Raltegravir versus Efavirenz regimens in treatment-naive HIV-1-infected patients: 96-week efficacy, durability, subgroup, safety, and metabolic analyses

Abstract

Background: We analyzed the 96-week results in the overall population and in prespecified subgroups from the ongoing STARTMRK study of treatment-naive HIV-infected patients.

Methods: Eligible patients with HIV-1 RNA (vRNA) levels >5000 copies per milliliter and without baseline resistance to efavirenz, tenofovir, or emtricitabine were randomized in a double-blind noninferiority study to receive raltegravir or efavirenz, each combined with tenofovir/emtricitabine.

Results: At week 96 counting noncompleters as failures, 81% versus 79% achieved vRNA levels <50 copies per milliliter in the raltegravir and efavirenz groups, respectively [Delta (95% confidence interval) = 2% (-4 to 9), noninferiority P < 0.001]. Mean change in baseline CD4 count was 240 and 225 cells per cubic millimeter in the raltegravir and efavirenz groups, respectively [Delta (95% confidence interval) = 15 (-13 to 42)]. Treatment effects were consistent across prespecified baseline demographic and prognostic subgroups. Fewer drug-related clinical adverse events (47% versus 78%; P < 0.001) occurred in raltegravir than efavirenz recipients. Both regimens had modest effects on serum lipids and glucose levels and on body fat composition.

Conclusions: When combined with tenofovir/emtricitabine in treatment-naive patients, raltegravir exhibited durable antiretroviral activity that was noninferior to the efficacy of efavirenz through 96 weeks of therapy. Subgroup analyses were generally consistent with the overall findings. Both regimens were well tolerated.

FIGURE 1

Subject accounting. A CONSORT diagram shows patient disposition through study week 96. A total of 3 randomized patients, including 1 patient in the raltegravir arm and 2 patients in the efavirenz arm, never received study drugs. For the calculation of percentages subsequent to entry, the number of treated patients in each group was assigned a value of 100%.

FIGURE 2

Forest plots showing the between-treatment group differences in the proportions (%) of patients with vRNA <50 copies per milliliter and vRNA <400 copies per milliliter alongside the mean change from baseline CD4 cell counts (cells/mm³) at week 96 by (A) subpopulations and (B) prognostic subgroups at baseline. Point estimates of treatment effects with 95% CIs are presented in Forest plots to provide an estimate of treatment effects at week 96 in subpopulations and prognostic subgroups identified at baseline using the observed failure approach to missing data. The vertical line indicates no treatment difference. For reference, the overall treatment effect is given for each parameter at the top of the graph. The 95% CIs were calculated using the method of Miettinen and Nurminen. The arrowheads on the horizontzal bars indicate that the 95% CIs exceed the scale used for the x axis.

FIGURE 3

Changes in lipid values over the first 96 weeks of therapy by treatment group. The graph shows the mean change from baseline to week 96 in total cholesterol, HDL-cholesterol, LDL-cholesterol, and TG in mg/dL between the raltegravir group (left column) and the efavirenz (right column). All 4 between-group comparisons were significantly different (P ≤ 0.001). The mean change in the total cholesterol:HDL-cholesterol ratio did not significantly differ between the raltegravir group (−0.18) and efavirenz group (0.04) (P = 0.192). HDL, high-density lipoprotein cholesterol; LDL, low-density lipoprotein cholesterol; TG, triglyceride.

FIGURE 4

Mean percent changes in body fat over time by treatment group. The graph displays the mean percent change from baseline in appendicular (A) and trunk (B) fat at week 48 and week 96. Measurements were made by DEXA. The mean % change in fat content from baseline was calculated as the difference between the measurements at baseline and at the specified time point (week 48 or week 96). The number of evaluable patients is shown for the treatment groups below each time point. Bars represent standard errors. There were 111 patients with DEXA scans at baseline; 86 patients had repeat scans at week 48; and 75 patients had repeat scans at week 96, including 68 patients evaluable at both time points. Repeat DEXA scans at the baseline visit were used as the baseline measurements in 7 patients for whom the original baseline scans were not available. Baseline total fat content was 20.4 kg and 17.5 kg for the raltegravir and efavirenz participants, respectively (Δ = 2.9 kg).