Browsing by Subject "Ritonavir"

Now showing 1 - 4 of 4
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    Effect of ritonavir-induced cytochrome P450 3A4 inhibition on plasma fentanyl concentrations during patient-controlled epidural labor analgesia: a pharmacokinetic simulation.
    (Int J Obstet Anesth, 2014-02) Cambic, CR; Avram, MJ; Gupta, DK; Wong, CA
    BACKGROUND: Ritonavir inhibition of cytochrome P450 3A4 decreases the elimination clearance of fentanyl by 67%. We used a pharmacokinetic model developed from published data to simulate the effect of sample patient-controlled epidural labor analgesic regimens on plasma fentanyl concentrations in the absence and presence of ritonavir-induced cytochrome P450 3A4 inhibition. METHODS: Fentanyl absorption from the epidural space was modeled using tanks-in-series delay elements. Systemic fentanyl disposition was described using a three-compartment pharmacokinetic model. Parameters for epidural drug absorption were estimated by fitting the model to reported plasma fentanyl concentrations measured after epidural administration. The validity of the model was assessed by comparing predicted plasma concentrations after epidural administration to published data. The effect of ritonavir was modeled as a 67% decrease in fentanyl elimination clearance. Plasma fentanyl concentrations were simulated for six sample patient-controlled epidural labor analgesic regimens over 24 h using ritonavir and control models. Simulated data were analyzed to determine if plasma fentanyl concentrations producing a 50% decrease in minute ventilation (6.1 ng/mL) were achieved. RESULTS: Simulated plasma fentanyl concentrations in the ritonavir group were higher than those in the control group for all sample labor analgesic regimens. Maximum plasma fentanyl concentrations were 1.8 ng/mL and 3.4 ng/mL for the normal and ritonavir simulations, respectively, and did not reach concentrations associated with 50% decrease in minute ventilation. CONCLUSION: Our model predicts that even with maximal clinical dosing regimens of epidural fentanyl over 24 h, ritonavir-induced cytochrome P450 3A4 inhibition is unlikely to produce plasma fentanyl concentrations associated with a decrease in minute ventilation.
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    Improved tuberculosis outcomes with daily vs. intermittent rifabutin in HIV-TB coinfected patients in India.
    (The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 2016-09) Jenks, JD; Kumarasamy, N; Ezhilarasi, C; Poongulali, S; Ambrose, P; Yepthomi, T; Devaraj, C; Benson, CA

    Setting

    Y R Gaitonde Centre for AIDS Research and Education, Chennai, India.

    Objective

    To compare anti-tuberculosis treatment outcomes in individuals with human immunodeficiency virus (HIV) and tuberculosis (TB) co-infection on atazanavir/ritonavir (ATV/r) antiretroviral therapy (ART) plus daily rifabutin (RBT) 150 mg with those on ATV/r plus thrice-weekly RBT 150 mg.

    Design

    A retrospective study was conducted of two HIV-TB co-infected cohorts between 2003 and 2014. Basic demographic and TB outcome data were obtained from an electronic database and patient records. The χ(2) and Fisher's exact test were used to compare daily and intermittent RBT treatment groups.

    Results

    Of 292 individuals on an ATV/r-based ART regimen plus RBT, 118 (40.4%) received thrice-weekly RBT and 174 (59.6%) daily RBT. Patients in the two RBT treatment groups were similar in sex, age, previous history of TB, site of TB and acid-fast bacilli smear status. More individuals in the daily vs. the intermittent RBT group achieved clinical cure (73.0% vs. 44.1%, P < 0.001), with no significant differences in relapse/recurrence or all-cause mortality between groups.

