Evaluation of a combined HIV and geriatrics clinic for older people living with HIV: the Silver clinic in Brighton, UK

As life expectancy in people living with HIV (PLWH) has increased, the focus of management has shifted to preventing and treating chronic illnesses, but few services exist for the assessment and management of these individuals. Here, we provide an initial description of a geriatric service for people living with HIV and present data from a service evaluation undertaken in the clinic. We conducted an evaluation of the first 52 patients seen in the clinic between 2016 and 2019. We present patient demographic data, assessment outcomes, diagnoses given, and interventions delivered to those seen in the clinic. The average age of attendees was 67. Primary reasons for referral to the clinic included management of complex comorbidities, polypharmacy, and suspected geriatric syndrome (falls, frailty, poor mobility, or cognitive decline). The median (range) number of comorbidities and comedications (non-antiretrovirals) was 7 (2–19) and 9 (1–15), respectively. All attendees had an undetectable viral load. Geriatric syndromes were observed in 26 (50%) patients reviewed in the clinic, with frailty and mental health disease being the most common syndromes. Interventions offered to patients included combination antiretroviral therapy modification, further health investigations, signposting to rehabilitation or social care services, and in-clinic advice. High levels of acceptability among patients and healthcare professionals were reported. The evaluation suggests that specialist geriatric HIV services might play a role in the management of older people with HIV with geriatric syndromes

Impact of musculoskeletal symptoms on physical functioning and quality of life among treated people with HIV in high and low resource settings: a case study of the UK and Zambia

Background Musculoskeletal symptoms in people living with HIV (PLWH) such as pain, joint stiffness, and fatigue are commonly reported. Prevalence rates of up to 45%, 79% and 88% respectively have been reported. However, very little is known about differences in prevalence and impact of musculoskeletal symptoms on physical functioning and quality of life of PLWH on effective combined antiretroviral treatment (cART) in high and low-resource settings. Methods A cross-sectional study of PLWH on effective cART enrolled from two large urban clinics in the UK and Zambia was conducted in 2016. Eligible participants had no history of trauma to the joints within 4 weeks of recruitment, or documented evidence of previous rheumatic disease. Current musculoskeletal symptoms, functional ability, and health-related quality of life were evaluated using the health assessment (HAQ) and quality-of-life short form (SF-36) self-reported questionnaires. Results 214 patients were enrolled (108:UK and 106:Zambia). Participants from Zambia were younger (47 vs 44 years) and had significantly lower CD4 counts (640 vs 439 cells/mL p = 0.018) compared to those from the UK, while the UK group had lived with HIV longer (11 vs 6 years; p<0.001) and reported more comorbidities than the Zambian group (66% vs 26%; p<0.001). Musculoskeletal pain was common in both groups (UK:69% vs Zambia:61% p = 0.263) but no significant differences in physical functional capacity between the groups were observed. However, the UK group had significantly worse quality of life measurements (general health, vitality, mental health, emotional, and social functioning) associated with musculoskeletal symptoms compared to the Zambian group (p<0.001). Conclusions Musculoskeletal symptoms in PLWH from both the UK and Zambia were common. PLWH in the UK reported worse quality of life measures associated with musculoskeletal symptoms compared to those in Zambia, suggesting that factors such as mental health, patient expectations and multimorbidity might play a role in determining well-being and quality of life of PLWH with musculoskeletal symptoms

Anal cancer screening in the UK: serial cross-sectional surveys on attitudes and practices

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Quality of life in people living with HIV-associated neurocognitive disorder: a scoping review study

