Neurocognitive impairment and survival in a cohort of HIV-infected patients treated with HAART.

Before the introduction of HAART, HIV-associated neurocognitive impairment (NCI) was recognized as an independent risk factor for death. Since 1996, we conducted a prospective study to assess whether NCI still represents a negative prognostic factor for mortality. Patients were administered measures of neurocognitive function (a battery of 17 neuropsychological tests), clinical and neurological evaluation, laboratory testing, and brain imaging studies. Among the 412 enrolled patients, 224 (54.4%) were neurocognitively impaired and 188 (45.6%) were neurocognitively unimpaired. A durable virological suppression under highly active antiretroviral therapy (HAART) was achieved by 63.3% of unimpaired patients and by 49.6% of impaired patients (p = 0.007). Overall, 47 deaths were recorded, 38 among impaired and 9 among unimpaired patients. At 84 months, the estimated survival proportions in impaired and unimpaired patients were 68.5% and 84.9%, respectively (p < 0.001). At univariate analysis the virological response to HAART was the variable most strongly associated with survival, since patients with virological failure had a nearly 10-fold increased risk of death than those with durable virological suppression (HR = 9.9, 95% CI: 3.9-25.0). After stratification for virological response to HAART, an increased risk of death for neurocognitively impaired patients was seen only among the 182 patients with virological failure (HR: 2.9, 95% CI: 1.2-7.1), while the survival probability of the 230 patients with durable virological suppression was not affected by neurocognitive impairment (p = 0.89). Our results highlight the clinical relevance of HIV-related central nervous system (CNS) involvement in the HAART era, and raise concerns regarding the clinical relevance of CNS involvement as potent antiretroviral therapies become less effective.

Neurocognitive performance and quality of life in patients with HIV infection.

We examined the relationship of HIV-related cognitive impairment and health-related quality of life (QoL). Subjects were administered measures of cognitive function (a battery of 17 neuropsychological tests) and of QoL (the MOS-HIV questionnaire). Study measures also included comprehensive clinical and neurological evaluation, laboratory testing, and brain imaging studies in patients with impaired neuropsychological evaluation. One-hundred and eleven subjects were examined. Cognitively impaired patients (33.3%) reported poorer QoL scores in all domains (p < 0.05): physical health summary score (PHS) (44.6 vs. 49.9), mental health summary score (MHS) (37.7 vs. 44.4), pain (67.6 vs. 79.4), physical functioning (75.9 vs. 87.7), role functioning (32.4 vs. 41.5), social functioning (70.3 vs. 83.5), mental health (48.2 vs. 61.0), energy (53.1 vs. 63.0), health distress (60.8 vs. 75.5), cognitive functioning (CF) (60.5 vs. 71.8), general health perceptions (29.2 vs. 43.4), and QoL (36.5 vs. 47.0). The number of altered neuropsychological tests correlated significantly with MHS (p < 0.001), PHS (p < 0.03), CF (p < 0.02), and QoL (p < 0.02) scores. A correlation between seven of seven neuropsychological measures exploring speed of mental processing, three of four exploring mental flexibility, four of six exploring memory, and two of two exploring fine motor functioning and MHS, PHS, CF, or QoL scores was also found. Poor performance on the Digit Symbol test was most strongly associated with poor MHS (OR 1.04, 95% CI 1.01-1.08, p < 0.009) and PHS (OR 1.04, 95% CI 1.01-1.08, p < 0.01) scores, controlling for CD4 count, previous AIDS diagnosis, receiving HAART, and drug abuse. Cognitive impairment is associated with poor QoL. People with more severe cognitive impairment have the highest probability of having a poor QoL. Cognitive impairment in any cognitive domain explored in our battery is also associated with poor QoL. Poor performance on the Digit Symbol Test is the strongest predictor of poor QoL.

Changes in cognition during antiretroviral therapy: comparison of 2 different ranking systems to measure antiretroviral drug efficacy on HIV-associated neurocognitive disorders.

OBJECTIVE: Although HIV-associated neurocognitive disorders should be treated with highly active antiretroviral treatment (HAART) regimens with good central nervous system (CNS) penetration, the definition of neuroactive HAART remains controversial. We compared 2 ranking systems to measure HAART neuroeffectiveness. METHODS: Patients with (n = 93) or at risk for (n = 92) HIV-associated neurocognitive disorders underwent neuropsychological (NP) test batteries before HAART initiation and at follow-up. Changes in normatively adjusted summary NP test z scores were calculated for each subject. Two neuropenetration scores were calculated: the central nervous system penetration reference score (number of drugs in the combination among zidovudine, abacavir, stavudine, lamivudine, efavirenz, nevirapine, indinavir, and lopinavir-ritonavir) and the CNS penetration-effectiveness (CPE) score: a summary score of 1 (high: penetration: [corrected] zidovudine, abacavir, delavirdine, [corrected] nevirapine, amprenavir-ritonavir, fosamprenavir-ritonavir, [corrected] indinavir-ritonavir, and lopinavir-ritonavir), 0.5 (intermediate penetration: [corrected] stavudine, lamivudine, emtricitabine, efavirenz, amprenavir, fosamprenavir, [corrected] atazanavir-ritonavir, atazanavir, [corrected] and indinavir), and 0 (low penetration: remaining ARVs) [corrected] for each drug in the combination. Main outcome measures were changes in global NPZ scores and in summary z scores on 5 domains. RESULTS: At regression analyses, higher CPE scores correlated with greater improvements in NPZ-4 (P = 0.0283), NPZ-8 (P = 0.0071), concentration and speed of mental processing (P = 0.0046), and mental flexibility (P = 0.0262) summary z scores. The correlation was stronger among NP-impaired patients. By contrast, higher estimates of neuroeffectiveness with the alternative system showed no correlation. No association was seen between CD4 and plasma viral load changes with both scores. CONCLUSIONS: The CPE score represents a step forward toward the identification of a clinically useful approach to estimating HAART ability to improve cognition.

