Clinical trial NCT00050908: Blood Vessel Function in HIV-Infected Patients Taking Anti-HIV Drugs
Official title: Endothelial Function in HIV-Infected Subjects Prior To and After Starting a Potent Antiretroviral Regimen
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV Infections
Keywords: Brachial Artery
Endothelium, Vascular
Vasodilation
Nitroglycerin
Reverse Transcriptase Inhibitors
HIV Protease Inhibitors
Drug Therapy, Combination
Ritonavir
efavirenz
lopinavir
stavudine
lamivudine
zidovudine
Treatment Naive
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2003-01-01
Enrollment: 75
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Time perspective: PROSPECTIVE

Brief summary: This is a substudy of ACTG A5142. The purpose of this substudy is to evaluate blood vessel function in HIV-infected patients taking anti-HIV drugs.

Detailed description: Endothelial dysfunction, assessed by measurement of brachial artery reactivity, is associated with coronary artery disease. Previous studies showed that patients taking HIV protease inhibitors (PIs) had a buildup of fatty deposits in their arteries and impaired flow-mediated vasodilation of the brachial artery, whereas endothelial function was normal in HIV-infected individuals not taking PIs. The effect of three different antiretroviral regimens on endothelial function in antiretroviral naïve HIV-infected patients will be examined in this substudy.

Patients in this substudy will have Brachial Artery Reactivity Tests (BARTs), which are painless ultrasound tests of an artery in the lower arm. Brachial artery reactivity will be measured at entry and at 4 and 24 weeks after patients are randomized to one of three open-label drug regimens in ACTG A5142. Brachial artery reactivity in response to two vasoactive stimuli (flow-mediated and nitroglycerin) will be assessed by measuring brachial artery diameter and flow velocity. Blood will be drawn at Weeks 4 and 24 for insulin and lipid tests. Patients will fast and refrain from tobacco and caffeine use for at least 8 hours prior to each study visit. For the duration of the substudy, patients will be asked not to change the amount of fruits, juices, antioxidants, and tea that they consume.

Eligibility criteria: Inclusion Criteria:

* Participation in ACTG A5142 .
* Able and willing to give written informed consent and to report current smoking status.
* Men who have been on stable testosterone replacement for at least 3 months prior to entry and plan to continue to receive a stable dose during the substudy may enroll. Men who have discontinued testosterone therapy must be off for at least 3 months to be eligible.
* Women receiving oral contraceptives, hormone replacement, or progestational derivatives must have been on stable regimens for at least 3 months prior to enrollment and must plan to remain on the same dose for the duration of the study. Women who have discontinued such therapy must be off for at least 3 months to be eligible.

Exclusion Criteria:

* Coronary heart disease, peripheral vascular disease, or cerebrovascular disease.
* Diabetes mellitus, with the exception of a previous history of gestational or steroid-induced diabetes mellitus within 12 weeks prior to substudy entry.
* Insulin-sensitizing agents such as metformin, pioglitazone, and rosiglitazone.
* Lipid-lowering drugs within 6 weeks prior to substudy entry.
* Systemic glucocorticoids, long-acting inhaled steroids, and certain anabolic steroids within 30 days prior to substudy entry.
* Uncontrolled hypertension.
* Heavy use of vitamin supplements.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA School of Med
state: California
city: San Diego
country: United States
facility: Univ of California, San Diego Antiviral Research Ctr
state: California
city: Honolulu
country: United States
facility: Univ of Hawaii
state: Hawaii
city: Chicago
country: United States
facility: Northwestern Univ
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Univ Hosp
state: Indiana
city: Indianapolis
country: United States
facility: Methodist Hosp of Indiana
state: Indiana
city: Indianapolis
country: United States
facility: Wishard Hosp
state: Indiana
city: New York
country: United States
facility: Chelsea Clinic
state: New York
city: Cincinnati
country: United States
facility: Univ of Cincinnati
state: Ohio
Study officials:
affiliation: University of California, San Diego
name: Francesca J. Torriani, M.D.
role: STUDY_CHAIR
References:
citation: Stein JH, Klein MA, Bellehumeur JL, McBride PE, Wiebe DA, Otvos JD, Sosman JM. Use of human immunodeficiency virus-1 protease inhibitors is associated with atherogenic lipoprotein changes and endothelial dysfunction. Circulation. 2001 Jul 17;104(3):257-62. doi: 10.1161/01.cir.104.3.257.
citation: Behrens G, Schmidt H, Meyer D, Stoll M, Schmidt RE. Vascular complications associated with use of HIV protease inhibitors. Lancet. 1998 Jun 27;351(9120):1958. doi: 10.1016/S0140-6736(98)26026-0. No abstract available.
citation: Cleland SJ, Sattar N, Petrie JR, Forouhi NG, Elliott HL, Connell JM. Endothelial dysfunction as a possible link between C-reactive protein levels and cardiovascular disease. Clin Sci (Lond). 2000 May;98(5):531-5.
citation: Henderson A. Endothelial dysfunction: a reversible clinical measure of atherogenic susceptibility and cardiovascular inefficiency. Int J Cardiol. 1997 Dec 1;62 Suppl 1:S43-8. doi: 10.1016/s0167-5273(97)00212-x. No abstract available.
citation: Wolf K, Tsakiris DA, Weber R, Erb P, Battegay M; Swiss HIV Cohort Study. Antiretroviral therapy reduces markers of endothelial and coagulation activation in patients infected with human immunodeficiency virus type 1. J Infect Dis. 2002 Feb 15;185(4):456-62. doi: 10.1086/338572. Epub 2002 Jan 18.
citation: Stein JH, Komarow L, Cotter BR, Currier JS, Dube MP, Fichtenbaum CJ, Gerschenson M, Mitchell CK, Murphy RL, Squires K, Parker RA, Torriani FJ; ACTG 5152s Study Team. Lipoprotein Changes in HIV-Infected Antiretroviral-Naive Individuals after Starting Antiretroviral Therapy: ACTG Study A5152s Stein: Lipoprotein Changes on Antiretroviral Therapy. J Clin Lipidol. 2008 Dec;2(6):464-471. doi: 10.1016/j.jacl.2008.08.442.