Barriers and facilitators to HIV care linkage and retention among older adults diagnosed with HIV in Malaysia: a qualitative study.

INTRODUCTION: Older adults newly diagnosed with HIV experience poorer prognosis and higher mortality compared to those diagnosed at younger ages. We explored the barriers and facilitators in HIV care linkage and retention among newly diagnosed older persons living with HIV (OPLWH) in Malaysia. METHODS: We conducted in-depth interviews with OPLWH and focus group discussions with healthcare providers (HCPs) from five specialties (primary care medicine, psychological medicine, gynecology, geriatrics and infectious disease) at a tertiary hospital between September 2021 to April 2022. All sessions were audio-recorded, transcribed verbatim and analysed thematically. RESULTS: We recruited 16 OPLWH and 7 HCPs. Thirteen OPLWH were male. Eight of them self-identified as men who have sex with men (MSM) and the rest were heterosexual. Diagnosis of HIV was between the ages of 50-61 years old. Barriers and facilitators could be categorized into three levels: individual, interpersonal and institutional. Individual barriers included misinformation about HIV treatment, unable to afford HIV-related services, and belief that life was futile. Interpersonal barriers were HIV-related stigma, poor social and family support, and social prejudice towards MSM. Lastly, institutional barriers were the need for frequent hospital visits, high cost for HIV-related services, a lack of guidance following diagnosis and poor communication with HCPs. Facilitators included doctor or friend support and positive institutional reputation. CONCLUSIONS: Multiple challenges hindered optimal care for OPLWH after HIV diagnosis. Issues like high costs, belief that treatment is futile, and a lack of family support need to be addressed as part of long-term support services for OPLWH.

Causes, risks and care circumstances associated with death in older adults diagnosed with HIV in a tertiary centre in Malaysia.

BACKGROUND: A substantial number of older adults succumb soon after HIV diagnosis despite ART. We explored the causes, risk factors and circumstances before death among older adults acquring HIV. METHODS: We recruited individuals newly diagnosed at our centre from 2016-2020 and analysed data of those who died. Patients were stratified to older (≥50 years) or younger (<50 years) based on their age at diagnosis and attributes were compared. The Cox proportional multivariable model was used to identify factors associated with all-cause mortality. RESULTS: Among 75 deaths reported, the majority of deaths were AIDS-related and late presentation was common in both age groups. The majority of deaths occurred in the first 12 months after care presentation and over two-thirds in both groups disengaged from care prior to death. Older age remained an independent factor associated with death after adjusting for confounders including opportunistic infections, late presentation to care, ART initiation and chronic comorbidities at presentation. CONCLUSION: Most causes of death in our setting were AIDS-related and associated with late care presentation both in young and older individuals, although older age at diagnosis remained an independent risk factor. Our findings highlight the urgent need to encourage prompt ART initiation following diagnosis, especially in older adults.

"I suppose in our culture, old means no sex": PLWH and healthcare provider views on factors influencing late HIV testing and diagnosis among older adults in Malaysia.

The proportion of new HIV diagnoses among older adults aged ≥50 years continues to rise. Older adults are at higher risk of late diagnosis which is associated with higher treatment complexity and poorer health outcomes. Few studies in the Asia-Pacific region have explored factors contributing to late presentation and diagnosis in this population. Thus, our study aimed to explore factors influencing late HIV diagnosis among older adults ≥50 years in Malaysia. We conducted in-depth interviews with 16 older adults newly diagnosed with HIV (OPLWH) and focus group discussions with seven healthcare providers (HCPs) from different specialties in an academic tertiary hospital in Malaysia. All sessions were audio-recorded, transcribed verbatim and analysed thematically. Three main themes related to late diagnosis among OPLWH emerged: (1) challenge in recognizing HIV symptoms among older persons, (2) older persons and HCPs having low index of suspicion of HIV and (3) poor acceptance of HIV testing among older persons due to perceived personal and social identities. HCPs often missed HIV symptoms and these collectively culminated in OPLWH experiencing complex diagnostic journeys resulting in late HIV diagnosis. To reduce delays in HIV diagnosis, strategies are needed to improve HIV knowledge and risk perception among both older adults and HCPs.

Investigating D-Amino Acid Oxidase Expression and Interaction Network Analyses in Pathways Associated With Cellular Stress: Implications in the Biology of Aging.

D-amino acid oxidase (DAO) is a flavoenzyme that metabolizes D-amino acids by oxidative deamination, producing hydrogen peroxide (H2O2) as a by-product. The generation of intracellular H2O2 may alter the redox-homeostasis mechanism of cells and increase the oxidative stress levels in tissues, associated with the pathogenesis of age-related diseases and organ decline. This study investigates the effect of DAO knockdown using clustered regularly interspaced short palindromic repeats (CRISPR) through an in silico approach on its protein-protein interactions (PPIs) and their potential roles in the process of aging. The target sequence and guide RNA of DAO were designed using the CCTop database, PPI analysis using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, Reactome biological pathway, protein docking using GalaxyTongDock database, and structure analysis. The translated target sequence of DAO lies between amino acids 43 to 50. The 10 proteins that were predicted to interact with DAO are involved in peroxisome pathways such as acyl-coenzyme A oxidase 1 (ACOX1), alanine-glyoxylate and serine-pyruvate aminotransferase (AGXT), catalase (CAT), carnitine O-acetyltransferase (CRAT), glyceronephosphate O-acyltransferase (GNPAT), hydroxyacid oxidase 1 (HAO1), hydroxyacid oxidase 2 (HAO2), trans-L-3-hydroxyproline dehydratase (L3HYPDH), polyamine oxidase (PAOX), and pipecolic acid and sarcosine oxidase (PIPOX). In summary, DAO mutation would most likely reduce activity with its interacting proteins that generate H2O2. However, DAO mutation may result in peroxisomal disorders, and thus, alternative techniques should be considered for an in vivo approach.

