Ruth J. Parsons, Xiao Huang, Jared Lindenberger, Susan Fetics, Katarzyna Janowska, Aurelie Niyongabo, Benjamin M. Janus, Anagh Astavans, Christopher B. Fox, Ipsita Mohanty, Tyler Evangelous, Yue Chen, Madison Berry, Helene Kirshner, Elizabeth Van Itallie, Kevin O. Saunders, Kevin Wiehe, Kristen W. Cohen, M. Juliana McElrath, Lawrence Corey, Priyamvada Acharya, Stephen R. Walsh, Lindsey R. Baden, Barton F. Haynes. Vaccine induction of heterologous HIV-1-neutralizing antibody B cell lineages in humans . Cell , 2024; DOI: 10.1016/j.cell.2024.04.033

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Strange & offbeat.

Trial HIV vaccine triggers elusive and essential antibodies, pointing the way toward a successful vaccine

A n HIV vaccine candidate developed at the Duke Human Vaccine Institute triggered low levels of an elusive type of broadly neutralizing HIV antibodies among a small group of people enrolled in a 2019 clinical trial.

The finding , reported May 17 in the journal Cell , not only provides proof that a vaccine can elicit these antibodies to fight diverse strains of HIV, but that it can also initiate the process within weeks, setting in motion an essential immune response.

The vaccine candidate targets an area on the HIV-1 outer envelope called the membrane proximal external region (MPER), which remains stable even as the virus mutates. Antibodies against this stable region in the HIV outer coat can block infection by many different circulating strains of HIV.

"This work is a major step forward as it shows the feasibility of inducing antibodies with immunizations that neutralize the most difficult strains of HIV," said senior author Barton F. Haynes, M.D., director of the Duke Human Vaccine Institute (DHVI). "Our next steps are to induce more potent neutralizing antibodies against other sites on HIV to prevent virus escape. We are not there yet, but the way forward is now much clearer."

The research team analyzed data from a Phase I clinical trial of a vaccine candidate developed by Haynes and S. Munir Alam, Ph.D., at DHVI.

Twenty healthy, HIV-negative people enrolled in the trial. Fifteen participants received two of four planned doses of the investigational vaccine, and five received three doses.

After just two immunizations, the vaccine had a 95% serum response rate and a 100% blood CD4 + T-cell response rate—two key measurements that demonstrated strong immune activation. Most of the serum responses mapped to the portion of the virus targeted by the vaccine.

Importantly, broadly neutralizing antibodies were induced after just two doses.

The trial was halted when one participant experienced a non-life-threatening allergic reaction, similar to rare incidences reported with COVID-19 vaccinations. The team investigated the cause of the event, which was likely from an additive.

"To get a broadly neutralizing antibody, a series of events needs to happen, and it typically takes several years post-infection," said lead author Wilton Williams, Ph.D., associate professor in Duke's Department of Surgery and member of DHVI.

"The challenge has always been to recreate the necessary events in a shorter space of time using a vaccine. It was very exciting to see that, with this vaccine molecule, we could actually get neutralizing antibodies to emerge within weeks."

Other features of the vaccine were also promising, most notably how the crucial immune cells remained in a state of development that allowed them to continue acquiring mutations, so they could evolve along with the ever-changing virus.

The researchers said there is more work to be done to create a more robust response, and to target more regions of the virus envelope. A successful HIV vaccine will likely have at least three components, all aimed at distinct regions of the virus.

"Ultimately, we will need to hit all the sites on the envelope that are vulnerable so that the virus cannot escape," Haynes said.

"But this study demonstrates that broadly neutralizing antibodies can indeed be induced in humans by vaccination. Now that we know that induction is possible, we can replicate what we have done here with immunogens that target the other vulnerable sites on the virus envelope."

More information: Vaccine Induction of Heterologous HIV-1 Neutralizing Antibody B Cell Lineages in Humans, Cell (2024). DOI: 10.1016/j.cell.2024.04.033 . www.cell.com/cell/fulltext/S0092-8674(24)00459-8

Provided by Duke University Medical Center

The epidemiology of delayed HIV diagnosis in Ibadan, Nigeria

Affiliations.

• 1 Clinical Epidemiology Unit, Faculty of Medicine, Division of Community Health and Humanities Faculty of Medicine, 7512Memorial University, St John's, Canada.
• 2 University College Hospital, Ibadan, Nigeria.
• 3 APIN Public Health Initiative, Nigeria.
• PMID: 35773231
• PMCID: PMC9388944
• DOI: 10.1177/09564624221106523

Background: Human immunodeficiency virus infection (HIV) is one of the major health burdens in Nigeria. Delayed HIV diagnosis remains a significant driver of HIV transmission. The risk factors of delayed HIV diagnosis have not been widely studied in Nigeria. This observational study examined demographic risk factors for delayed HIV diagnosis and the trends in the annual total cases of delayed HIV diagnosis in Ibadan, Nigeria.

Methods: We examined the data on HIV patients enrolled in care at the University College Hospital's Antiretroviral Therapy (ART) clinic in Ibadan, Nigeria. Delayed HIV diagnosis was defined as a Cluster of Differentiation 4 (CD4) count of less than 350 cells/mm³ at the time of diagnosis. The association between delayed HIV diagnosis and risk factors was analyzed using logistic regression. The trends in the annual total cases of delayed HIV diagnosis over time were examined.

Results: This study included 3458 HIV patients. There were 1993/3458 prevalent cases of delayed HIV diagnosis (57.6%). The risk factors for delayed HIV diagnosis were older age, retirement, marriage separation, never married, and widowed female. The factors that were significantly associated with a low risk of delayed HIV diagnosis were student and tertiary education. There was a progressive decline in the annual cases of delayed HIV diagnosis.

Conclusions: Although the cases of delayed HIV diagnosis are still high, they are declining. Human immunodeficiency virus testing should be targeted at populations at risk of delayed diagnosis. Considerable public awareness and education programs about HIV testing may significantly reduce delayed HIV diagnosis in Nigeria.

Keywords: Nigeria; delayed diagnosis; human immunodeficiency virus; prevention of transmission; risk factors; trends in annual cases.

