Anticholinergic medications associated with falls and frailty in people with HIV.

BACKGROUND: Anticholinergic 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. METHODS: Anticholinergic 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). RESULTS: ACM 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 < 0.001; frailty: 32% vs. 17%, respectively, p < 0.001). Use of two or more ACMs was associated with increased odds of falls after adjustment for demographic/lifestyle factors (odds ratio [OR] 4.53; 95% confidence interval [CI] 2.06-9.98) and for clinical factors (OR 3.58; 95% CI 1.37-9.38). Similar albeit weaker associations were seen with frailty (OR 2.26; 95% CI 1.09-4.70 and OR 2.12; 95% CI 0.89-5.0, respectively). CONCLUSIONS: ACM 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.

Factors associated with HIV testing in people aged ⩾50 years: an integrated qualitative analysis of patients and healthcare providers.

Background: Older people continue to be disproportionately affected by late HIV diagnosis, which results in increased morbidity and mortality. Despite high acceptance of HIV testing generally, older people are less likely to undergo testing than younger people. Two previous studies have been conducted, one focussing on patient-related and one focussing on clinician-related factors associated with HIV testing in older age (⩾50 years). Objective: This study is an integrated analysis from two linked studies - one focussed on patients, and one focussed on clinicians - to understand overlap in views and experiences of HIV testing in older age, to outline the clinical implications of the findings, and to highlight potential interventions to improve testing in this group. Methods: This qualitative study utilised semi-structured interviews conducted with 20 clinicians who were not HIV care specialists, but who had recently seen an older person prior to their HIV diagnosis, and 20 people who had been diagnosed late with HIV aged 50+. Interviews were audio recorded, transcribed verbatim and thematically analysed. The combined synthesis reported here was planned a priori as part of a sequential design. Results: Seven clinician- and seven patient-related themes were associated with undergoing HIV testing in older age. This article discusses the four themes that were common to both groups: poor knowledge, incorrect symptom attribution, inaccurate perception of risk, and stigma. Conclusion: Both clinician and patient factors associated with testing will have to be addressed in order to increase HIV testing in older people, and reduce the likelihood of late diagnosis. Findings from overlapping themes suggest several areas for intervention: (1) routine screening as part of existing clinical contacts aimed at older people to eliminate the need to attribute symptoms to HIV or assess risk; (2) specific and tailored education materials for clinicians and older people which utilise appropriate modalities; (3) tailored HIV testing services: either specific clinics for older people at existing sexual health services, or dedicated services in primary care.

Association between inflammatory biomarker profiles and cardiovascular risk in individuals with and without HIV.

BACKGROUND: People with HIV have an increased risk for cardiovascular morbidity and mortality. Inflammation and immune activation may contribute to this excess risk. METHODS: We assessed thirty-one biomarkers in a subset of POPPY participants and identified three distinct inflammatory profiles: 'gut/immune activation', 'neurovascular', and 'reference' (relatively low levels of inflammation). Ten-year cardiovascular disease (CVD) risk predictions were calculated using the QRISK, Framingham Risk Score (FRS) and the Data Collection on Adverse effects of anti-HIV Drugs (D:A:D) algorithms. The distributions of CVD risk scores across the different inflammatory profiles, stratified by HIV status, were compared using median quantile regression. RESULTS: Of the 312 participants included [70% living with HIV, median (interquartile range; IQR) age 55 (51-60) years; 82% male; 91% white], 36, 130, and 146 were in the 'gut/immune activation', 'neurovascular', and 'reference' cluster, respectively. The median (IQR) QRISK scores were 9.3% (4.5-14.5) and 10.2% (5.5-16.9) for people with and without HV, respectively, with similar scores obtained with the FRS and D:A:D. We observed statistically significant differences between the distributions of scores in the three clusters among people with HV. In particular, median QRISK [5.8% (1.0-10.7) and 3.1% (0.3-5.8)] scores were higher, respectively, for those in the 'gut/immune activation' and 'neurovascular' clusters compared to those in the reference cluster. CONCLUSIONS: People with HIV with increased gut/immune activation have a higher CVD risk compared to those with relatively low inflammation. Our findings highlight that clinically important inflammatory subgroups could be useful to differentiate risk and maximise prediction of CVD among people with HIV.

