Alzheimer's disease neuropathology may not predict functional impairment in HIV: a report of two individuals.

With aging of HIV populations, there is concern that Alzheimer's disease (AD) may become prevalent and difficult to distinguish from HIV-associated neurocognitive disorders. To date, there are no reports documenting histologically verified Alzheimer's neuropathology in individuals with HIV and dementia. Herein, we report two antiretroviral-treated, virally suppressed, HIV-infected individuals autopsied by the Manhattan HIV Brain Bank. Subject A presented to study at 52 years, already dependent in instrumental activities of daily living (ADLs), with severe cognitive impairment inclusive of learning and memory dysfunction. Her history was significant for educational disability and head trauma. She had rapid cognitive decline and, by death at age 59 years, was bed-bound, incontinent, and non-communicative. At autopsy, she exhibited severe AD neuropathologic change (NIA-AA score A3B3C3) and age-related tau astrogliopathy (ARTAG). She was homozygous for APOE ε3/ε3. No HIV DNA was detected in frontal lobe by nested polymerase chain reaction. Subject B was a community dwelling 81-year-old woman who experienced sudden death by pulmonary embolus. Prior to death, she was fully functional, living independently, and managing all ADLs. At autopsy, she displayed moderate amyloid and severe tau AD neuropathologic changes (A2B3C2), ARTAG, and cerebral congophilic angiopathy. She was an APOE ε3/ε4 heterozygote, and HIV DNA, but not RNA, was detected in frontal lobe, despite 20 years of therapy-induced viral suppression. We conclude that in the setting of HIV, AD neuropathology may occur with or without symptomatic cognitive dysfunction; as with seronegative individuals, there are likely to be complex factors in the generation of clinically relevant impairments.

Isolating cognitive and neurologic HIV effects in substance-dependent, confounded cohorts: a pilot study.

Controversy exists as to whether effects of HIV infection can be detected in the cognitive profiles of substance users, with methodological differences in degree of control for confounding factors a major contributor to empirical discrepancies. To address this shortcoming, we conducted a small but well-controlled study aimed at isolating HIV neurocognitive (NC) effects in a group of chronic substance users. Thirty HIV-negative substance users were individually matched to 30 HIV-positive substance users on relevant medical and demographic factors, including reading level and methadone therapy status. Results revealed that reading level, methadone maintenance therapy, and positive urine toxicology each exerted significant influence on NC function, and that HIV status was a significant predictor of learning and speeded processing after these control factors were considered. The HIV-positive group also displayed significantly more neurologically assessed motor impairment (p < .05), which was specifically related to impaired cognition in this group and independent of degree of immunocompromise. These data demonstrate the need for increased attention to clinical/demographic characteristics of groups under study. They also show that with applied methodological rigor, the deleterious effects of HIV on cognition can be parsed from substance use, even in small samples with chronic and active use histories.

Controlling neuropathic pain in HIV.

Neuropathic pain is associated with numerous systemic illnesses, including HIV infection. The diagnosis and management of peripheral neuropathy presents diagnostic and therapeutic challenges. Among various forms of HIV-associated peripheral neuropathies, distal symmetrical polyneuropathy (DSP) is the most common. DSP may be caused or exacerbated by neurotoxic antiretrovirals, particularly the dideoxynucleoside analogues (d-drugs). Selection of appropriate pharmacologic intervention for peripheral neuropathy should be based on efficacy, safety, ease of administration, and cost. We review treatment options for painful HIV neuropathy, including experimental agents studied in recent and ongoing clinical trials.

Controlling Neuropathic Pain in HIV.

Neuropathic pain is associated with numerous systemic illnesses, including HIV infection. The diagnosis and management of peripheral neuropathy presents diagnostic and therapeutic challenges. Among various forms of HIV-associated peripheral neuropathies, distal symmetrical polyneuropathy (DSP) is the most common. DSP may be caused or exacerbated by neurotoxic antiretrovirals, particularly the dideoxynucleoside analogues (d-drugs). Selection of appropriate pharmacologic intervention for peripheral neuropathy should be based on efficacy, safety, ease of administration, and cost. We review treatment options for painful HIV neuropathy, including experimental agents studied in recent and ongoing clinical trials.