Development and Validation of the RCOS Prognostic Index: A Bedside Multivariable Logistic Regression Model to Predict Hypoxaemia or Death in Patients with SARS-CoV-2 Infection.

Introduction: Previous COVID-19 prognostic models have been developed in hospital settings and are not applicable to COVID-19 cases in the general population. There is an urgent need for prognostic scores aimed to identify patients at high risk of complications at the time of COVID-19 diagnosis. Methods: The RDT COVID-19 Observational Study (RCOS) collected clinical data from patients with COVID-19 admitted regardless of the severity of their symptoms in a general hospital in India. We aimed to develop and validate a simple bedside prognostic score to predict the risk of hypoxaemia or death. Results: 4035 patients were included in the development cohort and 2046 in the validation cohort. The primary outcome occurred in 961 (23.8%) and 548 (26.8%) patients in the development and validation cohorts, respectively. The final model included 12 variables: age, systolic blood pressure, heart rate, respiratory rate, aspartate transaminase, lactate dehydrogenase, urea, C-reactive protein, sodium, lymphocyte count, neutrophil count, and neutrophil/lymphocyte ratio. In the validation cohort, the area under the receiver operating characteristic curve (AUROCC) was 0.907 (95% CI, 0.892-0.922), and the Brier Score was 0.098. The decision curve analysis showed good clinical utility in hypothetical scenarios where the admission of patients was decided according to the prognostic index. When the prognostic index was used to predict mortality in the validation cohort, the AUROCC was 0.947 (95% CI, 0.925-0.97) and the Brier score was 0.0188. Conclusions: The RCOS prognostic index could help improve the decision making in the current COVID-19 pandemic, especially in resource-limited settings with poor healthcare infrastructure such as India. However, implementation in other settings is needed to cross-validate and verify our findings.

Safety and tolerability of intrathecal liposomal amphotericin B (AmBisome) for cryptococcal meningitis: a retrospective study in HIV-infected patients.

BACKGROUND: While mortality of HIV-related cryptococcal meningitis (CM) in developed countries is relatively low, in developing countries over half of patients die within 10 weeks. Current recommended therapies are often not suitable for resource-poor settings, and new shorter regimens are urgently needed. Intrathecal administration of liposomal amphotericin B (lAmB) has shown promising results in animal models. However, the safety and tolerability of intrathecal lAmB in humans are not well known. METHODS: In this retrospective observational study, we report the tolerability and safety of intrathecal lAmB in patients with CM from an HIV cohort study in India. RESULTS: In all, 18 patients were included in the analysis. Six were female and the median age was 40 years [interquartile range (IQR): 35-45]. The median CD4 count was 42 cells/µl (IQR: 19-127). Compared with a historical control group, the hazard ratio for mortality was 0.59 (95% confidence interval: 0.26-1.29). Two patients complained of transient lumbar pain in single occasion. One patient had a skin reaction to chlorhexidine, which was used as skin disinfectant. After initial improvement, one patient requested to stop lumbar punctures for the last 2 days of treatment. CONCLUSION: Intrathecal lAmB was safe and well tolerated in HIV-infected patients with CM.

Trends and factors associated with antimicrobial resistance of Acinetobacter spp. invasive isolates in Europe: A country-level analysis.

OBJECTIVES: This study investigated trends and factors associated with antimicrobial resistance (AMR) in Acinetobacter spp. in Europe. METHODS: Using data from EARS-Net, population-weighted multilevel logistic regression models with random intercepts for each participating country were performed to assess trends in Acinetobacter AMR. Countries were divided into two groups (Northern versus Southern-Eastern) using a convenient US$35000 cut-off of the 2016 gross domestic product per capita (GDPPC). RESULTS: In most countries, there were no ascending or descending trends over time. The models showed a consistent higher prevalence of AMR to aminoglycosides, carbapenems and fluoroquinolones in countries with GDPPC US$35000 and

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.

Short-Course Induction Treatment with Intrathecal Amphotericin B Lipid Emulsion for HIV Infected Patients with Cryptococcal Meningitis.

