Nevirapine‐associated toxicity in HIV‐infected Thai men and women, including pregnant women

Abstract

ObjectivesThe aim of the study was to determine the incidence of, and risk factors for, nevirapine (NVP)-associated hepatotoxicity and rash in HIV-infected Thai men and women, including pregnant women, receiving NVP-containing highly active antiretroviral therapy (HAART). MethodsNVP-containing HAART was prescribed to eligible men and women enrolled in the Prevention of Mother-To-Child Transmission of HIV (PMTCT) and MTCT-Plus programmes. All pregnant women received zidovudine (ZDV)/lamivudine (3TC)/NVP from 414 weeks of gestational age if their CD4 cell count was 200 cells/mL or from 428 weeks if their CD4 cell count was 4200 cells/mL. Patients followed for at least 8 weeks after starting HAART or until delivery were included in the analyses. ResultsOf 409 patients, 244 were pregnant women, 87 were nonpregnant women and 78 were men. Hepatotoxicity occurred in 15.6% of all patients. Men had a significantly higher rate of asymptomatic hepatotoxicity (P 5 0.021). Pregnant women receiving HAART for PMTCT (92% had CD4 cell counts 4250 cells/mL) had a significantly higher rate of symptomatic hepatotoxicity (P 5 0.0003) than pregnant women receiving HAART for therapy. Rash occurred in 16.1% of all patients. The patients' sex and baseline CD4 cell count were not associated with the risk of hepatotoxicity or rash. NVP was discontinued in 4.2% and 6.8% of patients because of hepatotoxicity and rash, respectively. ConclusionsThe incidence of NVP-related hepatotoxicity and rash in Thai adults is similar to incidences reported for other populations. While larger studies are needed, our data support continued use of NVP-containing regimens as first-line treatment in developing countries for HIV-infected patients, including pregnant women. Pregnant women with high CD4 cell counts may experience higher rates of symptomatic hepatotoxicity and thus require careful clinical and laboratory monitoring.

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

“…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).…”

“…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.…”

“…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.…”

Hcv coinfection, an important risk factor for hepatotoxicity in pregnant women starting antiretroviral therapy

“…1e4,6,8,9 Only one study, performed in Asian patients, reported a substantially higher rate of hepatotoxicity (15.6%) in pregnant women using NVP. 7 This study however had only a small proportion of patients tested for HBV or HCV, and the presence of a coinfection in this study may have added to the high percentage of hepatotoxicity, as HIV-positive Asian communities were found to have a high prevalence of HCV. 13 cART in pregnant and non-pregnant womenCoinfection with HBV or HCV has been reported to be an independent risk factor for antiretroviral-associated hepatotoxicity, including NVP-related hepatotoxicity.…”

Nevirapine-Associated Toxicity in Clinical Practice in Buenos Aires, Argentina

“…Several European researchers reported no relationship between a high CD4 count and side effects. 27,33,34 Among pregnant women, reports from Mozambique, 21 Brazil, 32 Ireland, 34 Thailand, 35 and United States 36 describe a high risk to develop side effects if NVP is started at a high CD4 count, but other reports found not such relationship. [37][38][39] Based on our findings, we have found no evidence that the FDA warning is warranted to the population studied here.…”