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Detection of K103N in Ugandan women after repeated exposure to single dose nevirapine

Flys, Tamara Sa; Mwatha, Anthonyb; Guay, Laura Aa; Nakabiito, Clemensiac; Donnell, Deborahb; Musoke, Philippac; Mmiro, Francisd; Jackson, J Brooksa; Eshleman, Susan Ha

doi: 10.1097/QAD.0b013e3282703847
Epidemiology and Social

Objectives: Use of single dose nevirapine (SD NVP) for prevention of HIV-1 mother-to-child transmission (pMTCT) is associated with selection of K103N-containing HIV variants. Repeat use of SD NVP for pMTCT may influence emergence and persistence of NVP-resistant variants.

Design: K103N-containing variants were studied in 48 Ugandan women who received SD NVP in the HIVNET 012 trial, and were re-exposed to SD NVP in one (n = 44) or two (n = 4) subsequent pregnancies during a 5-year follow-up study.

Methods: Samples were analyzed using the LigAmp assay (assay cutoff: 0.5% K103N).

Results: Among 44 women who were re-exposed to SD NVP in one subsequent pregnancy, 37.8% had K103N detected within 1 year of SD-NVP re-exposure. Detection of K103N was independently associated with detection of K103N 6–8 weeks after the first SD NVP exposure and with pre-NVP viral load. The portion of women with undetectable K103N by 2 years after SD NVP administration was similar after first versus second use of SD NVP for pMTCT. K103N was undetectable in 93.2% of evaluable women by 3 years of re-exposure. Only two of four women who received SD NVP in two pregnancies during the follow-up study had K103N detected after the last SD NVP exposure.

Conclusions: K103N was detected in some women within 1 year of SD NVP re-exposure, but faded from detection in most women by 3 years after re-exposure. Detection of K103N by 1 year after SD NVP re-exposure was associated with prior selection of K103N-containing variants and with pre-NVP viral load.

From the aDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland

bStatistical Center for HIV/AIDS Research & Prevention, Fred Hutchinson Cancer Res. Ctr., Seattle, Washington, USA

cDepartment of Paediatrics, Uganda

dDepartment of Obstetrics and Gynaecology, Makerere University, Kampala, Uganda.

Received 16 January, 2007

Revised 31 March, 2007

Accepted 5 April, 2007

Correspondence to Susan Eshleman, MD/PhD, Dept. of Pathology, The Johns Hopkins Medical Institutions, Ross Bldg. 646, 720 Rutland Ave. Baltimore, MD 21205, USA. E-mail: seshlem@jhmi.edu

© 2007 Lippincott Williams & Wilkins, Inc.