Cryptococcal meningitis (CM) is a common cause of death among HIV infected patients in developing countries, especially in sub-Saharan Africa. In this observational HIV cohort study in a resource-limited setting in India, we compared the standard two-week intravenous amphotericin B deoxycholate (AmBd) (Regimen I) with one week of intravenous AmBd along with daily therapeutic lumbar punctures and intrathecal AmB lipid emulsion (Regimen II) during the intensive phase of CM treatment. 78 patients received Regimen I and 45 patients received Regimen II. After adjustment for baseline characteristics (gender, age, altered mental status or seizures at presentation, CD4 cell count, white blood cells, cerebrospinal fluid white cells, and haemoglobin), the use of Regimen II was associated with a significant relative risk reduction in mortality (adjusted hazard ratio 0.4, 95% confidence interval, 0.22-0.76) and 26.7% absolute risk reduction (95% confidence interval, 9.9-43.5) at 12 weeks. The use of Regimen II resulted in lower costs of drugs and hospital admission days. Since the study is observational in nature, we should be cautious about our results. However, the good tolerability of intrathecal administration of AmB lipid emulsion and the clinically important mortality reduction observed with the short-course induction treatment warrant further research, ideally through a randomized clinical trial.

Adding Streptomycin to an Intensified Regimen for Tuberculous Meningitis Improves Survival in HIV-Infected Patients.

In low- and middle-income countries, the mortality of HIV-associated tuberculous meningitis (TM) continues to be unacceptably high. In this observational study of 228 HIV-infected patients with TM, we compared the mortality during the first nine months of patients treated with standard antituberculosis therapy (sATT), intensified ATT (iATT), and iATT with streptomycin (iATT + STM). The iATT included levofloxacin, ethionamide, pyrazinamide, and double dosing of rifampicin and isoniazid and was given only during the hospital admission (median 7 days, interquartile range 6-9). No mortality differences were seen in patients receiving the sATT and the iATT. However, patients receiving the iATT + STM had significant lower mortality than those in the sATT group (hazard ratio [HR] 0.47, 95% confidence interval [CI] 0.24 to 0.93). After adjusting for other covariates, the mortality hazard of the iATT + STM versus the sATT remained statistically significant (adjusted HR 0.2, 95% CI 0.09 to 0.46). Other factors associated with mortality were previous ATT and low albumin concentrations. The mortality risk increased exponentially only with CD4+ lymphocyte concentrations below 100 cells/µL. In conclusion, the use of iATT resulted in a clinically important reduction in mortality compared with the standard of care only if associated with STM. The results of this study 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.

Induction with lopinavir-based treatment followed by switch to nevirapine-based regimen versus non-nucleoside reverse transcriptase inhibitors-based treatment for first line antiretroviral therapy in HIV infected children three years and older.

BACKGROUND: The World Health Organization recommends non-nucleoside reverse transcriptase inhibitors (NNRTIs)-based antiretroviral therapy (ART) for children three years and older. In younger children, starting ART with lopinavir boosted with ritonavir (LPVr) results in lower risk of virological failure, but data in children three years and older are scarce, and long-term ART with LPVr is problematic in resource-poor settings. METHODOLOGY: Retrospective cohort of children three years and older who started triple ART including LPVr or a NNRTI between 2007 and 2013 in a rural setting in India. Children who started LPVr were switched to nevirapine-based ART after virological suppression. We analysed two outcomes, virological suppression (HIV-RNA <400 copies/ml) within one year of ART using logistic regression, and time to virological failure (HIV-RNA >1000 copies/ml) after virological suppression using Cox proportional hazard regression. A sensitivity analysis was performed using inverse probability of treatment weighting (IPTW) based of propensity score methods. FINDINGS: Of 325 children having a viral load during the first year of ART, 74/83 (89.2%) in the LPVr group achieved virological suppression versus 185/242 (76.5%) in the NNRTI group. In a multivariable analysis, the use of LPVr-based ART was associated with higher probability of virological suppression (adjusted odds ratio 3.19, 95% confidence interval [CI] 1.11-9.13). After IPTW, the estimated risk difference was 12.2% (95% CI, 2.9-21.5). In a multivariable analysis including 292 children who had virological suppression and available viral loads after one year of ART, children switched from LPVr to nevirapine did not have significant higher risk of virological failure (adjusted hazard ratio 1.18, 95% CI 0.36-3.81). CONCLUSIONS: In a cohort of HIV infected children three years and older in a resource-limited setting, an LPVr induction- nevirapine maintenance strategy resulted in more initial virological suppression and similar incidence of virological failure after initial virological suppression than NNRTI-based regimens.

