Researchers document third known case of HIV remission involving stem cell transplant

A woman with HIV who received a cord blood stem cell transplant to treat acute myeloid leukemia has had no detectable levels of HIV for 14 months despite cessation of antiretroviral therapy (ART), according to a presentation at today’s Conference on Retroviruses and Opportunistic Infections (CROI).

Scanning electron micrograph of an HIV-infected H9 T cell, colorized in Halloween colors.NIAID

This is the third known case of HIV remission in an individual who received a stem cell transplant. The research was conducted by the International Maternal Pediatric Adolescent AIDS Clinical Trial Network (IMPAACT) P1107 observational study led by Yvonne Bryson, M.D., of the University of California Los Angeles, and Deborah Persaud, M.D., of Johns Hopkins University, Baltimore. The IMPAACT network is funded by the National Institutes of Health.

The IMPAACT P1107 study began in 2015 and was a U.S.-based observational study designed to describe the outcomes of up to 25 participants living with HIV who underwent a transplant with CCR5Δ32/Δ32 cord blood stem cells for the treatment of cancer, hematopoietic disease, or other underlying diseases. As a result of the genetic mutation CCR5Δ32/Δ32, missing cells lack CCR5 co-receptors, which is what HIV uses to infect cells. By killing off the cancerous immune cells via chemotherapy and then transplanting stem cells with the CCR5 genetic mutation, scientists theorize that people with HIV then develop an HIV-resistant immune system.

The case described today at the CROI meeting involves a woman of mixed race ancestry who had been on ART for HIV infection for four years at the time of her acute myeloid leukemia diagnosis. She achieved acute myeloid leukemia remission after chemotherapy. Prior to receiving the stem cell transplant, the participant’s HIV was well-controlled but detectable.

In 2017, she received a transplant of CCR5Δ32/Δ32 cord blood stem cells supplemented with adult donor cells from a relative (called haplo cells). After receiving the stem cell transplant, she engrafted with 100% cord blood cells at day 100 and had no detectable HIV. At 37 months post-transplant, the patient ceased ART. According to the study team, no HIV was detected in the participant for 14 months except for a transient detection of trace levels of HIV DNA in the woman’s blood cells at 14 weeks after stopping ART. The haplo cells only transiently engrafted and contributed to rapid recovery.

HIV remission resulting from a stem cell transplant had been previously observed in two cases. The first, known as the “Berlin patient” (a Caucasian male), experienced HIV remission for 12 years and was deemed cured of HIV; he died of leukemia in September 2020. The “London patient” (a Latino male) has been in HIV remission for more than 30 months. This third case of HIV remission suggests that CCRΔ5/Δ32 cord stem cell transplantation should be considered to achieve HIV remission and cure for people living with HIV who require such a transplant for other diseases, according to the study team.

FDA Approves Long-Acting Injectable Drug for HIV Prevention

Approval Marks Pivotal Expansion of HIV Prevention Options in the United States

The U.S. Food and Drug Administration has announced its first approval of a long-acting HIV prevention medication, marking a pivotal expansion of HIV prevention options in the United States.

Developed by ViiV Healthcare, the medicine is long-acting cabotegravir injected once every two months. FDA has approved the medicine for use by adults and adolescents weighing at least 35 kilograms who are at risk of sexually acquiring HIV. This milestone marks a vital expansion of biomedical HIV prevention options available to people in the United States. The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, thanks and congratulates everyone who led, conducted and participated in the research that led to this important development.

An estimated 34,800 people in the United States acquired HIV in 2019, the most recent year for which data are available. Men who have sex with men, transgender women who have sex with men, and Black cisgender women are among those disproportionately affected by HIV in this country.

Until today, the only FDA-licensed medications for HIV pre-exposure prophylaxis (PrEP) were daily oral pills containing the HIV drugs tenofovir and emtricitabine. These medications are highly effective at preventing HIV when taken daily as prescribed. However, taking a pill daily while feeling healthy can be challenging. Long-acting injectable cabotegravir PrEP is a less frequent, more discreet HIV prevention option that may be more desirable for some people. 

