An NRTI-Sparing Regimen for HIV-Infected, Treatment-Naive Patients?

Carlos del Rio, MD

In a multicenter trial, ritonavir-boosted darunavir plus raltegravir was noninferior to ritonavir-boosted darunavir plus tenofovir/FTC at 96 weeks for patients with CD4 counts >200 cells/mm3.

For antiretroviral treatment–naive individuals, several regimens are recommended; all include two nucleoside/nucleotide reverse-transcriptase inhibitors (NRTIs; either tenofovir/FTC or abacavir/lamivudine). Because of tolerability and toxicity issues with NRTIs, researchers have been investigating NRTI-free regimens for initial therapy.

In a randomized, open-label, noninferiority trial involving 805 treatment-naive HIV-infected individuals in 15 European countries (88% men, 82% white, 72% men who have sex with men, 4% with hepatitis C virus coinfection), researchers compared ritonavir-boosted darunavir (100/800 mg daily) plus raltegravir (400 mg twice daily) with the standard regimen of ritonavir-boosted darunavir plus tenofovir/FTC. Median CD4-cell counts and viral loads were similar between the two arms.

Treatment failure (a composite endpoint that included regimen change before 32 weeks because of insufficient virologic response; death; or an AIDS event) occurred in 19% and 15% of the experimental-regimen and standard-regimen arms, respectively. The adjusted between-group difference in treatment-failure rates at week 96 was 4%, which met the noninferiority criterion. The frequency of treatment-modifying adverse events was also similar between arms. In subgroup analysis, the NRTI-sparing regimen was inferior for patients with baseline CD4 counts <200 cells/mm3. Among individuals with treatment failure who underwent genotypic testing, none in the standard arm had resistance mutations compared with 21% in the NRTI-sparing arm. Also, discontinuation of the regimen was significantly more common in the NRTI-sparing arm.

Citation(s):

Raffi F et al. Ritonavir-boosted darunavir combined with raltegravir or tenofovir–emtricitabine in antiretroviral-naive adults infected with HIV-1: 96 week results for the NEAT001/ANRS143 randomised non-inferiority trial. Lancet 2014 Aug 5; [e-pub ahead of print].