A Phase-IV Non-interventional Study to Assess Virological Effectiveness, Safety, and Tolerability of DTG-based Antiretroviral Therapy in HIV-1 Infected Indian Persons Living with HIV.

BACKGROUND: Dolutegravir (DTG) is a novel yet preferential first- and -second-line treatment for persons living with HIV (PLH). Owing to its recent introduction, DTG-based regimens have not undergone a comprehensive, systematic evaluation regarding their real-world utilization and safety profile among a sizeable Indian population. OBJECTIVE: This study aimed to assess the 24 week immunovirological outcomes, anthropometric and metabolic changes, tolerability, and adverse events (AEs) of DTG-based antiretroviral (ART) regimens. METHODS: A single-centre phase-IV non-interventional observational study involving 322 ART naïve and treatment-experienced PLH initiating DTG-based-regimens until October 2022 were followed up for outcomes at 24 weeks. RESULTS: At 24 weeks, all PLH (n = 113) in the naïve group, all PLH (n = 67) in the first-line substitution group, 93.9% PLH (n = 46) in the first-line failure group, and 95.7% PLH (n = 89) in the second-line substitution group were virologically suppressed to plasma HIV-RNA <1000 copies/mL. Virological suppression rates to plasma HIV-RNA <200 copies/mL and <50 copies/mL were consistent among PLH who received DTG as first- or second-line ART. The mean-unadjusted weight gain observed was 3.5 kg (SE: 0.330), and it was significantly higher in PLH with poorer health at baseline (either HIV-RNA ≥ 1000 copies/ml or CD4 cell count <350 cells/µL). Overall, 27.3% PLH (n = 88) gained ≥10% of their baseline body weight, corresponding to 3.7% incidence (n = 12) of treatment-emergent clinical obesity. DTG had an overall lipid-neutral effect, with an advantageous effect being observed in PLH switching from non-nucleoside analogue reverse-transcriptase inhibitors (NNRTI) or ritonavir-boosted protease inhibitors (b/PI), especially in dyslipidemic pre-treated PLH (median change in total cholesterol: 28.5 mg/dL and triglycerides: 51 mg/dL), possibly emanating from the withdrawal of the offending ART. The incidence of DTG-specific AEs, including CNS AEs, was low. Two PLH developed proximal myopathy and one developed transaminitis, warranting DTG discontinuation. Asymptomatic serum-CPK elevation and drug-induced transaminitis were seen in 25.2% (n = 27) and 3.2% (n = 10) PLH, respectively. No apparent negative effects on renal function were detected. CONCLUSION: Our results from a large Indian cohort indicate a favourable virological and metabolic response, with good tolerance of DTG-based ART at 24 weeks.

Gastrointestinal manifestations in symptomatic Coronavirus disease - 19 patients and its relevance in predicting severity and outcome.

INTRODUCTION: Recent developments characterizing the pathophysiological basis of infection in the Coronavirus disease - 19 (COVID-19) have stirred great interest in studying this disease outside the purview of respiratory involvement and especially focusing on the gastrointestinal (GI) system. The present study involving a large cohort of COVID-19-infected patients reports on the characteristics of GI manifestations in patients infected with COVID-19 as well as the predictive role in their association with disease severity and adverse outcomes. METHODS: A retrospective cohort study was carried out in a tertiary care hospital in northern India. Descriptive analysis of GI symptoms was carried out followed by predictive analysis assessing COVID-19 severity and with the primary endpoint of 28-day in-hospital all-cause mortality. RESULTS: Of 3842 hospitalized COVID-19 patients, 2113 (55%) were symptomatic. GI symptoms were present in 163 (7.1%) patients. Common GI symptoms were diarrhea 65 (3.1%), anorexia 61 (2.9%) and vomiting 37 (1.8%). Mild and moderate-to-severe disease was seen in 1725 (81.6%) and 388 (18.4%) patients, respectively. Logistic regression showed greater odds of moderate-to-severe disease in patients with any GI symptoms (odds ratio [OR] 1.849, 95% CI 1.289-2.651 [p = 0.001]) and anorexia in particular (OR 2.797, 95% CI 1.647-4.753 [p = 0.001]); however, on multivariable-analysis, this association lost its significance. A total of 172 patients succumbed to illness. In the Cox proportional hazards model for mortality, patients with any GI symptom (HR 2.184, 95 CI 1.439-3.317 [p < 0.001]) and anorexia (HR 3.556, 95% CI 2.155-5.870 [p < 0.001]) had higher risk. In multi-variable analysis after adjustment to age, sex, oxygen saturation and comorbidities, the presence of any GI symptom was a significant predictor of mortality (hazard ratio adjusted [HRadj] 1.758, 95% CI 1.147-2.694 [p = 0.010]). CONCLUSION: GI symptoms were common among patients infected with COVID-19. The presence of any GI symptom was a significant predictor of the risk of mortality after adjustment to respiratory failure, age, sex and pre-existing comorbidities. The clinical and pathophysiological basis of these associations has been explored.

