Raltegravir Versus Efavirenz in Treatment-Naive HIV-1-Infected Patients
Raltegravir Versus Efavirenz in Treatment-Naive HIV-1-Infected Patients
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 [Δ (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 [Δ (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.
Combination antiretroviral therapy has resulted in longer survival and a better quality of life for many HIV-infected patients. Unfortunately, some patients cannot tolerate reverse transcriptase or protease inhibitors, and transmission of drug-resistant HIV jeopardizes the response to standard first-line regimens in certain treatment-naive patients. Additional agents from novel drug classes are needed to expand options for the initial treatment of HIV-1 infection and enhance the probability of achieving and maintaining virologic suppression. Raltegravir as part of combination therapy has been efficacious and generally well tolerated in patients infected with HIV-1 susceptible or resistant to other classes of antiretroviral drugs. In the Phase III STARTMRK study of treatment-naive patients, the efficacy of raltegravir was noninferior to the results with efavirenz when used in combination with tenofovir/emtricitabine through 48 weeks of therapy. Raltegravir recipients experienced significantly fewer clinical adverse events and central nervous system side effects than efavirenz recipients. In a Phase II trial, virologic suppression with a raltegravir-based regimen was maintained in most treatment-naive patients for at least 96 weeks. We now present the 96-week results from the ongoing Phase III STARTMRK study, including the first presentation of data regarding changes in body fat composition.
Abstract and Introduction
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 [Δ (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 [Δ (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.
Introduction
Combination antiretroviral therapy has resulted in longer survival and a better quality of life for many HIV-infected patients. Unfortunately, some patients cannot tolerate reverse transcriptase or protease inhibitors, and transmission of drug-resistant HIV jeopardizes the response to standard first-line regimens in certain treatment-naive patients. Additional agents from novel drug classes are needed to expand options for the initial treatment of HIV-1 infection and enhance the probability of achieving and maintaining virologic suppression. Raltegravir as part of combination therapy has been efficacious and generally well tolerated in patients infected with HIV-1 susceptible or resistant to other classes of antiretroviral drugs. In the Phase III STARTMRK study of treatment-naive patients, the efficacy of raltegravir was noninferior to the results with efavirenz when used in combination with tenofovir/emtricitabine through 48 weeks of therapy. Raltegravir recipients experienced significantly fewer clinical adverse events and central nervous system side effects than efavirenz recipients. In a Phase II trial, virologic suppression with a raltegravir-based regimen was maintained in most treatment-naive patients for at least 96 weeks. We now present the 96-week results from the ongoing Phase III STARTMRK study, including the first presentation of data regarding changes in body fat composition.
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