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Maraviroc vs TDF/FTC + Reyataz/r
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Virologic Response at 96 Weeks Slightly Lower With Maraviroc Than TDF/FTC
XIX International AIDS Conference, July 22-27, 2012, Washington, DC
Mark Mascolini
Virologic response rates were moderately lower with maraviroc plus atazanavir/ritonavir than with tenofovir/emtricitabine (TDF/FTC) plus atazanavir/ritonavir at week 96 of a small, randomized, open-label trial that did not have the statistical power to detect differences between arms [1]. Rates of protocol-defined virologic failure did not differ between the two groups.
Study A4001078 enrolled antiretroviral-naive adults and randomized them to once-daily maraviroc (150 mg) or TDF/FTC (300/200 mg), each with atazanavir/ritonavir (300/100 mg). All study participants had CCR5-using virus, a viral load at or above 1000 copies, a CD4 count at or above 100, and no documented resistance to atazanavir/ritonavir, TDF, or FTC.
Age averaged 38 in the 60 people randomized to maraviroc and 35 in the 61 randomized to TDF/FTC. Respective median CD4 counts were 344 and 358, and respective mean viral loads 4.6 and 4.7 log10 copies/mL (approximately 40,000 and 50,000 copies). About 90% of study participants were men.
Through 48 weeks, 7 people dropped out of the maraviroc arm (2 because of insufficient response and 2 because of adverse events) and 7 quit the TDF/FTC arm (1 because of kidney failure potentially related to tenofovir) [2]. Proportions of study participants with a viral load below 50 copies at week 48 were 74.6% in the maraviroc group and 83.6% in the TDF/FTC group.
After 96 weeks of follow-up [1], 10 people in the maraviroc arm and 9 in the TDF/FTC arm discontinued treatment. Between week 48 and week 96, there were no additional discontinuations for insufficient response or adverse events.
At week 96 virologic response rates continued to lag in the maraviroc arm in a noncompletion-equals-failure analysis:
Viral load below 50 copies at week 96:
-- 67.8% (40 of 59) assigned to maraviroc versus 82.0% (50 of 61) assigned to TDF/FTC
Viral load below 400 copies at week 96:
-- 78.0% (46 of 59) assigned to maraviroc versus 83.6% (51 of 61) assigned to TDF/FTC
The investigators attributed most of these virologic response differences to transient low-level viremia. Through 96 weeks 3 people in the maraviroc arm and 2 in the TDF/FTC arm met criteria for protocol-defined virologic failure. Four people assigned to maraviroc and 1 assigned to TDF/FTC had a viral load above 500 copies at failure or study discontinuation. Virologic analysis yielded no evidence of changed coreceptor use, resistance, or loss of susceptibility Virologic Response at 96 Weeks Slightly Lower With Maraviroc Than TDF/FTC
XIX International AIDS Conference, July 22-27, 2012, Washington, DC
Mark Mascolini
Virologic response rates were moderately lower with maraviroc plus atazanavir/ritonavir than with tenofovir/emtricitabine (TDF/FTC) plus atazanavir/ritonavir at week 96 of a small, randomized, open-label trial that did not have the statistical power to detect differences between arms [1]. Rates of protocol-defined virologic failure did not differ between the two groups.
Study A4001078 enrolled antiretroviral-naive adults and randomized them to once-daily maraviroc (150 mg) or TDF/FTC (300/200 mg), each with atazanavir/ritonavir (300/100 mg). All study participants had CCR5-using virus, a viral load at or above 1000 copies, a CD4 count at or above 100, and no documented resistance to atazanavir/ritonavir, TDF, or FTC.
Age averaged 38 in the 60 people randomized to maraviroc and 35 in the 61 randomized to TDF/FTC. Respective median CD4 counts were 344 and 358, and respective mean viral loads 4.6 and 4.7 log10 copies/mL (approximately 40,000 and 50,000 copies). About 90% of study participants were men.
Through 48 weeks, 7 people dropped out of the maraviroc arm (2 because of insufficient response and 2 because of adverse events) and 7 quit the TDF/FTC arm (1 because of kidney failure potentially related to tenofovir) [2]. Proportions of study participants with a viral load below 50 copies at week 48 were 74.6% in the maraviroc group and 83.6% in the TDF/FTC group.
