Long-term safety from the raltegravir clinical development program.

Abstract

BACKGROUND:

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.

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 meta-analysis 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.

• Authors: Hedy Teppler, Deborah D Brown, Randi Y Leavitt, Peter Sklar, Hong Wan, Xia Xu, Fabio Lievano, Heidi P Lehman, T Christopher Mast, Bach-Yen T Nguyen
• Journal: Current HIV research (Curr HIV Res) Vol. 9 Issue 1 Pg. 40-53 (Jan 2011) ISSN: 1873-4251 [Electronic] Netherlands
• PMID: 21198432 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-HIV Agents
• Pyrrolidinones
• Raltegravir Potassium

Topics

• Adolescent
• Adult
• Aged
• Anti-HIV Agents (administration & dosage, adverse effects)
• Clinical Trials, Phase III as Topic
• Female
• HIV Infections (drug therapy)
• Humans
• Male
• Middle Aged
• Pyrrolidinones (administration & dosage, adverse effects)
• Raltegravir Potassium
• Randomized Controlled Trials as Topic
• Young Adult