Incidence and determinants of nevirapine and efavirenz-related skin rashes in West Africans: nevirapine's epitaph?

Fred Stephen Sarfo,Richard Phillips,David Chadwick,Betty Norman,Maame Anima Sarfo,Julius Atashili

doi:10.1371/journal.pone.0094854

Abstract

Non-nucleoside reverse transcriptase inhibitor (NNRTI) associated rash is common and frequently leads to discontinuation of NNRTIs. This study assessed the risk of developing rashes and discontinuing NNRTIs and associated factors in a large clinic in central Ghana. In this retrospective cohort study, clinical data were obtained in patients starting efavirenz or nevirapine between 2004–2010. Factors associated with rashes were explored using a multivariate Cox proportional hazards regression model. Of 3,999 patients who started NNRTI-based ART, 281 (7.0%) experienced at least one episode of NNRTI-related rash with an incidence of 2.63 events/100 person-years, occurring in 10.2% and 5.6% of patients taking nevirapine and efavirenz respectively. Most rashes (94%) were grade 1 or 2 and were reported a median of 2 months following initiation of ART. In multivariate analysis developing a rash was associated with nevirapine use (aHR 1.67, 95% CI 1.28–2.10), female gender (aHR of 1.39, 95% CI 1.01–1.92) and lower baseline CD4 counts (aHR 0.88, 95% CI 0.82–0.95 per 50 cells/mm3 increment). Patients with nevirapine-associated rash were 11 times more likely to discontinue treatment as patients with efavirenz-associated rash. In contrast to findings in other studies, NNRTI-associated rashes in Ghanaians appear more common in patients with lower baseline CD4 counts. Given the increased frequency of rashes with nevirapine and subsequent discontinuations in many patients, along with other treatment-limiting toxicities, this provides further impetus for the replacement of nevirapine by efavirenz as the first-line NNRTI treatment of choice in Africa.

Highlights

There has been a rapid and successful scaling-up of antiretroviral therapy (ART) in most resource-constrained countries over the past decade
We report on the incidence and determinants of nucleoside reverse transcriptase inhibitor (NNRTI)-related skin rashes in a large cohort of Ghanaian HIV-infected patients starting NNRTI-based ART
No significant differences were present between the two groups with respect to their median age, World Health Organisation (WHO) clinical stages, median body mass index (BMI), serum transaminases as well as the nucleoside reverse transcriptase inhibitor (NRTI) backbone used to initiate therapy

Summary

Introduction

There has been a rapid and successful scaling-up of antiretroviral therapy (ART) in most resource-constrained countries over the past decade. More recently the WHO has recommended efavirenz as the preferred first line NNRTI in resource-limited settings [3]. The durability of these first line ART regimens is dependent on their efficacy and toxicity profile over the long-term. Adverse effects have been reported with all antiretroviral drugs and are one of the most common reasons for discontinuation of treatment [4,5]

Methods

Results

Conclusion