The FDA approval is based on data primarily from two NIH-supported clinical trials, HPTN 083 and HPTN 084. Both trials compared the safety and effectiveness of a PrEP regimen containing long-acting injectable cabotegravir with a regimen of daily oral PrEP. HPTN 083 enrolled more than 4,500 cisgender men who have sex with men and transgender women who have sex with men in Argentina, Brazil, Peru, South Africa, Thailand, the United States and Vietnam. HPTN 084 enrolled more than 3,200 cisgender women in Botswana, Eswatini, Kenya, Malawi, South Africa, Uganda and Zimbabwe. The two trials found that both HIV prevention methods were safe and highly effective, but injectable cabotegravir was more effective than daily oral PrEP at preventing HIV acquisition. 

The HPTN 083 and HPTN 084 trials were sponsored by NIAID and conducted by the NIH-funded HIV Prevention Trials Network (HPTN). NIAID and ViiV Healthcare co-funded both trials; the Bill & Melinda Gates Foundation also supported HPTN 084. HPTN is co-funded by NIAID, the National Institute of Mental Health, the National Institute on Drug Abuse, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, all part of NIH.

HIV Vaccine Candidate Does Not Sufficiently Protect Women Against HIV Infection

An investigational HIV vaccine tested in the “Imbokodo” clinical trial conducted in sub-Saharan Africa posed no safety concerns but did not provide sufficient protection against HIV infection, according to a primary analysis of the study data.

The Phase 2b proof-of-concept study, which began in November 2017, enrolled 2,637 women ages 18 to 35 years from five countries.

The Imbokodo primary analysis was conducted 24 months after participants received their first vaccinations.

The study’s primary endpoint was based on the difference in the number of new HIV infections between the placebo and vaccine groups from month seven (one month after the third vaccination timepoint) through month 24. When comparing the number of new HIV infections between study participants who were randomly assigned to receive either placebo or the investigational vaccine, statisticians found that 63 participants who received the placebo and 51 participants who received the experimental vaccine acquired HIV infection. Therefore, the investigational vaccine’s efficacy was 25.2% (95% confidence interval of vaccine efficacy -10.5% to 49.3%). The study vaccine was found to be safe with no serious adverse events associated with it. Study participants are being informed of the findings and will have follow-up visits with the study investigators. Further analysis of the Imbokodo study will continue, and the study is thought to have provided sufficient data for further immunological correlates research.

The Imbokodo study, also known as HVTN 705/HPX2008, is sponsored by Janssen Vaccines & Prevention B.V., part of the Janssen Pharmaceutical Companies of Johnson & Johnson. It is funded by two primary partners, the Bill & Melinda Gates Foundation (BMGF) and the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

“The development of a safe and effective vaccine to prevent HIV infection has proven to be a formidable scientific challenge,” said NIAID Director Anthony S. Fauci, M.D. “Although this is certainly not the study outcome for which we had hoped, we must apply the knowledge learned from the Imbokodo trial and continue our efforts to find a vaccine that will be protective against HIV.”

The investigational vaccine tested in the Imbokodo study is based on “mosaic” immunogens—vaccine components designed to induce immune responses against a wide variety of global HIV strains. The vaccine candidate used a strain of common-cold virus (adenovirus serotype 26, or Ad26), engineered to not cause illness, to deliver four (quadrivalent) mosaic antigens to spur an immune response. Earlier research indicated the vaccine was both well-tolerated and could induce an anti-HIV immune response. Imbokodo participants received four vaccinations during a one-year period. This included four doses of the investigational quadrivalent vaccine. The final two doses were administered together with doses of an HIV protein, clade C gp140, and an adjuvant to boost immune responses. Participants were followed for at least two years. The primary analysis occurred one year after the last study participant’s final vaccination.

Study participants were offered pre-exposure prophylaxis medication to prevent HIV infection during the clinical trial. The women who acquired HIV infection were directed to medical care and offered antiretroviral treatment.

NIAID provided funding for preclinical and early phase clinical development of the investigational mosaic HIV vaccine, which was initially developed by the laboratory of Dan H. Barouch, M.D., Ph.D., at Beth Israel Deaconness Medical Center, together with Janssen and other partners. The mosaic immunogens used in the experimental vaccine were designed by the Los Alamos National Laboratory. The Imbokodo study was conducted by the NIAID-funded HIV Vaccine Trials Network (HVTN), based at the Fred Hutchinson Cancer Research Center in Seattle. Additional support for the trial was provided by the U.S. Army Medical Research and Development Command; and the Ragon Institute of MGH, MIT and Harvard. The South African Medical Research Council helped to implement the study in South Africa.