Publication types

• Observational Study
• Research Support, Non-U.S. Gov't
• HIV Infections* / diagnosis
• HIV Infections* / drug therapy
• HIV Infections* / epidemiology
• Nigeria / epidemiology
• Risk Factors

• Case Report
• Open access
• Published: 27 May 2024

A complex case study: coexistence of multi-drug-resistant pulmonary tuberculosis, HBV-related liver failure, and disseminated cryptococcal infection in an AIDS patient

• Wei Fu 1 , 2   na1 ,
• Zi Wei Deng 3   na1 ,
• Pei Wang 1 ,
• Zhen Wang Zhu 1 ,
• Zhi Bing Xie 1 ,
• Yong Zhong Li 1 &
• Hong Ying Yu 1  

BMC Infectious Diseases volume  24 , Article number:  533 ( 2024 ) Cite this article

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Hepatitis B virus (HBV) infection can cause liver failure, while individuals with Acquired Immunodeficiency Virus Disease (AIDS) are highly susceptible to various opportunistic infections, which can occur concurrently. The treatment process is further complicated by the potential occurrence of immune reconstitution inflammatory syndrome (IRIS), which presents significant challenges and contributes to elevated mortality rates.

Case presentation

The 50-year-old male with a history of chronic hepatitis B and untreated human immunodeficiency virus (HIV) infection presented to the hospital with a mild cough and expectoration, revealing multi-drug resistant pulmonary tuberculosis (MDR-PTB), which was confirmed by XpertMTB/RIF PCR testing and tuberculosis culture of bronchoalveolar lavage fluid (BALF). The patient was treated with a regimen consisting of linezolid, moxifloxacin, cycloserine, pyrazinamide, and ethambutol for tuberculosis, as well as a combination of bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) for HBV and HIV viral suppression. After three months of treatment, the patient discontinued all medications, leading to hepatitis B virus reactivation and subsequent liver failure. During the subsequent treatment for AIDS, HBV, and drug-resistant tuberculosis, the patient developed disseminated cryptococcal disease. The patient’s condition worsened during treatment with liposomal amphotericin B and fluconazole, which was ultimately attributed to IRIS. Fortunately, the patient achieved successful recovery after appropriate management.

Enhancing medical compliance is crucial for AIDS patients, particularly those co-infected with HBV, to prevent HBV reactivation and subsequent liver failure. Furthermore, conducting a comprehensive assessment of potential infections in patients before resuming antiviral therapy is essential to prevent the occurrence of IRIS. Early intervention plays a pivotal role in improving survival rates.

Peer Review reports

HIV infection remains a significant global public health concern, with a cumulative death toll of 40 million individuals [ 1 ]. In 2021 alone, there were 650,000 deaths worldwide attributed to AIDS-related causes. As of the end of 2021, approximately 38 million individuals were living with HIV, and there were 1.5 million new HIV infections reported annually on a global scale [ 2 ]. Co-infection with HBV and HIV is prevalent due to their similar transmission routes, affecting around 8% of HIV-infected individuals worldwide who also have chronic HBV infection [ 3 ]. Compared to those with HBV infection alone, individuals co-infected with HIV/HBV exhibit higher HBV DNA levels and a greater risk of reactivation [ 4 ]. Opportunistic infections, such as Pneumocystis jirovecii pneumonia, Toxoplasma encephalitis, cytomegalovirus retinitis, cryptococcal meningitis (CM), tuberculosis, disseminated Mycobacterium avium complex disease, pneumococcal pneumonia, Kaposi’s sarcoma, and central nervous system lymphoma, are commonly observed due to HIV-induced immunodeficiency [ 5 ]. Tuberculosis not only contributes to the overall mortality rate in HIV-infected individuals but also leads to a rise in the number of drug-resistant tuberculosis cases and transmission of drug-resistant strains. Disseminated cryptococcal infection is a severe opportunistic infection in AIDS patients [ 6 ], and compared to other opportunistic infections, there is a higher incidence of IRIS in patients with cryptococcal infection following antiviral and antifungal therapy [ 7 ]. This article presents a rare case of an HIV/HBV co-infected patient who presented with MDR-PTB and discontinued all medications during the initial treatment for HIV, HBV, and tuberculosis. During the subsequent re-anti-HBV/HIV treatment, the patient experienced two episodes of IRIS associated with cryptococcal infection. One episode was classified as “unmasking” IRIS, where previously subclinical cryptococcal infection became apparent with immune improvement. The other episode was categorized as “paradoxical” IRIS, characterized by the worsening of pre-existing cryptococcal infection despite immune restoration [ 8 ]. Fortunately, both episodes were effectively treated.

A 50-year-old male patient, who is self-employed, presented to our hospital in January 2022 with a chief complaint of a persistent cough for the past 2 months, without significant shortness of breath, palpitations, or fever. His medical history revealed a previous hepatitis B infection, which resulted in hepatic failure 10 years ago. Additionally, he was diagnosed with HIV infection. However, he ceased taking antiviral treatment with the medications provided free of charge by the Chinese government for a period of three years. During this hospital visit, his CD4 + T-cell count was found to be 26/μL (normal range: 500–1612/μL), HIV-1 RNA was 1.1 × 10 5 copies/ml, and HBV-DNA was negative. Chest computed tomography (CT) scan revealed nodular and patchy lung lesions (Fig.  1 ). The BALF shows positive acid-fast staining. Further assessment of the BALF using XpertMTB/RIF PCR revealed resistance to rifampicin, and the tuberculosis drug susceptibility test of the BALF (liquid culture, medium MGIT 960) indicated resistance to rifampicin, isoniazid, and streptomycin. Considering the World Health Organization (WHO) guidelines for drug-resistant tuberculosis, the patient’s drug susceptibility results, and the co-infection of HIV and HBV, an individualized treatment plan was tailored for him. The treatment plan included BIC/TAF/FTC (50 mg/25 mg/200 mg per day) for HBV and HIV antiviral therapy, as well as linezolid (0.6 g/day), cycloserine (0.5 g/day), moxifloxacin (0.4 g/day), pyrazinamide (1.5 g/day), and ethambutol (0.75 g/day) for anti-tuberculosis treatment, along with supportive care.

