The quality of evidence (I-III) is defined at the end of the "Major Recommendations" field.
Human Immunodeficiency Virus (HIV)-Associated Dementia (HAD)
When patients with HAD present with accompanying depression, mania, psychosis, behavioral disturbance, or substance use, primary care clinicians should refer for psychiatric consultation to assist in psychopharmacologic treatment and management. (I)
Clinicians should use standardized tools to stage HAD. (III)
Key Point:
Psychiatric consultation may assist in differentiating between HAD and pseudodementia, and between HAD and cognitive impairment due to mania, psychosis, delirium, substance use, or psychotropic or HIV-related medications. Neuropsychological testing may also be helpful with diagnostic assessment.
Key Point:
The early signs and symptoms of HAD are often subtle and difficult to recognize.
Refer to Table 1 in the original guideline document for information on clinical manifestations of HIV-associated dementia.
Diagnosis
The following tests should be performed to exclude other possible etiologies of cognitive dysfunction: (III)
- Vitamin B12 and folate levels
- Serum syphilis screen (rapid plasma reagin [RPR] or venereal disease research laboratory [VDRL] test)
- Serum cryptococcal antigen
- Thyroid function tests
Cerebrospinal fluid testing to exclude other central nervous system infections that may cause cognitive dysfunction, such as neurosyphilis, cytomegalovirus encephalitis, tuberculous meningitis, and cryptococcal meningitis, should be performed when clinically indicated. (I)
Clinicians should obtain neuroimaging in patients with cognitive dysfunction. (I)
Clinicians should refer patients to a neuropsychologist for detailed neuropsychological evaluation when the presentation is not typical and differentiation from pseudodementia secondary to depression is necessary. (I)
Key Point:
Early-stage HAD differs from Alzheimer's disease in that it is more likely to present with behavioral changes, progresses more rapidly, may be associated with abnormal cerebrospinal fluid (CSF) findings, and is rarely associated with aphasia.
Treatment
When patients receiving highly active antiretroviral therapy (HAART) present with symptoms of HAD, clinicians should assess the efficacy of the HAART regimen. (III)
When patients not receiving HAART present with symptoms of HAD, clinicians should initiate HAART (III)
HIV-Associated Myelopathy
Key Point:
HIV-associated myelopathy should be part of the differential diagnosis in men with erectile dysfunction, especially in the setting of normal testosterone levels.
Diagnosis
In the differential diagnosis for HIV-associated myelopathy, clinicians should exclude other treatable conditions that could cause spinal cord disease, particularly compressive lesions and other infectious or neoplastic etiologies. (I)
Clinicians should obtain the following blood tests in patients with suspected HIV-associated myelopathy: (I)
- Serum RPR or VDRL
- Toxoplasma antibodies
- Cryptococcal antigen
- Vitamin B12 level
- Human T-lymphocyte virus (HTLV) I/II antibodies
Clinicians should obtain neuroimaging studies of the spinal cord in all patients who present with suspected spinal cord disease. (I)
Treatment
Clinicians should prescribe symptomatic therapy to patients with HIV-associated myelopathy. (I)
Key Point:
The effect of HAART on improving the symptoms or slowing the progression of HIV-associated myelopathy is not known.
Peripheral Neuropathy
Distal Symmetric Polyneuropathy (DSP)
Diagnosis
Clinicians should obtain blood tests to screen for diabetes and vitamin B12 deficiency in the evaluation of a patient with suspected distal symmetric polyneuropathy. (III)
Clinicians should refer patients with more complex suspected or proven peripheral neuropathy syndromes to a neurologist to assist with the diagnosis and management. (III)
Key Point:
Electrophysiologic studies are of great value in diagnosing more complex non-DSP neuropathy in HIV-infected patients.
Treatment and Management
Clinicians should provide pain control for distal symmetric polyneuropathy, (I) which is achieved by a careful, systematic, and stepwise evaluation of the patient's response to available analgesic agents (see Figure 2 in the original guideline document).
