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  1. Mustafa S, Yusuf WN, Woillard JB, Choon TS, Hassan NB
    Eur J Clin Pharmacol, 2016 Jul;72(7):831-8.
    PMID: 27025609 DOI: 10.1007/s00228-016-2049-6
    AIMS: Nevirapine is the first non-nucleoside reverse-transcriptase inhibitor approved and is widely used in combination therapy to treat HIV-1 infection. The pharmacokinetics of nevirapine was extensively studied in various populations with a parametric approach. Hence, this study was aimed to determine population pharmacokinetic parameters in Malaysian HIV-infected patients with a non-parametric approach which allows detection of outliers or non-normal distribution contrary to the parametric approach.

    METHODS: Nevirapine population pharmacokinetics was modelled with Pmetrics. A total of 708 observations from 112 patients were included in the model building and validation analysis. Evaluation of the model was based on a visual inspection of observed versus predicted (population and individual) concentrations and plots weighted residual error versus concentrations. Accuracy and robustness of the model were evaluated by visual predictive check (VPC). The median parameters' estimates obtained from the final model were used to predict individual nevirapine plasma area-under-curve (AUC) in the validation dataset. The Bland-Altman plot was used to compare the AUC predicted with trapezoidal AUC.

    RESULTS: The median nevirapine clearance was of 2.92 L/h, the median rate of absorption was 2.55/h and the volume of distribution was 78.23 L. Nevirapine pharmacokinetics were best described by one-compartmental with first-order absorption model and a lag-time. Weighted residuals for the model selected were homogenously distributed over the concentration and time range. The developed model adequately estimated AUC.

    CONCLUSIONS: In conclusion, a model to describe the pharmacokinetics of nevirapine was developed. The developed model adequately describes nevirapine population pharmacokinetics in HIV-infected patients in Malaysia.

    Matched MeSH terms: Nevirapine/blood; Nevirapine/pharmacokinetics*; Nevirapine/therapeutic use
  2. Mustafa S, Hassan NB, Tan SC, Ab Rahman AK, Low LL, Wan Yusuf WN
    Turk J Med Sci, 2016 Dec 20;46(6):1875-1881.
    PMID: 28081342 DOI: 10.3906/sag-1503-116
    BACKGROUND/AIM: Nevirapine is a reverse-transcriptase inhibitor widely used in combination therapy to treat HIV infection. Nevirapine is extensively metabolized in the liver and CYP2B6 is mainly responsible for oxidation of 3-hydroxynevirapine (3-OH NVP). This study aims to explore CYP2B6 activity by measuring 2-hydroxynevirapine (2-OH NVP) and 3-OH NVP in plasma and to identify factors associated with nevirapine pharmacokinetic parameters.

    MATERIALS AND METHODS: A total of 112 patients were recruited and treated with nevirapine-based antiretroviral therapy. Plasma nevirapine and metabolite concentrations were assayed using high-performance liquid chromatography via liquid-liquid extraction.

    RESULTS: Thirty-nine (34.8%) of the patients had no 3-OH NVP detected in their plasma while 2-OH NVP was detected in all patients. Metabolite concentrations were low compared to nevirapine. Positive correlations were observed between nevirapine and its metabolites, 2-OH NVP (P < 0.01) and 3-OH NVP (P = 0.012). Nevirapine concentration was decreased when concomitantly administered with methadone. Univariate analysis showed that ALT level, AST level, and detection of 3-OH NVP were associated with nevirapine pharmacokinetic parameters.

    CONCLUSION: The variability of nevirapine pharmacokinetic parameters was caused by liver enzymes and the presence of 3-OH NVP metabolites. The presence of 3-OH NVP can probably be used to distinguished CYP2B6 activity and efficacy of nevirapine in patients with HIV infection.

    Matched MeSH terms: Nevirapine
  3. Chua KY, Tey KE
    Int J STD AIDS, 2022 Aug;33(9):812-820.
    PMID: 35775121 DOI: 10.1177/09564624221103743
    BACKGROUND: Cutaneous adverse drug reactions (cADRs) among people living with HIV (PLWH) are common. Data on drug eruptions among PLWH in Malaysia are limited. Thus, our study aimed to determine the clinical patterns of cADRs among PLWH and the risk factors associated with severe cutaneous adverse reactions (SCAR).

