HUMAN-IMMUNODEFICIENCY-VIRUS IN SEMEN ARISES FROM A GENETICALLY DISTINCT VIRUS RESERVOIR

The reservoir of human immunodeficiency virus (HIV) in semen is unknow n. Several lines of evidence suggest that semen HIV may not arise from the same reservoir of infection as peripheral blood. If true, the vir al burden in the two compartments could be qualitatively and quantitat ively different, a scenario of potentially profound significance for t he design of effective strategies of treatment, disease monitoring, an d infection containment. We report here that the ratio of infected to uninfected leukocytes in ejaculated semen specimens is highly discorda nt with paired blood samples, demonstrating that they derive from dist inct populations of infected cells. In addition, infectious HIV was is olated from semen cells, but not from blood cells, of an individual on triple antiretroviral therapy; the absence of major resistance-confer ring mutations in the semen virus indicates that it was replicating in isolation from the antiviral agents. The compartmentalization of bloo d and semen infection was further supported by genetic analysis of sev eral infectious HIV clones isolated from semen cells and peripheral bl ood cells of another donor not on antiretroviral therapy, Protease gen e sequence analyses revealed significant divergence of the two viral p opulations. These findings confirm the distinct compartmentalization o f HIV in the semen of this study cohort, and support the concept that semen HIV arises from an isolated reservoir of infection that may func tion independently in the pathobiology of HIV disease.