New Data On Twice-yearly Lenacapavir For HIV Prevention Announced At HIVR4P 2024

7 October 2024 (Lima, Peru) – New data from the PURPOSE 2 study of twice-yearly lenacapavir for HIV prevention are among the scientific highlights at HIVR4P 2024, the 5th HIV Research for Prevention Conference, taking place in Lima, Peru, and virtually from 6 to 10 October.

At the official HIVR4P 2024 press conference today, PURPOSE 2 principal investigator Colleen Kelley of Emory University announced new efficacy, safety and demographic data from the trial, in which only two HIV acquisitions occurred among 2,184 trial participants who were randomized to receive subcutaneous lenacapavir every six months (for details, see the press release issued today by Gilead Sciences, which developed lenacapavir). Kelley will formally present these data at HIVR4P 2024 on 8 October at a session starting at 11:00 Peru time (PET).

PURPOSE 2 enrolled HIV-negative cisgender gay, bisexual and other men, trans women, trans men and gender non-binary individuals in Argentina, Brazil, Mexico, Peru, South Africa, Thailand and the United States who have sex with partners assigned male at birth. Last month, topline results from an interim analysis indicated that lenacapavir reduced HIV acquisitions by 96% compared to background HIV incidence and demonstrated superiority to daily F/TDF for HIV prevention. Prior to that, the PURPOSE 1 study demonstrated that lenacapavir reduced HIV acquisitions by 100% and demonstrated superiority to daily F/TDF among cisgender women in Africa. Gilead Sciences has said it will begin a series of global regulatory filings by the end of 2024.

“These findings confirm that lenacapavir for PrEP has the potential to transform the global HIV prevention landscape for people of all genders,” Beatriz Grinsztejn, the President of IAS – the International AIDS Society – said. “All stakeholders must work together now, ahead of regulatory approvals, to plan for a rapid, equitable global rollout of this important new prevention tool.”

“The IAS commends Gilead for signing voluntary licensing agreements with generic manufacturers to increase access to lenacapavir in high-incidence, resource-limited countries,” Grinsztejn added. “However, we’re highly concerned that these agreements do not cover large parts of the world, including the majority of countries in Latin America.”

Grinsztejn is also a member of the PURPOSE 2 study team, an HIVR4P 2024 Organizing Committee member and the Director of the HIV/AIDS Clinical Research Unit at the Evandro Chagas National Institute of Infectious Diseases – FIOCRUZ in Brazil.

Other scientific highlights at HIVR4P 2024 include:

• Evidence that the three-month dapivirine vaginal ring is pharmacokinetically superior to the monthly ring
• A PrEP choice study finding moderate uptake of the dapivirine vaginal ring among women in Africa
• A study finding no pharmacologic interactions between long-acting cabotegravir for HIV prevention and hormonal contraceptives
• A drug-agnostic transcutaneously refillable subdermal implant that provides ultra-long-acting delivery of antiretrovirals for HIV prevention
• Data showing that an innovative dosing strategy improves early immune responses to an experimental germline-targeting HIV vaccine

Hosted by the IAS, HIVR4P is the only global scientific conference focused exclusively on the rapidly evolving field of HIV prevention research. It brings together the global scientific community to address the biggest challenges and opportunities in HIV prevention, including vaccines, microbicides, PrEP, treatment as prevention and biomedical interventions, as well as the social and behavioural implications of these advances.

This year, the conference is being held in Latin America for the first time, creating an opportunity to highlight HIV prevention needs in the region.

“We hope that by holding the conference in Lima, we can help draw attention to the urgent need to scale up HIV prevention efforts across Latin America,” Grinsztejn said. “Ours is one of the only regions in the world where HIV is on the rise. It’s alarming that new HIV acquisitions in Latin America increased by 9% between 2010 and 2023 despite broadly expanded access to antiretroviral therapy. Unfortunately, the scale of powerful new prevention tools like PrEP remains significantly limited.”

Three-month dapivirine vaginal ring for HIV prevention shows promise

Efficacy of the three-month dapivirine vaginal ring (DVR) is likely to be "at least equal" to that of the monthly DVR, according to a study from South Africa.

The monthly DVR, which is the world's first woman-controlled HIV prevention product, has been approved for use in 11 African countries. When inserted into the vagina, it slowly releases dapivirine, an antiretroviral drug, over a one-month period, helping to reduce the woman’s likelihood of acquiring HIV. After a month, it must be replaced for continued protection.

While research has shown that the monthly DVR is appealing to many women, a longer-lasting version will have a lower annual cost and may be more convenient to users.

