AF4 HIV Drug Resistance in Nigeria, a Cost-Effective New Methodology

Abstract

Since 2004, we have provided PEPFAR support to HIV prevention, care and treatment programs at 35 hospitals in 10 states in Nigeria, providing ART to over 85,000 adult and 4,300 pediatric patients. A diverse array of non-subtype B HIV-1 viruses circulate in Africa and dominate the global pandemic. HIV-1 RT and PR sequences from 338 patients with treatment failure to first-line ART regimens were evaluated. Multivariate logistic regression examined the effect of subtype on each mutation controlling for regimen, time on therapy, and total mutations. CRF02_AG was less likely to have the M41L mutation compared to other subtypes (AOR. 0.35, P = 0.022). Subtype A patients showed a 42.5-fold increased risk (AOR. 42.5, P = 0.001) for the L210W mutation. Among NNRTI mutations, subtype G patients had an increased risk for A98G (AOR. 2.40, P = 0.036) and V106I (AOR. 6.15, P = 0.010). Given the shortcomings of genotyping systems that limit their utility in the developing world, we have created a less expensive, yet more sensitive, method using the ligation-amplification technique. We have designed sets of Nigerian subtype specific oligonucleotides that are used as probes in establishing the presence of the specific HIV drug resistance mutations K103N, M184V, and Y181C/I. Preliminary data have already shown high concordance with sequence data, and ability to amplify samples with low levels of the K103N, M184V and Y181C/I mutations. The lig-amp assay has the potential to provide high sensitivity at a 10 fold reduction in cost. Further study to understand the clinical impact of subtype-specific diversity on drug resistance will be critically important to the continued success of ART scale-up in resource-limited settings.