18th International HIV Drug Resistance Workshop Basic Principles & Clinical Implications June 9–13 2009, Fort Myers, Florida, USA

RESISTANCE MUTATIONS DETECTED BY OLIGONUCLEOTIDE LIGATION ASSAY OF HIV-1 DNA AT TIME OF INITIATION OF NEVIRAPINE-CONTAINING ANTIRETROVIRAL THERAPY ARE ASSOCIATED WITH VIROLOGIC FAILURE

Antivir Ther 2009; 14 Suppl 1:A46 (abstract no. 44)

T Wagner¹, G Jourdain^2,3, N Ngo-Giang-Huong^2,3, W Sirungsi⁴, V Klinbuayaem⁵, F Fregonese⁶, I Nantasen², G Halue⁷, M Techpornroong⁸, A Nilmanat⁹, P Wittayapraparat¹⁰, V Chalermpolprapa¹¹, P Pathipvanich¹², P Yuthavisuthi⁷, L Frenkel¹ and M Lallemant^2,3
1University of Washington and Seattle Children’s Research Institute, Seattle, WA, USA; ²Institut de Recherche pour le Développement (IRD), UMI 174/ PHPT, Thailand, France; ³Harvard School of Public Health, Boston, MA, USA; ⁴Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand; ⁵Sanpatong Hospital, Chiang Mai, Thailand; ⁶Padova University, Padova, Italy; ⁷Provincial Hospital, Department of Internal Medicine, Phayao, Thailand; ⁸Prapokklao Regional Hospital, Department of Obstetrics, Chantaburi, Thailand; ⁹Hat Yai Regional Hospital, Department of Internal Medicine, Songkla, Thailand; ¹⁰Provincial Hospital, Department of Internal Medicine, Chacheongsao, Thailand; ¹¹Regional Hospital, Department of Obstetrics, Nakhonpathom, Thailand; ¹²Lampang Hospital, Lampang, Thailand

BACKGROUND: Single-dose nevirapine (sdNVP) to prevent mother-to-child transmission (MTCT) of HIV-1 increases the mothers’ risk of failing subsequent NVP- based antiretroviral therapy (ART). Consensus genotypic resistance testing of plasma HIV-1 RNA 10 days following sdNVP detects NVP resistance in a substantial proportion of women, but previously was not independently associated with subsequent treatment failure. This study sought to determine whether NVP resistance detected using a sensitive assay applied to HIV-1 DNA at the time ART is initiated would be associated with virological failure of NVP ART.

METHODS: Women who participated in a randomized controlled trial of sdNVP or placebo added to zidovudine to prevent MTCT and subsequently started NVP ART, had blood from immediately prior to the initiation of NVP ART tested for NVP resistance. Using a sensitive oligonucleotide ligation assay (OLA), 100 copies of HIV-1 DNA were assayed to detect point-mutations (K103N, Y181C, and G190A) present at >5%. The endpoint was the risk of virological failure between 6 and18 months of NVP ART, defined by confirmed plasma HIV-1 RNA >50 copies/ml.

RESULTS: OLA identified resistance mutations in 26% of 148 women given sdNVP (K103N 13%, Y181C 5% and G190A 19%; 10% had ≥2 mutations) and none of the 33 given placebo. The cumulative rate of virological failure was 0.62 (CI 0.46–0.77) in women given NVP with ≥1 resistance mutation detected by OLA at NVP ART initiation compared with 0.25 (CI 0.17–0.45) in those with no resistance mutations (P<0.0001), which was not statistically greater than in those who received placebo 0.13 (CI 0.05–0.32). Other risk factors independently associated with an increased risk of failure were an interval of <6 months between delivery and NVP ART initiation (P=0.001) and a viral load above the median (4.77 log₁₀ copies/ml) at initiation of NVP ART (P=0.007).

DISCUSSION: NVP resistance detected in HIV-1 DNA by a sensitive method (OLA) immediately prior to the initiation of ART was strongly associated with virological failure in women previously exposed to sdNVP to prevent MTCT. Access to simple and inexpensive assays to detect low concentrations of NVP-resistant HIV-1 prior to the initiation of ART may improve ART selection and the associated outcomes of antiretroviral therapy.

2009-06-09
44

Copyright © 2009 - International Medical Press Ltd.. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the International Medical Press Ltd. 2-4 Idol Lane, London EC3R 5DD UK.