Directly-observed intermittent therapy versus unsupervised daily regimen during the intensive phase of antituberculosis therapy in HIV infected patients.

The World Health Organization strongly recommends using daily antituberculosis therapy (ATT) during the intensive phase for HIV infected patients. India has the highest burden of tuberculosis in the world, but HIV infected patients are still receiving intermittent ATT. In this study we compared the mortality in patients who received directly-observed intermittent ATT versus self-administered daily ATT with fixed dose combinations during the intensive phase in a context of freely available antiretroviral therapy. The study included 1460 patients, 343 in the intermittent ATT group and 1117 in the daily ATT group. Baseline covariates of the two groups were balanced using inverse probability of treatment weighting based on propensity score methods. In a sensitivity analysis, continuous variables (albumin, CD4 count, and age) were modelled using restricted cubic smoothing splines. Compared with patients who received daily ATT, patients who received intermittent ATT had a 40% higher risk of mortality (1.4 hazard ratio; 95% confidence interval, 1.14-1.7). We estimated that the use of daily ATT could achieve a 10% absolute reduction in mortality at 12 months. Self-administered daily ATT was not associated with an increased risk of default from treatment. These results support the immediate implementation of daily ATT for HIV infected patients during the intensive phase in India.

Mortality and Loss to Follow up Before Initiation of Antiretroviral Therapy Among HIV-Infected Children Eligible for HIV Treatment.

Data on attrition due to mortality or loss to follow-up (LTFU) from antiretroviral therapy (ART) eligibility to ART initiation of HIV-infected children are scarce. The aim of this study is to describe attrition before ART initiation of 247 children who were eligible for ART in a cohort study in India. Multivariable analysis was performed using competing risk regression. The cumulative incidence of attrition was 12.6% (95% confidence interval, 8.7-17.3) after five years of follow-up, and the attrition rate was higher during the first months after ART eligibility. Older children (>9 years) had a lower mortality risk before ART initiation than those aged <2 years. Female children had a lower risk of LTFU before ART initiation than males. Children who belonged to scheduled tribes had a higher risk of delayed ART initiation and LTFU. Orphan children had a higher risk of delayed ART initiation and mortality. Children who were >3 months in care before ART eligibility were less likely to be LTFU. The 12-month risk of AIDS, which was calculated using the absolute CD4 cell count and age, was strongly associated with mortality. A substantial proportion of ART-eligible children died or were LTFU before the initiation of ART. These findings can be used in HIV programmes to design actions aimed at reducing the attrition of ART-eligible children in India.

Predictors of loss to follow-up after engagement in care of HIV-infected children ineligible for antiretroviral therapy in an HIV cohort study in India.

INTRODUCTION: Previous studies performed in low- and middle-income countries have shown that nearly half of HIV-infected adults not eligible for antiretroviral therapy (ART) at the time of enrolment in care are lost to follow-up (LTFU). However, data about the attrition from enrolment in care to ART eligibility of HIV-infected children are scarce, especially outside sub-Saharan Africa. METHODS: This is a retrospective study about the attrition before ART eligibility of 282 children ineligible for ART at enrolment in care in a cohort study in India. Multivariate analysis was performed using competing risk regression. RESULTS: During 5695 child-months of follow-up, three children died, 36 were LTFU and 144 became ART eligible. The cumulative incidence of attrition (mortality and LTFU) was 15.6% (95% confidence interval [CI], 11.3-20.5) at five years, and the attrition rate was higher during the first year after enrolment in care. The cumulative incidence of LTFU and mortality was 14.4% (95% CI, 10.2-19.2) and 1.2% (95% CI, 0.3-3.3) at five years, respectively. Children with a 12-month AIDS risk <3% had a higher risk of LTFU (subdistribution hazard ratio [SHR] 10.77, 95% CI 1.93-60.07) than those with a risk >4%. Those children whose father had died had a lower risk of LTFU (SHR 0.26, 95% CI 0.09-0.75) than those whose parents were alive and were living in a rented house. Children aged 10-14 had a lower risk of LTFU (SHR 0.12, 95% CI 0.03-0.55) than those aged 5-9 years. CONCLUSION: In our setting, a substantial proportion of children ineligible for ART are lost to follow-up before ART eligibility, especially those with younger age, less severe immunosuppression or living with parents in poor socio-economic conditions. These findings can be used by HIV programmes to design interventions aimed at reducing the attrition of pre-ART care of HIV-infected children in India.