Does Raised Transaminases Predict Severity and Mortality in Patients with COVID 19?

Background: The most dreaded pandemic grappling world now, the Coronavirus Disease 2019 (COVID-19), chiefly involves the respiratory system; nevertheless, it is a multisystem disorder. Its involvement of the hepatic system is considerable; however, still emerging are its clinical implications and the effects on morbidity and mortality. Aim: The aim of this study is to report on the various aspects of its hepatic involvement by describing the alterations in tests of liver function and its significance in the disease outcome in a cohort of hospitalized COVID-19 patients at a tertiary center in northern India. Methods: This is a retrospective cohort study conducted in a tertiary-care hospital in northern India. All confirmed hospitalized COVID-19 cases aged 15 and above from Apr to Oct 2020 with no pre-existing liver disease were included. The primary endpoint was death at 28 days. Statistical analysis included descriptive analysis, sensitivity-specificity, and univariable and multivariable regression analysis as well as survival analysis. Results: A total of 708 patients with COVID-19 fulfilled the inclusion criteria included 561 (79.2%) males and 147 (20.8%) females. The median age was 49 (IQR = 25) years. Mild and moderate/severe disease were seen in 508 (71.8%) and 200 (28.2) patients, respectively. Serum bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were elevated in 6.92%, 69.91%, and 80.22% of patients, respectively. In univariable logistic regression, AST [odds ratio; OR 1.008 95% CI (1.005-1.012) per 1 IU/L increase] and ALT [OR 1.005 95% CI (1.002-1.007) per 1 IU/L increase] were significantly associated with the odds of moderate to severe disease but only AST was significant after adjustment to age, sex, and comorbidity [adjusted odds ratio; aOR 1.007 95% CI (1.003-1.011) per 1 IU/L increase]. Serum albumin was negatively associated with the odds of moderate to severe disease and remained significant in the adjusted model [aOR 0.217 95%CI (0.149-0.316) per 1 g/dL increase].Ninety-six patients succumbed to illness [case fatality rate; CFR 13.6%). In adjusted Cox Proportional-Hazards Model for mortality, AST [adjusted hazard ratio; aHR 1.002 95% CI (1.000-1.003) per 1 IU/L increase] and serum albumin [aHR 0.396 95% CI (0.285-0.549) per 1 g/dL increase] showed significant association with mortality. Conclusion: Liver function abnormalities are common in patients with COVID-19. In particular, AST and serum albumin levels are effective predictors of disease severity and mortality and can be used as markers of fatal disease in the management as well as prognostication of COVID-19.

Ferritin and Hemoglobin as Predictors of Fatal Outcome in COVID-19: Two Sides of the Same Coin.

