Genetic Variation Tied to Faster Progression to AIDS

A variation in the allele (one of two or more alternative forms of a gene) of HLA, a molecule that helps T-cells "initiat[e] a specific immune response" against diseases, has a "substantial effect" on how quickly an HIV patient progresses to AIDS, according to a study in yesterday's New England Journal of Medicine. Researchers led by Mary Carrington, an immunologist with the NIH, analyzed blood from 850 HIV-positive individuals with known infection dates and monitored their disease progression. "[A]ccelerated progression to AIDS was completely attributable" to a variation in the HLA-B*35 allele, called Px (NEJM, 5/31). Patients with a Px variation took about seven years to reach AIDS diagnosis, while patients without the variation averaged 11 to 12 years to an AIDS diagnosis. The Px variation is present in almost 12% of the population and differs "only slightly" from other versions of the HLA-B genetic code (Johannes, Wall Street Journal, 5/31).

What Does it All Mean?
It remains unclear why the variation speeds disease progression. "We don't know ... if B35Px actively causes damage to an HIV-infected person or whether it's just simply sitting there doing nothing and, because it's not being useful, it's actually hurting the individual," Carrington said. A blood test for the variation would be "relatively simple," she said. In the future, such a test could help doctors better tailor anti-AIDS medications to their patients' needs in order to "more aggressively" attack HIV, Bruce Walker, a Harvard AIDS researcher, said. He added that more research is needed to determine whether it would "prove to be beneficial" to treat patients with the variation earlier in order to slow the progression of the disease, as the study's authors suggested (Palca, "All Things Considered," NPR, 5/30). Walker cautioned that patients with the variation may be "less likely to have a good response" to sometimes "toxic" anti-AIDS medications (Wall Street Journal, 5/31).

Natural Selection May Reduce Susceptibility to AIDS
The "high prevalance of HIV in Africa creates conditions for natural selection" of traits that slow HIV progression, researcher Paul Schliekelman of the University of California-Berkeley and colleagues say in a study published in the current issue of Nature. The high infection level "exerts selection pressure" on the chemokine cell-surface receptor CCR5, which in some forms has been shown to delay disease progression to AIDS by two to four years (Senior, Lancet, 6/2). The team determined that in 100 years, the frequency of the CCR5 variation that delays AIDS onset will rise so that more than 50% of the population will carry the mutation, increasing the average amount of time it takes HIV to progress to AIDS by about a year. Although this seems a beneficial development, Schliekelman said that the higher prevalence of the CCR5 mutation "could make the epidemic worse," as HIV-positive individuals will live longer without developing symptoms and would have "more of a chance" of spreading the virus (Munro, National Post, 5/31). Rupert Kaul of the University of Oxford said that the findings provide "insight into the impact that the HIV epidemic will have at the public health level" and gives health workers "even greater incentive" to try and stem infections among adolescents. However, he noted that the researchers only looked at genetic variations that delay disease progression and researchers "would expect the HIV epidemic to select even more strongly for alleles associated with resistance to HIV infection" (Senior, Lancet, 6/2).