Clinical experience of raltegravir-containing regimens in HIV-infected patients during rifampicin-containing treatment of tuberculosis

Mena, Álvaro; Vázquez, Pilar; Castro, Ángeles; Lopez, Soledad; Bello, Laura; Pedreira, José

doi:10.1093/jac/dkq540

Cited by 14 publications

(12 citation statements)

References 4 publications

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“…However, initial data on use with TB treatment show promise. Pharmacokinetic studies suggest that doubling the dose of raltegravir to 800 mg twice daily compensates for the effect of RIF on overall exposure [89,90] and this approach seems to be well tolerated and effective in patients with HIV-associated TB [91]. However, preliminary results of the REFLATE TB study suggest that such dose adjustment may not even be necessary as virological responses were similar in ART-naive TB patients receiving RIF who were randomized to receive 400 mg or 800 mg of raltegravir twice daily or EFV daily [92].…”

Section: Introductionmentioning

confidence: 99%

Management of HIV-associated tuberculosis in resource-limited settings: a state-of-the-art review

Lawn

Meintjes

McIlleron

et al. 2013

BMC Med

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The HIV-associated tuberculosis (TB) epidemic remains a huge challenge to public health in resource-limited settings. Reducing the nearly 0.5 million deaths that result each year has been identified as a key priority. Major progress has been made over the past 10 years in defining appropriate strategies and policy guidelines for early diagnosis and effective case management. Ascertainment of cases has been improved through a twofold strategy of provider-initiated HIV testing and counseling in TB patients and intensified TB case finding among those living with HIV. Outcomes of rifampicin-based TB treatment are greatly enhanced by concurrent co-trimoxazole prophylaxis and antiretroviral therapy (ART). ART reduces mortality across a spectrum of CD4 counts and randomized controlled trials have defined the optimum time to start ART. Good outcomes can be achieved when combining TB treatment with first-line ART, but use with second-line ART remains challenging due to pharmacokinetic drug interactions and cotoxicity. We review the frequency and spectrum of adverse drug reactions and immune reconstitution inflammatory syndrome (IRIS) resulting from combined treatment, and highlight the challenges of managing HIV-associated drug-resistant TB.

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Section: Introductionmentioning

confidence: 99%

Management of HIV-associated tuberculosis in resource-limited settings: a state-of-the-art review

Lawn

Meintjes

McIlleron

et al. 2013

BMC Med

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“…Plasma concentrations of the fusion inhibitor enfuvirtide were not shown to be affected by 10 days of concomitant use with rifampicin, showing that these drugs can be coadministered without dose adjustments. 99 Raltegravir maintained its virological and immunological efficacy and was tolerated well. Recent data show that the dose of raltegravir needs to be doubled when combined with rifampicin, but this increased dose (800 mg) tolerated well in a small study with 2 patients.…”

Section: Interactions Between Rifampicin and Other Arvsmentioning

confidence: 90%

“…97,99 Unfortunately, these drugs are currently not available in resource-limited settings; a well-organized lobby should be triggered by the scientific community because of the high potential of these drugs in situations where NNRTIs are no longer useful and second-line ART is needed. Despite the effect of rifampicin on raltegravir metabolism, increasing the doses was shown to overcome the problem of decreased plasma concentrations and was tolerated well.…”

