Association between HIV subtype and detection of K103N
Polly Clayden, HIV i-Base
In a previous study Susan Eshlemans group analysed nevirapine resistance, at 6-8 weeks after receiving single dose nevirapine, in women with subtype C from the NVAZ trial, Malawi, and subtypes A and D from the HIVNET 012 trial, Uganda using the ViroSeq HIV-1 Genotyping System .
The authors found that nevirapine resistance was lowest for subtype A and highest for subtype C. The most common NVP-resistance mutation in all three subtypes was K103N.
A poster from Tamara S.Flys presented further analysis using a sensitive and quantitative point mutation assay, LigAmp to compare the level and prevalence of K103N containing variants in women with subtypes A,C and D at 6-8 weeks after receiving single dose nevirapine . The assay cutoff for detection of K103N was 0.5%.
Samples from 238 women were evaluated: 144 subtype A and 94 subtype D from HIVNET 012 and 63 subtype C from NVAZ.
The authors found that the proportion of women with K103N was lowest for subtype A and highest for C (A, 60/144 (41.7%); C, 44/63 (69.8%); D, 51/94 (54.3%); A vs C, p <0.0001; A vs D, p= 0.06; C vs D, p= 0.07). In a multivariate model, detection of K103N was independently associated with a higher delivery viral load (OR = 2.69, 95%CI 1.89 to 3.84) and subtype (C>A, OR = 2.48, 95%CI 1.24 to 4.93; D>A, OR = 1.71, 95%CI 0.94 to 3.11), but not with age or parity. Fewer days between receiving the single dose nevirapine and the 6-8 week visit was also significantly associated with the detection of K103N (OR=3.24, 95% CI 1.89-3.84)
Among those women who had detectable K103N, the median percentage of K103N was lower for subtype A (2.22%) than for C (11.8%, p= 0.0007) or D (4.95%, p= 0.06). In a multivariate model, a higher level of K103N-containing variants (log10 % K103N) was associated with HIV subtype (C>A, p= 0.0001, ݠ = 0.46, 95%CI 0.23 to 0.68; D>A: p= 0.02, ݠ= 0.27, 95%CI 0.05 to 0.49; C vs D, no difference, p= 0.12), but age (p= 0.70), parity (p= 0.62), the number of days between NVP dosing and the 6-8 week visit (p= 0.10), and delivery viral load (p= 0.46) were not.
The authors wrote: We found a significant association between HIV-1 subtype and detection of K103N for subtype C vs A. The portion of women with K103N detected was also higher for subtype C than D, and for subtype D than A, but these differences were not statistically significant. Additionally, In a multivariate analysis, restricted to women with >/= 0.5% K103N-containing variants, a higher level of K103N containing variants was associated with HIV subtype for both C>A and D>A.
- Eshleman SH, Hoover DR, Chen C et al. Nevirapine resistance in women with HIV-1 subtype C compared with subtypes A and D, after the administration of single-dose nevirapine. JID, 192:30-36; 2005.
- Flys TS, Chen S, Jones D et al. Analysis of K103N-containing HIV-1 variants in women with HIV-1 subtypes A, C, and D after single-dose nevirapine using a sensitive and quantitative point mutation assay. 13th CROI, Denver, 2006. Abstract 726.