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

Author:

Bozzi, G [ORCID]

Simonetti, F R [ORCID]

Watters, S A [ORCID]

Anderson, E M [ORCID]

Gouzoulis, M

Kearney,Mary [ORCID]

Rote, P [ORCID]

Lange,Camille

Shao,Wei

Gorelick,Robert [ORCID]

Fullmer,Brandie [ORCID]

Kumar, S [ORCID]

Wank, S

Hewitt, S [ORCID]

Kleiner, D E [ORCID]

Hattori, J [ORCID]

Bale,Michael

Hill,Shawn

Bell,Jennifer

Rehm, C [ORCID]

Grossman,Zehava

Yarchoan, R [ORCID]

Uldrick, T [ORCID]

Maldarelli,Frank [ORCID]
Author Address

HIV Dynamics and Replication Program, NCI, NIH, Frederick, MD, USA., Department of Biomedical and Clinical Sciences, L. Sacco Hospital, University of Milan, Milan, Italy., Department of Infection and Immunity, University College London, London, UK., Advanced Biomedical Computing Center, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA., AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD, USA., Laboratory of Pathology, NCI, NIH, Bethesda, MD, USA., Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA., Laboratory of Immunoregulation, NIAID, NIH, Bethesda, MD, USA., HIV and AIDS Malignancy Branch, NCI, NIH, Bethesda, MD, USA.,

Abstract:

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. Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

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