Polypharmacy and frailty among persons with HIV

Antiretroviral therapy (ART) in human immunodeficiency virus (HIV) markedly improved life expectancy in persons living with HIV (PLWH), but cardiac disease has emerged as the leading cause of death in this population. The prevalence of impaired diastolic function and heart failure with preserved ejection fraction (HFpEF) is higher among PLWH on ART. However, the specific role that HIV itself, and/or ART may have on the cardiomyocyte phenotype is unknown. We investigated modified molecular pathways in cardiomyocytes after exposure to serum from the same patients who were initially ART-naïve and then subsequently ART-treated. Rat cardiomyocytes were treated for 24 hours with serum obtained longitudinally from PLWH (N = 10) before and after being on ART for 6 months. Transcriptomic changes were determined by RNA sequencing. Measures of apoptosis, calcium handling, and extracellular matrix remodeling were analyzed using TUNEL assay and western blot. Here we show that exposure to serum from ART-naïve PLWH increases cardiomyocyte cell death. In contrast, exposure to serum obtained from the same PLWH after six months on ART results in altered expression of calcium-handling proteins and upregulation of profibrotic and extracellular matrix-related markers, indicating altered contraction and relaxation, and adverse cardiac remodeling. These findings demonstrate dysregulated molecular pathways in cardiomyocytes following exposure to untreated HIV serum versus ART-treated HIV serum from patients followed longitudinally. Altogether, these data suggest that HIV infection and ART contribute to changes seen in the cardiomyocyte phenotype and play complementary roles in the pathogenesis of diastolic dysfunction and HFpEF in PLWH.

BackgroundOlder persons living with human immunodeficiency virus (PLHIV) have more age-related comorbidities than the general population of PLHIV and greater potential for polypharmacy and drug-drug interactions with antiretroviral treatment (ART). Data comparing the real-world effectiveness of the two-drug dolutegravir/lamivudine (DTG/3TC) and three-drug bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) is limited in older PLHIV.MethodsTo assess the real-world effectiveness of switching to DTG/3TC versus BIC/FTC/TAF in older PLHIV, we conducted a retrospective chart review among people aged ≥50 years on ART who were virologically suppressed with ≥24 weeks of follow-up across 7 countries. Index date was defined as DTG/3TC or BIC/FTC/TAF initiation date.ResultsAmong 1144 PLHIV (326 United States, 221 China, 189 Spain, 140 Germany, 113 France, 100 Korea, 55 Taiwan), 593 were on DTG/3TC and 551 were on BIC/FTC/TAF. Demographic and clinical characteristics were similar between groups at index date (Table 1). Among PLHIV on DTG/3TC and BIC/FTC/TAF, 24.6% and 18.7%, were >65 years and 74.5% and 69.7% reported a non-ART comedication, respectively. Prior virological failure was reported in 6.2% of DTG/3TC and 7.7% of PLHIV on BIC/FTC/TAF. Total follow-up was 1463.3 and 1481.9 person-years among DTG/3TC and BIC/FTC/TAF groups, respectively. Approximately 25% of PLHIV had 240 weeks of follow-up. Virological failure was reported for 1 person in each group. The incidence rate of virological failure was 0.07 (95% confidence interval: 0.00-0.14) per 100 person-years for both groups. No resistance was reported.ConclusionIn older, virologically suppressed PLHIV with age-related comorbidities and comedications, switching to either two-drug DTG/3TC or three-drug BIC/FTC/TAF maintained long-term viral suppression without resistance.DisclosuresJeremy Fraysse, MS, GSK: Stocks/Bonds (Public Company)|ViiV Healthcare: Stocks/Bonds (Private Company) Jennifer Kuretski, DNP, APRN, NP-C, AAHIVS, Gilead Sciences: Speaker|ViiV: Speaker Emilio Letang, MD, MPH, PhD, GSK: Stocks/Bonds (Public Company)|ViiV Healthcare: Employee Maria Jesus Perez Elías, MD, PhD, Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Gilead: Honoraria|Janssen Cilag: Advisor/Consultant|Janssen Cilag: Grant/Research Support|Janssen Cilag: Honoraria|ViiV healthcare: Advisor/Consultant|ViiV healthcare: Grant/Research Support|ViiV healthcare: Honoraria Gustavo Verdier, BSc, BPharm, MBA, ViiV Healthcare: Employee Eva Fernvik, PhD, GSK: Stocks/Bonds (Public Company)|ViiV Healthcare: Stocks/Bonds (Private Company) Richard Grove, BSc, MSc, GSK: Stocks/Bonds (Public Company) Cynthia Firnhaber, MD, MS, DTM&H, MERCK: Advisor/Consultant|MERCK: Grant/Research Support Axel Baumgarten, MD, Abbvie: Board Member|Astra Zeneca: Board Member|Gilead: Advisor/Consultant|Gilead: Board Member|Gilead: Honoraria|GSK/ViiV Healthcare: Board Member|Janssen: Board Member|MSD: Board Member|Pfizer: Board Member Bryn Jones, MBChB, GSK: Stocks/Bonds (Public Company)|ViiV Healthcare: Employee Julie Priest, MSPH, GSK: Stocks/Bonds (Public Company)|ViiV Healthcare: Employee

