Mortality in HIV-infected patients with tuberculosis treated with streptomycin and a two-week intensified regimen: data from an HIV cohort study using inverse probability of treatment weighting.

Background. Despite the dramatic scale-up of antiretroviral therapy in low- and middle-income countries, tuberculosis (TB) is still the main cause of death among HIV-infected patients in resource-limited settings. Previous studies in patients with TB meningitis suggest that the use of higher doses of common anti-TB drugs could reduce mortality. Methods. Using clinical data from an HIV cohort study in India, we compared the mortality among HIV-infected patients diagnosed with TB according to the regimen received during the first two weeks of treatment: standard anti-tuberculosis therapy (ATT) (N = 847), intensified ATT (N = 322), and intensified ATT with streptomycin (N = 446). The intensified ATT comprised double dose of rifampicin and substitution of ethambutol with levofloxacin. Multivariate analysis was performed using Cox proportional hazard models and inverse probability of treatment weighting (IPTW) based on propensity scores. Patients with TB meningitis were excluded. Results. The use of intensified ATT alone did not improve survival. However, when streptomycin was added, the use intensified ATT was associated with reduced mortality in Cox models (adjusted hazard ratio 0.72, 95% CI [0.57-0.91]) and after IPTW (hazard ratio 0.77, 95% CI [0.67-0.96]). Other factors associated with improved survival were high serum albumin concentration, high CD4 lymphocyte cell-counts, and high glomerular filtration rates. Factors associated with increased mortality were high urea concentrations, being on antiretroviral therapy at the time of ATT initiation and high BUN/creatinine ratio. In an effect modification analysis, the survival benefits of the intensified ATT with streptomycin disappeared in patients with severe hypoalbuminemia. Conclusion. The results of this study are in accordance with a previous study from our cohort involving patients with TB meningitis, and suggest that an intensified 2-week ATT with streptomycin could reduce mortality in HIV infected patients with TB. As this is an observational study, we should be cautious about our conclusions, but given the high mortality of HIV-related TB, our findings deserve further research.

Incidence and mortality of tuberculosis before and after initiation of antiretroviral therapy: an HIV cohort study in India.

INTRODUCTION: India has the highest burden of tuberculosis (TB) in the world, but the epidemiology of HIV-associated TB is not well known. METHODS: We describe the incidence and the mortality of TB from HIV diagnosis to antiretroviral therapy (ART) initiation (pre-ART group) and after ART initiation (on-ART group) in an HIV cohort study in Anantapur, India. Multivariable analysis of factors associated with TB was performed using competing risk regression and restricted cubic spline methods. RESULTS: A total of 4590 patients and 3133 person-years (py) of follow-up were included in the pre-ART group, and 3784 patients and 4756 py were included in the on-ART group. In the pre-ART group, the incidence of TB was high during the first month after HIV diagnosis and dropped nearly four times soon after. In the on-ART group, the incidence of TB increased after ART initiation reaching a peak in the third month. The probability of having TB within 30 months was 22.3% (95% confidence interval [CI], 21.1-23.6) in the pre-ART group and 17.8% (95% CI, 16.3-19.3) in the on-ART group. In a multivariable analysis, women had a lower risk of TB in both groups. Poor socio-economical conditions were associated with an increased risk of TB in the pre-ART group, but not in the group on-ART. While the association between low CD4 counts and TB was strong in the pre-ART group, this association was weaker in the on-ART group, and the highest risk of TB was seen in those patients with CD4 counts around 110 cells/mm3. The cumulative incidence of mortality at 12 months in patients with TB was 29.6% (95% CI, 26.9-32.6) in pre-ART TB and 34.9% (95% CI, 31-39.1) in on-ART TB. Half deaths before ART initiation and two thirds of deaths after ART initiation occurred in patients with TB. CONCLUSIONS: The high incidence and mortality of TB seen in this study underscore the urgent need to improve the prevention and diagnosis of HIV-associated TB in India. We found substantial differences between TB before and after ART initiation.

Prevalence and severity of anaemia stratified by age and gender in rural India.

