A new phase III
HIV vaccine trial will soon be underway for men who have sex with men and
transgender people. The study, called Mosaico, will evaluate a four-shot
regimen of a vaccine designed to provide protection against the many different
strains of HIV around the world.
“We are committed to ensuring that HIV vaccine trial results are
generalizable to the populations that carry the greatest burden of HIV
infection,” said Dr Susan Buchbinder, Mosaico protocol chair and director of
Bridge HIV at the San Francisco Department of Public Health.
Buchbinder and
others involved in the vaccine's development and trial administration discussed
the Mosaico study at a session preceding the opening of the 10th International AIDS
Society Conference on HIV Science (IAS 2019) yesterday in Mexico City.
Mosaico, also
known as HVTN 706, is a joint public-private effort involving the US National
Institutes of Health (NIH), the HIV Vaccine Trials Network headquartered at the Fred Hutchinson Cancer
Research Center, the US Army Medical Research and Development Command and Janssen (part
of Johnson & Johnson).
The stage was set
for Mosaico by a series of earlier monkey and human studies, the first of which
began 15 years ago, according to Dr Dan Barouch, director
of the Center for Virology and Vaccine Research at Beth Israel Deaconess
Medical Center in Boston. These studies refined the vaccine's composition and determined the most
effective dosing regimen.
The vaccine to
be tested, dubbed Ad26.Mos4.HIV, uses an engineered adenovirus vector – a
harmless relative of the common cold virus – to deliver a so-called mosaic of
optimised HIV immunogens, or antigens that stimulate immune responses. This
antigen combination "is not found in
any individual virus, but rather it's bits and pieces of different
viruses," optimised to cover multiple global strains of HIV, Barouch said.
The third and fourth injections will be
accompanied by a combination of gp140 proteins, which make up the HIV envelope,
from Clade C (the predominant HIV type in much of Africa and Asia) and a mosaic
of gp140 from other strains.
Previously, the APPROACH study compared
different boosters for the third and fourth vaccine doses, the TRAVERSE trial
led to the selection of a tetravalent mosaic with four target HIV antigens and
the ASCENT trial compared different versions of gp140 for the booster. The
latest data from APPROACH and ASCENT will be presented later in the conference.
A similar vaccine regimen – but with only
Clade C and not mosaic gp140 in the booster – is now being tested in the ongoing
phase IIb Imbokodo trial (HVTN 705). Started in 2017, this study recently competed enrolment
of 2600 women living in southern Africa. Participants were randomly assigned to
receive the vaccine or placebo injections.
Mosaico will evaluate the selected vaccine in
3800 cisgender men who have sex with men and transgender people, aged 18 to 60,
living in North America, South America and Europe, where Clade B HIV is
predominant. There will be 24 study sites in the US, nine in Brazil, five in
Peru, four in Argentina and three in Mexico. European sites will be in Spain
(six sites), Italy and Poland (three sites each). Buchbinder said enrolment is
expected to start in September.
Eligible individuals must be at increased
risk for HIV, meeting one of the following criteria within the past six months:
- They have had condomless receptive anal or vaginal sex outside a
stable (12 months) monogamous relationship with a partner known to be either HIV
negative or HIV positive with viral suppression on antiretroviral therapy;
- They have been diagnosed with rectal or urethral gonorrhea or
chlamydia or a new case of syphilis;
- They have used any stimulants, including cocaine or amphetamine;
- They have had five or more sexual partners.
Here too, participants will be randomised to
receive the vaccine – four shots of AD26.Mos4.HIV at study entry, month 3,
month 6 and month 12, with the latter two shots accompanied by Clade C + mosaic
gp140 – or a placebo.
All participants will be offered a comprehensive
prevention package. The study will compare the rate of new HIV infections in
the group receiving the vaccine plus the prevention package versus those who
receive the prevention package with the placebo.
Importantly, the standard prevention package
has evolved since earlier vaccine trials and it now includes tenofovir disoproxil
fumarate/emtricitabine for pre-exposure prophylaxis (PrEP). The vaccine aims to
meet a need for people who are not already using an effective prevention method,
Buchbinder explained. For this reason, prospective participants will be
informed about and helped to access PrEP during the screening process, and
those who opt to use it will not be enrolled. That is, eligible prospects will
either be linked to PrEP services or enrolled in the trial. However, once
enrolled, participants may decide to start PrEP at any time and remain in the
study.
After
consultations with clinical trialists, statisticians, representatives of the US
Food and Drug Administration and NIH, ethicists, advocates and community
members, the investigators decided it would be ethical to enrol people who opt out of PrEP. "They must have a
real option to use PrEP and we acknowledge participants' views on PrEP might
change during the study," Buchbinder said.
Initial results
from Imbokodo are expected in 2021. Mosaico results are anticipated in
2023.