K103N containing variants persist longer in women with subtype D and with higher viral loads

3 August 2006. Related: Conference reports, Drug resistance, Intl Drug Resistance Workshop 15 Sitges 2006.

Polly Clayden, HIV i-Base

A group of women who had received single dose nevirapine in the HIVNET 012 trial were enrolled in a long-term (up to five years) follow-up study.

Tamara Flys and coworkers from John Hopkins, analysed plasma samples from 184 of these women. The group included 39 women who were re-exposed to single dose nevirapine in one or two subsequent pregnancies. The LigAmp sensitive and quantitative point mutation assay (cutoff: 0.5% K103N) was used to detect the K103N mutation.

The authors reported a cumulative percentage of women with undetectable K103N of 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 among women receiving only single dose nevirapine in one pregnancy.

They found that the rate of “fading” of detectable K103N containing variants was slower in women with subtype D than A.

In multivariate analysis, sub types (D versus. A, HR: 0.50, 95% CI: 0.33–0.76, p=0.0005) and pre-nevirapine viral load (per log increase, HR: 0.63, 95% CI: 0.48–0.83, p=0.0007), were independently associated with slower fading, while baseline CD4 cell count was not.

Of the 39 women who received single dose nevirapine for subsequent pregnancies during the follow-up study, most had undetectable K103N within a year of re-exposure.

They also found that when K103N was detected, it was present at low levels, and “faded” from detection within 1 year of additional follow-up.

The authors concluded that K103N was undetectable in plasma from most women within 6–8 weeks of receiving single dose nevirapine in pregnancy, 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. They noted, “K103N-containing variants persisted longer in women with subtype D and in women with higher baseline viral loads.”

Reference:

Flys TS, Mwatha A, Donnell D et al. 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). XV International HIV Drug Resistance Workshop, Sitges, Spain, July 2006. Abstract 46.