An analysis of the fitness landscape of genetic interactions in HIV-1 drug resistance is reported this week in Nature Genetics. Current drug regimens for treating HIV infection include over 20 different drugs, and over 200 mutations have been associated with drug resistance.
Sebastian Bonhoeffer and colleagues examined 70,081 virus samples from HIV-1 subtype B infected individuals undergoing routine drug resistance testing. They sequenced the protease and reverse transcriptase genes from the population of virus samples, and measured the in vitro fitness of virus samples in the absence of drugs, or in the presence of one of 15 different individual drugs. They find that interactions between variants contribute significantly to the fitness landscape of HIV-1 virus protease and reverse transcriptase.