Antiretroviral resistance mutation profiles among drug regimens and HIV-1 Subtypes in Uganda

Abstract

Antiretroviral drug resistance is highly considered as a key limiting factor in HIV management because of its varying impact across drug regimens and HIV-1 subtypes. In Uganda, there is a paucity of data on how this factor scores among the different drug regimens and HIV-1 subtypes. The purpose of this study was to determine mutation profile differences between first-line drug regimens; Tenofovir/Lamivudine/Efavirenz (TDF/3TC/EFV) & Zidovudine/Lamivudine/Efavirenz (AZT/3TC/EFV) and HIV-1 subtypes; A and D in Uganda. The study also investigated the potential usage of Rilpivirine and Etravirine in patients who failed treatment on Efavirenz. A retrospective study was done on 199 archived plasma samples which were collected from patients who had virological treatment failure between 2006 and 2017 at five (5) sites of Joint Clinical Research Center, Uganda. Sequencing of the Reverse Transcriptase gene from codon 1-300 was done and drug resistance reports were generated from Stanford University HIV database. A Chi-square test was used to determine the association between drug resistance mutation (DRM)s and drug regimens or HIV-1 subtypes. The prevalence of DRMs was 83.4% in treatment failure patients. M184V/I (67.3%), K219/Q/E (22.6%) and K65R (21.1%) as the most prevalent among nucleoside reverse transcriptase inhibitor (NRTI) mutations. K103N (50.8 %) and G190A/S/E/G (29.1 %) as the most prevalent among non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations. No significant difference (P=0.367) was found between AZT/3TC/EFV and TDF/3TC/EFV in the acquisition of overall DRMs. However, within the NRTI class, mutations K65R (p=0.00005), K70E/G/Q/T/N/S (P=0.004) and L74V/I (P=0.003) appeared more frequently in the TDF/3TC/EFV. On the other hand, mutations L210W (P=0.002), K70R (P=0.005), T215Y (P=0.022) were more in AZT/3TC/EFV. No significant difference (P=0.336) was found for overall DRMs across HIV-1 subtypes A and D. Among the patients who had resistance to EFV, 37 (23.6%) were susceptible to newer NNRTIs. It was concluded that resistance mutation profiles do not differ between AZT/3TC/EFV and TDF/3TC/EFV, therefore the choice of drug regimen should be based on other factors other than resistance profiles. However, individual mutations that confer resistance to particular drugs should be considered at treatment failure. The study also concluded that having either HIV-1 subtype A or D is not associated with acquisition of DRMs, therefore HIV diversity should not determine the choice of treatment. It was further concluded that Rilpivirine and Etravirine had minimal benefits for patients who failed on Efavirenz, therefore they should not to be considered as options for second line treatment in the national guidelines.