Concurrent measures of total and integrated HIV DNA monitor reservoirs and ongoing replication in eradication trials.
Enviado por Luis Montaner el
Título | Concurrent measures of total and integrated HIV DNA monitor reservoirs and ongoing replication in eradication trials. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Autores | Mexas, AM, Graf, EH, Pace, MJ, Yu, JJ, Papasavvas, E, Azzoni, L, Busch, MP, Di Mascio, M, Foulkes, AS, Migueles, SA, Montaner, LJ, O'Doherty, U |
Journal | AIDS |
Volume | 26 |
Issue | 18 |
Pagination | 2295-306 |
Date Published | 2012 Nov 28 |
ISSN | 1473-5571 |
Palabras clave | Adult, Anti-HIV Agents, Biological Markers, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, Clinical Trials as Topic, Disease Reservoirs, DNA, Viral, Female, HIV Infections, HIV-1, Humans, Interferon-alpha, Male, Middle Aged, Polymerase Chain Reaction, Viral Load, Viremia, Virus Integration, Virus Replication |
Abstract | OBJECTIVES: Interest in targeting HIV reservoirs is fueling trials that may decrease reservoir size and/or induce viral replication. Therefore, we aimed to develop strategies to sensitively measure changes in these parameters in patients on and off antiretroviral therapy (ART). Achieving these goals may help evaluate the effects of future clinical trials. DESIGN: To determine the relationship between measurements of total and integrated HIV DNA and their role as markers of reservoir size and ongoing replication, these parameters were measured during the first year of ART, during long-term effective ART, and during a clinical trial aimed at targeting reservoirs. METHODS: Total and integrated HIV DNA were measured in patient samples using quantitative PCR techniques. CD4(+)T cell counts and plasma viremia were also monitored. RESULTS: Unintegrated HIV DNA became undetectable during the first year of ART. Total and integrated HIV DNA levels were generally equal in well controlled patients on ART, and low-level plasma viremia correlated best with integration measures. Finally, patients who controlled plasma viremia (<400 copies/ml) during interferon-α monotherapy exhibited a decrease in the level of integrated but not total HIV DNA and a rise in the ratio of total to integrated HIV DNA over time. CONCLUSION: Our findings suggest that appearance of unintegrated HIV DNA reflects residual HIV expression and de-novo reverse transcription, providing insight into the mechanism by which interferon-α reduces the HIV reservoir. We conclude that concurrent measurements of total and integrated HIV DNA provide information regarding reservoir size and ongoing replication in trials targeting HIV. |
DOI | 10.1097/QAD.0b013e32835a5c2f |
Alternate Journal | AIDS |
PubMed ID | 23014521 |
Grant List | 5K08AI073102 / AI / NIAID NIH HHS / United States K02 AI078766 / AI / NIAID NIH HHS / United States K02AI078766 / AI / NIAID NIH HHS / United States K08 AI073102 / AI / NIAID NIH HHS / United States P30 AI 045008 / AI / NIAID NIH HHS / United States P30 CA10815 / CA / NCI NIH HHS / United States R21 AI087461 / AI / NIAID NIH HHS / United States R21 AI087461 / AI / NIAID NIH HHS / United States T32 AI007632 / AI / NIAID NIH HHS / United States U01 AI065279 / AI / NIAID NIH HHS / United States U01AI065279 / AI / NIAID NIH HHS / United States |