Nevirapine versus Rifampin
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Study Design
To determine whether rifampicin reduces serum concentrations of nevirapine and whether nevirapine modifies serum concentrations of rifampicin, levels of these agents were determined at steady state by high-performance liquid chromatography in 10 HIV-infected patients with tuberculosis.
Study Results
The median area under the curve (AUC) 0-12h of nevirapine before and after rifampicin was 56.2 and 32.8 microg/ml per hour, respectively ( p =.04). This represents a 31% reduction in serum nevirapine concentrations. The C(max) decreased from 5.6 to 4.5 microg/ml ( p =.04), which represented a 36% reduction. A 21% decrease in the C(min) was not statistically significant. Exposure to rifampicin did not significantly differ between those patients who were receiving and were not receiving nevirapine. However, our study shows that rifampicin reduces serum exposure to nevirapine. The clinical implications for this reduction remain to be established.
Study Conclusions
Given that the lowest trough serum concentration of nevirapine exceeded by more than 40 times the protein binding adjusted median infective dose (IC(50)) of wild-type HIV in all patients, we suggest that there is no need to increase nevirapine dosage when it is given with rifampicin.
References
Ribera E, Pou L, Lopez RM, Crespo M, Falco V, Ocana I, Pahissa A. Pharmacokinetic interaction between nevirapine and rifampicin in hiv-infected patients with tuberculosis. Journal Of Acquired Immunodeficiency Syndromes. 2001; 5: 450-453.
NVP Vs. Rifampin
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Study Design
ART-naïve HIV-infected children aged 3–35 months with and without TB were treated with NVP 200 mg/m2 twice daily plus two NRTIs. The new WHO recommended higher dosages of rifampin and isoniazid were used. After 4 weeks of ART, PK samples were collected at 0, 2, 6, and 12 hours post- dose to measure NVP plasma concentrations, using a validated LC/MS/MS assay. In the co-infected patients, sampling was repeated after 4 weeks off TB therapy. PK parameters were calculated using noncompartmental analysis and were compared between groups using Wilcoxon Rank-sum test and within group using Signed-rank test
Study Results
Of the 53 patients, 23 (43%) had TB coinfection, of whom 15 completed PK sampling on (PK1) and off (PK2) anti-TB therapy. Baseline characteristics were similar in the two groups except co-infected children had lower median height-for-age-Z-score. Median NVP concentrations were lowest in the children with TB/HIV coinfection on TB therapy, followed by HIV infection only and highest in the co-infected off TB therapy (Figure). Median NVP Cmax, Cmin and AUC0-12h were not significantly different between children with HIV and those with TB/HIV on or off anti-TB therapy. In multivariate analysis, TBtransition to LPV/r-based ART, thought to be adherence-related. Median NVP trough concentration at 1 and 2 wks was 3.01 mcg/mL (at median 15 hrs); 48% of concentrations were below the therapeutic target of 3.0 mcg/mL (including 10% BQL, indicating non-adherence); concentrations did not correlate with the magnitude of decline in HIV RNA log copies/mL at either 2 or 4 wks.
Study Conclusions
NVP, ZDV, 3TC started in the first week of life was safe and effective, even among infants with NVP levels below the ideal therapeutic PK target. Although poor tolerability often led to transient viral rebound following transition to LPV/r-based ART, almost all children were able to achieve HIV RNA declines to < 400 copies/mL by 12 weeks of life.
References
Enimil, A, Yang, H, Gillani, F, Alghamdi, W, Ortsin, A, Dompreh, A, etc.. Effect of antituberculosis therapy on nevirapine pharmacokinetics in young children. Conference On Retroviruses And Opportunistic Infections. 2019; : .
Nevirapine versus Rifampin
^
Study Design
To determine whether rifampicin reduces serum concentrations of nevirapine and whether nevirapine modifies serum concentrations of rifampicin, levels of these agents were determined at steady state by high-performance liquid chromatography in 10 HIV-infected patients with tuberculosis.
Study Results
The median area under the curve (AUC) 0-12h of nevirapine before and after rifampicin was 56.2 and 32.8 microg/ml per hour, respectively ( p =.04). This represents a 31% reduction in serum nevirapine concentrations. The C(max) decreased from 5.6 to 4.5 microg/ml ( p =.04), which represented a 36% reduction. A 21% decrease in the C(min) was not statistically significant. Exposure to rifampicin did not significantly differ between those patients who were receiving and were not receiving nevirapine. However, our study shows that rifampicin reduces serum exposure to nevirapine. The clinical implications for this reduction remain to be established.
Study Conclusions
Given that the lowest trough serum concentration of nevirapine exceeded by more than 40 times the protein binding adjusted median infective dose (IC(50)) of wild-type HIV in all patients, we suggest that there is no need to increase nevirapine dosage when it is given with rifampicin.
References
Enimil, A, Yang, H, Gillani, F, Alghamdi, W, Ortsin, A, Dompreh, A, etc.. Effect of antituberculosis therapy on nevirapine pharmacokinetics in young children. Conference On Retroviruses And Opportunistic Infections. 2019; : .
Nevirapine versus Rifampin
^
Study Design
To determine whether rifampicin reduces serum concentrations of nevirapine and whether nevirapine modifies serum concentrations of rifampicin, levels of these agents were determined at steady state by high-performance liquid chromatography in 10 HIV-infected patients with tuberculosis.
Study Results
The median area under the curve (AUC) 0-12h of nevirapine before and after rifampicin was 56.2 and 32.8 microg/ml per hour, respectively ( p =.04). This represents a 31% reduction in serum nevirapine concentrations. The C(max) decreased from 5.6 to 4.5 microg/ml ( p =.04), which represented a 36% reduction. A 21% decrease in the C(min) was not statistically significant. Exposure to rifampicin did not significantly differ between those patients who were receiving and were not receiving nevirapine. However, our study shows that rifampicin reduces serum exposure to nevirapine. The clinical implications for this reduction remain to be established.
Study Conclusions
Given that the lowest trough serum concentration of nevirapine exceeded by more than 40 times the protein binding adjusted median infective dose (IC(50)) of wild-type HIV in all patients, we suggest that there is no need to increase nevirapine dosage when it is given with rifampicin.
References
Enimil, A, Yang, H, Gillani, F, Alghamdi, W, Ortsin, A, Dompreh, A, etc.. Effect of antituberculosis therapy on nevirapine pharmacokinetics in young children. Conference On Retroviruses And Opportunistic Infections. 2019; : .
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