Quality of life (QoL) is recognized as an essential end point in the disease management of chronic conditions such as HIV with calls to include good QoL as a 'fourth 90' in the 90-90- 90 testing and treatment targets introduced by World Health Organization in 2016. Cognitive impairments impact a broad spectrum of experiences and are a common issue effecting people living with HIV (PLWH). Despite this, few studies have examined QoL in PLWH who also have a cognitive disorder. This study aimed to synthesize and describe what is known about QoL in those living with HIV-associated neurocognitive disorders (HAND). A scoping review of peer-reviewed literature was conducted to identify how QoL has been investigated and measured in PLWH with HAND, and how PLWH with HAND report and describe their QoL. We searched PsychInfo, Medline, Scopus, and Web of Science along with handsearching reference lists from relevant studies found. Included studies were those published in English after 1st January 2003 which included PLWH with cognitive impairment not due to other pre-existing conditions. Fifteen articles met criteria for inclusion. Two studies measured QoL as a primary aim, with others including QoL assessment as part of a broader battery of outcomes. The MOS-HIV and SF-36 were the most commonly used measures of overall QoL, with findings generally suggestive of poorer overall QoL in PLWH with HAND, compared to PLWH without cognitive impairment. Studies which examined dimensions of QoL focused exclusively on functionality, level of independence, and psychological QoL domains. There is a considerable dearth of research examining QoL in PLWH with HAND. The initiatives which advocate for healthy aging and improved QoL in PLWH must be extended to include and understand the experiences those also living with cognitive impairment. Research is needed to understand the broad experiential impacts of living with these two complex, chronic conditions, to ensure interventions are meaningful to patients and potential benefits are not missed

Improved central nervous system symptoms in people with HIV without objective neuropsychiatric complaints switching from Efavirenz to Rilpivirine containing cART

Objective: Occult central nervous system (CNS) symptoms not recognized by people living with HIV (PLWH) receiving efavirenz or their clinicians could occur and impact people’s quality of life. The aim of this study was to determine whether CNS parameters improve in PLWH when switching from efavirenz to rilpivirine. Methods: PLWH receiving tenofovir disoproxil fumarate, emtricitabine, efavirenz (Atripla™) with undetectable HIV RNA, and no CNS symptoms were switched cART to tenofovir disoproxil fumarate, emtricitabine, rilpivirine (Eviplera™). CNS parameters including sleep, anxiety, and depressive symptoms were evaluated using patient-reported outcome measures at baseline, 4, 12, and 24 weeks after switching therapy. A median CNS score was derived from the sum of CNS toxicities of all the grades collected in the study questionnaires. Cognitive function was assessed using a computerized test battery. Results: Of 41 participants, median age was 47 years, Interquartile range (IQR) 31, 92% were male and 80% were of white ethnicity. A significant reduction in total CNS score (10 to 7) was observed at 4 weeks (p = 0.028), but not thereafter. Significant improvements in sleep and anxiety were observed 4, 12 and 24 weeks after switching therapy (p < 0.05). No significant change in global cognitive scores was observed. Conclusions: Switching from efavirenz to rilpivirine based regimens in virologically suppressed PLWH without perceived CNS symptoms was well tolerated and slightly improved overall CNS symptoms

Nanoflow-nanospray mass spectrometry metabolomics reveals disruption of the urinary metabolite profiles of HIV-positive patients on combination antiretroviral therapy

Background: The use of combination antiretroviral therapy (cART) has substantially improved the outlook for patients with HIV infection. However, lifelong exposure to cART is also associated with adverse metabolic changes and an enhanced risk of renal, hepatic and cardiovascular dysfunction. This study investigated disruptions of the urinary metabolome of cART-exposed patients, thereby furthering our understanding of some of the side effects of pharmaceutical intervention. Methods: HIV-positive patients were recruited from an HIV clinic and divided into cART-naive and cART-exposed groups. HIV-negative patients were recruited from a sexual health clinic. All 89 subjects were white males. Targeted biochemistry analyses were performed on plasma samples. Urine samples were collected following an overnight fast and analysed with a highly sensitive untargeted metabolomic method using nanoflow/nanospray liquid chromatography-time of flight mass spectrometry. Datasets were analysed using projection modelling to detect metabolite markers of cART exposure. Results: Metabolites or parent compounds of all cART drugs were detected in urine extracts of all but one of the cART-exposed patients confirming adherence to the pharmaceutical regimen. Analysis of urine samples from patients on cART revealed significant reductions in selected bile acids, lipid, nucleoside and androgen metabolites. However, plasma concentrations of free or conjugated testosterone were unchanged indicating possible disruption of androgen transport or excretion in urine of patients on cART. Conclusions: Discovery-based metabolomics reveals the potential to identify novel markers of cART intervention and metabolite disruption in HIV-positive patients, which may enable the efficacy, compliance and side effects of these pharmaceutical mixtures to be investigated

Increased dolutegravir peak concentrations in people living with HIV aged 60 and over and analysis of sleep quality and cognition