Anaemia is a major public health problem in India. Although nearly three quarters of the Indian population live in rural areas, the epidemiology of anaemia in rural settings is not well known. We performed a retrospective observational study using routine clinical data from patients attending the out-patient clinics of a rural hospital in India from June 2011 to August 2014. The study included 73,795 determinations of haemoglobin. 49.5% of patients were female. The median haemoglobin concentration was 11.3 g/dL (interquartile range (IQR), 9.8-12.4) in females and 12.5 g/dL (IQR, 10.6-14.2) in males. Anaemia was present in the majority of children <10 years, women after puberty, and older adults. Children <5 years had the highest prevalence of anaemia, especially children aged 1-2 years. The high proportion of microcytic anaemia and the fact that gender differences were only seen after the menarche period in women suggest that iron deficiency was the main cause of anaemia. However, the prevalence of normocytic anaemia increased with age. The results of this study can be used by public health programmes to design target interventions aimed at reducing the huge burden of anaemia in India. Further studies are needed to clarify the aetiology of anaemia among older adults.

Factors associated with attrition, mortality, and loss to follow up after antiretroviral therapy initiation: data from an HIV cohort study in India.

BACKGROUND: Studies from sub-Saharan Africa have shown high incidence of attrition due to mortality or loss to follow-up (LTFU) after initiating antiretroviral therapy (ART). India is the third largest country in the world in terms of HIV infected people, but predictors of attrition after ART initiation are not well known. DESIGN: We describe factors associated with attrition, mortality, and LTFU in 3,159 HIV infected patients who initiated ART between 1 January 2007 and 4 November 2011 in an HIV cohort study in India. The study included 6,852 person-years with a mean follow-up of 2.17 years. RESULTS: After 5 years of follow-up, the estimated cumulative incidence of attrition was 37.7%. There was no significant difference between attrition due to mortality and attrition due to LTFU. Having CD4 counts <100 cells/µl and being homeless [adjusted hazard ratio (aHR) 3.1, 95% confidence interval (CI) 2.6-3.8] were associated with a higher risk of attrition, and female gender (aHR 0.64, 95% CI 0.6-0.8) was associated with a reduced risk of attrition. Living near a town (aHR 0.82, 95% CI 0.7-0.999) was associated with a reduced risk of mortality. Being single (aHR 1.6, 95% CI 1.2-2.3), illiteracy (aHR 1.3, 95% CI 1.1-1.6), and age <25 years (aHR 1.3, 95% CI 1-1.8) were associated with an increased risk of LTFU. Although the cumulative incidence of attrition in patients diagnosed with tuberculosis after ART initiation was 47.4%, patients who started anti-tuberculous treatment before ART had similar attrition to patients without tuberculosis (36 vs. 35.2%, P=0.19) after four years of follow-up. CONCLUSIONS: In this cohort study, the attrition was similar to the one found in sub-Saharan Africa. Earlier initiation of ART, improving the diagnosis of tuberculosis before initiating ART, and giving more support to those patients at higher risk of attrition could potentially reduce the mortality and LTFU after ART initiation.

Rapid Diagnosis of Pulmonary and Extrapulmonary Tuberculosis in HIV-Infected Patients. Comparison of LED Fluorescent Microscopy and the GeneXpert MTB/RIF Assay in a District Hospital in India.

HIV-related tuberculosis is difficult to diagnose and is associated with high morbidity and mortality. Recently, the World Health Organization has endorsed the GeneXpert MTB/RIF (Xpert) assay for the diagnosis of pulmonary tuberculosis in HIV-infected patients from developing countries, but information about the use of Xpert for the diagnosis of extrapulmonary tuberculosis is scarce. In this study, we compared the performance of light-emitting diode (LED) auramine fluorescent microscopy and the Xpert assay for the diagnosis of tuberculosis in HIV infected patients in a district hospital of India. Although at higher cost, Xpert outperformed LED fluorescent microscopy in all type of specimens, especially in cerebrospinal fluid where the number of positive results was increased 11 times. Pleural fluid, ascitic fluid, pus, and stool specimens also yielded positive results with the Xpert assay. When collecting two additional early-morning sputum samples, the increase of the number of positive results with the Xpert assay was lower than previously reported for HIV infected patients. Rifampicin resistance was observed in 2.2% of the cases. The results of this study show that the Xpert assay can dramatically improve the rapid diagnosis of tuberculous meningitis and other types of extrapulmonary tuberculosis of HIV infected patients.

Mortality associated with community-acquired cephalosporin-resistant Escherichia coli in patients admitted to a district hospital in a resource-limited setting.

