Manisha Ghate

Human immunodeficiency virus and tuberculosis (HIV/TB) coinfection remains a major global health challenge. Immune dysregulation in HIV complicates TB diagnosis. The type of immune response mounted in tuberculosis is a key determinant in deciding the outcome of the infection. Hence, estimating immune markers is critical for developing diagnostic, monitoring and treatment approaches. A study was conducted to evaluate the diagnostic potential of host-based biomarkers in individuals with HIV/TB coinfection in comparison to HIV monoinfection receiving antiretroviral therapy. Host-based biomarkers were quantified using commercially available kits. Receiver operated curve (ROC) analysis was conducted to determine diagnostic performance. Routine investigations showed significantly raised ratios of neutrophils, monocytes, and platelets-to-lymphocytes and alkaline phosphatase levels in HIV/TB coinfection (AUC values > 0.76). Plasma galectin-9 and osteopontin levels had an AUC > 0.8. IFN-γ, TNF-α and IL-12 levels were also significantly raised (AUC values > 0.95) while levels of GM-CSF and IL-6 were significantly low in HIV TB coinfection. The ROC analysis revealed the highest diagnostic accuracy of IL-12, indicating its potential as an adjunct immunological biomarker in identifying TB among HIV-infected individuals. However, a large-scale prospective study is required to confirm the findings and to understand their role in predicting the development of tuberculosis disease in people living with HIV.

Background: It is well recognized that parents play a central role in making decisions for their children. Understanding willingness of parents to vaccinate their children against COVID-19 is important as it helps to develop effective strategies for maximizing vaccination coverage. We aimed to evaluate parental acceptance regarding COVID-19 vaccination for children between 6 and 12 years of age in India.Methods: A mixed-method study (March–September 2023) employed a structured questionnaire and in-depth interviews with parents of school-going and non-school-going children across five purposively selected Indian states. Multistage random sampling was used for districts, schools, and students, while convenience sampling was applied for qualitative data. Multivariable logistic regression assessed factors influencing parental acceptance of COVID-19 vaccination, and qualitative analysis identified barriers and facilitators.Results: A total of 2017 parents participated in the study. The overall parental acceptance to vaccinate their children against COVID-19 was 76.4%. Multivariate logistic regression analysis showed that parents who were literate (p = 0.004), not vaccinated against COVID-19 (p = 0.012), had less than or equal to four family members (p < 0.001) and a history of COVID-19 infection in the family (p = 0.036) were less likely to accept the COVID-19 vaccine for their children. Key barriers to vaccination included uncertainty over the protection provided by the vaccine, fear about side effects, and misconceptions about the vaccine whereas belief in the vaccine, perceived severity of COVID-19 disease, and bundling with routine vaccination were the key facilitators.Conclusion: These findings highlight the importance of increasing adult COVID-19 vaccination. Developing policies focusing on parents with higher literacy, staying in smaller families, and previous COVID-19 infection among family members will help to increase the vaccine uptake among children. Interventions for the integration of these vaccines with routine immunization or availability at schools may help in increasing COVID-19 vaccine acceptance.

We asked if SARS-CoV-2 seropositivity in HIV/TB co-infected patients plays a role in precipitating active tuberculosis in HIV-infected individuals and alters inflammatory status. A prospective study was conducted on HIV/TB co-infected patients presenting with pulmonary (n = 20) or extrapulmonary (n = 12) tuberculosis. Abbott SARS-CoV-2 IgG kits assessed the presence of anti-nucleoprotein antibodies. Inflammatory markers viz. osteopontin, total and full-length galectin-9, and C-reactive protein were tested at baseline and the end of antituberculosis treatment. The inflammatory score (INS) was assessed based on the percentage of reduction in the inflammatory markers’ levels at the end of the treatment. Anti-SARS-CoV-2 antibodies were detected in five male patients diagnosed with pulmonary (n = 2) and extrapulmonary (n = 3) TB. None of them reported symptomatic COVID-19. Inflammatory marker levels did not differ significantly at baseline compared to those in seronegative patients. However, the INS correlated negatively with SARS-CoV-2 seropositivity (r = −0.386, p = 0.039), indicating persistently raised inflammatory markers in these patients at the end of the treatment compared to seronegative individuals. Among the four markers studied, total galectin-9 levels failed to decrease significantly in these patients (p = 0.030). The majority of HIV/TB co-infected patients enrolled in our study (84.5%) were SARS-CoV-2-seronegative, indicating that SARS-CoV-2 infection might not have played a role in precipitating TB reactivation.

Objectives: World Health Organization has recommended enhanced adherence counselling (EAC) for people living with HIV (PLHIV) with virological failure. This study aimed to assess the outcomes of EAC and its associated factors among PLHIV with virological failure. Methods: Data collected between March 2020 and February 2022 on viral load (VL) testing at antiretroviral therapy (ART) centre in Pune, India were reviewed. PLHIV with viral load ≥1000 copies/ml followed by three EAC sessions and a repeat viral load test were included. Multivariate logistic regression analysis was used to assess the factors associated with virological suppression (<1000 copies/ml). Results: Of 170 PLHIV, 81 (47.6%) showed virological suppression. Being literate ( p = 0.027), females ( p = 0.021), on second-line ART regimen ( p = 0.020), and with EAC initiation within a month ( p = 0.016) were significantly associated with virological suppression. No association was found between reported barriers to treatment adherence and virological suppression. Discussion: Early initiation of EAC is crucial for virological suppression among PLHIV with high viral load. It is important to highlight the significance of treatment adherence among individuals on first-line ART regimen. The use of effective visual tools during EAC sessions may help in achieving virological suppression among those with low literacy.