Biomarker associations with insomnia and secondary sleep outcomes in persons with and without HIV in the POPPY-Sleep substudy: a cohort study.

STUDY OBJECTIVES: We investigated associations between inflammatory profiles/clusters and sleep measures in people living with HIV and demographically-/lifestyle-similar HIV-negative controls in the Pharmacokinetic and clinical Observations in PeoPle over fiftY (POPPY)-Sleep substudy. METHODS: Primary outcome was insomnia (Insomnia Severity Index [ISI]>15). Secondary sleep outcomes included 7-day actigraphy (e.g. mean/standard deviation of sleep duration/efficiency), overnight oximetry (e.g. oxygen desaturation index [ODI]) and patient-reported measures (Patient-Reported Outcomes Measurement Information System (PROMIS) sleep questionnaires). Participants were grouped using Principal Component Analysis of 31 biomarkers across several inflammatory pathways followed by cluster analysis. Between-cluster differences in baseline characteristics and sleep outcomes were assessed using Kruskal-Wallis/logistic regression/Chi-squared/Fisher's exact tests. RESULTS: Of the 465 participants included (74% people with HIV, median [interquartile range] age 54 [50-60] years), only 18% had insomnia and secondary sleep outcomes suggested generally good sleep (e.g. ODI 3.1/hr [1.5-6.4]). Three clusters with distinct inflammatory profiles were identified: "gut/immune activation" (n = 47), "neurovascular" (n = 209), and "reference" (relatively lower inflammation; n = 209). The "neurovascular" cluster included higher proportions of people with HIV, obesity (BMI>30 kg/m2), and previous cardiovascular disease, mental health disorder, and arthritis of knee/hip relative to the other two clusters. No clinically relevant between-cluster differences were observed in proportions with insomnia (17%, 18%, 20%) before (p = .76) or after (p = .75) adjustment for potential confounders. Few associations were observed among actigraphy, oximetry, and PROMIS measures. CONCLUSIONS: Although associations could exist with other sleep measures or biomarker types not assessed, our findings do not support a strong association between sleep and inflammation in people with HIV.

Clinical and population-based study design considerations to accelerate the investigation of new antiretrovirals during pregnancy.

INTRODUCTION: Pregnant women are routinely excluded from clinical trials, leading to the absence or delay in even the most basic pharmacokinetic (PK) information needed for dosing in pregnancy. When available, pregnancy PK studies use a small sample size, resulting in limited safety information. We discuss key study design elements that may enhance the timely availability of pregnancy data, including the role and timing of randomized controlled trials (RCTs) to evaluate pregnancy safety; efficacy and safety outcome measures; stand-alone protocols, platform trials, single arm studies, sample size and the effect that follow-up time during gestation has on analysis interpretations; and observational studies. DISCUSSION: Pregnancy PK should be studied during drug development, after dosing in non-pregnant persons is established (unless non-clinical or other data raise pregnancy concerns). RCTs should evaluate the safety during pregnancy of priority new HIV agents that are likely to be used by large numbers of females of childbearing age. Key endpoints for pregnancy safety studies include birth outcomes (prematurity, small for gestational age and stillbirth) and neonatal death, with traditional adverse events and infant growth also measured (congenital anomalies are best studied through surveillance). We recommend that viral efficacy be studied as a secondary endpoint of pregnancy RCTs, once PK studies confirm adequate drug exposure in pregnancy. RCTs typically use a stand-alone protocol for new agents. In contrast, master protocols using a platform design can add agents over time, possibly speeding safety data ascertainment. To speed accrual, stand-alone pregnancy trial protocols can include pre-specified starting rules based upon adequate PK levels in pregnancy; and seamless master protocols or platform trials can include a pregnancy PK and safety component. When RCTs are unethical or cost-prohibitive, observational studies should be conducted, preferably using target trial emulation to avoid bias. CONCLUSIONS: Pregnancy PK needs to be obtained earlier in drug evaluation. Timely RCTs are needed to understand safety in pregnancy for high-priority new HIV agents. RCTs that enrol pregnant women should focus on outcomes unique to pregnancy, and observational studies should focus on questions that RCTs are not equipped to answer.

