Men who received
Thai RV144 vaccine who nonetheless became infected with HIV had lower viral
loads in their semen than men who received placebo, a new analysis of the
vaccine study reports in the Journal of
The report also
finds tantalising signs of long-term improvements in HIV viral load and CD4
count, starting four years after infection, in HIV-positive vaccine recipients.
However the researchers stress that this
finding is only just statistically significant and could either be the result
of the vaccine slowing long-term disease progression in general, or of it speeding
up progression and therefore increasing mortality in a subset of ‘fast
This study is
encouraging because it revives the idea that a vaccine or other biomedical
prevention technique could ‘work’ even in people who become infected, by
slowing down or stopping progression to AIDS and/or by permanently reducing
their viral load so they are less infectious. Vaccines such as the one in the STEP Study,
which aimed to stimulate immune cells to kill cells already infected with HIV, were
expected to do this, but proved disappointing.
published this month found similar, though stronger effects in a study of
monkeys who became infected with HIV despite taking pre-exposure prophylaxis
vaccine trial was the first-ever HIV vaccine efficacy trial to report a
positive result. However the efficacy observed was only 31% and hovered close
to the boundary of statistical insignificance.
hunt for the changes in the immune system that might have protected individuals
from infection found very few differences between recipients of vaccine and
placebo, but it
did find two. Firstly, vaccine recipients had higher levels of antibodies
to two specific parts of the HIV gp120 envelope protein, the V2 and V3 loops.
Secondly, vaccine recipients had lower
levels of a ubiquitous broad-spectrum antibody called immunoglobulin A (igA),
which is secreted in large amounts by the mucous membranes. It is thought that
too much igA may have interfered with a process called antibody-dependent
cellular cytotoxicity (ADCC) whereby other broad-spectrum antibodies stimulated
by the vaccine induce the anti-HIV activation of other parts of the immune
analysis looked at the course of HIV infection in 114 trial participants who
were infected with HIV over a period of 5.5 years, and compared what happened
to the 49 vaccine recipients with what happened to the 65 placebo recipients. This
total was a ‘modified intent-to-treat’ group, consisting of any trial
participant who was infected with HIV after receiving the first shot of vaccine
or placebo, but excluding six subjects who were infected before receiving a
shot. The study also looked at a ‘per-protocol’ group of 90 participants, 39 of
them receiving vaccine, who received all four shots of the vaccine or placebo
and who were infected al least six months after receiving their first shot.
It used a
composite primary endpoint of disease progression which combined time to initiation
of antiretroviral therapy (ART) or AIDS-defining illness or the CD4 count
falling below 350 cells/mm3; 80% of people reached this endpoint because
of this last criterion.