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.

Optimal Duration of Daily Antituberculosis Therapy before Switching to DOTS Intermittent Therapy to Reduce Mortality in HIV Infected Patients: A Duration-Response Analysis Using Restricted Cubic Splines.

Compared with thrice-weekly intermittent antituberculosis therapy (ATT), the use of daily ATT during the intensive phase has shown improved survival in HIV infected patients with tuberculosis. However, the optimal duration of daily ATT before initiating intermittent ATT is not well known. In this study, we analysed the mortality of HIV-related tuberculosis according to the duration of daily ATT before switching to thrice-weekly ATT in patients who completed at least two months of treatment in an HIV cohort study. Statistical analysis was performed using Cox proportional hazard models. To relax the linearity assumption in regression models and to allow for a flexible interpretation of the relationship between duration of daily ATT and mortality, continuous variables were modelled using restricted cubic splines. The study included 520 HIV infected patients with tuberculosis and 8,724.3 person-months of follow-up. The multivariable analysis showed that the mortality risk was inversely correlated with the duration of daily ATT before switching to intermittent therapy during the first 30 days of ATT but, after approximately 30 days of treatment, differences were not statistically significant. The results of this study suggest that daily ATT should be given for at least 30 days before switching to intermittent ATT in HIV infected patients with tuberculosis.

Predictors of delayed entry into medical care of children diagnosed with HIV infection: data from an HIV cohort study in India.

Data about the attrition before entry into care of children diagnosed with HIV in low- or middle-income countries are scarce. The aim of this study is to describe the attrition before engagement in HIV medical care in 523 children who were diagnosed with HIV from 2007 to 2012 in a cohort study in India. The cumulative incidence of children who entered into care was 87.2% at one year, but most children who did not enter into care within one year were lost to followup. The mortality before entry into care was low (1.3% at one year) and concentrated during the first three months after HIV diagnosis. Factors associated with delayed entry into care were being diagnosed after mother's HIV diagnosis, belonging to scheduled castes, age<18 months, female gender, and living >90 minutes from the HIV centre. Children whose parents were alive and were living in a rented house were at a higher risk of delayed entry into care than those who were living in an owned house. The results of this study can be used to improve the linkage between HIV testing and HIV care of children diagnosed with HIV in India.

Predictors of delayed antiretroviral therapy initiation, mortality, and loss to followup in HIV infected patients eligible for HIV treatment: data from an HIV cohort study in India.

Studies from Sub-Saharan Africa have shown that a substantial number of HIV patients eligible for antiretroviral therapy (ART) do not start treatment. However, data from other low- or middle-income countries are scarce. In this study, we describe the outcomes of 4105 HIV patients who became ART eligible from January 2007 to November 2011 in an HIV cohort study in India. After three years of ART eligibility, 78.4% started ART, 9.3% died before ART initiation, and 10.3% were lost to followup. Diagnosis of tuberculosis, being homeless, lower CD4 count, longer duration of pre-ART care, belonging to a disadvantaged community, being widowed, and not living near a town were associated with delayed ART initiation. Diagnosis of tuberculosis, being homeless, lower CD4 count, shorter duration of pre-ART care, belonging to a disadvantaged community, illiteracy, and age >45 years were associated with mortality. Being homeless, being single, not living near a town, having a CD4 count <150 cells/µL, and shorter duration of pre-ART care were associated with loss to followup. These results highlight the need to improve the timely initiation of ART in HIV programmes in India, especially in ART eligible patients with tuberculosis, low CD4 counts, living in rural areas, or having a low socioeconomic status.

