Cognitive ageing is premature among a community sample of optimally treated people living with HIV.

OBJECTIVES: Evidence of premature cognitive ageing amongst people living with HIV (PLHIV) remains controversial due to previous research limitations including underpowered studies, samples with suboptimal antiretroviral access, varying rate of virological control, high rate of AIDS, over-representation of non-community samples, and inclusion of inappropriate controls. The current study addresses these limitations, while also considering mental health and non-HIV comorbidity burden to determine whether PLHIV showed premature cognitive ageing compared with closely comparable HIV-negative controls. METHODS: This study enrolled 254 PLHIV [92% on antiretroviral therapy; 84% with HIV RNA < 50 copies/mL; 15% with AIDS) and 72 HIV-negative gay and bisexual men [mean (SD) age = 49 (10.2) years] from a single primary care clinic in Sydney, Australia. Neurocognitive function was evaluated with the Cogstate Computerized Battery (CCB) at baseline and 6 months after. Linear mixed-effects (LME) models examined main and interaction effects of HIV status and chronological age on the CCB demographically uncorrected global neurocognitive z-score (GZS), adjusting for repeated testing, and then adjusting sequentially for HIV disease markers, mental health and comorbidities. RESULTS: HIV status and age interacted with a lower GZS (ß = -0.43, P < 0.05). Higher level of anxiety symptoms (ß = -0.11, P < 0.01), historical AIDS (ß = -0.12, P < 0.05) and historical HIV brain involvement (ß = -0.12, P < 0.05) were associated with lower GZS. CONCLUSIONS: We found a robust medium-sized premature ageing effect on cognition in a community sample with optimal HIV care. Our study supports routine screening of cognitive and mental health among PLHIV aged ≥ 50 years.

HIV eradication symposium: will the brain be left behind?

On 18 July 2014, the National Institute of Mental Health in collaboration with ViiV Health Care and Boehringer Ingelheim supported a symposium on HIV eradication and what it meant for the brain. The symposium was an affiliated event to the 20th International AIDS Conference. The meeting was held in Melbourne, Australia, and brought together investigators currently working on HIV eradication together with investigators who are working on the neurological complications of HIV. The purpose of the meeting was to bring the two fields of HIV eradication and HIV neurology together to foster dialogue and cross talk to move the eradication field forward in the context of issues relating to the brain as a potential reservoir of HIV. The outcomes of the symposium were that there was substantive but not definitive evidence for the brain as an HIV reservoir that will provide a challenge to HIV eradication. Secondly, the brain as a clinically significant reservoir for HIV is not necessarily present in all patients. Consequently, there is an urgent need for the development of biomarkers to identify and quantify the HIV reservoir in the brain. Lastly, when designing and developing eradication strategies, it is critical that approaches to target the brain reservoir be included.

Factors associated with neurocognitive test performance at baseline: a substudy of the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.

OBJECTIVES: We describe neuropsychological test performance (NP) in antiretroviral treatment (ART)-naïve HIV-positive individuals with CD4 cell counts above 500 cells/µL. METHODS: In a neurology substudy of the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) Strategic Timing of AntiRetroviral Treatment (START) study, eight neurocognitive tests were administered. The primary measure of NP was the quantitative NP z-score (QNPZ-8), the average of the z-scores for the eight tests. Associations of baseline factors with QNPZ-8 scores were assessed by multiple regression. Mild neurocognitive impairment (NCI) was defined as z-scores < -1 in at least two of six cognitive domains. RESULTS: A total of 608 participants had a median age of 34 years; 11% were women and 15% were black; the median time since HIV diagnosis was 0.9 years; the median CD4 cell count was 633 cells/µL; 19.9% had mild NCI. Better NP was independently associated with younger age, being white, higher body mass index (0.10 per 10 kg/m(2) higher), and higher haematocrit percentage (0.19 per 10% higher). Worse NP was associated with longer time since HIV diagnosis (-0.17 per 10 years), diabetes (-0.29) and higher Framingham risk score (-0.15 per 10 points higher). QNPZ-8 scores differed significantly between geographical locations, with the lowest scores in Brazil and Argentina/Chile. CONCLUSIONS: This is the largest study of NP in ART-naïve HIV-positive adults with CD4 counts > 500 cells/µL. Demographic factors and diabetes were most strongly associated with NP. Unmeasured educational/sociocultural factors may explain geographical differences. Poorer NP was independently associated with longer time since HIV diagnosis, suggesting that untreated HIV infection might deleteriously affect NP, but the effect was small.

Symptoms of depression and rates of neurocognitive impairment in HIV positive patients in Beijing, China.

