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AF2 Pattern of Drug Resistant Mutations Among Nigerian Patients on PEPFAR NRTINNRTI Regimens

Ndembi Nicaise; Enzama, Richard; Peters, Samuel; Akolo, Christopher; Etiebet, Mary-Ann; Gabou, Mendy; Dakum, Patrick; Blattner, William; Abimiku, Alash'le
JAIDS Journal of Acquired Immune Deficiency Syndromes: April 2012
doi: 10.1097/01.qai.0000413822.65296.b4

BackgroundThe Institute for Human Virology-Nigeria (IHVN), a PEPFAR implementing partner, supports antiretroviral therapy (ART) to over 70,000 public sector HIV-infected patients through the AIDS Care and Treatment in Nigeria (ACTION) program. Patterns of antiretroviral drug resistance associated mutations in a cross-sectional study, at the time of first-line ART failure at two ACTION supported sites in Abuja are described.

MethodsThis study was conducted at IHVN supported sites, University of Abuja Teaching Hospital (UATH) and National Hospital Abuja (NHA). Patients were included if they received HIV-1 RNA testing within 2010; were over 18 years; were on NNRTIbased first-line regimens;and had not received any protease inhibitor (PI) based therapy prior to viral load testing. Plasma samples from 219 adult patients failing their first-line NNRTI-backbone regimens were assayed for HIV-1 RNA viral load (VL) by Roche Cobas AmpliPrep TaqMan. Plasma virus from samples with >1000 c/mL at time of failures were sequenced in the pol gene (codons 1–99 of protease and codons 1–257 of reverse transcriptase). Analysis for resistance mutations was done using the IAS-US 2010 Drug Resistance Mutation (DRM) list.

ResultsOf 219 patients with virologic failure, 36.5% were subtype G (including CRF43_cpx and G'), 34.7% CRF02_AG, 20.5% URFs, 3.6% CRF06.cpx, 2.3% subtype A1, 1.4% subtype C and 1.0%CRF11.cpx. Forty-two samples (28%) had no resistance; 160 (73.1%) harbored NRTI resistance; 151 (68.9%) M184I/V; 29 (13.2%) had ≥3 TAMs, and 37 (17%) had K65R, of which 6 were on TDF. The longer the duration of failure the greater the risk of developing ≥3 TAMs (P < 0.005). One hundred and sixty-two samples (74.0%) harbored NNRTI resistance; 72 (36.1%) Y181C and 68 (31.0%) K103N with 53% having ≥2 etravirine associated mutations. Six (2.7%) patients had IAS protease inhibitors (M46I, I54V, V82T and L76V) major mutations.

ConclusionsAdult patients failing first-line ART regimens from 2 PEPFAR supported ACTION sites in Nigeria had predominantly subtypes G and CRF02_AG, and advanced drug resistance limiting second-line options. These findings argue for the need for genomic monitoring of patients failing their ART regimen even in low resource settings.

© 2012 Lippincott Williams & Wilkins, Inc.