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Atazanavir/RTV Stopped Less Than Other Key First-Line Drug in Large French Analysis
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Tenth International Congress on Drug Therapy in HIV Infection, November 7-11, 2010, Glasgow
Mark Mascolini
French patients starting their first antiretrovirals were almost 25% less likely to stop atazanavir/ritonavir in 24 months than to stop lopinavir/ritonavir, fosamprenavir/ritonavir, or efavirenz when any of those drugs were taken with tenofovir/emtricitabine [1]. This analysis of the French Hospital Database on HIV ANRS CO4 cohort found no response differences between atazanavir/ritonavir and the other drugs, except in those who started treatment with a CD4 count under 200. In that subgroup, atazanavir stood a significantly better chance of adding at least 100 CD4 cells in 24 months.
Dominique Costagliola and ANRS colleagues analyzed outcomes in 2910 antiretroviral-naive cohort members who started one of the four regimens, including 517 people starting atazanavir/ritonavir, 1129 starting efavirenz, 1045 starting lopinavir/ritonavir, and 219 starting fosamprenavir/ritonavir. Everyone began treatment after December 31, 2003 and at least 12 months before the analysis closing date. Median pretreatment CD4 count was significantly higher in the atazanavir group than in the combined comparison group (246 versus 228, P = 0.0064), but pretreatment viral loads were equivalent (4.87 and 4.89 log, about 75,000 copies).
A significantly higher proportion of people starting other drugs were from sub-Saharan Africa (22% versus 14%, P < 0.001), and time since HIV diagnosis was shorter in the non-atazanavir group (13.1 versus 25.5 months, P < 0.001). A higher proportion starting non-atazanavir regimens had AIDS before beginning treatment (20% versus 13%, P < 0.001).
At the end of follow-up, 24% had stopped or switched atazanavir/ritonavir and 27% had stopped or switched one of the three comparison drugs. Although the percentage difference seems small, multivariate analysis that considered age, gender, geographical origin, HIV transmission group, pretreatment CD4 count and viral load, AIDS stage, HCV coinfection, and year of starting treatment calculated a 24% lower adjusted risk of stopping atazanavir/ritonavir in 24 months: adjusted hazard ratio (AHR) 0.76, 95% confidence interval (CI) 0.61 to 0.94).
Four other outcome analyses showed no significant 24-month differences between atazanavir/ritonavir and the comparator drugs: virologic suppression below 50 copies (83% with atazanavir/ritonavir versus 84%, AHR 0.96, 95% CI 0.86 to 1.07); gain of at least 100 CD4 cells (83% with atazanavir/ritonavir versus 80%, AHR 1.10, 95% CI 0.99 to 1.23); AIDS or death (7% with atazanavir/ritonavir versus 10%, AHR 0.90, 95% CI 0.62 to 1.31); or hospital admission, AIDS, or death (17% with atazanavir/ritonavir versus 21%, AHR 0.93, 95% CI 0.73 to 1.18).
The ANRS team repeated the analysis looking only at 95 people starting atazanavir and 417 starting other drugs who began treatment with a CD4 count below 200 and a viral load below 100,000 copies. This time the stop-or-switch rate was 18% with atazanavir and 26% with other drugs. The adjusted hazard ratio indicated that people starting atazanavir were 57% less likely to stop or switch in 24 months than people starting other drugs (AHR 0.43, 95% CI 0.23 to 0.80). Again rates of virologic suppression, AIDS or death, and hospital admission, AIDS, or death did not differ significantly between the atazanavir group and the comparison drugs. But people starting atazanavir were 56% more likely to gain at least 100 CD4 cells in 24 months (81% versus 72%, AHR 1.56, 95% CI 1.17 to 2.07).
A final analysis considered 96 people starting atazanavir and 572 starting other drugs with a CD4 count below 200 and a viral load at or above 100,000 copies. Once again, atazanavir held a significant advantage in the switch-or-stop rate at 24 months (17% versus 31%, AHR 0.46, 95% CI 0.27 to 0.79), and a significantly edge in boosting CD4 counts at least 100 cells (89% versus 74%, AHR 1.38, 95% CI 1.08 to 1.75). In this subgroup, atazanavir did not differ from the other drugs in rates of virologic suppression, AIDS or death, or hospital admission, AIDS, or death.
Reference
1. Billaud E, Lacombe JM, Abgrall S, et al. Outcomes in antiretroviral-naive HIV-infected patients initiating therapy with TDF/FTC plus either atazanavir/r or another third recommended drug. Tenth International Congress on Drug Therapy in HIV Infection. November 7-11, 2010. Glasgow. Abstract P009.
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