| Raltegravir
(Isentress) Is as Effective as Efavirenz (Sustiva) at 48 Weeks in Treatment-naive
Patients: STARTMRK Trial By
Liz Highleyman STARTMRK
Trial |  | |  | |
The
first integrase inhibitor, raltegravir
(Isentress), was approved in October 2007 for use by treatment-experience
patients with drug-resistant HIV. In
a late-breaker session at the 48th International Conference
on Antimicrobial Agents and Chemotherapy (ICAAC 2008), taking place this week
in Washington, DC, researchers presented data from a study of raltegravir in people
starting therapy for the first time.
The STARTMRK trial included 563 treatment-naive
patients randomly assigned (1:1) to start therapy with either 400 mg twice-daily
raltegravir or 600 mg once-daily efavirenz
(Sustiva), both in combination with tenofovir
(Viread) plus emtricitabine (Emtriva),
the 2 drugs in the fixed-dose Truvada
pill. Participants
entered the study with a viral load of at least 5000 copies/mL and no documented
resistance to efavirenz, tenofovir, or emtricitabine. About 80% were men, the
mean age was about 38 years, about 40% were white, the mean baseline CD4 count
was just under 220 cells/mm3, and mean viral loads were approximately 103,000
copies/mL in the raltegravir arm and 106,000 copies/mL in the efavirenz arm. About
half had HIV RNA > 105 copies/mL (53%) and a CD4 count < 200 cells/mm3 (47%).
Results
•
At
week 48, raltegravir was found to be non-inferior to efavirenz.
•
In
a non-completer = failure analysis, 86% of patients taking raltegravir achieved
HIV RNA < 50 copies/mL, compared with 82% of those taking efavirenz (P <
0.001).
•
Time
to virological response was significantly shorter in the raltegravir arm compared
with the efavirenz arm (P < 0.001).
•
10%
of raltegravir recipients and 14% of efavirenz recipients experienced virological
failure.
•
The
mean CD4 cell increase from baseline was 189 cells/mm3 in the raltegravir arm
versus 163 cells/mm3 in the efavirenz group (not a significant difference).
•
9%
of raltegravir recipients and 12% of efavirenz recipients discontinued therapy
before week 48.
•
44%
of raltegravir recipients and 77% of efavirenz recipients experienced drug-related
clinical adverse events (P < 0.001).
•
Moderate-to-severe
drug-related adverse events occurred half as often in the raltegravir group (16%
vs 32%; P < 0.001).
•
About
10% of patients in both groups experienced serious clinical adverse events:
•
Malignancies
(mostly Kaposi's sarcoma): 1 raltegravir recipient (0.4) and 9 efavirenz recipients
(3.2%); 2 cases in the efavirenz group were considered drug-related.
•
Deaths:
2 raltegravir recipients (0.4%) and 0 efavirenz recipients (0.0%).
•
Patients
in the raltegravir group were significantly less likely to report central nervous
system (CNS) symptoms such as depression and abnormal dreams during the first
8 weeks of treatment (10% vs 18%; P < 0.001).
•
At
week 48, raltegravir recipients experienced significantly smaller increases from
baseline in total cholesterol, low-density lipoprotein (LDL or "bad")
cholesterol, and triglycerides (all P < 0.001).
•
Modest
increases in high-density lipoprotein (HDL or "good") cholesterol were
observed in both groups, but were significantly larger in the efavirenz arm.
•
Of
the 12 patients who experienced virological failure while on raltegravir, 4 had
integrase resistance mutations (2 with G120S + Q148H/R; 1 with Y143R; 1 with Y143H
+ L47M + E92Q + T97A), 5 had no detectable resistance mutations, and 3 could not
be tested.
Based
on these findings, the researchers concluded that in treatment-naive patients
given 48 weeks of therapy, raltegravir/tenofovir/emtricitabine "had non-inferior
antiretroviral activity" compared with efavirenz/tenofovir/emtricitabine
and "was associated with greater increases in CD4 counts and fewer CNS symptoms." Emory
Univ., Atlanta, GA; Orlando Immunology Ctr., Orlando, FL; Univ. Vita-Salute San
Raffaele, Milan, Italy; Univ. of California Davis, Sacramento, CA; Centro de Referencia
d Treinamento DST/AIDS, Sao Paulo, Brazil; Merck Research Labs, North Wales, PA.
10/28/08
Reference
J
Lennox, E Dejesus, A Lazzarin, and others. STARTMRK, A Phase III study of the
safety & efficacy of raltegravir (RAL)-based vs efavirenz (EFV)-based combination
therapy in treatment-naive HIV-infected patients. 48th International Conference
on Antimicrobial Agents and Chemotherapy (ICAAC 2008). Washington, DC. October
25-28, 2008. Abstract H-896a. |
