Optimizing long-term health in patients with HIV

Modern HIV treatment has transformed HIV from a life-threatening infection into a chronic, manageable medical condition for many people. Antiretroviral therapy, or ART, is one of the great success stories in modern medicine. For people living with HIV, staying on effective ART is essential for viral suppression, immune protection, long-term health, and prevention of transmission.

At the same time, people living with HIV are living longer, training harder, working, aging, and managing the same metabolic and musculoskeletal challenges as everyone else. Many also face additional risks related to chronic inflammation, prior exposure to older HIV medications, changes in body composition, endocrine dysfunction, bone density loss, insulin resistance, lipid changes, and visceral fat accumulation.

The goal is not to create fear around HIV medications. The goal is to recognize that long-term health requires more than viral suppression alone. Muscle mass, strength, bone health, visceral fat, glucose control, lipid levels, testosterone status, sleep, inflammation, and physical function all matter. When these are measured and addressed systematically, patients can often improve energy, body composition, strength, mobility, and long-term resilience.

How HIV And ART Can Affect the Musculoskeletal System

The musculoskeletal system includes muscle, bone, tendon, joint, connective tissue, and the nervous system that controls movement. HIV can affect this system through several pathways, including chronic immune activation, systemic inflammation, altered mitochondrial function, medication effects, endocrine changes, nutritional factors, and reduced physical activity during periods of illness.

Some older antiretroviral medications were more strongly associated with lipodystrophy, mitochondrial toxicity, peripheral fat loss, insulin resistance, and metabolic complications. Many modern regimens are safer and better tolerated, but body composition and metabolic changes can still occur. Some patients experience increased central or visceral fat, weight gain, lipid changes, or changes in bone density depending on the medication regimen, baseline health, age, sex, genetics, and lifestyle factors.

This is why musculoskeletal and metabolic monitoring should be part of long-term HIV care. A person can have an undetectable viral load and still be developing low muscle mass, reduced strength, visceral adiposity, prediabetes, dyslipidemia, low testosterone, or low bone mineral density. These changes are often gradual, which makes them easy to miss unless they are specifically measured.

Muscle Loss, Sarcopenia, And Strength Decline

Sarcopenia refers to low muscle mass, reduced strength, and impaired physical performance. It is usually discussed in aging, but people living with HIV may be at higher risk because of chronic inflammation, prior medication exposure, metabolic disease, low testosterone, neuropathy, low physical activity, and changes in protein metabolism.

Muscle loss does not always show up as weight loss. Some patients maintain the same body weight while gaining fat and losing muscle. This can make the scale misleading. A patient may look "stable" on paper while their strength, glucose control, waist size, energy, and physical function are worsening.

This is why body composition testing is useful. Measuring skeletal muscle mass, lean mass, body fat mass, visceral fat, waist circumference, grip strength, and functional performance gives a more accurate picture than body weight alone. The goal is not just to weigh less. The goal is to preserve or increase muscle, reduce excess visceral fat, and improve strength and metabolic health.

Visceral Fat And HIV-Associated Lipodystrophy

Visceral fat is the deep abdominal fat that surrounds internal organs. It is different from the fat under the skin. Excess visceral fat is metabolically active and is associated with insulin resistance, abnormal cholesterol, inflammation, fatty liver disease, cardiovascular risk, sleep apnea, and reduced quality of life.

Some people living with HIV develop a pattern of body composition change that includes increased central abdominal fat, loss of peripheral fat, or both. This has historically been called HIV-associated lipodystrophy. It was more common with older ART regimens, but visceral adiposity remains clinically relevant today.

Visceral fat can be especially frustrating because it may not respond as well to simple dieting alone. Treatment usually requires a comprehensive strategy that includes resistance training, aerobic conditioning, protein optimization, sleep improvement, reduction of alcohol when relevant, glucose and lipid control, and medication review. In selected patients with HIV-associated lipodystrophy, tesamorelin may also be considered because it is specifically approved for reducing excess visceral abdominal fat in adults with HIV-associated lipodystrophy.

Bone Density and Fracture Risk

Bone health is another important part of long-term HIV care. HIV infection itself is associated with higher rates of low bone mineral density, and some ART regimens can contribute to additional bone loss, especially early after treatment initiation. Tenofovir disoproxil fumarate, or TDF, has been associated with greater bone mineral density loss than some other options, while newer regimens may have less bone impact.

Bone density matters because low bone mineral density increases fracture risk. This is especially important in patients who are older, have low testosterone, low vitamin D, low body weight, smoking history, heavy alcohol use, kidney disease, steroid exposure, prior fracture, or low muscle mass.

Assessment may include vitamin D testing, calcium intake review, testosterone evaluation when appropriate, DEXA scan, fall risk assessment, medication review, and evaluation for secondary causes of bone loss. Treatment may include resistance training, impact loading when safe, vitamin D optimization, adequate protein, adequate calcium intake, reducing smoking and excess alcohol, and prescription osteoporosis therapy when indicated.

