Adverse Events in a Cohort of HIV Infected Pregnant and Non-Pregnant Women Treated with Nevirapine versus Non-Nevirapine Antiretroviral Medication

Abstract

BackgroundPredictors of adverse events (AE) associated with nevirapine use are needed to better understand reports of severe rash or liver enzyme elevation (LEE) in HIV+ women.MethodologyAE rates following ART initiation were retrospectively assessed in a multi-site cohort of 612 women. Predictors of onset of rash or LEE were determined using univariate and multivariate analyses.Principal FindingsOf 612 subjects, 152 (24.8%) initiated NVP-based regimens with 86 (56.6%) pregnant; 460 (75.2%) initiated non-NVP regimens with 67 (14.6%) pregnant.LEENo significant difference was found between regimens in the development of new grade ≥2 LEE (p = 0.885). Multivariate logistic regression demonstrated an increased likelihood of LEE with HCV co-infection (OR 2.502, 95% CI: 1.04 to 6, p = 0.040); pregnancy, NVP-based regimen, and baseline CD4 >250 cells/mm3 were not associated with this toxicity.RashNVP initiation was associated with rash after controlling for CD4 and pregnancy (OR 2.78; 95%CI: 1.14–6.76), as was baseline CD4 >250 cells/mm3 when controlling for pregnancy and type of regimen (OR 2.68; 95% CI: 1.19–6.02 p = 0.017).ConclusionsCD4 at initiation of therapy was a predictor of rash but not LEE with NVP use in HIV+ women. Pregnancy was not an independent risk factor for the development of AEs assessed. The findings from this study have significant implications for women of child-bearing age initiating NVP-based ART particularly in resource limited settings. This study sheds more confidence on the lack of LEE risk and the need to monitor rash with the use of this medication.

Safety of nevirapine in HIV-infected pregnant women initiating antiretroviral therapy at higher CD4 counts: A systematic review and meta-analysis

“…Two studies with CD4 cut-offs of 500 29 Fourteen studies were reviewed, including a total of 2 663 participants (Table 2). 4,5,[27][28][29][30][31][32][33][34][35][36][37][38] One study was funded by the NVP manufacturer Boehringer Ingelheim. 30 The studies, mostly undertaken between 2001 and 2006, were predominantly observational with participant numbers ranging from 17 to 703.…”

“…Participants with hepatitis B or C infection were excluded from 2 studies, 4,27 whereas 7 studies reported the prevalence of hepatitis co-infection. [28][29][30]34,[36][37][38] NVP was initially commenced at 200 mg daily for 14 days in all women. The CD4 cut-off was 250 cells/µl for toxicity analyses in all studies, except for one (CD4 cut-off of 200 cells/ µl).…”

“…24,29,30 Nelfinavir use is rarely associated with hepatotoxicity. 11 Combining hepatotoxicity data for NFV and NVP may potentially dilute the association between NVP and hepatotoxicity at higher CD4 counts.…”

“…Several papers included comparisons of all NIH-DAIDS grades of toxicity. 4,5,28,30,33,[35][36][37][38] In the WHO meta-analysis, the authors did not evaluate cutaneous reactions in pregnancy, and NVP hepatotoxicity was analysed for all grades of severity. 8 They correctly emphasised the need for cautious interpretation of their results based only on grades 3 and 4 toxicities, given limited cohort numbers and open-labelled designs of included studies.…”

“…All studies except Aaron et al included mortality data. 30 The cumulative mortality rate was 0.5% (14 of 2 584 women), with at least 4 maternal deaths directly attributable to NVP use. 5,27,36 We could not perform an NVP-related mortality analysis stratified by CD4 count due to data limitations.…”