Register now to take part in an important conversation about National HIV Vaccine Awareness Day—an annual observation to recognize the many community members, health professionals, and scientists working together to develop a vaccine to prevent HIV. The HIV.gov-hosted Live with Leadership conversation will take place on Thursday, May 18, from 2:30–3:00pm ET.

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This engaging conversation will provide participants with an understanding of recent developments and future opportunities to develop an HIV vaccine. Additionally, it will focus on how an HIV vaccine fits into the National HIV/AIDS Strategy and efforts to end the HIV epidemic domestically and around the globe.

Dr. Timothy Harrison, Principal Deputy Director of the Office of Infectious Disease & HIV/AIDS Policy (OIDP), HHS, will moderate the conversation. He will be joined by panelists, including:

• Carl Dieffenbach, Ph.D., Director, Division of AIDS, National Institutes of Health
• Julie Patterson, Director, AIDS Funding Collaborative, The Center for Community Solutions
• Harold Phillips, Director, The White House Office of National AIDS Policy

This Live with Leadership conversation provides an opportunity to hear directly from key federal leaders and a nonpartisan think tank director with expertise in HIV and efforts regarding a vaccine for the virus.

Registration is required for the Live with Leadership session. This event is open to everyone. Please note capacity is limited, so register early! The conversation will be recorded and made available after the session for those unable to attend.

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As the latest research on HIV and other infectious diseases continued to be presented at the 2023 Conference on Retroviruses and Opportunistic Infections (CROI), HIV.gov spoke with Dr. Carl Dieffenbach about some of the highlights. Dr. Dieffenbach is the Director of the Division of AIDS at NIH’s National Institute of Allergy and Infectious Disease. He shared updates about some research on long-acting HIV prevention and treatment and COVID treatment and prevention. He also discussed news of another reported case of HIV cure. Watch our conversation with Dr. Dieffenbach below:

Long-Acting HIV Prevention and Treatment

Dr. Dieffenbach highlighted three NIH-supported studies that focused on the effectiveness of long-acting HIV prevention in specific populations and a demonstration of how long-acting HIV treatment can be used to reach people with multiple challenges to treatment adherence. First, he discussed a study presented by Dr. Hyman Scott of the San Francisco Department of Public Health that demonstrated the safety and effectiveness of long-acting injectable cabotegravir (CAB-LA) for HIV pre-exposure prophylaxis (PrEP) among Black men who have sex with men and transgender women who have sex with men, concluding that CAB-LA can be a powerful HIV prevention tool to reduce HIV incidence among these groups that are disproportionately affected by HIV. Next, Dr. Dieffenbach highlighted a study presented by Dr. Sybil Hosek of Stroger Hospital of Cook County that found that CAB-LA for HIV PrEP was found to be safe, tolerable, and acceptable to sexually active adolescent females under the age of 18 in three African countries, where young women and girls are disproportionately affected by HIV.

Finally, Dr. Dieffenbach highlighted a real-world demonstration study by Dr. Monica Gandhi of the University of California San Francisco that found that long-acting antiretroviral treatment (LA-ART) given every four to eight weeks and delivered with comprehensive support services suppressed HIV in people who were previously not virologically suppressed and who experienced housing insecurity, mental illnesses, and substance use disorders. Notably, the study participants included individuals who were on ART but were not virally suppressed and others who were not on ART, which would generally make them ineligible to start LA-ART. Dr. Gandhi reported that all of those participants achieved viral suppression on LA-ART, concluding that LA-ART can be effective for individuals facing challenges to adhering to daily oral ART, particularly when combined with wrap-around services to address challenges such as unstable housing, mental health issues, and/or substance use disorders. Read more about this study.

HIV Cure News

Dr. Dieffenbach addressed news that broke while the conference was taking place about another case of an apparent HIV cure. He briefly discussed the 53-year-old man known as “the Dusseldorf patient” who is in long-term HIV remission nine years after a stem-cell transplant and five years after stopping ART. He is one of a handful of people with both HIV and leukemia who received HIV-resistant stem cells through a bone marrow transplant intended to treat leukemia, a very serious and potentially life-threatening procedure. Dr. Dieffenbach explained that this approach is not one that can be used with all people with HIV because of the very high health risks of a stem cell transplant. But this case does provide researchers with insights into possible paths to a more scalable HIV cure.

