Quality of life among PLHIV enrolled under TANSACS during COVID era - a mixed method study.

The burden of avoidable illness, accidents and impairments can be estimated by understanding the quality of life, and it can also offer important new insights into the connections between risk factors and the quality of life. This study assessed the quality of life of people living with HIV during the COVID-19 pandemic which would have caused substantial difficulties for such individuals. Data were collected using WHOQOL-BREF SCALE and FGD Semi-Structured Questionnaire. People living with HIV enrolled under TANSACS were included. Chi-square analysis was used to evaluate the association between the demographic variables and the domains of the quality of life. The quality of life was determined using 4 domains. The average score for each domain includes physical health, 54.39, psychological, 44.85, social relationships, 48.48 and environment 57.69. The average overall score for the quality of life was 51.35. The occupation variable is significant with all the domains; physical health (P = 0.030), psychological (P = 0.046), social relationships (P = 0.027) and environment (P = 0.023) and the gender variable is significant with physical health (P = 0.026), social relationship (P = 0.007) domains. COVID-19 worsened quality of life for HIV patients, impacting healthcare, support, jobs, and stigma. The employment status also significantly impacted.

Targeted modifications in adeno-associated virus serotype 8 capsid improves its hepatic gene transfer efficiency in vivo.

Recombinant adeno-associated virus vectors based on serotype 8 (AAV8) have shown significant promise for liver-directed gene therapy. However, to overcome the vector dose dependent immunotoxicity seen with AAV8 vectors, it is important to develop better AAV8 vectors that provide enhanced gene expression at significantly low vector doses. Since it is known that AAV vectors during intracellular trafficking are targeted for destruction in the cytoplasm by the host-cellular kinase/ubiquitination/proteasomal machinery, we modified specific serine/threonine kinase or ubiquitination targets on the AAV8 capsid to augment its transduction efficiency. Point mutations at specific serine (S)/threonine (T)/lysine (K) residues were introduced in the AAV8 capsid at the positions equivalent to that of the effective AAV2 mutants, generated successfully earlier. Extensive structure analysis was carried out subsequently to evaluate the structural equivalence between the two serotypes. scAAV8 vectors with the wild-type (WT) and each one of the S/T→Alanine (A) or K-Arginine (R) mutant capsids were evaluated for their liver transduction efficiency in C57BL/6 mice in vivo. Two of the AAV8-S→A mutants (S279A and S671A), and a K137R mutant vector, demonstrated significantly higher enhanced green fluorescent protein (EGFP) transcript levels (~9- to 46-fold) in the liver compared to animals that received WT-AAV8 vectors alone. The best performing AAV8 mutant (K137R) vector also had significantly reduced ubiquitination of the viral capsid, reduced activation of markers of innate immune response, and a concomitant two-fold reduction in the levels of neutralizing antibody formation in comparison to WT-AAV8 vectors. Vector biodistribution studies revealed that the K137R mutant had a significantly higher and preferential transduction of the liver (106 vs. 7.7 vector copies/mouse diploid genome) when compared to WT-AAV8 vectors. To further study the utility of the K137R-AAV8 mutant in therapeutic gene transfer, we delivered human coagulation factor IX (h.FIX) under the control of liver-specific promoters (LP1 or hAAT) into C57BL/6 mice. The circulating levels of h.FIX:Ag were higher in all the K137R-AAV8 treated groups up to 8 weeks post-hepatic gene transfer. These studies demonstrate the feasibility of the use of this novel AAV8 vectors for potential gene therapy of hemophilia B.