No evidence of ongoing HIV replication or compartmentalization in tissues during combination antiretroviral therapy: Implications for HIV eradication

• Published in: Science advances Vol. 5; no. 9; p. eaav2045
• Main Authors: Bozzi, G, Simonetti, F R, Watters, S A, Anderson, E M, Gouzoulis, M, Kearney, M F, Rote, P, Lange, C, Shao, W, Gorelick, R, Fullmer, B, Kumar, S, Wank, S, Hewitt, S, Kleiner, D E, Hattori, J, Bale, M J, Hill, S, Bell, J, Rehm, C, Grossman, Z, Yarchoan, R, Uldrick, T, Maldarelli, F
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 01.09.2019
• Subjects: Adolescent; Adult; Anti-HIV Agents - pharmacology; Anti-HIV Agents - therapeutic use; Antiretroviral Therapy, Highly Active; Child; Diseases and Disorders; Female; HIV - classification; HIV - drug effects; HIV - genetics; HIV - physiology; HIV Infections - drug therapy; HIV Infections - virology; Humans; Male; Organ Specificity; Phylogeny; RNA, Viral; SciAdv r-articles; Sequence Analysis, DNA; Virus Replication - drug effects; Young Adult
• ISSN: 2375-2548; 2375-2548
• DOI: 10.1126/sciadv.aav2045

HIV persistence during combination antiretroviral therapy (cART) is the principal obstacle to cure. Mechanisms responsible for persistence remain uncertain; infections may be maintained by persistence and clonal expansion of infected cells or by ongoing replication in anatomic locations with poor antiretroviral penetration. These mechanisms require different strategies for eradication, and determining their contributions to HIV persistence is essential. We used phylogenetic approaches to investigate, at the DNA level, HIV populations in blood, lymphoid, and other infected tissues obtained at colonoscopy or autopsy in individuals who were on cART for 8 to 16 years. We found no evidence of ongoing replication or compartmentalization of HIV; we did detect clonal expansion of infected cells that were present before cART. Long-term persistence, and not ongoing replication, is primarily responsible for maintaining HIV. HIV-infected cells present when cART is initiated represent the only identifiable source of persistence and is the appropriate focus for eradication.