Raltegravir achieves superiority over efavirenz after four years

Four year results from a five year, double-blind, randomised, non-inferiority study comparing raltegravir to efavirenz (each with tenofovir plus FTC) in treatment-naive patients were presented by Jurgen Rockstroh.

The study design, matched baseline characteristics and safety and efficacy results from earlier analyses have already been presented at earlier meetings. The new subgroup analyses (including baseline CD4 <200 copies/mm3, viral load >100,000 copies/mL, hepatitis and demographic responses) focused on virological efficacy with discontinuations related to viral failure included but discontinuations for other reasons excluded and using an observed failure approach.

From approximately 280 patients in each arm at baseline, 223 (79%) and 197 (70%) completed the 192 week analysis, in the raltegravir and efavirenz arms respectively. Discontinuations were all less frequent in the raltegravir arm: virological failure (n=5 vs 8); side effects (n=13 vs 26); and loss to follow-up (n=8 vs 17)

At 192 weeks, the primary analysis of viral suppression to <50 copies/mL (non-completer=failure) saw raltegravir achieve statistical superiority compared to efavirenz [76% vs 67% (difference = +9.0; 95%CI 1.6, 16.4, p < 0.001: with the lower limit for non-inferiority set at ?12% and superiority being achieved when both confidence intervals became greater than 1.0].

Overall clinical events (96% vs 98%, p = 0.16), discontinuations due to drug-related events (5% vs 8%, p = 0.173) and serious adverse events (18% in each arm, p = 0.91) were similar between the two study groups, raltegravir was associated with significantly fewer drug-related events (50% vs 80%, p < 0.001).

There were no statistically significant differences in response between groups by gender, age, race/ethnicity, viral load >100,000 c/mL, CD4 > 200 cells/mm3, hepatitis coinfection or HIV sub-type. Raltegravir showed a significantly stronger virological response in the <100,000 c/mL group (93% vs 81%; difference +12; 95% CI 3, 22). Interpretation of a difference in favour of raltegravir when baseline CD4 was 50-<200 cells/mm3 is complicated by a trend to favour efairenz when CD4 counts were <50 cells/mm3.

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These results support durability and safety of raltegravir. they also show that after week 192 raltegravir achieves superiority compared to efavirenz with the difference largely driven by efavirenz-related side effects.

The CD4 difference may also be important for patients with sub-optimal CD4 responses on other HAART combinations.

Rockstroh JK et al. Long-term efficacy of raltegravir or efavirenz combined with TDF/FTC in treatment-na? HIV-1-infected patients: week-192 subgroup analyses from STARTMRK. 13th EACS, 12?15 October 2011, Belgrade. Abstract PS 1/1.