The patient’s pulmonary CT scan shows patchy and nodular lesions accompanied by a small amount of pleural effusion, later confirmed to be MDR-PTB

Unfortunately, after 3 months of follow-up, the patient discontinued all medications due to inaccessibility of the drugs. He returned to our hospital (Nov 12, 2022, day 0) after discontinuing medication for six months, with a complaint of poor appetite for the past 10 days. Elevated liver enzymes were observed, with an alanine aminotransferase level of 295 IU/L (normal range: 0–40 IU/L) and a total bilirubin(TBIL) level of 1.8 mg/dL (normal range: 0–1 mg/dL). His HBV viral load increased to 5.5 × 10 9 copies/ml. Considering the liver impairment, elevated HBV-DNA and the incomplete anti-tuberculosis treatment regimen (Fig.  2 A), we discontinued pyrazinamide and initiated treatment with linezolid, cycloserine, levofloxacin, and ethambutol for anti-tuberculosis therapy, along with BIC/TAF/FTC for HIV and HBV antiviral treatment. Additionally, enhanced liver protection and supportive management were provided, involving hepatoprotective effects of medications such as glutathione, magnesium isoglycyrrhizinate, and bicyclol. However, the patient’s TBIL levels continued to rise progressively, reaching 4.4 mg/dL on day 10 (Fig.  3 B). Suspecting drug-related factors, we discontinued all anti-tuberculosis medications while maintaining BIC/TAF/FTC for antiviral therapy, the patient’s TBIL levels continued to rise persistently. We ruled out other viral hepatitis and found no significant evidence of obstructive lesions on magnetic resonance cholangiopancreatography. Starting from the day 19, due to the patient’s elevated TBIL levels of 12.5 mg/dL, a decrease in prothrombin activity (PTA) to 52% (Fig.  3 D), and the emergence of evident symptoms such as abdominal distension and poor appetite, we initiated aggressive treatment methods. Unfortunately, on day 38, his hemoglobin level dropped to 65 g/L (normal range: 120–170 g/L, Fig.  3 A), and his platelet count decreased to 23 × 10 9 /L (normal range: 125–300 × 10 9 /L, Fig.  3 C). Based on a score of 7 on the Naranjo Scale, it was highly suspected that “Linezolid” was the cause of these hematological abnormalities. Therefore, we had to discontinue Linezolid for the anti-tuberculosis treatment. Subsequently, on day 50, the patient developed recurrent fever, a follow-up chest CT scan revealed enlarged nodules in the lungs (Fig.  2 B). The patient also reported mild dizziness and a worsening cough. On day 61, the previous blood culture results reported the growth of Cryptococcus. A lumbar puncture was performed on the same day, and the cerebrospinal fluid (CSF) opening pressure was measured at 130 mmH 2 O. India ink staining of the CSF showed typical encapsulated yeast cells suggestive of Cryptococcus. Other CSF results indicated mild leukocytosis and mildly elevated protein levels, while chloride and glucose levels were within normal limits. Subsequently, the patient received a fungal treatment regimen consisting of liposomal amphotericin B (3 mg/kg·d −1 ) in combination with fluconazole(600 mg/d). After 5 days of antifungal therapy, the patient’s fever symptoms were well controlled. Despite experiencing bone marrow suppression, including thrombocytopenia and worsening anemia, during this period, proactive symptom management, such as the use of erythropoietin, granulocyte colony-stimulating factor, and thrombopoietin, along with high-calorie dietary management, even reducing the dosage of liposomal amphotericin B to 2 mg/kg/day for 10 days at the peak of severity, successfully controlled the bone marrow suppression. However, within the following week, the patient experienced fever again, accompanied by a worsened cough, increased sputum production, and dyspnea. Nevertheless, the bilirubin levels did not show a significant increase. On day 78 the patient’s lung CT revealed patchy infiltrates and an increased amount of pleural effusion (Fig.  2 C). The CD4 + T-cell count was 89/μL (normal range: 500–700/μL), indicating a significant improvement in immune function compared to the previous stage, and C-reactive protein was significantly elevated, reflecting the inflammatory state, other inflammatory markers such as IL-6 and γ-IFN were also significantly elevated. On day 84, Considering the possibility of IRIS, the patient began taking methylprednisolone 30 mg once a day as part of an effort to control his excessive inflammation. Following the administration of methylprednisolone, the man experienced an immediate improvement in his fever. Additionally, symptoms such as cough, sputum production, dyspnea, and poor appetite gradually subsided over time. A follow-up lung CT showed significant improvement, indicating a positive response to the treatment. After 28 days of treatment with liposomal amphotericin B in combination with fluconazole, liposomal amphotericin B was discontinued, and the patient continued with fluconazole to consolidate the antifungal therapy for Cryptococcus. Considering the patient’s ongoing immunodeficiency, the dosage of methylprednisolone was gradually reduced by 4 mg every week. After improvement in liver function, the patient’s anti-tuberculosis treatment regimen was adjusted to include bedaquiline, contezolid, cycloserine, moxifloxacin, and ethambutol. The patient’s condition was well controlled, and a follow-up lung CT on day 117 indicated a significant improvement in lung lesions (Fig.  2 D).

Upon second hospitalization admission ( A ), nodular lesions were already present in the lungs, and their size gradually increased after the initiation of ART ( B , C ). Notably, the lung lesions became more pronounced following the commencement of anti-cryptococcal therapy, coinciding with the occurrence of pleural effusion ( C ). However, with the continuation of antifungal treatment and the addition of glucocorticoids, there was a significant absorption and reduction of both the pleural effusion and pulmonary nodules ( D )

During the patient's second hospitalization, as the anti-tuberculosis treatment progressed and liver failure developed, the patient’s HGB levels gradually decreased ( A ), while TBIL levels increased ( B ). Additionally, there was a gradual decrease in PLT count ( C ) and a reduction in prothrombin activity (PTA) ( D ), indicating impaired clotting function. Moreover, myelosuppression was observed during the anti-cryptococcal treatment ( C )

People living with HIV/AIDS are susceptible to various opportunistic infections, which pose the greatest threat to their survival [ 5 ]. Pulmonary tuberculosis and disseminated cryptococcosis remain opportunistic infections with high mortality rates among AIDS patients [ 9 , 10 ]. These infections occurring on the basis of liver failure not only increase diagnostic difficulty but also present challenges in treatment. Furthermore, as the patient’s immune function and liver function recover, the occurrence of IRIS seems inevitable.

HIV and HBV co-infected patients are at a higher risk of HBV reactivation following the discontinuation of antiviral drugs

In this case, the patient presented with both HIV and HBV infections. Although the HBV DNA test was negative upon admission. However, due to the patient’s self-discontinuation of antiretroviral therapy (ART), HBV virologic and immunologic reactivation occurred six months later, leading to a rapid increase in viral load and subsequent hepatic failure. Charles Hannoun et al. also reported similar cases in 2001, where two HIV-infected patients with positive HBsAg experienced HBV reactivation and a rapid increase in HBV DNA levels after discontinuing antiretroviral and antiviral therapy, ultimately resulting in severe liver failure [ 11 ]. The European AIDS Clinical Society (EACS) also emphasize that abrupt discontinuation of antiviral therapy in patients co-infected with HBV and HIV can trigger HBV reactivation, which, although rare, can potentially result in liver failure [ 12 ].

