Histological evidence and clinical Correlations of renal TB-IRIS in HIV-positive patients and outcomes

Background Tuberculosis immune reconstitution inflammatory syndrome [TBCIRIS] is a well described clinical entity in HIV-infected patients that can affect multiple organs. There is however a paucity of information regarding renal involvement. This study aimed to illustrate the clinical, biochemical and histopathological features of HIV patients with suspected renal TBCIRIS, and to assess the mortality and renal outcomes of these patients. Methods The study was an observational, retrospective review of two established HIV positive renal biopsy registries [Groote Schuur Hospital and Livingstone Hospital Port Elizabeth, Eastern Cape].Renal biopsies were reviewed for the presence of granulomatous interstitial nephritis [GIN]. Patients’ folders and laboratory records were reviewed for evidence of tuberculosis [TB] and TBCIRIS. They were also reviewed for other causes of GIN i.e. drugs, fungal infection, sarcoidosis and infection. The study was approved by the UCT research ethics committee. The data was then analysed comparing 3 groups: [TB: no IRIS] (all TB cases with no features of IRIS), [TB + IRIS] (all cases with features of TBCIRIS) and [Other] (other causes of GIN). Results 68 HIV-positive renal biopsies were identified with GIN. The mean age was 37.5±9.1 years. There were 33 males (48.5%); 61 (89.7%) were of African black ethnicity, and there were no Caucasians in the study. 29 patients (43%) were noted to be on other medications known to cause GIN. The mean time from ART initiation to biopsy was 12 weeks, with the shorter average time being in the [TB + IRIS] group (6 weeks). The mean CD4 at biopsy was 105cells/µL, with the lowest CD4 seen in the in the [TB + IRIS] group (81cells/µL) (PC value 0.0175). The granulomas in the [TB + IRIS] group were noted to be more well-formed, with the highest number of poorly formed granulomas found in the [TB: no IRIS] group (25%) Sixteen (25%) of subjects had died within 2 years of their biopsy, with the majority of deaths occurring in the [TB : no IRIS] group (12/48, 44%), (PCvalue!0.01). Conclusion This study is the largest series of renal TBCIRIS that adds to the very limited case reports in the literature. There is a clinical entity of TB renal CIRIS that is associated with GIN on renal biopsy. Significant findings were those of a shorter time from ART initiation to biopsy in the [TB + IRIS] group, a lower CD4 count at biopsy and nadir in the [TB + IRIS] group with more well-formed granulomas. The majority of deaths within 2 years were noted in the [TB: no IRIS] group. This entity seems to be in keeping with other TBC IRIS descriptions previously published

Risk factors for Coronavirus disease 2019 (Covid-19) death in a population cohort study from the Western Cape province, South Africa

Risk factors for coronavirus disease 2019 (COVID-19) death in sub-Saharan Africa and the effects of human immunodeficiency virus (HIV) and tuberculosis on COVID-19 outcomes are unknown. We conducted a population cohort study using linked data from adults attending public-sector health facilities in the Western Cape, South Africa. We used Cox proportional hazards models, adjusted for age, sex, location, and comorbidities, to examine the associations between HIV, tuberculosis, and COVID-19 death from 1 March to 9 June 2020 among (1) public-sector “active patients” (≥1 visit in the 3 years before March 2020); (2) laboratory-diagnosed COVID-19 cases; and (3) hospitalized COVID-19 cases. We calculated the standardized mortality ratio (SMR) for COVID-19, comparing adults living with and without HIV using modeled population estimates.Among 3 460 932 patients (16% living with HIV), 22 308 were diagnosed with COVID-19, of whom 625 died. COVID19 death was associated with male sex, increasing age, diabetes, hypertension, and chronic kidney disease. HIV was associated with COVID-19 mortality (adjusted hazard ratio [aHR], 2.14; 95% confidence interval [CI], 1.70–2.70), with similar risks across strata of viral loads and immunosuppression. Current and previous diagnoses of tuberculosis were associated with COVID-19 death (aHR, 2.70 [95% CI, 1.81–4.04] and 1.51 [95% CI, 1.18–1.93], respectively). The SMR for COVID-19 death associated with HIV was 2.39 (95% CI, 1.96–2.86); population attributable fraction 8.5% (95% CI, 6.1–11.1)