icon-folder.gif   Conference Reports for NATAP  
  49th ICAAC
San Francisco, CA
September 12-15, 2009
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Raltegravir Demonstrates Durable Efficacy Through 96 Weeks: Results from STARTMRK, A Phase III Study of Raltegravir-based vs. Efavirenz-based Therapy in Treatment-Naïve HIV+ Patients
  Reported by Jules Levin
ICCAC Sept 12 2009 San Francisco
J. Lennox1, E. DeJesus2, A. Lazzarin3, D. Berger4, R. Pollard5, J. Madruga6, J. Zhao7, C. Gilbert7, A. Rodgers7, H. Teppler7, B-Y. Nguyen7, R. Leavitt7, and P. Sklar7 for the STARTMRK (P021) Investigators
1Emory University, Atlanta, GA, USA; 2Orlando Immunology Center, Orlando, FL, USA; 3University Vita-Salute San Raffaele, Milan, Italy; 4Northstar Medical Center, University of Illinois at Chicago, Chicago, IL, USA;
5University of California @ Davis, Sacramento, CA, USA; 6Centro de Referencia e Treinamento DST/AIDS, Sao Paulo, Brazil; 7Merck Research Labs, North Wales, PA, USA


In treatment-naïve patients given 96 weeks of therapy, RAL + TDF/FTC compared with EFV+TDF/FTC
- had potent, durable, and statistically non-inferior efficacy
· was associated with more rapid responses
· was associated with similar increases in CD4 cell counts
- was generally better tolerated
· significantly fewer overall and drug-related clinical adverse events
· significantly lower cumulative percentages of patients with CNS adverse experiences
· both RAL and EFV in combination with TDF/FTC exerted only modest effects on serum lipids
· In both treatment arms, the increase in CD4 count at Week 48 and 96 was predicted by Week 8 decrease in HIV RNA level
- Further analyses will be performed to corroborate these findings
Background: In STARTMRK, an ongoing, double-blind study, raltegravir (RAL) had potent and non-inferior antiretroviral activity compared to efavirenz (EFV) & was generally well tolerated through 48 weeks; RAL also showed more rapid time to HIV(v)RNA<50 c/mL than EFV.
Methods: Patients with vRNA >5000 c/mL & no resistance to EFV, tenofovir (TDF) or emtricitabine (FTC) were randomized (1:1) to RAL (400 mg bid) or EFV (600 mg qhs), with TDF/FTC. Standard 96-week endpoints were evaluated. Exploratory analyses investigated the potential relationship between early virologic response and long-term CD4 response.
Results: Baseline characteristics were comparable. Results at Week 48 and 96 are shown:


Conclusion: In treatment-naïve patients, RAL+TDF/FTC had durable, non-inferior antiretroviral activity sustained to 96-weeks compared to EFV+TDF/FTC & continued to be generally well tolerated.
Efficacy and Safety Results through Week 48

RAL provided potent and statistically non-inferior viral suppression compared to EFV
RAL exerted a greater immunological effect than EFV, measured by the increase in CD4 cell counts



RAL was generally better tolerated than EFV
- significantly fewer overall and drug-related clinical adverse events
- significantly lower percentages of patients with CNS side-effects
Safety profile was similar in subjects with or without hepatitis B and/or hepatitis C
RAL had modest effects on serum lipids




Patient Disposition at Week 96




Proportion (%) of Patients With HIV RNA <400 c/mL At 96 Weeks (Non-Completer = Failure)
- RAL group 85% vs. EFV group 81%
- Non-inferiority p<0.001




At week 48, statistically significant predictors of increase in CD4 count were baseline CD4 count, log drop in week 8 vRNA level, and treatment group.
At Week 96, statistically significant predictors of increase in CD4 count were baseline CD4 count and log drop in week 8 vRNA level.