Reducing Gender and Age-Group Disparities in HIV Diagnosis and Treatment Through Community-Wide HIV Testing, Linkage Case Management, and Defaulter Tracing Services in Tanzania, Outcomes of the Bukoba Combination Prevention Evaluation

BackgroundHuman Immunodeficiency Virus (HIV) infection remains a public health concern in many countries. The increased life expectancy in the post-Antiretroviral Therapy (ART) era has led to an increased risk of cardiovascular disease and death among Persons Living with HIV (PLHIV). Hypertension remains a significant risk factor for cardiovascular disease among PLHIV. Some studies have suggested associations between hypertension among PLHIV and HIV-related health factors.ObjectiveTo determine the prevalence of hypertension among PLHIV on antiretroviral medications and examine its association with HIV-related health factors.MethodsA cross-sectional study was conducted among attendants at an adult HIV clinic. 362 study participants were selected by systematic sampling. Data on hypertension diagnosis, HIV-related health factors, sociodemographic and other traditional cardiovascular risk factors were collected using a standardized questionnaire and patient chart review. Multivariate logistic regression model was used to determine the association between hypertension and HIV-related factors, adjusting for other risk factors for hypertension.ResultsThe mean age of participants was 47.9 years and majority of participants were female (77.1%). 42% of study participants had been on antiretroviral medications for > 10 years. The prevalence of hypertension was 17.4%. Age > 50 years was associated with higher odds of hypertension (aOR: 3.75, 95%CI 1.68, 8.55, p-value: 0.002). BMI in overweight and obese categories, and a history of comorbid medical conditions (diabetes, hyperlipidemia) were also associated with higher odds of hypertension (aOR: 3. 76, 95%CI 1.44, 9.81, p-value: 0.007), (aOR: 3.17, 95%CI 1.21, 8.32, p-value: 0.019) and (aOR: 14.25, 95%CI 7.41, 27.41, p-value: < 0.001) respectively. No HIV-related health factors were associated with hypertension.ConclusionHypertension was a common condition among PLHIV on antiretroviral medications. No HIV-related health factors were associated with hypertension. Traditional risk factors associated with hypertension were increased age > 50 years, increased BMI, and a history of comorbid medical conditions.

Background Effectively treated and virally suppressed persons living with HIV (PLWH) have an increased risk of heart failure compared with the general population. Currently, no methods to predict heart failure risk are available in PLWH. Purpose To create a proteomics-based model of incident heart failure risk in a longitudinal cohort of PLWH in the Veterans Aging Cohort Study Biomarker Cohort. Methods We characterized the baseline plasma proteome of 1,398 PLWH using an aptamer-based platform. Traditional risk factors and HIV-specific variables were incorporated into Cox proportional hazards models for incident heart failure. For risk models involving proteins, least absolute shrinkage and selection operator (LASSO) regression with 10-fold cross-validation was used to identify the optimal set of predictors. Model performance was evaluated using Harrell’s Concordance Index (C-index). Results Among 1,398 PLWH, 165 (11.8%) developed incident heart failure over a mean follow-up period of 9.6 years. The sample was divided randomly 2:1 into training (n = 932) and testing (n = 466) sets. In the training set, 4,248 proteins were screened, identifying 774 significant markers (false discovery rate- [FDR] adjusted p-value &amp;lt; 0.05); 492 of these were validated in the test set (p &amp;lt; 0.05) and were included as candidate predictors in downstream LASSO models. LASSO-Cox regression was used to identify a subset of predictor proteins in combination with clinical and laboratory risk factors, as well as protein-only models. Test concordance indices (C-index) in the validation data set are presented in Table 1. Among the clinical risk factor models, individual traditional risk factors in combination with HIV disease markers (CD4+ T-cell count, viral load) exhibited the best predictive performance (C-index 0.634; standard error [SE] 0.038). Addition of serum inflammatory and coagulation markers (soluble CD-14 [sCD14], interleukin-6 [IL-6], D-dimer) did not substantially improve performance (C-index 0.611, SE 0.042). By contrast, a protein-only model incorporating 11 markers achieved an improved C-index of 0.704 (SE 0.061), while the addition of CD4+ count and viral load performed similarly (C-index 0.708, SE 0.062). The protein-only risk model demonstrated improved risk discrimination compared with clinical risk factors, particularly in the highest-risk quartile (Figure 1; quartile-based C-indices 0.604 (SE 0.042) and 0.672 (0.036) for clinical and protein models, respectively). Conclusion An 11-protein signature demonstrated superior predictive performance for 10-year incident heart failure risk among PLWH compared with baseline traditional risk factors and inflammatory markers. If these findings can be externally validated, they highlight the potential of a proteomics-based approach for risk stratification in this population, which provides additive value beyond traditional or HIV-specific clinical risk factors.

