A Randomized, Double-Blind Trial on the Use of a Triple Combination Including Nevirapine, a Nonnucleoside Reverse Transcriptase HIV Inhibitor, in Antiretroviral-Naive Patients With Advanced Disease

Floridia, Marco; Bucciardini, Raffaella; Ricciardulli, Daniela; Fragola, Vincenzo; Pirillo, Maria Franca; Weimer, Liliana Elena; Tomino, Carlo; Giannini, Giacomo; Galluzzo, C. M.; Andreotti, Mauro; Cargnel, Antonietta; Alberici, F.; Rienzo, B. De; Leoncini, F; Fiaccadori, F; Francisci, Daniela; Grillone, W; Ortona, L; Piazza, Marcello; Scalzini, Alfredo; Nigra, Ezio; Tumietto, Fabio; Vella, Stefano

doi:10.1097/00042560-199901010-00002

Cited by 44 publications

(24 citation statements)

References 10 publications

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“…Although this study is the first with an unselected outpatient clinic population including both antiretroviral naive and pretreated patients, the observed incidence was comparable to that reported in several clinical trials [9,10,11,12,13,14] and retrospective analyses [16,22,23,24]. Only seven patients (3.2%) in this population discontinued nevirapine because of rash, which is fairly low compared to other studies and reports [9,10,11,12,13,14,16,22,23]. The difference in median time to occurrence of rash after start with nevirapine between the two types of outcome of this study, i.e., 23 days for outpatient medical record vs. 42 days for prescription of cetirizine, is noteworthy.…”

Section: Discussionsupporting

confidence: 82%

Section: Discussionsupporting

confidence: 74%

“…To account for this phenomenon an initial dose of 200 mg once daily was administered during the first 2 weeks before escalation to 400 mg/day in several clinical studies. 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].…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 82%

Section: Discussionsupporting

confidence: 74%

Section: Introductionmentioning

confidence: 99%

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Incidence and risk factors for nevirapine-associated rash

Maat

Heine

Mulder

et al. 2003

Eur J Clin Pharmacol

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“…30 33 34 36 37 39 42 – 45 51 55 58 60 61 63 68 69 72 73 75 76 81 82 84 86 Dropout rates were higher with monotherapy than with placebo but no different between double therapy and monotherapy. The results of triple compared with double therapy were heterogeneous.…”

Section: Resultsmentioning

confidence: 97%

Systematic review and meta-analysis of evidence for increasing numbers of drugs in antiretroviral combination therapy

Jordan

Gold²,

Cummins³

et al. 2002

BMJ

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Objective To assess the evidence for the effectiveness of increasing numbers of drugs in antiretroviral combination therapy. Design Systematic review, meta-analysis, and meta-regression of fully reported randomised controlled trials. Results 54 randomised controlled trials, most of good quality, with 66 comparison groups were included in the analysis. For both the clinical outcomes and surrogate markers, combinations with up to and including three (triple therapy) were progressively and significantly more effective. The odds ratio for disease progression or death for triple therapy compared with double therapy was 0.6 (95% confidence interval 0.5 to 0.8). Heterogeneity in effect sizes was present in many outcomes but was largely related to the drugs used and trial quality. Conclusions Evidence from randomised controlled trials supports the use of triple therapy. Research is needed on the effectiveness of quadruple therapies and the relative effectiveness of specific combinations of drugs.

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“…The effectiveness of the drug, if used in triple combination therapy with two nucleoside reverse transcriptase inhibitors (NRTI), has been demonstrated since 1996, also in advanced patients. 8,9 Recently, two randomized trials did not show significant differences in response to therapy between HAART regimens including NVP or PI. 10,11 The same finding was observed in patients treated with a HAART regimen including efavirenz (EFV), a second NNRTI, approved for use in Italy in late 1999, and that was considered as first-line therapy in the more recent guidelines.…”

Section: Introductionmentioning

confidence: 99%

Factors Related to Virologic Failure among HIV-Positive Injecting Drug Users Treated with Combination Antiretroviral Therapy Including Two Nucleoside Reverse Transcriptase Inhibitors and Nevirapine

Zaccarelli

Barracchini

Longis

et al. 2002

AIDS Patient Care and STDs

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Treatment strategies in human immunodeficiency virus (HIV)-positive active injecting drug users (IDUs) must take into account their lifestyles, that often result in low adherence to therapy. The nonnucleoside reverse transcriptase inhibitors (NNRTI) offer simpler treatment regimens, but the appearance of drug resistance during treatment failure may cause high levels of cross-resistance to all NNRTIs. We adopted a combination therapy of two NRTIs and nevirapine (NVP) for treatment of IDU patients to evaluate its feasibility in such patients. From October 1998 to December 1999, demographic, clinical, and laboratory data from 80 IDUs on this regimen were collected. Fisher's exact test, Kaplan Meier method, and Cox model were used for statistical analysis. Overall, 20 IDUs discontinued the treatment because of side effects and 20 IDUs experienced treatment failure. Considering the treatment failure as an end point, 55.6% (95% confidence interval [CI]: 37.9%-72.6%) of patients was still undergoing treatment after 12 months compared to 44.6% (31.8%-58.6%) when discontinuation was also taken into account. An increasing trend over time was observed in the CD4+ lymphocyte count, among failing and nonfailing IDUs. By multivariate analysis, baseline HIV-RNA, treatment breaks and low adherence and active injecting drug use turned out to be significantly associated with treatment failure. Our results show that continuing injecting drug use and treatment breaks are the main factors that can lead to treatment failure in IDUs and easily to NNRTI class resistance.

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A Randomized, Double-Blind Trial on the Use of a Triple Combination Including Nevirapine, a Nonnucleoside Reverse Transcriptase HIV Inhibitor, in Antiretroviral-Naive Patients With Advanced Disease

Cited by 44 publications

References 10 publications

Incidence and risk factors for nevirapine-associated rash

Incidence and risk factors for nevirapine-associated rash

Systematic review and meta-analysis of evidence for increasing numbers of drugs in antiretroviral combination therapy

Factors Related to Virologic Failure among HIV-Positive Injecting Drug Users Treated with Combination Antiretroviral Therapy Including Two Nucleoside Reverse Transcriptase Inhibitors and Nevirapine

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