Peripheral neuropathy (PN) is a condition resulting from damage to the nerves located outside the brain and spinal cord. This damage interferes with the communication pathway between the central nervous system and the rest of the body, leading to symptoms affecting sensation, movement, and organ function. The link between PN and Human Immunodeficiency Virus (HIV) infection is important, particularly regarding whether this nerve damage can be a sign of early infection. Assessing its meaning requires understanding the different stages and causes of PN.
Defining Peripheral Neuropathy and Common Causes
Peripheral neuropathy is categorized by the type of nerve fiber affected: sensory, motor, or autonomic. Sensory neuropathy involves nerves that transmit feelings like touch, pain, and temperature, often resulting in numbness, tingling, or a burning sensation, usually starting in the hands and feet. Motor neuropathy affects nerves controlling muscle movement, leading to weakness, cramps, or loss of coordination. Autonomic neuropathy targets nerves regulating involuntary functions such as heart rate, digestion, and bladder control.
PN is a widespread condition with numerous causes, making it a non-specific symptom not exclusive to HIV infection. The most common cause is diabetes, where high blood sugar levels damage nerve fibers over time. Other frequent causes include:
- Chronic alcohol consumption.
- Nutritional deficiencies, especially a lack of vitamin B12.
- Exposure to various toxins.
- Autoimmune disorders like lupus and rheumatoid arthritis.
- Kidney or liver disease.
- Side effects of certain medications, such as some chemotherapy drugs.
The Timing of Neuropathy in HIV Infection
Whether peripheral neuropathy is an early sign of HIV infection is complex, but in most cases, it is not. Neurological symptoms can occur during the acute phase of HIV, the period immediately following infection often called seroconversion. Rare case reports describe forms of neuropathy, such as facial nerve palsy or acute inflammatory demyelinating polyneuropathy (similar to Guillain-Barré Syndrome), appearing around seroconversion.
The most common form associated with the virus itself is Distal Symmetric Polyneuropathy (DSPN). DSPN typically manifests much later, when the immune system is significantly compromised, such as when the CD4 cell count drops below 200 cells/mm³ or in individuals with long-standing, untreated infection. This form is a symptom of advanced or chronic HIV, not an early indicator. While one study found signs of subclinical PN in 35% of individuals within the first year of primary infection, the development of noticeable and debilitating DSPN symptoms caused by the virus is more common in the chronic phase. New-onset neuropathy is far more likely to be due to common causes like diabetes or vitamin deficiency than acute HIV infection.
Distinct Mechanisms of HIV-Associated Nerve Damage
HIV-associated nerve damage occurs through two main mechanisms: immune-mediated injury and medication-induced toxicity. The first mechanism is linked to the presence of the virus and the resulting chronic inflammation, which leads to the development of HIV-DSPN. Infected immune cells, such as macrophages, release inflammatory mediators.
These inflammatory proteins and chemokines, along with viral components like the envelope protein gp120, are neurotoxic to the peripheral nerves. This chronic inflammatory environment causes a “dying-back” degeneration of the longest nerve fibers, explaining why symptoms often start in the feet. This damage to the sensory nerves is primarily an axonal degeneration, leading to the characteristic pain, numbness, and tingling of DSPN.
The second major mechanism is Antiretroviral Toxic Neuropathy (ATN), which results from the side effects of specific antiretroviral medications. This type of damage was historically common with older nucleoside reverse transcriptase inhibitors (NRTIs), particularly stavudine (d4T), didanosine (ddI), and zalcitabine (ddC), often referred to as “d-drugs.” These medications could cause mitochondrial dysfunction in nerve cells, essentially starving them of energy. While modern Antiretroviral Therapy (ART) regimens rarely include these neurotoxic drugs, ATN remains a possibility for individuals still on older treatment plans.
Diagnosis and Management of HIV-Related Peripheral Neuropathy
When peripheral neuropathy is suspected in an individual with HIV, or someone at risk, the first step is a thorough clinical evaluation to rule out other common causes. Blood tests are routinely performed to check for nutritional deficiencies, such as low vitamin B12 levels, and to screen for metabolic conditions like diabetes or thyroid disorders. An accurate HIV status is confirmed through testing, and if the patient is already diagnosed, their current ART regimen is reviewed to identify any potentially neurotoxic medications.
Diagnosis of the specific type of neuropathy can be supported by nerve conduction studies, which measure the electrical signaling of the nerves, and sometimes by a skin biopsy to assess the density of small nerve fibers. Management focuses on controlling the underlying cause and providing symptomatic relief for the pain. For patients on older neurotoxic ART, switching to a less toxic regimen is a primary intervention that may help alleviate symptoms.
Sustained suppression of the viral load with effective ART is also helpful in managing the virus-related DSPN. For pain relief, standard medications for neuropathic pain are used, including:
- Certain anti-seizure medications like gabapentinoids.
- Tricyclic antidepressants.
- Serotonin-norepinephrine reuptake inhibitors (SNRIs).
- Topical treatments, such as capsaicin patches, for localized relief.