Abstract
Background: Raltegravir has demonstrated potent and durable efficacy and a favorable safety profile in 3 phase III studies in treatment-naive 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.
Methods: 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.
Results: 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 metaanalysis were similar to those observed in the phase III studies.
Conclusions: 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.
Keywords: Raltegravir, integrase inhibitor, long-term safety, BENCHMRK, STARTMRK
Current HIV Research
Title: Long-Term Safety from the Raltegravir Clinical Development Program
Volume: 9 Issue: 1
Author(s): Hedy Teppler, Deborah D. Brown, Randi Y. Leavitt, Peter Sklar, Hong Wan, Xia Xu, Fabio Lievano, Heidi P. Lehman, T. Christopher Mast and Bach-Yen T. Nguyen
Affiliation:
Keywords: Raltegravir, integrase inhibitor, long-term safety, BENCHMRK, STARTMRK
Abstract: Background: Raltegravir has demonstrated potent and durable efficacy and a favorable safety profile in 3 phase III studies in treatment-naive 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.
Methods: 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.
Results: 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 metaanalysis were similar to those observed in the phase III studies.
Conclusions: 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.
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Cite this article as:
Teppler Hedy, D. Brown Deborah, Y. Leavitt Randi, Sklar Peter, Wan Hong, Xu Xia, Lievano Fabio, P. Lehman Heidi, Christopher Mast T. and T. Nguyen Bach-Yen, Long-Term Safety from the Raltegravir Clinical Development Program, Current HIV Research 2011; 9 (1) . https://dx.doi.org/10.2174/157016211794582650
DOI https://dx.doi.org/10.2174/157016211794582650 |
Print ISSN 1570-162X |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4251 |
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