The purpose of this study is to evaluate the potential effectiveness of losartan (100mg daily) for reducing inflammation and improving immune recovery.

Our general goal is to evaluate the potential effectiveness of losartan (100mg daily) for reducing inflammation and improving immune recovery, given the potential for these treatment effects to reduce risk for long-term non-AIDS-defining complications among older HIV positive participants. Prior to conducting a clinical outcome trial, candidate treatments must be studied among HIV positive patients given the unique pathogenesis driving inflammation and disease risk.

The potential benefits of losartan (100mg daily) will be studied among HIV positive individuals over age 50 years whose CD4 counts remain ≤600 cells/mm3. Participants (n=110, 55 per group) will be randomized to receive losartan or matching placebo daily. After randomization, participants will start losartan (or placebo) at a dose of 50mg once daily, increasing to 100mg once daily at the 2-week study visit pending results of a week 2 toxicity lab evaluation (see 2.4 below for criteria). Following month 1, participants will return for follow-up study visit procedures at months 3, 6, 9, and 12.

Changes from baseline in measures of inflammation, immune activation, immune recovery and fibrosis within lymphatic tissues will be studied. The primary outcome will be the average of IL-6 levels over 12 months, and the main secondary outcome will be change in CD4 count in blood over 12 months.

Inclusion Criteria:

• HIV infection (verified by previous positive antibody or detectable HIV RNA level)
• Age > 50 years
• Receiving continuous ART for >= 2 years (regimen changes > 6 months prior to enrollment are allowed)
• HIV RNA level < 200 copies/mL for >= 1 year (1 measure >= 200 allowed if also < 1000 and preceded and followed by values < 200 copies/mL)
• Blood CD4+ T-cell count < 600 cells/mm cubed
• Systolic blood pressure > 120 mmHg (mean value if >= 2 measures obtained)
• Estimated glomerular filtration rate (GFR )> 30 mL/min/1.73 m squared
• Do not anticipate starting or stopping statin or aspirin therapy during the study

Exclusion Criteria:

• Pregnancy or breastfeeding
• A contra-indication to taking an angiotensin receptor blocker (ARB) (e.g., cirrhosis, prior angioedema with angiotensin-converting enzyme inhibitor (ACE-I), or use of drug with potential drug-interaction [e.g., rifaximin])
• A clinical indication for ARB or ACE-I therapy (e.g., cardiovascular disease (CVD), stroke, or diabetes mellitus (DM))
• Current treatment with ARB or medication with overlapping mechanism (e.g., ACE-I or aldosterone antagonist)
• Current treatment with immunomodulatory drugs within the past 6 months
• Current hepatitis treatments (e.g., interferon, ribavirin) within the past 6 months
• Serum potassium > 5.0 millimoles per liter (mmol/L) within 3 months of entry
• Invasive cancer in the prior year or receiving cancer treatment (not including carcinoma-in-situ or basal cell cancer of the skin)
• Cirrhosis or end-stage liver disease
• Rheumatologic or chronic inflammatory disease (e.g., systematic lupus erythematous, psoriasis, rheumatoid arthritis, vasculitis, sarcoidosis, Crohn's disease)

12 months