Clinicians should initiate mild analgesics, including acetaminophen, aspirin, or other non-steroidal anti-inflammatory agents, with or without adjunctive agents (e.g., anticonvulsants, antidepressants, topical agents), as the first line of therapy for pain control. (I)
Clinicians should use narcotic analgesia when pain control is not achieved by first line and adjunctive measures. (I)
Clinicians should refer patients to a pain management specialist when adequate pain control cannot be achieved. (I)
In cases of ARV therapy-associated DSP, the decision to discontinue a neurotoxic antiretroviral (ARV) drug is not automatic and should only be made after carefully weighing the risks and benefits of virologic control versus neuropathic symptom control. (III)
Inflammatory Demyelinating Polyneuropathy (IDP)
Diagnosis
Clinicians should perform lumbar puncture and electromyography/nerve conduction velocities (EMG/NCV) in patients with suspected IDP. (III)
Key Point:
Inflammatory demyelinating polyneuropathy should be part of the differential diagnosis in HIV-infected patients presenting with progressive muscle weakness.
Treatment
Clinicians should initiate immunomodulating therapy, such as corticosteroids, high-dose intravenous immunoglobulin (2.0 gm/kg divided over 2 to 5 days), or plasmapheresis (4-5 exchanges), for patients with HIV-associated IDP. (I)
When IDP is associated with symptomatic hyperlactatemia or lactic acidosis, clinicians should immediately discontinue ARV therapy, especially nucleoside reverse transcriptase inhibitors (NRTIs). (I)
Mononeuropathy Multiplex (MM)
Diagnosis
Clinicians should establish the diagnosis and etiology of mononeuritis multiplex based on neurologic consultation, electrophysiologic studies, and/or nerve biopsy. (III)
Key Point:
Mononeuritis multiplex should be part of the differential diagnosis in HIV-infected patients presenting with asymmetric multifocal motor and sensory nerve abnormalities. Other etiologies, such as hepatitis B, may cause vasculitic mononeuropathy multiplex and should also be considered in the differential diagnosis.
Treatment
Clinicians should observe patients with early-onset MM because it may spontaneously resolve within weeks to several months. (III)
Clinicians should initiate HAART in patients with late-onset MM occurring in advanced HIV infection. (I)
Key Point:
Empiric therapy for cytomegalovirus (CMV) should be considered for patients with late-onset MM, particularly if CSF or nerve biopsy is revealing of CMV infection. However, there is no sufficient data to make any conclusive recommendation.
Progressive Polyradiculopathy (PP)
Diagnosis
Clinicians should establish the diagnosis of progressive polyradiculopathy based on neurologic consultation, spinal MRI, CSF analysis, and electrophysiologic studies. (III)
Key Point:
The severe and widespread proximal axonal pathology in lumbar nerve root segments help differentiate progressive polyradiculopathy from mononeuropathy multiplex or inflammatory demyelinating polyneuropathy.
Treatment
Clinicians should promptly initiate anti-CMV therapy for improvement of symptoms and/or stabilization of signs in progressive polyradiculopathy secondary to CMV. (II)
Clinicians should initiate or optimize HAART in patients with progressive polyradiculopathy. (I)
Myopathy
Diagnosis
Clinicians should use creatine phosphokinase (CPK) determinations combined with EMG and/or muscle biopsy to confirm the diagnosis of HIV-associated myopathy. (III)
Clinicians should consider referring patients to a neurologist or rheumatologist to confirm and manage HIV-associated myopathy. (III)
Key Point:
An isolated CPK elevation is not sufficient to make a diagnosis of myopathy without accompanying clinical features because CPK levels may be elevated from other causes.
HIV-Associated Neuromuscular Weakness Syndrome (HANWS)
Diagnosis
Clinicians should exclude other possible causes of weakness by performing a complete neurologic examination and obtaining blood tests. (III)
Clinicians should consult with a neurologist for evaluation and management of patients with suspected HANWS. (III)
Treatment
Clinicians should discontinue the use of NRTIs in patients with HANWS. (I)
For patients with HANWS, clinicians should initiate systemic treatment for lactic acidosis syndrome and supportive treatment for the neurologic component in a monitored setting. (I)
Definitions:
Quality of Evidence for Recommendation
- Evidence from one or more properly randomized, controlled trial
- Evidence from one or more well-designed clinical trial without randomization; from cohort or case-controlled studies
- Evidence from opinions of respected authorities based on clinical experience, descriptive studies, or reports of expert committees