Efavirenz Pharmacokinetics and Pharmacodynamics in HIV-Infected Persons Receiving Rifapentine and Isoniazid for Tuberculosis Prevention

Podany, Anthony T.; Bao, Yajing; Swindells, Susan; Chaisson, Richard E.; Andersen, Janet; Mwelase, Thando; Supparatpinyo, Khuanchai; Mohapi, Lerato; Gupta, Amita; Benson, Constance A.; Kim, Peter; Fletcher, Courtney V.

doi:10.1093/cid/civ464

Cited by 65 publications

(38 citation statements)

References 22 publications

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“…However, recent studies have demonstrated that rifapentine, given either once-weekly or daily, has minimal interaction with daily efavirenz. [15, 16] Furthermore, additional studies have demonstrated that once-weekly rifapentine may be given with the integrase strand transfer inhibitor raltegravir. [17] Although studies of the effectiveness of 3HP when given with efavirenz-or raltegravir-based antiretroviral therapy are needed, these pharmacokinetic studies suggest that such regimens can be given concomitantly.…”

Section: Discussionmentioning

confidence: 99%

Three months of weekly rifapentine and isoniazid for treatment of Mycobacterium tuberculosis infection in HIV-coinfected persons

Sterling

Scott

Miró

et al. 2016

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Objective Compare the effectiveness, tolerability, and safety of three months of weekly rifapentine plus isoniazid under direct observation (3HP) vs. 9 months of daily isoniazid (9H) in HIV-infected persons. Design prospective, randomized, open-label non-inferiority trial Setting U.S., Brazil, Spain, Peru, Canada, and Hong Kong Participants HIV-infected persons who were tuberculin skin test positive or close contacts of tuberculosis cases. Intervention 3HP vs. 9H. Main Outcome Measures The effectiveness endpoint was tuberculosis; the non-inferiority margin was 0.75%. The tolerability endpoint was treatment completion; the safety endpoint was drug discontinuation due to adverse drug reaction. Results Median baseline CD4+ counts were 495 (IQR:389–675) and 538 (IQR:418–729) cells/mm3 in the 3HP and 9H arms, respectively (P=0.09). In the modified intention to treat analysis, there were two tuberculosis cases among 206 persons (517 person-years (p-y) of follow-up) in the 3HP arm (0.39 per 100 p-y) and six tuberculosis cases among 193 persons (481 p-y of follow-up) in the 9H arm (1.25 per 100 p-y). Cumulative tuberculosis rates were 1.01% vs. 3.50% in the 3HP and 9H arms, respectively (rate difference: −2.49%; upper bound of the 95% confidence interval (CI) of the difference: 0.60%). Treatment completion was higher with 3HP (89%) than 9H (64%) (P<0.001), and drug discontinuation due to an adverse drug reaction was similar (3% vs. 4%; P=0.79) in 3HP and 9H, respectively. Conclusions Among HIV-infected persons with median CD4+ count of approximately 500 cells/mm3, 3HP was as effective and safe for treatment of latent M. tuberculosis infection as 9H, and better tolerated. Trial Registration ClinicalTrials.gov (identifier: NCT00023452)

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Section: Discussionmentioning

confidence: 99%

Three months of weekly rifapentine and isoniazid for treatment of Mycobacterium tuberculosis infection in HIV-coinfected persons

Sterling

Scott

Miró

et al. 2016

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135

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“…We modeled LTBI therapy as 3 months of self-administered rifapentine and isoniazid 4,14–16 and assumed that LTBI treatment without toxic effects causes no change in quality of life. Completed LTBI therapy reduces the monthly probability of TB reactivation.…”

