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

Summary and Comment |
August 27, 2014

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

  1. 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.

  1. Carlos del Rio, MD

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.

Comment

Ninety-six–week virologic results were comparable between boosted darunavir plus raltegravir and boosted darunavir plus tenofovir/FTC, but only for patients with baseline CD4 counts >200 cells/mm3. In addition, among those with treatment failure on the NRTI-sparing regimen, a substantial proportion developed raltegravir-specific mutations.

These results are not as encouraging as one would have liked, and I believe that NRTI-sparing regimens are not ready for “prime time.” Furthermore, data from this study do not provide evidence to support the use of the tested NRTI-sparing regimen in any particular subgroup of patients (e.g., individuals with low viral loads, high CD4-cell counts, and certain comorbidities or risks for complications from NRTIs).

Editor Disclosures at Time of Publication

  • Disclosures for Carlos del Rio, MD at time of publication Grant / Research support NIH; NIH/National Institute of Allergy and Infectious Diseases; NIH/Fogarty International Center; CDC; NIH/National Institute on Drug Abuse; MANILA Consulting Group, Inc.; NIH/National Institute of Mental Health; Janssen Services; Addis Ababa University; George Washington University Editorial boards AIDS Research and Human Retroviruses; Journal of AIDS Leadership positions in professional societies HIV Medicine Association (Board of Directors); International AIDS Society-USA (Board of Directors)

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