Antiretroviral Drug Activity in Macaques Infected during Pre-Exposure Prophylaxis Has a Transient Effect on Cell-Associated SHIV DNA Reservoirs

• Published in: PloS one Vol. 11; no. 11; p. e0164821
• Main Authors: Cong, Mian-Er, Pau, Chou-Pong, Heneine, Walid, García-Lerma, J Gerardo
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 02.11.2016; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; AIDS; Animals; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - pharmacology; Antiretroviral agents; Antiretroviral drugs; Biology and life sciences; Case-Control Studies; Comparative analysis; Deoxyribonucleic acid; Disease control; Disease Models, Animal; Disease prevention; DNA; Emtricitabine; Exposure; Highly active antiretroviral therapy; HIV; HIV infections; Human immunodeficiency virus; Infection; Infections; Lentivirus; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - virology; Lymphoid tissue; Lymphoid Tissue - drug effects; Lymphoid Tissue - virology; Macaca; Macaca mulatta; Medicine and Health Sciences; Pre-Exposure Prophylaxis; Prophylaxis; Proviruses - drug effects; Proviruses - genetics; Research and analysis methods; Reservoirs; Retroviridae; Ribonucleic acid; RNA; Simian Acquired Immunodeficiency Syndrome - prevention & control; Simian Acquired Immunodeficiency Syndrome - transmission; Simian Acquired Immunodeficiency Syndrome - virology; Simian Immunodeficiency Virus - drug effects; Studies; Tenofovir; Time Factors; Tissues; Viral Load; Viruses; Atlanta Georgia; United States > US; Georgia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0164821

Pre-exposure prophylaxis (PrEP) with emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) is a novel HIV prevention strategy. Suboptimal PrEP adherence and HIV infection creates an opportunity for continued antiretroviral drug activity during undiagnosed infection. We previously showed that macaques infected with SHIV during PrEP with FTC/TDF display reduced acute plasma viremias and limited virus diversity. We investigated the effect of PrEP on acute SHIV DNA dynamics and on the size of the persistent virus reservoir in lymphoid tissues. Cell-associated SHIV DNA levels in PBMCs were measured in 8 macaques infected during PrEP with FTC/TDF or single-agent TAF and was compared to those seen in untreated infections (n = 10). PrEP breakthrough infections continued treatment with 1-2 weekly drug doses to model suboptimal drug exposure during undiagnosed HIV infection in humans. SHIV DNA was also measured in lymphoid tissues collected from FTC/TDF PrEP breakthroughs after 1 year of infection. Compared to untreated controls, PrEP infections had reduced plasma RNA viremias both at peak and throughout weeks 1-12 (p<0.005). SHIV DNA levels were also reduced at peak and during the first 12 weeks of infection (p<0.043) but not throughout weeks 12-20. At 1 year, SHIV DNA reservoirs in lymphoid tissues were similar in size among macaques that received PrEP or placebo. Antiviral drug activity due to PrEP limits acute SHIV replication but has only a transient effect on cell-associated SHIV DNA levels. Our model suggests that suboptimal drug exposure in persons that are taking PrEP and become infected with HIV may not be sufficient to reduce the pool of HIV-infected cells, and that treatment intensification may be needed to sustain potential virological benefits from the PrEP regimen.