Factors associated with offering HIV testing to people aged ≥ 50 years: A qualitative study.

BACKGROUND: Individuals aged ≥ 50 years continue to be disproportionately affected by late HIV diagnosis, which is associated with poorer health outcomes and onward transmission. Despite HIV testing guidelines and high acceptability of HIV testing among all patients, clinicians are less likely to offer a test to an older individual. The aim of this study was to identify clinician-related factors associated with offering HIV testing to patients aged ≥ 50 years. METHODS: Twenty clinicians who had been involved in the care of an older patient diagnosed late with HIV were interviewed. RESULTS: Thematic analysis identified seven factors associated with offering HIV testing to older people: knowledge, stigma, stereotyping and perception of risk, symptom attribution, discussing HIV with patients, consent procedures and practical issues. CONCLUSIONS: Although some factors are not unique to older patients, some are unique to this group. Many clinicians lack up-to-date HIV-related knowledge, feel anxious discussing HIV with older patients and perceive asexuality in older age. In order to increase the offer of HIV testing to this group, we identified clinician-related barriers to test offer that need to be addressed.

Associations between plasma nucleoside reverse transcriptase inhibitors concentrations and cognitive function in people with HIV.

OBJECTIVES: To investigate the associations of plasma lamivudine (3TC), abacavir (ABC), emtricitabine (FTC) and tenofovir (TFV) concentrations with cognitive function in a cohort of treated people with HIV (PWH). METHODS: Pharmacokinetics (PK) and cognitive function (Cogstate, six domains) data were obtained from PWH recruited in the POPPY study on either 3TC/ABC or FTC/tenofovir disoproxil fumarate (TDF)-containing regimens. Association between PK parameters (AUC0-24: area under the concentration-time curve over 24 hours, Cmax: maximum concentration and Ctrough: trough concentration) and cognitive scores (standardized into z-scores) were evaluated using rank regression adjusting for potential confounders. RESULTS: Median (IQR) global cognitive z-scores in the 83 PWH on 3TC/ABC and 471 PWH on FTC/TDF were 0.14 (-0.27, 0.38) and 0.09 (-0.28, 0.42), respectively. Higher 3TC AUC0-24 and Ctrough were associated with better global z-scores [rho = 0.29 (p = 0.02) and 0.27 (p = 0.04), respectively], whereas higher 3TC Cmax was associated with poorer z-scores [rho = -0.31 (p<0.01)], independently of ABC concentrations. Associations of ABC PK parameters with global and domain z-scores were non-significant after adjustment for confounders and 3TC concentrations (all p's>0.05). None of the FTC and TFV PK parameters were associated with global or domain cognitive scores. CONCLUSIONS: Whilst we found no evidence of either detrimental or beneficial effects of ABC, FTC and TFV plasma exposure on cognitive function of PWH, higher plasma 3TC exposures were generally associated with better cognitive performance although higher peak concentrations were associated with poorer performance.

Agreement between self-reported and objective measures of sleep in people with HIV and lifestyle-similar HIV-negative individuals.

OBJECTIVES: The aim of this study was to evaluate the agreement between self-reported sleep measures and insomnia with objectively measured sleep parameters in people with HIV (PWH) and HIV-negative individuals. DESIGN: A cross-sectional analysis of PWH and lifestyle-similar HIV-negative individuals. METHODS: Self-reported measures included time spent in bed, sleep onset latency and a validated insomnia questionnaire. Objective measures were assessed via 7-days/nights of actigraphy data to determine average and intra-individual variability of several sleep measures (including time spent in bed and onset latency). Spearman's correlation coefficient and Cohen's κ were used to assess the agreement between self-reported and actigraphy-assessed measures. Associations between insomnia and actigraphy-assessed sleep parameters were evaluated using partial least-square discriminant analysis (PLS-DA). RESULTS: We found fair correlation between self-reported and actigraphy-assessed time spent in bed in 342 PWH (rs = 0.46) and 119 HIV-negative individuals (rs = 0.48). Among PWH, the correlation did not differ by age, education, depressive symptoms and self-reported insomnia (all P > 0.05), but was stronger in men (P = 0.05) and in those with a BMI of at least 25 kg/m2 (P < 0.001). Agreement between self-reported and actigraphy-assessed sleep onset latency was poor in both PWH (κ = 0.002, P = 0.49) and HIV-negative individuals (κ = 0.009, P = 0.65). According to PLS-DA, self-reported insomnia most strongly correlated with intra-individual variability of sleep duration, movement index and efficiency. CONCLUSION: We report poor-to-fair agreement between self-reported and actigraphy-assessed sleep measures in PWH. Insomnia symptoms correlated with regularity of sleep duration, quality and efficiency. These findings highlight the importance of both patient-reported and objective measures of daily sleep variation, for better understanding sleep disorders in PWH.

