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Philippa Musoke - One of the best experts on this subject based on the ideXlab platform.
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efficacy and safety of an extended Nevirapine regimen in infant children of breastfeeding mothers with hiv 1 infection for prevention of postnatal hiv 1 transmission hptn 046 a randomised double blind placebo controlled trial
The Lancet, 2012Co-Authors: Tsungai Chipato, Philippa Musoke, Hoosen Coovadia, Elizabeth R Brown, Mary Glenn Fowler, Dhayendre Moodley, Karim P Manji, Lynda Stranixchibanda, Vani ChettyAbstract:Summary Background Nevirapine given once-daily for the first 6, 14, or 28 weeks of life to infants exposed to HIV-1 via breastfeeding reduces transmission through this route compared with single-dose Nevirapine at birth or neonatally. We aimed to assess incremental safety and efficacy of extension of such prophylaxis to 6 months. Methods In our phase 3, randomised, double-blind, placebo-controlled HPTN 046 trial, we assessed the incremental benefit of extension of once-daily infant Nevirapine from age 6 weeks to 6 months. We enrolled breastfeeding infants born to mothers with HIV-1 in four African countries within 7 days of birth. Following receipt of Nevirapine from birth to 6 weeks, infants without HIV infection were randomly allocated (by use of a computer-generated permuted block algorithm with random block sizes and stratified by site and maternal antiretroviral treatment status) to receive extended Nevirapine prophylaxis or placebo until 6 months or until breastfeeding cessation, whichever came first. The primary efficacy endpoint was HIV-1 infection in infants at 6 months and safety endpoints were adverse reactions in both groups. We used Kaplan-Meier analyses to compare differences in the primary outcome between groups. This study is registered with ClinicalTrials.gov, number NCT00074412. Findings Between June 19, 2008, and March 12, 2010, we randomly allocated 1527 infants (762 Nevirapine and 765 placebo); five of whom had HIV-1 infection at randomisation and were excluded from the primary analyses. In Kaplan-Meier analysis, 1·1% (95% CI 0·3–1·8) of infants who received extended Nevirapine developed HIV-1 between 6 weeks and 6 months compared with 2·4% (1·3–3·6) of controls (difference 1·3%, 95% CI 0–2·6), equating to a 54% reduction in transmission (p=0·049). However, mortality (1·2% for Nevirapine vs 1·1% for placebo; p=0·81) and combined HIV infection and mortality rates (2·3% vs 3·2%; p=0·27) did not differ between groups at 6 months. 125 (16%) of 758 infants given extended Nevirapine and 116 (15%) of 761 controls had serious adverse events, but frequency of adverse events, serious adverse events, and deaths did not differ significantly between treatment groups. Interpretation Nevirapine prophylaxis can safely be used to provide protection from mother-to-child transmission of HIV-1 via breastfeeding for infants up to 6 months of age. Funding US National Institutes of Health.
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antiretroviral treatment for children with peripartum Nevirapine exposure
The New England Journal of Medicine, 2010Co-Authors: Paul Palumbo, Tammy Meyers, Michael Hughes, Philippa Musoke, Jane C Lindsey, Portia Kamthunzi, Mark F Cotton, Raziya Bobat, Mutsawashe Bwakuradangarembizi, Werner SchimanaAbstract:Background Single-dose Nevirapine is the cornerstone of the regimen for prevention of mother-to-child transmission of human immunodeficiency virus (HIV) in resource-limited settings, but Nevirapine frequently selects for resistant virus in mothers and children who become infected despite prophylaxis. The optimal antiretroviral treatment strategy for children who have had prior exposure to single-dose Nevirapine is unknown. Methods We conducted a randomized trial of initial therapy with zidovudine and lamivudine plus either Nevirapine or ritonavir-boosted lopinavir in HIV-infected children 6 to 36 months of age, in six African countries, who qualified for treatment according to World Health Organization (WHO) criteria. Results are reported for the cohort that included children exposed to single-dose Nevirapine prophylaxis. The primary end point was virologic failure or discontinuation of treatment by study week 24. Enrollment in this cohort was terminated early on the recommendation of the data and safety ...
