Integrated chronic care models for people with comorbid of HIV and non-communicable diseases in Sub-Saharan Africa: A scoping review.

BACKGROUND: Integrated health care is an approach characterized by a high degree of collaboration and communication among health professionals. Integration of HIV/NCD is recommended to enhance the quality of healthcare services being provided. Duplication of limited resources is minimized, and a holistic care approach is promoted by shifting from acute and reactive care to care that embraces patient-centredness that includes promotive health and disease surveillance. The high burden of HIV disease in sub-Saharan Africa (SSA) combined with the increasing prevalence of chronic non-communicable diseases (NCDs) necessitates a review of how health systems has been doing to deliver quality integrated care for people living with HIV (PLWH) and comorbid chronic NCDs. METHODS: A scoping review was conducted to identify and describe all publications on integrated chronic care management models at the primary care level in the SSA context, particularly those that addressed the care of PLHIV with co-morbid chronic NCDs. The inclusion and exclusion criteria were applied, and duplicates were removed. RESULTS: A total of twenty-one articles were included in the final review. Integrated healthcare systems were reported in only eight SSA countries-(South Africa, Uganda, Kenya, the United Republic of Tanzania, Zambia, Malawi, Zimbabwe and Swaziland). Integrated care systems adopted one of three health models. These included added-on NCD services to previously dedicated HIV care facilities, expansion of primary care facilities to include HIV care and establishment of integrated care services. Short-term benefits included staff capacitation, improved retention of patients and improved screening and detection of NCDs. However, the expansion of existing services resulted in an increased workload with no additional staff. A significant positive change noted by communities was that there was less or no stigmatisation of people living with HIV when attending dedicated HIV clinics. CONCLUSION: Evidence of integrated healthcare services for PLWH and co-morbid of NCDs in SSA is scanty. Data on some short-term benefits of integrated care was available, but evidence was absent on the long-term outcomes. Randomized clinical trials with clearly defined comparator groups and standardized measures of HIV and NCD outcomes are needed to demonstrate non-inferiority of integrated against non-integrated care.

Correlation Between Persistent HPV Infection and Vaginal Microecological Imbalance After Treatment of Cervical High-Grade Squamous Intraepithelial Lesion.

Objective: To analyze the association between persistent human papillomavirus (HPV) infection and vaginal microecological imbalance after surgical treatment of cervical high-grade squamous intraepithelial lesion (HSIL). Methods: This is a retrospective study, 180 cervical HSIL patients admitted to our hospital from May 2019 to May 2021 were selected, of these, 84 were treated with loop electrosurgical excision procedure (LEEP) and 96 with cold knife conization (CKC). Patients were followed up for HPV infection 1 year after surgery. There is a division into a persistent infection group (positive group) and a negative group based on the presence or absence of HPV, the detection technique was PCR amplification. The two groups were compared regarding preoperative HPV infection, vaginal micro-ecological indicators 1 year after surgery, and the correlation between persistent HPV infection and vaginal microecological imbalance. Results: At 1 year after surgery, among 180 cervical HSIL patients, 64 (35.56%) were persistently infected with HPV, with an age of (40.20 ± 4.85) years, including 36 (56.25%) with cervical intraepithelial neoplasia (CIN) grade II, 28 (43.75%) with cervical intraepithelial neoplasia (CIN) grade III, 116 (64.44%) with HPV negative, with an age of (40.22 ± 5.15) years, including 67 (57.76%) with CIN grade II and 49 (42.24%) with CIN grade III, the differences in age and CIN classification between the two groups were not statistically significant (P > .05). Preoperatively, 53 people (82.81%) with HPV viral load >100 RLU/CO in the HPV persistent infection group and 76 people (65.52%) with HPV viral load >100 RLU/CO in the HPV negative group, with statistically significant differences between the two groups (P < .05); The difference in HPV virus typing and HPV infection type between the two groups was not statistically significant (P > .05). At 1 year after surgery, the composition ratio of flora density class IV and flora diversity class IV were significantly higher in the HPV persistent infection group than in the HPV negative group, and the dominant bacteria were mainly gram-positive large bacillus, accounting for 83.33%, the difference between the two groups was statistically significant (P < .05); The differences in Nugent scores and pH values between the two groups were not statistically significant (P > .05). Logistic regression analysis showed that flora density, flora diversity, and dominant bacteria were all independent risk factors for persistent HPV infection after treatment in patients with HSIL (P < .05). Conclusion: After treatment of HSIL patients, clinical attention should be paid to monitoring of HPV infection but also to the changes in vaginal microecology, as timely correction of vaginal microecology can facilitate HPV regression and improve the patient's prognosis.

