Featured news from NHIVNA
HIV-related news from NAM
It’s all go for a new HIV vaccine efficacy trial this year
Gus Cairns, 2016-07-19 21:10:00
A new efficacy trial for an HIV vaccine – only the seventh
ever conducted in the history of the epidemic – will start this November, the AIDS 2016 conference heard today.
The HVTN 702
study will enrol 5400 men and women in southern Africa, and is planned to
last for four years. It was actually announced that it would go forward on May
18 this year because a pilot study, HVTN 100, had met the criteria for the
vaccine being taken forward into the larger study. But today was the first time
that researchers revealed how well it had met those criteria.
Presenter Linda Gail-Bekker of the Desmond Tutu HIV Foundation
told the conference that the story of HVTN 100 goes back to 2009, when the RV144 vaccine study
was the first to show signs of efficacy, with 31% fewer infections in people given
vaccine than in ones given placebo. Subsequent investigations showed that the
vaccine’s effect were real and due
to an unpredicted kind of immune response.
However RV144’s effect was very weak and tailed off rapidly
over time; at the end of the first year it was 60%, but a post-hoc analysis
showed that after two years it had stopped contributing any further degree of
protection against HIV.
There was clearly a need for a more potent vaccine of the
same type. It took a long time to develop this partly because few people had
expected RV144 to be successful and partly because a decision was taken to
refashion the vaccine so it was tuned to HIV subtype C, the predominant
subtype found in southern Africa, rather than to subtypes B and E, the ones
most common in Thailand where RV144 was conducted. HVTN702 will be conducted in the countries where subtype C predominates, namely southern Africa up to Tanzania. It is not known if it will have cross-efficacy against other subtypes.
Like RV144, the HVTN100 vaccine consisted of two different kinds
of shot; a ‘prime’ vaccine, ALVAC, consisting of HIV subtype C components
contained inside a vector, the shell of another virus, canarypox, that gets
into cells but is harmless to humans; and a ‘boost’ shot of naked gp120
envelope protein from HIV, coupled with an adjuvant or chemical booster called MF
The HVTN100 vaccine was given in five doses; there are two
initial shots of ALVAC a month apart, then shots of both components at months
three, six and twelve. Two hundred and ten people were given the actual vaccine
and 42 a placebo, and the trial was conducted at five centres in South Africa.
The HVTN100 study is still going on; the immunogenicity
results presented here only come from 6.5 months into the study, with the
12-month booster not yet given, and primary results remain blinded. However,
the HVTN has met its secondary objective of passing the immunogenicity criteria
that would lead to it being carried forward into HVTN702.
These four criteria, with the actual responses, are as
Criterion: The vaccine produces an antibody response to the HIV
env protein in 75% of subjects.
Response: It produced an antibody response in 100% of subjects.
Criterion: The vaccine
produced an antibody response to the HIV env protein that was at least 1.5
times greater than that seen in RV144.
Response: The antibody response was in fact 3.6
to 8.8 times larger than that seen in RV144, depending on the specific HIV
antigen responded to.
vaccine produced a CD4 response to the vaccine in at least 36% of subjects’ CD4
cells, and non-inferior to RV144.
Response: In fact, a CD4 response was seen in 58%
of subjects, 16% more than in RV144.
Criterion: At least
63% of subjects given vaccine show an antibody response to the V1 and V2
regions of the HIV envelope protein. This criterion is particularly important
as it was this response that correlated with efficacy in RV144. The 63% was
chosen as the degree of response that would predict a 50% efficacious vaccine
that sustained its efficacy for at least two years.
Response: In fact there was a cumulative response
to the V1 and V2 regions in over 80% of subjects.
Linda Gail-Bekker showed evidence of other immunogenicity
that was not included in these original criteria, including the fact that the
HVTN100 vaccine produced nearly twice as many CD4 cells displaying ‘polyfunctionality’,
a versatile immune response to HIV that predicts significant efficacy.
In short, the HVTN100 vaccine comfortably out-performed
RV144, at least in terms of immune indicators that are regarded as correlates
of efficacy. However, there is no substitute in vaccine trials for actually
giving it to large numbers of at-risk people and measuring how many, if any,
infections it prevents. There have been disappointments before, as when the human response
in the STEP trial, which closed due to lack of efficacy in 2007, did not
match that predicted by animal models and did not correlate with efficacy.
We can say therefore that the signs are very promising
that the HVTN702 trial may show significant efficacy, but we have been unpleasantly surprised
before, and may not know that full results for four years.