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resistance after single dose Nevirapine prophylaxis emerges in a high proportion of malawian newborns
AIDS, 2005Co-Authors: Susan H Eshleman, Donald R Hoover, Shu Chen, Sarah E Hudelson, Laura A Guay, Anthony Mwatha, Susan A Fiscus, Francis Mmiro, Philippa Musoke, Brooks J JacksonAbstract:The administration of single-dose Nevirapine to women in labor and their infants can prevent HIV-1 mother-to-child transmission. We examined Nevirapine resistance in infants who were HIV-1 infected despite single-dose Nevirapine prophylaxis, including 18 Ugandan infants (HIVNET 012 trial, nine subtype A and nine subtype D) and 23 Malawian infants (NVAZ trial, all subtype C). Nevirapine resistance was more frequent in infants with subtype C than with subtypes A and D (87 versus 50%, P = 0.016).
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a phase i ii study of the safety and pharmacokinetics of Nevirapine in hiv 1 infected pregnant ugandan women and their neonates hivnet 006
AIDS, 1999Co-Authors: Philippa Musoke, Mark Mirochnick, Laura A Guay, Danstan Bagenda, Clemensia Nakabiito, Thomas R Fleming, Terry Elliott, Scott Horton, Kevin Dransfield, Amal MurarkaAbstract:The transmission of HIV-1 infection from an infected mother to her infant is estimated to be 15-40% with more than half of transmission probably occurring late in pregnancy or during labor and delivery. Nevirapine a non-nucleoside reverse transcriptase inhibitor is an excellent candidate for a single-dose antiretroviral intervention administered during labor. Findings are presented from a study assessing the safety pharmacokinetics tolerance antiretroviral activity and infant HIV infection status following the administration of 1 dose of Nevirapine to HIV-1-infected pregnant women during labor and their newborns during the first week of life. 200 mg of Nevirapine were given as a single dose during labor to 21 HIV-1-infected pregnant women in Kampala Uganda. 8 of their infants did not receive the drug while 13 infants received 1 dose of Nevirapine at 2 mg/kg at 72 hours of age. Nevirapine was well tolerated by both the women and infants with no serious adverse events related to the drug observed. Median Nevirapine concentration in breast milk 1 week after delivery was 103 ng/ml. Plasma Nevirapine concentrations remained above 100 ng/ml in all infants from both cohorts tested at age 7 days. Maternal HIV-1 RNA levels decreased by a median of 1.3 logs at 1 week postpartum and returned to baseline by 6 weeks postpartum. Detectable plasma HIV-1 RNA was observed in 1 of 22 (4.5%) infants at birth 3/21 (14%) at 6 weeks and 4/21 (19%) at 6 months of age. This regimen has promise as a prophylaxis against intrapartum and early breast milk HIV transmission in a breast-feeding population.
Shahin Lockman - One of the best experts on this subject based on the ideXlab platform.
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antiretroviral therapies in women after single dose Nevirapine exposure
The New England Journal of Medicine, 2010Co-Authors: Shahin Lockman, Michael Hughes, James A Mcintyre, Yu Zheng, Tsungai Chipato, Francesca Conradie, Fred Sawe, Aida Asmelash, Mina C Hosseinipour, Lerato MohapiAbstract:Background Peripartum administration of single-dose Nevirapine reduces mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) but selects for Nevirapine-resistant virus. Methods In seven African countries, women infected with HIV-1 whose CD4+ T-cell counts were below 200 per cubic millimeter and who either had or had not taken single-dose Nevirapine at least 6 months before enrollment were randomly assigned to receive antiretroviral therapy with tenofovir–emtricitabine plus Nevirapine or tenofovir-emtricitabine plus lopinavir boosted by a low dose of ritonavir. The primary end point was the time to confirmed virologic failure or death. Results A total of 241 women who had been exposed to single-dose Nevirapine began the study treatments (121 received Nevirapine and 120 received ritonavir-boosted lopinavir). Significantly more women in the Nevirapine group reached the primary end point than in the ritonavir-boosted lopinavir group (26% vs. 8%) (adjusted P=0.001). Virologic failure occu...