Diagnosing disseminated Cryptococcus becomes more challenging in AIDS patients with liver failure, and the selection of antifungal medications is significantly restricted

In HIV-infected individuals, cryptococcal disease typically manifests as subacute meningitis or meningoencephalitis, often accompanied by fever, headache, and neck stiffness. The onset of symptoms usually occurs approximately two weeks after infection, with typical signs and symptoms including meningeal signs such as neck stiffness and photophobia. Some patients may also experience encephalopathy symptoms like somnolence, mental changes, personality changes, and memory loss, which are often associated with increased intracranial pressure (ICP) [ 13 ]. The presentation of cryptococcal disease in this patient was atypical, as there were no prominent symptoms such as high fever or rigors, nor were there any signs of increased ICP such as somnolence, headache, or vomiting. The presence of pre-existing pulmonary tuberculosis further complicated the early diagnosis, potentially leading to the clinical oversight of recognizing the presence of cryptococcus. In addition to the diagnostic challenges, treating a patient with underlying liver disease, multidrug-resistant tuberculosis, and concurrent cryptococcal infection poses significant challenges. It requires considering both the hepatotoxicity of antifungal agents and potential drug interactions. EACS and global guideline for the diagnosis and management of cryptococcosis suggest that liposomal amphotericin B (3 mg/kg·d −1 ) in combination with flucytosine (100 mg/kg·d −1 ) or fluconazole (800 mg/d) is the preferred induction therapy for CM for 14 days [ 12 , 14 ]. Flucytosine has hepatotoxicity and myelosuppressive effects, and it is contraindicated in patients with severe liver dysfunction. The antiviral drug bictegravir is a substrate for hepatic metabolism by CYP3A and UGT1A1 enzymes [ 15 ], while fluconazole inhibits hepatic enzymes CYP3A4 and CYP2C9 [ 16 ]. Due to the patient's liver failure and bone marrow suppression, we reduced the dosage of liposomal amphotericin B and fluconazole during the induction period. Considering the hepatotoxicity of fluconazole and its interaction with bictegravir, we decreased the dosage of fluconazole to 600 mg/d, while extending the duration of induction therapy to 28 days.

During re-antiviral treatment, maintaining vigilance for the development of IRIS remains crucial

IRIS refers to a series of inflammatory diseases that occur in HIV-infected individuals after initiating ART. It is associated with the paradoxical worsening of pre-existing infections, which may have been previously diagnosed and treated or may have been subclinical but become apparent due to the host regaining the ability to mount an inflammatory response. Currently, there is no universally accepted definition of IRIS. However, the following conditions are generally considered necessary for diagnosing IRIS: worsening of a diagnosed or previously unrecognized pre-existing infection with immune improvement (referred to as “paradoxical” IRIS) or the unmasking of a previously subclinical infection (referred to as “unmasking” IRIS) [ 8 ]. It is estimated that 10% to 30% of HIV-infected individuals with CM will develop IRIS after initiating or restarting effective ART [ 7 , 17 ]. In the guidelines of the WHO and EACS, it is recommended to delay the initiation of antiviral treatment for patients with CM for a minimum of 4 weeks to reduce the incidence of IRIS. Since we accurately identified the presence of multidrug-resistant pulmonary tuberculosis in the patient during the early stage, we promptly initiated antiretroviral and anti-hepatitis B virus treatment during the second hospitalization. However, subsequent treatment revealed that the patient experienced at least two episodes of IRIS. The first episode was classified as “unmasking” IRIS, as supported by the enlargement of pulmonary nodules observed on the chest CT scan following the initiation of ART (Fig.  2 A). Considering the morphological changes of the nodules on the chest CT before antifungal therapy, the subsequent emergence of disseminated cryptococcal infection, and the subsequent reduction in the size of the lung nodules after antifungal treatment, although there is no definitive microbiological evidence, we believe that the initial enlargement of the lung nodules was caused by cryptococcal pneumonia. As ART treatment progressed, the patient experienced disseminated cryptococcosis involving the blood and central nervous system, representing the first episode. Following the initiation of antifungal therapy for cryptococcosis, the patient encountered a second episode characterized by fever and worsening pulmonary lesions. Given the upward trend in CD4 + T-cell count, we attributed this to the second episode of IRIS, the “paradoxical” type. The patient exhibited a prompt response to low-dose corticosteroids, further supporting our hypothesis. Additionally, the occurrence of cryptococcal IRIS in the lungs, rather than the central nervous system, is relatively uncommon among HIV patients [ 17 ].

Conclusions

From the initial case of AIDS combined with chronic hepatitis B, through the diagnosis and treatment of multidrug-resistant tuberculosis, the development of liver failure and disseminated cryptococcosis, and ultimately the concurrent occurrence of IRIS, the entire process was tortuous but ultimately resulted in a good outcome (Fig.  4 ). Treatment challenges arose due to drug interactions, myelosuppression, and the need to manage both infectious and inflammatory conditions. Despite these hurdles, a tailored treatment regimen involving antifungal and antiretroviral therapies, along with corticosteroids, led to significant clinical improvement. While CM is relatively common among immunocompromised individuals, especially those with acquired immunodeficiency syndrome (AIDS) [ 13 ], reports of disseminated cryptococcal infection on the background of AIDS complicated with liver failure are extremely rare, with a very high mortality rate.

A brief timeline of the patient's medical condition progression and evolution

Through managing this patient, we have also gained valuable insights. (1) Swift and accurate diagnosis, along with timely and effective treatment, can improve prognosis, reduce mortality, and lower disability rates. Whether it's the discovery and early intervention of liver failure, the identification and treatment of disseminated cryptococcosis, or the detection and management of IRIS, all these interventions are crucially timely. They are essential for the successful treatment of such complex and critically ill patients.

(2) Patients who exhibit significant drug reactions, reducing the dosage of relevant medications and prolonging the treatment duration can improve treatment success rates with fewer side effects. In this case, the dosages of liposomal amphotericin B and fluconazole are lower than the recommended dosages by the World Health Organization and EACS guidelines. Fortunately, after 28 days of induction therapy, repeat CSF cultures showed negative results for Cryptococcus, and the improvement of related symptoms also indicates that the patient has achieved satisfactory treatment outcomes. (3) When cryptococcal infection in the bloodstream or lungs is detected, prompt lumbar puncture should be performed to screen for central nervous system cryptococcal infection. Despite the absence of neurological symptoms, the presence of Cryptococcus neoformans in the cerebrospinal fluid detected through lumbar puncture suggests the possibility of subclinical or latent CM, especially in late-stage HIV-infected patients.

