Genotypic resistance at viral rebound among patients who received lopinavir/ritonavir-based or efavirenz-based first antiretroviral therapy in South Africa

Abstract

Nonnucleoside reverse transcriptase inhibitor-drug resistance mutations (DRM) are increasingly reported in Africans failing their first antiretroviral regimen. The Phidisa II trial randomized treatment-naive participants to lopinavir/ritonavir or efavirenz with stavudine + lamivudine or zidovudine + didanosine. We report the prevalence of DRM in subjects who achieved HIV RNA <400 copies per milliliter at 6 months, but subsequently had 2 consecutive HIV RNA >1000 copies per milliliter. Sixty-eight participants fulfilled the inclusion criteria. nonnucleoside reverse transcriptase inhibitor-DRM were found in 17 of 36 (47.2%) efavirenz recipients, and M184V/I mutation in 14 of 40 (35.0%) lamivudine recipients. No protease inhibitor mutation was identified in 38 lopinavir/ritonavir recipients. This is one of the first studies in Africa confirming the paucity of protease inhibitor-associated DRM despite virologic failure.

Figure 1. Antiretroviral Therapy, Pre-Treatment CD4 and HIV RNA, Time to Failure, CD4 and HIV RNA at Failure, and Major Genotypic Resistance Mutations for Individual Participants with Detected Mutations at Failure

¹ (cells/mm³) ² (copies/mL) ³ Major reverse transcriptase mutations according to the International AIDS Society-USA Drug Resustance Mutations in HIV-1, December 2009[14] 3TC = lamivudine, ART = antiretroviral therapy, cART = combination antiretroviral therapy, chg = change, d4T = stavudine, ddI = didanosine, EFV = efavirenz, LPV = lopinavir/ritonavir, mon = months