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Clinical Trial
. 2010 Apr 1;53(4):456-63.
doi: 10.1097/qai.0b013e3181c9c967.

Long-term efficacy and safety of the HIV integrase inhibitor raltegravir in patients with limited treatment options in a Phase II study

Jose M Gatell  1 , Christine Katlama, Beatriz Grinsztejn, Joseph J Eron, Adriano Lazzarin, Daniel Vittecoq, Charles J Gonzalez, Robert M Danovich, Hong Wan, Jing Zhao, Anne R Meibohm, Kim M Strohmaier, Charlotte M Harvey, Robin D Isaacs, Bach-Yen T Nguyen; Protocol 005 Team
Collaborators, Affiliations
Clinical Trial

Long-term efficacy and safety of the HIV integrase inhibitor raltegravir in patients with limited treatment options in a Phase II study

Jose M Gatell et al. J Acquir Immune Defic Syndr. .

Abstract

Background: Raltegravir in combination therapy has demonstrated potent suppression of HIV-1 with a favorable safety profile. This report provides 96-week efficacy and safety data from Protocol 005, a Phase II study.

Methods: HIV-infected patients with very limited treatment options and failing antiretroviral therapy were randomized to raltegravir 200, 400, or 600 mg or placebo b.i.d., plus optimized background therapy for >or=24 weeks; all patients were then offered open-label raltegravir 400 mg b.i.d. Efficacy measurements included changes in viral load and CD4 count from baseline and percent of patients with HIV-1 RNA <400 and <50 copies/mL.

Results: One hundred and thirty-three patients received raltegravir and 45 received placebo. No dose-dependent differentiation in the safety or antiviral activity of raltegravir was observed during the double-blind phase. For the combined raltegravir groups, mean change in viral load from baseline was -1.60 log10 copies/mL at week 48 and -1.38 log10 copies/mL at week 96 (observed failure approach). At week 48, HIV-1 RNA levels were <400 copies/mL in 68% of raltegravir recipients and <50 copies/mL in 55%; these levels were maintained in 55% and 48% of raltegravir recipients, respectively, at week 96 (noncompleter = failure). There were few discontinuations of raltegravir (4%) due to adverse events.

Conclusions: In patients with limited treatment options, raltegravir with OBT had a potent and sustained antiretroviral effect and was generally well tolerated through 96 weeks.

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Conflict of interest statement

Potential Conflicts of Interest: R.M.D., H.W., J.Z., A.R.M., C.M.H., K.M.S., R.D.I., and B.-Y.T.N. are current or former employees of Merck & Co. Inc and may own stock and/or stock options in the company. The remaining authors participated as clinical investigators for Protocol 005. In addition, the following potential conflicts of interest have been disclosed by the authors: J.M.G. has received research grants, honoraria, speaker fees, and/or consultancy payments from Merck, Gilead, Pfizer, Bristol-Myers Squibb, Glaxo-SmithKline, and Abbott. C.K. has received honoraria for advisory boards or lectures from Merck, Gilead, Roche, GlaxoSmithKline, Tibotec, Bristol Myers Squibb, and Boehringer Ingelheim. J.J.E. received research grants from Merck, Panacos, Glaxo-SmithKline, and TaiMed; and honoraria, speaker fees, and/or consultancy payments from Merck, Avexa, Panacos, Bristol-Myers Squibb, Glaxo-SmithKline, Tibotec, Virco Laboratories, Pfizer, Tobira, Chimerix, Roche, and Gilead. A.L. has received honoraria for lectures or Advisory Board meetings and/or research support from Merck, Glaxo-SmithKline, Bristol-Myers Squibb, Gilead, Roche, Tibotec, Pfizer, Boehringer-Ingelheim, Abbott, Monogram, and Schering-Plough.

Figures

FIGURE 1.
FIGURE 1.
Response to raltegravir: entire study period. A, Mean change from baseline in log10 HIV RNA (OF approach); B, proportion of patients achieving HIV RNA <400 copies/mL (NC = F approach);C, proportion of patients achieving HIV RNA <50 copies/mL (NC = F approach); D, mean change from baseline in CD4+ T-cell count (OF approach). Error bars indicate 95% CI.
See this image and copyright information in PMC

References

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