    METHODS: A cross-sectional study was conducted among PLWH who developed cADRs presenting to our dermatology clinic from June 2020 to December 2020. The Naranjo scale was used for drug causality assessment.

    RESULTS: A total of 78 PLWH were recruited with a male-to-female ratio of 12:1. The maculopapular eruption was the commonest type of cADRs (75.6%), followed by drug reaction with eosinophilia and systemic symptoms (DRESS) (15.4%). SCAR is defined as a potentially life-threatening, immunologically mediated, drug-induced disease, accounting for 17.9% of the cases. Most of the patients were on antiretroviral therapy (ART) (85.9%), with efavirenz + tenofovir/emtricitabine being the most common combination (80.6%). Efavirenz (51.3%) was the main culprit drug implicated, followed by trimethoprim/sulfamethoxazole (23.1%) and nevirapine (11.5%). CD4 T-cell count <100 cells/μL (p = 0.006) was the independent risk factor for SCAR. Most cases had probable causal relationships with the culprit drugs (84.6%) and were not preventable (93.6%).

    CONCLUSIONS: The commonest cADR seen in PLWH was maculopapular eruption, while efavirenz, trimethoprim/sulfamethoxazole, and nevirapine were the three main implicated drugs. Most of the cases had probable drug causality and were not preventable. PLWH with CD4 count <100 cells/μL were particularly at risk of developing SCAR. Overall, this study showed that immune suppression and polypharmacy as a consequence of opportunistic infection prophylaxis are important factors contributing to the increased risk of ADRs among PLWH.

    Matched MeSH terms: Nevirapine/adverse effects
  4. Leng LK, Pancharoen C, Bunupuradah T, Thisyakorn U, Trinavarat P, Sosothikul D, et al.
    J Med Assoc Thai, 2007 Sep;90(9):1937-42.
    PMID: 17957942
    This report documents a case of infiltrating cervical spinal mass, most likely a spinal tumor, in a girl with HIV infection that regressed following HAART and without treatment of the tumor or any anti-infectives.
    Matched MeSH terms: Nevirapine/therapeutic use
  5. Sudjaritruk T, Boettiger DC, Nguyen LV, Mohamed TJ, Wati DK, Bunupuradah T, et al.
    J Int AIDS Soc, 2019 Jun;22(6):e25312.
    PMID: 31179641 DOI: 10.1002/jia2.25312
    INTRODUCTION: Recommendations on the optimal frequency of plasma viral load (pVL) monitoring in children living with HIV (CLWH) who are stable on combination antiretroviral therapy (cART) are inconsistent. This study aimed to determine the impact of annual versus semi-annual pVL monitoring on treatment outcomes in Asian CLWH.

    METHODS: Data on children with perinatally acquired HIV aged <18 years on first-line, non-nucleoside reverse transcriptase inhibitor-based cART with viral suppression (two consecutive pVL <400 copies/mL over a six-month period) were included from a regional cohort study; those exposed to prior mono- or dual antiretroviral treatment were excluded. Frequency of pVL monitoring was determined at the site-level based on the median rate of pVL measurement: annual 0.75 to 1.5, and semi-annual >1.5 tests/patient/year. Treatment failure was defined as virologic failure (two consecutive pVL >1000 copies/mL), change of antiretroviral drug class, or death. Baseline was the date of the second consecutive pVL <400 copies/mL. Competing risk regression models were used to identify predictors of treatment failure.

