Reasons for Seeking HIV-test: Evidence from a Private Hospital in Rural Andhra Pradesh, India

This study sought to describe the development of HIV counselling and testing services in a rural private hospital and to explore the factors associated with reasons for seeking HIV testing and sexual behaviours among adults seeking testing in the rural hospital. Data for this study were drawn from a voluntary counselling and testing clinic in a private hospital in rural Andhra Pradesh state in southern India. In total, 5,601 rural residents sought HIV counselling and testing and took part in a behavioural risk-assessment survey during October 2003–June 2005. The prevalence of HIV was 1.1%. Among the two reported reasons for test-seeking—based on past sexual behaviour and based on being sick at the time of testing—men, individuals reporting risk behaviours, such as those having multiple pre- and postmarital sexual partners, individuals whose recent partner was a sex worker, and those who reported using alcohol before sex, were more likely to seek testing based on their past sexual behaviour. Men also were more likely to seek testing because they were sick. The findings from this large sample in rural India suggest that providing HIV-prevention and care services as part of an ongoing system of healthcare-delivery may benefit rural residents who otherwise may not have access to these services. The implications of involving the private sector in HIV-related service-delivery and in conducting research in rural areas are discussed. It is argued that services that are gaining prominence in urban areas, such as addressing male heterosexual behaviours and assessing the role of alcohol-use, are equally relevant areas of intervention in rural India

Initial Commitment to Pre-Exposure Prophylaxis and Circumcision for HIV Prevention amongst Indian Truck Drivers

Studies of HIV prevention interventions such as pre-exposure prophylaxis (PREP) and circumcision in India are limited. The present study sought to investigate Indian truck-drivers initial commitment to PREP and circumcision utilizing the AIDS Risk Reduction Model. Ninety truck-drivers completed an in-depth qualitative interview and provided a blood sample for HIV and HSV-2 testing. Truck-drivers exhibited low levels of initial commitment towards PREP and even lower for circumcision. However, potential leverage points for increasing commitment were realized in fear of infecting family rather than self, self-perceptions of risk, and for PREP focusing on cultural beliefs towards medication and physicians. Cost was a major barrier to both HIV prevention interventions. Despite these barriers, our findings suggest that the ARRM may be useful in identifying several leverage points that may be used by peers, health care providers and public health field workers to enhance initial commitment to novel HIV prevention interventions in India.</p

Reasons for Seeking HIV-test: Evidence from a Private Hospital in Rural Andhra Pradesh, India

This study sought to describe the development of HIV counselling and testing services in a rural private hospital and to explore the factors associated with reasons for seeking HIV testing and sexual behaviours among adults seeking testing in the rural hospital. Data for this study were drawn from a voluntary counselling and testing clinic in a private hospital in rural Andhra Pradesh state in southern India. In total, 5,601 rural residents sought HIV counselling and testing and took part in a behavioural risk-assessment survey during October 2003\u2013June 2005. The prevalence of HIV was 1.1%. Among the two reported reasons for test-seeking-based on past sexual behaviour and based on being sick at the time of testing-men, individuals reporting risk behaviours, such as those having multiple pre- and postmarital sexual partners, individuals whose recent partner was a sex worker, and those who reported using alcohol before sex, were more likely to seek testing based on their past sexual behaviour. Men also were more likely to seek testing because they were sick. The findings from this large sample in rural India suggest that providing HIV-prevention and care services as part of an ongoing system of healthcare-delivery may benefit rural residents who otherwise may not have access to these services. The implications of involving the private sector in HIV-related service-delivery and in conducting research in rural areas are discussed. It is argued that services that are gaining prominence in urban areas, such as addressing male heterosexual behaviours and assessing the role of alcohol-use, are equally relevant areas of intervention in rural India

Spherical nucleic acids as an infectious disease vaccine platform

Despite recent efforts demonstrating that organization and presentation of vaccine components are just as important as composition in dictating vaccine efficacy, antiviral vaccines have long focused solely on the identification of the immunological target. Herein, we describe a study aimed at exploring how vaccine component presentation in the context of spherical nucleic acids (SNAs) can be used to elicit and maximize an antiviral response. Using COVID-19 as a topical example of an infectious disease with an urgent need for rapid vaccine development, we designed an antiviral SNA vaccine, encapsulating the receptor-binding domain (RBD) subunit into a liposome and decorating the core with a dense shell of CpG motif toll-like receptor 9 agonist oligonucleotides. This vaccine induces memory B cell formation in human cells, and in vivo administration into mice generates robust binding and neutralizing antibody titers. Moreover, the SNA vaccine outperforms multiple simple mixtures incorporating clinically employed adjuvants. Through modular changes to SNA structure, we uncover key relationships and proteomic insights between adjuvant and antigen ratios, concepts potentially translatable across vaccine platforms and disease models. Importantly, when humanized ACE2 transgenic mice were challenged in vivo against a lethal live virus, only mice that received the SNA vaccine had a 100% survival rate and lungs that were clear of virus by plaque analysis. This work underscores the potential for SNAs to be implemented as an easily adaptable and generalizable platform to fight infectious disease and demonstrates the importance of structure and presentation in the design of next-generation antiviral vaccines

