9th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 19-21 July 2007, Sydney, Australia

CONTROL OF HIV VIRAL REPLICATION IS ASSOCIATED WITH RAPID IMPROVEMENT IN ENDOTHELIAL FUNCTION SUSTAINED OVER 24 WEEKS: A5152S, A SUBSTUDY OF A5142

Antiviral Therapy 2007; 12(Suppl. 2):L15 (abstract no. O-18)

FJ Torriani¹, L Komarow², BR Cotter¹, RL Murphy³, CJ Fichtenbaum⁴, JS Currier⁵, MP Dubé⁶, KE Squires⁷, M Gerschenson⁸, CK Mitchell⁹ and JH Stein^9
1University of California San Diego, San Diego, CA, USA; ²Harvard School of Public Health, Boston, MA, USA; ³Northwestern University, Chicago, IL, USA; ⁴University of Cincinnati Medical Center, Cincinnati, OH, USA; ⁵University of California Los Angeles, Los Angeles, CA, USA; ⁶Indiana University School of Medicine, Indianapolis, IN, USA; ⁷University of Southern California, Los Angeles, CA, USA; ⁸University of Hawaii, Honolulu, HI, USA; ⁹University of Wisconsin Medical School, Madison, WI, USA

BACKGROUND: In HIV-infected patients, endothelial dysfunction, an early marker of atherosclerosis, has been attributed to HIV and associated with use of protease inhibitors (PI) and nucleoside reverse transcriptase inhibitors (NRTI).

METHODS: On ACTG A5142, a class-sparing ART trial, subjects were randomly assigned to: (1) NRTIs + efavirenz (EFV), (2) NRTIs + lopinavir/ritonavir (LPV) or (3) EFV + LPV. NRTIs were lamivudine plus stavudine or zidovudine or tenofovir. On substudy A5152s, brachial artery flow-mediated dilation (FMD) of subjects from five institutions was determined by high-resolution B-mode ultrasound before starting on ART, then after 4 and 24 weeks. Relationships between changes in FMD and changes in HIV RNA, CD4, metabolic, and inflammatory markers were analysed to identify predictors of changes in endothelial function on treatment.

RESULTS: Eighty-two treatment-naïve individuals (median age 35 years, 91% men, 54% white and 44% active smokers) entered. Baseline mean [SD] CD4 and HIV RNA values were 252 [168] cells/ml and 4.9 [0.6] log₁₀ copies/ml, respectively. Pre-ART FMD was impaired (4.0 % [3.1] versus normal >7%). After 4 and 24 weeks of ART, FMD increased by 1.1 % [2.8] (P=0.003) and 1.9 % [3.0] (P<0.001). FMD improvement was similar in each arm (P@gt;0.50). Total and HDL cholesterol increased significantly in each arm (P<0.01); triglycerides in the LPV-containing arms only (P<0.01). Log HIV RNA decreased by 2.1 and 3.0 log₁₀ copies/ml at 4 and 24 weeks of ART (P<0.001); CD4 counts increased by 152 after 24 weeks (P<0.01). Of all metabolic and inflammatory markers analysed, FMD improvement was significantly associated only with log HIV RNA reduction at week 24 (rs=-0.30, P=0.02).

CONCLUSIONS: During the first 24 weeks of ART, effective control of HIV replication improves endothelial function regardless of initial ART regimen or lipid effects. These data suggest that suppression of HIV replication may be more important in decreasing cardiovascular risk than the initial ART combination.

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2007-07-24
O-18

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