Genital shedding of human immunodeficiency virus type-1 (HIV) when antiretroviral therapy (ART) suppresses HIV replication in the plasma.

BACKGROUND: During antiretroviral treatment (ART) with plasma HIV RNA below the limit-of-quantification, HIV RNA can be detected in genital or rectal secretions, termed "discordant shedding" (DS). We hypothesized that proliferating cells produce virions without HIV replication. METHODS: ART-naive Peruvians initiating ART were observed for DS over two years. Single HIV env and pol genomes were amplified from DS. Antiretrovirals and cytokines/chemokines concentrations were compared at DS and control timepoints. RESULTS: Eighty-two participants had ART-suppression. DS was detected in 24/82 (29%) participants, including 13/253 (5%) cervicovaginal lavages, 20/322 (6%) seminal plasmas and 6/85 (7%) rectal secretions. HIV RNA in DS specimens was near the limit-of-quantification and not reproducible in repeated assays. HIV DNA was detected in 6/13 (46%) DS cervicovaginal lavages at low levels. Following DNase treatment, 5/39 DS specimens yielded HIV sequences, all without increasing genetic distances. Women with and without DS had similar plasma antiretroviral levels, and DS in one woman's was associated with inflammation. CONCLUSIONS: HIV RNA and DNA sequences and therapeutic antiretroviral plasma levels did not support HIV replication as the cause of DS from the genital tract. Rather, our findings infer that HIV RNA is shed due to proliferation of infected cells with virion production.