Response to treatment after single dose NVP exposure in women
Polly Clayden, HIV i-Base
In an oral presentation, Paul Weidle showed findings from a prospective cohort study of treatment response to an NNRTI-based regimen in women exposed or unexposed to single dose nevirapine for PMTCT. 
The study was conducted in Zambia (n=201), Thailand (n=87), and Kenya (n=67) between May 2005 and January 2007. The investigators looked at treatment failure (viral load >/=400 copies/mL, not on NNRTI, died) at 6 months after initiation of HAART.
Of the 878 women, 355 were single dose NVP-exposed (including with short course AZT) and 523 unexposed. Single dose NVP-exposed women were younger (29 vs 33 years, p <0.001), had a higher median CD4 (160 vs 139 cells/mm3, p= 0.007), and lower median viral load (97,300 vs 142,000 copies/mL, p= 0.02).
The investigators reported that at 6 months after initiation of HAART, 186 (21%) women had failed (76 had viral load >/=400 copies/mL, 51 left the study, 48 died, and 11 had been switched to a protease inhibitor).
In a primary analysis looking at treatment failure at 24 weeks, they found women exposed to single dose NVP </=6 months before initiating NNRTI-based HAART, with baseline CD4 0 to 49 cells/mm3 or viral load >100,000 copies/mL responded less well to treatment (see table for odds ratios for treatment failure).
They also reported that women exposed to single dose NVP >12 months before NNRTI-based HAART did as well as unexposed women at time of analysis.
In a secondary on-treatment analysis, including only those still on NNRTI-based ART at 6 months, they reported similar results.
The investigators wrote: These data do suggest an increased risk of treatment failure among women with recent single dose NVP exposure, but not with single dose NVP exposure >12 months before initiation of NNRTI-based ART. Treatment with ART or perinatal HIV prevention strategies other than single dose NVP should be considered for pregnant women who are likely to initiate ART within 1 year after delivery.
Table 1: Odds ratios for treatment failure at 24 weeks, primary analysis
|Baseline characteristics (n=878)||Adjusted odds ratio (95% CI),also adjusted for age|
|Time since exposure: Unexposed <6 months 7-12 months >12 months||Ref 1.9 (1.1-3.1) 1.6 (0.9-3.0) 0.9 (0.8-2.7)|
|Thailand Zambia Kenya||Ref 2.0 (1.2-3.2) 1.5 (0.8-2.7)|
|CD4 >200 cells/mm3 50-199 0-49||Ref 1.4 (0.9-2.2) 3.2 (1.9-5.5)|
|Viral load <10,000 10,000-99,000 =100,000||Ref 1.9 (0.95-3.6) 2.3 (1.2-4.3)|
|WHO stage I or II III IV||Ref 1.4 (0.85-21) 1.7 (0.96-2.8)|
The failure rates in Africa versus Thailand reported in this study are scary.
Following this presentation John Mellors remarked that, 24 weeks is not long enough for emergence of archived resistance. One problem now seems to be that we could be getting a false sense of security from some of these studies with short follow up and the just wait 6 months school-of-thought gains momentum. [2, 3, 4]
From the early days of denial, the emergence of resistance following single NVP to prevent MTCT story has swung past the alarmingly high rates of resistance seen if you looked early enough and hard enough to the most important question of when does it matter? Single dose NVP alone should not be given if there are sufficient resources to use more effective strategies. These would include HAART for pregnant women with advanced disease (some would say HAART for all) and short course AZT plus single dose NVP plus cover for the NVP tail for women not eligible for HAART.
Unfortunately, where resources are such that single dose NVP is the only option, the chances of initiating HAART in the mother less than 12 months later seem small.
- Weidle P, Stringer J, McConnell et al. Effectiveness of NNRTI-containing ART in women previously exposed to a single dose of nevirapine: A multi-country cohort study. 15th CROI. February 2008. Boston USA. Oral abstract 48.
- Lockman S, Shapiro RL, Smeaton LM, et al. Response to antiretroviral therapy after a single, peripartum dose of nevirapine. N Engl J Med 2007; 356: 135-147.
- Coovadia H, Marais B, Abrams E, et al. Virologic responses to NNRTI treatment among women who took single-dose nevirapine 18 to 36 months earlier. 13th Conference on Retroviruses and Opportunistic Infections, Denver, Feb 58, 2006
- HTB January/February 2007. Response to nevirapine containing HAART following single dose nevirapine for PMTCT