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response to antiretroviral therapy after a single peripartum dose of Nevirapine
The New England Journal of Medicine, 2007Co-Authors: Shahin Lockman, Roger L Shapiro, Ibou Thior, Carolyn Wester, Laura M Smeaton, Lisa Stevens, Fatima Chand, Joseph Makhema, Claire Moffat, Aida AsmelashAbstract:Background A single dose of Nevirapine during labor reduces perinatal transmission of human immunodeficiency virus type 1 (HIV-1) but often leads to viral Nevirapine resistance mutations in mothers and infants. Methods We studied the response to Nevirapine-based antiretroviral treatment among women and infants who had previously been randomly assigned to a single, peripartum dose of Nevirapine or placebo in a trial in Botswana involving the prevention of the transmission of HIV-1 from mother to child. All women were treated with antenatal zidovudine. The primary end point for mothers and infants was virologic failure by the 6-month visit after initiation of antiretroviral treatment, estimated within groups by the Kaplan–Meier method. Results Of 218 women who started antiretroviral treatment, 112 had received a single dose of Nevirapine and 106 had received placebo. By the 6-month visit after the initiation of antiretroviral treatment, 5.0% of the women who had received placebo had virologic failure, as co...
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maternal single dose Nevirapine versus placebo as part of an antiretroviral strategy to prevent mother to child hiv transmission in botswana
AIDS, 2006Co-Authors: Roger L Shapiro, Ibou Thior, Peter B Gilbert, Shahin Lockman, Carolyn Wester, Laura M Smeaton, Lisa Stevens, Jody S Heymann, Thumbi Ndungu, Simani GaseitsiweAbstract:Single-dose Nevirapine given to women and infants reduces mother-to-child HIV transmission but Nevirapine resistance develops in a large percentage of women. The objective was to determine whether the maternal Nevirapine dose could be eliminated in the setting of zidovudine prophylaxis. A 2 x 2 factorial randomized clinical trial with a double-blinded peripartum factor designed to assess the equivalence of maternal single-dose Nevirapine versus placebo with respect to HIV transmission. A total of 709 HIV-infected pregnant women were randomized from four district hospitals in Botswana resulting in 694 live first-born infants. HAART was available for women with AIDS. All women received a background of zidovudine from 34 weeks gestation through delivery and all infants received single-dose Nevirapine at birth and zidovudine from birth through 1 month. Women were randomized to receive either single-dose Nevirapine or placebo during labor. Main outcome measures: The primary endpoint was infant HIV infection by the 1-month visit. Of the 694 infants in this equivalence study 15 (4.3%) of 345 in the maternal Nevirapine arm were HIV infected by 1 month versus 13 (3.7%) of 349 in the maternal placebo arm (95% confidence interval for difference _2.4% to 3.8%) meeting pre-determined equivalence criteria. Nevirapine resistance at 1 month postpartum was detected in 45% of a random sample of women who received Nevirapine. In the setting of maternal zidovudine and infant zidovudine plus singledose Nevirapine infant HIV infection rates were similar whether women received single-dose Nevirapine or placebo. This strategy avoids the potential for maternal Nevirapine resistance. (authors)
David B Hall - One of the best experts on this subject based on the ideXlab platform.
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toxicogenomics of Nevirapine associated cutaneous and hepatic adverse events among populations of african asian and european descent
AIDS, 2011Co-Authors: Jing Yuan, David B Hall, Piroon Mootsikapun, Kiat Ruxrungtham, Anna M Cammett, Supriya Jayadev, Manuel Distel, Stephen Storfer, Zimei Huang, Daniel PodzamczerAbstract:OBJECTIVE Nevirapine is widely prescribed for HIV-1 infection. We characterized relationships between Nevirapine-associated cutaneous and hepatic adverse events and genetic variants among HIV-infected adults. DESIGN We retrospectively identified cases and controls. Cases experienced symptomatic Nevirapine-associated severe (grade III/IV) cutaneous and/or hepatic adverse events within 8 weeks of initiating Nevirapine. Controls did not experience adverse events during more than 18 weeks of Nevirapine therapy. METHODS Cases and controls were matched 1: 2 on baseline CD4 T-cell count, sex, and race. Individuals with 150 or less CD4 T cells/μl at baseline were excluded. We characterized 123 human leukocyte antigen (HLA) alleles and 2744 single-nucleotide polymorphisms in major histocompatibility complex (MHC) and drug metabolism and transport genes. RESULTS We studied 276 evaluable cases (175 cutaneous adverse events, 101 hepatic adverse events) and 587 controls. Cutaneous adverse events were associated with CYP2B6 516G→T (OR 1.66, all), HLA-Cw*04 (OR 2.51, all), and HLA-B*35 (OR 3.47, Asians; 5.65, Thais). Risk for cutaneous adverse events was particularly high among Blacks with CYP2B6 516TT and HLA-Cw*04 (OR 18.90) and Asians with HLA-B*35 and HLA-Cw*04 (OR 18.34). Hepatic adverse events were associated with HLA-DRB*01 (OR 3.02, Whites), but not CYP2B6 genotypes. Associations differed by population, at least in part reflecting allele frequencies. CONCLUSION Among patients with at least 150 CD4 T cells/μl, polymorphisms in drug metabolism and immune response pathways were associated with greater likelihood of risk for Nevirapine-related adverse events. Results suggest fundamentally different mechanisms of adverse events: cutaneous, most likely MHC class I-mediated, influenced by Nevirapine CYP2B6 metabolism; hepatic, most likely MHC class II-mediated and unaffected by such metabolism. These risk variants are insensitive for routine clinical screening.
