Differential associations of anti-cytomegalovirus antibodies and soluble CD14 levels with immunosenescence in people living with HIV on long term antiretroviral therapy.

Background: People living with HIV (PLHIV) demonstrate accelerated aging and immunosenescence in spite of immune-restoration following long-term antiretroviral treatment (ART). Low level inflammation leading to inflammaging plays an important role in mediating premature immunosenescence. Ongoing viral replication, antiretrovirals and subclinical infections with the common viruses like Cytomegalovirus (CMV) are known to induce inflammaging.

Dynamics of Matricellular Protein Levels in Blood Predict Recovery in Patients with Human Immunodeficiency Virus-Tuberculosis Coinfection.

Chronic immune activation in tuberculosis (TB) associated with human immunodeficiency virus (HIV) infection (HIV/TB) modifies their clinical course. We prospectively measured osteopontin (OPN), full-length galectin-9 (FL-Gal9), and total-Gal9 (T-Gal9) levels in 32 patients with HIV/TB coinfection treated with anti-tuberculosis and antiretroviral therapies over 6-18 months to determine the amelioration of inflammatory conditions in response to the therapies. We observed a significant time-dependent decrease in FL-Gal9 in both pulmonary TB (PTB, n = 20) and extrapulmonary TB (EPTB, n = 12) patients.

MiR-155 Negatively Regulates Anti-Viral Innate Responses among HIV-Infected Progressors.

HIV infection impairs host immunity, leading to progressive disease. An anti-retroviral treatment efficiently controls viremia but cannot completely restore the immune dysfunction in HIV-infected individuals. Both host and viral factors determine the rate of disease progression.

Antiretroviral Treatment-Induced Galectin-9 Might Impact HIV Viremia in Addition to Contributing to Inflammaging.

Background: Galectin-9 induces HIV reactivation and also contributes to non-AIDS events through inflammaging. Hence, it is important to assess its levels in HIV-infected individuals to determine their association with HIV viremia and other comorbidities.

Methods: Plasma galectin-9 levels were estimated in viremic = 152) and aviremic ( = 395) individuals on first-line antiretroviral therapy (ART).

Safety and Immunogenicity of SARS-CoV-2 Recombinant Spike Protein Vaccine in Children and Adolescents in India: A Phase 2-3 Randomized Clinical Trial.

Importance: The recombinant COVID-19 vaccine NVX-CoV2373 has demonstrated efficacy of approximately 90% in adults; however, its safety and efficacy in children is unknown.

Objective: To assess the noninferiority of SII-NVX-CoV2373 in children and adolescents compared to adults and to evaluate its safety in comparison with placebo.

Design, Setting, And Participants: This phase 2-3 observer-blind randomized clinical trial was conducted in 2 cohorts, children (aged 2 to 11 years) and adolescents (aged 12 to 17 years) between August 2021 and August 2022.

Higher proinflammatory responses possibly contributing to suppressed cytotoxicity in patients with COVID-19 associated mucormycosis.

Introduction: COVID-19 Associated Mucormycosis (CAM), an opportunistic fungal infection, surged during the second wave of SARS Cov-2 pandemic. Since immune responses play an important role in controlling this infection in immunocompetent hosts, it is required to understand immune perturbations associated with this condition for devising immunotherapeutic strategies for its control. We conducted a study to determine different immune parameters altered in CAM cases as compared to COVID-19 patients without CAM.

Safety and immunogenicity of SII-NVX-CoV2373 (COVID-19 vaccine) in adults in a phase 2/3, observer-blind, randomised, controlled study.

Background: NVX-CoV2373, a Covid-19 vaccine was developed in the USA with ∼90% efficacy. The same vaccine is manufactured in India after technology transfer (called as SII-NVX-CoV2373), was evaluated in this phase 2/3 immuno-bridging study.

Methods: This was an observer-blind, randomised, phase 2/3 study in 1600 adults.

Both N- and C-terminal domains of galectin-9 are capable of inducing HIV reactivation despite mediating differential immunomodulatory functionalities.

Background: The shock-and-kill strategy for HIV cure requires the reactivation of latent HIV followed by the killing of the reactivated cellular reservoir. Galectin-9, an immunomodulatory protein, is shown to induce HIV reactivation as well as contribute to non-AIDS- and AIDS-defining events. The protein is prone to cleavage by inflammatory proteases at its linker region separating the N- and C-terminal carbohydrate-binding domains (N- and C-CRDs) which differ in their binding specificities.

