Analysis of HIV-1 variation in blood and semen during treatment and treatment interruption

The variability of populations of human immunodeficiency virus type 1 (HIV-1) in blood and semen, with respect to envelope and polymerase gene sequences, was examined longitudinally in a patient experiencing treatment failure, interruption of treatment, and successful reintroduction of therapy. During treatment failure, there was little evidence of compartmentalisation between blood and semen, with virus with identical resistance-associated mutations observed in both compartments and lack of clustering with respect to envelope gene sequences. After cessation of treatment, wild-type virus became the predominant population, displaying distinct envelope gene populations, indicating that wild-type virus had overgrown the resistant virus, rather than the resistant virus reverting to wild-type. Once successful therapy had been recommenced, it was possible to distinguish distinct populations of virus in the two compartments. These data support the hypothesis that the male genital tract represents a distinct HIV-1 reservoir.