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. The levels of T-Gal9, OPN, and CRP decreased significantly after treatment in only PTB patients. We calculated the inflammatory score (INS) indicating immunologic recovery based on the decline in OPN, FL-Gal9, T-Gal9, and CRP levels. Baseline levels of T-Gal9 and OPN positively correlated with INS in all TB and only PTB patients, respectively, indicating that their levels predict better recovery. In contrast, FL-Gal9 levels at the second visit negatively correlated with INS in EPTB patients. The decrease rate in OPN levels at the second visit also correlated positively with INS in PTB patients. Women showed a higher INS and lower levels of FL-Gal9 than men. The patients with moderate grade severity on chest X-ray had higher CD4 cell numbers than those with limited grade severity. Monitoring these markers will help to predict and assess the response to therapy as well as to devise strategies to reduce the complications caused by chronic immune activation in patients with HIV/TB coinfection.

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 (n = 152) and aviremic (n = 395) individuals on first-line antiretroviral therapy (ART). They were assessed for correlation with HIV-1 viral load (VL), CD4 count, and ART duration, as well as for receiver operating characteristic curve analysis. Result: Plasma galectin-9 levels correlated positively with VL (r = 0.507, p < 0.0001) and ART duration (r = 0.308, p = 0.002) and negatively with CD4 count (r = −0.186, p < 0.0001). Area under the curve for galectin-9/CD4 count ratio for identifying viremic individuals was 0.906. Sensitivity and specificity of the ratio at a cutoff of 14.47 were 90.13% and 70.05%, respectively, for detecting viremic individuals. Further, galectin-9 levels correlated with cystatin C (r = 0.239, p = 0.0183), IL-18 (r = 0.311, p = 0.006), and systolic blood pressure (r = 0.220, p = 0.0355). Galectin-9-induced HIV reactivation was significantly lower in individuals on long-term ART than those on short-term ART. Conclusion: The galectin-9-to-CD4 count ratio indicated the potential of galectin-9 as a cheaper monitoring tool to detect HIV viremia. Strategies for countering the effects of galectin-9 for controlling HIV viremia and non-AIDS events are urgently warranted.

Background: We aimed to determine the anti-SARS-CoV-2 IgG antibodies among people living with HIV (PLHIV) in Pune, India. Methods: This cross-sectional study was conducted between March 2021 and June 2021. Demographic and clinical information related to coronavirus disease 2019 (COVID-19) were recorded on structured questionnaires. Blood samples were collected and tested for anti-SARS-CoV-2 IgG antibodies using commercial ELISA. Results: Of the 405 HIV infected individuals enrolled in the study, 223(55.1%) were females. Mean age and CD4 count of participants were 42 years (SD: 10) and 626 cells/mm³ (SD: 284) respectively. A total of 382 (95%) PLHIV were virologically suppressed. The seropositivity against SARS-CoV-2 was found in 221 PLHIV (54.6%, 95% CI: 49.7-59.4). No significant association was found between demographic or clinical factors and seropositivity. Conclusion: A high prevalence of anti-SARS-CoV-2 IgG antibodies was found among PLHIV attending ART centre indicating an exposure to the virus among them.

Objective: We aimed to determine the ocular manifestation and refractive error prevalences among people living with HIV (PLHIV) in Pune, India. Methods: This cross-sectional study included HIV-infected adults attending a National AIDS Research Institute clinic. Ophthalmologic examination included visual acuity estimation, refraction, orthoptic evaluation, slit lamp and fundus examination, and photography. Results: In total, 441 HIV-infected individuals were enrolled. The participants' median age was 44 (interquartile range 38–49) years and 227 (51.5%) were men. Refractive errors occurred in 132 (29.9%) individuals. Ocular manifestations were present in 93 (21.1%) participants and the most frequent was cataract in 59 (13.4%) participants. Multivariate logistic regression analysis showed that participants who were illiterate (adjusted odds ratio [AOR] 2.80, 95% confidence interval [CI] 1.47–5.33) and those aged greater than 40 years (AOR 5.59, 95% CI 2.69–11.61) were more likely to have ocular manifestations. The odds of having ocular manifestations were greater in participants with treatment substitution or changes (AOR 2.11, 95% CI 1.16–3.82). Conclusions: Cataract and refractive errors were prevalent among PLHIV. PLHIV should be encouraged to have regular ophthalmic checkups. Individuals with lower education levels and older age should be counseled regarding eye care and timely reporting of ocular symptoms.

The importance of anti-HIV antibodies mediating antibody-dependent cell-mediated cytotoxicity (ADCC) in protective immunity against HIV is recognized recently. The purpose of this study was to measure the functional ADCC response at different stages of HIV infection in a well-defined HIV+ cohort, including 20 recently infected individuals, 30 with long-term slow-progressive, 24 with short-term slow-progressive and 32 with progressive HIV infection using a rapid fluorometric ADCC assay. The antibodies mediating ADCC were found in all disease stages. These antibodies were detectable at as early as 25 days after the estimated date of infection, however, did not influence the viral load set point probably indicating no major influence on the early course of the disease. However, the frequency and magnitude of functional ADCC responses were associated with higher CD4⁺T cell count and lower viral load and were significantly lower in progressors compared with other groups. The usefulness of the ADCC responses in longer viral control was assessed in a subset of participants with slowly progressing HIV infection. In these individuals, the ADCC responses observed at the visit 1 were found to be increased over time and were associated with lower plasma viral load estimated 4 to 15 years later in the disease course. Overall, the study findings confirm the role of ADCC antibodies in reducing the viral burden and also indicate the probable role of sustained functional ADCC responses in reducing the viral burden during the later period of HIV infection.