Immediate versus delayed surgical intervention for reconstructive therapy of HIV-associated facial lipoatrophy: a randomized open-label study.

We assessed the safety and efficacy of reconstructive therapy with facial fillers for the treatment of HIV-associated facial lipoatrophy (FLA) through a randomized, controlled, open-label single-center study. A total of 134 HIV-infected patients with severe FLA were randomly assigned to receive immediate (67 patients) or delayed (67 patients) facial injections of poly-l-lactic acid (PLA) or polyacrylamide gel (PAIG). Outcome measures included changes in physician and patient FLA severity scale, adverse events, and changes in health-related quality of life (HRQoL) and anxiety using validated measures. The mean average study follow-up was 27 weeks for the immediate and 25 weeks for the delayed subjects. Adverse events were mild and resolved after a mean of 4 days. Compared to patients randomized to the delayed treatment group, patients assigned to the immediate treatment group had significantly lower physician-rated (0.0 versus -3.0; p < 0.0001) and patient-rated (0.1 versus -1.8; p < 0.0001) FLA severity scores. By contrast, measures exploring HRQoL and anxiety did not show any significant difference between patients randomized to the immediate and deferred groups. Reconstructive therapy with facial fillers was effective and safe and led to significant improvements in FLA severity. However, no significant gains in HRQoL, relational and psychological consequences of body changes, and anxiety-related concerns were observed. Studies should be performed to identify patients who could maximally benefit from filling interventions for FLA.

Persistence of neuropsychologic deficits despite long-term highly active antiretroviral therapy in patients with HIV-related neurocognitive impairment: prevalence and risk factors.

OBJECTIVE: Although highly active antiretroviral therapy (HAART) can reverse HIV-related neurocognitive impairment (NCI), neuropsychologic (NP) deficits may persist in a substantial proportion of patients despite antiretroviral treatment. We assessed the prevalence and predictors of persistent NP deficits despite long-term HAART in patients with HIV-related NCI. METHODS: A group of 94 patients with HIV-related NCI underwent 2 to 7 serial NP batteries, neurologic examination, and brain imaging studies. Patients received HAART for a mean of 63 (range: 6-127) months. According to NP assessment results, patients were considered to have reversible or persistent NP deficits. Kaplan-Meier analyses and Cox proportional hazards models were used to analyze time to first evidence of NP deficit reversion. RESULTS: Persistent NP deficits were observed in 59 (62.8%) patients. Age, gender, Centers for Disease Control and Prevention stage, risk category, CD4 cell count, plasma viral load, and use of central nervous system-penetrating drugs were not associated with persistent NP deficits. By contrast, patients with persistent NP deficits were less educated and showed poorer baseline performances in NP measures exploring concentration and speed of mental processing, memory, and mental flexibility. In multivariable analyses, only the baseline severity of NCI, as measured by the composite NPZ8 global score (odds ratio = 3.07, 95% confidence interval: 1.54 to 6.08; P = 0.001) remained significantly associated with persistent NP deficits. CONCLUSIONS: The severity of NCI at HAART initiation seems to be the strongest predictor of persistent NP deficits despite long-term HAART. Our data indicate that HAART should be initiated as soon as NCI is diagnosed to avoid potentially irreversible neurologic damage.

Prevalence and risk factors for human immunodeficiency virus-associated neurocognitive impairment, 1996 to 2002: results from an urban observational cohort.

To assess prevalence and risk factors for human immunodeficiency virus (HIV)-related neurocognitive impairment (NCI), the authors performed a 7-year survey in the period 1996 to 2002. A total of 432 patients were examined. HIV-related NCI was diagnosed in 238 patients (55.1%), meeting the HIV dementia (HIV-D) criteria in 45 (10.4%). The prevalence of both NCI and HIV-D did not change significantly during the study period. Compared with patients without NCI, patients with NCI were older (40.4 versus 38.2 years; P = .003), had a higher prevalence of positive HCV serology (61.1% versus 38.9%; P = .003), and a lower nadir CD4 cell count (156 versus 222 cells/microl; P < .001). Compared with patients seen during 1996 to 1999, patients with NCI seen during 2000 to 2002 were older (40.7 versus 38.8 years; P = .004), had a less advanced disease stage (previous acquired immunodeficiency syndrome [AIDS] 28.8% versus 65.7%; P < .001) and a higher nadir CD4 count (174 versus 132 cells/microl; P = .026). This study showed an unchanged prevalence of both HIV-related NCI and HIV-D in the period 1996 to 2002. The authors found evidences for new additional potential risk factors for HIV-related NCI (older age, lower nadir CD4 count, positive hepatitis C virus [HCV] serology), and for a change of risk factors for NCI in the late highly active antiretroviral therapy (HAART) era (older age, less advanced disease, higher nadir CD4 count).