Future Perspectives in NNRTI-Based Therapy: Bases for Understanding Their Toxicity

Blas‐García, Ana; Apostolova, Nadezda; Esplugues, Juan V.

doi:10.5772/22458

Cited by 3 publications

(5 citation statements)

References 67 publications

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“…A total of 509 and 152 patients were included in Zambia and Kenya, respectively. With regard to the study design, most were retrospective cohort [ 9 ]. The minimum and maximum median age for the included studies were 32 (IQR 28–36) and 40 (IQR 35–47) years, respectively.…”

Section: Resultsmentioning

confidence: 99%

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Choice of initial antiretroviral drugs and treatment outcomes among HIV-infected patients in sub-Saharan Africa: systematic review and meta-analysis of observational studies

et al. 2017

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BackgroundThe effectiveness of antiretroviral therapy (ART) depends on the choice of regimens during initiation. Most evidences from developed countries indicated that there is difference between efavirenz (EFV) and nevirapine (NVP). However, the evidences are limited in resource poor countries particularly in Africa. Thus, this systematic review and meta-analysis was carried out to summarize reported long-term treatment outcomes among people on first line therapy in sub-Saharan Africa.MethodsObservational studies that reported odds ratio, relative risk, hazard ratio, or standardized incidence ratio to compare risk of treatment failure among HIV/AIDS patients who initiated ART with EFV versus NVP were systematically searched. Searches were conducted using the MEDLINE database within PubMed, Google Scholar, HINARI, and Research Gates between 2007 and 2016. Information was extracted using standardized form. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated using random-effect, generic inverse variance method.ResultA total of 6394 articles were identified, of which, 29 were eligible for review and abstraction in sub-Saharan Africa. Seventeen articles were used for the meta-analysis. Of a total of 121,092 independent study participants, 76,719 (63.36%) were females. Of these, 40,480 (33.43%) initiated with NVP containing regimen. Two studies did not report the median CD4 cell counts at initiation. Patients who have low CD4 cell counts initiated with EFV containing regimen. The pooled effect size indicated that treatment failure was reduced by 15%, 0.85 (95%CI: 0.75–0.98), and non-nucleoside reverse transcriptase inhibitor (NNRTI) switch was reduced by 43%, 0.57 (95%CI: 0.37–0.89).ConclusionThe risk of treatment failure and NNRTI switch were lower in patients who initiated with EFV than NVP-containing regimen. The review suggests that initiation of patients with EFV-containing regimen will reduce treatment failure and NNRTI switch.Electronic supplementary materialThe online version of this article (doi:10.1186/s13643-017-0567-7) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

“…In resource-limited countries, World Health Organization (WHO) recommends the use of two NNRTI (nevirapine (NVP) and efavirenz (EFV)) as first-line ART regimen. EFV, combined with two NRTIs, is the recommended option for initial therapy and is the most widely used NNRTI [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Choice of initial antiretroviral drugs and treatment outcomes among HIV-infected patients in sub-Saharan Africa: systematic review and meta-analysis of observational studies

et al. 2017

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“…These drugs have been reported to cause hypersensitivity reactions with primary manifestation in the form of skin rashes from mild to potentially life-threatening. [2][3][4][5] The influence of race to NNRTI-related rash was unknown. High incidence of NVP-associated rash in Asian population ranging from 2.6% to 54.4% and commonly emerges at 12 days to 6 weeks after initiation.…”

Section: Introductionmentioning

confidence: 99%

“…High incidence of NVP-associated rash in Asian population ranging from 2.6% to 54.4% and commonly emerges at 12 days to 6 weeks after initiation. 1,4,5 Incidence of skin rash in those receiving efavirenz was reported at 8.2% to 20% with mild to moderate skin manifestations. They usually emerge on the 8 days after initiation.…”

Section: Introductionmentioning

confidence: 99%

Incidence and predictors of nevirapine and efavirenz-associated rash among Indonesian HIV patients