COVID Treatment and Prevention

Research on COVID-19 is also being discussed at CROI and Dr. Dieffenbach discussed two studies of interest. The first involved research on the investigational drug ensitrelvir, a protease inhibitor, which demonstrated a significant reduction in the time to resolution of five typical COVID symptoms and was well tolerated. In his presentation of the study findings, Dr. Takeki Uehara of Shionogi & Co. also noted that early analysis suggests that the drug may have an impact on long COVID. Dr. Dieffenbach noted that the NIH-support Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections (ACTG) is conducting a study, called ACTIV-2d, of this once-daily treatment for non-hospitalized adults with early COVID-19 and that the trial is enrolling participants. On the COVID prevention front, Dr. Dieffenbach highlighted a study presented by Dr. Paul Bieniasz of Rockefeller University about his lab’s work to develop monoclonal antibodies against the ACE2 receptor to block COVID entry into human cells. The antibodies are now being evaluated in what Dr. Dieffenbach notes is a promising step since this approach would make it much harder for the SARS-CoV-2 virus to evolve around this form of antibody prevention.

About CROI

CROI is an annual scientific meeting that brings together leading researchers and clinical investigators from around the world to present, discuss, and critique the latest studies that can help accelerate global progress in the response to HIV and AIDS and other infectious diseases, including viral hepatitis, COVID-19, and mpox. More than 3,400 HIV and infectious disease researchers from 72 countries gathered in Seattle and virtually for this forum. Among the studies that are being presented are many that were conducted or supported by NIH, CDC, and other federal agencies. Visit the conference website for more information; abstracts, session webcasts, and e-posters will be published there for public access in 30 days.

To reduce the spread of HIV infection, the World Health Organization (WHO) recommends pre-exposure prophylaxis (PrEP) in populations with an annual HIV infection incidence greater than 3%. Given that the annual HIV incidence in Uganda is estimated at 0.40% (0.46% among females and 0.35% among males), there are people who may have a higher HIV risk and may benefit from PrEP but are not targeted for services. To further reduce the spread of HIV in Uganda, researchers used results from three survey rounds of HIV-negative participants within the Rakai Community Cohort Study (RCCS) to estimate the prevalence of high-risk individuals eligible for PrEP within the general population and the incidence of HIV infection associated with eligibility. 

In this study, a subset of questions from Uganda’s PrEP eligibility tool that are routinely asked within the RCCS surveys were used to determine PrEP eligibility. Eligibility was defined as reporting at least one of the following HIV risk behaviors in the past 12 months: sexual intercourse with more than one partner of unknown HIV status; nonmarital sex act without a condom; sex engagement in exchange for money, goods, or services; or experiencing genital ulcers. HIV incidence was estimated by analyzing seroconversion from HIV-negative to HIV-positive in participants who contributed to at least two of the survey rounds.

Overall, 29% of participants in the analysis met the eligibility criteria. Of these, 22% reported one HIV risk, 6% reported two HIV risks, and 1% reported three HIV risks. The results showed that PrEP eligible participants had twice the risk of acquiring HIV than their non-eligible counterparts. Furthermore, risk increased threefold in uncircumcised males but not circumcised males. Additionally, men who reported higher prevalence of risky behaviors had lower increase in HIV incidence compared to women, likely due to circumcision status and higher antiretroviral therapy coverage in HIV-infected females, leading to a decrease in transmission to men. The findings of this study support the use of PrEP eligibility screening in general populations with HIV incidence lower than 3% to reduce HIV acquisition even further in these populations.

Reference: Ssempijja et al. High Rates of Pre-exposure Prophylaxis Eligibility and Associated HIV Incidence in a Population With a Generalized HIV Epidemic in Rakai, Uganda, JAIDS Journal of Acquired Immune Deficiency Syndromes, July 1, 2022 - Volume 90 - Issue 3 - p 291-299.

The National Institutes of Health has awarded approximately $34 million annually over the next five years to fund six independent Centers for HIV Structural Biology. The National Institute of Allergy and Infectious Diseases (NIAID) committed approximately $30 million in funding, with an additional $4 million from the NIH Office of AIDS Research.

The Centers program, established in 2007 by the National Institute of General Medical Sciences (NIGMS), was transitioned to NIAID in 2019 as part of the transfer of the NIGMS HIV/AIDS portfolio to the NIAID Division of AIDS (DAIDS). Last year, NIAID solicited applications to RFA AI-21-030: Centers for HIV Structural Biology using the U54 specialized center funding mechanism. The U54 mechanism was utilized to allow enhanced NIAID program oversight and encourage the involvement of NIH intramural researchers. The new Centers largely maintained the structure of the existing Centers while refocusing on research topics that support NIAID priorities of HIV prevention, therapy and cure. In addition, a new Developmental Core was added to foster mentoring and training of young scientists in HIV research.