We also encountered several challenges and identified certain issues that deserve attention. Limitations: (1) The withdrawal of antiviral drugs is a critical factor in the occurrence and progression of subsequent diseases in patients. Improved medical education is needed to raise awareness and prevent catastrophic consequences. (2) Prior to re-initiating antiviral therapy, a thorough evaluation of possible infections in the patient is necessary. Caution should be exercised, particularly in the case of diseases prone to IRIS, such as cryptococcal infection. (3) There is limited evidence on the use of reduced fluconazole dosage (600 mg daily) during antifungal therapy, and the potential interactions between daily fluconazole (600 mg) and the antiviral drug bictegravir and other tuberculosis medications have not been extensively studied. (4) Further observation is needed to assess the impact of early-stage limitations in the selection of anti-tuberculosis drugs on the treatment outcome of tuberculosis in this patient, considering the presence of liver failure.

In conclusion, managing opportunistic infections in HIV patients remains a complex and challenging task, particularly when multiple opportunistic infections are compounded by underlying liver failure. Further research efforts are needed in this area.

Availability of data and materials

All data generated or analyzed during this study are included in this published article.

Abbreviations

Hepatitis B virus

Acquired immunodeficiency virus disease

Immune reconstitution inflammatory syndrome

Human immunodeficiency virus

Multi-drug resistant pulmonary tuberculosis

Bronchoalveolar lavage fluid

Bictegravir/tenofovir alafenamide/emtricitabine

Cryptococcal meningitis

World Health Organization

Computed tomography

Total bilirubin

Cerebrospinal fluid

European AIDS Clinical Society

Intracranial pressure

Antiretroviral therapy

Prothrombin activity

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Acknowledgements

We express our sincere gratitude for the unwavering trust bestowed upon our medical team by the patient throughout the entire treatment process.

This work was supported by the Scientific Research Project of Hunan Public Health Alliance with the approval No. ky2022-002.

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Wei Fu and Zi Wei Deng contributed equally to this work.

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Center for Infectious Diseases, Hunan University of Medicine General Hospital, Huaihua, Hunan, China

Wei Fu, Pei Wang, Zhen Wang Zhu, Ye Pu, Zhi Bing Xie, Yong Zhong Li & Hong Ying Yu

Department of Tuberculosis, The First Affiliated Hospital of Xinxiang Medical University, XinXiang, Henan, China

Department of Clinical Pharmacy, Hunan University of Medicine General Hospital, Huaihua, Hunan, China

Zi Wei Deng

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WF and ZWD integrated the data and wrote the manuscript, YHY contributed the revision of the manuscript, PW and YP provided necessary assistance and provided key suggestions, ZWZ, YZL and ZBX contributed data acquisition and interpretation for etiological diagnosis. All authors reviewed and approved the final manuscript.

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Correspondence to Hong Ying Yu .

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Fu, W., Deng, Z.W., Wang, P. et al. A complex case study: coexistence of multi-drug-resistant pulmonary tuberculosis, HBV-related liver failure, and disseminated cryptococcal infection in an AIDS patient. BMC Infect Dis 24 , 533 (2024). https://doi.org/10.1186/s12879-024-09431-9

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• Prevalence and viral suppression of hepatitis B virus infection among people living with HIV on antiretroviral therapy in Sierra Leone
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• http://orcid.org/0000-0002-8582-8012 Jin-Wen Song 1 ,
• Sulaiman Lakoh 2 , 3 , 4 ,
• Si-Yuan Chen 1 ,
• Mohamed Boie Jalloh 2 , 5 ,
• Stephen Sevalie 2 , 4 , 5 ,
• Mamadu Baldeh 2 , 3 ,
• Mohamed K Nyambe 3 ,
• Victoria Donicia Nicholas 3 ,
• George Yendewa 6 , 7 , 8 ,
• Fu-Sheng Wang 1 ,
• http://orcid.org/0000-0003-0356-8569 Guang Yang 9
• 1 Senior Department of Infectious Diseases , The Fifth Medical Center of Chinese PLA General Hospital , Beijing , China
• 2 College of Medicine and Allied Health Sciences , University of Sierra Leone , Freetown , Sierra Leone
• 3 Ministry of Health and Sanitation , Government of Sierra Leone , Freetown , Sierra Leone
• 4 Sustainable Health Systems Sierra Leone , Freetown , Sierra Leone
• 5 34 Military Hospital , Freetown , Sierra Leone
• 6 Department of Medicine , Case Western Reserve University School of Medicine , Cleveland , Ohio , USA
• 7 Division of Infectious Diseases and HIV Medicine , University Hospitals Cleveland Medical Center , Cleveland , Ohio , USA
• 8 Johns Hopkins Bloomberg School of Public Health , Baltimore , Maryland , USA
• 9 Department of Clinical Laboratory , The Fifth Medical Center of Chinese PLA General Hospital , Beijing , China
• Correspondence to Guang Yang, Department of Clinical Laboratory, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China; guang.23{at}163.com ; Fu-Sheng Wang, Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China; fswang302{at}163.com

Objective Sub-Saharan Africa is one of the regions with the highest burdens of HIV and hepatitis B virus (HBV), but data on the impact of antiretroviral therapy (ART) on HBV DNA suppression is limited. In this study, we aimed to determine the prevalence and associated factors of a positive hepatitis B surface antigen (HBsAg) among people living with HIV, and assess the suppression of ART on HBV replication in people living with HIV in Sierra Leone.

Methods A cross-sectional study was designed to recruit people living with HIV aged 18 years or older in ten public hospitals in Sierra Leone between August 2022 and January 2023. Statistical analyses were performed using R software. Logistic regression analysis was used to assess factors independently associated with positive HBsAg and HBV DNA suppression.

Results Of the 3106 people living with HIV recruited in this study, 2311 (74.4%) were women. The median age was 36 years, 166 (5.3%) had serological evidence of HBV vaccination. The overall prevalence of HBsAg positivity was 12.0% (95% CI: 10.9% to 13.2%). Male sex (adjusted OR (aOR) 2.11, 95% CI: 1.67 to 2.68; p<0.001) and being separated (aOR 1.83, 95% CI: 1.06 to 3.16, p=0.031; reference group: being married) were independent predictors of HBsAg seropositivity. Among 331 people living with HIV and HBV receiving ART, 242 (73.1%) achieved HBV DNA suppression (below 20 IU/mL). HBV suppression rate was higher in HIV-virally suppressed patients than those with unsuppressed HIV viral load (p<0.001). In addition, the male sex was more likely to have unsuppressed HBV DNA (aOR 1.17, 95% CI: 1.17 to 3.21; p=0.010).