Introduction: HIV-related stigma hampers treatment and prevention efforts worldwide. Effective interventions to counter HIV-related stigma are greatly needed. Although the “contact hypothesis” suggests that personal contact with persons living with HIV (PLHIV) may reduce stigmatizing attitudes in the general population, empirical evidence in support of this hypothesis is lacking. Our aim was to estimate the association between personal contact with PLHIV and HIV-related stigma among the general population of sub-Saharan Africa.Methods: Social distance and anticipated stigma were operationalized using standard HIV-related stigma questions contained in the Demographic and Health Surveys and AIDS Indicator Surveys of 26 African countries between 2003 and 2008. We fitted multivariable logistic regression models with country-level fixed effects, specifying social distance as the dependent variable and personal contact with PLHIV as the primary explanatory variable of interest.Results: We analyzed data from 206,717 women and 91,549 men living in 26 sub-Saharan African countries. We estimated a statistically significant negative association between personal contact with PLHIV and desires for social distance (adjusted odds ratio [AOR] = 0.80; p < 0.001; 95% Confidence Interval [CI], 0.73–0.88). In a sensitivity analysis, a similar finding was obtained with a model that used a community-level variable for personal contact with PLHIV (AOR = 0.92; p < 0.001; 95% CI, 0.89–0.95).Conclusions: Personal contact with PLHIV was associated with reduced desires for social distance among the general population of sub-Saharan Africa. More contact interventions should be developed and tested to reduce the stigma of HIV.

In Sub-Saharan Africa, efficacy trials of brief interventions to reduce unhealthy drinking among persons living with HIV (PLWH) have yielded mixed results. A better understanding of the perceptions of drinking, especially by PLWH, and how drinking is talked about at HIV treatment clinics in this setting, may guide more optimal designs for future trials. We conducted a qualitative study at an HIV treatment clinic in South Western Uganda to better understand perceptions of drinking, how drinking is talked about, and perceptions of interventions, especially a protocolled screening and brief intervention (SBI) for unhealthy drinking among PLWH. We conducted in-depth interviews with 17 PLWH who engaged in unhealthy drinking and 6 health workers, and one focus group discussion with 3 community advisory-board members. We performed manual preliminary data analysis and computer-assisted detailed thematic analysis to identify emergent themes. Four themes emerged: perceptions of alcohol use in the general population; perceptions of alcohol use in PLWH; interaction between PLWH and health workers about alcohol use; perceptions of interventions for unhealthy drinking including SBI. Unhealthy drinking was seen as a problem in the general population and among those with HIV, where it was negatively perceived. Communication about drinking was done by counselors, but doctors participated in screening for unhealthy alcohol use. Messages about drinking covered reduction and abstinence. Participants expressed positive attitudes towards SBI and preference for person-delivered SBI over technological alternatives. A protocolled SBI for unhealthy alcohol use among PLWH would be well-received but successful implementation may depend on mode of delivery.

