Definition, diagnosis, and management of COVID-19-associated pulmonary mucormycosis: Delphi consensus statement from the Fungal Infection Study Forum and Academy of Pulmonary Sciences, India.

COVID-19-associated pulmonary mucormycosis (CAPM) remains an underdiagnosed entity. Using a modified Delphi method, we have formulated a consensus statement for the diagnosis and management of CAPM. We selected 26 experts from various disciplines who are involved in managing CAPM. Three rounds of the Delphi process were held to reach consensus (≥70% agreement or disagreement) or dissensus. A consensus was achieved for 84 of the 89 statements. Pulmonary mucormycosis occurring within 3 months of COVID-19 diagnosis was labelled CAPM and classified further as proven, probable, and possible. We recommend flexible bronchoscopy to enable early diagnosis. The experts proposed definitions to categorise dual infections with aspergillosis and mucormycosis in patients with COVID-19. We recommend liposomal amphotericin B (5 mg/kg per day) and early surgery as central to the management of mucormycosis in patients with COVID-19. We recommend response assessment at 4-6 weeks using clinical and imaging parameters. Posaconazole or isavuconazole was recommended as maintenance therapy following initial response, but no consensus was reached for the duration of treatment. In patients with stable or progressive disease, the experts recommended salvage therapy with posaconazole or isavuconazole. CAPM is a rare but under-reported complication of COVID-19. Although we have proposed recommendations for defining, diagnosing, and managing CAPM, more extensive research is required.

Human immunodeficiency virus-associated lipodystrophy: an objective definition based on dual-energy x-ray absorptiometry-derived regional fat ratios in a South Asian population.

OBJECTIVE: To develop an objective definition of human immunodeficiency virus (HIV)-associated lipodystrophy by using regional fat mass ratios and to assess the utility of anthropometric and skinfold measurements in the initial screening for lipodystrophy. METHODS: Male patients between 25 and 50 years old with proven HIV infection (highly active antiretroviral therapy [HAART]-naïve subjects and those receiving successful HAART) were studied and compared with body mass index (BMI)-matched HIV-negative control subjects. Anthropometric variables, body composition, dual-energy x-ray absorptiometry findings, and metabolic variables were compared among the 3 study groups and between those patients with and those without lipodystrophy. RESULTS: Trunk fat/lower limb fat mass ratio >2.28 identified 54.3% of patients with HIV receiving HAART as having lipodystrophy and had the highest odds ratio for predicting metabolic syndrome. The "clinical diagnosis of lipodystrophy" and the "clinical scoring system" had too many false-positive and false-negative results. Triceps skinfold thickness (SFT)/BMI ratio ≤0.49 and abdominal SFT/triceps SFT ratio >1.385 have good sensitivity but poor specificity in identifying lipodystrophy. In comparison with HAART-naïve patients with HIV, those receiving HAART had significantly higher insulin resistance, and a significantly greater proportion had impaired glucose tolerance and dyslipidemia. Among patients receiving HAART, those with lipodystrophy had a greater degree of insulin resistance, higher triglyceride levels, and lower levels of high-density lipoprotein cholesterol. CONCLUSION: The trunk fat/lower limb fat mass ratio in BMI-matched normal subjects can be used to derive cutoff values to define lipodystrophy objectively in HIV-infected patients. Defining lipodystrophy in this way is better than other methods of identifying those patients with increased cardiovascular risk. Triceps SFT/BMI and abdominal SFT/triceps SFT ratios may be useful as screening tools in resource-poor settings.

Risk factors for mortality in a south Indian population on generic antiretroviral therapy.

BACKGROUND: Antiretroviral treatment (ART) programs from low-income countries utilizing standardized ART regimens, simplified approaches to clinical decision making and basic lab monitoring have reported high mortality rates. We determined the risk factors for mortality among HIV-infected adults following the initiation of ART from a single center in south India. METHODS: ART-naive HIV-infected south Indian adults attending the Infectious Diseases clinic in a 2000-bed academic medical center in south India who were initiated on ART (generic, fixed-dose combinations) as per the national guidelines were followed up. Cases (32 patients who died) were compared with age and sex matched controls. RESULTS: Eight-hundred and twenty-two patients were started on ART from January 1, 2000 to December 31, 2008. The cumulative mortality was 6.8% (56/822). Among the cases mean age was 44 years, 18% were women and mean CD4 counts was 107 cells/microl. Among the controls mean age was 41 years, 18% were women and mean CD4 counts were 113 cells/microl. Stavudine based ART was predominant 62.5% in the cases vs 37.5% in the controls, followed by zidovudine based therapy in 31.2% of cases and 43.7% in the controls. Tenofovir based therapy was used in 6.2% of cases vs 18.7% in the controls. The commonest causes of death were drug toxicity 19%, advanced Acquired Immunodeficiency Syndrome (AIDS) in 37%, Immune Reconstitution Inflammatory Syndrome (IRIS) in 16%, non AIDS related deaths in 22% and malignancies 6%. In a univariate analysis, absolute lymphocyte count <1200 cells/cmm (p=0.03), development of immune reconstitution inflammatory syndrome (IRIS) (p=0.000) and mean CD4 cell count increase <75 cells/microl after 1 year of ART (p=0.001) were significantly associated with mortality. CONCLUSIONS: The mortality among our patients was comparable to that reported from other low-income countries. Earlier initiation of ART may reduce the high mortality rates observed.

Aetiology of prolonged fever in antiretroviral-naïve human immunodeficiency virus-infected adults.

BACKGROUND: Prolonged fever is a common symptom among human immunodeficiency virus (HIV) infected individuals, and is usually due to a cause that is easily treatable. Limited data are available regarding the causes of fever in HIV-infected Indian patients. In this paper, we have profiled the causes of prolonged fever in a cohort of HIV-infected Indian patients and have developed suitable algorithms to assist in an early diagnosis. METHODS: From February 1997 to October 1998 (20 months), 100 HIV-infected patients (age > 12 years) were evaluated for 100 episodes of prolonged fever (fever > 100 degrees F for more than 2 weeks in outpatients and > 3 days in inpatients). Patients with terminal acquired immunodeficiency syndrome (AIDS) were excluded. Patients were evaluated on the basis of the symptoms associated with prolonged fever and investigated according to pre-existing algorithms. RESULTS: Among such episodes of fever, infection was the major cause and included tuberculosis, especially the extra-pulmonary and disseminated forms (69%), cryptococcosis (10%) and Pneumocystis carinii pneumonia (7%). Other causes included bacterial pneumonia, amoebic liver abscess, disseminated histoplasmosis and cerebral toxoplasmosis. Patients were naïve for antiretroviral therapy and did not receive prophylaxis for opportunistic infections. The diagnostic yield of ultrasound of the abdomen (85%), fine-needle aspiration cytology of enlarged lymph nodes (75.6%) and bone marrow trephine biopsy (41.6%) were found to be high in our study. CONCLUSIONS: Tuberculosis is the commonest cause of prolonged fever in HIV-infected adults in India. Non-infectious causes were not seen in this series. We have suggested an algorithmic approach for establishing the cause of fever in these patients. In situations where laboratory evaluation does not reveal a cause for prolonged fever, a therapeutic trial with antituberculous therapy in selected patients is justified.