Genital Shedding of Human Immunodeficiency Virus Type-1 (HIV) When Antiretroviral Therapy Suppresses HIV Replication in the Plasma. (10th April 2020)

• Record Type: Journal Article
• Authors: Bull, Marta; Mitchell, Caroline; Soria, Jaime; Styrchak, Sheila; Williams, Corey; Dragavon, Joan; Ryan, Kevin J; Acosta, Edward; Onchiri, Frankline; Coombs, Robert W; La Rosa, Alberto; Ticona, Eduardo; Frenkel, Lisa M
• Is Part Of: Journal of infectious diseases. Volume 222:Number 5(2020)
• Page Start: 777
• Page End: 786
• Publication Date: 2020-04-10
• Subjects: genital HIV shedding -- HIV phylogenetics -- drug levels -- inflammation; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiaa169
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: 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 2 years. HIV env and pol genomes were amplified from DS. Antiretrovirals and cytokines/chemokines concentrations were compared at DS and control time points. Results: Eighty-two participants had ART suppression. DS was detected in 24/82 (29%) participants: 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. 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 increased genetic distances. Women with and without DS had similar plasma antiretroviral levels and DS in 1 woman 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. Abstract : Findings suggest that, during ART suppression, discordant shedding of HIV in genital secretions arises from HIV-infected cells producing virions near the limit of quantification in association with infected cell proliferation. HIV replication isolated to the genital tract was not detected.