Short Communication: Comparative Evaluation of Coformulated Injectable Combination Antiretroviral Therapy Regimens in Simian Immunodeficiency Virus-Infected Rhesus Macaques

Gregory Q. Del Prete, Jeremy Smedley, Rhonda Macallister, Gregg S. Jones, Bei Li, Jillian Hattersley, Jim Zheng, Michael Piatak, Brandon F. Keele, Joseph Hesselgesser, Romas Geleziunas, Jeffrey D. Lifson

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

The use of nonhuman primate (NHP) models to study persistent residual virus and viral eradication strategies in combination antiretroviral therapy (cART)-treated individuals requires regimens that effectively suppress SIV replication to clinically relevant levels in macaques. We developed and evaluated two novel cART regimens in SIVmac239-infected rhesus macaques: (1) a "triple regimen" containing the nucleo(s/t)ide reverse transcriptase inhibitors emtricitabine (FTC) and tenofovir disoproxil fumarate [TDF, prodrug of tenofovir (TFV, PMPA)] with the integrase strand transfer inhibitor dolutegravir (DTG) (n = 3), or (2) a "quad regimen" containing the same three drugs plus the protease inhibitor darunavir (DRV) (n = 3), with each regimen coformulated for convenient administration by a single daily subcutaneous injection. Plasma drug concentrations were consistent across animals within the triple and quad regimen-treated groups, although DTG levels were lower in the quad regimen animals. Time to achieve plasma viral loads stably <30 viral RNA copies/ml ranged from 12 to 20 weeks of treatment between animals, and viral loads <30 viral RNA copies/ml plasma were maintained through 40 weeks of follow-up on cART. Notably, although we show virologic suppression and development of viral resistance in a separate cohort of SIV-infected animals treated with oral DRV monotherapy, the addition of DRV in the quad regimen did not confer an apparent virologic benefit during early treatment, hence the quad regimen-treated animals were switched to the triple regimen after 4 weeks. This coformulated triple cART regimen can be safely, conveniently, and sustainably administered to durably suppress SIV replication to clinically relevant levels in rhesus macaques.

Original languageEnglish (US)
Pages (from-to)163-168
Number of pages6
JournalAIDS Research and Human Retroviruses
Volume32
Issue number2
DOIs
StatePublished - Feb 2016

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

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