Conditions: HIV Aging Sarcopenia Angiotensin Receptor Antagonists
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 1
Healthy volunteers: no

Brief summary:
This study is designed to evaluate specific factors in mitochondria that may precipitate premature aging and physical weakness in HIV patients. Angiotensin receptors 1 and 2 (AT1R and AT2R) are found in virtually every cell type. This study will evaluate how the relationships among these receptors in immune and skeletal muscle cells change with HIV, and how these changes might trigger mitochondrial dysfunction, declines in muscle strength, and cellular decline in people living with HIV.

Detailed description:
HIV related premature cellular aging and declines in mitochondrial function are closely linked. Dysfunctional mitochondria generate higher levels of reactive oxygen species (ROS) and provide less ATP supply cellular energy. Impaired turnover of damaged mitochondria leads to gradual but progressive decline in energy metabolism, increases in muscle fibrosis and clinically apparent weakness. The Renin Angiotensin System (RAS) is a central hormonal system that contributes to mitochondrial dysfunction and impacts both lifespan and function across multiple organ systems. Deletion of the angiotensin type 1 receptor (AT1R) results in a 25-30% extension of lifespan in mouse models, partly through increasing mitochondrial numbers. Blocking of AT1R reduces a number of age-related morbidities in mice, and in human studies. A plethora of data implicates RAS modulation in marked effects on fitness, frailty and beneficial responses to exercise in older adults. Despite this, there are virtually no data examining RAS biology in HIV+ vs. age-matched HIVsubjects, no data of RAS in relation to key HIV-specific variables (duration of HIV, treatment history, immune markers), and no data examining the effects of blocking AT1R on physical function in HIV infected subjects. In this study, we will examine the RAS and its contribution to premature mitochondrial failure in HIV patients. We will begin to fill this void by enrolling 40 HIV+ subjects in a randomized, double-blinded, placebo controlled pilot study of treatment with AT1R blocker to determine the feasibility of a larger trial, estimate effect size, assess the correlation of angiotensin receptor (AR) expression in peripheral blood cells and muscle cells, and the association of AR expression with physical function measures and immunity.

Arms:
arm 1: 20 HIV-infected participants will be randomized into a blinded arm where they will receive 24 weeks of placebo therapy. During this time, they will undergo the same study procedures as the intervention arm. arm 2: 20 HIV-infected participants will be randomized into a blinded arm where they receive 24 weeks of valsartan therapy. For those subjects randomized to the valsartan group, they will receive valsartan 40 mg by mouth daily for 2 weeks, then increase to 80 mg by mouth daily for the remaining 22 weeks. During this time, they will undergo the same study procedures as the placebo arm.

Interventions: intervention 1: valsartan intervention 2: Placebo
Intervention descriptions: intervention 1: Valsartan will be given in increasing doses (from 40 mg to 80 mg) to those in the valsartan arm. intervention 2: None

Protocol document: