Molecular insights in HIV-associated cardiac dysfunction.

BackgroundWith antiretroviral therapy, Human Immunodeficiency Virus (HIV) infection has become a life-long chronic condition. Persons Living with HIV (PLWH) have increased risk of cardiovascular diseases including congestive heart failure (CHF) and increased morbidity and mortality from these diseases due to factors such as HIV-induced chronic inflammation. This study will assess if providers at University Hospital in Newark, NJ are providing standard of care for CHF in PLWH.MethodsThis study was approved by Rutgers IRB (Pro2020000391). A database of 154 charts including all patients with diagnoses of both HIV and CHF was generated using ICD-10 codes for HIV and CHF. After screening, 79 patient charts were eligible. Patients were excluded if their CHF was managed elsewhere, if they were misdiagnosed or deceased. Nine were diagnosed with heart failure with preserved ejection fraction (HFpEF) defined as an ejection fraction above 50%. Seventy were diagnosed with heart failure with reduced ejection fraction (HFrEF) defined as an ejection fraction below 40%. Treatment was assessed using the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines.Recommendations for treatment of HFrEFRecommendations for treatment of HFpEFResultsFor patients with HFrEF, 10% of eligible patients were not prescribed aldosterone antagonists due to an incorrect contraindication. Thirty eight percent of patients requiring consideration for device therapy were not considered. Fourteen percent of patients did not have NYHA/ACC/AHA class documented. Three additional charts were found to not follow class-based management. Thirty five percent of patients with hypertension did not have guideline-based titrated therapy. In terms of HFpEF, 43% of patients did not have proper hypertension treatment.Heart Failure with Reduced Ejection FractionHeart Failure with Preserved Ejection FractionConclusionAdherence to evidence-based guidelines for CHF in PLWH is important due to their increased risk of mortality and morbidity. Improvements such as documentation of heart failure class, contraindications to medications, and consideration for devices may improve outcomes going forward.DisclosuresAll Authors: No reported disclosures

Extracellular vesicles (EVs) and their cargo have been studied intensively as potential sources of biomarkers in HIV infection; however, their DNA content, particularly the mitochondrial portion (mtDNA), remains largely unexplored. It is well known that human immunodeficiency virus (HIV) infection and prolonged antiretroviral therapy (ART) lead to mitochondrial dysfunction and reduced mtDNA copy in cells and tissues. Moreover, mtDNA is a well-known damage-associated molecular pattern molecule that could potentially contribute to increased immune activation, oxidative stress, and inflammatory response. We investigated the mtDNA content of large and small plasma EVs in persons living with HIV (PLWH) and its implications for viral replication, ART use, and immune status. Venous blood was collected from 196 PLWH, ART-treated or ART-naïve (66 with ongoing viral replication, ≥20 copies/mL), and from 53 HIV-negative persons, all recruited at five HIV testing or treatment centers in Burkina Faso. Large and small plasma EVs were purified and counted, and mtDNA level was measured by RT-qPCR. Regardless of HIV status, mtDNA was more abundant in large than small EVs. It was more abundant in EVs of viremic than aviremic and control participants and tended to be more abundant in participants treated with Tenofovir compared with Zidovudine. When ART treatment was longer than six months and viremia was undetectable, no variation in EV mtDNA content versus CD4 and CD8 count or CD4/CD8 ratio was observed. However, mtDNA in large and small EVs decreased with years of HIV infection and ART. Our results highlight the impact of viral replication and ART on large and small EVs’ mtDNA content. The mechanisms underlying the differential incorporation of mtDNA into EVs and their effects on the surrounding cells warrant further investigation.

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

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.

CD4 Tcells are rapidly depleted from tuberculosis granulomas following acute SIV co-infection.