Anti-HIV-1 ADCC and HIV-1 Env Can Be Partners in Reducing Latent HIV Reservoir.

Background: Persistence of HIV reservoir even in suppressive ART is the key obstacle in HIV-1 cure. We evaluated the ability of HIV-1 C Env to reactivate the latently infected resting memory CD4 cells and the ability of polyclonal HIV antibodies mediating ADCC to lyse the reactivated targets.

Methodology: HIV-1 antibodies from 25 HIV infected individuals (14 ADCC responders and 11 non-responders) were tested against the Env-C reactivated primary cells; CD4+ and CD4+CD45RO+ memory T cells in the presence of autologous or heterologous effector cells using multicolor flow cytometry.

Agreement between dried blood spots and HemoCue in Tamil Nadu, India.

India retains the world's largest burden of anemia despite decades of economic growth and anemia prevention programming. Accurate screening and estimates of anemia prevalence are critical for successful anemia control. Evidence is mixed on the performance of HemoCue, a point-of-care testing device most widely used for large-scale surveys.

Unsterile injection equipment associated with HIV outbreak and an extremely high prevalence of HCV-A case-control investigation from Unnao, India.

The integrated counseling and testing center (ICTC) located in the district hospital, Unnao in the northern state of Uttar Pradesh (UP), India witnessed an increased detection of HIV among its attendees in July 2017. Subsequently, health camps were organized by the UP State AIDS Control Society in the villages and townships contributing to such detection. We conducted a case-control study to identify factors associated with this increased detection; 33 cases and 125 controls were enrolled.

Elevated Levels of Galectin-9 but Not Osteopontin in HIV and Tuberculosis Infections Indicate Their Roles in Detecting MTB Infection in HIV Infected Individuals.

Galectin-9 (Gal-9) and osteopontin (OPN) play immunomodulatory roles in tuberculosis and HIV infections. Evaluation of their levels as well as their interplay with different pro-inflammatory cytokines is critical to understand their role in immunopathogenesis of HIV/tuberculosis co-infection considering the complexity of the disease. Plasma levels of these proteins were measured by ELISAs in HIV-negative individuals with pulmonary ( = 21), extrapulmonary ( = 33), and latent tuberculosis ( = 22) and in HIV infected patients with pulmonary ( = 14), latent tuberculosis ( = 17), and without tuberculosis ( = 41).

Possible role of plasma Galectin-9 levels as a surrogate marker of viremia in HIV infected patients on antiretroviral therapy in resource-limited settings.

Background: Early detection of viremia in HIV infected patients on anti-retroviral therapy (ART) is important to prevent disease progression as well as accumulation of drug resistance mutations. This makes HIV viral load (VL) monitoring indispensable in HIV infected patients on ART. However VL, being an expensive test, results in heavy financial burden on health services.

Urgent need for evaluating agonists of angiotensin-(1-7)/Mas receptor axis for treating patients with COVID-19.

ACE2 is a receptor of entry of SARS-CoV-2 into the host cells, and its upregulation has been implicated in increasing susceptibility of individuals to this infection. The clinical picture of COVID-19 suggests a role of ACE2 blockade, rather than its overexpression, in causing the pathogenesis. ACE2 blockade results in increased angiotensin II activity with simultaneous hampering of functions of angiotensin-(1-7)/MasR axis.

High IL-5 levels possibly contributing to HIV viremia in virologic non-responders at one year after initiation of anti-retroviral therapy.

Lack of viral monitoring in HIV infected patients on anti-retroviral therapy in low income countries may result in missing virologic non-responders (VNR) who show immunologic recovery in spite of unsuppressed viral replication. Biomarkers and drug resistance patterns in these discordant patients in comparison to the concordant treatment failure group need to be studied to understand possible risk factors associated with this condition. HIV infected patients on anti-retroviral therapy for one year were enrolled under three categories namely VNRs (n = 25), treatment failures (n = 18) and treatment responders (n = 40).

Persons living with HIV continue to present late for care: A trend analysis from 2011 to 2015.

Context: The clinical and prevention benefits of early initiation of antiretroviral therapy (ART) have led to the adoption of test and treat policy for HIV. Early diagnosis of HIV is crucial for maximal benefits from ART.