    Conclusion

    There were higher rates of clinical TB cure in individuals on a boosted protease inhibitor-based ART regimen with daily RBT compared to intermittently dosed RBT. Optimal RBT dosing in this setting requires further investigation.
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    Lopinavir/ritonavir monotherapy after virologic failure of first-line antiretroviral therapy in resource-limited settings.
    (AIDS, 2012-07-17) Bartlett, John A; Ribaudo, Heather J; Wallis, Carole L; Aga, Evgenia; Katzenstein, David A; Stevens, Wendy S; Norton, Michael R; Klingman, Karin L; Hosseinipour, Mina C; Crump, John A; Supparatpinyo, Khuanchai; Badal-Faesen, Sharlaa; Kallungal, Beatrice A; Kumarasamy, Nagalingeswaran
    OBJECTIVE: To evaluate virologic response rates of lopinavir/ritonavir (LPV/r) monotherapy as second-line antiretroviral treatment (ART) among adults in resource-limited settings (RLSs). DESIGN: An open-label pilot study of LPV/r monotherapy in participants on first-line nonnucleoside reverse transcriptase inhibitor three-drug combination ART with plasma HIV-1 RNA 1000-200 000  copies/ml. METHODS: Participants were recruited from five sites in Africa and Asia within the AIDS Clinical Trials Group (ACTG) network. All participants received LPV/r 400/100  mg twice daily. The primary endpoint was remaining on LPV/r monotherapy without virologic failure at week 24. Participants with virologic failure were offered addition of emtricitabine and tenofovir (FTC/TDF) to LPV/r. RESULTS: Mutations associated with drug resistance were encountered in nearly all individuals screened for the study. One hundred and twenty-three participants were enrolled, and 122 completed 24 weeks on study. A high proportion remained on LPV/r monotherapy without virologic failure at 24 weeks (87%). Archived samples with HIV-1 RNA levels less than 400  copies/ml at week 24 (n=102) underwent ultrasensitive assay. Of these individuals, 62 had levels less than 40  copies/ml and 30 had levels 40-200  copies/ml. Fifteen individuals experienced virologic failure, among whom 11 had resistance assessed and two had emergent protease inhibitor mutations. Thirteen individuals with virologic failure added FTC/TDF and one individual added FTC/TDF without virologic failure. At study week 48, 11 of 14 adding FTC/TDF had HIV-1 RNA levels less than 400  copies/ml. CONCLUSION: In this pilot study conducted in diverse RLS, LPV/r monotherapy as second-line ART demonstrated promising activity.
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    Lopinavir/Ritonavir Monotherapy as Second-line Antiretroviral Treatment in Resource-Limited Settings: Week 104 Analysis of AIDS Clinical Trials Group (ACTG) A5230.
    (Clin Infect Dis, 2015-05-15) Kumarasamy, Nagalingeswaran; Aga, Evgenia; Ribaudo, Heather J; Wallis, Carole L; Katzenstein, David A; Stevens, Wendy S; Norton, Michael R; Klingman, Karin L; Hosseinipour, Mina C; Crump, John A; Supparatpinyo, Khuanchai; Badal-Faesen, Sharlaa; Bartlett, John A
    BACKGROUND: The AIDS Clinical Trials Group (ACTG) A5230 study evaluated lopinavir/ritonavir (LPV/r) monotherapy following virologic failure (VF) on first-line human immunodeficiency virus (HIV) regimens in Africa and Asia. METHODS: Eligible subjects had received first-line regimens for at least 6 months and had plasma HIV-1 RNA levels 1000-200 000 copies/mL. All subjects received LPV/r 400/100 mg twice daily. VF was defined as failure to suppress to <400 copies/mL by week 24, or confirmed rebound to >400 copies/mL at or after week 16 following confirmed suppression. Subjects with VF added emtricitabine 200 mg/tenofovir 300 mg (FTC/TDF) once daily. The probability of continued HIV-1 RNA <400 copies/mL on LPV/r monotherapy through week 104 was estimated with a 95% confidence interval (CI); predictors of treatment success were evaluated with Cox proportional hazards models. RESULTS: One hundred twenty-three subjects were enrolled. Four subjects died and 2 discontinued prematurely; 117 of 123 (95%) completed 104 weeks. Through week 104, 49 subjects met the primary endpoint; 47 had VF, and 2 intensified treatment without VF. Of the 47 subjects with VF, 41 (33%) intensified treatment, and 39 of 41 subsequently achieved levels <400 copies/mL. The probability of continued suppression <400 copies/mL over 104 weeks on LPV/r monotherapy was 60% (95% CI, 50%-68%); 80%-85% maintained levels <400 copies/mL with FTC/TDF intensification as needed. Ultrasensitive assays on specimens with HIV-1 RNA level <400 copies/mL at weeks 24, 48, and 104 revealed that 61%, 62%, and 65% were suppressed to <40 copies/mL, respectively. CONCLUSIONS: LPV/r monotherapy after first-line VF with FTC/TDF intensification when needed provides durable suppression of HIV-1 RNA over 104 weeks. CLINICAL TRIALS REGISTRATION: NCT00357552.