Antiretroviral therapy in HIV infection: are neurologically active drugs important?

BACKGROUND: The effect on neuropsychological function of antiretroviral drugs that are able to penetrate into the brain in effective concentration (neuroactive drugs) remains unclear. OBJECTIVE: To investigate whether highly active antiretroviral therapy (HAART) containing neuroactive drugs is associated with better neuropsychological performance in patients with human immunodeficiency virus disease. DESIGN: Cross-sectional survey. SETTING: Tertiary referral hospital outpatient clinics. PATIENTS: The study population consisted of 97 individuals positive for human immunodeficiency virus (stage C3, 1993 Centers for Disease Control and Prevention classification) whose condition had been stable on their current HAART regimen for a mean +/- SD of 18.5 +/- 16.5 months and who were aged 48.14 +/- 9.38 years. The patient groups were analyzed according to whether their regimen contained 3 or more neuroactive drugs (neuroHAART group; n = 41) or not (HAART group; n = 56). Thirty seronegative men matched for age and education were recruited as controls. MAIN OUTCOME MEASURE: Neuropsychological performance on 7 cognitive domains. RESULTS: The neuroHAART and HAART groups did not differ from one another on neuropsychological performance, but both patient groups were impaired compared with controls. Impaired patients in each treatment group were compared, and the neuroHAART group showed significantly better memory performance, unrelated to plasma viral load, than the HAART group. CONCLUSION: No direct benefit of neuroactive HAART therapy was found in patients with advanced human immunodeficiency virus infection. However, in neuropsychologically impaired patients, there was a benefit in memory function. This suggests that a threshold of neuropsychological impairment is required for the benefit of neuroactive HAART.     

Incident major depression does not affect neuropsychological functioning in HIV-infected men.

The diagnosis of lifetime major depressive disorders (MDDs) and of current major depressive episodes (MDEs) are relatively common in HIV-infected individuals, and often are assumed to influence neuropsychological (NP) performance. Although cross-sectional studies of HIV-infected individuals generally have found no systematic link between current MDE or depressive symptoms and NP performance, longitudinal studies are needed to clarify whether incident MDE may impact NP functioning in at least some cases. Two hundred twenty-seven human immunodeficiency virus (HIV)-infected adult men, who did not meet criteria for a current MDE at baseline, participated in a longitudinal NP study for an average of two years. Participants received repeated NP assessments, as well as structured psychiatric interviews to ascertain presence or absence of both lifetime MDD and current MDE. Ninety-eight participants had a lifetime history of MDD, and 23 participants met criteria for incident MDE at one of their follow-up evaluations. Groups with and without lifetime MDD and/or incident MDE had comparable demographics, HIV disease status and treatment histories at baseline, and numbers of intervening assessments between baseline and the final follow-up. Lifetime MDD was associated with greater complaints of cognitive difficulties in everyday life, and such complaints were increased at the times of incident MDE. However, detailed group comparisons revealed no NP performance differences in association with either lifetime or incident major depression. Finally, NP data from consistently nondepressed participants were used to develop "norms for change" and these findings failed to show any increased rates of NP worsening among individuals with incident MDE. Our results suggest that neurocognitive impairment and major depression should be considered as two independent processes.     

Prevalence of non-confounded HIV-associated neurocognitive impairment in the context of plasma HIV RNA suppression

HIV-associated neurocognitive disorder is known to occur in the context of successful combination antiretroviral therapy (cART; plasma HIV RNA <50 copies/ml). Here, we newly provide an analysis of its prevalence and nature in the absence of medical or psychiatric confounds that may otherwise inflate the prevalence rate. We enrolled a cohort of 116 advanced HIV + individuals on cART (51% virally suppressed (VS)). They were screened for active Hepatitis C, current substance use disorder and were assessed with standard neuropsychological (NP) testing. Our results showed that out of the entire sample, NP impairment occurred in 18.1% (21/116) in VS individuals which was not statistically different from the 24.1% (28/116) that were found to be NP-impaired and not VS. In comparison with NP-normal-VS persons, NP impairment in VS individuals was associated with shorter duration of current cART and lower pre-morbid ability. Higher cART CNS penetration effectiveness tended to be associated with lesser cognitive severity in NP-impaired VS individuals. Current CD4 cell count, depression symptoms and past CNS HIV-related diseases did not specifically account for persistent NP impairment in VS individuals. In conclusion, despite suppression of systemic viral load, non-confounded HIV-related NP-impairment prevalence reached 18.1%. Of the potential explanations for this persistent deficit, a “burnt-out” form of the disease and immune reconstitution inflammatory syndrome were the less likely explanations, while a shorter current cART duration and lower pre-morbid intellectual capacity were significant. Nonetheless, predictive modelling with these last two factors misclassified 27% and had low sensitivity (43%) emphasising that other yet-to-be-defined factors were operative.     

