Long-Term Musculoskeletal Effects of HIV Medications and the Role of Metabolic Optimization
Advances in HIV treatment have transformed the condition from a fatal disease into a chronic, manageable illness. However, the long-term use of antiretroviral therapy (ART) can lead to adverse effects on musculoskeletal health. These include loss of lean body mass, increased visceral adiposity, reduced bone mineral density, and sarcopenia. At the Performance Medicine Institute, we use an evidence-informed strategy that includes testosterone replacement therapy (TRT) and metabolic optimization to preserve muscle, reduce fat, and support immune function.
How HIV Medications Affect the Musculoskeletal System
Some classes of ART, especially protease inhibitors and older nucleoside reverse transcriptase inhibitors, have been associated with lipodystrophy and mitochondrial toxicity. Over time, this can lead to a redistribution of body fat, characterized by central adiposity and loss of peripheral fat, as well as accelerated loss of bone and muscle. Chronic systemic inflammation, even with suppressed viral load, further drives catabolism and disrupts the balance of anabolic hormones.
Muscle Loss and Fat Gain: A Hidden Burden
People living with HIV often experience a gradual decline in muscle mass even with stable body weight. This shift in body composition, with increased fat and less muscle, has metabolic consequences including insulin resistance, higher triglycerides, reduced energy, and impaired glucose disposal. Loss of muscle also correlates with physical frailty and worsened long-term outcomes, especially in older patients or those with chronic inflammation.
Testosterone Deficiency Is Common but Underrecognized
Hypogonadism is significantly more prevalent in HIV-positive men compared to the general population, even when controlling for age and comorbidities. Low testosterone levels contribute to reduced libido, fatigue, depression, and increased fat mass. These changes further impair quality of life and may blunt immune response. Despite this, testosterone deficiency is often overlooked or undertreated in this population.
TRT Can Restore Anabolic Balance and Improve Immunometabolic Health
Testosterone therapy, when clinically indicated, can reverse many of the body composition changes seen in long-term ART. TRT improves lean muscle mass, reduces visceral adiposity, and enhances insulin sensitivity. Emerging data also suggest that testosterone therapy may increase CD4+ T-cell counts and improve the CD4/CD8 ratio, a marker of immune reconstitution. These effects are more pronounced when TRT is combined with resistance training and nutritional support.
Metabolic Optimization Beyond Testosterone
Comprehensive care also includes strategies to optimize mitochondrial health, reduce oxidative stress, and improve nutrient status. This may include the use of supplements such as L-carnitine, alpha-lipoic acid, and vitamin D, along with interventions to address sleep quality, inflammation, and glycemic control. Weight training and structured aerobic exercise enhance both musculoskeletal and cardiovascular function, and personalized nutrition can reduce excess visceral fat and support anabolic signaling.
A Personalized, Data-Driven Approach
We begin with a full-body composition scan and metabolic lab profile to assess hormone levels, inflammatory markers, lipid panels, and immune metrics. From there, we develop an individualized program that integrates TRT (when appropriate), targeted supplementation, and structured exercise under physician guidance. This approach addresses both the visible and invisible effects of long-term ART and promotes resilience in the aging HIV-positive population.
Conclusion
While ART has extended life expectancy in people with HIV, it can come at the cost of musculoskeletal and metabolic health. Testosterone therapy and metabolic optimization offer a powerful way to counteract these effects, reduce fat, build muscle, and support immune restoration. Contact Us to learn more about how our personalized approach can support your long-term health.
References
Grinspoon, S., & Carr, A. (2005). Cardiovascular risk and body-fat abnormalities in HIV-infected adults. New England Journal of Medicine, 352(1), 48-62.
Mulligan, K., et al. (2006). Effects of testosterone and resistance exercise in HIV-infected men with abdominal obesity and reduced testosterone. The Journal of Clinical Endocrinology & Metabolism, 91(11), 4289–4294.
Basaria, S., et al. (2001). Androgen deficiency in human immunodeficiency virus–infected men: clinical and therapeutic implications. The Journal of Clinical Endocrinology & Metabolism, 86(7), 3476–3482.
Koethe, J. R., et al. (2013). The HIV-infected older adult: a new challenge to HIV care and management. The Lancet Infectious Diseases, 13(11), 826–835.