The Human Immunodeficiency Virus (HIV) is a persistent viral infection that targets and compromises the body’s immune system. Beyond its direct effects, HIV can disrupt normal endocrine function, leading to a recognized comorbidity known as hypogonadism, or low testosterone. Testosterone is present in both men and women, playing a role in maintaining muscle mass, bone density, energy levels, and mood. Recognizing and treating this deficiency is important for people living with HIV (PLWH), as it impacts their quality of life and long-term health.
How HIV Infection Affects Testosterone Levels
HIV infection is strongly associated with an increased risk of developing low testosterone levels compared to the general population. Before the widespread use of effective combination antiretroviral therapy (ART), up to 50% of men with advanced HIV disease had hypogonadism. While modern treatment has lowered this rate, the prevalence of low testosterone in men living with HIV remains high, ranging from approximately 13% to 40%.
This hormonal complication can occur even when the virus is well-controlled and the individual maintains an undetectable viral load. The occurrence of hypogonadism in PLWH is complex, involving disruptions to the system that regulates hormone production, and requires continuous monitoring and management.
Factors Contributing to Low Testosterone
The mechanisms behind low testosterone in PLWH involve viral effects, treatment impacts, and general health status. Chronic systemic inflammation, triggered by the persistent presence of HIV, is a significant factor. This immune activation disrupts the hypothalamic-pituitary-gonadal (HPG) axis, the communication pathway between the brain and the testes that controls testosterone production.
The resulting deficiency is most commonly secondary hypogonadism, meaning the problem originates from the brain failing to send signals to the testes. In rare cases, uncontrolled HIV or opportunistic infections can damage the testes, leading to primary hypogonadism.
Certain ART medications, particularly older classes like protease inhibitors, have been historically linked to endocrine disruption. Even some current medications, such as integrase inhibitors, have been implicated as potential factors in hypogonadism development over time.
Co-existing health conditions also contribute. Chronic wasting syndrome, involving involuntary weight loss and nutritional deficiencies, severely suppresses the HPG axis. Common comorbidities such as obesity, insulin resistance, chronic liver disease, and opioid use can independently lower testosterone levels.
Identifying Symptoms and Diagnosis
The symptoms of low testosterone in people living with HIV are often non-specific and can overlap with signs of the infection or other related conditions. Common complaints include severe fatigue, decreased libido, and erectile dysfunction. Patients may also experience a reduction in muscle mass and strength, along with an increase in body fat, particularly around the abdomen.
Psychological symptoms frequently include depressed mood, difficulty concentrating, and poor sleep quality. Less common but serious signs involve a reduction in bone mineral density, which increases the risk of osteoporosis and fractures, and the development of mild anemia. Diagnosis requires a laboratory confirmation alongside the presence of clinical symptoms.
The diagnostic process begins with a blood test to measure serum testosterone levels, ideally drawn in the morning when levels are highest. Because HIV can alter sex hormone-binding globulin (SHBG) levels, which carry testosterone in the blood, it is important to measure both Total Testosterone and Free Testosterone. A diagnosis of hypogonadism is confirmed when a patient presents with clear clinical symptoms and consistently low testosterone values on at least two separate morning tests.
Treatment Approaches
The treatment for confirmed hypogonadism in people living with HIV is Testosterone Replacement Therapy (TRT). TRT restores serum testosterone levels to alleviate symptoms and improve overall health. It is available in several forms, including injections, transdermal gels, and patches.
Effective management requires a specialist, such as an endocrinologist or an HIV clinician. Adherence to the ART regimen is a primary strategy, as controlling the viral load is the most effective way to improve endocrine health.
Patients on TRT require careful monitoring for potential side effects, such as excessive red blood cell production (erythrocytosis). Monitoring includes regular checks of prostate-specific antigen (PSA) and hematocrit levels to ensure safety. TRT is an effective intervention that restores energy, improves body composition, and enhances quality of life for many PLWH.