Human Immunodeficiency Virus (HIV) epidemic remains a significant burden in Malaysia. Stigma related to HIV and its effect on the quality of life (QOL) of persons living with HIV (PLHIV) remains under-reported. The aim of the present study was to assess self-perceived stigma amongst PLHIV attending an urban community clinic and its influence on their QOL. Data was collected using HIV Stigma Scale and WHO-QOL HIV BREF Scale. The overall stigma experienced by PLHIV in this community was higher than previous studies (mean ± SD; 103.37 ±18.14). Majority participants had fear disclosing their disease status, while personalized stigma or the experience of prejudice and rejection was the least experienced. The overall QOL was low and was significantly impaired in social relationship domain (mean ± SD; 12.72 ± 3.59). However, their ability to perform daily activities was not affected by the illness (mean ± SD; 14.48 ± 2.91). PLHIV with higher spiritual values demonstrate lower perception of negative self-image and inferiority (r= -0.54). This finding was unique to PLHIV in this study and suggested the importance of spirituality and personal beliefs on their self-esteem. In conclusion, stigma remains as a significant problem among PLHIV in this community. Primary care offers the best platform to promote a holistic management of PLHIV, where the integration between counselors, religious experts, family and non-governmental associations could come together. The management of PLHIV is unique in every community, hence individualized approach based on cultural norms and beliefs could assist in the overall management of PLHIV.

Access to antiretroviral therapy (ART) led to epidemiological changes in human immunodeficiency virus (HIV) associated lymphoma in high-income countries such as reductions in diffuse large B-cell lymphoma (DLBCL) and stable or increased Hodgkin lymphoma (HL) and Burkitt lymphoma (BL). In 2016, Malawi implemented a universal ART (UART) policy, expanding ART eligibility to all persons living with HIV (PLWH). We compare the distribution of lymphoma subtypes and baseline HIV and prognostic characteristics for lymphoma patients in Malawi before and after implementation of UART. We enrolled patients with pathologically confirmed incident lymphoproliferative disorders into a observational clinical cohort. At diagnosis, a comprehensive clinicopathological evaluation was performed. Of 412 participants, 156 (38%) were pre-UART (2013-June 2016) and 256 (62%) post-UART (July 2016–2020). HIV prevalence was 50% in both groups. The most common pre-UART diagnoses were DLBCL [75 (48%)], low-grade non-Hodgkin lymphoma (NHL) [19 (12%)], HL [17 (11%)] and, BL [13 (8%)]. For post-UART they were DLBCL [111 (43%)], NHL [28 (11%)], BL [27 11%)] and, HL [20 (8%)]. Among PLWH, 44 (57%) pre-UART initiated ART prior to lymphoma diagnosis compared to 99 (78%) post-UART (p = 0.02). HIV-ribonucleic acid was suppressed <1000 copies/mL in 56% (33/59) pre-UART and 71% (73/103) post-UART (p = 0.05). CD4 T-cell counts were similar for both groups. We observed similar findings in the subset of participants with DLBCL. Overall, there were no significant changes in incident lymphoma subtypes (p = 0.61) after implementation of UART, but HIV was better controlled. Emerging trends bear monitoring and may have implications for prognosis and health system priority setting.Trial registration: ClinicalTrials.gov identifier:NCT02835911.

As the importance of quality in health care provision is increasingly recognised, it is opportune to consider quality care as a key link between clinical and public health approaches to human immunodeficiency virus (HIV) infection in developing countries, especially in sub-Saharan Africa. This region has the lion's share of the global epidemic and the least resources to respond. Looking at health problems using a 'quality lens' may help bridge the gaps between clinical care and public health, the current and desired standard of care, and prevention and treatment. Quality care, with prompt diagnosis and effective treatment, of people with HIV infection is crucial for good individual health outcomes, public health outcomes (in terms of decreased HIV transmission) and societal outcomes (increased productivity and decreased costs of health provision for HIV-related care). A spotlight on quality care can bring clinicians and public health practitioners together in working towards universal access to quality HIV care and prevention - one of the greatest health challenges faced in developing countries in Africa today.

