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BACKGROUND: Observational data suggests that low vitamin D status is associated with an increased incidence of pulmonary tuberculosis (TB) and mortality among people living with HIV. The primary aims of this study were to assess the effect of vitamin D(3) supplementation on the risk of mortality and incidence of pulmonary TB among adults initiating antiretroviral therapy (ART). METHODS: We conducted a randomized, double-blind, placebo-controlled trial of vitamin D(3) supplementation among adults living with HIV who initiated ART with low serum 25-hydroxyvitamin D (25(OH)D) levels at four large HIV care and treatment centers in Dar es Salaam, Tanzania. The vitamin D group received weekly 50,000 IU vitamin D(3) supplements for the first month of ART followed by daily 2,000 IU vitamin D(3) supplements. The placebo arm received a matching weekly and daily placebo regimen. The trial follow-up duration was one year and the primary efficacy outcomes were death and incident pulmonary TB. An intent-to-treat analysis was followed. This study is registered with ClinicalTrials.gov, NCT01798680, and is completed. FINDINGS: Between 24 February 2014 and 7 March 2018, 4,000 adults initiating ART were enrolled in the trial and followed-up for one year. A total of 415 deaths were recorded; 211 in the vitamin D(3) group and 204 in the placebo group. Among all randomized participants, there was no overall effect of vitamin D(3) supplementation on the risk of mortality (hazard ratio (HR): 1·04; 95% CI: 0·85–1·25; P=0·73). There was also no difference in the overall incidence of pulmonary TB between the vitamin D(3) (50 events) and placebo groups (67 events) (HR: 0·78; 95% CI: 0·54–1·13; P=0·19). In terms of adverse events, the vitamin D(3) regimen did not increase the risk of hypercalcemia (3 events vitamin D(3) group, 2 events placebo group, relative risk: 1.25; 95% CI: 0.43–3.66; Fisher’s exact P =1·00). There were 101 hospitalizations reported in the vitamin D(3) group and 94 in the placebo group (incidence rate ratio: 1.06; 95% CI: 0.80–1.41; P=0·66). INTERPRETATION: Additional research is needed before vitamin D(3) supplementation should be considered for implementation in HIV care and treatment programs for the prevention of pulmonary TB or mortality.

Background : Feline idiopathic pulmonary fibrosis is an irreversible disease that is rarely reported in veterinary clinical routine, with this case as the second reported in Brazil. This study aimed to describe a case of idiopathic pulmonary fibrosis in a domestic cat. Case : A 10-year-old female cat with a history of respiratory distress was treated at the Veterinary Hospital of the State University of Santa Cruz (HV-UESC). The first signs were observed three months before clinical care, characterized mainly by dyspnea that was more pronounced during nighttime. There was no history of previous illnesses or prior drug use. The cat lived with two other domiciled cats, did not have access to the street, and had restricted access to the terrace of the building, from where other animals could have possibly entered. Physical examination showed a poor body condition with a temperature of 37°C and dehydration estimated at 9%.The animal was observed to remain in an orthopedic position, with tachypnea (109 mvm), wheezing through the mouth, and severe expiratory dyspnea. Pulmonary auscultation detected fine discontinuous adventitious noises. There were no changes in the cardiac function in terms of rhythm, frequency, or auscultation. Oxygen therapy and slow administration of 0.9% NaCl solution were performed; moreover, blood was collected for complete blood count, in which no abnormalities were observed. Thoracic radiography was performed on the cat, and the results showed a mixed pulmonary pattern characterized by bronchiectasis, thickening of the bronchiolar wall, and an unstructured interstitial pattern throughout the pulmonary area. Shortly after the beginning of the clinical care, the animal died due to respiratory arrest and was necropsied. The main macroscopic finding was pulmonary edema. Lung samples were subjected to microscopic evaluation, which revealed extensive multifocal areas of alveolar septa thickening characterized by smooth muscle hyperplasia, hypertrophy associated with intense fibroplasia, type II pneumocyte hyperplasia, and discrete intra-alveolar and interstitial lymphohistiocytic inflammatory infiltrate. Based on the clinical, radiographic, macroscopic, and histopathological findings, the diagnosis of idiopathic pulmonary fibrosis was established. Discussion : This is the second case of feline idiopathic pulmonary fibrosis reported in Brazil. The observations in the physical examination, namely, the orthopedic positioning, dyspnea, and mouth breathing, are characteristic of respiratory distress and showed the severity of the lesions in the respiratory system. The clinical manifestation of idiopathic pulmonary fibrosis in cats reveals that gas exchange had already been compromised, which indicates an advanced stage of disease. In addition to respiratory signs, systemic signs such as apathy, anorexia, weight loss, and dehydration also confirm the severity of the condition. Because of the severity of the clinical condition at the time of the clinical care, it was not possible to adopt a more aggressive therapeutic approach, and the animal eventually died. Taken together, the clinical, radiographic, macroscopic, and histopathological findings led to the diagnosis of idiopathic pulmonary fibrosis. Literature states that the diagnosis of idiopathic pulmonary fibrosis requires clinical, radiographic, and histopathological findings consistent with the alterations observed in this cat. Much remains to be understood with regard to idiopathic pulmonary fibrosis in felines, since the currently available information is sparse and divergent. The description of these cases is extremely important to increase the available knowledge and to improve the prognosis and therapy for this serious disease.

