Pentoxifylline and Combination Antiretroviral Therapy to Improve Blood Vessel Function in HIV-Infected People

People infected with HIV have an increased risk for cardiovascular disease, which is a
leading cause of death for those with HIV. This may be due to increased inflammation of the
blood vessels, which is often observed in HIV-infected people and which can lead to
endothelial dysfunction—a condition that involves the malfunctioning of the thin layer of
cells that line the interior surface of blood vessels. Endothelial dysfunction increases the
risk of developing both atherosclerosis and cardiovascular disease.

Much of the focus on the causes of HIV-related endothelial dysfunction has been centered on
the use of several types of antiretroviral medications used to treat HIV infection. However,
more recent data suggest that newer protease inhibitors, a type of antiretroviral
medication, are not associated with endothelial dysfunction and that newer combination
antiretroviral therapy (cART) regimens result in an initial improvement in endothelial
dysfunction. Yet, preliminary research has also shown that in people who receive cART, the
risk of endothelial dysfunction in fact persists with time, suggesting that a mechanism
other than viral control, notably inflammation, is playing a role in endothelial
dysfunction. Pentoxifylline is a medication that is currently used to reduce leg pain in
people with blockages in the blood vessels in their legs. Previous research has shown that
pentoxifylline may improve blood vessel function and reduce inflammation in people infected
with HIV, but more research is needed to confirm these benefits. The purpose of this study
is to compare the safety and effectiveness of pentoxifylline and cART versus cART alone at
improving endothelial function and reducing inflammation in HIV-infected people.

This study will enroll people infected with HIV who are about to start receiving cART. At a
baseline study visit, participants will undergo a medical history review; physical
examination; measurements of blood pressure, heart rate, height, weight, temperature, waist,
and hip; and blood and urine collection. An ultrasound imaging test of the arm will measure
blood vessel function. Participants will then be randomly assigned to receive either
pentoxifylline or placebo three times a day for 48 weeks. All participants will also receive
cART medications, as prescribed by their primary HIV doctor. At study visits at Weeks 4, 8,
16, 24, 32, and 48, participants will undergo repeat baseline measurements; however, the
ultrasound testing will only occur at Weeks 8, 24, and 48.