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

As lifespans for persons living with HIV (PLWH) have improved over the last decade, there has been a simultaneous increase in non-AIDS-related cancer in that group. However, there is a paucity of data regarding the incidence of glioblastoma multiforme (GBM) in PLWH. Better understanding of the oncogenesis, natural history, and treatment outcomes of GBM in PLWH should lead to improved treatment strategies. We performed a comprehensive literature search of six electronic databases to identify eligible cases of GBM among PLWH. Kaplan-Meier estimates, Fisher's exact test, and logistic regression were used to interrogate the data. Epidemiologic data on global HIV prevalence was obtained from the 2016 UNAIDS incidence report, and CNS cancer incidence was obtained from the GDB 2016 Brain and Other CNS Cancer Collaborators. There is an inverse relationship between the incidence of HIV and CNS cancer globally. Median overall survival (OS) from GBM diagnosis was 8months. Estimates for survival at 1 and 2years were 28 and 5%, respectively. There were no statistically significant predictors of OS in this setting. There was a significant difference (p < 0.01) in OS in PLWH and GBM when compared to TCGA age matched cohorts. The diagnosis of GBM in PLWH is severely underreported in the literature. Despite maximal treatment, OS in this patient population is significantly less than in HIV-negative people. There was a poor prognosis of GBM in PLWH, which is inconsistent with previous reports. Further investigation is required for PLWH and concomitant GBM. Analyses must consider if HAART is maintained in PLWH during GBM treatment.

Diastolic Dysfunction in Individuals With Human Immunodeficiency Virus Infection: Literature Review, Rationale and Design of the Characterizing Heart Function on Antiretroviral Therapy (CHART) Study

Heart failure with preserved ejection fraction (HFpEF) is commonly found in persons living with HIV (PLWH) even when antiretroviral therapy suppresses HIV viremia. However, studying this condition has been challenging because an appropriate animal model is not available. In this article, we studied calcium transient in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in culture to simulate the cardiomyocyte relaxation defect noted in PLWH and HFpEF and assess whether various drugs have an effect. We show that treatment of hiPSC-CMs with inflammatory cytokines (such as interferon-γ or TNF-α) impairs their Ca2+ uptake into sarcoplasmic reticulum and that SGLT2 inhibitors, clinically proven as effective for HFpEF, reverse this effect. Additionally, treatment with mitochondrial antioxidants (like mito-Tempo) and certain antiretrovirals resulted in the reversal of the effects of these cytokines on calcium transient. Finally, incubation of hiPSC-CMs with serum from HIV patients with and without diastolic dysfunction did not alter their Ca2+-decay time, indicating that the exposure to the serum of these patients is not sufficient to induce the decrease in Ca2+ uptake in vitro. Together, our results indicate that hiPSC-CMs can be used as a model to study molecular mechanisms of inflammation-mediated abnormal cardiomyocyte relaxation and screen for potential new interventions.

Are HIV-infected patients candidates for liver transplantation?

Polypharmacy is associated with frailty in the general population, but little is known about polypharmacy among persons living with HIV (PLWH) on antiretroviral (ARV) therapy. We determined the association between polypharmacy and an adapted frailty-related phenotype (aFRP) via a cross-sectional study in FY 2009 of 1762 PLWH on ARV with suppressed viral load and 2679 uninfected participants in the Veterans Aging Cohort Study. The primary predictor was number of chronic outpatient non-ARV medications using pharmacy fill/refill data. The outcome was self-report of four aFRP domains: shrinking, exhaustion, slowness, low physical activity. Frailty was defined as reporting 3–4 domains while pre-frailty was 1–2. Frailty was uncommon (2% PLWH, 3% uninfected); a larger proportion demonstrated any aFRP domain (31% PLWH, 41% uninfected). Among PLWH and uninfected, median chronic non-ARV medications was 6 and 16 respectively if having any aFRP domain, and 4 and 10 when without aFRP domains. In adjusted analyses, each additional chronic non-ARV medication conferred an 11% increased odds of having any aFRP domain in PLWH (OR [95% CI] = 1.11 [1.08, 1.14]), and a 4% increase in those uninfected (OR [95% CI] = 1.04 [1.03, 1.04]). The stronger association between polypharmacy and frailty in PLWH warrants further study and potential deprescribing of medications.

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.