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high exposure to Nevirapine in plasma is associated with an improved virological response in hiv 1 infected individuals
AIDS, 2001Co-Authors: Agnes I Veldkamp, Stefano Vella, David A Cooper, Peter Reiss, David B Hall, Julio S G Montaner, Joep M A Lange, Jos H Beijnen, Gerrit Jan Weverling, Richard M W HoetelmansAbstract:OBJECTIVE: To explore relationships between exposure to Nevirapine and the virological response in HIV-1-infected individuals participating in the INCAS trial. METHODS: The elimination rate constant of plasma HIV-1 RNA (k) was calculated during the first 2 weeks of treatment with Nevirapine, zidovudine and didanosine in 51 antiretroviral-naive HIV-1-infected patients. The relationships between the value of k, the time to reach an undetectable HIV-1 RNA concentration in plasma (< 20 copies/ml) and the success of therapy after 52 weeks of treatment as dependent variables and the exposure to Nevirapine, baseline HIV-1 RNA and baseline CD4 cell count as independent variables, were explored using linear regression analyses, proportional hazard models and logistic analyses, respectively. RESULTS: The value of k for HIV-1 RNA in plasma was positively and significantly associated with the mean plasma Nevirapine concentration during the first 2 weeks of therapy (P = 0.011) and the baseline HIV-1 RNA (P = 0.008). Patients with a higher exposure to Nevirapine reached undetectable levels of HIV-1 RNA in plasma more rapidly (P = 0.03). From 12 weeks on, the median Nevirapine plasma concentration was significantly correlated with success of therapy after 52 weeks (P < 0.02). CONCLUSIONS: A high exposure to Nevirapine (in a twice daily regimen) is significantly associated with improved virological response in the short as well as in the long term. These findings suggest that optimization of Nevirapine concentration might be used as a tool to improve virological outcome in (antiretroviral-naive) patients treated with Nevirapine.
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antiviral effect and pharmacokinetic interaction between Nevirapine and indinavir in persons infected with human immunodeficiency virus type 1
The Journal of Infectious Diseases, 1999Co-Authors: Robert L Murphy, David B Hall, Michael Lamson, Jean Pierre Sommadossi, Maureen W Myers, Alex DusekAbstract:Nevirapine and indinavir have the potential of affecting the pharmacokinetics of each other. In a prospective trial, 24 human immunodeficiency virus (HIV)-infected subjects on stable nucleoside or no therapy were treated with 800 mg of indinavir every 8 h. After 7 days, 200 mg of Nevirapine a day was added for 14 days and then increased to 200 mg twice a day. At day 7 (before Nevirapine), there was a sevenfold difference among the subjects in indinavir area under the curve (AUC), and there was a significant correlation between indinavir AUC (r 2 = 0.378, P = .019), minimum plasma concentration (C min ; r 2 = 0.359, P = .023), maximum plasma concentration (C max ; r 2 = 0.340, P = .028), and plasma HIV RNA decline. Nevirapine significantly reduced median indinavir C min (47.5%) and AUC (27.4%) and, to a lesser extent, C max (11%). Plasma HIV RNA values were ≤20 copies/mL in 10 of 17 (58.8%) subjects at 58 weeks or last visit. These data suggest that indinavir dosing should be dependent on drug exposure and not on cotherapy with Nevirapine.
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a randomized double blind trial comparing combinations of Nevirapine didanosine and zidovudine for hiv infected patients the incas trial
JAMA, 1998Co-Authors: Julio S G Montaner, Stefano Vella, Brian Conway, Patrick A Robinson, Marianne Harris, Mark A. Wainberg, David A Cooper, Peter Reiss, Don Smith, David B HallAbstract:Context.—Current guidelines recommend that individuals infected with the human immunodeficiency virus type 1 (HIV-1) be treated using combinations of antiretroviral agents to achieve sustained suppression of viral replication as measured by the plasma HIV-1 RNA assay, in the hopes of achieving prolonged remission of the disease. However, until recently, many drug combinations have not led to sustained suppression of HIV-1 RNA.Objective.—To compare the virologic effects of various combinations of Nevirapine, didanosine, and zidovudine.Design.—Double-blind, controlled, randomized trial.Setting.—University-affiliated ambulatory research clinics in Italy, the Netherlands, Canada, and Australia (INCAS).Patients.—Antiretroviral therapy–naive adults free of the acquired immunodeficiency syndrome with CD4 cell counts between 0.20 and 0.60×109/L (200-600/µL).Intervention.—Patients received zidovudine plus Nevirapine (plus didanosine placebo), zidovudine plus didanosine (plus Nevirapine placebo), or zidovudine plus didanosine plus Nevirapine.Main Outcome Measure.—Plasma HIV-1 RNA.Results.—Of the 153 enrolled patients, 151 were evaluable. At week 8, plasma HIV-1 RNA levels had decreased by log 2.18, 1.55, and 0.90 in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus Nevirapine groups, respectively (P<.05). The proportions of patients with plasma HIV-1 RNA levels below 20 copies per milliliter at week 52 were 51%, 12%, and 0% in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus Nevirapine groups, respectively (P<.001). Viral amplification was attempted in 59 patients at 6 months. Viral isolation was unsuccessful in 19 (79%) of 24, 10 (53%) of 19, and 5 (31%) of 16 patients in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus Nevirapine groups, respectively. Among patients from whom virus could be amplified, resistance to Nevirapine was found in all 11 patients receiving zidovudine plus Nevirapine and in all 5 patients receiving triple drug therapy. Rates of disease progression or death were 23% (11/47), 25% (13/53), and 12% (6/51) for the zidovudine plus Nevirapine, zidovudine plus didanosine, and triple drug therapy groups, respectively (P=.08).Conclusions.—Triple drug therapy with zidovudine, didanosine, and Nevirapine led to a substantially greater and sustained decrease in plasma viral load than the 2-drug regimens studied. Our results also suggest that suppression of viral replication, as demonstrated by a decrease in the plasma HIV-1 RNA load below the level of quantitation of the most sensitive test available, may at least forestall the development of resistance.
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Alternating Nevirapine and Zidovudine Treatment of Human Immunodeficiency Virus Type 1-Infected Persons Does Not Prolong Nevirapine Activity
The Journal of Infectious Diseases, 1994Co-Authors: Menno D. De Jong, David B Hall, Mark Loewenthal, Charles A. Boucher, Ineke Van Der Ende, Pauline Schipper, Allison Imrie, H. M. Weigel, R. H. Kauffmann, Roel KosterAbstract:: The potential use of an alternating treatment strategy with Nevirapine and zidovudine in prolonging the antiretroviral effects of Nevirapine was evaluated. Ten human immunodeficiency virus type 1 (HIV-1)-infected p24 antigen-positive persons who had not received prior antiretroviral therapy were treated for 9-13 weeks with an alternating regimen of 1 week of Nevirapine (200 mg/day) and 3 weeks of zidovudine (600 mg/day). Serum p24 antigen levels declined during the first week of Nevirapine treatment (median, 59%); however, subsequent courses of Nevirapine were characterized by rising p24 antigen levels, while antigen levels remained stable or declined during zidovudine treatment. Serum beta 2-microglobulin levels and CD4+ cell counts exhibited similar responses. HIV-1 isolates obtained from 2 patients revealed 40- and 1000-fold reductions in Nevirapine sensitivity after 8 weeks. These findings demonstrate that alternating treatment with zidovudine and Nevirapine does not prolong the effectiveness of Nevirapine and does not prevent the development of Nevirapine resistance.
Jos H Beijnen - One of the best experts on this subject based on the ideXlab platform.
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No pharmacokinetic drug-drug interaction between Nevirapine and paclitaxel.
