Psychosocial risk factors and cognitive decline in people living with HIV: results from the Malaysian HIV and aging (MHIVA) study.

HIV-associated mortality has improved with the advent of antiretroviral therapy, yet neurocognitive decline persists. We assessed the association between psychosocial risk factors and cognitive function among Malaysian PLWH. Data of virally suppressed PLWH (n = 331) on stable ART, from the Malaysian HIV and Aging study was assessed. Psychosocial factors were assessed using the Lubben Social Network Scale-6 (social isolation) and Depression Anxiety Stress Scale-21 (DASS-21). The Montreal Cognitive Assessment (MoCA) with normative standards for the Malaysian population was used to determine cognitive function. Linear and logistic regression were used to assess the associations between cognition, and psychosocial risk factors. Median age of participants was 43.8 years (IQR 37.7-51.0). Participants were predominantly male (82.8%), with secondary education or higher (85.2%). Participants were on ART for 5.7 years (IQR 3.0-9.7), with a mean MoCA score of 24.6 (±3.7). Social isolation was found in 34.6% of participants, and severe depression, severe stress, and severe anxiety in 10.6%, 15.4%, and 6.0% respectively. After adjusting for demographic, clinical, and HIV parameters, MoCA scores were significantly associated with severe stress (ß = -0.11, p = 0.02) and having marginal friendship ties (ß = -0.13, p = 0.03). Social isolation and severe stress are associated with neurocognitive impairment in PLWH.

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.

Plasma d-amino acids are associated with markers of immune activation and organ dysfunction in people with HIV.

BACKGROUND: d-Amino acids (d-AAs) have been associated with age-associated conditions in the general population but their relevance in people with HIV (PWH), who experience accentuated/accelerated aging has not been studied. We compared d-AA levels in HIV-infected and uninfected controls and explored their association with markers of immune activation, gut permeability and organ dysfunction. DESIGN: Case-control analysis. METHOD: Plasma samples from 60 antiretroviral therapy-treated HIV-infected individuals and 59 uninfected controls were analysed. A three-dimensional HPLC system was used to measure d-and l-asparagine, serine, alanine and proline and presented as %d-AA. Additionally, cell-associated and soluble markers of immune activation and senescence were characterized. Kidney and liver functions were expressed as estimated glomerular filtration rate and fibrosis-4 scores, respectively. Mann-Whitney and Spearman rank correlation coefficients were used for statistical analysis. RESULTS: d-Asparagine, d-serine, d-alanine and d-proline were detectable in all plasma samples and correlated with age in HIV-infected and uninfected but not different between groups. Kynurenine/tryptophan ratio was positively correlated with all %d-AAs in PWH and with %d-serine and %d-proline in controls. %d-AAs were not consistently correlated with markers of gut permeability in both groups. All %d-AAs were also correlated with kidney function in both groups whereas age-associated accumulation of %d-asparagine, %d-serine and %d-proline were correlated with liver function and the VACS score in controls. CONCLUSION: Plasma d-AAs are associated with chronological age and correlated with markers of immune activation and organ decline, though variably, in PWH and controls. Their role in the biology of aging warrants further investigation.

IL7RA single nucleotide polymorphisms are associated with the size and function of the MAIT cell population in treated HIV-1 infection.

MAIT cells are persistently depleted and functionally exhausted in HIV-1-infected patients despite long-term combination antiretroviral therapy (cART). IL-7 treatment supports MAIT cell reconstitution in vivo HIV-1-infected individuals and rescues their functionality in vitro. Single-nucleotide polymorphisms (SNPs) of the IL-7RA gene modulate the levels of soluble(s)IL-7Rα (sCD127) levels and influence bioavailability of circulating IL-7. Here we evaluate the potential influence of IL-7RA polymorphisms on MAIT cell numbers and function in healthy control (HC) subjects and HIV-1-infected individuals on long-term cART. Our findings indicate that IL-7RA haplotype 2 (H2*T), defined as T-allele carriers at the tagging SNP rs6897932, affects the size of the peripheral blood MAIT cell pool, as well as their production of cytokines and cytolytic effector proteins in response to bacterial stimulation. H2*T carriers had lower sIL-7Rα levels and higher MAIT cell frequency with enhanced functionality linked to higher expression of MAIT cell-associated transcription factors. Despite an average of 7 years on suppressive cART, MAIT cell levels and function in HIV-1-infected individuals were still significantly lower than those of HC. Notably, we observed a significant correlation between MAIT cell levels and cART duration only in HIV-1-infected individuals carrying IL-7RA haplotype 2. Interestingly, treatment with sIL-7Rα in vitro suppressed IL-7-dependent MAIT cell proliferation and function following cognate stimulations. These observations suggest that sIL-7Rα levels may influence MAIT cell numbers and function in vivo by limiting IL-7 bioavailability to MAIT cells. Collectively, these observations suggest that IL-7RA polymorphisms may play a significant role in MAIT cell biology and influence MAIT cells recovery in HIV-1 infection. The potential links between IL7RA polymorphisms, MAIT cell immunobiology, and HIV-1 infection warrant further studies going forward.