Diagnostic and Prognostic Value of Serum Albumin for Tuberculosis in HIV Infected Patients Eligible for Antiretroviral Therapy: Datafrom an HIV Cohort Study in India.

INTRODUCTION: Tuberculosis is difficult to diagnose and it is the leading cause of death in HIV infected individuals in developing countries. There is an urgent need of low-cost diagnostic markers for resource-limited settings. METHODS: The study involved 1571 patients from an HIV cohort study in India with known serum albumin concentrations at the time of becoming eligible for antiretroviral therapy (ART). We investigated the diagnostic accuracy of serum albumin to predict tuberculosis within six months of ART eligibility and the prognostic value in patients who experienced tuberculosis. RESULTS: The diagnostic accuracy of serum albumin, measured by the area under the receiver operating characteristic curve, to predict tuberculosis was 0.81 (95% confidence interval 0.78-0.83). Serum albumin concentrations <3.2 g/dL were associated with 85% specificity and <4.1 g/dL were associated with negative predictive values >90%, even in settings with high tuberculosis prevalence. Hypoalbuminemia was associated with an increased risk of mortality in patients with tuberculosis. CONCLUSION: Serum albumin can be a useful low-cost diagnostic marker for tuberculosis in HIV infected patients eligible for ART. However, we failed to find thresholds to rule out or rule in tuberculosis. If these results are confirmed by other studies, serum albumin could be used to improve the diagnostic accuracy of intensive case finding algorithms for HIV-related tuberculosis. In patients who experience tuberculosis, hypoalbuminemia is associated with poor prognosis.

Intra-abscess administration of antibiotics through ultrasound-guided percutaneous catheter for the treatment of pyogenic liver abscess.

Pyogenic liver abscess is a potentially life-threatening disease. The treatment of a pyogenic liver abscess usually involves ultrasound guided percutaneous drainage because of the poor penetration of the systemic administration of antibiotics inside the abscess. However, a sizable proportion of patients will necessitate surgical interventions, which involves high peri- and post-operative risks. Theoretically, the local instillation of antibiotics inside the pyogenic liver abscess fluid could achieve a high concentration of the antibiotic for a long period of time. This could be especially beneficial for time-dependent bactericidal antibiotics such as beta-lactams, because their bactericidal effectiveness depends on the amount of time that bacteria are exposed to the antibiotic. We are reporting two patients with complicated pyogenic liver abscesses, who were successfully treated with systemic antibiotics and local instillation of meropenem inside the cavities of the abscesses. These cases suggest that the local instillation of the beta-lactam antibiotics could be an effective and a safe strategy for the treatment of pyogenic liver abscesses that cannot be completely drained through an ultrasound guided percutaneous catheter.

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.

Initial Antituberculous Regimen with Better Drug Penetration into Cerebrospinal Fluid Reduces Mortality in HIV Infected Patients with Tuberculous Meningitis: Data from an HIV Observational Cohort Study.

Tuberculous meningitis (TM) is the deadliest form of tuberculosis. Nearly two-thirds of HIV infected patients with TM die, and most deaths occur within one month. Current treatment of TM involves the use of drugs with poor penetration into the cerebro-spinal fluid (CSF). In this study, we present the mortality before and after implementing a new antituberculous regimen (ATR) with a higher drug penetration in CSF than the standard ATR during the initial treatment of TM in an HIV cohort study. The new ATR included levofloxacin, ethionamide, pyrazinamide, and a double dose of rifampicin and isoniazid and was given for a median of 7 days (interquartile range 6-9). The new ATR was associated with an absolute 21.5% (95% confidence interval (CI), 7.3-35.7) reduction in mortality at 12 months. In multivariable analysis, independent factors associated with mortality were the use of the standard ATR versus the new ATR (hazard ratio 2.05; 95% CI, 1.2-3.5), not being on antiretroviral therapy, low CD4 lymphocyte counts, and low serum albumin levels. Our findings suggest that an intensified initial ATR, which likely results in higher concentrations of active drugs in CSF, has a beneficial effect on the survival of HIV-related TM.