15th International HIV Drug Resistance Workshop 13-17 June 2006, Sitges, Spain

FADING OF K103N-CONTAINING HIV-1 VARIANTS AFTER INITIAL AND REPEATED EXPOSURE TO SINGLE DOSE NEVIRAPINE FOR PREVENTION OF HIV-1 MOTHER-TO-CHILD TRANSMISSION (HIVNET 012)

Antivir Ther. 2006, 11:S53 (abstract no. 45)

TS Flys¹, A Mwatha², D Donnell², C Nakabiito³, P Musoke³, F Mmiro³, JB Jackson¹, LA Guay¹ and SH Eshleman
¹Johns Hopkins University School of Medicine, Baltimore, MD, USA; ²Fred Hutchinson Cancer Research Center, Seattle, WA USA; ³Makerere University, Kampala, Uganda

BACKGROUND: The K103N nevirapine resistance mutation is often detected in women after administration of single dose nevirapine for prevention of HIV-1 mother-to-child transmission. We analysed fading of K103N-containing HIV variants over several years in Ugandan women who received single dose nevirapine in the HIVNET 012 trial.

METHODS: Some women who received single dose nevirapine in HIVNET 012 were enrolled in a long-term follow-up study, with plasma samples collected up to 5 years after single dose nevirapine exposure. We analysed 184 of those women, including 39 who were re-exposed to single dose nevirapine in one or two subsequent pregnancies. K103N was detected in plasma samples using a sensitive and quantitative point mutation assay, LigAmp (assay cutoff: 0.5% K103N).

RESULTS: Among women who were not re-exposed to single dose nevirapine, the cumulative percentage of women with undetectable K103N was 58.6% by 6–8 weeks, 85.2% by 2 years, 92.1% by 3 years, 99.1% by 4 years, and 99.1% by 5 years. The rate of fading of K103N-containing variants was slower in women with subtype D than A. In a multivariate model, HIV-1 subtype (D versus. A, hazard ratio: 0.50, 95% confidence intervals (CI): 0.33–0.76, P=0.0005) and pre-nevirapine viral load (per log increase, hazard ratio: 0.63, 95% CI: 0.48–0.83, P=0.0007) were independently associated with slower fading, but baseline CD4 cell count was not. Among 39 women who were re- exposed to single dose nevirapine during the follow-up study, most had undetectable K103N within a year of re-exposure. When K103N was detected, it was present at low levels, and faded from detection within 1 year of additional follow-up.

CONCLUSIONS: K103N was undetectable in plasma from most women within 6–8 weeks of single dose nevirapine exposure, and in plasma from all evaluable women within 4 years. This included women who were re-exposed to single dose nevirapine in a subsequent pregnancy during the follow-up period. K103N-containing variants persisted longer in women with subtype D and in women with higher baseline viral loads.

2006-06-13
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