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. 2017 Jun 27;61(7):e00277-17.
doi: 10.1128/AAC.00277-17. Print 2017 Jul.

In Vitro Cross-Resistance Profiles of Rilpivirine, Dapivirine, and MIV-150, Nonnucleoside Reverse Transcriptase Inhibitor Microbicides in Clinical Development for the Prevention of HIV-1 Infection

Nicholas S Giacobbi  1 , Nicolas Sluis-Cremer  2
Affiliations

In Vitro Cross-Resistance Profiles of Rilpivirine, Dapivirine, and MIV-150, Nonnucleoside Reverse Transcriptase Inhibitor Microbicides in Clinical Development for the Prevention of HIV-1 Infection

Nicholas S Giacobbi et al. Antimicrob Agents Chemother. .

Abstract

Rilpivirine (RPV), dapivirine (DPV), and MIV-150 are in development as microbicides. It is not known whether they will block infection of circulating nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant human immunodeficiency virus type 1 (HIV-1) variants. Here, we demonstrate that the activity of DPV and MIV-150 is compromised by many resistant viruses containing single or double substitutions. High DPV genital tract concentrations from DPV ring use may block replication of resistant viruses. However, MIV-150 genital tract concentrations may be insufficient to inhibit many resistant viruses, including those harboring K103N or Y181C.

Keywords: HIV-1; MIV-150; NNRTI; antiretroviral resistance; dapivirine; prevention.

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Figures

FIG 1
FIG 1
NNRTI cross-resistance profiles for RPV, DPV, and MIV-150. Low-, intermediate- and high-level resistance was defined as 2- to 8-fold, 8- to 20-fold, and >20-fold changes in drug susceptibility compared to the WT virus. The black arrows indicate the four most commonly transmitted drug resistance mutations, G190A, K101E, Y181C, and K103N.
See this image and copyright information in PMC

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