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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Laboratory Branch, Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
Mian-Er
ME
Cong
Laboratory Branch, Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
Chou-Pong
CP
Pau
Laboratory Branch, Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
Walid
W
Heneine
Laboratory Branch, Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
J Gerardo
JG
García-Lerma
D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016022:Case-Control Studies; D004195:Disease Models, Animal; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000821:virology; D008221:Lymphoid Tissue / Q000187:drug effects / Q000821:virology; D008253:Macaca mulatta; D065129:Pre-Exposure Prophylaxis; D011533:Proviruses / Q000187:drug effects* / Q000235:genetics; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control* / Q000635:transmission / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000187:drug effects*; D013997:Time Factors; D019562:Viral Load
D019380:Anti-HIV Agents