The role of depression chronicity and recurrence on neurocognitive dysfunctions in HIV-infected adults

Research assessing whether major depressive disorders (MDD) impacts neurocognitive functions in HIV+ persons has yielded inconsistent results. However, none have considered the role of MDD remission, chronicity, and stability on treatment. Ninety-five HIV+ adults clinically stable on combined antiretroviral treatment completed a psychiatric interview, a depression scale, a neuropsychological, daily living, and cognitive complaints assessments at baseline and 18 months. Participants were screened for current (within 12 months of study entry) alcohol and/or substance use disorder. History of alcohol and/or substance abuse disorder prior to the 12 months entry screen and MDD treatments were recorded. Participants were grouped into two psychiatric nomenclatures: (1) lifetime: no MD episode (MDE), single MDE life-event treated and fully remitted, chronic MDD treated and stable, chronic MDD treated and unstable, and baseline untreated MDE; (2) recent: last 2 years MDE (yes or no). We found that lifetime and recent psychiatric history were more strongly associated with decreased in independence in daily living and cognitive complaints than with baseline neuropsychological performance. However, lack of full remission, instability on treatment in chronic MDD, and severity of symptoms in current MDE were factors in whether MDD impacted baseline neuropsychological performance. Depressive symptoms improved at follow-up in those with baseline moderate-severe symptoms, and MDD was not associated with neurocognitive change at 18 months. A history of alcohol and/or substance abuse disorder was significantly more frequent in those with treated and unstable chronic MDD but it was not associated with neuropsychological performance. MDD recurrence, chronicity profiles, and associated comorbidities are keys factors to understand any potential impact on neurocognitive abilities in HIV infection. More comprehensive consideration of these complex effects could serve at constructively updating the HAND diagnostic criteria.     

Variable benefit in neuropsychological function in HIV-infected HAART-treated patients

The authors examined cognitive performance change in 101 individuals with advanced HIV infection on highly active antiretroviral therapy (HAART), using standard neuropsychological testing in three visits, over a 27-month-period. Cognitive performance stabilized in a majority of HIV+ participants over time. A neuroactive HAART regimen was associated with neuropsychological improvement. Decline occurred in a minority with lower nadir CD4. The current CD4 count and plasma viral load were not associated with cognitive change.     

203例农村有偿献血感染HIV患者抑郁障碍及生活质量调查

目的：调查通过献血途径感染人类免疫缺陷病毒（HIV）的203例患者的情绪状况及生活质量。方法：采用贝克抑郁问卷、复合性国际诊断用检查提纲和SF-36对203例通过献血途径感染HIV的患者（HIV阳性组）及年龄、性别和受教育年限相匹配的198例HIV阴性献血者进行调查。结果：①HIV阳性组献血次数多于HIV阴性组（52．2&#177;95．4／13．2&#177;23．9，P〈0．001），已婚者少于HIV阴性组（88．6％／95．5％，P=0．020），丧偶者多于HIV阴性组（10．9％／4．5％，P=0．020），失业率高于HIV阴性组（21．7％／4．0％，P〈0．001），前一年全年工作时间少于HIV阴性组（5．0&#177;3．5／7．5&#177;3．0，P〈0．001），家庭月收入低于HIV阴性组（476．3&#177;412．7／709．9&#177;513．7，P〈0．001）。②HIV阳性组被诊断为获得性免疫缺陷综合征（AIDS）者占56．6％。HIV阳性组抑郁症的终生患病率为13．8％，HIV阴性组的终生患病率为5．1％。HIV阳性组的抑郁总分（11．3&#177;11．3／6．6&#177;9．6）、躯体（3．3&#177;2．9／2．0&#177;2．6）和非躯体因子分（8．0&#177;8．8／4．6&#177;7．4）均高于HIV阴性组（P〈0．001）。HIV阳性组达轻度抑郁以上者占40．4％。HIV阳性组已制定自杀计划者高于HIV阴性组（8．4％／3．0％，P〈0．05）。HIV阳性组总体生理健康（48．3&#177;9．7／55．5&#177;7．0）和心理健康（48．8&#177;-8．9／55．1&#177;7．8）得分均低于HIV阴性组（P〈0．001）。③HIV阳性组的贝克抑郁问卷总分与T细胞亚群CD4细胞计数无显著相关，与总体生理健康及心理健康呈显著负相关（r=-0．46～-0．68，P〈0．001）。结论：HIV阳性患者生存状况较差。对HIV阳性感染者而言，抑郁给患者生活质量造成全面的影响，抑郁和自杀风险仍然是需要干预和处理的问题。     

The assessment of cognitive function in advanced HIV-1 infection and AIDS dementia complex using a new computerised cognitive test battery.

The validity of a new computerised battery called CogState was determined in 60 individuals with advanced human immunodeficiency virus-1 (HIV-1) infection from which eleven were assessed as AIDS dementia complex (ADC) stage 1 or 2. Twenty-one seronegative individuals were recruited as controls. Participants were evaluated with a brief computerised examination, lasting 10-15 min, assessing reaction time, accuracy in working memory and learning. They were also assessed with a standard neuropsychological examination lasting 1h 30 min on average. The computerised assessment demonstrated a good sensitivity of 81.1% and specificity of 69.9% as well as good positive predictive value (81%) and acceptable construct validity (.45-.62). Slowed reaction time and learning deficits in the computerised battery were characteristic of ADC. This study supports the utility of a brief computerised battery in the detection of HIV-associated neurocognitive impairment that could be used for wide-scale screening.     

HIV and age do not substantially interact in HIV-associated neurocognitive impairment

The authors investigated the combined age and HIV effects on cognitive functions in 146 individuals, 116 of whom had HIV infection. Forty-two percent had HIV-associated neurocognitive disorder, and all were receiving highly active antiretroviral therapy. Using linear and nonlinear regression modeling, the authors found only a trending effect of the quadratic term HIV status × age, both including dementia cases (p=0.12) and excluding dementia cases (p<0.06). Our results suggest that either this early-2000 cohort is not old enough to detect a clear interactive age and HIV effect or that there may be a survivor bias for individuals with long-term infection. Further longitudinal studies are warranted.