Sleep health and cognitive function among people with and without HIV: the use of different machine learning approaches.

STUDY OBJECTIVES: We investigated associations between actigraphy-assessed sleep measures and cognitive function in people with and without HIV using different analytical approaches to better understand these associations and highlight differences in results obtained by these approaches. METHODS: Cognitive and 7-day/night actigraphy data were collected from people with HIV (PWH) and lifestyle-similar HIV-negative individuals from HIV and sexual health clinics in the United Kingdom/Ireland. A global cognitive T-score was obtained averaging the standardized individual cognitive test scores accounting for sociodemographics. Average and SD of 11 sleep measures over 7 days/nights were obtained. Rank regression, partial least-squares (PLS) regression, random forest, sleep dimension construct, and latent class analysis (LCA) were applied to evaluate associations between global T-scores and sleep measures. RESULTS: In 344 PWH (median age 57 years, 86% males), average sleep duration, efficiency, and wake after sleep onset were not associated with global T-scores according to rank regression (p = 0.51, p = 0.09, p = 0.16, respectively). In contrast, global T-scores were associated with average and SD of length of nocturnal awakenings, SD of maintenance efficiency, and average out-of-bed time when analyzed by PLS regression and random forest. No associations were found when using sleep dimensions or LCA. Overall, findings observed in PWH were similar to those seen in HIV-negative individuals (median age 61 years, 67% males). CONCLUSIONS: Using multivariable analytical approaches, measures of sleep continuity, timing, and regularity were associated with cognitive performance in PWH, supporting the utility of newer methods of incorporating multiple standard and novel measures of sleep-wake patterns in the assessment of health and functioning.

Sleep Disorders in Human Immunodeficiency Virus: A Substudy of the Pharmacokinetics and Clinical Observations in People Over Fifty (POPPY) Study.

BACKGROUND: Self-reported sleep quality is poor in persons with human immunodeficiency virus (PWH), but prior studies commonly used nonspecific questionnaires, investigated only single sleep disorders, or lacked human immunodeficiency virus (HIV)-negative controls. We addressed these limitations in the Pharmacokinetics and Clinical Observations in People Over Fifty (POPPY) Sleep Substudy by assessing PWH and HIV-negative controls for insomnia, restless legs syndrome (RLS), and sleep apnea (SA). METHODS: Previously enrolled POPPY participants coenrolled in this substudy without regard to sleep symptoms. Participants completed validated sleep assessments including the Insomnia Severity Index questionnaire, International Restless Legs Syndrome Study Group questionnaire, and in-home, wrist-worn overnight oximetry. They also completed health-related quality of life questionnaires including 36-item Short Form (SF-36) and Patient-Reported Outcomes Measurement Information System (PROMIS) sleep questionnaires. RESULTS: We enrolled 357 PWH (246 >50 years of age; 111 between 18 and 50 years) and 126 HIV-negative controls >50 years of age. Among PWH, criteria were met by 21% for insomnia, 13% for RLS, and 6% for SA. Compared with HIV-negative controls, PWH had a higher risk of insomnia (adjusted odds ratio, 5.3; 95% confidence interval, 2.2-12.9) but not RLS or SA. Compared with PWH without insomnia, those with insomnia reported significantly worse scores on all SF-36 and PROMIS components; fewer than 30% reported previous diagnosis or treatment for insomnia. CONCLUSIONS: Insomnia was more common in PWH, associated with worse health-related quality of life, and frequently undiagnosed. Further research should focus on the pathogenesis of insomnia in PWH and the development of effective screening and intervention strategies for this unique population.