Aims: This study aims to assess trends in CD4 cell counts at diagnosis and determinants of late presentation.

Incomplete functional T-cell reconstitution in immunological non-responders at one year after initiation of antiretroviral therapy possibly predisposes them to infectious diseases.

Background: Immunological non-responders (INR) represent a unique category of HIV-infected patients on antiretroviral therapy. These patients have suppressed viremia but a suboptimal increase in CD4 cell count, which might have opposing effects on functional immune reconstitution. Hence, the extent of immune reconstitution in INR patients was investigated in order to determine their susceptibility to opportunistic infections.

Higher expression of human telomerase reverse transcriptase in productively-infected CD4 cells possibly indicates a mechanism for persistence of the virus in HIV infection.

Mechanisms involved in survival of productively-infected memory CD4+cells after initial antigenic stimulation and their subsequent reversion to the resting state are critical for the development of a predominant replication-competent HIV reservoir. These mechanisms may also counter their elimination after HIV reactivation through latency-reversing agents (LRA). Thus, their evaluation is critical when using an appropriate HIV latency model that recapitulates the predominant replication-competent HIV reservoir to develop strategies for HIV eradication.

Effect of Combination Antiretroviral Therapy on HIV-1-specific Antibody-Dependent Cellular Cytotoxicity Responses in Subtype B- and Subtype C-Infected Cohorts.

Background: There is growing interest in immune therapies to clear the latent HIV-1 after combination antiretroviral therapy (cART). There is limited information on the effect of cART on antibody-dependent cellular cytotoxicity (ADCC), and no studies have directly compared ADCC in HIV-1 subtype B- and subtype C-infected subjects. The effect of improving immunocompetence on ADCC to influenza also remains unexplored.

Indian Long-term Non-Progressors Show Broad ADCC Responses with Preferential Recognition of V3 Region of Envelope and a Region from Tat Protein.

HIV-specific antibody-dependent cell cytotoxicity (ADCC) is likely to be important in governing protection from human immunodeficiency virus (HIV) and slowing disease progression. Little is known about the ADCC responses to HIV-1 subtype C. We characterized ADCC responses in HIV-1 subtype C-infected Indian subjects with slow disease progression and identified the dominant antigenic regions recognized by these antibodies.

Development of IFN-γ secretory ELISPOT based assay for screening of ADCC responses.

Antibody dependent cell mediated cytotoxicity has been established as one of the important protective immune mechanisms against HIV making it essential to evaluate it while testing immunogenicity of emerging vaccine candidates. IFN-γ secretory ELISPOT assay, widely used for evaluation of CTL response in HIV vaccine trials, was adapted for measuring ADCC responses and the results were compared with the standard ICS based assays. IFN-γ responses elicited by plasma samples of 23 HIV infected individuals against Env and Gag peptides using granulocytes as antigen presenting cells were assessed by both the methods.

Duplicate analysis method: a cheaper alternative to commercial IQC materials in limited resource settings for monitoring CD4 testing.

Background: India has a large number of HIV infected patients being followed up at anti-retroviral therapy (ART) centers. The patients are regularly offered CD4 count estimation for deciding their eligibility for ART initiation as well as for monitoring response to ART, making CD4 count estimation a very critical test. Hence, quality control of CD4 testing is utmost important for ultimate success of ART program.

Pseudomembranous Type of Oral Candidiasis is Associated with Decreased Salivary Flow Rate and Secretory Immunoglobulin A Levels.

Saliva plays an important role in maintaining microbial homeostasis in the oral cavity, while salivary gland hypofunction predisposes the oral mucosa to pathologic alteration and increases the risk for oral candidiasis. This study sought to determine the salivary flow rate (SFR) and secretory immunoglobulin A (SIgA) levels in HIV-positive and HIV-negative individuals and evaluate their relationship with the determinants of oral candidiasis. Sixty HIV-positive (30 with and 30 without oral candidiasis) and 30 healthy HIV-negative individuals were enrolled.

Differential modulation of phenotypic composition of HIV-infected and -uninfected PBMCs during cryopreservation.

This article was designed to determine variations in phenotypic composition of fresh and frozen PBMCs for assessing utility of cryopreserved PBMCs for phenotypic assays. Relative percentages of effector memory cells increased significantly as against percentages of naïve cells which showed significant decrease after cryopreservation in HIV-uninfected samples. These differences were not significant in HIV-infected individuals.