Studies performed in developed countries have shown that infections by third generation cephalosporin resistant Escherichia coli (G3CREC) are associated with increased mortality, but data from developing countries are scarce. In this observational study, we collected clinical and microbiological information of 194 patients admitted to a district hospital in India who had community-acquired isolation of Escherichia coli. The proportion of patients with G3CREC was 79.4%. In a multivariable logistic regression analysis, factors associated with 21-day mortality were isolation from a normally sterile site, HIV infection and isolation of G3CREC. Strains of Escherichia coli isolated from normally sterile sites had lower levels of resistance to quinolones and beta-lactam antibiotics. The proportion of meropenem and ciprofloxacin resistance was 11.1% and 80.9% respectively. The high proportion of G3CREC in the community and the association of G3CREC with 21-day mortality indicate that G3CREC is a major public health problem in developing countries.

Socio-demographic Risk Factors Associated with HIV Infection In Patients Seeking Medical Advice in a Rural Hospital of India.

Despite the fact that two thirds of HIV infected people in India are rural residents, risk factors associated with HIV infection in rural areas are not well known. In this study we have collected socio-demographic data of 6406 patients who were tested for HIV infection in a rural hospital of India and we have investigated risk factors associated with HIV. In women the most important risk factor was being a widow and the risk was higher in younger than in older widows. Other variables found to be associated with HIV infection were age between 25 and 45 years in men, low education level (especially those who only completed primary education) and working in a field not related to agriculture in scheduled castes and men from scheduled tribes. The results of this study express the need for HIV screening of widows who live in rural areas of Indian States with high HIV prevalence.

Evaluation of a Low-Cost Strategy for Enumerating CD4 Lymphocyte Absolute Count and Percentage Using the FACSCalibur Flow Cytometer in HIV-Infected Patients from a Resource-Limited Setting.

Enumeration of CD4 lymphocytes is essential for the clinical management of HIV-infected patients, but it can be difficult to afford in developing countries. In this study we evaluated a reagent reduction strategy for reducing the cost of enumerating CD4 cell absolute count and percentage using the FACSCalibur flow cytometer (Becton Dickinson). We compared the protocol recommended by the manufacturer with a protocol that used half of the usual amount of CD3/CD4/CD45 monoclonal antibody reagent in 100 samples from HIV-infected patients in a rural hospital in India. The concordance correlation coefficient between the two protocols was 0.976 for CD4 cell count and 0.984 for CD4 cell percentage. We did not find significant bias when performing Deming regression or Bland-Altman analysis. Sensitivity and specificity were 97% and 98.5% for identifying patients with less than 200 CD4 cells/ µ L, 98.1% and 93.8% for identifying patients with less than 350 CD4 cells/ µ L, and 100% and 94.7% for identifying patients with less than 25% CD4 cells, respectively. This reagent reduction strategy can be used for reducing the cost of enumerating CD4 lymphocytes in high-volume laboratories from resource-limited settings.

False negative HIV antibody test in HIV infected children who receive early antiretroviral treatment in a resource-limited setting.

With the implementation of 2010 World Health Organization guidelines, the number of infants from developing countries who will initiate antiretroviral therapy (ART) will increase considerably. In this study we describe the HIV antibody tests of 14 HIV infected children who initiated ART at age less than one year in a rural setting of India. The HIV rapid test was negative in seven and indeterminate in two cases, whereas the HIV enzyme-linked immunosorbent assay (ELISA) antibody test was negative in three and indeterminate in one case. In one child who had both negative HIV rapid test and ELISA initially, HIV serology turned positive after having a virological failure to ART, suggesting the possibility of utilizing HIV serology for monitoring ART effectiveness in children who experience HIV seroreversion. In conclusion, HIV seroreversion of children with early initiation of ART is common and should be considered for avoiding misdiagnosis of HIV infection.

Trends and risk factors for HIV infection among young pregnant women in rural India.

OBJECTIVES: To study the trends of the HIV epidemic and risk factors associated with HIV in a rural area of India. We utilized HIV prevalence among young pregnant women as an indicator of population trends in HIV infection. METHODS: This was an observational study of pregnant women aged less than 25 years who were counseled and tested for HIV infection in a rural hospital between August 2007 and June 2011. Information on age, education, occupation, and community were collected prospectively from all of the women. RESULTS: The HIV prevalence in young pregnant women decreased from 1.22% in 2007 to 0.35% in 2011. Comparing the periods 2007-2009 and 2010-2011, a reduction in HIV prevalence was seen in all subgroups except in women from forward castes. Women whose job was not related to agriculture and women who had only completed primary education were more likely to be HIV-infected. CONCLUSIONS: These results indirectly indicate that the incidence of HIV infection is decreasing in this rural setting. However, an increase in the HIV prevalence in women from forward castes was observed. In rural areas, HIV testing of pregnant women who have only completed primary education or who are working in a field not related to agriculture should be encouraged, because of their higher risk of HIV infection.