Population pharmacokinetics of lopinavir in combination with rifampicin-based antitubercular treatment in HIV-infected South African children

Elsherbiny, Doaa A.; Ren, Yuan; McIlleron, Helen; Maartens, Gary; Simonsson, Ulrika S. H.

doi:10.1007/s00228-010-0847-9

Cited by 24 publications

(19 citation statements)

References 26 publications

(12 reference statements)

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“…However, in a subsequent study, poorer response to rifampinbased therapy was only observed if only ritonavir or doubledose LPV/r was used, but positive short-term virological outcomes were seen in HIV-TB co-infected children who received super-boosted LPV/r [60]. Another study also found that super-boosting of LPV to achieve a LPV/r ratio of 1:1 in children on rifampin-based TB treatment resulted in minimum concentrations of LPV >1 mg/l [59].…”

Section: Concomitant Tuberculosis Treatmentmentioning

confidence: 86%

“…In another South African study, 95% of HIV-infected children not co-treated for concomitant TB achieved virological suppression, in contrast to 52% among children who were also treated for TB [58]. Furthermore, increasing the dose of ritonavir to achieve a 1:1 ratio when given with rifampin did not fully compensate for increased clearance of LPV in children [59]. However, in a subsequent study, poorer response to rifampinbased therapy was only observed if only ritonavir or doubledose LPV/r was used, but positive short-term virological outcomes were seen in HIV-TB co-infected children who received super-boosted LPV/r [60].…”

Section: Concomitant Tuberculosis Treatmentmentioning

confidence: 93%

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Tackling virological failure in HIV-infected children living in Africa

Jenabian

Costiniuk

Bouassa

et al. 2015

Expert Review of Anti-infective Therapy

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Drug resistance in HIV-infected children is one of the main contributors to antiretroviral treatment (ART) failure, especially in developing countries. Sub-Saharan Africa has the largest burden of pediatric HIV infection in the world. Herein, we systematically review the current status of ART failure in HIV-infected African children. A literature search for publications within 10 years was performed through PubMed to identify relevant articles. Included studies examined the impact of timing of ART initiation, criteria for diagnosing therapeutic failure, predictors of therapeutic failure, management strategies and future directions to minimize failure rates in these pediatric populations. Although there is scale-up of ART programs in Africa, novel therapeutic and management strategies are needed to overcome current challenges.

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Section: Concomitant Tuberculosis Treatmentmentioning

confidence: 86%

Section: Concomitant Tuberculosis Treatmentmentioning

confidence: 93%

Tackling virological failure in HIV-infected children living in Africa

Jenabian

Costiniuk

Bouassa

et al. 2015

Expert Review of Anti-infective Therapy

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“…Elsherbiny et al performed a study to characterize these pharmacokinetic interactions, and to compare two treatment regimens, through population pharmacokinetic analysis [26]. One of the treatment regimens was lopinavir (LPV) and ritonavir (/r) in a 4: 1 ratio without RIF; this group consisted of 15 children with HIV but without TB.…”

Section: Rifampinmentioning

confidence: 99%

Population Pharmacokinetics and its Role in Anti-Tuberculosis Drug Development and Optimization of Treatment

Egelund

Barth²,

Peloquin³

2011

CPD

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Tuberculosis (TB) has survived for millennia due to its unique physiochemical properties and its ability to persist in a "dormant" state. Because of these unique properties, the treatment of TB involves multiple drugs for half of a year or longer. Although the incidence of TB has declined in most developing countries, it remains poorly controlled in much of the developing world. This is partly driven by co-infection with HIV in these settings. Concern about this dual epidemic has renewed interest in anti-tuberculosis drugs, and this in turn has led to increasing amounts of pharmacokinetic data regarding TB drugs. Population pharmacokinetics has proven useful for many disease states, providing a valuable tool with which to explore data and predict future events. It not only generates pharmacokinetic parameter estimates, but it includes patient characteristics (covariates) that may alter those parameters. We review the population pharmacokinetic studies undertaken with anti-TB medications. In addition to the primary medications used in TB treatment (rifampin, isoniazid, pyrazinamide, and ethambutol) we discuss the fluoroquinolones, various software packages, and the covariates that were found to be significant in each study.

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“…[59] This strategy did not completely compensate for the enhancement of lopinavir oral clearance. [60] Whether this approach is effective in infants <6 months of age is currently not known. Since TB may complicate the course of HIV-infection during early infancy, this is an important question to resolve.…”

Section: Overcoming the Effect Of Rifampicin On Lopinavir Metabolismmentioning

confidence: 99%

Antiretroviral Therapy for Children in Resource-Limited Settings

Eley

Meyers

2011

Pediatric Drugs

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WHO antiretroviral treatment guidelines for HIV-infected children have influenced the design of treatment programmes in resource-limited settings. This review analyses the latest WHO first- and second-line regimen recommendations. The recommendation to use lopinavir/ritonavir-containing first-line regimens in young children with prior non-nucleoside reverse transcriptase inhibitor (NNRTI) exposure is based on good quality evidence. Recent research suggests that lopinavir/ritonavir-containing first-line regimens should be extended to all young children, irrespective of prior NNRTI exposure. Strategies for overcoming the adverse metabolic effects of rifampicin-containing anti-tuberculosis therapy on antiretroviral therapy regimens have been under-researched in HIV-infected children, creating uncertainty about global recommendations. Preferred second-line recommendations are largely predictable. The exception is that NNRTI-containing second-line regimens are recommended for children previously exposed to NNRTIs and who subsequently did not respond to lopinavir/ritonavir-containing first-line therapy. In these patients, second-line regimens containing newer protease inhibitors (PIs) such as darunavir and tipranavir, or integrase inhibitors such as raltegravir, should be evaluated. Newer antiretroviral agents including second-generation NNRTIs and PIs, C-C chemokine receptor type 5 inhibitors, and integrase inhibitors may assist in further refinement of existing regimen options.

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Population pharmacokinetics of lopinavir in combination with rifampicin-based antitubercular treatment in HIV-infected South African children

Cited by 24 publications

References 26 publications

Tackling virological failure in HIV-infected children living in Africa

Tackling virological failure in HIV-infected children living in Africa

Population Pharmacokinetics and its Role in Anti-Tuberculosis Drug Development and Optimization of Treatment

Antiretroviral Therapy for Children in Resource-Limited Settings

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