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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