Reverse Transcriptase Inhibitors as Microbicides

Title: Reverse Transcriptase Inhibitors as Microbicides

Volume: 10 Issue: 1

Author(s): Paul Lewi, Jan Heeres, Kevin Arien, Muthusamy Venkatraj, Jurgen Joossens, Pieter Van der Veken, Koen Augustyns and Guido Vanham

Affiliation:

Keywords: Microbicide, HIV, reverse transcriptase, NtRTI, NNRTI, NRTI, gel, intravaginal ring, Anti-Retroviral, infection

Abstract: The CAPRISA 004 study in South Africa has accelerated the development of vaginal and rectal microbicides containing antiretrovirals that target specific enzymes in the reproduction cycle of HIV, especially reverse transcriptase inhibitors (RTI). In this review we discuss the potential relevance of HIV-1 RTIs as microbicides, focusing in the nucleotide RTI tenofovir and six classes of nonnucleoside RTIs (including dapivirine, UC781, urea and thiourea PETTs, DABOs and a pyrimidinedione). Although tenofovir and dapivirine appear to be most advanced in clinical trials as potential microbicides, several issues remain unresolved, e.g., the importance of nonhuman primates as a “gatekeeper” for clinical trials, the emergence and spread of drug-resistant mutants, the combination of microbicides that target different phases of viral reproduction and the accessibility to microbicides in low-income countries. Thus, here we discuss the latest research on RTI as microbicides in the light of the continuing spread of the HIV pandemic from the point of view of medicinal chemistry, virological, and pharmaceutical studies.

Cite this article as:

Lewi Paul, Heeres Jan, Arien Kevin, Venkatraj Muthusamy, Joossens Jurgen, Van der Veken Pieter, Augustyns Koen and Vanham Guido, Reverse Transcriptase Inhibitors as Microbicides, Current HIV Research 2012; 10 (1) . https://dx.doi.org/10.2174/157016212799304643