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

A Zambian study authored by Benjamin Chi and co-workers, published in the 11 May 2007 edition of AIDS, evaluated outcomes for women receiving NNRTI-containing HAART after prior exposure to single dose nevirapine (NVP) from April 2004 to 31 July 2006. This was an open cohort evaluation in programme sites across Zambia.

In this study of 6740 women initiating NNRTI-containing ART, 751 (11%) reported prior use of NVP for PMTCT.

The investigators found of the 229 NVP-exposed and 1530 NVP-unexposed women for whom CD4 data were available at baseline and at 6 months, the mean increase was 202 cells/mm3 and 182 cells/mm3 respectively, p=0.20. At 12 months for the 110 NVP-exposed and 659 NVP-unexposed with data available, the mean increase was 201 cells/mm3 and 211 cells/mm3, p=0.60.

Multivariable analyses showed no significant differences in mortality (adjusted HR, 1.2; 95% CI, 0.8-1.8) or clinical treatment failure (adjusted HR, 1.1; 95% CI, 0.8-1.5).

434 (58%) NVP-exposed women had timing data available from NVP-exposure to initiation of therapy. The median interval time was 15.6 months (IQR 7.5-29.9). Of this group, 81 (19%) were exposed within 6 months prior to initiation of therapy. The remaining 353 (81%) reported remote (defined as 6 months or greater) NVP exposure prior to initiation of therapy.

Comparison of recent NVP exposure with remote exposure suggested a less favorable CD4 cell response at 6 months (+150 versus +219 cells/mm3; p=0.06) and 12 months (+149 versus +215 cells/mm3, p= 0.39) months. Women with recent NVP exposure also had a trend towards increased risk for clinical treatment failure (adjusted HR, 1.6; 95% CI, 0.9-2.7).

Exposure to maternal single-dose NVP was not associated with substantially different short-term treatment outcomes in this study. However, evidence was suggestive that exposure within 6 months of ART initiation may be a risk factor for poor treatment outcomes.

The investigators acknowledged the limitations of this study, including the short duration of follow up; they suggest longer periods (2 years or more) may be needed for comparisons to manifest. Additionally, viral load data would allow a more critical evaluation of this question and the study relies on self-report of NVP exposure. Finally, although this is one of the largest cohorts yet available to look at this question, the sample may still be too small to detect subtle differences in survival or treatment failure.

They write. In the meantime, links between PMTCT and ART services should be strengthened so that women requiring ART start therapy prior to delivery and thus avoid treatment initiation following NVP exposure occurring less than 6 months previously.

Comment

The authors are absolutely right – the short follow up and lack of viral load and resistance data make it difficult to comment on what this means for those mothers who have already taken sdNVP alone for PMTCT and have deferred starting NVP based HAART for at least 6 months.

The recommendation is that links between PMTCT and ART services should be strengthened, so that women who require treatment for their own health receive it in pregnancy cannot be stressed more and is echoed in findings from many other cohorts.

Chi B H, Sinkala M, Stringer E M et al. Early clinical and immune response to NNRTI-based antiretroviral therapy among women with prior exposure to single-dose nevirapine. AIDS. 21(8):957-964, May 11, 2007.