In the Mitra plus study of prevention of mother-to-child transmission of HIV-1, which included 501 women in Dar es Salaam, Tanzania, triple antiretroviral therapy (ART) was given from late pregnancy throughout breastfeeding up to 6 months postnatally. Here we report findings in a sub-cohort of women with ≤200 CD4cells/μL at enrolment who were continued on ART for life and followed up during 24 months after delivery to determine virologic and immunologic responses, drug resistance and mortality. Blood samples for viral load and CD4 counts testing were collected at enrolment and at 3, 6, 12 and 24 months postpartum. HIV drug resistance testing was performed at 12 months. Data analysis included descriptive statistics and multivariate analysis using Generalized Estimated Equations of 73 women with at least two postpartum assessments. The mortality analysis included 84 women who had delivered. The proportion of women with a viral load ≥400 copies/mL was 97% (71/73) at enrolment, 16% (11/67), 22% (15/69), 61% (36/59) and 86% (48/56) at 3, 6, 12 and 24 months postpartum, respectively. The proportion of women with immunologic failure was 12% (8/69), 25% (15/60) and 41% (24/58) at 6, 12 and 24 months, respectively. At 12 months, drug resistance was demonstrated in 34% (20/59), including 12 with dual-class resistance. Self-report on drug adherence was 95% (64/68), 85% (56/66), 74% (39/53) and 65% (30/46) at 3, 6, 12 and 24 months, respectively. The mortality rate was 5.9% (95% CI 2.5-13.7%) at 24 months. The probability of virologic and immunologic failure was significantly higher among women who reported non-perfect adherence to ART at month 24 postpartum. Following an initial decline of viral load, virologic failure was common at 12 and 24 months postpartum among women initiated on ART for life during pregnancy because of low CD4 cell counts. A high proportion of viremic mothers also had resistance mutations. However, at 24 months follow-up, the mortality rate was still fairly low. Continuous adherence counseling and affordable means of monitoring of the virologic response are crucial for successful implementation of the WHO Option B+ guidelines to start all HIV-infected pregnant women on ART for life

Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 checklist. (PDF 131Â kb)

SPIRIT 2013 checklist: recommended items to address in a clinical trial protocol and related documents (DOC 122 kb)

SPIRIT 2013 checklist: recommended items to address in a clinical trial protocol and related documents (DOC 122 kb)

Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 checklist. (PDF 131Â kb)