The new study, IPM 054, is a Phase I, open-label, randomized crossover trial investigating the relative bioavailability of a three-month (100mg) DVR compared with the one-month (25mg) DVR. A total of 124 HIV-negative women enrolled in the study. Based on dapivirine concentrations in plasma after women used each type of ring, the study team determined that the three-month DVR is pharmacokinetically superior to the monthly DVR.

According to presenter Jeremy Nuttall of the Population Council’s Center for Biomedical Research, the three-month DVR will expand options and choice for women to protect their health and accelerate global efforts to end the HIV epidemic. By increasing convenience to women, the three-month ring may also increase acceptability and adherence, which may lead to increased effectiveness.

Abstract and session: Pharmacokinetic superiority of a 3-month dapivirine vaginal ring (100 mg) compared to the 1-month dapivirine vaginal ring (25 mg), HIVR4P 2024 late-breaker selection (2343).

PrEP choice study finds moderate uptake of dapivirine vaginal ring among women in Africa

A study conducted in five African countries found that when given a choice between different types of PrEP for HIV prevention, many women selected the dapivirine vaginal ring (DVR) – also known as the PrEP ring – although most chose daily oral PrEP, according to presenter Elizabeth Irungu of Jhpiego.

The CATALYST study, which is funded by PEPFAR and USAID through the MOSAIC project, aims to characterize an enhanced service delivery package for informed PrEP choice for women at public health sites in Kenya, Lesotho, South Africa, Uganda and Zimbabwe. Of 3,967 participants enrolled, 45% were aged 24 years or younger, 26% reported sex work, 9% were pregnant, 12% were breastfeeding and 68% had never taken PrEP.

At enrolment, 66% of participants chose oral PrEP, 30% chose the DVR and 4% chose no PrEP method. DVR uptake was 15% among pregnant women and 21% among breastfeeding women, where allowed.

In multivariable analysis among those who had choice, those having multiple sex partners in the past three months and those currently using a contraceptive method were more likely to choose the DVR instead of oral PrEP. Participants under the age of 25, new PrEP users and participants who were pregnant or breastfeeding were less likely to choose the DVR.

Participants who chose oral PrEP said they did so because it is easy to use (59%) and works well (32%); those who chose the DVR did so because it is easy to use (57%) and does not require swallowing pills (53%). According to the study team, women are taking advantage of PrEP choice. The results demonstrate moderate uptake of the DVR when offered within existing real-world PrEP programmes, and the findings will inform implementation of PrEP choice in the region.

The CATALYST study is ongoing and will soon produce evidence of how patterns of PrEP use change with choice of oral PrEP, the DVR and long-acting cabotegravir for HIV prevention.

Abstract and session: PrEP choice for women in Africa: Uptake of oral PrEP and PrEP ring, Delivering on the promise of PrEP choice (257)

HPTN 084 finds no pharmacologic interactions between long-acting cabotegravir and hormonal contraceptives

A sub-study of HPTN 084 observed no pharmacologic interactions between long-acting cabotegravir (CAB-LA) and hormonal contraceptives, according to presenter Mark Marzinke of the Johns Hopkins University School of Medicine.

HPTN 084 reported in 2020 that CAB-LA, injected once every eight weeks, was well tolerated and significantly reduced the likelihood of HIV acquisition in women compared to daily oral TDF/FTC. During the blinded phase of the trial, participants were required to use long-acting reversible contraceptives.

The sub-study assessed potential pharmacologic interactions between two types of PrEP (CAB-LA or TDF/FTC) and three hormonal contraceptives: etonogestrel, norethindrone or medroxyprogesterone acetate (MPA).

A total of 190 participants consented to take part in the sub-study across both study arms. Plasma CAB concentrations were evaluated from enrolment through study week 73; plasma tenofovir concentrations were measured at enrolment and study weeks 25, 49 and 73. Plasma concentrations of etonogestrel, norethindrone and MPA were also evaluated at enrolment and weeks 25, 49 and 73 for participants using each reported contraceptive type.

Post-enrolment contraceptive concentrations were comparable between study arms for all three contraceptive types. The percentage of participants with concentrations above thresholds associated with ovulation suppression was high and did not differ between arms. CAB concentrations were comparable across contraceptive types. However, tenofovir concentrations were unquantifiable for most participants, irrespective of contraceptive agent; this was attributed to low adherence to TDF/FTC among participants included in this analysis.

The study team concluded that while interactions between CAB-LA and etonogestrel, norethindrone and MPA were not observed, associations between TDF/FTC and hormone concentrations could not be effectively evaluated due to low adherence to TDF/FTC.

