Risk of side effects associated with the use of nevirapine in treatment‐naïve patients, with respect to gender and CD4 cell count

Abstract

A warning about the use of nevirapine (NVP) by its pharmaceutical manufacturer has been issued in which it has been recommended that NVP should not be prescribed in patients with increased risk of toxicity based on CD4 cut-offs and gender. The aim of this study was to determine whether these recommendations are of use in preventing side effects. MethodsThis retrospective study included antiretroviral drug-naïve patients who started treatment with NVP. Patients were divided into two groups: those with high CD4 counts (H; women: CD4 count 4250 cells/mL; men: CD4 count 4400 cells/mL) and those with low CD4 counts (L; women: CD4 count o250 cells/mL; men: CD4 count o400 cells/mL). ResultsA total of 142 patients were included in the study, 61 in the H group and 81 in the L group. Skin rash developed in 6.56% of patients [95% confidence interval (CI) 2.67-15.70%] in the H group and in 14.81% of patients (95% CI 8.72-24.17%) in the L group (P 5 0.18). Hepatotoxicity developed in 4.92% (95% CI 1.79-13.50%) and 6.17% (95% CI 2.73-13.66%) of patients with high and low CD4 cell counts, respectively (P 5 1.0). ConclusionThe recommendations not to use NVP in drug-naïve patients at increased risk of toxicity on the basis of gender and CD4 cell count do not seem to be of use in preventing the occurrence of side effects. However, a small number of patients were included in this study, and hence the possibility cannot be excluded that the recommendations are appropriate in another clinical practice setting.Keywords: adverse events, hepatotoxicity, nevirapine, rash Introduction Nevirapine (NVP) was the first nonnucleoside reverse transcriptase inhibitor approved for use in HIV-infected patients and is a widely used antiretroviral drug, the efficacy of which has been well demonstrated in numerous clinical trials. It is easy to administer and is generally well tolerated [1]. The main limitation of its use is the risk of the occurrence of potentially serious side effects, such as hepatic toxicity and hypersensitivity reactions.In order to avert or reduce such reactions, an attempt has been made to identify the risk factors for presentation of hypersensitivity reactions or hepatotoxicity. In a retrospective analysis of Boehringer-Ingelheim databases, it was found that the risk of symptomatic hepatotoxicity was 12 times greater in women with a CD4 count above 250 cells/ mL, in comparison with women with a CD4 count below 250 cells/mL (11 vs. 0.9%) [2]. In men, there was a 6.3% risk if the CD4 count was above 400 cells/mL, compared with 1.2% when the CD4 count was below 400 cells/mL [2]. In the case of hepatotoxicity with skin rash, the increased risk was This warning about NVP also appears in the guidelines for antiretroviral treatment [6,15]; the purpose of the warning is to decrease the frequency of symptomatic liver toxicity. Analysis of the results of a large randomized clinical trial, the 2NN study, demonstrated that the rate of skin rash and hepatic events was higher in patients with CD4 counts 4200 cells/mL, and also that women ...

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.…”

“…26 Other studies, evaluating the same variables, found antagonistic results. 17,[27][28][29][30] There are 2 previous experiences from South America evaluating NVP-associated toxicity, both in pregnant women.…”

The 2010 South African guidelines for the management of HIV and AIDS: A review

“…NVP has been avoided in women with nadir CD4 counts >250 cells/µl because of the risk of fatal hepatotoxicity. 20 Despite recent studies not confirming this risk, 21 we advise caution and more frequent ALT monitoring since deaths have been reported, mostly in the higher CD4 category (>250 cells/µl) and mostly among women.…”

Drug-Induced Liver Injury

“…Nevirapine is associated with a high incidence of liver toxicity, 112 and the risk is associated with HLA-DRB*0101 and low body mass index (BMI). [113][114][115][116][117][118][119] Clinically, hepatotoxicity due to nevirapine occurs either early or after several months of therapy and it has a mixed pattern of liver injury. 120 A risk factor for abacavir-induced DILI is HLA-B*5701 positivity, thus patients should be screened for this phenotype prior to abacavir treatment.…”