No subtype-based differences in baseline levels of K103N-containing variants in women receiving single dose nevirapine
3 August 2006. Related: Conference reports, Drug resistance, Intl Drug Resistance Workshop 15 Sitges 2006.
Polly Clayden, HIV i-Base
Previous research has found the frequency of nevirapine resistance after receiving single dose nevirapine is higher in women with HIV-1 subtype C (69%) than D (36%), and lowest in women with subtype A (19%). K103N is the most common nevirapine-associated resistance mutation, detected 68 weeks after nevirapine administration in all three subtypes.
In another poster from the same group, Jessica Church and coworkers presented findings from a study, in which they quantified the level of K103N-containing variants in baseline samples from antiretroviral drug naive women with subtypes A, C and D. All women were receiving single dose nevirapine, in the HIVNET 012 trial (Uganda, 1997-1999) or the NVAZ trial (Malawi, 20002003).
Samples were taken prior to the women receiving single dose nevirapine in the HIVNET 012 trial, and at delivery (within hours after receiving single dose nevirapine) in the NVAZ trial. Samples were available from 279 women (125 subtype A, 63 subtype C and 91 subtype D).
Using the ViroSeq HIV-1 Genotyping system HIV genotyping was successful for 254 (91.4%) women (120 subtype A, 47 subtype C, and 87 subtype D). None of the samples had K103N detected by Viroseq.
Five (2%) of the 254 women had polymorphisms at or near codon 103: 1 each with K101Q, K103R, K103Q, and 2 with V106I.
Samples were also analysed for K103N containing variants using the Ligamp point mutation assay. 236 (92.9%) of the 254 genotyped samples were successfully re-amplified (110/120 subtype A, 46/47 subtype C and 80/87 subtype D).
The investigators found the percentage of K103N was <0.5% in 231/236 (97.9%) samples. K103N was detected at >/=0.5% in 5 samples: 4 samples had 0.5-1% K103N and 1 had 3.9% K103N (a sample with K103Q). They reported that this was likely to represent a false positive result, since K103N was not detected in any of 92 clones from that sample. Only 2 of the 5 women with K103N detected at baseline had K103 detected 6-8 weeks after single dose nevirapine.
The investigators noted that the lack of detection of K103N was unlikely to be due to low viral load. The median viral load was >20,000 copies/mL for all three subtypes, and >2,000 copies/mL (the minimum viral load required to detect 0.5% K103N) in 210(93%) of the 225 samples with viral load data.
They concluded that nevirapine resistance mutations are uncommonly detected in antiretroviral naive African women with subtypes A, C and D. They wrote: We did not find any differences in the baseline levels of K103N containing variants that could explain the subtype-based differences in the frequencies of nevirapine resistance seen in these women after single dose nevirapine exposure.
Reference:
Church JD, Gua yLA, Taha TE et al. Analysis of levels of K103N-containing HIV-1 variants in antiretroviral drug naive African women with HIV-1 subtypes A, C and D who subsequently received single dose nevirapine for prevention of HIV-1 mother-infant transmission. XV International HIV Drug Resistance Workshop, Sitges, Spain, July 2006. Abstract 96.