The Center researchers integrate techniques from structural biology, biochemistry and cell biology to capture in unprecedented detail the three-dimensional structures of HIV proteins and nucleic acids and their interactions with cellular components. This information provides an entirely new perspective on HIV infection and immune control that helps elucidate how the different components interact and reveal new approaches for disrupting those interactions, potentially leading to new targets for HIV therapies and preventative vaccines. In total over 300 scientists from dozens of institutions in the US and abroad will participate in the studies put forward by the Centers. 

The six applications selected for funding include research across the HIV life cycle, aiming, for example, to elucidate the mechanism the HIV envelope protein uses to enter a target cell, the interactions of virus structures with host proteins that either facilitate or antagonize infection, and the way that the HIV RNA genome folds into complex assemblies with other viral components before being packaged into newly formed virions.

The following awardees will receive the indicated funds annually for five years: 

Duke University

Duke Center for HIV Structural Biology (DCHSB)

Director: Priyamvada Acharya

Award: $5.5 million

Seattle Children’s Hospital

Behavior of HIV in Viral Environments (B-HIVE)

Co-Directors: Bruce Torbett, Stefan Sarafianos

Award: $6.3 million 

University of California, San Francisco

HIV Accessory and Regulatory Complexes (HARC)

Director: Nevan Krogan

Award: $5.7 million

University of Michigan

Center for Structural Biology of HIV RNA (CRNA)

Director: Alice Telesnitsky

Award: $5.5 million

University of Pittsburgh

Pittsburgh Center for HIV Protein Interactions (PCHPI)

Directors: Angela Gronenborn, Tatyana Polenova

Award: $5 million

University of Utah

Center for the Structural Biology of HIV Infection, Restriction, and Viral Dynamics (CHEETAH)

Director: Wesley Sundquist

Award: $5.5 million

Despite major advances in testing and treating HIV, including highly effective oral pre-exposure prophylaxis, there were 1.7 million new cases of HIV in 2019.  Fifty-nine percent of these occurred in sub-Saharan Africa, where a high proportion of newly infected individuals are women. In order to see if facilitating PrEP delivery decreased HIV transmission in these areas, a flexible care delivery model of PreP for high-risk individuals was tested in 16 rural communities in Kenya and Uganda. The study paired community HIV testing with same-day access to PrEP in HIV-negative high-risk individuals, as well as follow-up appointments at week 4, week 12 and every 12 weeks thereafter until week 144.  Location of follow-up visits, care, and PrEP refills was flexibly scheduled at local areas including homes, nearby schools, or community locations to facilitate follow-up and adherence.

Overall, 79% of individuals who started PrEP adhered to the program and follow-up visits.  In 8 of the 16 communities, data from those who started PrEP was compared to data from people with similar demographic and risk profiles from the year before PrEP was available. In women, incidence of HIV was 76% lower in women and 74% in the overall population among individuals who initiated PrEP compared to control groups who did not.  These finding suggest that this intervention strategy including access to PrEP in conjunction with existing testing, treatment and prevention sites can reduce HIV spread in these rural settings, especially when scaled up to meet the community’s needs through a flexible care delivery model.

Reference: Koss et al. HIV incidence after pre-exposure prophylaxis initiation among women and men at elevated HIV risk: A population-based study in rural Kenya and Uganda. PLoS Medicine. 2021 Feb 9; 18(2): e1003492.

Although the spread of HIV has slowed down thanks to risk-reduction measures, prevention efforts, and oral antiretroviral preexposure prophylaxis (PrEP), there are more than 1.5 million new cases of the human immunodeficiency virus (HIV) each year worldwide. The Antibody Mediated Prevention trials included two clinical trial cohorts, to test the ability of the monoclonal antibody VRC01 to prevent HIV acquisition. The study enrolled participants from three different continents, including at-risk cisgender men and transgender people and at-risk women in sub-Saharan Africa. Participants were healthy, HIV-uninfected adults 18-40 years old randomly assigned to receive either the VRCO1 antibody or a placebo 8 weeks at a time for a total of 10 infusions over the course of 20 months.

