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Lower seminal viral load and hints of long-term viral control seen in Thai HIV vaccine recipients
Gus Cairns, 2012-08-17 09:20:00

Men who received the Thai RV144 vaccine who nonetheless became infected with HIV had lover viral loads in their semen than men who received placebo, a new analysis of the vaccine study reports in the Journal of Infectious Diseases.   

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 progressors’.

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.

Another study published this month found similar, though stronger effects in a study of monkeys who became infected with HIV despite taking pre-exposure prophylaxis (PrEP).

The RV144 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.

A subsequent 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 system.

The current 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.

Source:1