Section: Use Of New Antiretroviral Drugsmentioning

confidence: 99%

Pharmacological Interactions Between Rifampicin and Antiretroviral Drugs

Semvua

Kibiki

Kisanga

et al. 2015

Therapeutic Drug Monitoring

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Coadministration of antituberculosis and antiretroviral therapy is often inevitable in high-burden countries where tuberculosis (TB) is the most common opportunistic infection associated with HIV/AIDS. Concurrent use of rifampicin and many antiretroviral drugs is complicated by pharmacokinetic drug-drug interactions. Rifampicin is a very potent enzyme inducer, which can result in subtherapeutic antiretroviral drug concentrations. In addition, TB drugs and antiretroviral drugs have additive (pharmacodynamic) interactions as reflected in overlapping adverse effect profiles. This review provides an overview of the pharmacological interactions between rifampicin-based TB treatment and antiretroviral drugs in adults living in resource-limited settings. Major progress has been made to evaluate the interactions between TB drugs and antiretroviral therapy; however, burning questions remain concerning nevirapine and efavirenz effectiveness during rifampicin-based TB treatment, treatment options for TB-HIV-coinfected patients with nonnucleoside reverse transcriptase inhibitor resistance or intolerance, and exact treatment or dosing schedules for vulnerable patients including children and pregnant women. The current research priorities can be addressed by maximizing the use of already existing data, creating new data by conducting clinical trials and prospective observational studies and to engage a lobby to make currently unavailable drugs available to those most in need.

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“…This study indicated that even though rifampin reduces the effective raltegravir concentration in plasma, raltegravir is still safe and effective in controlling HIV-1 replication in TB patients undergoing rifampin treatment. 39 Pharmacokinetic study of raltegravir (800 mg twice a day) in two HIV-2 patients (one with HIV-1/HIV-2 dual infection) treated concurrently with rifampin for TB suggested that AUC value 40 was as high as geometric mean value observed in phase II study with standard 400 mg twice a day dosage. 30 A phase II clinical trial (NCT00822315) (Table 2) with treatment naïve HIV-1 infected patients receiving rifampin for TB, is underway to compare the efficacy and safety of two different doses of raltegravir (400 mg and 800 mg) and efavirenz in combination with tenofovir and lamivudine.…”

Section: Metabolism and Pharmacokineticsmentioning

confidence: 99%

Raltegravir in HIV-1 Infection: Safety and Efficacy in Treatment-Naïve Patients

Pandey

2011

Clinical Medicine Reviews in Therapeutics

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The hunt for a compound which inhibits the HIV-1 integrase had been painstakingly difficult. Integrase is essential for viral replication as it mediates the integration of the viral DNA genome into the host DNA resulting in the establishment of the permanent provirus. Persistent efforts have resulted in the discovery of Raltegravir (Isentress, MK-0518), the first integrase inhibitor approved by US Food and Drug Administration for the treatment in HIV-1 infected patients. Numerous clinical studies with raltegravir have found it to be safe and effective in treatment naïve as well as treatment experienced patients. Adverse events associated with raltegravir based therapy are milder compared to previously available regimens. Raltegravir is metabolized primarily via glucuronidation mediated by uridine diphosphate glucuronosyltransferase and has a favorable pharmacokinetics independent of age, gender, race, food, and drug-drug interactions. Within a short period of time of its introduction, raltegravir has been included as one of DHHS recommended preferred regimen for the treatment of HIV-1 infection in treatment naïve patients.

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Clinical experience of raltegravir-containing regimens in HIV-infected patients during rifampicin-containing treatment of tuberculosis

Cited by 14 publications

References 4 publications

Management of HIV-associated tuberculosis in resource-limited settings: a state-of-the-art review

Management of HIV-associated tuberculosis in resource-limited settings: a state-of-the-art review

Pharmacological Interactions Between Rifampicin and Antiretroviral Drugs

Raltegravir in HIV-1 Infection: Safety and Efficacy in Treatment-Naïve Patients

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Clinical experience of raltegravir-containing regimens in HIV-infected patients during rifampicin-containing treatment of tuberculosis

Cited by 14 publications

References 4 publications

Management of HIV-associated tuberculosis in resource-limited settings: a state-of-the-art review

Management of HIV-associated tuberculosis in resource-limited settings: a state-of-the-art review

Pharmacological Interactions Between Rifampicin and Antiretroviral Drugs

Raltegravir in HIV-1 Infection: Safety and Efficacy in Treatment-Na&iuml;ve Patients

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Raltegravir in HIV-1 Infection: Safety and Efficacy in Treatment-Naïve Patients