To End HIV Epidemic, We Must Address Health Disparities – Expert Report

Scientific strides in HIV treatment and prevention have reduced transmissions and HIV-related deaths significantly in the United States in the past two decades. However, despite coordinated national efforts to implement HIV services, the epidemic persists, especially in the South.

It also disproportionately impacts marginalized groups, such as Black/African-American and Latinx communities, women, people who use drugs, men who have sex with men, and other sexual and gender minorities. Following the release of the HIV National Strategic Plan and marking two years since the launch of the Ending the HIV Epidemic: A Plan for America (EHE)—a U.S. Department of Health and Human Services initiative to reduce new HIV transmissions by at least 90% by 2030—researchers, advocates, and other stakeholders reported on the HIV epidemic response in The Lancet HIV in the USA Series, published online today.

Literature reviews, commentaries, and data analyses in the series outline recommendations to overcome barriers to implementing HIV services, such as counseling, testing, treatment, pre-exposure prophylaxis (PrEP), and syringe services programs. These services are critical to preventing new HIV transmissions and helping people living with HIV achieve and maintain a “durably undetectable” viral load (the amount of HIV in the blood). Maintaining an undetectable viral load both preserves individual health and eliminates the risk of sexually transmitting the virus to others, a concept known as Undetectable = Untransmittable (U=U).

By leveraging these services and addressing structural barriers, the experts argued, the EHE goals remain attainable and important, even as the COVID-19 pandemic presents new challenges and exacerbates existing health disparities.

The series was funded in part by the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health within HHS. The authors received additional support from the NIH-funded Centers for AIDS Research and NIH’s National Institute of Allergy and Infectious Diseases (NIAID).

“Scientific advances have transformed the course of HIV in individuals. To transform the course of the epidemic, we need to expand care and prevention strategically to those who need it most,” said NIDA Director Nora D. Volkow, M.D. “That means taking a hard look at who has been excluded from services and take immediate steps to overcome systemic barriers like stigma, structural racism, and other forms of discrimination to connect hardly reached people—such as individuals with substance use disorders—with HIV testing, prevention, and treatment.”

The series’ authors recommend allocating resources to the areas and populations most hard-hit by the HIV epidemic, especially the U.S. South, where 52% of new HIV transmissions occurred in 2018 despite being home to only 37% of the U.S. population. The recommendation echoes a key EHE strategy to prioritize the 57 counties, U.S. territories, and states in which more than half of U.S. HIV transmissions occurred in 2016 and 2017 for targeted interventions.

“To end the HIV epidemic, we must continue to develop and deploy novel HIV treatment and prevention strategies suited to the different needs and preferences of diverse populations disproportionately affected by HIV,” says NIAID Director Anthony S. Fauci, M.D. “It is also essential that HIV health services continue during the COVID-19 pandemic.” 

The authors explained that stark disparities in HIV outcomes also exist between certain age, racial, and ethnic groups, as well as between sexual and gender identities. While HIV diagnoses decreased overall and among white men who have sex with men between 2009 and 2018, new cases remained stable among Black/African-American men who have sex with men and increased among young people aged 25-34 and Latino men who have sex with men. While Blacks/African Americans make up only about 13% of the U.S. population, they accounted for 43% of HIV-related deaths in 2018. Researchers suggested that culturally appropriate, tailored interventions may help communities respond to the unique needs of people in—or at the intersections of—these groups.

Such interventions to promote HIV prevention and treatment adherence, the authors suggested, should take a multi-faceted approach and address the whole individual. 

“We have incredible tools to prevent and treat HIV, but people may not fully utilize them if they are facing personal or structural issues that pose more immediate hardship like substance use and mental health disorders,” said Chris Beyrer, M.D., M.P.H., investigator at the Johns Hopkins Bloomberg School of Public Health, Baltimore, and a lead author on the series. “You may struggle to take a daily medication if you are facing food insecurity or cannot find affordable treatment for your substance use disorder.”

The authors detailed additional economic barriers to accessing HIV health services in the United States. These included unequal access to Medicaid, on which 40% of people living with HIV rely, depending on one’s state of residence. The series’ authors recommended implementing universal healthcare coverage and expanding safety net programs for the uninsured or underinsured, such as the Ryan White HIV/AIDS Program, on which 82% of uninsured people living with HIV rely for medical care.