2022

Asian Pac J Allergy Immunol

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Background: Many drugs used for the treatment of HIV disease can cause drug hypersensitivity reactions. Since 2002, World Health Organization (WHO) has recommended the use of nevirapine and efavirenz as part of first line antiretroviral therapies for several years. Both of the drugs had equivalent clinical efficacy but differences in toxicity profile.Objectives: We aimed to determine the incidence and predictors of nevirapine and efavirenz-associated rash among Indonesian HIV-infected patients.Methods: A retrospective cohort study was conducted among Indonesian patients who were using nevirapine or efavirenz between January 2004 to December 2013. All eligible predictors were analyzed using bivariate and multivariate analysis.Results: 2,071 patients received nevirapine and 1,212 received efavirenz as first line therapies. The cumulative incidence of nevirapine-associated rash was 14% (95%CI: 12.5-15.5%) and evafirenz-associated rash was 4.5% (95%CI: 3.4-5.8%). Severe reactions occurred 1% patients receiving NVP and 0.1% patients receiving EFV, but no patients died due to these conditions. Predictors independently related with nevirapine-associated rash were female gender (adjusted RR = 1.622; 95%CI: 1.196-2.199; p = 0.002), baseline absolute CD4 count above 200 cells/mm 3 (adjusted RR = 1.387; 95%CI: 1.041-1.847; p = 0.025), and hepatitis C co-infection (adjusted RR = 1.507; 95%CI: 1.138-1.995; p = 0.004). Baseline ALT level > 1.25 times upper normal limit (adjusted RR = 1.508; 95%CI: 0.998-2.278; p = 0.051) had a tendency to be a good predictor. None of the risk factors investigated was associated with developing efavirenz-associated rash. Conclusion:Female, baseline absolute CD4 count above 200 cells/mm 3 , hepatitis C co-infection and baseline ALT levels more than 1.25 times upper normal limit were predictors for nevirapine-associated rash in HIV patients.

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“…This is because early exposure to ART may precipitate early evolution of resistance and unnecessary side-effects [17]. The standard therapy consists of three nucleoside reverse transcriptase inhibitors (NRTIs): Zidovudine (AZT), Tenofovir (TDF), and Stavudine (D4T) and one non-nucleoside reverse transcriptase inhibitor (NNRTI): nevirapine (NVP) or efavirenz (EFV) [18].…”

Section: Introductionmentioning

confidence: 99%

Model-based prediction of CD4 cells counts in HIV-infected adults on antiretroviral therapy in Northwest Ethiopia: A flexible mixed effects approach

et al. 2019

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Background CD4 cell counts is widely used as a biomarker for treatment progression when studying the efficacy of drugs to treat HIV-infected patients. In the past, it had been also used in determining eligibility to initiate antiretroviral therapy. The main aim of this was to model the evolution of CD4 counts over time and use this model for an early prediction of subject-specific time to cross a pre-specified CD4 threshold. Methods Hospital based retrospective cohort study of HIV-infected patients was conducted from January 2009 to December 2014 at University of Gondar hospital, Northwest Ethiopia. Fractional polynomial random effect model is used to model the evolution of CD4 counts over time in response to treatment and to estimate the individual probability to be above a pre-selected CD4 threshold. Human subject research approval for this study was received from University of Gondar Research Ethics Committee and the medical director of the hospital. Results A total of 1347 patients were included in the analysis presented in this paper. The cohort contributed a total of 236.58 per 100 person-years of follow-up. Later the data were divided into two periods: the first is the estimation period in which the parameters of the model are estimated and the second is the prediction period. Based on the parameters from the estimation period, model based prediction for the time to cross a threshold was estimated. The correlations between observed and predicted values of CD4 levels in the estimation period were 0.977 and 0.982 for Neverapine and Efavirenz containing regimens, respectively; while the correlation between the observed and predicted CD4 counts in the prediction period are 0.742 and 0.805 for NVP and EFV, respectively. Conclusions The model enables us to estimate a subject-specific expected time to cross a CD4 threshold and to estimate a subject-specific probability to have CD4 count above a pre-specified threshold at each time point. By predicting long-term outcomes of CD4 count of the patients one can advise patient about the potential ART benefits that accrue in the long-term.

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Future Perspectives in NNRTI-Based Therapy: Bases for Understanding Their Toxicity

Cited by 3 publications

References 67 publications

Choice of initial antiretroviral drugs and treatment outcomes among HIV-infected patients in sub-Saharan Africa: systematic review and meta-analysis of observational studies

Choice of initial antiretroviral drugs and treatment outcomes among HIV-infected patients in sub-Saharan Africa: systematic review and meta-analysis of observational studies

Incidence and predictors of nevirapine and efavirenz-associated rash among Indonesian HIV patients

Model-based prediction of CD4 cells counts in HIV-infected adults on antiretroviral therapy in Northwest Ethiopia: A flexible mixed effects approach

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