Jeffrey S A StringerMichelle S. McConnellJames KiarieOmotayo BoluThanomsak AnekthananonTavatchai JariyasethpongDara PotterWinnie MutsotsoCraig B. BorkowfDorothy Mbori-NgachaPeter MuiruriJohn Odero Ong'echIsaac ZuluLungowe NjobvuBongkoch JetsawangSonal PathakMarc BulterysNathan ShafferPaul J. WeidleCentre for Infectious Disease Research in ZambiaThailand Ministry of Public HealthCenters for Disease Control and PreventionKenyatta National HospitalUniversity of NairobiMahidol UniversityRajavithi HospitalCDC Global AIDS ProgramGlobal AIDS ProgramNational Center for HIV/AIDS, Viral Hepatitis, STD, and TB PreventionUniversity Teaching Hospital LusakaNorthrop Grumman corporation2018-09-242018-09-242010-02-01PLoS Medicine. Vol.7, No.2 (2010)15491676154912772-s2.0-77649083137https://repository.li.mahidol.ac.th/handle/20.500.14594/29790Background: Intrapartum and neonatal single-dose nevirapine (NVP) reduces the risk of mother-to-child HIV transmission but also induces viral resistance to non-nucleoside reverse transcriptase inhibitor (NNRTI) drugs. This drug resistance largely fades over time. We hypothesized that women with a prior single-dose NVP exposure would have no more than a 10% higher cumulative prevalence of failure of their NNRTI-containing antiretroviral therapy (ART) over the first 48 wk of therapy than would women without a prior exposure. Methods and Findings: We enrolled 355 NVP-exposed and 523 NVP-unexposed women at two sites in Zambia, one site in Kenya, and two sites in Thailand into a prospective, non-inferiority cohort study and followed them for 48 wk on ART. Those who died, discontinued NNRTI-containing ART, or had a plasma viral load ≥400 copies/ml at either the 24 wk or 48 wk study visits and confirmed on repeat testing were characterized as having failed therapy. Overall, 114 of 355 NVP-exposed women (32.1%) and 132 of 523 NVP-unexposed women (25.2%) met criteria for treatment failure. The difference in failure rates between the exposure groups was 6.9% (95% confidence interval [CI] 0.8%-13.0%). The failure rates of women stratified by our predefined exposure interval categories were as follows: 47 of 116 women in whom less than 6 mo elapsed between exposure and starting ART failed therapy (40%; p<0.001 compared to unexposed women); 25 of 67 women in whom 7-12 mo elapsed between exposure and starting ART failed therapy (37%; p = 0.04 compared to unexposed women); and 42 of 172 women in whom more than 12 mo elapsed between exposure and starting ART failed therapy (24%; p = 0.82 compared to unexposed women). Locally weighted regression analysis also indicated a clear inverse relationship between virologic failure and the exposure interval. Conclusions: Prior exposure to single-dose NVP was associated with an increased risk of treatment failure; however, this risk seems largely confined to women with a more recent exposure. Women requiring ART within 12 mo of NVP exposure should not be prescribed an NNRTI-containing regimen as first-line therapy.Mahidol UniversityMedicineArticleSCOPUS10.1371/journal.pmed.1000233