Reduced HIV-1 latent reservoir outgrowth and distinct immune correlates among women in Rakai, Uganda
| Autor: | Adam A. Capoferri, David Serwadda, Katherine E. Schlusser, Thomas C. Quinn, Yun Hee Choi, Steven J. Reynolds, Jingo Kasule, Paul Buule, Jun Lai, Kyungyoon J. Kwon, Taddeo Kityamuweesi, Andrew D. Redd, Katherine Yu, Craig Martens, Jessica L. Prodger, Eileen P. Scully |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes Male 0301 basic medicine Chemokine Anti-HIV Agents T cell HIV Infections Virus Replication Virus Persistence (computer science) Pathogenesis 03 medical and health sciences 0302 clinical medicine Immune system medicine Humans Uganda Disease Reservoirs Sex Characteristics biology General Medicine Viral Load Provirus Virus Latency 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Immunology Cohort HIV-1 biology.protein Female Research Article |
| Zdroj: | JCI Insight |
| ISSN: | 2379-3708 |
| DOI: | 10.1172/jci.insight.139287 |
| Popis: | HIV-1 infection remains incurable owing to the persistence of a viral reservoir that harbors integrated provirus within host cellular DNA. Increasing evidence links sex-based differences in HIV-1 immune responses and pathogenesis; however, little is known about differences in HIV-1 infection persistence. Here, we quantified persistent HIV-1 infection in 90 adults on suppressive antiretroviral therapy in Rakai, Uganda (57 female patients). Total HIV-1 DNA was quantified by PCR, and replication-competent provirus by quantitative viral outgrowth assay (QVOA). Immune phenotyping of T cell subsets and plasma biomarkers was also performed. We found that whereas both sexes had similar total HIV DNA levels, female patients had significantly fewer resting CD4(+) T cells harboring replication-competent virus, as measured by viral outgrowth in the QVOA. Factors associated with viral outgrowth differed by sex; notably, frequency of programmed cell death 1 (PD1(+)) CD4(+) T cells correlated with reservoir size in male but not female patients. The sex-based differences in HIV-1 persistence observed in this cohort warrant additional research, especially given the widespread use of the QVOA to assess reservoir size and current explorations of PD1 agonists in cure protocols. Efforts should be made to power future cure studies to assess outcomes in both male and female patients. |
| Databáze: | OpenAIRE |
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