Testosterone Deficiency in Men Living With HIV

Testosterone deficiency is more common in men living with HIV than in the general population. Symptoms may include fatigue, low libido, erectile dysfunction, depressed mood, reduced motivation, loss of muscle, increased fat mass, poor exercise recovery, low bone density, anemia, and reduced quality of life.

Low testosterone can worsen the same body composition problems that are already common in long-term HIV care. It may contribute to less muscle, more visceral fat, lower bone density, and reduced training response. This does not mean every man living with HIV needs testosterone therapy. It means symptoms and labs should be evaluated carefully.

Diagnosis should include symptoms plus appropriate laboratory testing. Total testosterone, free testosterone when appropriate, SHBG, LH, FSH, estradiol, CBC, CMP, PSA when appropriate, and other endocrine testing may be useful depending on the situation. Treatment decisions should consider fertility goals, cardiovascular risk, prostate history, sleep apnea, hematocrit, and patient preferences.

When clinically indicated and monitored appropriately, testosterone therapy may help improve lean mass, strength, libido, sexual function, mood, anemia, and bone health. The best outcomes usually occur when testosterone optimization is paired with resistance training, adequate protein intake, sleep improvement, and metabolic care.

Metabolic Health: Glucose, Insulin Resistance, And Lipids

People living with HIV may have increased risk of insulin resistance, dyslipidemia, fatty liver disease, and cardiovascular disease. These risks can be influenced by chronic inflammation, body composition, ART regimen, family history, aging, diet, physical activity, sleep, smoking, and alcohol intake.

Metabolic optimization begins with measurement. Useful labs may include fasting glucose, hemoglobin A1c, fasting insulin when appropriate, lipid panel, ApoB, hs-CRP, liver enzymes, kidney function, thyroid testing, and hormone evaluation when clinically indicated. Blood pressure, waist circumference, body composition, and sleep apnea risk should also be assessed.

Treatment depends on the pattern. Some patients need nutrition and exercise changes. Others may benefit from medications such as statins, GLP-1 receptor agonists, SGLT2 inhibitors, metformin, antihypertensives, or other therapies. ART regimen review with an HIV specialist may also be appropriate when weight gain, lipid changes, or bone effects are clinically significant.

The Role of Resistance Training

Resistance training is one of the most important interventions for people living with HIV who want to preserve muscle, improve strength, reduce frailty risk, support bone health, and improve metabolic function. Muscle is not just cosmetic. It is a major glucose disposal organ, an endocrine tissue, and a key determinant of long-term physical independence.

A good resistance training plan should be progressive, measurable, and matched to the patient's starting point. For some patients, this means traditional strength training with weights. For others, it may begin with machines, bands, bodyweight movements, blood flow restriction training, neuromuscular re-education, or supervised rehabilitation.

The most effective plans usually train major muscle groups at least two to three times per week. The goal is to improve strength over time, not simply move around. Tracking strength, repetitions, load, grip strength, and body composition helps patients see whether the program is actually working.

Aerobic Exercise and Cardiometabolic Health

Aerobic exercise is also important. Walking, cycling, swimming, jogging, interval training, and other forms of conditioning can improve cardiovascular fitness, insulin sensitivity, blood pressure, mood, sleep, and fat metabolism.

The best exercise plan often combines resistance training and aerobic training. Resistance training helps preserve muscle and bone, while aerobic training improves cardiovascular and metabolic health. Patients do not need to start with extreme training. Consistency matters more than intensity at the beginning.

For patients with neuropathy, joint pain, back pain, pelvic pain, or deconditioning, exercise selection should be individualized. The goal is to find forms of training that can be done consistently without flaring symptoms.

Nutrition for Muscle, Metabolism, And Immune Health

Nutrition should support muscle preservation, metabolic health, gut health, and overall energy. Many patients benefit from a higher-protein, high-fiber, minimally processed dietary pattern. Protein supports muscle repair and adaptation. Fiber supports glucose control, cholesterol, satiety, gut microbiome health, and bowel function.

A practical approach includes protein at each meal, plenty of vegetables, legumes, fruit, whole grains when tolerated, nuts, seeds, olive oil, and adequate hydration. Patients with insulin resistance, fatty liver, or visceral adiposity may benefit from reducing added sugars, refined starches, ultra-processed foods, and excess alcohol.

Supplements can be useful, but they should not replace the foundation. Vitamin D, omega-3 fatty acids, creatine monohydrate, magnesium, protein powder, and other supplements may be appropriate for selected patients. However, supplement plans should be reviewed carefully because some products may interact with medications or contain unreliable ingredients.

Mitochondrial Health and Fatigue

Some patients living with HIV experience fatigue, exercise intolerance, neuropathy, or muscle symptoms that may involve mitochondrial dysfunction, inflammation, sleep disruption, anemia, hormone changes, medication effects, or deconditioning. Older ART medications were more strongly associated with mitochondrial toxicity, but mitochondrial and metabolic health remain relevant in long-term care.