INTRODUCTION: Infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have multisystemic involvement with hyperinflammation being a cardinal feature and deranged iron metabolism having a possible role. In this premise, we studied the prognostic value of two markers of iron metabolism ferritin and hemoglobin. METHODOLOGY: A retrospective-cohort study was carried out in a tertiary hospital in northern India involving 210 hospitalized COVID-19 patients aged 15-and above. Analysis was done for clinical profile, comorbidities and basic laboratory indices including ferritin-hemoglobin ratio (FHR) with primary end-point being in-hospital all-cause mortality. RESULTS: Median serum ferritin levels (640.00ng/mL vs 220.00ng/mL) were significantly higher among non-survivors as against survivors while median hemoglobin levels were significantly lower (12.12g/dL vs 13.73g/dL). Serum ferritin levels >400ng/mL (Sn 80%, Sp 70%) predicted mortality with high sensitivity and specificity. Notably, serum ferritin levels >400ng/mL (HR 11.075 [1.481-82.801]) and anemia, defined as a hemoglobin of <12g/dL for females and < 13g/dL for males and were significantly associated with the risk of mortality in a univariable Cox-proportional hazards regression. The median FHR was significantly higher among non-survivors compared to survivors (56.98 vs 17.17). FHR>31 (Sn 85% Sp 71.6%) was highly sensitive and specific for predicting mortality. The multivariable analysis indicated that FHR >31 remained an independent risk factor for mortality (HR 12.293 [3.147-48.028]). CONCLUSION: Ferritin-hemoglobin ratio (FHR), which encompasses into a single index, the effects of both elevated levels of ferritin and the severity of anemia, seems to perform particularly well as a prognostic marker and emerged as an independent risk factor for mortality in COVID-19 patients. Hyperferritinemia and anemia, both, are inexorably interlinked in addition to having a role, directly or indirectly in the disease pathophysiology. Ferritin and hemoglobin, hence should be seen as two sides of the same coin rather than as two discrete entities.

Clinical characteristics and clinical predictors of mortality in hospitalised patients of COVID 19 : An Indian study.

BACKGROUND: The rapid spread of the coronavirus disease 2019 (COVID-19) with high mortality rate necessitates disease characterization and accurate prognostication for prompt clinical decision-making. The aim of this study is to study clinical characteristics and predictors of mortality in hospitalized patients with COVID-19 in India. METHODS: Retrospective cohort study was conducted in a tertiary care hospital in northern India. All consecutive confirmed hospitalized COVID-19 cases aged 15 years and older from 13 Apr till 31 Aug 2020 are included. Primary end point was 30-day mortality. RESULTS: Of 1622 patients ,1536 cases were valid. Median age was 36 years, 88.3% were men and 58.1% were symptomatic. Fever (37.6%) was commonest presenting symptom. Dyspnea was reported by 15.4%. Primary hypertension (8.5%) was commonest comorbidity, followed by diabetes mellitus (6.7%). Mild, moderate, and severe hypoxemia were seen in 3.4%, 4.3%, and 0.8% respectively. Logistic regression showed greater odds of moderate/severe disease in patients with dyspnea, hypertension, Chronic Kidney Disease (CKD), and malignancy. Seventy six patients died (4.9%). In adjusted Cox proportional hazards model for mortality, patients with dyspnea (hazard ratio [HR]: 14.449 [5.043-41.402]), altered sensorium (HR: 2.762 [1.142-6.683]), Diabetes Mellitus (HR: 1.734 [1.001-3.009]), malignancy (HR:10.443 [4.396-24.805]) and Chronic Liver Disease (CLD) (HR: 14.432 [2.321-89.715]) had higher risk. Rising respiratory rate (HR: 1.098 [1.048-1.150]), falling oxygen saturation (HR: 1.057 per unit change 95% CI: 1.028-1.085) were significant predictors. CONCLUSION: Analysis suggests that age, dyspnea, and malignancy were associated with both severe disease and mortality. Diabetes Mellitus and Chronic Liver Disease were associated with increased the risk of fatal outcome. Simple clinical parameters such as respiratory rate and oxygen saturation are strong predictors and with other risk factors at admission can be effectively used to triage patients.