Switching from abacavir to tenofovir disoproxil fumarate is associated with rises in soluble glycoprotein VI, suggesting changes in platelet-collagen interactions.

OBJECTIVES: Altered platelet function has been proposed as an underlying mechanism to explain increased risk of myocardial infarction in people living with HIV associated with use of the nucleoside reverse transcriptase inhibitor abacavir (ABC). We aimed to examine changes in platelet biomarkers in people living with HIV switching from ABC. METHODS: In a prospective, 48-week substudy of virally suppressed HIV-1-positive subjects randomized to remain on ABC/lamivudine (ABC/3TC) or switch to tenofovir disoproxil fumarate/emtricitabine, we measured soluble glycoprotein VI (sGPVI), soluble P-selectin, soluble CD40 ligand and von Willebrand factor in plasma collected over time and assessed differences using mixed effect models. RESULTS: Of 312 randomized participants, 310 were included in the analysis. Mean (SD) age 46.4 (9.3) years, 262 (85%) men and 201 (65%) white. At baseline, there was no significant between-group difference in sGPVI [tenofovir disoproxil fumarate/emtricitabine 3.75 (0.25) versus ABC/3TC 3.61 (0.22) ng/ml, P = 0.69]. Greater increases in sGPVI from baseline to week 48 occurred in those switched from ABC/3TC (effect size +0.57 ng/ml; 95% confidence interval, 0.2-0.94; P = 0.003). There was no significant baseline difference or change overtime in soluble P-selectin, soluble CD40 ligand or von Willebrand factor between groups. CONCLUSION: The significant increases in sGPVI that occur with a switch from ABC/3TC are suggestive of changes in platelet function centred on platelet/collagen interactions and potentially represent an underlying mechanism to explain increased risk of myocardial infarction with ABC.</p

Changes in multimorbidity burden over a 3–5 year period among people with HIV

Introduction: As people living with HIV age, the increasing burden of multimorbidity poses a significant health challenge. The aims of this study were to identify common patterns of multimorbidity and examine changes in their burden, as well as their associations with risk factors, over a 3–5 year period in people with HIV, enrolled in the Pharmacokinetic and clinical Observations in PeoPle over fiftY (POPPY) study.Methods: Common multimorbidity patterns were identified in POPPY participants with HIV using principal component analysis, based on Somers’ D statistic. Multimorbidity burden scores were calculated for each participant/pattern at study entry/follow-up and were standardised relative to the mean in the sample at baseline (scores >0 thus reflect a greater number of comorbidities relative to the mean). Two multivariable linear regression models were fitted to examine the associations between risk factors and burden z-scores at baseline and change in z-scores over a 3–5 year period.Results: Five patterns were identified among the 1073 POPPY participants with HIV {median age [interquartile range (IQR)], 52 (47–59) years; 85% male and 84% white}: Cardiovascular diseases (CVDs), Sexually transmitted diseases (STDs), Neurometabolic, Cancer and Mental-gastro-joint. The multivariable linear regression showed that older age, behavioural factors (i.e., body mass index (BMI), history of injection drug use, current recreational drug use and sex between men), and HIV-specific factors (i.e., duration since HIV diagnosis and a prior AIDS diagnosis) were associated with higher multimorbidity burden at baseline. However, only three of the factors (age, BMI and duration since HIV diagnosis) were significantly associated with an increase in burden across specific patterns over time.Discussion: Key modifiable and non-modifiable factors contributing to an increase in burden of multimorbidity were identified. Our findings may inform the development of more targeted interventions and guidelines to effectively prevent and manage the rising burden of multimorbidity in people with HIV.</p

Anticholinergic medications associated with falls and frailty in people with HIV

BackgroundAnticholinergic medications (ACMs) are associated with poorer age-related outcomes, including falls and frailty. We investigate associations between ACM use and recurrent falls and frailty among older (aged ≥50 years) people with HIV in the POPPY study.MethodsAnticholinergic potential of co-medications at study entry was coded using the anticholinergic burden score, anticholinergic risk score, and Scottish Intercollegiate Guidelines Network score; drugs scoring ≥1 on any scale were defined as ACM. Associations with recurrent falls (two or more falls in the previous 28 days) and frailty (modified Fried's) were assessed using logistic regression adjusting for (1) possible demographic/lifestyle confounders and (2) clinical factors and depressive symptoms (Patient Health Questionnaire-9).ResultsACM use was reported by 193 (28%) of 699 participants, with 64 (9%) receiving two or more ACM; commonly prescribed ACMs were codeine (12%), citalopram (12%), loperamide (9%), and amitriptyline (7%). Falls were reported in 63/673 (9%), and 126/609 (21%) met the frailty criteria. Both recurrent falls and frailty were more common in ACM users than in non-users (recurrent falls: 17% in users vs. 6% in non-users, p ConclusionsACM are commonly prescribed for people living with HIV, and evidence exists for an association with recurrent falls and frailty. Clinicians should be alert to this and reduce ACM exposure where possible.</p