D-Amino acids differentially trigger an inflammatory environment in vitro.

Studies in vivo have demonstrated that the accumulation of D-amino acids (D-AAs) is associated with age-related diseases and increased immune activation. However, the underlying mechanism(s) of these observations are not well defined. The metabolism of D-AAs by D-amino oxidase (DAO) produces hydrogen peroxide (H2O2), a reactive oxygen species involved in several physiological processes including immune response, cell differentiation, and proliferation. Excessive levels of H2O2 contribute to oxidative stress and eventual cell death, a characteristic of age-related pathology. Here, we explored the molecular mechanisms of D-serine (D-Ser) and D-alanine (D-Ala) in human liver cancer cells, HepG2, with a focus on the production of H2O2 the downstream secretion of pro-inflammatory cytokine and chemokine, and subsequent cell death. In HepG2 cells, we demonstrated that D-Ser decreased H2O2 production and induced concentration-dependent depolarization of mitochondrial membrane potential (MMP). This was associated with the upregulation of activated NF-кB, pro-inflammatory cytokine, TNF-α, and chemokine, IL-8 secretion, and subsequent apoptosis. Conversely, D-Ala-treated cells induced H2O2 production, and were also accompanied by the upregulation of activated NF-кB, TNF-α, and IL-8, but did not cause significant apoptosis. The present study confirms the role of both D-Ser and D-Ala in inducing inflammatory responses, but each via unique activation pathways. This response was associated with apoptotic cell death only with D-Ser. Further research is required to gain a better understanding of the mechanisms underlying D-AA-induced inflammation and its downstream consequences, especially in the context of aging given the wide detection of these entities in systemic circulation.

Poor HIV-related Knowledge, Perceived Risks and Attitudes Among Urban-dwelling Malaysian Older Adults: Key Barriers to Zero HIV Transmission by 2030.

Globally and in Malaysia, there are increasing rates of HIV infection among older adults but a corresponding decline in other younger age groups. We aimed to investigate the HIV-related knowledge, perceived risks, attitudes, and risk behaviours among multi-ethnic urban-dwelling older adults in Malaysia. A cross-sectional, questionnaire-based study was conducted among 320 adults aged 50 years and above residing in urban Klang Valley, Malaysia. Participants were recruited via convenience sampling in the community and in the outpatient clinics and pharmacy of University Malaya Medical Centre, Malaysia, from April 2021 to January 2022. The median (IQR) age of participants was 58 (55-64) and 42.5% were males. The median (IQR) knowledge score was 10 (8-12) out of 14. Significant knowledge gaps were noted and ethnic Chinese, higher education levels and better HIV-related attitudes were associated with better scores. The median (IQR) attitude score was 49 (41-55) out of 65. Ethnic Chinese and Indian, knowing people living with HIV (PLHIV), and better HIV-related knowledge were associated with better attitude scores. Many (43.8%) older adults were sexually active however rates of consistent condom use was low (19%) and the majority (89.9%) of participants had low self-perceived risk of HIV. These findings highlight underlying drivers for HIV transmission and delayed treatment among older adults in Malaysia and indicate a need for targeted HIV prevention programs for this population.

Significant loss of retinal nerve fibre layer and contrast sensitivity in people with well controlled HIV disease: implications for aging with HIV.

Objective: Antiretroviral therapy has decreased the prevalence of retinal opportunistic infections in people living with HIV (PLWH). However, abnormalities in visual function are evident and may be associated with an early onset of aging in PLWH. In this study, we examined the Retinal Nerve Fibre Layer (RNFL) thickness and visual function in PLWH and HIV non-infected controls in Malaysia. Design: Cross-sectional study. Methods: Two hundred and two (202) PLWH without retinal opportunistic infection and 182 age-matched, HIV seronegative individuals were enrolled. PLWH were recruited from the Infectious Disease clinic at the University Malaya Medical Centre. Controls were recruited among the hospital staff and community volunteers. RNFL thickness was measured with spectral domain optical coherence tomography (SDOCT). Visual functions include visual acuity using LogMAR chart and contrast sensitivity using Pelli- Robson Chart. Results: All PLWH (mean age 46.1 years ± 9.9 years) in the study were on ART and 61.2% had a CD4+ T-cell count more than 500 cell/µl. The mean visual acuity was similar between the two groups (LogMAR 0.05 vs. 0.07, p = 0.115). Contrast sensitivity was lower in PLWH compared to HIV seronegative individuals (1.90 vs 1.93, p = 0.032). RNFL thickness was significantly thinner in the temporal quadrant for PLWH compared to controls (68.89 µm vs 74.08 µm, p = 0.001). Conclusion: Changes in RNFL thickness and contrast sensitivity were seen in PLWH despite their relatively young age and well controlled HIV disease. The changes reflect structural and functional deficits, and could have long-term implications on their health trajectory.