Incidence and risk factors of rash associated with efavirenz in HIV‐infected patients with preceding nevirapine‐associated rash

Abstract

ObjectiveTo determine the incidence and risk factors of rash associated with efavirenz in HIV-infected patients with preceding nevirapine-associated rash. MethodsA retrospective cohort study was conducted in HIV-infected patients diagnosed with nevirapineassociated rash who subsequently received efavirenz between July 2003 and January 2005. Patients were followed up for 3 months after receiving efavirenz. Possible risk factors, including demographics, previous opportunistic infections, CD4 cell count, viral load, severity of nevirapineassociated rash and concurrent drugs, were studied and compared between those who had (group A) and did not have (group B) rash associated with efavirenz. ResultsA total of 122 patients (52.5% male) were included in the study, with a mean age of 38.2 years. Median (and interquartile range) CD4 cell count and viral load were 55 (20-167) cells/mL and 86 150 (35 321-700 750) HIV-1 RNA copies/mL, respectively. Of the 122 patients, 10 (8.2%) developed rash associated with efavirenz and all required discontinuation of efavirenz. The baseline characteristics of group A (10 patients) and group B (112 patients) were similar. Median (and interquartile range) time from nevirapine discontinuation to efavirenz initiation was 12 (9-21) days in group A and 11 (7-21) days in group B (P 5 0.765). None of the risk factors investigated was associated with developing rash associated with efavirenz. The preceding development of severe nevirapineassociated rash had a trend towards a higher rate in group A than in group B (20.0% vs 10.7%; odds ratio 5 2.08; 95% confidence interval 0.39-10.97; P 5 0.322). ConclusionsThe majority (490%) of HIV-infected patients with CD4 counts o200 cells/mL who had preceding nevirapine-associated rash could tolerate efavirenz well. Efavirenz may be an option for subsequent use in these patients, particularly in those who had preceding nevirapine-associated rash.Keywords: efavirenz, HIV, incidence, nevirapine, rash, risk factor IntroductionHighly active antiretroviral therapy (HAART) has been widely used for treatment of patients with advanced HIV infection, and has been successful in achieving immune restoration and thus reducing morbidity and mortality [1][2][3]. Nevirapine (NVP) and efavirenz (EFV) are nonnucleoside reverse transcriptase inhibitors (NNRTIs) that have been shown to have high antiretroviral efficacy [4][5][6]. NNRTI-based HAART regimens are preferred because of their high efficacy and tolerability and lower long-term toxicity [7][8][9]. In developing countries, NVP-based HAART has been widely used because it is more readily available than other types of HAART. Skin rash is the most frequently observed adverse event associated with NVP, manifesting as a diffuse maculopapular rash or erythematous rash with or without constitutional symptoms. The risk of rash of any severity is greatest in the first 6 weeks of treatment [10]. Generally, the rash is mild and transient. However, a more severe rash including extensive maculopapular rash, serum sickness-like rea...

Efavirenz challenge in patients with nevirapine induced Stevens-Johnson Syndrome

“…[11][12][13] Kiertiburanakul et al found that history of drug allergy and CD4 cell count < 100 cells/µl at the time of NVP initiation were predictive factors for unsuccessful switching from NVP to EFV in HIV-infected patients with preceding NVP-associated skin rash. 12 SJS often demands prolonged hospitalisation with reported length of hospitalisation ranging from 2 to 49 days.…”

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

“…Wit et al 28 , reporting the results of the ATHENA Cohort Study in 2008 suggested that the majority (>90%) of HIV infected patients with CD4 counts >200 cells/L who had preceding NVP-associated rash could tolerate EFV well, suggesting that use of EFV is safe in these cases. In their study from Thailand in 2006, Manosuthi et al 20 also observed that only 8.2% developed rash associated with EFV following history of rash with NVP and a conclusion was drawn that HIV-infected patients with CD4 counts of >200 cells/mL who had preceding NVP-associated rash could tolerate EFV well.…”

“…19 Similarly, in a study conducted on Thai patients in 2006, by Manosuthi et al, only 10 (8.2%) of 122 patients who had NVP rash developed rash from EFV, leading to its discontinuation. 20 Clinical safety data regarding use of NVP in HIV-infected patients with preceding EFV associated rash are still quite limited, 13,21 whereas, switching from NVP to EFV in cases of skin rash or hepatotoxicity have seemed safer and effective. Accordingly, most clinicians are unwilling to challenge patients with NVP once rashes have been documented with EFV as both are from the same class of NNRTI and higher incidence of severe rashes associated with NVP makes such switch unsafe.…”

Hypersensitivity reactions to HIV therapy

“…Switching from nevirapine to efavirenz and vice versa following cutaneous hypersensitivity was associated with a recurrence of severe rash although the evidence for this comes from small retrospective cases [129][130][131]. Cross-reactivity is reported to be higher between nevirapine and delavirdine which have a similar structure, but delavirdine is no longer used for the treatment of HIV disease due to its toxicity profile [132].…”