Control of HIV viral replication is associated with rapid improvement in endothelial function sustained over twenty-four weeks: A5152s, a substudy of A5142
Objectives: 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 5 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 analyzed to identify predictors of changes in endothelial function on treatment.
Results: 82 treatment-naïve individuals (median age 35 years, 91% men, 54% white, 44% active smokers) entered. Baseline mean [SD] CD4 and HIV RNA values were 252  cells/ml and 4.9 [0.6] log10 copies/ml, respectively. Pre-ART FMD was impaired (4.0 [3.1]% vs. 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>0.50). Total and HDL cholesterol increased significantly in each arm (p<0.01); triglycerides in the LPV-containing arms only (p<0.01). LogHIV 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 analyzed, FMD improvement was significantly associated only with logHIV 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.
4th IAS Conference on HIV Pathogenesis, Treatment and Prevention
"TorrianiF., et al.
Control of HIV viral replication is associated with rapid improvement in endothelial function sustained over twenty-four weeks: A5152s, a substudy of A5142.
Oral abstract session:
4th IAS Conference on HIV Pathogenesis, Treatment and Prevention: