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Session 137 Poster Abstracts
Vertical Transmission and Antiretroviral Resistance
Friday, 1:30 - 3:30 pm
Hall B


799    
Comparison of Nevirapine Rresistance in Women with Subtype C Compared with Subtypes A and D after Single-dose NVP
Susan H Eshleman*1, D Hoover2, S Chen1, S Hudelson1, L Guay1, A Mwatha3, E Brown4, F Mmiro5, P Musoke5, J Jackson1, N Kumwenda1, and T Taha1
1Johns Hopkins Med Inst, Baltimore, MD, USA; 2Rutgers Univ, Piscataway, NJ, USA; 3Fred Hutchinson Cancer Res Ctr, Seattle, WA, USA; 4Univ of Washington, Seattle, USA; and 5Makerere Univ, Kampala, Uganda

Background:  The HIVNET 012 trial in Uganda demonstrated that single dose nevirapine (NVP) can prevent mother-to-child transmission of HIV-1 (MTCT). However, NVP-resistance mutations were detected in 25% of women 6 to 8 weeks after NVP, with a higher rate of NVP resistance in women with subtype D than subtype A HIV-1. Subtype C is the most common HIV-1 subtype both worldwide and in many resource-poor countries likely to use single-dose NVP  to prevent MTCT. We compared the rate of NVP resistance in women with HIV-1 subtypes A, C, and D, 6 to 8 weeks after single-dose NVP administration.

Methods:  Subjects included 67 women with subtype C (NVAZ trial, Malawi), 147 women with subtype A and 98 women with subtype D (HIVNET 012, Uganda). HIV-1 genotyping was performed using the ViroSeq system. Subtyping was performed by phylogenetic analysis of pol region sequences. The probability of NVP resistance and of individual NVP-resistance mutations were compared with the c2 test. Risk factors associated with NVP resistance were analyzed with univariate and multivariate logistic regression.

Results:  The rate of NVP resistance (detection of any NVP-resistance mutation) was higher in women with subtype C (45 of 67 = 67%) than in women with subtype A (28 of 147 = 19%, p < 0.001) or D (35 of 98 = 36%, p < 0.001). The portion of women with 2 or more NVP resistance mutations was also higher for subtype C (29 of 67 = 43%) than for subtype A (12 of 147 = 8%, p < 0.001) or D (16 of 98 = 16%, p < 0.001). The most common NVP resistance mutations detected in all 3 subtypes were K103N and Y181C. The rate of detection of both mutations was higher in women with subtype C than subtypes A or D (p < 0.0001). In a multivariate model, subtype (C vs A OR = 8.38, 95% CI 4.19 to 16.76; C vs D OR = 3.27, 95% CI 1.63 to 6.59) and delivery viral load (OR = 2.23, 95% CI 1.53 to 3.25) were independent predictors of NVP resistance, but age, parity, and NVP dosing time relative to delivery were not. There were no significant differences in age, parity, NVP dosing time, or delivery viral load among women with subtypes A, C, and D.

Conclusions:  HIV-1 subtype influences selection of HIV-1 variants with NVP-resistance mutations after single dose NVP exposure. The rate of NVP resistance 6 to 8 weeks after single dose NVP administration was significantly higher in subtype C than subtypes A or D.

Keywords: nevirapine; subtype; resistance