Efficacy of a 6-month versus 9-month Intermittent Treatment Regimen in HIV-infected Patients with Tuberculosis

Swaminathan, Soumya; Narendran, Gopalan; Venkatesan, P; Iliayas, Sheik; Santhanakrishnan, Rameshkumar; Menon, Pradeep A.; Padmapriyadarsini, Chandrasekharan; Ramachandran, Ranjani; C, George Priya Doss; Suhadev, Mohanarani; Sakthivel, R.; Narayanan, P R

doi:10.1164/rccm.200903-0439oc

Cited by 83 publications

(83 citation statements)

References 28 publications

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“…WHO currently recommends that tuberculosis patients who are living with HIV should receive at least the same duration of treatment as HIV-negative patients. Increased risk of treatment failure and acquired rifamycin resistance have also been shown to be associated with intermittent regimens among HIV-infected patients [29][30][31]. WHO currently recommends that HIV-positive patients with tuberculosis and all tuberculosis patients living in HIV-prevalent settings should receive daily treatment, at least during the intensive phase [16].…”

Section: Chemotherapy Of Pulmonary Tuberculosis Short-course Chemothementioning

confidence: 99%

“…As there may be a genuine chance of resistance amplification with additional resistance to rifampicin [20,72] (especially for HIV status and/or intermittent dosing [20,28,31]) some authorities recommend changing to alternative regimens, such as REZ or RE, for more prolonged durations of administration, often f1 yr (grade D) [73,74]. Currently, the most optimal regimen for treatment of isoniazid-resistant tuberculosis appears unknown [16].…”

Section: Clinical Relevance Of Antituberculosis Drug Resistancementioning

confidence: 99%

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Treatment of tuberculosis: update 2010

Yew¹,

Lange²,

Leung³

2010

European Respiratory Journal

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Currently, the standard short-course chemotherapy for tuberculosis comprises a 6-month regimen, with a four-drug intensive phase and a two-drug continuation phase. Alternative chemotherapy using more costly and toxic drugs, often for prolonged durations generally .18 months, is required for multidrug-resistant and extensively drug-resistant tuberculosis. Directly observed treatment, as part of a holistic care programme, is a cost-effective strategy to ensure high treatment success and curtail development of drug resistance in tuberculosis. New antituberculosis drugs are urgently needed to improve the present standard short-course and alternative chemotherapies, by shortening administration durations and increasing cure rates, through the greater potency of these agents. At the same time, the role of adjunctive surgery for drug-resistant tuberculosis has to be better defined. Immunotherapy might improve treatment outcomes of both drug-susceptible and -resistant tuberculosis, and warrants further exploration.

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Section: Chemotherapy Of Pulmonary Tuberculosis Short-course Chemothementioning

confidence: 99%

Section: Clinical Relevance Of Antituberculosis Drug Resistancementioning

confidence: 99%

Treatment of tuberculosis: update 2010

Yew¹,

Lange²,

Leung³

2010

European Respiratory Journal

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“…Relevant to standard treatments regimens for M. tuberculosis infection (36,37), model simulations were conducted for three repeated dosing scenarios for which well-controlled experimental data were available: regimen A consisted of a 600-mg dose every day starting 3 days after an initial 600-mg dose (9), regimen B consisted of a 900-mg dose every 2 days (15), and regimen C consisted of a 600-mg dose every 3 days (9). Both the experimental data and corresponding simulation results are displayed in Fig.…”

Section: Model Parameter Valuesmentioning

confidence: 99%

Physiologically Based Pharmacokinetic Model of Rifapentine and 25-Desacetyl Rifapentine Disposition in Humans