    RESULTS: During January 2008 to March 2015, there were 1220 eligible children from 10 sites that performed at least annual pVL monitoring, 1042 (85%) and 178 (15%) were from sites performing annual (n = 6) and semi-annual pVL monitoring (n = 4) respectively. Pre-cART, 675 children (55%) had World Health Organization clinical stage 3 or 4, the median nadir CD4 percentage was 9%, and the median pVL was 5.2 log10 copies/mL. At baseline, the median age was 9.2 years, 64% were on nevirapine-based regimens, the median cART duration was 1.6 years, and the median CD4 percentage was 26%. Over the follow-up period, 258 (25%) CLWH with annual and 40 (23%) with semi-annual pVL monitoring developed treatment failure, corresponding to incidence rates of 5.4 (95% CI: 4.8 to 6.1) and 4.3 (95% CI: 3.1 to 5.8) per 100 patient-years of follow-up respectively (p = 0.27). In multivariable analyses, the frequency of pVL monitoring was not associated with treatment failure (adjusted hazard ratio: 1.12; 95% CI: 0.80 to 1.59).

    CONCLUSIONS: Annual compared to semi-annual pVL monitoring was not associated with an increased risk of treatment failure in our cohort of virally suppressed children with perinatally acquired HIV on first-line NNRTI-based cART.

    Matched MeSH terms: Nevirapine/therapeutic use*
  6. George C, Yesoda A, Jayakumar B, Lal L
    J Clin Pharm Ther, 2009 Feb;34(1):33-40.
    PMID: 19125901 DOI: 10.1111/j.1365-2710.2008.00988.x
    This prospective, observational, study evaluates the clinical outcomes, drug utilization patterns, and adherence to treatment of patients on highly active anti retroviral therapy (HAART) at a government institution in Kerala, India.
    Matched MeSH terms: Nevirapine/economics; Nevirapine/therapeutic use
  7. Cain LE, Phillips A, Lodi S, Sabin C, Bansi L, Justice A, et al.
    AIDS, 2012 Aug 24;26(13):1691-705.
    PMID: 22546987
    OBJECTIVE: To compare regimens consisting of either efavirenz or nevirapine and two or more nucleoside reverse transcriptase inhibitors (NRTIs) among HIV-infected, antiretroviral-naive, and AIDS-free individuals with respect to clinical, immunologic, and virologic outcomes.

    DESIGN: Prospective studies of HIV-infected individuals in Europe and the US included in the HIV-CAUSAL Collaboration.

    METHODS: Antiretroviral therapy-naive and AIDS-free individuals were followed from the time they started an NRTI, efavirenz or nevirapine, classified as following one or both types of regimens at baseline, and censored when they started an ineligible drug or at 6 months if their regimen was not yet complete. We estimated the 'intention-to-treat' effect for nevirapine versus efavirenz regimens on clinical, immunologic, and virologic outcomes. Our models included baseline covariates and adjusted for potential bias introduced by censoring via inverse probability weighting.

    RESULTS: A total of 15 336 individuals initiated an efavirenz regimen (274 deaths, 774 AIDS-defining illnesses) and 8129 individuals initiated a nevirapine regimen (203 deaths, 441 AIDS-defining illnesses). The intention-to-treat hazard ratios [95% confidence interval (CI)] for nevirapine versus efavirenz regimens were 1.59 (1.27, 1.98) for death and 1.28 (1.09, 1.50) for AIDS-defining illness. Individuals on nevirapine regimens experienced a smaller 12-month increase in CD4 cell count by 11.49 cells/μl and were 52% more likely to have virologic failure at 12 months as those on efavirenz regimens.

    CONCLUSIONS: Our intention-to-treat estimates are consistent with a lower mortality, a lower incidence of AIDS-defining illness, a larger 12-month increase in CD4 cell count, and a smaller risk of virologic failure at 12 months for efavirenz compared with nevirapine.

    Matched MeSH terms: Nevirapine/therapeutic use*
  8. Boettiger DC, Kerr S, Ditangco R, Merati TP, Pham TT, Chaiwarith R, et al.
    PLoS One, 2014;9(9):e106525.
    PMID: 25184314 DOI: 10.1371/journal.pone.0106525
    Antiretroviral therapy (ART) has evolved rapidly since its beginnings. This analysis describes trends in first-line ART use in Asia and their impact on treatment outcomes.
    Matched MeSH terms: Nevirapine/therapeutic use
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