Correlation between computerised and standard cognitive testing in people with HIV and HIV-negative individuals.

We investigated the correlations and agreement between cognitive assessments made using a computerised (CogState™, six domains) and a standard pen-and-paper battery (five domains) in PWH and lifestyle-similar HIV-negative individuals. Demographically adjusted domain and global T-scores were obtained and used to define cognitive impairment according to the multivariate normative comparison (MNC) criteria. Correlations between T-scores and the agreement between the classifications of cognitive impairment obtained from the two batteries were assessed using the Spearman's rank correlation and Cohen's κ, respectively. The correlation between global T-scores from the two batteries was 0.52 (95% CI 0.44-0.60) in PWH and 0.45 (0.29-0.59) in controls (p = 0.38 for their difference). Correlations were generally stronger between domains within the same battery than between those from different batteries. The agreement between the two batteries in classifying individuals as cognitively impaired or not impaired was fair in PWH (κ = 0.24) and poor in HIV-negative individuals (κ = -0.02). The moderate correlation between overall cognitive function and the modest agreement between binary classifications of cognitive impairment obtained from two different batteries indicate the two batteries may assess slightly different components of cognition.

The predictors of pain extent in people living with HIV.

OBJECTIVE: To investigate the prevalence of widespread pain among people with HIV (PWH) and describe associations with antiretroviral therapy (ART) and markers of HIV disease stage. DESIGN: Cross-sectional analysis of cohort study in the United Kingdom and Ireland. METHODS: Pain information was collected during the baseline visit (conducted from 2013 to 2015) through a self-completed manikin identifying pain at 15 sites from five body regions. Pain was classified as widespread if reported at at least four regions and at least seven sites, or regional otherwise. Chi-squared tests, Kruskal-Wallis tests and ordinal logistic regression were used to consider associations between pain extent and sociodemographic and HIV-related factors. RESULTS: Among the 1207 participants (614 PWH ≥ 50 years, 330 PWH < 50 years, 263 HIV-negative controls ≥50 years), pain was most commonly reported at the upper (left: 28.9%, right: 28.0%) and lower (left: 25.7%; right: 24.5%) leg, upper (18.6%) and lower (29.7%) back and shoulders (left: 16.0%; right: 16.8%). Widespread pain was more commonly reported in PWH than in HIV-negative controls (PWH ≥ 50 years: 18.7%; PWH < 50 years: 12.7%; HIV-negative ≥50 years: 9.5%) with regional pain reported in 47.6, 44.8 and 49.8%, respectively (global P = 0.001). In multivariable analyses, pain extent was greater in those with lower educational attainment, those exposed to more ART drugs, and those with a higher current CD4 cell count but longer exposure to immunosuppression. CONCLUSION: Widespread pain is commonly reported in PWH and is associated with longer duration of exposure to HIV, immunosuppression and ART. Our findings call for greater awareness, and interventions to support the management, of pain in PWH.

The effect of HIV status on the frequency and severity of acute respiratory illness.

