| Publication Abstract Display | | Type: Published Manuscript | | Title: HIV RNA rebound in seminal plasma after antiretroviral treatment interruption. | | Authors: Gianella S, Chaillon A, Chun T, Sneller MC, Ignacio C, Vargas-Meneses MV, Caballero G, Ellis RJ, Kovacs C, Benko E, Huibner S, Kaul R | | Year: 2020 | | Publication: Journal of Virology | | Volume: 94 Issue: 15 Pages: e00415- | | Abstract:Background: If strategies currently in development succeed in eradicating HIV reservoirs in peripheral blood and lymphoid tissues, residual sources of virus may remain in anatomic compartments.Methods: Paired blood and semen samples were collected from 12 individuals enrolled in a randomized, double-blind, placebo-controlled therapeutic vaccine clinical trial in people with HIV (PWH) who began ART during acute or early infection (NCT01859325). After the week 56 visit (post intervention), all participants interrupted antiretroviral therapy (ART). At the first available time-points after viral rebound, we sequenced HIV-1 env (C2-V3), gag (p24), and pol (reverse transcriptase) regions amplified from cell-free HIV RNA in blood and seminal plasma using the MiSeq Illumina platform. Comprehensive sequence and phylogenetic analyses were performed to evaluate viral population structure, compartmentalization and viral diversity in blood and seminal plasma.Results: Compared to blood, HIV RNA rebound in semen occurred significantly later (median of 66 versus 42 days post ART interruption, P<0.01) and reached lower levels (median 164 versus 16,090 copies/ml, P<0.01). Three out of 5 participants with available sequencing data, presented compartmentalized viral rebound between blood and semen in one HIV coding region. Despite early ART initiation, HIV RNA molecular diversity was higher in semen compared to blood in all three coding regions for most participants.Conclusions: Higher HIV RNA molecular diversity in the genital tract (as compared to blood plasma), and evidence of compartmentalization illustrate the distinct evolutionary dynamics between these two compartments after ART interruption. Future research should evaluate whether the genital compartment might contribute to viral rebound in some PWH interrupting ART.Importance. To cure HIV, we likely need to target the reservoirs in all anatomic compartments. Here, we used sophisticated statistical and phylogenetic methods to analyze blood and semen samples collected from 12 persons with HIV who began antiretroviral therapy (ART) during very early HIV-infection and who interrupted their ART as part of a clinical trial. First, we found that HIV RNA rebound in semen occurred significantly later and reached lower levels, as compared to blood. Second, we found that the virus in semen was genetically different in some participants, as compared to blood. Finally, we found increased HIV RNA molecular diversity in semen compared to blood in almost all study participants. These data suggest that the HIV RNA populations emerging from the genital compartment after ART interruption might not be the same as those emerging from blood plasma. Future research should evaluate whether the genital compartment might contribute to viral rebound in some PWH interrupting ART. |
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