Nevirapine resistance
sdNVP given during to the HIV-infected mothers during labour, and the infant soon after birth, significantly reduces the risk of HIV transmission. However, studies have found that the single exposure to monotherapy with nevirapine could put the woman at risk of nevirapine-resistance. These studies detected mutations in the virus that confer resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) in a high percentage of women for four to eight weeks after delivery.
What's more, a study in Thailand found that if ART treatment was begun within several months
of delivery, women exposed to sdNVP were less likely to achieve virologic suppression when treated with an NNRTI-regimen than unexposed women.
However, studies have also shown that the detection of NNRTI-resistance mutations decreases over time suggesting that women who have longer to wait before initiating ART might have better response to treatment.
Prior exposure to single-dose nevirapine (sdNVP, Viramune) for the prevention of mother-to-child transmission (PMTCT) does not necessarily impair a woman’s subsequent response to nevirapine-containing antiretroviral treatment (ART), particularly if enough time passes between that exposure and the need for ART, according to studies presented at the Thirteenth Conference on Retroviruses and Opportunistic Infections in Denver. The studies suggest that nevirapine-containing regimens are still a good first-line option for ART for many sdNVP-exposed women in resource-limited settings.
Zimbabwean study in women exposed more than one year ago
Another study presented as a poster at the conference produced generally supportive results in women who had been involved in PMTCT programmes more than one year earlier. This Zimbabwean study compared responses to NNRTI-based ART in women who had been exposed to either sdNVP or short-course AZT (scAZT) for PMTCT, and compared responses to ART in their spouses. (The complete poster can be downloaded as a pdf file from the conference site http://www.retroconference.org/2006/PDFs/544.pdf).
The study involved 87 patients (54 women and 33 men); 20 women and 34 women had pre-exposure to sdNVP and scAZT respectively. Although the median age was significantly lower in the women than the men, viral loads and CD4 cell counts were similar.
At weeks 16, 24 and 48, 83%, 85% and 74% had viral loads below 400 copies/ml, respectively. Median CD4 cell counts for both women and men increased significantly.
Yet, at week 16, the proportion of women (76%) with
However, when the women with exposure to sdNVP were compared to those with exposure to scAZT, there were no statistically significant differences in viral load responses throughout the 48 weeks study period, p > 0.30. This isn’t all that reassuring however, given that resistance to either drug would make triple drug therapy less effective.
Even if minor, the differences between the men and women exposed to treatment for PMTCT might be a cause for concern. The difference could not be accounted for by differences in treatment adherence, which was 98% for both men and women throughout the study period.
Women exposed to sdNVP more than 18 months ago
A South African team set out to test this theory at Coronation Hospital in Johannesburg. The study compared responses to NNRTI-based ART in women exposed to sdNVP 18 to 36 months earlier to responses in women with no prior nevirapine exposure. Researchers attempted to match groups by CD4 cell count and by time since last delivery. Women are followed for 24 weeks with monthly viral load tests, after which point viral load will be monitored every three months out to week 96.
At present, the study involves 65 women with prior sdNVP exposure and 40 without. Those without prior exposure to sdNVP appear slightly more likely to be from a disadvantaged socio-economic background, though only one indicator of this, having a refrigerator in their home, reached statistical significance.
There also seem to be some slight differences at baseline between the groups which probably reflect a longer time under clinical care for those with prior sdNVP exposure. For example, viral loads at baseline were roughly 50% lower in those with prior sdNVP (90,000 copies/ml vs. 177,000 copies/ml) though their CD4 cell counts were slightly lower (139mm3 vs. 165mm3) as well. Symptomatic disease (WHO clinical stage) were very well matched but women were more likely to have been hospitalised within the last twelve months (17% vs. 8%) — although this difference was not quite significant — or to be on cotrimoxazole prophylaxis (34% vs. 15%, p
These differences may account for some of the differences in outcomes, because the women with prior sdNVP exposure actually were significantly more likely to have viral loads below 50 copies/ml at weeks eight, 16, 20 and 24 than the unexposed controls. In fact, all 48 women with prior sdNVP exposure to have reached week 24 have viral loads under 50 copies/ml compared to only 17 out of 23 of the unexposed controls. Both groups experienced similar rises in CD4 cell counts.
References:
Coovadia A et al. Virologic Response to NNRTI Treatment among Women Who Took Single-dose Nevirapine 18 to 36 Months Earlier. Thirteenth Conference on Retroviruses and Opportunistic Infections, Denver, abstract 641, 2006.
Zijenah L. Community-based Generic ART following Single-dose Nevirapine or Short-course Zidovudine in Zimbabwe. Thirteenth Conference on Retroviruses and Opportunistic Infections, Denver, abstract 544, 2006.
Conclusion
t is possible that the Zimbabwean study represents the midway point between the experience in Thailand and the South African study, and that, if ART treatment is required less than 18 months after participation in PMTCT programmes, that women should rather be put on a PI-based regimen, at least temporarily. Nevertheless, most women have a good response to treatment regardless.
A better option would be, as the South African study authors wrote, "as treatment programs are rolled out, most women in immediate need of treatment should be identified before delivery." Such women should either be enrolled directly into ART programmes, or offered a short-course AZT/3TC post-delivery to prevent the development of resistance to nevirapine.