EACS 2011: Raltegravir Demonstrates Continued Efficacy at 4 Years

People taking the HIV integrase inhibitor raltegravir (Isentress) continued to show good viral suppression with few side effects at 192 weeks after starting antiretroviral therapy (ART) for the first time, researchers reported at the 13th European AIDS Conference (EACS 2011) this week in Belgrade.

[Produced in collaboration with Aidsmap]

Jürgen Rockstroh from the University of Bonn in Germany presented the latest findings from a pre-specified subgroup analysis of the Phase 3 STARTMRK trial. This study compared first-line therapy with 400 mg twice-daily raltegravir vs 600 mg once-daily efavirenz (Sustiva), both taken in combination with coformulated tenofovir/emtricitabine (Truvada).

The primary analysis at 48 weeks showed that raltegravir was comparable to efavirenz in overall efficacy, but caused fewer side effects, especially central nervous system symptoms. Raltegravir also produced slightly larger CD4 cell gains.

STARTMRK was designed to follow participants on blinded therapy for 5 years -- longer than most randomized trials, Rockstroh noted. Exploratory analyses of patient subgroups were scheduled for weeks 156, 192 and 240. Participants were sorted according to demographic factors including sex, age, and race/ethnicity, HIV subtype (B or non-B), baseline viral load, CD4 T-cell count, and hepatitis B or C coinfection.

The study randomly assigned 281 patients to the raltegravir arm and 282 to the efavirenz arm. The 2 groups were well-matched for demographic factors and health status. Most (about 80%) were men and the median age was about 37 years. About 40% were white, nearly one-quarter were Hispanic/Latino, and the remainder were evenly divided between black, Asian and multiracial. About one-quarter had hepatitis C and 7% had hepatitis B.

Participants had relatively advanced HIV disease; the mean CD4 count was approximately 220 cells/mm³ and about 10% started treatment with less than 50 cells/mm³. They were about evenly divided between those who started with viral load above and below 100,000 copies/mL. About 80% had clade B HIV, the rest had non-B types.

Results

• A total of 58 people (21%) quit taking raltegravir during the study:
  • 5 due to lack of efficacy;
  • 8 lost to follow-up;
  • 13 due to adverse events.
• There were 85 discontinuations (30%) in the efavirenz arm:
  • 8 due to lack of efficacy;
  • 17 lost to follow-up;
  • 26 due to adverse events.
• This left 223 raltegravir recipients and 197 efavirenz recipients in the 192-week analysis.
• In a non-completer equals failure analysis, 76% of raltegravir recipients and 67% of efavirenz recipients achieved viral load below 50 copies/mL.
• In an "observed failure" analysis -- meaning people who discontinued therapy due to poor efficacy were counted as treatment failures, but those who quit for other reasons were excluded -- the corresponding rates were 91% and 85%, respectively.
• Proportions of people with undetectable viral load remained stable overall from about week 16 onward.
• By week 192, however, raltegravir appeared to work slightly better than efavirenz; this study was only designed to evaluate non-inferiority, so the researchers could not claim raltegravir was superior.
• In statistical terms, the confidence interval for the difference in efficacy no longer included zero, suggesting the 2 drugs were no longer equal.
• CD4 cell gains from baseline remained higher in the raltegravir arm, 360 vs 301 cells/mm³, respectively.
• Response to treatment in the 2 groups did not differ according to sex, age, race/ethnicity, hepatitis coinfection status, or HIV clade.
• There was no differences in efficacy for people who started therapy with viral load above 100,000 copies/mL, but raltegravir worked "especially well" for people with lower levels.
• CD4 cell gains were also similar across subgroups.
• Raltegravir continued to be well-tolerated during extended follow-up.
• The overall rate of drug-related adverse events was lower for raltegravir compared with efavirenz (50% vs 80%, respectively).
• There were few serious clinical adverse events or deaths in either arm.
• No signal of raltegravir liver toxicity was observed.

Based on these findings, the researchers concluded that in the STARTMRK trial of previously untreated patients, raltegravir "demonstrated consistent virologic and immunologic efficacy" relative to efavirenz across groups with varying demographic and prognostic factors.

Investigator affiliations: Medizinische Universitätsklinik, Bonn, German; Univ Vita-Salute San Raffaele, Milan, Italy; Merck Sharp & Dohme, Corp., Whitehouse Station, NJ.

10/14/11

Reference

JK Rockstroh, A Lazzarin, J Zhao, et al. Long-term Efficacy of Raltegravir (RAL) or Efavirenz (EFV) Combined with Tenofovir (TDF) and Emtricitabine (FTC) in Treatment-naive HIV-1-infected Patients: Wk-192 Subgroup Analysis from the STARTMRK trial. 13th European AIDS Conference (EACS 2011). Belgrade, October 12-15, 2011. Abstract PS1/1.

Other Source

Merck. Merck's ISENTRESS (raltegravir) in Combination Therapy Demonstrated Virological and Immunological Efficacy Versus the Efavirenz Regimen at 192 Weeks of Treatment in Previously Untreated Adults with HIV-1. Press release. October 13, 2010.