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<p><strong>Introduction and Objectives: </strong>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.</p><p><strong> </strong></p><p><strong>Methods: </strong>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 &gt; 400 cells/cmm and females &gt;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.</p><p><strong> </strong></p><p><strong>Results: </strong>Of the 23 selected patients, only 3 (13%) patients developed recurrence of rash, all being mild in nature.</p><p><strong> </strong></p><p><strong>Conclusions: </strong>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.</p>