Impact of Integrase Inhibitors on Cardiovascular Disease Events in People With Human Immunodeficiency Virus Starting Antiretroviral Therapy.

BACKGROUND: Integrase strand transfer inhibitors (INSTIs) have been associated with an increased risk for cardiovascular disease (CVD) events. We investigated the impact of starting INSTI-based antiretroviral therapy (ART) on CVD events among treatment-naïve people with human immunodeficiency virus using a target trial framework, which reduces the potential for confounding and selection bias. METHODS: We included Swiss HIV Cohort Study participants who were ART-naïve after May 2008, when INSTIs became available in Switzerland. Individuals were categorized according to their first ART regimen (INSTI vs other ART) and were followed from ART start until the first of CVD event (myocardial infarction, stroke, or invasive cardiovascular procedure), loss to follow-up, death, or last cohort visit. We calculated hazard ratios and risk differences using pooled logistic regression models with inverse probability of treatment and censoring weights. RESULTS: Of 5362 participants (median age 38 years, 21% women, 15% of African origin), 1837 (34.3%) started INSTI-based ART, and 3525 (65.7%) started other ART. Within 4.9 years (interquartile range, 2.4-7.4), 116 CVD events occurred. Starting INSTI-based ART was not associated with an increased risk for CVD events (adjusted hazard ratio, 0.80; 95% confidence interval [CI], .46-1.39). Adjusted risk differences between individuals who started INSTIs and those who started other ART were -0.17% (95% CI, -.37 to .19) after 1 year, -0.61% (-1.54 to 0.22) after 5 years, and -0.71% (-2.16 to 0.94) after 8 years. CONCLUSIONS: In this target trial emulation, we found no difference in short- or long-term risk for CVD events between treatment-naïve people with human immunodeficiency virus who started INSTI-based ART and those on other ART.

One for all, all for one: neuro-HIV multidisciplinary platform for the assessment and management of neurocognitive complaints in people living with HIV.

BACKGROUND: With ageing, comorbidities such as neurocognitive impairment increase among people living with HIV (PLWH). However, addressing its multifactorial nature is time-consuming and logistically demanding. We developed a neuro-HIV clinic able to assess these complaints in 8 h using a multidisciplinary approach. METHODS: People living with HIV with neurocognitive complaints were referred from outpatient clinics to Lausanne University Hospital. Over 8 h participants underwent formal infectious disease, neurological, neuropsychological and psychiatric evaluations, with opt-out magnetic resonance imaging (MRI) and lumbar puncture. A multidisciplinary panel discussion was performed afterwards, with a final report weighing all findings being produced. RESULTS: Between 2011 and 2019, a total of 185 PLWH (median age 54 years) were evaluated. Of these, 37 (27%) had HIV-associated neurocognitive impairment, but they were mainly asymptomatic (24/37, 64.9%). Most participants had non-HIV-associated neurocognitive impairment (NHNCI), and depression was prevalent across all participants (102/185, 79.5%). Executive function was the principal neurocognitive domain affected among both groups (75.5% and 83.8% of participants impaired, respectively). Polyneuropathy was found in 29 (15.7%) participants. Abnormalities in MRI were found in 45/167 participants (26.9%), being more common among NHNCI (35, 77.8%), and HIV-1 RNA viral escape was detected in 16/142 participants (11.2%). Plasma HIV-RNA was detectable in 18.4% out of 185 participants. CONCLUSIONS: Cognitive complaints remain an important problem among PLWH. Individual assessment from a general practitioner or HIV specialist is not enough. Our observations show the many layers of HIV management and suggest that a multidisciplinary approach could be helpful in determining non-HIV causes of NCI. A 1-day evaluation system is beneficial for both participants and referring physicians.

Anticholinergic and Sedative Medications Are Associated With Neurocognitive Performance of Well Treated People With Human Immunodeficiency Virus.

Background: We previously showed that anticholinergic (ACH) medications contribute to self-reported neurocognitive impairment (NCI) in elderly people with human immunodeficiency virus (PWH). The current cross-sectional study further evaluated the effect of ACH and sedative drugs on neurocognitive function in PWH who underwent comprehensive neuropsychological evaluation. Methods: A medication review was performed in PWH enrolled in the prospective Neurocognitive Assessment in Metabolic and Aging Cohort within the Swiss HIV Cohort Study. Neurocognitive functions were analyzed in 5 domains (motor skills, speed of information, attention/working memory, executive functions, and verbal learning memory). The effect of ACH and sedative medications on neurocognitive functioning was evaluated using linear regression models for the continuous (mean z-score) outcome and multivariable logistic regression models for the binary (presence/absence) outcome. Results: A total of 963 PWH (80% male, 92% Caucasian, 96% virologically suppressed, median age 52) were included. Fourteen percent of participants were prescribed ≥1 ACH medication and 9% were prescribed ≥1 sedative medication. Overall, 40% of participants had NCI. Sedative medication use was associated with impaired attention/verbal learning and ACH medication use with motor skills deficits both in the continuous (mean z-score difference -0.26 to -0.14, P < .001 and P = .06) and binary (odds ratio [OR], ≥1.67; P < .05) models. Their combined use was associated with deficits in overall neurocognitive functions in both models (mean z-score difference -0.12, P = .002 and OR = 1.54, P = .03). These associations were unchanged in a subgroup analysis of participants without depression (n = 824). Conclusions: Anticholinergic and sedative medications contribute to NCI. Clinicians need to consider these drugs when assessing NCI in PWH.

Neurocognitive course at 2-year follow-up in a Swiss cohort of people with well-treated HIV.

OBJECTIVE: The aim of this study was to examine neurocognitive course over time among people with well treated HIV. DESIGN: The Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study is an ongoing, prospective, longitudinal, multicenter and multilingual study within the Swiss HIV Cohort Study (SHCS). Participants undergo neuropsychological assessment at baseline and two-yearly follow-up. SETTING: Seven SHCS centres. PARTICIPANTS: Patients aged at least 45 years enrolled in the SHCS with fluency in the local language (French, German or Italian) and agreeing to participate in the NAMACO study: 981 participants at baseline, 720 at 2-year follow-up of whom 644 had complete data sets. INTERVENTION: Standardized neuropsychological assessment at baseline and 2-year follow-up. MAIN OUTCOME MEASURE: Neurocognitive performance using Frascati criteria and mean z-scores. RESULTS: Four participants (of 644, 0.6%) had plasma HIV-1 RNA more than 50 copies/ml; median CD4+ cell count was 660 cells/µl. According to Frascati criteria, 204 participants (31.7%) had neurocognitive impairment (NCI) at baseline. NCI severity in these participants changed little over 2 years and comprehensive models based on Frascati criteria were not feasible. Examining mean z-scores, however, we observed neurocognitive stability or improvement over two years in five of seven neurocognitive domains assessed. Age at least 65 years (P = 0.02) and cognitive complaints (P = 0.004) were associated with neurocognitive decline, while black race (P = 0.01) and dolutegravir treatment (P = 0.002) were associated with improvement. CONCLUSION: Frascati criteria were less sensitive in measuring NCI change and therefore unsuitable for following neurocognitive course in our cohort of people with well treated HIV. Examining neurocognitive course by mean z-score change, we observed stability or improvement.