Anti-Cancer Drugs, 2005Co-Authors: Bregt S Kappelhoff, Alwin D R Huitema, Albert T A Mairuhu, Jan H.m. Schellens, Jos H BeijnenAbstract:: We have investigated the pharmacokinetics of Nevirapine and paclitaxel in a patient who used both drugs concomitantly, as there are strong theoretical indications for a potential pharmacokinetic drug-drug interaction. Plasma concentrations of Nevirapine (dose: 200 mg twice daily orally) and paclitaxel (dose: 100 mg/m(2) 3-h i.v. infusion) were determined in a HIV-1-infected patient with Kaposi's sarcoma. Since both drugs are metabolized via the same cytochrome P450 isoenzymes, investigation of a drug-drug interaction was considered important. We found that the plasma concentrations of Nevirapine given together with paclitaxel were similar to those given without paclitaxel. The exposures to paclitaxel (AUC(0-infinity) = 3787 h.ng/ml) and its hydroxy metabolites when co-administered with Nevirapine were comparable to the mean exposure to paclitaxel and its metabolites from eight historical controls (AUC(0-infinity) = 3614 h.ng/ml) treated with the same dose. No pharmacokinetic drug-drug interaction between Nevirapine and paclitaxel could be demonstrated in our HIV-1-infected patient.
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Nevirapine and efavirenz pharmacokinetics and covariate analysis in the 2nn study
Antiviral Therapy, 2005Co-Authors: Bregt S Kappelhoff, Frank Van Leth, Thomas R Macgregor, Joep M A Lange, Jos H Beijnen, Alwin D R HuitemaAbstract:Objective: The aim of this 2NN pharmacokinetic substudy was to investigate the population pharmacokinetics of Nevirapine and efavirenz. Methods: Treatment-naive, HIV-1-infected patients received Nevirapine (once or twice daily), efavirenz or a combination with lamivudine and stavudine. Blood samples were collected on day 3 and weeks 1, 2, 4, 24 and 48. Using non-linear mixed effects modelling, pharmacokinetics of Nevirapine and efavirenz and factors involved in the inter-individual variability were investigated. Results: Clearance of Nevirapine in the induction phase ( 28 days) were 2.02 l/h and 2.81 l/h, respectively. Volume of distribution and absorption rate constant were 77.0 l and 1.66 h ‐1 , respectively. Clearance of Nevirapine was lower in females (13.8%) and in patients with hepatitis B (19.5%). Patients from South America and Western countries had higher clearance of Nevirapine compared with Thai and South African patients. The clearances of efavirenz in the induction phase and at steady state were 7.95 l/h and 8.82 l/h, respectively. The volume of distribution and absorption rate constant were 418 l and 0.287 h ‐1 , respectively. Concomitant use of Nevirapine increased clearance of efavirenz (43%). Patients from Thailand had lower clearance than the rest of the population. Conclusions: The population pharmacokinetics of Nevirapine and efavirenz were assessed in the 2NN trial. For both drugs, an induction phase was distinguished from the steady-state phase. Gender, hepatitis B and geographical region were involved in the variability of the pharmacokinetics of Nevirapine. Region and concomitantly used Nevirapine were determinants of the pharmacokinetics of efavirenz.
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Incidence and risk factors for Nevirapine-associated rash.
European journal of clinical pharmacology, 2003Co-Authors: Monique M R De Maat, Alwin D R Huitema, Rob Ter Heine, Jan W Mulder, Pieter L Meenhorst, Albert T A Mairuhu, Eric C M Van Gorp, Jos H BeijnenAbstract: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. 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 Nevirapine-containing regimen. 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 Nevirapine-containing 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. 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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Incidence and risk factors for Nevirapine-associated rash
European Journal of Clinical Pharmacology, 2003Co-Authors: Monique M R De Maat, Alwin D R Huitema, Jan W Mulder, Pieter L Meenhorst, Albert T A Mairuhu, Eric C M Van Gorp, Rob Ter Heine, Jos H BeijnenAbstract: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.
