A 46-year-old man comes to the office for follow-up. The patient was diagnosed with HIV 10 years ago and has had episodes of pneumocystis pneumonia, cryptococcal meningitis, and oropharyngeal candidiasis. He has been treated with several different antiretroviral combinations due to drug resistance from medication nonadherence. Over the past year, he notes a sensation of numbness and pinpricks in his feet, which has now progressed proximally up his lower legs. Vital signs are within normal limits. There is loss of sensation to touch, pain, and temperature over the distal legs and feet bilaterally. Motor strength is intact, but ankle jerk reflex is decreased bilaterally. Cranial nerve examination is normal, and there are no signs of meningeal irritation. Blood cell counts, liver and renal function tests, and fasting plasma glucose are within normal limits. CD4 count is 180/mm³. In addition to counseling about the importance of adherence to antiretroviral therapy, which of the following is the most appropriate treatment for this patient's current symptoms?

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11ec25c8_d562_9fec_bc81_6593261c4d86_MD0003_00 Bilateral distal extremity numbness/pain with loss of sensation and loss of ankle jerk reflex is consistent with distal symmetrical polyneuropathy. In this patient with long-standing HIV and a low CD4 count, this presentation is most likely due to HIV neuropathy, particularly given his laboratory results that make other common causes of distal symmetrical polyneuropathy unlikely (eg, diabetic neuropathy [normal fasting glucose level], uremic polyneuropathy [normal renal function], vitamin B₁₂ deficiency [no anemia]). Although the exact mechanism is unclear, HIV neuropathy is thought to occur due to the accumulation of HIV antigens (eg, gp120) on distal sensory nerve fibers, which triggers macrophage/T-cell infiltration, cytokine release, and subsequent axonal damage. The risk is greatest in older patients with long-standing HIV, particularly those who have high viral loads, low CD4 counts, and a history of exposure to neurotoxic antiretroviral medications (eg, didanosine, stavudine). Manifestations generally begin insidiously with numbness, tingling, and a pinprick sensation/burning pain in the bilateral toes/feet; this progresses proximally over time. Examination shows loss of sensation and diminished ankle jerk reflex. Because motor neurons are relatively spared, motor strength is usually intact. Treatment with antiretroviral therapy reduces the risk of progression. Gabapentin is first-line to help reduce sensory symptoms (eg, dysesthesias, neuropathic pain); serotonin-norepinephrine reuptake inhibitors (eg, duloxetine, venlafaxine) can also be used. (Choice A) Opioid medications (eg, acetaminophen-hydrocodone) have an unclear benefit for neuropathic pain and a high risk of abuse/misuse/addiction. Therefore, they are typically reserved for patients whose condition is not adequately managed with gabapentin, antidepressants (eg, nortriptyline, venlafaxine), and/or topical capsaicin. (Choice C) Lamotrigine is sometimes used to treat neuropathic facial pain due to a CNS lesion. However, it does not improve peripheral neuropathy in patients with HIV. (Choice D) Magnesium supplementation is occasionally administered with platinum-based chemotherapy (eg, cisplatin) to prevent chemotherapy-associated neuropathy, but more recent studies indicate no benefit. It is not commonly used in HIV neuropathy. (Choice E) Prednisone is sometimes used to treat neuropathic pain in cancer patients. However, it is not a primary treatment in patients with HIV neuropathy due to its limited efficacy and increased risk of immunosuppression. Educational objective: HIV neuropathy is a distal, symmetrical polyneuropathy that typically begins with numbness/tingling/pain in the feet and progresses proximally. Older patients with long-standing, poorly controlled HIV are at greatest risk. Antiretroviral treatment reduces the risk of progression. Gabapentin is first-line for symptomatic management.

A 46-Year-Old Man Comes to the Office for Follow-Up