Conclusions We reported a high prevalence of HBsAg seropositivity and low HBV immunisation coverage in people living with HIV in Sierra Leone. In addition, we observed that ART can efficiently result in a viral suppression rate of HBV infection. Therefore, achieving the global target of eliminating HBV infection by 2030 requires accelerated access to care for people living with HIV and HBV, including HBV testing, antiviral treatment and hepatitis B vaccination.

• HEPATITIS B
• Anti-HIV Agents
• HIV Infections

Data availability statement

Data are available upon reasonable request. The data for this study is available at Fifth Medical Centre of PLA General Hospital, Beijing, China, and Ministry of Health of Sierra Leone and will be made available upon request.

https://doi.org/10.1136/sextrans-2023-056042

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WHAT IS ALREADY KNOWN ON THIS TOPIC

Only two small studies reported the prevalence of hepatitis B virus (HBV) in patients with HIV, and none reported data on HBV virological suppression, making it difficult to understand the impact of antiretroviral therapy on HBV suppression in Sierra Leone.

WHAT THIS STUDY ADDS

We found that the national prevalence of HBV among patients with HIV was 12% and the HBV DNA suppression rate below 20 IU/mL was 73.1%.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

Our findings call for the integration of HBV-HIV services to achieve elimination by 2030.

Introduction

Viral hepatitis is the seventh leading cause of death worldwide. 1 The WHO estimates that 1.1 million people died from chronic viral hepatitis in 2019. 1 2 Vaccines against hepatitis B have proven effective in prevention and control, leading to a significant reduction in the prevalence of hepatitis B virus (HBV). More than 296 million of the world population chronically live with HBV, 90% of whom live in low-income and middle-income countries. 2 The global prevalence of HBV is 3.5%, but the prevalence in sub-Saharan Africa is higher, estimated at 6.1%. 1–3

Owing to these abysmal global and regional statistics, the World Health Assembly proposed the elimination of viral hepatitis as a public health threat by 2030. The goal is to achieve a 90% reduction in new infections and a 65% reduction in death from HBV from the 2015 baseline. 4 However, achieving these goals is hampered by several challenges, including limited access to testing services and high rates of HIV/HBV co-infection in many low-income and middle-income countries. 5

Co-infection with HBV is common in people living with HIV because of shared transmission routes which may accelerate the clinical course and affect the response to therapy. 6 Of the 36 million people living with HIV worldwide, approximately 2.6 million people co-infected with HBV live in sub-Saharan Africa. 7

Sierra Leone’s health system response to public health problems such as viral hepatitis has been challenged by a series of viral outbreaks in recent years, including Ebola and SARS-CoV-2. Although there is no published data on the national seroprevalence of HBV to date, small studies in Sierra Leone reported a positive rate of hepatitis B surface antigen (HBsAg) above 8% in different population groups, indicating a high endemicity of HBV in this country. 8–14

The national HIV prevalence in Sierra Leone is 1.7%, but HIV service delivery faces many challenges, such as the lack of routine HBV screening of people living with HIV. 15 Therefore, data reporting the prevalence of HBV among people living with HIV in Sierra Leone are limited to two small single-centre studies. 9 10 Nonetheless, fixed-dose combination antiviral drugs containing tenofovir disoproxil fumarate (TDF) and lamivudine (3TC) recommended in HIV treatment guidelines in Sierra Leone are effective against both HBV and HIV. Consequently, the HIV treatment programme has been providing treatment to people living with HIV using these drugs to maintain both HIV and HBV viral suppression in those co-infected. 16 However, unlike HIV, Sierra Leone lacks data on HBV virological suppression in individuals co-infected with HBV and HIV, which hinders the understanding of the impact of antiretroviral therapy (ART) on HBV virological suppression. 17

Given the many challenges in HIV service delivery, such as the high rates of late diagnosis and treatment interruption among people living with HIV in Sierra Leone, understanding the prevalence of HIV and HBV co-infection and the impact of ART on HBV viral suppression in this population has important policy implications. 18 19 In this study, we aimed to (1) determine the prevalence and associated factors of a positive HBsAg in people living with HIV, and (2) assess the impact of ART on HBV DNA suppression in people living with HIV in Sierra Leone.

This study was conducted in accordance with the relevant guidelines and regulations and the Declaration of Helsinki. Each participant provided written informed consent. For illiterate participants, the study, and the consent form content were explained to them verbally and they gave their consent using fingerprints.

Study design, study population and study setting

Sierra Leone is divided into five regions, and almost 22% of Sierra Leone’s population resides in the Western Area where the country’s capital Freetown is located ( online supplemental figure 1 ). We selected facilities with more than 800 people living with HIV receiving ART at a time when the study was being planned. The hospitals, the people living with HIV populations and levels of care are shown in online supplemental table 1 . Two health facilities in the East (Well Body Clinic and Koidu Hospital) and two hospitals in Western Sierra Leone (Wellness Clinic and United Methodist Church Urban Centre) with more than 800 people living with HIV were excluded due to the distance or delay in obtaining consent to conduct the study. The study employed a cross-sectional design to collect primary data on adult patients aged 18 years or older in 10 public hospitals in Sierra Leone ( online supplemental figure 1 ). Six tertiary/regional hospitals (Connaught Hospital, Princess Christian Maternity Hospital, 34 Military Hospital and Bo, Kenema and Makeni Government Hospitals), two secondary hospitals (Rokupa and Lumley Government Hospitals) and two primary health facilities (Jenner Wright Clinic and Waterloo Community Health Centre) were included.

Supplemental material

Participants selection and sample processing.

We consecutively recruited all people living with HIV presenting to the 10 health facilities between August 2022 and January 2023, with the majority recruited in Western Sierra Leone ( online supplemental table 1 ). We recruited participants aged above 18 years and above who were able and willing to provide their informed consent. The demographic and HIV-related information of these individuals were collected by completing a questionnaire.

Following informed written consent, blood samples were collected in EDTA-containing vacutainer tubes from each participant and processed at the Infectious Disease Prevention and Control Center of the 34 Military Hospital. Plasma samples were separated from 10 mL of collected venous blood by centrifugation at 2000 revolutions per minute for 10 min and transferred to cryogenic vials. All samples were stored at −80°C until analysis.

