Comparison of the “Other” Regimens for HIV-Naive Patients

Summary and Comment |
October 7, 2014

Comparison of the “Other” Regimens for HIV-Naive Patients

  1. Helmut Albrecht, MD

Darunavir was superior to atazanavir — and raltegravir was superior to both — for the combined efficacy/tolerability endpoint, but between-regimen differences were entirely driven by tolerability.

  1. Helmut Albrecht, MD

The 2014 Department of Health and Human Services Guidelines for the Use of Antiretroviral Agents in HIV-1–Infected Adults and Adolescents recommends 10 different regimens for treatment-naive HIV-infected patients. Although all the newer regimens have been compared with nonnucleoside reverse transcriptase inhibitor (NNRTI)–based ones, the relative efficacy and tolerability of non-NNRTI–anchored regimens has not been studied in large non-company-supported trials.

In the open-label ACTG A5257 trial, 1809 treatment-naive HIV-infected adults were randomized to receive one of three regimens (once-daily atazanavir 300 mg with ritonavir 100 mg; once-daily darunavir 800 mg with ritonavir 100 mg; or twice-daily raltegravir 400 mg), all plus a once-daily single-tablet combination of emtricitabine (FTC) and tenofovir. At 96 weeks, rates of virologic control were high and similar among the three regimens. Among participants with treatment failure, resistance to the randomized medications at the time of failure was rare but was most frequent with raltegravir. Toxicity-associated discontinuation was significantly more common with ritonavir-boosted atazanavir than with the other two regimens.

Comment

Atazanavir “inferiority” was mostly attributable to a much higher than previously documented treatment-discontinuation rate because of atazanavir-induced hyperbilirubinemia. One can speculate that the open-label design and a preexisting patient or provider bias contributed to the surprisingly high atazanavir discontinuation rate. It would be interesting to see whether these rates were higher in certain subgroups, such as Hispanic patients (who, in my experience, are more aware of the stigmatizing scleral jaundice often attributed to chronic hepatitis).

Another surprising result was that raltegravir, despite its twice-daily dosing, beat out both once- daily protease inhibitor (PI)-based regimens. It should be noted that all drugs except ritonavir were provided. Although copay support was available, requiring an extra step to obtain one of the medications may have created a difficult-to-quantify bias against the PI-based regimens.

Finally, since the start of the study, two once-daily integrase-inhibitor options have become available. This development plus the pending approval of the new tenofovir prodrug may soon render all the studied regimens obsolete.

Editor Disclosures at Time of Publication

  • Disclosures for Helmut Albrecht, MD at time of publication Grant / Research support Health Resources and Services Administration

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