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.

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.

Background: It is important to identify and manage determinants of virological failure among HIV infected individuals on treatment for achieving viral suppression. This study aimed to identify proportion and factors associated with virological failure among HIV infected individuals receiving first line antiretroviral therapy (ART).Methods: A total of 2670 adult HIV infected individuals attending ART centre at ICMR-National AIDS Research Institute, between January 2005 and June 2019 and having their recent viral load done after implementation of guidelines on routine viral load testing were included. Data were reviewed and analysed.Results: Of the 2670 people living with HIV (PLHIV) on first line antiretroviral therapy, 48% were male and 69% were more than 40 years of age. Mean baseline CD4 count at ART initiation was 252 cells/mm3 (SD:210, IQR 116-313) Overall, 13% (340/2670) of the participants showed virological failure. In multivariate analyses, participants with younger age and males retained significant association. Those with baseline CD4 counts of less than or equal to 500 cells/mm3 at treatment initiation (adjusted OR 1.71; 95% CI 1.08-2.70; p=0.022) and ART adherence ≤95% within last three months of recent viral load determination (adjusted OR 1.55, 95% CI of AOR 1.04-2.32; p=0.031) had higher risk for virological failure as compared to others. PLHIV with ART substitution due to various reasons were almost twice as likely to have virological failure (adjusted OR 1.83, 95% CI 1.44-2.33; p<0.001).Conclusions: It is crucial to focus on factors leading to virological failure among HIV infected individuals attending ART centre. Early linkage to treatment and ART initiation along with adherence counselling at every follow up visit play an important role in mitigating virological failure.

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: HIV-1 Viral load (VL) measures efficiency of the antiretroviral therapy (ART) after treatment initiation and helps to diagnose virological failures at an early stage. Current VL assays require sophisticated laboratory facilities. As well as there are other challenges pertaining to insufficient laboratory access, cold-chain management and sample transportation. Hence the number of HIV-1 VL testing laboratories is inadequate in the resource limited settings. The revised national tuberculosis elimination programme (NTEP) in India has developed a vast network of point of care (PoC) testing facilities for diagnosis of tuberculosis and several GeneXpert platforms are functional under this programme. Both the GeneXpert HIV-1 assay and HIV-1 Abbott real time assay are comparable and GeneXpert HIV-1 assay can be used as PoC for HIV-1 Viral load testing. Also, the dried blood spot (DBS) as a sample type has been considered as a good option for HIV-1 VL testing in hard to reach areas. This protocol is therefore developed to assess the feasibility of integrating HIV-1 VL testing among people living with HIV (PLHIV) attending ART centres using the two public health models under the current programme: 1. HIV-1 VL testing using GeneXpert platform and plasma as a sample type, and 2. HIV-1 VL testing using Abbott m2000 platform and DBS as a sample type. Methods: This ethically approved feasibility study will be implemented at two moderate to high burden ART centres where VL testing facility is not available in the town. Under Model-1, arrangements will be made to carry out VL testing on the adjacent GeneXpert facility and under Model-2, DBS will be prepared on site and couriered to identified viral load testing laboratories. In order to assess the feasibility, data will be collected on pretested questionnaire pertaining to number of samples tested for VL testing, number of samples tested for tuberculosis (TB) diagnosis and the turnaround time (TAT). In-depth interviews will be conducted among the service providers at ART centre and different laboratories for addressing any issues regarding the model implementation. Results: The proportion of PLHIV tested for VL at ART centres, total TAT for both models including TAT for sample transportation, sample testing and receipt of results as well as proportion of sample rejections and reasons for the same, correlation coefficient between DBS based and plasma based VL testing will be estimated using various statistical tools. Conclusion: If found promising, these public health approaches will be helpful for the policy makers and program implementation in scaling up HIV-1 viral load testing within India.

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.