HBV serological detection and determination of HBV DNA

We used the Wondfo One Step HBV Whole Blood/Serum/Plasma Test Kit (Wondfo, Guangzhou, China), a rapid immunochromatographic assay, to determine the serological markers of HBV such as HBsAg and hepatitis B surface antibody (HBsAb). The sensitivity and specificity of HBsAg were 96.2% and 99.3%, respectively. For HBsAb, the sensitivity and specificity were 93.0% and 99.0%, respectively.

HBV DNA was determined using a one-step HBV PCR kit (Sansure Biotech, Hunan, China). About 5 µL nucleic lysis buffer and 5 µL plasma specimen were mixed and incubated at room temperature for 10 min to allow rapid lysis and release of HBV DNA. Then, 40 µL of the reaction mixture was added. Each reaction mixture contained 38 µL of HBV PCR mixture, 2 µL of enzyme mixture and 0.2 µL of positive internal control. HBV amplification and detection were performed with the CFX96 real-time PCR detection system (Bio-Rad Laboratories, Hercules, California, USA). HBV DNA was detected in the FAM/Green channel and internal control was detected in the VIC/Yellow channel. The Lower Limit of Quantitation and Lower Limit of Detection for the Definition of undetectable HBV DNA is 20 and 5 IU/mL, respectively.

Data analysis

Statistical analyses were performed using R (R Core Team, Vienna, Austria). Baseline characteristics were summarised using frequencies and medians. We used Pearson’s χ 2 and Fisher’s exact test to assess statistical significance. Binomial logistic regression was used to construct a model to identify risk factors for hepatitis B infection among demographic parameters. A p value≤0.05 was considered statistically significant. For univariate analysis, categorical variables were analysed separately with the function glm . Multivariate testing for comparing the significance of each variable was performed using the function glm . To avoid over-fitting and collinearity, we first estimated Pearson correlation coefficients (PCC) between every two variables with the function corr.test from the package psych and adjusted R squared (adjusted R 2 ) using the function regsubsets from the package leaps . The variables ‘ART status’ were excluded due to the PCC>0.5, and ‘HIV-1 viral load’ was excluded based on adjusted R 2 results. Subsequently, characteristics that are not clinically or biologically relevant were also excluded, such as ‘Duration of ART’ and ‘ART regimen’. Besides, ‘Geography information’ which is likely to HBsAg status was included to construct the model. Eventually, we used ‘Age’, ‘Gender’, ‘Marital status’, ‘Hospital level’ and ‘Hospital location’ for further logistic regression analysis to calculate OR with 95% CIs. The same method was also used to identify risk factors for unsuppressed HBV DNA. We provided p values with Wald and likelihood-ratio test for each category with the function Wald test and analysis of variance, respectively.

Demographic characteristics of study participants

Of the 3106 people living with HIV recruited in this study, 2311 (74.4%) were women. The median age and duration of ART were 36 years (IQR: 29–45 years) and 38 months (IQR: 9–80 months), respectively. Most used the fixed-dose combination of TDF, 3TC and dolutegravir (1856, 59.8%), while a majority were virally suppressed (defined as HIV viral load below 200 copies/mL) (2442, 78.6%) ( table 1 ).

• View inline

Basic demographic characteristics of people living with HIV in this study

Prevalence and risk factors of HBV infection among people living with HIV

The overall prevalence of HBsAg was 12.0% (95% CI: 10.9% to 13.2%) ( table 2 and figure 1 ). The median age of people living with HIV co-infected with HBV was 37 years (IQR: 29–46 years) compared with 36 years (IQR: 29–45) in those without HBV co-infection. The seroprevalence of HBsAg was higher in men (18.1%, 95% CI: 15.6% to 20.9%) than women (9.9%, 95% CI: 8.7% to 11.2%) (p<0.001), but not statistically different for age, marital status, hospital level of care, hospital location and ART treatment and duration. In univariate analysis, the risk of a positive HBsAg was higher in age 40–50 years (OR 1.40, 95% CI: 1.05 to 1.86; p=0.023; reference group: age <30), male sex (OR 2.04, 95% CI: 1.63 to 2.56; p<0.001) and separated people (OR 1.71, 95% CI: 1.00 to 2.92, p=0.05). In multivariable analysis, male sex (adjusted OR (aOR) 2.11, 95% CI: 1.67 to 2.68; p<0.001) and being separated (aOR 1.83, 95% CI: 1.06 to 3.16, p=0.031; reference group: being married) were independent predictors of HBsAg seropositivity ( table 2 ). Among 3106 people living with HIV who were screened for HBV serological markers ( table 1 ), 166 (5.3%, 95% CI: 4.6% to 6.2%) were HBsAb positive and were regarded immunised by HBV vaccination.

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Prevalence of hepatitis B infection among people living with HIV. Forest plot showing the prevalence of HBV infection stratified by demographic characteristics. The blue dotted line indicates the overall prevalence of HBV among people living with HIV. The red dot represents the prevalence of HBV in each group and the horizontal lines indicate the CI. ART, antiretroviral therapy; HBV, hepatitis B virus; TLD, tenofovir, lamivudine and dolutegravir; TLE, tenofovir, lamivudine and efavirenz.

Prevalence and risk factor analysis of hepatitis B infection by demographic parameters

Impact of ART on HBV replication

We used multivariable analysis to investigate the factors associated with HBV DNA suppression rate ( online supplemental table 2 ). We found male sex (aOR 1.72, 95% CI: 1.01 to 2.91; p=0.044) and those with HIV-1 viral load of more than 1000 copies/mL (aOR: 3.29, 95% CI: 1.68 to 6.46; p<0.001) are more likely to have unsuppressed HBV DNA.

We further explored the impact of ART on HBV replication in patients receiving ART containing at least one drug with anti-HBV activity. In patients with detectable HBV DNA, the median HBV DNA was 306.6 (IQR: 72.2–15 217.4) IU/mL. Among 331 HIV/HBV co-infected patients receiving ART, 242 (73.1%) achieved HBV DNA suppression below 20 IU/mL and HBV DNA suppression rate was 75.6% (183/242) in those treated for more than 12 months. Among 286 individuals receiving TDF-containing regimen, the HBV DNA suppression rate was 73.4% (210/286) and HBV DNA suppression rate was 75.4% (156/207) for those treated for more than 12 months. We then evaluated the duration of ART on HBV DNA suppression and found that patients on ART for 12–24 months had the highest HBV DNA suppression rate (77.78%, 28/36), following with patients on ART for more than 24 months (75.24%, 155/206) ( figure 2A ). For patients who received ART for more than 6 months with HIV viral load below 200 copies/mL, the rate of patients with undetectable HBV DNA was 78.40% (185/236). In contrast, the rate decreased to 52.17% (24/46) in those receiving ART with an unsuppressed HIV viral load (p<0.001) ( figure 2B ). We also evaluated the HBV DNA suppression rate in HIV/HBV co-infected patients receiving treatment containing TDF and 3TC ( online supplemental figure S2 ). Similarly, we found that 78.13% (25/32) patients on ART for 12–24 months and 78.43% (160/204) patients with suppressed HIV viral load achieved suppressed HBV replication.

