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Benefits and Risks of Stepdown to Atazanavir/Ritonavir Plus Lamivudine
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XVIII International AIDS Conference, July 18-23, 2010, Vienna
Mark Mascolini
Stopping tenofovir or abacavir and continuing standard doses of atazanavir/ritonavir and lamivudine preserved viral control and improved glomerular filtration rate, a marker of kidney function, in a small noncomparative study [1]. But new grade 3 or 4 lab abnormalities cropped up in 18 of 36 patients who reached 24 weeks of follow-up.
Clinicians in Rome and Siena planned the study to assess the efficacy and safety of this novel simplification strategy. All patients had maintained a viral load below 50 copies for more than 3 months while taking atazanavir/ritonavir and lamivudine plus a third nucleoside. The study excluded people in whom a regimen containing lamivudine or a protease inhibitor had failed, people in whom another regimen had failed and who had genotype resistance to lamivudine or atazanavir, people with hepatitis B surface antigen, people taking a proton pump inhibitor, and pregnant women. Everyone had a CD4 count above 200 for more than 6 months. Enrollment took place from June 2009 through May 2010.
The study is planned for 48 weeks but will end if 5 people have a confirmed viral rebound above 50 copies. Of the 40 people who entered the trial, 39 stopped tenofovir and 1 stopped abacavir. Twenty-three enrollees (57.5%) were men, and 9 (22.5%) had an earlier AIDS diagnosis. Nine people (22.5%) became infected with HIV through injection drug use. Median time with a viral load below 50 copies was 663 days (interquartile range [IQR] 320 to 896), and median CD4 count stood at 598 (IQR 472 to 777). Median CD4 nadir was 21 (IQR 10 to 30). Median time since HIV diagnosis was 11.4 years (IQR 7.1 to 15.2), and median time since starting combination therapy was 21 months (IQR 10 to 30).
At the time of this analysis, 36 participants had made their week 24 visit, and none had a virologic spike above 50 copies. Median CD4 count did not change significantly. As would be expected in people stopping tenofovir, estimated glomerular filtration rate improved significantly through 24 weeks (mean +7 mL/min/1.73m(2) by MDRD, P < 0.001). Creatinine declined significantly in that time (mean -0.08 mg/dL, P < 0.001).
But some lab measures worsened, and 5 serious clinical adverse events developed: 2 cases of renal colic, 1 hypertensive crisis, 1 brain hemorrhage (judged not related to study drugs), and 1 pregnancy. Only the patient who became pregnant dropped out of the study. Eighteen patients (50%) endured new grade 3 or 4 lab abnormalities, including 4 low-density lipoprotein (LDL) elevations, and 3 grade 4 total cholesterol jumps. Thirteen people had new grade 3 total bilirubin elevations. Atazanavir concentrations did not change significantly after tenofovir or abacavir stopped, despite reported low atazanavir concentrations in people taking tenofovir.
Median total cholesterol rose 21 mg/dL, LDL cholesterol climbed 17 mg/dL, and high-density lipoprotein (HDL) cholesterol rose 4 mg/dL. There was no significant change in the total/HDL cholesterol ratio or the HDL/LDL ratio. The investigators speculated that the rising lipid levels may reflect a postulated lipid-suppressing effect of tenofovir [2].
References
1. De Luca A, Bracciale L, Doino M, et al. Safety and efficacy of treatment simplification to atazanavir/ritonavir plus lamivudine in patients on two NRTIs plus atazanavir/ritonavir with optimal virologic control: 24 weeks results from a pilot study (atazanavir and lamivudine simplification study, ATLAS). XVIII International AIDS Conference. July 18-23, 2010. Vienna. Abstract THLBB207.
2. Tungsiripat M, Kitch D, Glesby MJ, et al. A pilot study to determine the impact on dyslipidemia of adding tenofovir to stable background antiretroviral therapy: ACTG 5206. AIDS. 2010:1781-1784.
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