Send to:

Choose Destination
See comment in PubMed Commons below
Proc Natl Acad Sci U S A. 2011 May 31;108(22):9202-7. doi: 10.1073/pnas.1105688108. Epub 2011 May 16.

Role of low-frequency HIV-1 variants in failure of nevirapine-containing antiviral therapy in women previously exposed to single-dose nevirapine.

Author information

  • 1National Cancer Institute, Frederick, MD 21702, USA.


In the OCTANE/A5208 study of initial antiretroviral therapy (ART) in women exposed to single-dose nevirapine (sdNVP) ≥ 6 mo earlier, the primary endpoint (virological failure or death) was significantly more frequent in the NVP-containing treatment arm than in the lopinavir/ritonavir-containing treatment arm. Detection of NVP resistance in plasma virus at study entry by standard population genotype was strongly associated with the primary endpoint in the NVP arm, but two-thirds of endpoints occurred in women without NVP resistance. We hypothesized that low-frequency NVP-resistant mutants, missed by population genotype, explained excess failure in the NVP treatment arm. Plasma samples from 232 participants were analyzed by allele-specific PCR at study entry to quantify NVP-resistant mutants down to 0.1% for 103N and 190A and to 0.3% for 181C. Of 201 women without NVP resistance by population genotype, 70 (35%) had NVP-resistant mutants detected by allele-specific PCR. Among these 70 women, primary endpoints occurred in 12 (32%) of 38 women in the NVP arm vs. 3 (9%) of 32 in the lopinavir/ritonavir-containing arm (hazard ratio = 3.84). The occurrence of a primary endpoint in the NVP arm was significantly associated with the presence of K103N or Y181C NVP-resistant mutations at frequencies >1%. The risk for a study endpoint associated with NVP-resistant mutant levels did not decrease with time. Therefore, among women with prior exposure to sdNVP, low-frequency NVP-resistant mutants were associated with increased risk for failure of NVP-containing ART. The implications for choosing initial ART for sdNVP-exposed women are discussed.

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk