Selecting patients who can be re-challenged with Nevirapine in case of skin rash with Efavirenz – A Study

N Dutta,D Modak,S K Guha,R De,S Pain

doi:10.4038/sljid.v7i1.8120

Abstract

Introduction and Objectives: A common adverse effect of Efavirenz (EFV) – a first line drug used in treatment of patients with HIV infections is skin rash. In case of EFV-induced skin rash, the usual practice is to switch to a Protease Inhibitor (PI), as another non-nucleoside reverse transcriptase inhibitor (NNRTI) might have cross-reactivity with a higher incidence of skin rash which is often severe. The aim of the study was therefore to determine whether with careful evaluation and stratification, using predefined criteria of patients who developed rash with EFV, it might be possible to find a subset of patients among whom Nevirapine (NVP) may be safely used, sparing PIs for second-line treatment. Methods: Of 7000 ART naive patients initiated on EFV in an 18 month period from November 2014 to April 2016, 97(1.9%) developed a rash. Patients developing rash with EFV were carefully selected using predefined criteria: grade of rash (only Grade I/II rash were selected), hepatic function, age, gender and CD4 levels (males > 400 cells/cmm and females >250 cells/cmm were excluded if hepatic function was deranged), co-infection status (Hepatitis B/C were excluded), opportunistic infections, concomitant use of other drugs. Based on these stratification criteria, 23 of the 97 patients were selected for challenge with NVP. Results: Of the 23 selected patients, only 3 (13%) patients developed recurrence of rash, all being mild in nature. Conclusions: In carefully selected patients, challenge with NVP can be done in case of rash with EFV as the theory of cross-reactivity does not always hold true. This might help spare PIs in the initial phase, which could then be used as second line therapy - a particularly helpful strategy in developing countries, where newer drugs are still not available under public health programmes.

Highlights

Introduction and ObjectivesA common adverse effect of Efavirenz (EFV) – a first line drug used in treatment of patients with HIV infections is skin rash
According to the updated Indian National guidelines on Highly Active Antiretroviral Treatment (HAART) published in November, 2014, antiretroviral treatment (ART) is initiated with 2 nucleos(t)ide reverse transcriptase inhibitors (NRTI) (Tenofovir and Lamivudine) along with 1 nucleoside reverse transcriptase inhibitor (NNRTI) (Efavirenz) for ART naive patients
Patients who have been initiated on first line ART prior to November, 2014 with Zidovudine, Lamivudine and Nevirapine were retained on the same regimen

Summary

Introduction

Introduction and ObjectivesA common adverse effect of Efavirenz (EFV) – a first line drug used in treatment of patients with HIV infections is skin rash. Initiating an anti-retroviral regimen with two NRTIs (nucleos[t]ide reverse transcriptase inhibitors) together with a NNRTI (non-nucleoside reverse transcriptase inhibitors) is the latest recommendation by WHO for naïve patients in low and middle income countries.[1] NNRTI’s have become one of the key components of first line antiretroviral treatment (ART) as they are affordable, efficacious and capable of reducing the viral load quickly They are prone to single mutations in the virus causing cross class resistance.[2,3,4] Though long term toxicities of NNRTIs are less, their propensity to have interactions with other drugs often limits their use

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