Raltegravir Demonstrates Rapid and Durable Anti-HIV Activity as Part of Combination Therapy in Treatment-naive Patients

The first HIV integrase inhibitor, raltegravir (Isentress), was recently recommended for approval in the U.S. for treatment-experienced HIV patients.

Though raltegravir has been most widely tested in highly treatment-experienced patients who need new classes of anti-HIV drugs to overcome viral resistance, it has also been studied in people starting antiretroviral therapy for the first time.

Results from a study of raltegravir in treatment-naive patients were reported at the recent 4th International AIDS Society Conference on HIV Treatment, Pathogenesis, and Prevention (July 22-25) and published online ahead of print in the Journal of Acquired Immune Deficiency Syndromes (August 23, 2007).

An international team of researchers conducted a double-blind, controlled trial to assess the antiretroviral activity and safety of raltegravir in treatment-naive patients with plasma HIV RNA levels > 5000 copies/mL and CD4 cell counts > 100 cells/mm3. At baseline, the mean viral load across the study arms ranged from 4.6 to 4.8 log10 copies/mL.

A total of 198 patients were randomly assigned to receive raltegravir at doses of 100, 200, 400, or 600 mg twice daily (n = 160) or else efavirenz (Sustiva) at a dose of 600 once daily (n = 38), all in combination with 300 mg once-daily tenofovir (Viread) plus 300 mg once-daily 3TC (Epivir).

Results

• At weeks 2, 4, and 8, the proportion of patients achieving an HIV RNA level below 50 copies/mL was greater in each of the raltegravir dose arms than in the efavirenz group.

• By week 24, outcomes in all treatment groups appeared similar.

• Plasma HIV RNA levels were below 400 copies/mL in 85%-98% of patients, and below 50 copies/mL in 85%-95% of patients across all arms.

• These reductions were maintained through week 48 in 85%-98% (below 400 copies/mL) and 83%-88% (below 50 copies/mL).

• 5 patients (3%) taking raltegravir and 1 subject (3%) taking efavirenz experienced virological failure before week 48.

• Drug-related clinical adverse events were less common with raltegravir than with efavirenz.

• After 24 and 48 weeks of treatment, raltegravir did not result in increased serum levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, or triglycerides.

Conclusion

"Raltegravir at all doses studied was generally well tolerated in combination with tenofovir and lamivudine," the study authors wrote. "Raltegravir exhibited potent and durable antiretroviral activity similar to that of efavirenz at 24 and 48 weeks, but achieved HIV-1 RNA levels below detection at a more rapid rate."

Aaron Diamond AIDS Research Center, Rockefeller University, New York, NY; Merck Research Laboratories, West Point, PA; Hospital Nacionale Cayetano Heredia, Lima, Peru; Hospital Nacionale Edgardo Rebagliati, Lima, Peru; Siriraj Hospital, Bangkok, Thailand; Canadian Immunodeficiency Research Collaborative, Toronto, Ontario, Canada; Fundación Santafe de Bogota University Hospital, Bogotá, Colombia; Clinical Research Puerto Rico, Inc., San Juan, PR; Beth Israel Deaconess Medical Center, Boston, MA.

09/07/07

Reference

M Markowitz, BY Nguyen, E Gotuzzo, and others. Rapid and Durable Antiretroviral Effect of the HIV-1 Integrase Inhibitor Raltegravir as Part of Combination Therapy in Treatment-Naive Patients. JAIDS. August 23, 2007 [Epub ahead of print].

M Markowitz, B-Y Nguyen, E Gotuzzo, and others (for the Protocol 004 Part II Study Team). Rapid onset and durable antiretroviral effect of raltegravir (MK-0518), a novel HIV-1 integrase inhibitor, as part of combination ART in treatment-naive HIV-1 infected patients: 48-week data. 4th International AIDS Society Conference on HIV Treatment, Pathogenesis and Prevention. Sydney, Australia, July 22-25, 2007. Abstract TuAb104.