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author:("birungi, asna")
1.  Detection of HIV-1 DNA resistance mutations by a sensitive assay at initiation of antiretroviral therapy is associated with virologic failure 
Background
Antiretroviral therapy (ART) has become more available throughout the developing world during the past five years. The World Health Organization recommends nonnucleoside reverse transcriptase inhibitor-based regimens as initial ART. However, their efficacy may be compromised by resistance mutations selected by single-dose nevirapine (sdNVP) used to prevent mother-to-child-transmission of HIV-1 (PMTCT). There is no simple and efficient method to detect such mutations at initiation of ART.
Methods
181 women participating in a PMTCT clinical trial who started NVP-ART after they had received sdNVP or placebo were tested for nevirapine-resistance point-mutations (K103N, Y181C, and G190A) using 100 copies of HIV-1 DNA with a sensitive oligonucleotide ligation assay (OLA) able to detect mutants at low concentrations (≥5% of the viral population). Virologic failure was defined as plasma HIV-1 RNA confirmed >50 copies/mL between 6–18 months of NVP-ART.
Results
At initiation of NVP-ART, resistance mutations were identified in 26% of 148 participants given sdNVP (K103N-13%, Y181C-5%, G190A-19%; ≥2 mutations-10%) at a median 9.3 months after sdNVP. The risk of virologic failure was .62 (95% confidence interval (CI), 0.46–0.77) in women with ≥1 resistance mutation, compared to 0.25 (95% CI, 0.17–0.35) in those without detectable resistance mutations (P<.0001). Failure was independently associated with resistance, an interval of <6 months between sdNVP and NVP-ART initiation, and a viral load above the median at NVP-ART initiation.
Conclusions
Access to simple and inexpensive assays to detect low-concentrations of NVP-resistant HIV-1 DNA prior to the initiation of ART could help improve the outcome of first-line antiretroviral therapy.
doi:10.1086/652148
PMCID: PMC2856716  PMID: 20377404
HIV-1; resistance mutations; nevirapine; HAART; oligonucleotide ligation assay; developing countries

Results 1-1 (1)