Long-Term Efficacy and Safety of Raltegravir Combined with Optimized Background Therapy in Treatment-Experienced Patients with Drug-Resistant HIV Infection: Week 96 Results of the BENCHMRK 1 and 2 Phase III Trials
ABSTRACT BENCHMRK-1 and -2 are ongoing double-blind phase III studies of raltegravir in patients experiencing failure of antiretroviral therapy with triple-class drug-resistant human immunodeficiency virus infection. At week 96 (combined data), raltegravir (400 mg twice daily) plus optimized background therapy was generally well tolerated, with superior and durable antiretroviral and immunological efficacy, compared with optimized background therapy alone. © 2010 by the Infectious Diseases Society of America. All rights reserved.
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- "Baseline values were those obtained at the baseline study visit before initiation of study therapy. In the BENCHMRK studies, all clinical AIDS defining conditions (ADC) were reported as submitted by investigators for safety analysis; these events were submitted for blinded adjudication for separate consideration of confirmed ADCs as an efficacy parameter   . "
ABSTRACT: Raltegravir has demonstrated potent and durable efficacy and a favorable safety profile in 3 phase III studies in treatment-naïve and treatment-experienced patients with HIV-1 infection. This manuscript provides a review of the raltegravir safety profile using data from these and other studies in the clinical development program. Comprehensive 96-week safety data from STARTMRK (raltegravir versus efavirenz, each with tenofovir/emtricitabine) and BENCHMRK (raltegravir versus placebo, each with optimized background therapy) are summarized. A cumulative meta-analysis of raltegravir 400 mg bid was conducted across the entire development program. In STARTMRK, drug-related adverse events (AEs) occurred less frequently with raltegravir than efavirenz. In BENCHMRK, the most common drug-related AEs occurred at generally similar frequencies in both groups. Drug-related serious AEs were uncommon. Rash was observed in raltegravir-treated patients at a higher frequency than placebo but a lower frequency than efavirenz. Depression and immune reconstitution inflammatory syndrome occurred at similar rates for raltegravir and comparators. Isolated elevations of creatine kinase were more common with raltegravir than placebo but occurred without clinical manifestations. The frequency of aminotransferase elevations was greater in patients with viral hepatitis co-infection, but similar in the raltegravir and comparator groups. The relative risk (95% CI) of cancer was 0.75 (0.30, 1.91) indicating no difference between raltegravir and comparator. Overall trends in the cumulative meta-analysis were similar to those observed in the phase III studies. Long-term data from the phase III clinical trials demonstrate that raltegravir was generally well-tolerated in both treatment-naïve and treatment-experienced patients with HIV infection.Current HIV research 01/2011; 9(1):40-53. DOI:10.2174/157016211794582650 · 2.14 Impact Factor
- Value in Health 11/2006; 9(6). DOI:10.1016/S1098-3015(10)63251-2 · 2.89 Impact Factor
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ABSTRACT: Raltegravir, the first approved HIV-1 integrase inhibitor, is able to block the strand transfer step of the HIV proviral DNA integration process into the cellular host DNA. The selected dosage for the pivotal phase III studies (subsequently approved by the regulatory agencies) was 400 mg bid by oral route with or without food. Raltegravir has a week effect (either inhibition or induction) on the hepatic cytochrone P450 activity. There is not need of dose adjustments in renal insufficiency or in mild-to-moderate hepatic impairment. The emerging paradigm in the field of salvage therapy was to achieve a viral load below limit of detection in almost all patients. Pretty soon it became apparent that this was feasible in more than 70-90% of patients. Raltegravir proved to be pivotal for this new paradigm. Raltegravir vs placebo both with an optimized background therapy has been tested for salvage therapy in the 005 and in the BENCHMRK studies (018 and 019). In all three studies proved to be superior to the placebo at 24, 48 and 96 weeks. Tolerance was remarkably good and virological failure was often associated with selection of integrase gene resistance mutations following the Y143C/H/R, Q148H/K/R o less frequently the NI55H paths. Finally, in the two SWITCHMRK studies non-inferiority vs Lopinavir/r could not be demonstrated in virogically suppressed patients with an stable cART containing Lopinavir/r. Most likely explanation was the presence of archived resistance mutationts to background therapy leading to a functional monotherapy with raltegravir.European journal of medical research 11/2009; 14 Suppl 3(Suppl 3):30-5. DOI:10.1186/2047-783X-14-S3-30 · 1.40 Impact Factor