Failure of a Short-Term Prednisone Regimen to Prevent Nevirapine-Associated Rash: A Double-Blind Placebo-Controlled Trial: The GESIDA 09/99 Study

Knobel, Hernando; Miró, José M.; Domingo, Peré; Rivero, Antonio; Márquez, Manuel; Force, Luis; González, Alicia; Miguel, Verónica de; Sanz, José; Boix, Vicente; Blanco, José Luis Santiago; Locutura, Jaime

doi:10.1097/00042560-200109010-00003

Cited by 32 publications

(10 citation statements)

References 13 publications

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“…12 Subsequent randomized trials have proven that in fact prednisone increases the risk of nevirapine-associated rash. [13][14][15] Rash was more frequent among females, a phenomenon that has already been reported. 16 Further studies are needed to understand the mechanism for the gender-associated differences in nevirapine-associated rash.…”

Section: Figsupporting

confidence: 66%

Evaluation of the Virological and Metabolic Effects of Switching Protease Inhibitor Combination Antiretroviral Therapy to Nevirapine-Based Therapy for the Treatment of HIV Infection

Tebas

Yarasheski

Henry

et al. 2004

AIDS Research and Human Retroviruses

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Bordenave, B. Regions Hospital; Klebert, Michael; and Powderly, William G., ,"Evaluation of the virological and metabolic effects of switching protease inhibitor combination antiretroviral therapy to nevirapine-based therapy for the treatment of HIV infection." AIDS Research and Human Retroviruses.20,6. 589-594. (2004 ABSTRACTIn spite of indisputable benefits, the use of antiretroviral therapy is associated with multiple metabolic complications. Switching to simpler regimens might maintain viral suppression, improve metabolic side effects, and provide insight into the pathogenesis of these complications. Our objective was to carefully characterize the virological and metabolic effects of switching from a successful protease inhibitor (PI)-based antiretroviral regimen to a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen with nevirapine (NVP).Forty patients, taking their first successful (less than 40 HIV RNA copies/ml) PI-based regimen, switched their PI to NVP. If patients did not tolerate NVP, substitution with efavirenz was allowed. The duration of the study was 48 weeks. At 12 weeks intervals subjects had multiple virological and metabolic parameters including glucose, insulin, C-peptide, glucagon, proinsulin, blood lipids, and lipoproteins. A subgroup of 18 patients also had body composition evaluations with DEXA scans and MRIs of the abdomen and the thighs as well as insulin tolerance tests. Ninety-five percent of the patients maintained viral suppression (95% CI 88-100%); only one patient failed and another developed hepatitis. There were improvements in glucose (decreased fasting glucose, insulin, and improved insulin tolerance) and lipid metabolism (decreased triglycerides and increased HDL), but no changes in body composition and bone mineral density. Our study supports a pathogenic role for PIs in the development of hypertriglyceridemia and insulin resistance, but a more limited role in the fat redistribution syndrome. 589

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Section: Figsupporting

confidence: 66%

Evaluation of the Virological and Metabolic Effects of Switching Protease Inhibitor Combination Antiretroviral Therapy to Nevirapine-Based Therapy for the Treatment of HIV Infection

Tebas

Yarasheski

Henry

et al. 2004

AIDS Research and Human Retroviruses

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“…The skin rash was classified using a previously established scale [9]. Hepatotoxicity was diagnosed when transaminases were raised by more than five times the normal value, in patients whose baseline levels had been normal, and by more than 3.5 times the baseline measurement in patients whose baseline levels were abnormal prior to commencing treatment.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2008

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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 ...

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“…With this strategy the incidence of rash reduced to 9-32% [9,10,11,12,13]. Other strategies that have been evaluated to reduce the occurrence of rashes include the use of corticosteroids and antihistamines as prophylaxis and the use of a slower induction phase of treatment [14,15,16,17]. The use of prophylaxis when initiating therapy with nevirapine remains controversial as contradictory results have been reported [14,15,16,17].…”

Section: Introductionmentioning

confidence: 99%

“…Other strategies that have been evaluated to reduce the occurrence of rashes include the use of corticosteroids and antihistamines as prophylaxis and the use of a slower induction phase of treatment [14,15,16,17]. The use of prophylaxis when initiating therapy with nevirapine remains controversial as contradictory results have been reported [14,15,16,17]. However, a slowly escalating dose of nevirapine (e.g., nevirapine 100 mg for the first week, and increasing 100 mg daily per week until achieving the full nevirapine dose by the fourth week) diminished the incidence of rash by approximately 40% compared to patients using the advised escalation dose (200 mg once daily the first 2 weeks) [14].…”

Section: Introductionmentioning

confidence: 99%

Incidence and risk factors for nevirapine-associated rash

Maat

Heine

Mulder

et al. 2003

Eur J Clin Pharmacol

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Objective: To determine the incidence of rash in HIV-1 infected individuals starting a nevirapine-containing regimen in an unselected outpatient clinic population. Possible risk factors including plasma concentrations of nevirapine were evaluated for their relationship with the occurrence of a rash. Methods: The occurrence of rash was extracted from the outpatient medical records or based on a prescription of the antihistaminic cetirizine as documented by the community pharmacy within the first 90 days of nevirapine use. During regular visits to the clinic blood samples were collected for the determination of nevirapine plasma concentrations. Possible risk factors such as demographics, immunology, virology, clinical chemistry and antiretroviral pretreatment were collected at baseline for each patient. In addition, concomitantly used drugs during the nevirapine-based regimen were recorded. The association between these factors and the occurrence of rash was studied. Primary outcome was the onset of rash within the first 90 days after initiation of a nevirapinecontaining regimen. Results: Data from 216 HIV-1-infected patients were used in this study. Thirty-eight patients (17.6%) developed a rash of some grade that led to discontinuation of nevirapine in seven patients (3.2% of the included patients). The median time to occurrence of rash was 26 days (interquartile range 17-46 days). The multivariate analysis showed that patients pretreated with antiretroviral drugs less than 12 months before the initiation of a nevirapinecontaining regimen had a more than 2.5-fold increased risk of developing rash. Furthermore, nevirapine plasma concentrations were also significantly related to the occurrence of rash. A more than twofold increased risk for developing rash was observed for patients with nevirapine plasma concentrations above 5.3 mg/l. Conclusions: This is the first study demonstrating that patients with antiretroviral pretreatment less than 12 months and with nevirapine plasma concentrations above 5.3 mg/l during the first 90 days of treatment are at a higher risk for the development of rash. It is therefore advised to monitor this group of patients carefully when initiating nevirapine-containing therapy.

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Failure of a Short-Term Prednisone Regimen to Prevent Nevirapine-Associated Rash: A Double-Blind Placebo-Controlled Trial: The GESIDA 09/99 Study

Abstract: Short-term prednisone administration does not prevent nevirapine rash, but might even increase its incidence.

Cited by 32 publications

References 13 publications

Evaluation of the Virological and Metabolic Effects of Switching Protease Inhibitor Combination Antiretroviral Therapy to Nevirapine-Based Therapy for the Treatment of HIV Infection

Evaluation of the Virological and Metabolic Effects of Switching Protease Inhibitor Combination Antiretroviral Therapy to Nevirapine-Based Therapy for the Treatment of HIV Infection

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

Incidence and risk factors for nevirapine-associated rash

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