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BMJ 2008; 337 doi: (Published 19 November 2008) Cite this as: BMJ 2008;337:a2571

Failed vaccine is another blow for HIV control

An adenovirus vaccine designed to boost cell mediated immunity against HIV has failed, disappointing HIV researchers and casting doubt on the animal models that suggested it might work. The vaccine, which expressed three HIV genes—gag, pol, and nef—did not prevent infections in participants in a placebo controlled trial and had no effect on viral replication in those infected. The data monitoring committee recognised the futility of the trial at its first meeting, when it became clear that men given the vaccine were, if anything, more likely than controls to get HIV (4.6% v 3.1% each year; hazard ratio 1.5, 95% CI 0.97 to 2.3). The trial included 3000 men and women at high risk, mostly men who have sex with men and women at high risk because of sex work or drug use. Exploratory analyses suggested the increased risk was confined to uncircumcised men (3.8, 1.5 to 9.3) and those with antibodies against the adenovirus vector (2.3, 1.2 to 4.3).

The researchers don’t know yet why the vaccine failed, when a prototype worked well in standard primate models. They looked for differences in immune responses between men who became HIV positive and those who didn’t (doi:10.1016/S0140-6736(08)61593-7). There weren’t any—the vaccine looked immunogenic in both groups, inducing HIV specific T cells as expected. But the response clearly wasn’t good enough, possibly because it was too weak, too narrow, or somehow qualitatively wrong, say the researchers. After decades of research, we still don’t know what an effective immune response to HIV looks like.

Antioxidant supplements fail to prevent cardiovascular disease, again

Antioxidant vitamins C and E do not prevent cardiovascular disease in healthy middle aged men, according to a placebo controlled trial of US doctors. The trial lasted 10 years and included 14 641 male doctors who were at least 50 when enrolled. Most (94.9%) had no cardiovascular disease …

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