Early clinical and immune response to NNRTI-based antiretroviral therapy among women with prior exposure to single-dose nevirapine

Abstract

Objective: To determine whether prior exposure to single-dose nevirapine (NVP) for prevention of mother-to-child HIV transmission (PMTCT) is associated with attenuated CD4 cell response, death, or clinical treatment failure in women starting antiretroviral therapy (ART) containing non-nucleoside reverse transcriptase inhibitors (NNRTI).

Methods: Open cohort evaluation of outcomes for women in program sites across Zambia. HIV treatment was provided according to Zambian/World Health Organization guidelines.

Results: Peripartum NVP exposure status was known for 6740 women initiating NNRTI-containing ART, of whom 751 (11%) reported prior use of NVP for PMTCT. There was no significant difference in mean CD4 cell change between those exposed or unexposed to NVP at 6 (+202 versus +182 cells/microl; P = 0.20) or 12 (+201 versus +211 cells/microl; P = 0.60) months. Multivariable analyses showed no significant differences in mortality [adjusted hazard ratio (HR), 1.2; 95% confidence interval (CI), 0.8-1.8] or clinical treatment failure (adjusted HR, 1.1; 95% CI, 0.8-1.5). Comparison of recent NVP exposure with remote exposure suggested a less favorable CD4 cell response at 6 (+150 versus +219 cells/microl; P = 0.06) and 12 (+149 versus +215 cells/microl; P = 0.39) months. Women with recent NVP exposure also had a trend towards elevated risk for clinical treatment failure (adjusted HR, 1.6; 95% CI, 0.9-2.7).

Conclusion: Exposure to maternal single-dose NVP was not associated with substantially different short-term treatment outcomes. However, evidence was suggestive that exposure within 6 months of ART initiation may be a risk factor for poor treatment outcomes, highlighting the importance of ART screening and initiation early in pregnancy.

Fig. 1

Description of primary evaluation cohort, comprising HIV-infected women initiating antiretroviral therapy (ART) with nevirapine (NVP) exposure status determined at time of enrollment, April 2004 to July 2006, Zambia.

Fig. 2. Changes in mean CD4 cell count at 6 and 12 months among women with nevirapine exposure and non-exposure determined at time of enrollment, April 2004 to July 2006, Zambia

Results were controlled for baseline World Health Organization stage, CD4 cell count, tuberculosis status, body mass index, and age; CD4 cell responses were adjusted to the mean value of each variable.

Fig. 3

One-year mortality alone (a) and treatment failure including death (b) among women with nevirapine (NVP) exposure and non-exposure determined at time of enrollment, April 2004 to July 2006, Zambia.