BACKGROUND: In China an estimated 780,000 people are living with HIV (PLWH). In high-income countries PLWH are at increased risk of depression, with subsequent adverse consequences for quality of life, and HIV-related morbidity and mortality. There are few data from low-and middle-income countries. The aims of this country-specific investigation of the Asia Pacific NeuroAIDS Consortium (APNAC) study were to establish the point prevalence, severity and HIV-related and non-HIV related correlates of depressive symptoms in PLWH, in Beijing, China. METHOD: PLWH attending an outpatient clinic at Ditan Hospital, Beijing were recruited consecutively. Data sources were: study-specific questions about demographic characteristics, and health behaviours, the Centre for Epidemiological Studies Depression Scale (CES-D), the World Health Organisation Self-Reporting Questionnaire (SRQ-20) translated into Mandarin and administered as structured individual interviews, and a screen battery of four standard neuropsychological tests. RESULTS: In total 50/51 (98%) eligible patients agreed to participate. Overall 28% scored CES-D≥16 or SRQ20≥10 and 18% in these clinical ranges on both measures; 69% were classified as being neuropsychologically impaired (scoring below 1 SD of the control value on at least two tests). Higher depressive symptom scores were associated with lower education, alcohol overuse and diminished motor ability (all p<0.05), but not neuropsychological impairment CONCLUSION: Clinically significant depressive symptoms among this cohort of PLWH in Beijing occurred at 5 times the rate reported among a general Chinese urban population. No participants had been assessed for depression prior to the study and none were treated, indicating that consideration of psychological morbidity and its consequences for health behaviours should be incorporated into routine HIV care in China.

A screening algorithm for HIV-associated neurocognitive disorders.

BACKGROUND: HIV physicians have limited time for cognitive screening. Here we developed an extra-brief, clinically based tool for predicting HIV-associated neurocognitive impairment (HAND) in order to determine which HIV-positive individuals require a more comprehensive neurological/neuropsychological (NP) assessment. METHODS: Ninety-seven HIV-positive individuals with advanced disease recruited in an HIV out-patient clinic received standard NP testing. A screening algorithm was developed using support vector machines, an optimized prediction procedure for classifying individuals into two groups (here NP-impaired and NP-normal) based on a set of predictors. RESULTS: The final algorithm utilized age, current CD4 cell count, past central nervous system HIV-related diseases and current treatment duration and required approximately 3 min to complete, with a good overall prediction accuracy of 78% (against the gold standard; NP-impairment status derived from standard NP testing) and a good specificity of 70%. CONCLUSION: This noncognitive-based algorithm should prove useful to identify HIV-infected patients with advanced disease at high risk of HAND who require more formal assessment. We propose staged guidelines, using the algorithm, for improved HAND therapeutic management. Future larger, international studies are planned to test the predictive effect of nadir CD4 cell count, hepatitis C virus infection, gender, ethnicity and HIV viral clade. We recommend the use of this first version for HIV-infected Caucasian men with advanced disease.

Dynamics of cognitive change in impaired HIV-positive patients initiating antiretroviral therapy.

OBJECTIVE: To rigorously evaluate the time course of cognitive change in a cohort of individuals with HIV-associated neurocognitive disorders (HAND) initiating combination antiretroviral therapy (CART), and to investigate which demographic, laboratory, and treatment factors are associated with neuropsychological (NP) outcome (or "any NP improvement"). METHODS: Study participants included 37 HIV+ individuals with mild to moderate NP impairment who initiated CART and underwent NP testing at 12, 24, 36, and 48 weeks thereafter. NP change was assessed using a regression-based change score that was normed on a separate NP-stable group thereby controlling for regression toward the mean and practice effect. Mixed-effect regression models adjusting for loss to follow-up were used to evaluate the time course of cognitive change and its association with baseline and time-varying predictors. RESULTS: In persons with HAND initiating CART, cognitive improvement happens soon after initiation (13% at week 12), but more often 24, 36, and up to 48 weeks after initiation (up to 41%), with fewer than 5% demonstrating significant worsening. In multivariate analyses, unique predictors of NP improvement included more severe baseline NP impairment and higher CART CNS penetration index. Greater viral load decrease was associated with NP improvement only in univariate analyses. CONCLUSION: Clinically meaningful neuropsychological improvement seemed to peak around 24-36 weeks after combination antiretroviral therapy initiation and was prolonged over the 1-year study period. This study also provides new evidence that benefit may be maximized by choosing antiretroviral medications that reach therapeutic concentrations in the CNS.