Zurlinden

Eppers

Reisfeld

2016

Antimicrob Agents Chemother

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b Rifapentine (RPT) is a rifamycin antimycobacterial and, as part of a combination therapy, is indicated for the treatment of pulmonary tuberculosis (TB) caused by Mycobacterium tuberculosis. Although the results from a number of studies indicate that rifapentine has the potential to shorten treatment duration and enhance completion rates compared to other rifamycin agents utilized in antituberculosis drug regimens (i.e., regimens 1 to 4), its optimal dose and exposure in humans are unknown. To help inform such an optimization, a physiologically based pharmacokinetic (PBPK) model was developed to predict time course, tissue-specific concentrations of RPT and its active metabolite, 25-desacetyl rifapentine (dRPT), in humans after specified administration schedules for RPT. Starting with the development and verification of a PBPK model for rats, the model was extrapolated and then tested using human pharmacokinetic data. Testing and verification of the models included comparisons of predictions to experimental data in several rat tissues and time course RPT and dRPT plasma concentrations in humans from several singleand repeated-dosing studies. Finally, the model was used to predict RPT concentrations in the lung during the intensive and continuation phases of a current recommended TB treatment regimen. Based on these results, it is anticipated that the PBPK model developed in this study will be useful in evaluating dosing regimens for RPT and for characterizing tissue-level doses that could be predictors of problems related to efficacy or safety. R ifapentine (RPT) is a rifamycin-class antibiotic indicated for the treatment of pulmonary tuberculosis (TB) caused by Mycobacterium tuberculosis and in the treatment of latent TB infection in patients at high risk of progression to TB disease. RPT has a longer half-life, increased affinity to serum protein binding (1), and a lower MIC against M. tuberculosis than rifampin, which is currently used as part of several first-line TB treatment regimens (2, 3). Moreover, the primary metabolite for RPT, 25-desacetyl rifapentine (dRPT), has also been found to be active against M. tuberculosis, although at markedly lower MICs (1, 3, 4). Because of these characteristics, RPT has been the subject of a number of clinical pharmacology studies aimed at evaluating pharmacokinetics and developing effective therapies (5-15). Although data from these investigations are valuable in their own right, mathematical modeling offers a way to complement these studies, synthesize their disparate data, and provide the clinician an additional tool to characterize and predict the absorption, distribution, metabolism, and excretion (ADME) of RPT under dosing conditions of interest.One of the very few such mathematical models was developed by Savic et al. (16), who used a classical compartmental modeling approach to assess human population pharmacokinetics of both RPT and dRPT. This model described the absorption, metabolism, and clearance of these two species and accurately predicted their time cour...

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“…There is some evidence to suggest that longer treatment regimens reduce relapse rates (125,126) but not survival (127,128) and a metaanalysis suggests no statistically significant benefit beyond 6 months of therapy (123). However, more studies are required to resolve this controversy, particularly because the influence of early HAART on treatment duration is not well understood.…”

Section: Management Of Hiv-tb Coinfectionmentioning

confidence: 99%

Novel Developments in the Epidemic of Human Immunodeficiency Virus and Tuberculosis Coinfection

Anandaiah¹,

Dheda²,

Keane³

et al. 2011

Am J Respir Crit Care Med

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Tuberculosis (TB) disease remains one of the highest causes of mortality in HIV-infected individuals, and HIV-TB coinfection continues to grow at alarming rates, especially in sub-Saharan Africa. Surprisingly, a number of important areas regarding coinfection remain unclear. For example, increased risk of TB disease begins early in the course of HIV infection; however, the mechanism by which HIV increases this risk is not well understood. In addition, there is lack of consensus on the optimal way to diagnose latent TB infection and to manage active disease in those who are HIV infected. Furthermore, effective point-of-care testing for TB disease remains elusive. This review discusses key areas in the epidemiology, pathogenesis, diagnosis, and management of active and latent TB in those infected with HIV, focusing attention on issues related to high-and low-burden areas. Particular emphasis is placed on controversial areas where there are gaps in knowledge and on future directions of study.

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Efficacy of a 6-month versus 9-month Intermittent Treatment Regimen in HIV-infected Patients with Tuberculosis

Cited by 83 publications

References 28 publications

Treatment of tuberculosis: update 2010

Treatment of tuberculosis: update 2010

Physiologically Based Pharmacokinetic Model of Rifapentine and 25-Desacetyl Rifapentine Disposition in Humans

Novel Developments in the Epidemic of Human Immunodeficiency Virus and Tuberculosis Coinfection

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