Leg pain is common, but in people living with HIV, it signals a complex interplay between the virus, the immune system, and long-term treatment effects. While HIV does not typically cause acute, direct leg pain in the earliest stages, the chronic presence of the virus can lead to various musculoskeletal and neurological complications. Understanding these underlying issues is necessary for effective intervention against chronic or acute discomfort in the lower limbs.
Inflammation and Autoimmune Responses
The persistent presence of the human immunodeficiency virus triggers chronic, systemic inflammation throughout the body, even when suppressed by medication. This ongoing immune activation can directly cause pain in the legs by affecting the joints and muscles, a condition known as HIV-associated arthropathy. This inflammation, the body’s reaction to the virus, can lead to joint swelling, stiffness, and pain.
Systemic inflammation can also result in specific rheumatic diseases, such as reactive arthritis or psoriatic arthritis, frequently affecting large joints like the knees and ankles. Furthermore, myopathy, or muscle disease, is a direct consequence of the virus or the inflammatory state, causing muscle weakness and deep aches in the hips and lower extremities. This muscle discomfort can range from mild myalgia to serious myositis, which is inflammation of the muscle tissue itself.
HIV-Associated Nerve Damage
The most common cause of chronic leg pain associated with HIV infection is damage to the peripheral nervous system, known as peripheral neuropathy (PN). This condition frequently presents as Distal Symmetrical Polyneuropathy (DSP), affecting the longest nerves first, causing symptoms to begin in the feet and lower legs. The pain is distinct from muscle or joint aches, often described as burning, tingling, numbness, or sharp, shooting sensations.
Nerve damage has a dual causation: the HIV virus itself and the neurotoxicity of certain older antiretroviral drugs (ART). The virus contributes through chronic inflammation, as viral proteins and inflammatory cells release cytotoxins that impair nerve function. This viral-related DSP typically emerges gradually as the infection progresses.
A second significant cause is toxicity from specific nucleoside reverse transcriptase inhibitors, often called “d-drugs,” such as stavudine (\(\text{d}4\text{T}\)) and didanosine (\(\text{ddI}\)). These older drugs damage nerves by interfering with mitochondria, the energy-producing structures within nerve cells. While modern ART regimens rarely use these medications, prior exposure can result in long-lasting nerve damage clinically indistinguishable from viral-related neuropathy.
The sensory disturbance often follows a characteristic “stocking-and-glove” pattern, with sensations starting in the feet and hands before moving up the limbs. Patients may experience allodynia, where a non-painful stimulus, such as the touch of a bedsheet, becomes intensely painful. For those whose neuropathy is linked to the older \(\text{d}\)-drugs, discontinuing the medication is the primary step, though nerve healing is slow and symptoms may temporarily worsen.
Long-Term Treatment Effects on Bones and Tissue
Long-term HIV infection and certain ART regimens can lead to structural and metabolic complications causing deep leg pain. Avascular Necrosis (AVN), or osteonecrosis, is a severe complication where bone tissue dies due to an interrupted blood supply. The hip joint (femoral head) is the most common site affected, presenting as pain in the groin, thigh, or buttock that worsens with weight-bearing.
HIV infection is an independent risk factor for AVN, with incidence significantly higher than in the general population. Older protease inhibitor (PI) regimens are implicated due to their association with metabolic changes, such as hyperlipidemia and hypertriglyceridemia. These elevated fat levels may lead to fat emboli that block small blood vessels supplying the bone, causing tissue death and eventual joint collapse.
Another structural issue is HIV-associated lipodystrophy, an abnormal redistribution of body fat linked to older ART. Lipoatrophy, the loss of subcutaneous fat in the arms, legs, and buttocks, can affect biomechanics and cushioning in the lower limbs. For instance, the loss of the natural fat pad under the heel removes the foot’s shock absorber, predisposing individuals to plantar fasciitis and causing pain, particularly with the first steps after rest.
Diagnosis and Pain Management Strategies
Accurately diagnosing HIV-related leg pain requires a comprehensive evaluation, starting with a physical exam and a detailed history of the pain and medication regimen. Diagnostic workups distinguish between nerve damage, joint inflammation, or structural bone issues, often involving imaging studies like Magnetic Resonance Imaging (MRI) to detect Avascular Necrosis. Achieving and maintaining optimal viral suppression through effective ART is foundational, as reducing viral load and chronic inflammation can prevent or alleviate many pain syndromes.
Management strategies are tailored to the specific type of pain identified. For musculoskeletal pain resulting from inflammation, first-line pharmacological options include nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen. Neuropathic pain often responds poorly to traditional pain relievers and requires specific treatments like the anti-convulsant medications gabapentin or pregabalin, which act on nerve signaling pathways to reduce symptoms.
Topical treatments, such as the high-concentration capsaicin patch, are effective for localized neuropathic pain in the feet. Beyond medication, non-pharmacological interventions are recommended, with physical therapy playing a major role in improving strength, gait, and mobility. Cognitive Behavioral Therapy (CBT) is an additional tool that helps individuals develop self-management strategies and coping skills for chronic pain.