Abstract and session: Evaluation of potential pharmacologic interactions between CAB-LA or TDF/FTC and hormonal contraceptive agents: a tertiary analysis of HPTN 084, PrEP in pregnancy and lactation (719)

Drug-agnostic transcutaneously refillable subdermal implant provides ultra-long-acting delivery of antiretrovirals for HIV prevention

Alessandro Grattoni of Houston Methodist Hospital presented preclinical data on a subdermal implant designed for ultra-long-acting delivery of antiretrovirals for HIV prevention.

The implant consists of a titanium casing and a silicon nanochannel membrane that controls drug release. Unlike traditional implants, it can be refilled through the skin with a minimally invasive injection.

Tests in nonhuman primates showed that when loaded with islatravir, an antiretroviral drug, the implant was safe and tolerable, sustained drug release for 29 months without fluctuation, and provided 100% protection against rectal and vaginal SHIV exposures. When loaded with MK-8527, a different antiretroviral drug, the implant was also tolerable and sustained drug release.

The study team concluded that the implant offers safe, effective and long-lasting protection against HIV with minimally invasive transcutaneous refillability that "extends release potentially throughout the recipient’s lifespan".

The team anticipates that the implant could serve as a "multiprevention technology" because it could deliver one or more antiretrovirals for PrEP or HIV treatment, potentially in combination with contraceptives. They also estimate that a drug-loaded implant could be produced at a low cost, making it a viable option for low-resource countries.

Abstract and session: Drug-agnostic transcutaneously-refillable subdermal implant for ultra-long-acting delivery of antiretrovirals for HIV prevention, Prevention advances: PrEP, DoxyPEP and MPTs (2159)

Innovative dosing strategy improves early immune responses in HIV vaccine study

A vaccination strategy called "fractional escalating dosing" improves early immune responses to an experimental germline-targeting HIV vaccine, according to research presented by William Hahn of the Fred Hutchinson Cancer Institute.

Vaccines are typically delivered through a single “bolus” administration. However, in preclinical models, HIV vaccination strategies, pioneered by Darrell Irvine, Shane Crotty, Dennis Burton and others, that mimic the sustained antigen load that the immune system experiences during acute infection have produced a more robust immune response. This study tested the effectiveness and tolerability of fractional escalating dosing, a strategy based on these concepts.

HVTN 301 is a first-in-human, double-blind, placebo-controlled trial evaluating an HIV immunogen nanoparticle (426.Mod.Core-C4b) adjuvanted with the TLR7 agonist 3M-052 AF/Alum intended to expand CD4-binding site bnAb lineage B cells. The study compared 426.mod.Core administered as a single 100mcg bolus dose versus a fractional escalating dose – a series of smaller, incremental doses that also totalled 100mcg, given over three weeks in the priming phase.

Testing in 53 HIV-negative adults showed that the vaccine was safe and tolerable with either bolus or fractional administration. Four weeks after the initial prime, fractional escalating dosing led to enhanced antibody, B cell and CD4+ T cell responses.

According to the study team, these results establish proof of concept that sustained antigen/adjuvant exposure can improve immune responses for preventive HIV vaccines intended to elicit broadly neutralizing antibodies during the priming phase. Additional research is needed to identify strategies based on this concept that can be more readily translated into clinical practice.

Abstract and session: Vaccination with a novel fractional escalating dose strategy improves early humoral responses with a novel germline targeting HIV vaccine (426.mod.core-C4b): preliminary results from HVTN 301, Emerging data from recent human clinical vaccine trials (225)

The summaries above are based on submitted abstracts; in some cases, presenters have provided updated information. Final data presented at the conference may change.

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About the HIV Research for Prevention Conference (HIVR4P)

The HIV Research for Prevention Conference is the only global scientific conference focused exclusively on the challenging and fast-growing field of HIV prevention research. This conference fosters interdisciplinary knowledge exchange on HIV vaccines, microbicides, PrEP, treatment as prevention and biomedical interventions, as well as their social and behavioural implications. HIVR4P 2024, the 5th HIV Research for Prevention Conference, will take place in Lima, Peru, and virtually from 6 to 10 October 2024, with an estimated 1,500 participants attending, mostly in person.

About the International AIDS Society

IAS – the International AIDS Society – convenes, educates and advocates for a world in which HIV no longer presents a threat to public health and individual well-being. After the emergence of HIV and AIDS, concerned scientists created the IAS to bring together experts from across the world and disciplines to promote a concerted HIV response. Today, the IAS and its members unite scientists, policy makers and activists to galvanize the scientific response, build global solidarity and enhance human dignity for all those living with and affected by HIV. The IAS also hosts the world’s most prestigious HIV conferences: the International AIDS Conference, the IAS Conference on HIV Science and the HIV Research for Prevention Conference.

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