The malate shuttle detoxifies ammonia in exhausted T cells by producing 2-ketoglutarate.

The malate shuttle is traditionally understood to maintain NAD+/NADH balance between the cytosol and mitochondria. Whether the malate shuttle has additional functions is unclear. Here we show that chronic viral infections induce CD8+ T cell expression of GOT1, a central enzyme in the malate shuttle. Got1 deficiency decreased the NAD+/NADH ratio and limited antiviral CD8+ T cell responses to chronic infection; however, increasing the NAD+/NADH ratio did not restore T cell responses. Got1 deficiency reduced the production of the ammonia scavenger 2-ketoglutarate (2-KG) from glutaminolysis and led to a toxic accumulation of ammonia in CD8+ T cells. Supplementation with 2-KG assimilated and detoxified ammonia in Got1-deficient T cells and restored antiviral responses. These data indicate that the major function of the malate shuttle in CD8+ T cells is not to maintain the NAD+/NADH balance but rather to detoxify ammonia and enable sustainable ammonia-neutral glutamine catabolism in CD8+ T cells during chronic infection.

Beyond bulevirtide: Alternative therapeutic options for the management of hepatitis delta virus.

Hepatitis delta virus (HDV) is a small RNA virus which needs Hepatitis B Surface Antigen for its envelope, for entry into hepatocytes and secretion. HDV chronic infection affects around 12 million people worldwide. HDV infection is believed to be the most severe form of viral hepatitis, with a high risk of developing cirrhosis and hepatocellular carcinoma. Pegylated interferons has been used and recommended by guidelines, although not approved, with low efficacy and poor tolerability. Bulevirtide (entry inhibitor) has been recently conditionally approved by the European Medicines Agency. These treatments have many advantages, but they have also limitations since there are non-responders to these previous therapies. There is an urgent need to develop new drugs. In this article, we review antiviral treatments under development for HDV chronic infection (except bulevirtide reviewed in a specific article), including those in the HBV cure programme, outlining their respective mechanisms-of-action.

Agonistic Activation of Cytosolic DNA Sensing Receptors in Woodchuck Hepatocyte Cultures and Liver for Inducing Antiviral Effects.

Immune modulation for the treatment of chronic hepatitis B (CHB) has gained more traction in recent years, with an increasing number of compounds designed for targeting different host pattern recognition receptors (PRRs). These agonistic molecules activate the receptor signaling pathway and trigger an innate immune response that will eventually shape the adaptive immunity for control of chronic infection with hepatitis B virus (HBV). While definitive recognition of HBV nucleic acids by PRRs during viral infection still needs to be elucidated, several viral RNA sensing receptors, including toll-like receptors 7/8/9 and retinoic acid inducible gene-I-like receptors, are explored preclinically and clinically as possible anti-HBV targets. The antiviral potential of viral DNA sensing receptors is less investigated. In the present study, treatment of primary woodchuck hepatocytes generated from animals with CHB with HSV-60 or poly(dA:dT) agonists resulted in increased expression of interferon-gamma inducible protein 16 (IFI16) or Z-DNA-binding protein 1 (ZBP1/DAI) and absent in melanoma 2 (AIM2) receptors and their respective adaptor molecules and effector cytokines. Cytosolic DNA sensing receptor pathway activation correlated with a decline in woodchuck hepatitis virus (WHV) replication and secretion in these cells. Combination treatment with HSV-60 and poly(dA:dT) achieved a superior antiviral effect over monotreatment with either agonist that was associated with an increased expression of effector cytokines. The antiviral effect, however, could not be enhanced further by providing additional type-I interferons (IFNs) exogenously, indicating a saturated level of effector cytokines produced by these receptors following agonism. In WHV-uninfected woodchucks, a single poly(dA:dT) dose administered via liver-targeted delivery was well-tolerated and induced the intrahepatic expression of ZBP1/DAI and AIM2 receptors and their effector cytokines, IFN-ß and interleukins 1ß and 18. Receptor agonism also resulted in increased IFN-γ secretion of peripheral blood cells. Altogether, the effect on WHV replication and secretion following in vitro activation of IFI16, ZBP1/DAI, and AIM2 receptor pathways suggested an antiviral benefit of targeting more than one cytosolic DNA receptor. In addition, the in vivo activation of ZBP1/DAI and AIM2 receptor pathways in liver indicated the feasibility of the agonist delivery approach for future evaluation of therapeutic efficacy against HBV in woodchucks with CHB.