HBV DNA suppression rate in ART-experienced HIV/HBV co-infected patients. HBV DNA suppression rate was evaluated in HIV-HBV co-infected patients receiving more than 6 months of ART based on (A) different duration of ART and (B) HIV viral load. ART, antiretroviral therapy; HBV, hepatitis B virus.

We observed an overall HBV prevalence of 12.0%, which was in agreement with the 13.0% reported in a systematic review of studies from different populations in Sierra Leone. 20 Moreover, sub-Saharan African countries such as Ethiopia, Nigeria, Ghana and Kenya reported lower prevalence rates of HBV in people living with HIV than that reported in our study. 21–24 These differences in the prevalence of HBV could reflect on the variation in public health interventions across Africa and emphasise the need for Sierra Leone to take immediate steps to integrate HBV services such as routine HBV screening and vaccination of susceptible people living with HIV to the HIV response in the country. It has been reported elsewhere that the integration of hepatitis B care into routine HIV services is feasible and widely acceptable by service providers and recipients of care if the health system is properly planned to avoid inherent challenges. 25

We identified age 40–50 and male sex as risk factors for HBV infection among people living with HIV, similar to a report from Ethiopia. 26 Hence, we recommend offering specific support, including routine HBV screening and HBV vaccination, to people living with HIV who have been identified as being at higher risk for HBV infection in the country.

Only 5.3% of the people living with HIV have serological evidence of past HBV vaccination. This could be explained by the fact that individuals that participated in our study were born before 2007, when the government introduced the HBV vaccine into the routine immunisation programme. Therefore, we were unable to assess the impact of routine HBV vaccination on preventing maternal HBV transmission to children of HIV/HBV co-infected mothers, which could be done in future studies. In addition, the low hepatitis B vaccination coverage reflects the lack of a hepatitis B prevention programme for people living with HIV in Sierra Leone.

We explored the impact of ART with anti-HBV activity on the HBV DNA suppression rate. There are limited studies in sub-Saharan Africa evaluating the effect of ART on HBV DNA viral suppression rates, particularly in people living with HIV. In Senegal, a study of children with HBV reported an HBV DNA suppression rate of 71.4% at 3.5 years after starting ART. 27 Correspondingly, Day et al in Kenya reported an HBV DNA suppression rate of 82% after a median follow-up of 3.4 years. 28

HBV infection poses a threat to long- term liver health among people living with HIV in West Africa, a study conducted in Ghana by Villa et al reported that people living with HIV co-infected with HBV had a higher prevalence of ≥F2 fibrosis measured by FibroScan. 29 In addition, liver fibrosis measured by transient elastography was independently associated with HBV DNA load in lamivudine-treated people living with HIV, and tenofovir treatment can improve HBV control and reduce liver stiffness in subjects with high HBV DNA load. 30

In our study, the rate of HBV DNA suppression was higher in people living with HIV with suppressed HIV viral load than those with unsuppressed HIV viral load. We are concerned about this finding because of the high rate of unsuppressed HIV RNA levels and late HIV diagnosis in our setting. 17–19 As liver-related mortality and potential for aggravated HIV-associated immune deficiency in people living with HIV co-infected with HBV could worsen with these challenges, we emphasise that the introduction of routine HBV screening to HIV services and the provision of effective HIV treatment with TDF and 3TC in a combined regimen can save lives. 6

Our study has limitations. First, we were unable to differentiate between acute and chronic HBV infection because the kit used in this study did not detect HBcAb (Hepatitis B core antibody) IgM. Second, we did not assess liver function and liver fibrosis in people living with HIV to determine the extent of liver disease in this patient population. Third, owing to logistical challenges, we recruited participants primarily from four of the five geographical regions of Sierra Leone, the majority of which are from Western Sierra Leone, making this study not truly representative of the hepatitis B situation in Sierra Leone. Additionally, this was a cross-sectional study assessing the effect of ART on HBV replication, but baseline HBV DNA levels were not assessed. Future studies should recruit patients with active HBV replication to longitudinally assess the effect of ART on HBV replication in Sierra Leone. In addition, HBV/HIV resistance testing is not available in our setting. Finally, the lack of immunisation records and HBcAb status makes it difficult to differentiate prior vaccination from naturally acquired infection. Nonetheless, this study provides the first large-scale data on HBV prevalence and the first evidence of the impact of ART on HBV replication in Sierra Leonean people living with HIV.

In summary, we reported a high prevalence of HBsAg seropositivity and low HBV immunisation coverage in people living with HIV in Sierra Leone. In addition, we observed that ART can efficiently result in a viral suppression rate of HBV infection. Therefore, achieving the global target by eliminating HBV infection by 2030 requires accelerated access to care for people living with HIV with chronic HBV infection, including HBV testing, antiviral treatment and HBV vaccination.

Abstract translation

Ethics statements, patient consent for publication.

Not applicable.

Ethics approval

This study was approved by the Sierra Leone Ethics and Scientific Review Committee (SLESRC) of the Ministry of Health and Sanitation of Sierra Leone. Until January 2023, the Sierra Leone Ethics and Scientific Review Committee of the Ministry of Health and Sanitation did not issue out ethics approval numbers. Participants gave informed consent to participate in the study before taking part.

Acknowledgments

We gratefully acknowledge all the participants enrolled in this study and healthcare workers in the different hospitals where the patients were recruited.

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Supplementary materials

Supplementary data.

This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

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Handling editor Apostolos Beloukas

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J-WS, SL and S-YC contributed equally.

Contributors J-WS, GYa and F-SW conceived and designed the study. J-WS, GYa and SL performed the experiment. MBJ, SS, MKN, VDN and MB collected the blood samples and clinical information. S-YC analysed the data and performed the statistical analysis. J-WS, GYa, SL, F-SW and GYe wrote the manuscript. All authors read and approved the final manuscript. GYa is responsible for the overall content as guarantor.

Funding This work was supported by grants from the Beijing Natural Science Foundation (grant number 7222171), the National Natural Science Foundation of China (grant number 82101837, 82371766).

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Competing interests None declared.

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