Effectiveness of Non-nucleoside Reverse-Transcriptase Inhibitor-Based Antiretro viral Therapy in Women Preexposed to a Single Intrapartum Dose of Nevirapine: A Multi-country, Prospective Cohort Study
Date
2010-02Author
Stringer, Jeffrey S. A.
McConnell, Michelle S.
Kiarie, James
Bolu, Omotayo
Anekthananon, Thanomsak
Jariyasethpong, Tavatchai
Potter, Dara
Mutsotso, Winnie
Borkowf, Craig B
Ngacha, Dorothy Mbori
Muiruri, Peter
Ong’ech, John Odero
Zulu, Isaac
Njobvu, Lungowe
Jetsawang, Bongkoch
Pathak, Sonal
Bulterys, Marc
Shaffer, Nathan
Weidle, Paul J.
Type
ArticleLanguage
enMetadata
Show full item recordAbstract
Background:
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.
Please see later in the article for the Editors’ Summary
URI
http://erepository.uonbi.ac.ke:8080/xmlui/handle/123456789/10531http://www.ncbi.nlm.nih.gov/pubmed/20169113
Citation
February 2010 | Volume 7 | Issue 2Collections
- Faculty of Health Sciences (FHS) [10377]