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population pharmacokinetics of Nevirapine in an unselected cohort of hiv 1 infected individuals
British Journal of Clinical Pharmacology, 2002Co-Authors: Monique M R De Maat, Alwin D R Huitema, Eric C M Van Gorp, Jan Mulder, P L Meenhorst, Jos H BeijnenAbstract:Aims To study the population pharmacokinetics of Nevirapine and to identify relationships between patient characteristics and pharmacokinetics in an unselected population of patients attending our outpatient clinic. Methods Ambulatory HIV-1-infected patients from the outpatient clinic of the Slotervaart Hospital who were being treated with a Nevirapine-containing regimen were included. During each visit, blood samples were collected for the determination of Nevirapine plasma concentrations and clinical chemistry parameters. Variables that were collected at baseline were serology for hepatitis B (HBV) and C (HCV) viruses, liver enzymes, and total bilirubin (TBR). In addition, information about concomitant use of St John's wort and patient demographics were included. The pharmacokinetics of Nevirapine were described by first-order absorption and elimination using nonlinear mixed effect modelling (NONMEM V1.1). Population pharmacokinetic parameters (apparent clearance (CL/F), volume of distribution (V/F), absorption rate constant (ka)) were estimated, as were interindividual, interoccasion, and residual variability in the pharmacokinetics. The influence of patient characteristics on the pharmacokinetics of Nevirapine was determined. Results From 173 outpatients a total number of 757 Nevirapine plasma concentrations at a single random time point and full pharmacokinetic curves for 13 patients were available resulting in a database of 1329 Nevirapine plasma concentrations. Mean CL/F, V/F, and ka were 3.27 l h−1, 106 l, and 01.66 h−1, respectively. CL/F of Nevirapine was correlated with weight, chronic HCV infection, and baseline aspartate aminotransferase (ASAT). Chronic HCV and baseline ASAT> 1.5 × upper limit of normal (ULN) decreased CL/F by 27.4% and 13.2%, respectively, whereas an increase in body weight of 10 kg increased CL/F by 0.14 l h−1. A trend towards a lower CL/F in patients of the Negroid race was observed. No significant covariates were found for V/F. Conclusions The pharmacokinetics of Nevirapine were adequately described by our population pharmacokinetic model. Weight, chronic HCV infection, and baseline ASAT were found to be significant covariates for CL/F of Nevirapine. The model incorporating these significant covariates may be an important aid in further optimizing Nevirapine-containing therapy.
Aida Asmelash - One of the best experts on this subject based on the ideXlab platform.
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antiretroviral therapies in women after single dose Nevirapine exposure
The New England Journal of Medicine, 2010Co-Authors: Shahin Lockman, Michael Hughes, James A Mcintyre, Yu Zheng, Tsungai Chipato, Francesca Conradie, Fred Sawe, Aida Asmelash, Mina C Hosseinipour, Lerato MohapiAbstract:Background Peripartum administration of single-dose Nevirapine reduces mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) but selects for Nevirapine-resistant virus. Methods In seven African countries, women infected with HIV-1 whose CD4+ T-cell counts were below 200 per cubic millimeter and who either had or had not taken single-dose Nevirapine at least 6 months before enrollment were randomly assigned to receive antiretroviral therapy with tenofovir–emtricitabine plus Nevirapine or tenofovir-emtricitabine plus lopinavir boosted by a low dose of ritonavir. The primary end point was the time to confirmed virologic failure or death. Results A total of 241 women who had been exposed to single-dose Nevirapine began the study treatments (121 received Nevirapine and 120 received ritonavir-boosted lopinavir). Significantly more women in the Nevirapine group reached the primary end point than in the ritonavir-boosted lopinavir group (26% vs. 8%) (adjusted P=0.001). Virologic failure occu...
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response to antiretroviral therapy after a single peripartum dose of Nevirapine
The New England Journal of Medicine, 2007Co-Authors: Shahin Lockman, Roger L Shapiro, Ibou Thior, Carolyn Wester, Laura M Smeaton, Lisa Stevens, Fatima Chand, Joseph Makhema, Claire Moffat, Aida AsmelashAbstract:Background A single dose of Nevirapine during labor reduces perinatal transmission of human immunodeficiency virus type 1 (HIV-1) but often leads to viral Nevirapine resistance mutations in mothers and infants. Methods We studied the response to Nevirapine-based antiretroviral treatment among women and infants who had previously been randomly assigned to a single, peripartum dose of Nevirapine or placebo in a trial in Botswana involving the prevention of the transmission of HIV-1 from mother to child. All women were treated with antenatal zidovudine. The primary end point for mothers and infants was virologic failure by the 6-month visit after initiation of antiretroviral treatment, estimated within groups by the Kaplan–Meier method. Results Of 218 women who started antiretroviral treatment, 112 had received a single dose of Nevirapine and 106 had received placebo. By the 6-month visit after the initiation of antiretroviral treatment, 5.0% of the women who had received placebo had virologic failure, as co...