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:
doi: 10.1097/01.qai.0000413822.65296.b4

Background: The 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.

Methods: This 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.

Results: Of 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.

Conclusions: Adult 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.

(C) 2012 Lippincott Williams & Wilkins, Inc.