Endothelial function in human immunodeficiency virus-infected antiretroviral-naive subjects before and after starting potent antiretroviral therapy: The ACTG (AIDS Clinical Trials Group) Study 5152s.
OBJECTIVE
This study evaluated the effects of 3 class-sparing antiretroviral therapy (ART) regimens on endothelial function in human immunodeficiency virus (HIV)-infected subjects participating in a randomized trial.


BACKGROUND
Endothelial dysfunction has been observed in patients receiving ART for HIV infection.


METHODS
This was a prospective, multicenter study of treatment-naive subjects who were randomly assigned to receive a protease inhibitor-sparing regimen of nucleoside reverse transcriptase inhibitors (NRTIs) + efavirenz, a non-nucleoside reverse transcriptase inhibitor-sparing regimen of NRTIs + lopinavir/ritonavir, or a NRTI-sparing regimen of efavirenz + lopinavir/ritonavir. The NRTIs were lamivudine + stavudine, zidovudine, or tenofovir. Brachial artery flow-mediated dilation (FMD) was determined by B-mode ultrasound before starting on ART, then after 4 and 24 weeks.


RESULTS
There were 82 subjects (median age 35 years, 91% men, 54% white). Baseline CD4 cell counts and plasma HIV ribonucleic acid (RNA) values were 245 cells/mm(3) and 4.8 log(10) copies/ml, respectively. At baseline, FMD was 3.68% (interquartile range [IQR] 1.98% to 5.51%). After 4 and 24 weeks of ART, plasma HIV RNA decreased by 2.1 and 3.0 log(10) copies/ml, respectively. FMD increased by 0.74% (IQR -0.62% to +2.74%, p = 0.003) and 1.48% (IQR -0.20% to +4.30%, p < 0.001), respectively, with similar changes in each arm (Kruskal-Wallis p value >0.600). The decrease in plasma HIV RNA at 24 weeks was associated with greater FMD (r(s) = -0.30, p = 0.017).


CONCLUSIONS
Among treatment-naive individuals with HIV, 3 different ART regimens rapidly improved endothelial function. Benefits were similar for all ART regimens, appeared quickly, and persisted at 24 weeks.
Torriani
Francesca J
FJ
Infection Prevention and Clinical Epidemiology Unit, University of California-San Diego, 200 West Arbor Drive, MC 8951, San Diego, California 92103, USA. ftorriani@ucsd.edu
Komarow
Lauren
L
Parker
Robert A
RA
Cotter
Bruno R
BR
Currier
Judith S
JS
Dubé
Michael P
MP
Fichtenbaum
Carl J
CJ
Gerschenson
Mariana
M
Mitchell
Carol K C
CK
Murphy
Robert L
RL
Squires
Kathleen
K
Stein
James H
JH
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D048588:Benzoxazines / Q000008:administration & dosage; D001916:Brachial Artery / Q000187:drug effects / Q000503:physiopathology; D018791:CD4 Lymphocyte Count; D003521:Cyclopropanes; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000503:physiopathology*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage; D015497:HIV-1; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage; D061466:Lopinavir; D008297:Male; D063065:Organophosphonates / Q000008:administration & dosage; D011446:Prospective Studies; D011744:Pyrimidinones / Q000008:administration & dosage; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage*; D019438:Ritonavir / Q000008:administration & dosage; D018119:Stavudine / Q000008:administration & dosage; D000068698:Tenofovir; D013997:Time Factors; D015215:Zidovudine / Q000008:administration & dosage
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D017320:HIV Protease Inhibitors; D063065:Organophosphonates; D011744:Pyrimidinones; D018894:Reverse Transcriptase Inhibitors; D061466:Lopinavir; D019259:Lamivudine; D015215:Zidovudine; D000068698:Tenofovir; D018119:Stavudine; D000225:Adenine; C098320:efavirenz; D019438:Ritonavir