Community antiretroviral groups (CAGs) is one of the innovative and efficient differentiated service delivery models (DSDM) for reaching persons needing human immunodeficiency virus (HIV) treatment in the community. Since DSDM adoption in Uganda, evidence suggests better care outcomes for patients in DSDM compared to counterparts in routine health facility care. However, uptake of CAG models for eligible community groups of persons living with HIV (PLHIV) has been slow in Arua district, Uganda and stakeholders’ perceptions regarding its implementation unexplored. The objective of the study was to determine the uptake, barriers and facilitators influencing CAG model implementation in Arua district, Uganda. We conducted a parallel convergent mixed-methods study from March 2020 to December 2020 at Adumi health centre IV and Kuluva hospital in Arua district. We enrolled and extracted data for every fifth virally suppressed participant on antiretroviral therapy (ART) at the two health facilities. Data were analysed using STATA 13.0. Uptake was determined as the proportion of eligible PLHIV that were enrolled into a group. We performed logistic regression to determine factors associated with uptake. We conducted one focus group discussion per facility among healthcare workers involved in the management of PLHIV. We also conducted 7 focus group discussions among PLHIV across the two facilities. Thematic analysis was used to describe the data. A total of 399 PLHIV were eligible for CAG, 61.6% were female, and 44.9% were on dolutegravir (DTG) based regimen. Uptake was 6.8%, 95% CI (4.7–9.7) and was found to be significantly associated with being divorced or separated in a marriage (OR; 0.14, 95%CI; 0.02–0.92, P = 0.014). Members picking drugs in turns, comforting and encouraging others to take the drugs, and health workers advising them to join and stay with other group members were perceived as facilitators to uptake of community antiretroviral group delivery model. Having few and distant eligible members in the local area to form a group, lack of transport among the member to pick the drugs when it’s their turn, misunderstandings and lack of confidentiality amongst the members, and lack of partner disclosure were perceived as barriers to uptake of community antiretroviral group delivery model. Uptake of community antiretroviral group delivery model in Arua district is very low. There may be a need to support community antiretroviral group delivery models with income- generating activities, transport facilitation, closer community drug pick-up points and improved partner disclosure support mechanisms among married group members.

<h3>Objectives</h3> For persons living with HIV (PLWH) in long-term care, clinic transfers are common and influence sustained engagement in HIV care, as they are associated with significant time out-of-care, low...

Introduction: Hypertension has been reported to be on the rise among persons living with HIV (PLHIV) with a global and highest recorded Kenya prevalence of 35% and 18% respectively in 2021. Identification of context-specific hypertension-associated factors among PLHIV is needed to design targeted interventions. We sought to determine the factors associated with hypertension among PLHIV in Mombasa, Kenya. Methods: A cross-sectional study using a standardized questionnaire was conducted among adult PLHIV in the Comprehensive Care Clinics in Mombasa County, Kenya from December 2021 to February 2022. Hypertension was defined as having two or more blood pressure readings of ≥140/90mmHg. Prevalence ratio (P.R), and Adjusted Prevalence Ratio (A.P.R) were calculated to determine the associated factors of hypertension. Results: A total of 235 participants were enrolled with a mean age of 42.8±10.7 years. About 71% (167/235) of the patients were female, and the age group 35–44 years was at 35%. The prevalence of hypertension among PLHIV was 25%. Factors identified to be independently associated with hypertension were having a body mass index (BMI) 25–29.9 (A.P.R: 2.41, 95%CI: 1.30–4.42), BMI≥30 (A.P.R: 3.37 95% CI: 1.69–6.73) and use of tenofovir-based antiretroviral regimen (A.P.R: 0.32, 95%CI: 0.17–0.60). Conclusion: The prevalence of hypertension among PLHIV in Mombasa was higher than previous recorded findings. One of the key risk factors for hypertension was having an elevated BMI. Weight monitoring and management as well as tenofovir-based therapy are recommended among PLHIV to reduce their risk of developing hypertension.

HIV-related stigma could delay the identification and treatment of persons living with HIV (PLHIV), particularly in regions affected by ethnic conflicts. The aims of this study were to assess attitudes towards PLHIV and examine factors associated with stronger positive attitudes towards PLHIV among university students in the Serbian province of Kosovo. A cross-sectional study was conducted at the University of Pristina temporarily settled in Kosovska Mitrovica during the academic year 2013-2014. A total of 1,017 first- and fourth-year students completed an anonymous questionnaire about socio-demographic characteristics, PLHIV, high-risk groups for acquiring HIV and health behaviour. The main outcome measure was the Attitude Score (ATS), calculated as a sum of points awarded for all attitude-related items. The majority of students (84%) expressed positive attitudes towards PLHIV, while others were indecisive. Most students held negative opinions about persons who use drugs (64%), homosexual persons of both genders (50%) and sex workers (42%). Being female (odds ratio [OR]=1.49, 95% confidence interval [CI] 1.05-2.09) and older (OR=1.13, 95% CI 1.03-1.24), not doing paid work while studying (OR=3.35, 95% CI=1.63-6.84), studying health-related disciplines (β=-0.113, 95% CI=-0.085 to -2.747), having stronger positive attitudes towards homosexual persons of both genders (OR=0.77, 95% CI=0.64-0.94) and not using illicit drugs (β=2.08, 95% CI=1.03-4.20) were associated with stronger positive attitudes towards PLHIV. Social inclusion of PLHIV and individuals at high risk for acquiring HIV could help reduce the HIV-related stigma.

Both traditional and HIV-specific risk factors contribute to greater incidence of cardiovascular disease in persons living with HIV (PLWH). Using state-of-the-art, high-resolution magnetic resonance (MR) imaging of the common carotid arteries, this study aimed to evaluate the relationship between carotid vessel wall thickness (c-VWT) and atherosclerotic cardiovascular disease (ASCVD) risk score in PLWH. Cross-sectional determinations of c-VWT using MR imaging in virally suppressed PLWH without known cardiovascular disease (n=32) and matched controls (n=13) were completed. Clinical data, including ASCVD risk and c-VWT, were compared between groups and regression analyses performed to identify predictors of c-VWT. PLWH had significantly higher c-VWT (1.15 ±0.11 mm versus 1.08 ±0.08 mm; P=0.02) as well as higher diastolic blood pressure compared to controls, but exhibited no differences in 10-year ASCVD risk score, systolic blood pressure or smoking. Ten-year ASCVD risk score (r=0.53, P-value =0.0002), age (r=0.30, P-value <0.05), triglycerides (r=0.33, P-value =0.03) and waist circumference (r=0.36, P-value =0.02) were significantly associated with increased c-VWT. Among PLWH, c-VWT did not differ by protease inhibitor use. In a multivariate regression analysis, ASCVD risk score was the only variable significantly associated with c-VWT (P-value =0.02), whereas, HIV status was not. In this cross-sectional study MR imaging demonstrated that c-VWT, a known marker for CVD risk, was increased in PLWH relative to controls, and that 10-year ASCVD risk was closely related to c-VWT, independent of HIV infection. Our data suggest that traditional cardiovascular disease risk factors in PLWH are adequately captured in the ASCVD risk score which was closely associated with subclinical carotid disease.

Sleep disturbance is common among persons living with HIV (PLWH) causing significant health impacts. Nigeria recently switched from efavirenz to dolutegravir (DTG) for first-line antiretroviral therapy (ART). This study aimed to assess the prevalence of sleep disturbance and to determine factors associated with sleep disturbance among treatment-experienced PLWH. Using a cross-sectional study design and systematic random sampling, 300 participants were recruited from the Infectious Diseases Institute, Ibadan, Nigeria (IDI). Interviewer administered questionnaire was used to collect data regarding sociodemographic, sleep disturbance (Pittsburgh Sleep Quality Index; PSQI), depression (Patient Health Questionnaire; PHQ-9), anxiety (Generalized Anxiety Disorder-7; GAD-7), and psychoactive substance use. HIV-specific data were retrieved from IDI's medical records. The relationship between the PSQI score and the scores on the PHQ-9 and GAD-7 were explored with the Pearson correlation coefficient. Chi-square global tests of independence were used to assess factors associated with sleep disturbance and a multivariable binary logistic model was used to determine independent predictors of sleep disturbance. The mean age of the sample was 44.5 ± 11.4 (years), the average duration of HIV diagnosis was 8.13 ± 5.33 (years) and the majority were on DTG-based regimens (95%). Depression and anxiety were present in 14 and 17.3%, respectively. Prevalence of sleep disturbance (PSQI score of 6 or more) was 21.7%. Higher PSQI scores were associated with higher PHQ-9 scores (r = 0.526; p < 0.001) and higher GAD-7 scores (r = 0.529; p < 0.001). Sleep disturbance was associated with age (χ2 = 4.483, p = 0.038), marital status (χ2 = 7.187, p < 0.01), depression (χ2 = 46.589, p < 0.001), and anxiety (χ2 = 38.379, p < 0.001). There was no significant association between sleep disturbance and HIV clinical stage at diagnosis, virological suppression status, and ART regimen type (p > 0.05), whereas tea intake was associated with an absence of sleep disturbance (χ2 = 6.334, p < 0.014). Age (>45 years), depression and anxiety were associated with higher odds of sleep disturbance among PLWH. Sleep disturbance remains common among PLWH in the DTG era. Depression and anxiety are significant factors associated with sleep disturbance. Assessing these factors in future studies may improve the sleep health of PLWH.

Skin cancer and HIV

Factors associated with isoniazid preventive treatment interruption and completion among PLHIV in Gombe Hospital, Uganda, 2017–2019