[50] DISTINCT PATTERNS OF SELECTION AND FADING OF K103N AND Y181C ARE SEEN IN WOMEN WITH SUBTYPE A VS D HIV-1 AFTER SINGLE DOSE NEVIRAPINE: HIVNET 012

13th International HIV Drug Resistance Workshop

8–12 June 2004, Tenerife Sur-Costa Adeje, Canary Islands, Spain

DISTINCT PATTERNS OF SELECTION AND FADING OF K103N AND Y181C ARE SEEN IN WOMEN WITH SUBTYPE A VS D HIV-1 AFTER SINGLE DOSE NEVIRAPINE: HIVNET 012

Antiviral Therapy 2004; 9:S59 (abstract 50)

SH Eshleman¹, J Wang², LA Guay¹, SP Cunningham¹, A Mwatha², ER Brown³, P Musoke⁴, F Mmiro⁴ and JB Jackson¹
¹The Johns Hopkins Medical Institutions, Baltimore, Md., USA; ²Fred Hutchinson Cancer Research Center, Seattle, Wash., USA; ³University of Washington, Seattle, Wash., USA; and ⁴Makerere University, Kampala, Uganda

BACKGROUND: The Ugandan HIVNET 012 trial demonstrated that a single dose nevirapine (NVP) regimen can prevent HIV-1 mother-to-child transmission. NVP resistance (NVPR) mutations were detected in 25% of women 6–8 weeks after NVP. Women with subtype D had a higher rate of NVPR than women with subtype A. In an exploratory study of 65 women, the major NVPR mutation detected shifted from Y181C at 7 days to K103N at 6–8 weeks. This study examined emergence and fading of Y181C and K103N in women with subtype A vs D.

METHODS: Plasma HIV-1 was analysed with the ViroSeq™ HIV-1 Genotyping System. HIV-1 subtypes were determined by phylogenetic analysis of pol region sequences. Genotypes were obtained for 7 day and 6–8 week samples (paired data) for 159 women, including 83 with subtype A and 57 with subtype D. The rate of NVPR at the two time points was compared in women with subtype A vs D using the Generalized Estimating Equation (GEE).

RESULTS: In the subset of 140 women with subtypes A and D, the rate of NVPR increased from 7 days to 6–8 weeks. The rate of NVPR was similar in women with subtype A vs D at 7 days, but was higher in women with subtype D at 6–8 weeks. The higher rate of NVPR in women with subtype D at 6–8 weeks was explained by at least two factors: 1) Y181C faded from detection at a significantly greater rate in women with subtype A (OR: 3.06; 95% CI: 1.04, 8.90); and 2) K103N tended to accumulate at a greater rate in women with subtype D, although that difference was not statistically significant (OR: 1.74; 95% CI: 0.62, 4.87). Other NVPR mutations were detected, but the number of women with those mutations was too small for meaningful statistical analysis.

CONCLUSIONS: HIV-1 subtype influences selection and fading of NVPR mutations after single-dose NVP. Different patterns of selection and fading were observed for K103N and Y181C in women with subtypes A vs D. This suggests that HIV-1 subtype influences how specific drug resistance mutations impact viral replication in the presence and absence of antiretroviral drugs.

PRESENTING AUTHOR: SH Eshleman

2004-06-08
50

Copyright © 2004 - International Medical Press Ltd.. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the International Medical Press Ltd. 2-4 Idol Lane, London EC3R 5DD UK.