Background Demographic data show an increasingly aging HIV population worldwide. Recent concerns over dolutegravir-related neuropsychiatric toxicity have emerged, particularly amongst older HIV patients. We describe the pharmacokinetics (PK) of dolutegravir (DTG) 50mg once daily in people living with HIV (PLWH) aged 60 and older. Additionally, to address the call for prospective neuropsychiatric toxicodynamic data, we evaluate changes in sleep quality and cognitive function after switching to abacavir (ABC)/lamivudine (3TC)/DTG, over 6 months in this population. Methods PLWH aged≥60years with HIV-RNA<50copies/mL on any non-DTG based antiretroviral combination were switched to ABC/3TC/DTG. On day 28, 24-hour PK sampling was undertaken. Steady-state PK parameters were compared to a published historical control population aged≤50years. Six validated sleep questionnaires and neurocognitive (Cogstate®) testing were administered pre-switch and over 180 days (NCT02509195). Results Forty-three participants were enrolled; 40 completed the PK phase. Overall, five discontinued (two due adverse events, both sleep related, 4.6%). DTG maximum concentration (Cmax) was significantly higher in patients≥60 versus controls (GM 4246ng/mL versus 3402ng/mL, p=0.005). In those who completed day 180 (n=38), sleep impairment was higher at day 28 (PSQI median global score 5.0 versus 6.0 p=0.02) but not at day 90 or 180. Insomnia, daytime function, fatigue test scores did not change statistically over time. Conclusion DTG Cmax was significantly higher in older PLWH. Our data provides clinicians with key information on the safety of prescribing DTG in older PLWH

Changes in functional connectivity in people with HIV switching antiretroviral therapy

We assessed changes in functional connectivity by fMRI (functional magnetic resonance imaging) and cognitive measures in otherwise neurologically asymptomatic people with HIV (PWH) switching combination antiretroviral therapy (cART). In a prospective study (baseline and follow-up after at least 4 months), virologically suppressed PWH switched non-nuclease reverse-transcriptase inhibitors (NNRTI; tenofovir-DF/emtricitabine with efavirenz to rilpivirine) and integrase-strand-transfer inhibitors (INSTI; tenofovir-DF/emtricitabine with raltegravir to dolutegravir). PWH were assessed by resting-state fMRI and stop-signal reaction time (SSRT) task fMRI as well as with a cognitive battery (CogState™) at baseline and follow-up. Switching from efavirenz to rilpivirine (n = 10) was associated with increased functional connectivity in the dorsal attention network (DAN) and a reduction in SSRTs (p = 0.025) that positively correlated with the time previously on efavirenz (mean = 4.8 years, p = 0.02). Switching from raltegravir to dolutegravir (n = 12) was associated with increased connectivity in the left DAN and bilateral sensory-motor and associative visual networks. In the NNRTI study, significant improvements in the cognitive domains of executive function, working memory and speed of visual processing were observed, whereas no significant changes in cognitive function were observed in the INSTI study. Changes in fMRI are evident in PWH without perceived neuropsychiatric complaints switching cART. fMRI may be a useful tool in assisting to elucidate the underlying pathogenic mechanisms of cART-related neuropsychiatric effects

Health-related quality of life in people living with HIV with cognitive symptoms: assessing relevant domains and associations

This study aimed to validate and assess a comprehensive set of illness-specific health-related quality of life (HRQL) domains in people living with HIV (PLWH) with cognitive symptoms. One hundred and three HIV patients with cognitive symptoms (n = 93 male, 90.3%) were identified from two UK HIV clinics and complete a series of validated scales measuring seven HRQL domains identified as important to HRQL by PLWH with cognitive impairment. These included: physical functioning, cognition, social connectedness, self-concept, HIV stigma, acceptance of and perceived control over cognitive health, and physical and mental health and wellbeing. Exploratory factor analysis confirmed that domain total scores loaded onto one main factor, representing HRQL. Scale cut-off scores revealed a significant proportion of patients scored outside the normal range on single domains (between 26.2% and 79.6%), and many patients on multiple domains (40.8% on 4 or more domains). We found evidence of poor HRQL across domains in the majority of PLWH with cognitive symptoms and identified domains driving these experiences. This provides targets for intervention development and clinical action to maintain or improve HRQL in PLWH with cognitive symptoms or impairment