Stigma, discrimination, and bias by healthcare providers were among major barriers to care identified by the series authors and disproportionately affected marginalized racial groups, people who use drugs, and sexual and gender minorities. Healthcare professionals may help address these concerns by cultivating informed, supportive care practices that integrate mental health care and substance counselling. Because internalized HIV stigma can also negatively affect a person’s mental health and adherence to medication, the authors recommended promoting awareness of U=U through a national campaign.

While the series’ authors cite a large body of HIV research in making these recommendations, they also highlighted opportunities for additional research that could help end the HIV epidemic. Women make up one out of every four people living with HIV in the United States, and rates of HIV transmission are high among transgender people, demonstrating the need for continued efforts to ensure the needs of these populations are taken into account at all stages of clinical research. The authors also supported continued investment in efforts to develop a preventive HIV vaccine and HIV cure, both of which would accelerate an end to the HIV epidemic in the U.S. and around the globe.

Long-Acting Injectable Drug Prevents HIV Among Men Who Have Sex with Men and Transgender Women

An investigational long-acting form of the HIV drug cabotegravir injected once every 8 weeks safely and effectively prevents HIV acquisition in men who have sex with men and transgender women who have sex with men.

This finding, from a planned interim analysis of study data, marks the first time a large-scale clinical trial has shown a systemic, long-acting form of HIV prevention to be highly effective. The trial and an ongoing companion study evaluating long-acting injectable cabotegravir for HIV prevention in women are sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. 

Injection syringe with medicine on the buttock

Daily oral pills containing the drugs tenofovir and emtricitabine, such as Truvada or Descovy, are the only currently FDA-approved form of HIV pre-exposure prophylaxis, or PrEP. Taking a daily pill while feeling healthy can be challenging for some people, so investigators have been working to develop a long-acting alternative to oral PrEP that would be at least equally effective at preventing HIV. Such a long-acting prevention method may offer an easier, discreet option that may be more desirable for some people.       

NIAID collaborated on the Phase 2b/3 clinical trial in men who have sex with men and transgender women with ViiV Healthcare, Gilead Sciences, Inc., and the NIH-funded HIV Prevention Trials Network (HPTN). NIAID and ViiV Healthcare co-funded the trial, called HPTN 083, and ViiV Healthcare and Gilead Sciences, Inc., provided the study medications.

Beginning in 2016, the HPTN 083 study team enrolled 4,570 HIV-negative men who have sex with men and transgender women who have sex with men at 43 sites in Argentina, Brazil, Peru, South Africa, Thailand, the United States and Vietnam. The participants were considered at risk for HIV acquisition. Two-thirds of study participants were under 30 years of age, and 12% were transgender women. Half of the participants in the United States identified as black or African American. Participants were randomly assigned to receive either injections of cabotegravir and placebo oral tablets or placebo injections and daily oral Truvada tablets. Neither the participants nor the study team knew who was receiving which medication.

In a planned interim review of HPTN 083 on May 14, 2020, an independent data and safety monitoring board (DSMB) found that the study data clearly indicated that long-acting injectable cabotegravir was highly effective at preventing HIV in the study population. Among the 50 people in the trial who acquired HIV, 12 were receiving long-acting cabotegravir and 38 were receiving daily oral Truvada. This translated to an HIV incidence rate of 0.38% (95% confidence interval [CI] 0.20%-0.66%) in the cabotegravir group and 1.21% (95% CI 0.86%-1.66%) in the Truvada group. 

Both cabotegravir and Truvada were generally safe and well-tolerated in the study population, and the DSMB found no safety concerns. Most participants in the cabotegravir group (80%) reported pain or tenderness at the injection site, compared to only 31% of those in the Truvada group, who received placebo injections.

Consequently, the DSMB recommended that NIAID stop the blinded phase of the trial, which was originally expected to continue until 2021, and share the results. NIAID has accepted the DSMB’s recommendations and is releasing the results now to serve the interests of public health. The study investigators will report more detailed information about the HPTN 083 results in the coming weeks.

The HPTN 083 study team and participants are being notified of the study results. All study participants, including those who initially received Truvada, will be offered long-acting cabotegravir as soon as it can be made available. Study investigators will continue following HPTN 083 participants to gather additional data about the long-term safety of injectable cabotegravir for HIV prevention. 