INTRODUCTION: Antiretroviral therapy has improved the health of people living with HIV (PLW-HIV), though less is known about how this impacts on acute respiratory illness. These illnesses are a common cause of ill health in the general population and any increase in their frequency or severity in PLW-HIV might have significant implications for health-related quality of life and the development of chronic respiratory disease. METHODS: In a prospective observational cohort study following PLW-HIV and HIV negative participants for 12 months with weekly documentation of any acute respiratory illness, we compared the frequency, severity and healthcare use associated with acute respiratory illnesses to determine whether PLW-HIV continue to have a greater frequency or severity of such illnesses despite antiretroviral therapy. RESULTS: We followed-up 136 HIV positive and 73 HIV negative participants for 12 months with weekly documentation of any new respiratory symptoms. We found that HIV status did not affect the frequency of acute respiratory illness: unadjusted incidence rates per person year of follow-up were 2.08 illnesses (95% CI 1.81-2.38) and 2.30 illnesses (1.94-2.70) in HIV positive and negative participants respectively, IRR 0.87 (0.70-1.07) p = 0.18. However, when acute respiratory illnesses occurred, PLW-HIV reported more severe symptoms (relative fold-change in symptom score 1.61 (1.28-2.02), p <0.001) and were more likely to seek healthcare advice (42% vs 18% of illnesses, odds ratio 3.32 (1.48-7.39), p = 0.003). After adjustment for differences in baseline characteristics, PLW-HIV still had higher symptom scores when unwell. CONCLUSIONS: HIV suppression with antiretroviral therapy reduces the frequency of acute respiratory illness to background levels, however when these occur, they are associated with more severe self-reported symptoms and greater healthcare utilisation. Exploration of the reasons for this greater severity of acute respiratory illness may allow targeted interventions to improve the health of people living with HIV. TRIAL REGISTRATION: ISRCTN registry (ISRCTN38386321).

Associations Between Widespread Pain and Sleep Quality in People With HIV.

BACKGROUND: We investigate the association of widespread pain with sleep quality among people with HIV and HIV-negative controls. SETTING: UK-based cohort. METHODS: Pain information was collected through a pain mannikin identifying affected body sites; pain was classified as widespread if pain was reported in ≥4 of 5 body regions and in ≥7 of 15 body sites, and as regional otherwise. Sleep was assessed a median of 3.2 years later through 7-night actigraphy and through self-reported assessments of sleep quality. Chi-squared tests, Kruskal-Wallis tests, and linear/logistic regression considered associations between pain extent and sleep quality. RESULTS: Of the 414 participants, 74 (17.9%) reported widespread and 189 (45.7%) regional pain. Although there were few clear associations between actigraphy outcomes and pain extent, those with widespread and regional pain consistently reported poorer sleep quality on all self-reported measures than those with no pain. Median (interquartile range) insomnia severity index and Patient-reported Outcomes Measurement Information System (PROMIS) for sleep disturbance and sleep-related impairment scores were 12 (7-16), 55.3 (48.0-58.9), and 57.2 (48.9-61.3), respectively, for those with widespread pain, 8 (4-13), 51.2 (45.5-58.3), and 50.3 (43.6-56.1) for those with regional pain, and 5 (2-9), 47.9 (42.9-54.3), and 45.5 (41.4-50.3) for those with no pain (all P values 0.0001). Associations remained strong after adjustment for HIV status and other confounders, and were reduced but remained significant, after adjustment for depressive symptoms. CONCLUSIONS: Widespread pain was not associated with objective measures of sleep but was strongly associated with self-reported assessments of sleep quality in people with HIV.

Cognitive function, depressive symptoms and syphilis in HIV-positive and HIV-negative individuals.

We evaluated associations between history of syphilis infection and both cognitive function and depressive symptoms in people living with HIV (PLHIV) and comparable HIV-negative controls. Syphilis serological tests, cognitive function and depression were assessed in PLHIV and controls participating in the Pharmacokinetic and Clinical Observations in People Over Fifty study. Cognitive test scores were converted to demographically adjusted T-scores (mean = 50, SD = 10) and then averaged to obtain a global T-score. Severity of depressive symptoms was assessed via the Patient Health Questionnaire-9. Associations of syphilis with global T-scores and depression were assessed using median regression. The 623 PLHIV and 246 HIV-negative controls were predominantly male (89.3% and 66.5%) with median age (interquartile range [IQR]) of 57 (53-63) and 58 (53-63) years, respectively. PLHIV had lower global cognitive T-scores (median [IQR] 48.7 [45.1, 52.1] versus 50.5 [47.0, 53.9], p < 0.001), more severe depressive symptoms (median [IQR] 4 [1, 10] versus 1 [0, 3], p < 0.001) and were more likely to report history of syphilis infection (22.0% versus 8.1%) than controls. There was no significant association between history of syphilis and global cognitive function in either PLHIV (p = 0.69) or controls (p = 0.10). Participants with a history of syphilis had more severe depressive symptoms (median [IQR] 4 [1, 9] versus 2 [0, 8], p = 0.03); however, the association became non-significant (p = 0.62) after adjusting for HIV status and potential confounders. Despite the higher prevalence of syphilis infection in PLHIV, there was no evidence of an association between history of syphilis infection and impaired cognitive function nor depressive symptoms after accounting for potential confounders.