Pharmacological Inhibition of Toll-Like Receptor-4 Signaling by TAK242 Prevents and Induces Regression of Experimental Organ Fibrosis

Systemic sclerosis (SSc) is a poorly understood heterogeneous condition with progressive multi-organ fibrosis. Recent genetic and genomic evidence suggest a pathogenic role for dysregulated innate immunity and toll-like receptor (TLR) activity in SSc. Levels of both TLR4, as well as certain endogenous TLR ligands, are elevated in skin and lung tissues from patients with SSc and correlate with clinical disease parameters. Conversely, genetic targeting of TLR4 or its endogenous “damage-associated” ligands ameliorates progressive tissue fibrosis. Targeting TLR4 signaling therefore represents a pharmacological strategy to prevent intractable fibrosis. We examined the effect of TAK242, a small molecule TLR4 inhibitor, in preclinical fibrosis models and in SSc fibroblasts. TAK242 treatment prevented, promoted regression of, bleomycin-induced dermal and pulmonary fibrosis, and reduced the expression of several pro-fibrotic mediators. Furthermore, TAK242 ameliorated peritoneal fibrosis and reduced spontaneous hypodermal thickness in TSK/+ mice. Importantly, TAK242 abrogated collagen synthesis and myofibroblasts differentiation in explanted constitutively active SSc fibroblast. Altogether, these findings identify TAK242 as an anti-fibrotic agent in preclinical models of organ fibrosis. TAK242 might potentially represent a novel strategy for the treatment of SSc and other fibrotic diseases

Absence of Spontaneous Peroxisome Proliferation in Enoyl-CoA Hydratase/l-3-Hydroxyacyl-CoA Dehydrogenase-deficient Mouse Liver: FURTHER SUPPORT FOR THE ROLE OF FATTY ACYL CoA OXIDASE IN PPARα LIGAND METABOLISM

Peroxisomes contain a classical L-hydroxy-specific peroxisome proliferator-inducible beta-oxidation system and also a second noninducible D-hydroxy-specific beta-oxidation system. We previously generated mice lacking fatty acyl-CoA oxidase (AOX), the first enzyme of the L-hydroxy-specific classical beta-oxidation system; these AOX-/- mice exhibited sustained activation of peroxisome proliferator-activated receptor alpha (PPARalpha), resulting in profound spontaneous peroxisome proliferation in liver cells. These observations implied that AOX is responsible for the metabolic degradation of PPARalpha ligands. In this study, the function of enoyl-CoA hydratase/L-3-hydroxyacyl-CoA dehydrogenase (L-PBE), the second enzyme of this peroxisomal beta-oxidation system, was investigated by disrupting its gene. Mutant mice (L-PBE-/-) were viable and fertile and exhibited no detectable gross phenotypic defects. L-PBE-/- mice showed no hepatic steatosis and manifested no spontaneous peroxisome proliferation, unlike that encountered in livers of mice deficient in AOX. These results indicate that disruption of classical peroxisomal fatty acid beta-oxidation system distal to AOX step does not interfere with the inactivation of endogenous ligands of PPARalpha, further confirming that the AOX gene is indispensable for the physiological regulation of this receptor. The absence of appreciable changes in lipid metabolism also indicates that enoyl-CoAs, generated in the classical system in L-PBE-/- mice are diverted to D-hydroxy-specific system for metabolism by D-PBE. When challenged with a peroxisome proliferator, L-PBE-/- mice showed increases in the levels of hepatic mRNAs and proteins that are regulated by PPARalpha except for appreciable blunting of peroxisome proliferative response as compared with that observed in hepatocytes of wild type mice similarly treated. This blunting of peroxisome proliferative response is attributed to the absence of L-PBE protein in L-PBE-/- mouse liver, because all other proteins are induced essentially to the same extent in both wild type and L-PBE-/- mice

CD59a deficiency exacerbates influenza-induced lung inflammation through complement-dependent and-independent mechanisms

Influenza-specific immune activity not only promotes virus clearance but also causes immunopathology, thereby underlining the importance of mounting a measured anti-viral immune response. Since complement bridges both the innate and adaptive immune systems and has been implicated in defence against influenza, the role of the complement regulator CD59a in modulating the response to influenza was explored. For this purpose, immune responses to influenza virus, strain E61-13-H17, in mice deficient in the complement regulator protein CD59a (Cd59a–/– mice) were compared to those in wild-type mice. The severity of lung inflammation was significantly enhanced in the lungs of Cd59a–/– mice with increased numbers of infiltrating neutrophils and CD4+ T cells. When complement was inhibited using soluble complement receptor1, the frequency of lung-infiltrating neutrophils in influenza-infected Cd59a–/– mice was much reduced whilst numbers of CD4+ T cells remained unchanged. These results demonstrate that CD59a, previously defined as a complement regulator, modulates both the innate and adaptive immune response to influenza virus by both complement-dependent and-independent mechanisms