The most evidence-based way to support mitochondrial function is not usually a single supplement. It is a combination of regular exercise, adequate sleep, nutrient repletion, metabolic control, reduced smoking and alcohol exposure, and management of inflammation and endocrine issues.

Selected supplements such as L-carnitine, alpha-lipoic acid, CoQ10, creatine, or vitamin D may be considered depending on the patient's symptoms, labs, medications, and goals. These should be used thoughtfully rather than as a generic protocol.

Tesamorelin for HIV-Associated Visceral Fat

Tesamorelin (Egrifta) is a growth hormone-releasing hormone analog approved for reduction of excess visceral abdominal fat in adults with HIV-associated lipodystrophy. It stimulates the body's own growth hormone axis, which can reduce visceral adipose tissue in appropriately selected patients.

Tesamorelin is not a general weight loss drug and is not the same as GLP-1 therapy. Its strongest role is in patients with HIV-associated visceral adiposity or lipodystrophy patterns where deep abdominal fat is a major concern. It may improve waist circumference and visceral fat, but it requires monitoring and is not appropriate for everyone.

Potential side effects may include injection-site reactions, fluid retention, joint symptoms, glucose changes, and changes in IGF-1. Patients need careful screening and follow-up. Tesamorelin should be considered as part of a broader metabolic plan that includes resistance training, nutrition, sleep, and cardiovascular risk management.

GLP-1 and Incretin-Based Therapies

GLP-1 receptor agonists and dual incretin therapies like tirzepatide (Mounjaro, Zepbound) and semaglutide (Wegovy, Ozempic) may be useful for selected patients with obesity, type 2 diabetes, prediabetes, fatty liver risk, or metabolic syndrome. These medications can reduce appetite, body weight, glucose levels, and cardiometabolic risk in appropriate patients.

For people living with HIV, incretin therapy should be coordinated with the overall care plan. Weight loss can be beneficial, but preserving muscle is especially important. Patients using GLP-1 or related medications should prioritize resistance training, adequate protein intake, hydration, fiber, and monitoring of body composition.

These medications should not be used as a substitute for strength training or nutrition. The goal is improved body composition and metabolic health, not simply a lower number on the scale.

What We Measure

A data-driven approach is especially useful because many changes occur gradually. Depending on the patient, assessment may include:

• Body composition testing
• Skeletal muscle mass and body fat mass
• Waist circumference or visceral fat estimate
• Grip strength or functional strength testing
• Blood pressure
• Hemoglobin A1c and fasting glucose
• Lipid panel and ApoB when appropriate
• hs-CRP or other inflammatory markers when appropriate
• Testosterone, free testosterone, SHBG, LH, FSH, and estradiol when indicated
• CBC and CMP
• Vitamin D
• Thyroid testing when indicated
• DEXA scan for bone density when appropriate
• Sleep apnea screening
• Review of ART regimen, medications, and supplements

This allows treatment to be individualized. A patient with low muscle mass needs a different plan than a patient with visceral adiposity, low testosterone, low bone density, insulin resistance, or fatigue from poor sleep.

A Practical Metabolic Optimization Plan

Most patients benefit from a plan built around a few core priorities.

First, preserve and build muscle. This usually means progressive resistance training, adequate protein intake, and monitoring of strength and body composition.

Second, reduce excess visceral fat when present. This may involve nutrition, exercise, sleep, alcohol reduction, GLP-1 therapy when appropriate, tesamorelin in selected HIV-associated lipodystrophy patients, or other metabolic treatments.

Third, protect bone health. This includes vitamin D optimization, resistance training, impact loading when safe, testosterone evaluation when indicated, DEXA screening when appropriate, and treatment of osteoporosis or osteopenia when present.

Fourth, control cardiometabolic risk. Blood pressure, glucose, cholesterol, smoking, sleep apnea, and inflammation should all be addressed.

Fifth, coordinate with the HIV care team. ART should remain effective, tolerable, and aligned with the patient’s long-term health.

A Better Way to Think About Long-Term HIV Health

The success of modern HIV therapy means that many patients are now focused on long-term performance, body composition, sexual health, metabolic health, strength, and healthy aging. That is exactly where musculoskeletal and metabolic optimization become important.

Viral suppression remains the foundation. But long-term health also depends on muscle, bone, fat distribution, hormone balance, glucose control, cardiovascular risk, sleep, nutrition, and exercise capacity.

At the Performance Medicine Institute, we take a comprehensive approach for people living with HIV who want to optimize strength, body composition, hormone health, metabolic function, and long-term resilience. This may include body composition testing, lab evaluation, testosterone therapy when appropriate, resistance training, nutrition planning, metabolic medications, bone health evaluation, and coordination with HIV specialists.

If you are living with HIV and are concerned about muscle loss, visceral fat, low testosterone, fatigue, bone density, weight gain, or long-term metabolic health, we can help build a personalized plan. Reach out for more information.

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