Polypharmacy and drug-drug interactions in older and younger people living with HIV: the POPPY study.

BACKGROUND: Polypharmacy (use of ≥ five medications) increases the risk of drug-drug interactions and can lead to negative health outcomes. This study aimed to review the medications of people living with HIV (PLWH) and HIV-negative controls in the POPPY study and evaluate the frequency of polypharmacy and potential drug-drug interactions (PDDIs). METHODS: PDDIs between non-antiretroviral (ARV) drugs were analysed using the Lexicomp® database, and PDDIs between non-ARV and ARV drugs using the Liverpool drug interaction database. Between-group differences were assessed using χ2, Mann-Whitney U and Kruskal-Wallis tests. RESULTS: This analysis included 698 PLWH ≥50 years, 374 PLWH <50 years and 304 HIV-negative controls ≥50 years. The prevalence of polypharmacy was 65.8% in older PLWH, 48.1% in younger PLWH and 13.2% in the HIV-negative group. When ARVs were excluded, 29.8% of older PLWH and 14.2% of younger PLWH had polypharmacy. The prevalence of ≥1 PDDI involving non-ARV drugs was 36.1%, 20.3% and 16.4%, respectively, in older PLWH, younger PLWH and HIV-negative controls. In PLWH the prevalence of ≥1 PDDI involving ARV and non-ARV drugs was 57.3% in older PLWH and 32.4% in younger PLWH. CONCLUSIONS: Polypharmacy and PDDIs involving non-ARV/ARV drugs and non-ARV/non-ARV drugs were common among older PLWH, highlighting the need for increased awareness and additional research on all types of PDDI.

Factors associated with testing for HIV in people aged ≥50 years: a qualitative study.

BACKGROUND: Despite a decline in the number of new HIV infections in the UK overall, the number and proportion of new HIV diagnoses in people aged ≥50 years continues to increase. People aged ≥50 years are disproportionately affected by late diagnosis, which is associated with poorer health outcomes, increased treatment complexity and increased healthcare costs. Late HIV diagnosis also has significant public health implications in terms of onward HIV transmission. It is not fully understood what factors affect the decision of an older person to test for HIV. The aim of this study was to identify factors associated with testing for HIV in people aged ≥50 years who tested late for HIV. METHODS: We interviewed 20 people aged ≥50 years diagnosed late with HIV to identify factors associated with HIV testing. Interviews were audio recorded, transcribed verbatim and thematically analysed. RESULTS: Seven themes associated with HIV testing in people aged ≥50 years were identified: experience of early HIV/AIDS campaigns, HIV knowledge, presence of symptoms and symptom attribution, risk and risk perception, generational approaches to health and sexual health, stigma, and type of testing and testing venue. CONCLUSION: Some factors associated with testing identified in this study were unique to older individuals. People aged ≥50 years often do not perceive themselves to be at risk of HIV. Further, stigma and a lack of knowledge of how to access HIV testing suggest a need for health promotion and suggest current sexual health services may need to adapt to better meet their needs.

Pain in people living with HIV and its association with healthcare resource use, well being and functional status.

