title: Persistence of viral reservoirs in multiple tissues after antiretroviral therapy suppression in a macaque RT-SHIV model.
abstract: Although antiretroviral therapy (ART) can suppress HIV-1 replication sufficiently to eliminate measurable plasma viremia, infected cells remain and ensure viral recrudescence after discontinuation of ART. We used a macaque model of HIV-1/AIDS to evaluate the location of infected cells during ART. Twelve macaques were infected with RT-SHIVmne, a SIV containing HIV-1 reverse transcriptase, conferring sensitivity to non-nucleoside reverse transcriptase inhibitors (NNRTIs). Ten to fourteen weeks post-infection, 6 animals were treated with 3 or 4 antiretroviral drugs for 17-20 weeks; 6 control animals remained untreated. Viral DNA (vDNA) and RNA (vRNA) were measured in peripheral blood mononuclear cells (PBMC) and at necropsy in multiple tissues by quantitative PCR and RT-PCR. The majority of virally infected cells were located in lymphoid tissues with variable levels in the gastrointestinal tract of both treated and untreated animals. Tissue viral DNA levels correlated with week 1 plasma viremia, suggesting that tissues that harbor proviral DNA are established within the first week of infection. PBMC vDNA levels did not correlate with plasma viremia or tissue levels of vDNA. vRNA levels were high in lymphoid and gastrointestinal tissues of the untreated animals; animals on ART had little vRNA expressed in tissues and virus could not be cultured from lymph node resting CD4+ cells after 17-20 weeks on ART, indicating little or no ongoing viral replication. Strategies for eradication of HIV-1 will need to target residual virus in ART suppressed individuals, which may not be accurately reflected by frequencies of infected cells in blood.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Christopher
authors.initials: C
authors.lastname: Kline
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Jean
authors.initials: J
authors.lastname: Ndjomou
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Tamera
authors.initials: T
authors.lastname: Franks
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Incorporated, (formerly SAIC-Frederick, Incorporated), Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Kiser
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Incorporated, (formerly SAIC-Frederick, Incorporated), Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
authors.forename: Vicky
authors.initials: V
authors.lastname: Coalter
authors.affiliation: Laboratory Animal Sciences Program, Leidos Biomedical Research, Incorporated, (formerly SAIC-Frederick, Incorporated), Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Smedley
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Incorporated, (formerly SAIC-Frederick, Incorporated), Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Piatak
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors.forename: John W
authors.initials: JW
authors.lastname: Mellors
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Incorporated, (formerly SAIC-Frederick, Incorporated), Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Zandrea
authors.initials: Z
authors.lastname: Ambrose
mesh_terms: D000818:Animals; D044966:Anti-Retroviral Agents / Q000494:pharmacology*; D004279:DNA, Viral / Q000378:metabolism; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D054303:HIV Reverse Transcriptase / Q000378:metabolism*; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000821:virology; D008251:Macaca; D008297:Male; D012367:RNA, Viral / Q000378:metabolism; D015302:Simian Immunodeficiency Virus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D014766:Viremia / Q000821:virology; D017735:Virus Latency / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D044966:Anti-Retroviral Agents; D004279:DNA, Viral; D012367:RNA, Viral; D054303:HIV Reverse Transcriptase