Neurologic disease burden in treated HIV/AIDS predicts survival: a population-based study

Abstract

Background: Combination antiretroviral therapy (cART) has improved the survival of patients with HIV/AIDS but its impact remains uncertain on the changing prevalence and incidence of neurologic disorders with ensuing effects on mortality.

Methods: The prevalence and incidence of neurologic disorders were examined in patients receiving active care in a regional HIV care program from 1998 to 2008. The mortality hazard ratio (HR) was calculated by Cox proportional hazard models with adjustment for demographic and clinical variables.

Results: Of 1,651 HIV-infected patients assessed, 404 (24.5%) were identified as having one or more neurologic disorders, while 41% of AIDS-affected persons exhibited neurologic disease. Symptomatic distal sensory polyneuropathy (DSP, 10.0%) and HIV-associated neurocognitive disorder (HAND, 6.2%) represented the most prevalent disorders among 53 recognized neurologic disorders. Patients with at least one neurologic disorder exhibited higher mortality rates (17.6% vs 8.0%, p < 0.0001), particularly AIDS-related deaths (9.7% vs 3.2%, p < 0.0001), compared with those without neurologic disorders. The highest mortality HR was associated with opportunistic infections of CNS (HR 5.3, 95% confidence interval [CI] 2.5-11.2), followed by HAND (HR 3.1, 95% CI 1.8-5.3) and the presence of any neurologic disorder (HR 2.0, 95% CI 1.2-3.2). The risk of AIDS-related death with a neurologic disorder was increased by 13.3% per 100 cells/mm(3) decrement in blood CD4+ T-cell levels or by 39% per 10-fold increment in plasma viral load.

Conclusions: The burden and type of HIV-related neurologic disease have evolved over the past decade and despite the availability of cART, neurologic disorders occur frequently and predict an increased risk of death.

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Figure 1 Prevalence and incidence of neurologic diagnoses (A) There were 8 major neurologic disorders that presented in more than 5% (>20 patients) among 404 patients with at least one neurologic diagnosis. The most prevalent neurologic disorder in HIV-infected patients (filled box) was symptomatic distal sensory polyneuropathy (DSP, 10.0%), followed by HIV-associated neurocognitive disorders (HAND, 6.2%). A subset of AIDS-defined patients (open box) exhibited higher prevalences of DSP, HAND, seizures/epilepsy, and CNS opportunistic infection (CNS-OI). (B) Almost half of HIV-infected patients with neurologic disorders (45.7%) showed multiple neurologic disorders. Patients with AIDS had a similar trend in the number of neurologic diagnoses but with more patients manifesting 1 to 3 neurologic disorders. (C) From 1998 to 2007, the incidence of the first neurologic diagnosis declined from 122 to 57 per 1,000 active-care patients (χ2 test, p < 0.05). (D) Although the incidence of DSP or HAND as a first neurologic diagnosis was lower in 2007 compared to 1998 (χ2 test, p < 0.05), there was no change in the incidence of other major neurologic disorders, including mononeuropathy, seizures/epilepsy, and CNS-OI.

Figure 2 Prevalence of neurologic disorders based on immunologic or virologic status (A, B) Univariate analyses of prevalence showed that the risks of distal sensory polyneuropathy (DSP), HIV-associated neurocognitive disorders (HAND), movement disorders, seizure, and CNS opportunistic infection (CNS-OI) were greater among persons with baseline and nadir CD4+ T-cell levels below 200 cells/mm3. (C) Low baseline CD8+ T-cell levels were also associated with higher prevalence of HAND and CNS-OI. (D) The prevalence of DSP and HAND was higher in patients with plasma viral load greater than 10,000 copies/mL (χ2 test, *p < 0.05). In contrast to other neurologic disorders, prevalence of mononeuropathy and headache/migraine was not associated with immunologic and virologic variables.

Figure 3 Cox survival curves in HIV-infected persons with or without neurologic disorders (A) The survival plot obtained by removing the presence of neurologic disorder as a covariate from the model and using it to stratify the survival function showed that patients with at least one neurologic disorder (Neuro) exhibited lower survival times than patients without a neurologic disorder (Non-Neuro). The survival plot was stratified by the presence or absence of (B) HIV-associated neurocognitive disorders (HAND) or (C) opportunistic infection of CNS (CNS-OI). The lower survival time was more evident in patients with HAND or patients who had a history of CNS-OI. All survival plots were estimated at the mean of all covariates including age at HIV diagnosis, gender, ethnicity, HIV risk factors, baseline CD4+ T cells, baseline CD8+ T cells, and baseline viral load.