Section: Methodsmentioning

confidence: 99%

Cost-effectiveness of Testing and Treatment for Latent Tuberculosis Infection in Residents Born Outside the United States With and Without Medical Comorbidities in a Simulation Model

et al. 2017

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IMPORTANCE Testing for and treating latent tuberculosis infection (LTBI) is among the main strategies to achieve TB elimination in the United States. The best approach to testing among non-US born residents, particularly those with comorbid conditions, is uncertain.OBJECTIVE To estimate health outcomes, costs, and cost-effectiveness of LTBI testing and treatment among non-US born residents with and without medical comorbidities. DESIGN, SETTING, AND PARTICIPANTS Decision analytic tree and Markov cohort simulation model among non-US born residents with no comorbidities, with diabetes, with HIV infection, or with end-stage renal disease (ESRD) using a health care sector perspective with 3% annual discounting. Strategies compared included no testing, tuberculin skin test (TST), interferon gamma release assay (IGRA), confirm positive (initial TST, IGRA only for TST-positive results; both tests positive indicates LTBI), and confirm negative (initial IGRA, then TST for IGRA-negative; any test positive indicates LTBI). All strategies were coupled to treatment with 3 months of self-administered rifapentine and isoniazid. MAIN OUTCOMES AND MEASURESNumber needed to test and treat to prevent 1 case of TB reactivation, discounted quality-adjusted life-years (QALYs), discounted lifetime medical costs, and incremental cost-effectiveness ratios (ICERs).RESULTS Improving health outcomes increased costs, with choice of test dependent on willingness to pay. Strategies ranked by ascending costs and benefits: no testing, confirm positive, TST, IGRA, and confirm negative. The ICERs varied by non-US born patient risk group: patients with no comorbidities, IGRA

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“…Further improvements in the ease of administering and taking preventive therapy are anticipated, as a new fixed-dose combination tablet of rifapentine and isoniazid is expected to be marketed later this year, and a bold four-week regimen of daily rifapentine and isoniazid is currently being evaluated. 48,49 Unfortunately, in resource-constrained high tuberculosis burden countries, preventive therapy with 6–36 months of isoniazid is uninspiringly presented as the only option. This is perceived as a pragmatic choice probably because most of the historical evidence for preventive therapy is with isoniazid, which is cheap and widely available.…”

Section: Challengesmentioning

confidence: 99%

Controlling the seedbeds of tuberculosis: diagnosis and treatment of tuberculosis infection

et al. 2015

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The billions of people with latent tuberculosis infection serve as the seedbeds for future cases of active tuberculosis. Virtually all episodes of tuberculosis disease are preceded by a period of asymptomatic Mycobacterium tuberculosis infection; therefore, identifying infected individuals most likely to progress to disease and treating such subclinical infections to prevent future disease provides a critical opportunity to interrupt tuberculosis transmission and reduce the global burden of tuberculosis disease. Programs focusing on single strategies rather than comprehensive programs that deliver an integrated arsenal for tuberculosis control may continue to struggle. Tuberculosis preventive therapy is a poorly utilized tool that is essential for controlling the reservoirs of disease that drive the current epidemic. Comprehensive control strategies that combine preventive therapy for the most high-risk populations and communities with improved case-finding and treatment, control of transmission and health systems strengthening could ultimately lead to worldwide tuberculosis elimination. This paper outlines challenges to implementation of preventive therapy and provides pragmatic suggestions for overcoming them. It further advocates for tuberculosis preventive therapy as the core of a renewed global focus to implement a comprehensive epidemic control strategy that would reduce new tuberculosis cases to elimination targets. This strategy would be underpinned by accelerated research to further understand the biology of subclinical tuberculosis infections, develop novel diagnostics, and drug regimens specifically for subclinical tuberculosis infection, strengthen health systems, community engagement, and enhance sustainable large scale implementation of preventive therapy programs.

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Efavirenz Pharmacokinetics and Pharmacodynamics in HIV-Infected Persons Receiving Rifapentine and Isoniazid for Tuberculosis Prevention

Abstract: NCT 01404312.

Cited by 65 publications

References 22 publications

Three months of weekly rifapentine and isoniazid for treatment of Mycobacterium tuberculosis infection in HIV-coinfected persons

Three months of weekly rifapentine and isoniazid for treatment of Mycobacterium tuberculosis infection in HIV-coinfected persons

Cost-effectiveness of Testing and Treatment for Latent Tuberculosis Infection in Residents Born Outside the United States With and Without Medical Comorbidities in a Simulation Model

Controlling the seedbeds of tuberculosis: diagnosis and treatment of tuberculosis infection

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