Safety of nevirapine‐containing antiretroviral triple therapy regimens to prevent vertical transmission in an African cohort of HIV‐1‐infected pregnant women

Abstract

ObjectiveTo assess the incidence and consequences of adverse reactions among African HIV-positive pregnant women treated with fixed-dose combinations of a nevirapine-containing antiretroviral (ARV) triple therapy. MethodsA retrospective analysis of the clinical files of 703 HIV-1-positive pregnant women treated with a nevirapine-containing regimen between May 2002 and July 2004 was conducted. Selection criteria for inclusion in the analysis were: (a) taking ARV for more than 14 days; (b) baseline values of transaminases below the threshold of 2.5 times the upper limit of normal (ULN). The women were on a nevirapine-containing regimen for a median of 127 days [interquartile range (IQR) 86-190 days], starting on average at the 27th week of gestation (standard deviation AE 9.5) and continuing up to a maximum of 6 months after delivery. All women were offered formula milk to feed the babies. Highly active antiretroviral therapy (HAART) was continued beyond 6 months only if the patient qualified on the first visit. The main outcome measures were incidence of hepatotoxicity, skin rashes and Stevens-Johnson syndrome. Multivariate analysis to assess the impact of several factors on the adverse reaction rate was performed. ResultsAs of 1 August 2004, 554 pregnancies reached term, 96 women were still pregnant, and 53 women dropped out of the programme before giving birth. After 2 months of therapy the percentage of patients with a viral load less than 1000 HIV-1 RNA copies/mL increased to 78.6%; average CD4 cell counts increased from 490 cells/mL before therapy to 630 after therapy. The incidence of grade 3-4 adverse reactions (hepatotoxicity, skin rashes and Stevens-Johnson syndrome) was 6.5, 2.4 and 1.1%, respectively. Five women died during pregnancy (0.88%). Only one of the deaths could be associated with ARV treatment. ConclusionNevirapine-containing regimens in pregnant woman, at all CD4 cell count levels, appear to be safe in African settings.Keywords: hepatotoxicity, HIV mother-to-child transmission, nevirapine-containing regimen, public health, resource-limited settings A major focus of the programme is the prevention of mother-to-child transmission during pregnancy, delivery and breast-feeding. Mothers are kept on highly active antiretroviral therapy (HAART) if they qualify for this treatment at the time of diagnosis. Antiretrovirals (ARVs), nutritional supplements and laboratory tests are provided free of charge.To assess the potential toxicity of, and damage caused by, NVP-containing regimens, a cohort of 703 pregnant women enrolled in DREAM were analysed retrospectively. Patients and methods PatientsThe clinical files of all 999 pregnant women enrolled in the programme between 1 May 2002 and 31 July 2004 were reviewed. The baseline characteristics of the patients are presented in Table 1.Of these patients, 28 had taken HAART for less than 14 days; 109 had not yet begun HAART because of the stage of their pregnancy; 84 refused to continue treatment after the first visit, and 53 stopped treatment before deliver...

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

“…Additional unpublished data were obtained from Coffie et al, 31 Lyons et al 36 and Marazzi et al 5 There was a significant reduction in ART-naive = number of ART-naive pregnant women who initiated NVP-based ART; TTT = time to toxicity (days); Liver = severe hepatotoxicity; Skin = severe cutaneous reaction; N/R = not reported.…”

“…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.…”

“…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.…”

“…[4][5][6] Current World Health Organization (WHO) guidelines recommend NVP as part of first-line antiretroviral therapy (ART) for pregnant women with CD4 ≤350 cells/µl, 7 based on their own analysis of 836 pregnant women, which showed no increased hepatotoxicity risk at CD4 ≥250 cells/µl (relative risk 1.04; 95% confidence interval (CI) 0.22 -4.93). 9 In contrast, the 2011 perinatal guidelines from the US Department of Health and Human Services recommend a protease inhibitor as part of the ART regimen for pregnant women with a CD4 count ≥250 cells/µl, while cautioning against starting NVP above this count.…”

“…3 However, results from several subsequent studies with larger datasets demonstrated no association between CD4 count and NVP toxicity. [4][5][6] Current World Health Organization (WHO) guidelines recommend NVP as part of first-line antiretroviral therapy (ART) for pregnant women with CD4 ≤350 cells/µl, 7 based on their own analysis of 836 pregnant women, which showed no increased hepatotoxicity risk at CD4 ≥250 cells/µl (relative risk 1.04; 95% confidence interval (CI) 0.22 -4.93). 8 The 2010 South African Prevention of Mother-to-Child Transmission (PMTCT) guidelines recommend lifelong NVP-based ART for HIV-infected pregnant women with WHO clinical stage 3 or 4 disease, regardless of CD4 count.…”