Researchers found that, although the VRC01 antibody did not prevent overall HIV-1 transmission, VRC01 treatment was linked to lower risk of acquisition of HIV-1 isolates that had in vitro sensitivity to the antibody. For women in sub-Saharan Africa who were at risk for HIV-1 infection and were exposed to subtype C variants, VRC-01 demonstrated 75% protection against this group of viruses. This was also the case at other sites, including at-risk persons in South America, Switzerland, and the United States who were as­signed male sex at birth or were transgender, and who were exposed to subtype B variants.  These findings support that pre-exposure prophylaxis using broadly neutralizing antibodies can be a promising strategy to prevent HIV spread. 

Reference: Corey L et al. Two Randomized Trials of Neutralizing Antibodies to Prevent HIV-1 Acquisition. N Engl J Med. 2021 Mar 18;384(11):1003-1014.

Viral suppression of HIV during pregnancy is important for both maternal health and prevention of mother-to-child transmission. Antiretroviral therapy (ART) is an effective method to manage HIV, but rigorous studies on the safety and efficacy of different ART regimens in pregnant women have been limited. To address this, a recent phase 3 trial was conducted to compare three ART regimens: dolutegravir, emtricitabine, and tenofovir alafenamide fumarate; dolutegravir, emtricitabine, and tenofovir disoproxil fumarate; and efavirenz, emtricitabine, and tenofovir disoproxil fumarate.

This randomized controlled, phase 3 clinical trial was conducted across 22 clinical research sites in 9 countries across the world. Pregnant women with confirmed HIV-1 infection were randomly assigned to one of the three ART regimens. The study showed that when started during pregnancy, dolutegravir-containing regimens were superior at suppressing viral RNA levels at delivery compared with the efavirenz, emtricitabine, and tenofovir disoproxil fumarate regimen. Additionally, the dolutegravir, emtricitabine, and tenofovir alafenamide fumarate regimen had the lowest frequency of adverse pregnancy outcomes and neonatal deaths.

These results support the WHO recommendation for use of dolutegravir in all populations, including pregnant women, and highlights a preference for the use of tenofovir alafenamide fumarate in combination with dolutegravir and emtricitabine over the other combinations. The findings of this study support efforts to reduce mortality, adverse outcomes, and transmission of HIV to the fetus through optimization of safe and effective ART regimens in pregnant individuals.   

Lockman et al. Efficacy and safety of dolutegravir with emtricitabine and tenofovir alafenamide fumarate or tenofovir disoproxil fumarate, and efavirenz, emtricitabine, and tenofovir disoproxil fumarate HIV antiretroviral therapy regimens started in pregnancy (IMPAACT 2010/VESTED): a multicentre, open-label, randomised, controlled, phase 3 trial.  Lancet. 2021 Apr 3;397(10281):1276-1292.

For pregnant women living with HIV, antiretroviral treatment (ART) is recommended to treat the infection in the mother and prevent mother-to-child HIV transmission. However, pregnancy may affect the way antiretroviral drugs are metabolized and may result in rendering the drug less effective. Studies that address the pharmacokinetics (rates of distribution, absorption, metabolism, and excretion) of drugs in pregnant women are critical to ensure the most appropriate dose is prescribed for maximum protection of mother and child.

This study evaluated the pharmacokinetics and safety of the combination of two antiretroviral drugs—darunavir and cobicistat—among pregnant women with HIV in the United States. Pregnant women in their second and third trimester taking daily darunavir and cobicistat were enrolled and followed up to twelve weeks after delivery, along with their infants. To assess drug pharmacokinetics over time, study participants underwent intensive sampling for a 24-hour period, starting just prior to taking their daily dose of ART. This 24-hour assessment occurred once during the second trimester, the third trimester, and post-delivery, to compare how the drugs were processed at different stages of pregnancy. Infants enrolled in the study were screened four times after birth on a harmonized schedule. Researchers found that both darunavir and cobicistat levels were much lower during the second and third trimesters when compared to postpartum levels. Additionally, the data revealed that transfer of these drugs across the placenta is limited.

The findings of this study suggest that standard darunavir and cobicistat dosing during pregnancy results in significantly lower exposure to the drug, which may increase the risk of treatment failure and mother-to-child transmission and should be avoided during pregnancy.

Reference: Momper et al. Pharmacokinetics of darunavir and cobicistat in pregnant and postpartum women with HIV, AIDS: July 1, 2021 - Volume 35 - Issue 8 - p 1191-1199.