After 96 weeks of follow-up [1], 10 people in the maraviroc arm and 9 in the TDF/FTC arm discontinued treatment. Between week 48 and week 96, there were no additional discontinuations for insufficient response or adverse events.
At week 96 virologic response rates continued to lag in the maraviroc arm in a noncompletion-equals-failure analysis:
Viral load below 50 copies at week 96:
-- 67.8% (40 of 59) assigned to maraviroc versus 82.0% (50 of 61) assigned to TDF/FTC
Viral load below 400 copies at week 96:
-- 78.0% (46 of 59) assigned to maraviroc versus 83.6% (51 of 61) assigned to TDF/FTC
The investigators attributed most of these virologic response differences to transient low-level viremia. Through 96 weeks 3 people in the maraviroc arm and 2 in the TDF/FTC arm met criteria for protocol-defined virologic failure. Four people assigned to maraviroc and 1 assigned to TDF/FTC had a viral load above 500 copies at failure or study discontinuation. Virologic analysis yielded no evidence of changed coreceptor use, resistance, or loss of susceptibility relevant to treatment in either arm.
CD4 gains through week 96 were equivalent with maraviroc (+240) and TDF/FTC (+264).
Rates of serious adverse events through week 96 were 21.7% with maraviroc and 18% with TDF/FTC. Respective rates of grade 3 or 4 adverse events were 53.3% and 32.8%. Two people (3.3%) in the maraviroc arm and none in the TDF/FTC arm discontinued treatment because of adverse events.
Creatinine clearance dropped substantially more in the TDF/FTC group (-18 mL/min) than in the maraviroc group (-5.5 mL/min). Hyperbilirubinemia affected more people taking maraviroc than TDF/FTC, possibly because TDF lowers atazanavir concentrations.
A phase 3 trial randomizing participants to maraviroc or TDF/FTC will substitute darunavir/ritonavir for atazanavir/ritonavir.
References
1. Mills A, Mildvan D, Podzamczer D, et al. Once-daily maraviroc in combination with ritonavir-boosted atazanavir in treatment-naive patients infected with CCR5-tropic HIV-1 (study A4001078): 96-week results. XIX International AIDS Conference. July 22-27, 2012. Abstract TUAB0102.
2. Portsmouth S, Craig C, Mills A, et al. 48-week results of a dual-therapy regimen of once-daily maraviroc (MVC) 150 mg in combination with ritonavir-boosted atazanavir (ATV/r) compared to emtricitabine/tenofovir (FTC/TDF) + ATV/r in treatment-naive (TN) patients infected with CCR5-tropic HIV. 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention. July 17-20, 2011. Rome. Abstract TUAB0103.
relevant to treatment in either arm.
CD4 gains through week 96 were equivalent with maraviroc (+240) and TDF/FTC (+264).
Rates of serious adverse events through week 96 were 21.7% with maraviroc and 18% with TDF/FTC. Respective rates of grade 3 or 4 adverse events were 53.3% and 32.8%. Two people (3.3%) in the maraviroc arm and none in the TDF/FTC arm discontinued treatment because of adverse events.
Creatinine clearance dropped substantially more in the TDF/FTC group (-18 mL/min) than in the maraviroc group (-5.5 mL/min). Hyperbilirubinemia affected more people taking maraviroc than TDF/FTC, possibly because TDF lowers atazanavir concentrations.
A phase 3 trial randomizing participants to maraviroc or TDF/FTC will substitute darunavir/ritonavir for atazanavir/ritonavir.
References
1. Mills A, Mildvan D, Podzamczer D, et al. Once-daily maraviroc in combination with ritonavir-boosted atazanavir in treatment-naive patients infected with CCR5-tropic HIV-1 (study A4001078): 96-week results. XIX International AIDS Conference. July 22-27, 2012. Abstract TUAB0102.
2. Portsmouth S, Craig C, Mills A, et al. 48-week results of a dual-therapy regimen of once-daily maraviroc (MVC) 150 mg in combination with ritonavir-boosted atazanavir (ATV/r) compared to emtricitabine/tenofovir (FTC/TDF) + ATV/r in treatment-naive (TN) patients infected with CCR5-tropic HIV. 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention. July 17-20, 2011. Rome. Abstract TUAB0103.
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