OBJECTIVE: We describe the prevalence of pain and its associations with healthcare resource utilization and quality-of-life. DESIGN: The POPPY Study recruited three cohorts: older people living with HIV (PLWH; ≥50 years, n = 699), younger demographically/lifestyle similar PLWH (less than 50 years, n = 374) and older demographically/lifestyle similar HIV-negative (≥50 years, n = 304) people from April 2013 to February 2016. METHODS: Current pain and pain-related healthcare use was collected via a self-reported questionnaire. Logistic regression assessed between-group differences in the prevalence of pain in the past month and current pain after controlling for potential confounders. Associations between current pain and healthcare resource use, reported joint problems, depressive symptoms, quality-of-life and functional status were assessed in PLWH using Mann-Whitney U and chi-squared tests. RESULTS: Pain in the past month was reported by 473 out of 676 (70.0%) older PLWH, 224 out of 357 (62.7%) younger PLWH and 188 out of 295 (63.7%) older HIV-negative controls (P = 0.03), with current pain reported in 330 (48.8%), 134 (37.5%) and 116 (39.3%), respectively (P = 0.0007). Older PLWH were more likely to experience current pain, even after adjustment for confounders. Of those with pain in the past month, 56 out of 412 (13.6%) had missed days of work or study due to pain, and 520 (59%) had seen a doctor about their pain. PLWH experiencing current pain had more depressive symptoms, poorer quality-of-life on all domains and greater functional impairment, regardless of age group. CONCLUSION: Even in the effective antiretroviral therapy era, pain remains common in PLWH and has a major impact on quality-of-life and associated healthcare and societal costs. Interventions are required to assist clinicians and PLWH to proactively manage pain.

Self-sampling kits to increase HIV testing among black Africans in the UK: the HAUS mixed-methods study.

BACKGROUND: Timely diagnosis of human immunodeficiency virus (HIV) enables access to antiretroviral treatment, which reduces mortality, morbidity and further transmission in people living with HIV. In the UK, late diagnosis among black African people persists. Novel methods to enhance HIV testing in this population are needed. OBJECTIVES: To develop a self-sampling kit (SSK) intervention to increase HIV testing among black Africans, using existing community and health-care settings (stage 1) and to assess the feasibility for a Phase III evaluation (stage 2). DESIGN: A two-stage, mixed-methods design. Stage 1 involved a systematic literature review, focus groups and interviews with key stakeholders and black Africans. Data obtained provided the theoretical base for intervention development and operationalisation. Stage 2 was a prospective, non-randomised study of a provider-initiated, HIV SSK distribution intervention targeted at black Africans. The intervention was assessed for cost-effectiveness. A process evaluation explored feasibility, acceptability and fidelity. SETTING: Twelve general practices and three community settings in London. MAIN OUTCOME MEASURE: HIV SSK return rate. RESULTS: Stage 1 - the systematic review revealed support for HIV SSKs, but with scant evidence on their use and clinical effectiveness among black Africans. Although the qualitative findings supported SSK distribution in settings already used by black Africans, concerns were raised about the complexity of the SSK and the acceptability of targeting. These findings were used to develop a theoretically informed intervention. Stage 2 - of the 349 eligible people approached, 125 (35.8%) agreed to participate. Data from 119 were included in the analysis; 54.5% (65/119) of those who took a kit returned a sample; 83.1% of tests returned were HIV negative; and 16.9% were not processed, because of insufficient samples. Process evaluation showed the time pressures of the research process to be a significant barrier to feasibility. Other major barriers were difficulties with the SSK itself and ethnic targeting in general practice settings. The convenience and privacy associated with the SSK were described as beneficial aspects, and those who used the kit mostly found the intervention to be acceptable. Research governance delays prevented implementation in Glasgow. LIMITATIONS: Owing to the study failing to recruit adequate numbers (the intended sample was 1200 participants), we were unable to evaluate the clinical effectiveness of SSKs in increasing HIV testing in black African people. No samples were reactive, so we were unable to assess pathways to confirmatory testing and linkage to care. CONCLUSIONS: Our findings indicate that, although aspects of the intervention were acceptable, ethnic targeting and the SSK itself were problematic, and scale-up of the intervention to a Phase III trial was not feasible. The preliminary economic model suggests that, for the acceptance rate and test return seen in the trial, the SSK is potentially a cost-effective way to identify new infections of HIV. FUTURE WORK: Sexual and public health services are increasingly utilising self-sampling technologies. However, alternative, user-friendly SSKs that meet user and provider preferences and UK regulatory requirements are needed, and additional research is required to understand clinical effectiveness and cost-effectiveness for black African communities. STUDY REGISTRATION: This study is registered as PROSPERO CRD42014010698 and Integrated Research Application System project identification 184223. FUNDING: The National Institute for Health Research Health Technology Assessment programme and the BHA for Equality in Health and Social Care.