The DSMB also reviewed data on May 14 from the Phase 3 companion study of long-acting cabotegravir for HIV prevention in women in southern and east Africa, called HPTN 084. That trial began a year later than HPTN 083, and the DSMB recommended that it continue as planned. To date, more than 3,000 sexually active women in seven African countries have enrolled in HPTN 084, which is co-funded by NIAID, ViiV Healthcare and the Bill & Melinda Gates Foundation.

Coming of age: Adolescent health

The world now has more young people than ever before – of the 7.2 billion people worldwide, over 3 billion are younger than 25 years, making up 42% of the world population. Around 1.2 billion of these young people are adolescents aged between 10 and 19 years.

Adolescence is a critical time of life. It is a time when people become independent individuals, forge new relationships, develop social skills and learn behaviours that will last the rest of their lives. It can also be one of the most challenging periods.
In this turbocharged neurological, physical, and emotional transition from childhood to adulthood, young people face a range of health risks. They are often exposed to harmful products such as tobacco, alcohol and drugs, they face greater risks of violence (including homicide) and road traffic injuries than in childhood, and can experience devastating mental health issues such as depression, anxiety, self-harm, substance abuse and addiction to video games, as well as eating disorders and suicide. Young people can also face sexual health issues such as sexually transmitted diseases or teenage pregnancy.

Many of these issues are linked to wider societal determinants and social norms. For example, pressures to conform to ideals about body image, normalization of recreational drinking in media, social exclusion, challenges in accessing support services, coupled with rapid physiological and neurological changes and the urge for exploration and experimentation, can make it hard to cope with the varied challenges that today’s youth will almost certainly encounter.

Depending on where they live in the world, young people may face an even wider range of threats to their health, including racial or gender discrimination or violence, human rights violations, conflict or social disruption from natural disasters, being overweight or obese, female genital mutilation (FGM), forced child marriages or sexual exploitation and abuse.  

The numbers are striking: about 3000 adolescents die every day; in 2016, more than 1.1 million adolescents aged 10-19 lost their lives, mainly to preventable causes such as road injuries, complications of pregnancy or giving birth, or because of HIV/AIDS. 

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Story published courtesy of the WHO

Meeting the challenge of engaging men in HIV prevention and treatment

A new commentary from National Institutes of Health scientists asserts that engaging men in HIV prevention and care is essential to the goal of ending the HIV pandemic.

Navy Petty Officer 1st Class Oliver Arceo draws blood from a sailor for routine HIV testing.U.S. Navy photo by Petty Officer 1st Class Marie Montez

The article by Adeola Adeyeye, M.D., M.P.A., and David Burns, M.D., M.P.H., of the National Institute of Allergy and Infectious Diseases (NIAID) and Michael Stirratt, Ph.D., of the National Institute of Mental Health (NIMH) also discusses potential solutions.

Scientific research has proven that people with HIV who take antiretroviral therapy (ART) as prescribed and achieve and maintain an undetectable level of virus in the blood have effectively no risk of transmitting the virus to their HIV-uninfected sexual partners.

Other research has shown that when HIV-uninfected people consistently take a single daily oral tablet of the antiretroviral drugs emtricitabine/tenofovir disoproxil fumarate, their risk of acquiring HIV infection is reduced by as much as 95 percent. The challenge is implementing these approaches, known as treatment as prevention and pre-exposure prophylaxis (PrEP), and other forms of HIV prevention in a timely manner among everyone who needs them.

The authors point out that in sub-Saharan Africa, men are less likely than women to know their HIV status, engage in HIV care in a timely manner, stay in care and maintain an undetectable level of virus in the blood. The authors also note that in the United States, disparities by age, race and ethnicity persist in the use of ART among men who have sex with men.

New strategies to engage men in HIV prevention and treatment must address three critical issues, the authors write. These are the lack of “touch points” where men naturally interact with the health care system; gender norms and prevailing constructs of masculinity, which typically subordinate health care to other concerns; and HIV stigma and discrimination.

The authors describe innovative approaches being explored to overcome these challenges, including establishing HIV testing and care in workplaces and sports programs, ART home delivery, HIV self-testing, and the MenStar Coalition(link is external) created by the President’s Emergency Plan for AIDS Relief (PEPFAR), Unitaid, the Elton John AIDS Foundation and others to expand HIV diagnosis and treatment for men.

Also, NIAID and NIMH are co-sponsoring two research Funding Opportunity Announcements designed to support development and testing of strategies to increase the engagement of men in HIV prevention and care domestically and globally.