Factors associated with delayed entry into HIV medical care after HIV diagnosis in a resource-limited setting: Data from a cohort study in India

Studies from sub-Saharan Africa have shown that a substantial proportion of patients diagnosed with HIV enter into HIV medical care late. However, data from low or middle-income countries outside Africa are scarce. In this study, we investigated risk factors associated with delayed entry into care stratified by gender in a large cohort study in India. 7701 patients were diagnosed with HIV and 5410 entered into care within three months of HIV diagnosis. Nearly 80% entered into care within a year, but most patients who did not enter into care within a year remained lost to follow up or died. Patient with risk factors related to having a low socio-economic status (poverty, being homeless, belonging to a disadvantaged community and illiteracy) were more likely to enter into care late. In addition, male gender and being asymptomatic at the moment of HIV infection were factors associated with delayed entry into care. Substantial gender differences were found. Younger age was found to be associated with delayed entry in men, but not in women. Widows and unmarried men were more likely to enter into care within three months. Women belonging to disadvantaged communities or living far from a town were more likely to enter into care late. The results of this study highlight the need to improve the linkage between HIV diagnosis and HIV treatment in India. HIV programmes should monitor patients diagnosed with HIV until they engage in HIV medical care, especially those at increased risk of attrition

Entry, Retention, and Virological Suppression in an HIV Cohort Study in India: Description of the Cascade of Care and Implications for Reducing HIV-Related Mortality in Low- and Middle-Income Countries

HIV treatment, care, and support programmes in low- and middle-income countries have traditionally focused more on patients remaining in care after the initiation of antiretroviral therapy (ART) than on earlier stages of care. This study describes the cumulative retention from HIV diagnosis to the achievement of virological suppression after ART initiation in an HIV cohort study in India. Of all patients diagnosed with HIV, 70% entered into care within three months. 65% of patients ineligible for ART at the first assessment were retained in pre-ART care. 67% of those eligible for ART initiated treatment within three months. 30% of patients who initiated ART died or were lost to followup, and 82% achieved virological suppression in the last viral load determination. Most attrition occurred the in pre-ART stages of care, and it was estimated that only 31% of patients diagnosed with HIV engaged in care and achieved virological suppression after ART initiation. The total mortality attributable to pre-ART attrition was considerably higher than the mortality for not achieving virological suppression. This study indicates that early entry into pre-ART care along with timely initiation of ART is more likely to reduce HIV-related mortality compared to achieving virological suppression

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

Effect of Formula Feeding and Breastfeeding on Child Growth, Infant Mortality, and HIV Transmission in Children Born to HIV-Infected Pregnant Women Who Received Triple Antiretroviral Therapy in a Resource-Limited Setting: Data from an HIV Cohort Study in India

We describe a programme for the prevention of mother-to-child transmission (PMTCT) of HIV that provided universal antiretroviral therapy (ART) to all pregnant women regardless of the CD4 lymphocyte count and formula feeding for children with high risk of HIV transmission through breastfeeding in a district of India. The overall rate of HIV transmission was 3.7%. Although breastfeeding added a 3.1% additional risk of HIV acquisition, formula-fed infants had significantly higher risk of death compared to breastfed infants. The cumulative 12-month mortality was 9.6% for formula-fed infants versus 0.68% for breastfed infants. Anthropometric markers (weight, length/height, weight for length/height, body mass index, head circumference, mid-upper arm circumference, triceps skinfold, and subscapular skinfold) showed that formula-fed infants experience severe malnutrition during the first two months of life. We did not observe any death after rapid weaning at 5-6 months in breastfed infants. The higher-free-of HIV survival in breastfed infants and the low rate of HIV transmission found in this study support the implementation of PMTCT programmes with universal ART to all HIV-infected pregnant women and breastfeeding in order to reduce HIV transmission without increasing infant mortality in developing countries

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

Factors Associated with Late Presentation of HIV and Estimation of Antiretroviral Treatment Need according to CD4 Lymphocyte Count in a Resource-Limited Setting: Data from an HIV Cohort Study in India

We describe the CD4 lymphocyte count at HIV presentation in an HIV cohort from a rural district of India. The majority of patients were diagnosed for their HIV-related symptoms, although a sizeable proportion of women were diagnosed because of antenatal screening or for having an HIV-positive partner. Patients diagnosed of HIV for antenatal screening or having an HIV-positive sexual partner had higher CD4 lymphocyte count than patients having tuberculosis or HIV-related symptoms. The proportion of patients diagnosed with CD4 count <200 and <350 cells/mm3 were 46% and 68.7%, respectively, and these figures did not change during the five years of the study. Factors associated with late presentations were male sex, older age, not having a permanent house, and, in women, lower education and being a widow or separated. With the implementation of 2010 WHO guidelines, the number of newly diagnosed patients who will require HIV treatment will increase 13.8%. If the CD4 count threshold for initiating HIV treatment is increased from 350 to 500 cells/mm3, the number of patients in need of treatment would increase 15.7%. Therefore, new strategies for avoiding HIV late presentation are urgently needed in developing countries

Clinical Study 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 cerebrospinal 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

Antimicrobial resistance surveillance in low- and middle-income countries: Progress and challenges in eight South Asian and Southeast Asian countries

SUMMARYAntimicrobial resistance (AMR) is a serious global health threat and is predicted to cause significant health and economic impacts, particularly in low- and middle-income countries (LMICs). AMR surveillance is critical in LMICs due to high burden of bacterial infections; however, conducting AMR surveillance in resource-limited settings is constrained by poorly functioning health systems, scarce financial resources, and lack of skilled personnel. In 2015, the United Nations World Health Assembly endorsed the World Health Organization\u27s Global Action Plan to tackle AMR; thus, several countries are striving to improve their AMR surveillance capacity, including making significant investments and establishing and expanding surveillance networks. Initial data generated from AMR surveillance networks in LMICs suggest the high prevalence of resistance, but these data exhibit several shortcomings, such as a lack of representativeness, lack of standardized laboratory practices, and underutilization of microbiology services. Despite significant progress, AMR surveillance networks in LMICs face several challenges in expansion and sustainability due to limited financial resources and technical capacity. This review summarizes the existing health infrastructure affecting the establishment of AMR surveillance programs, the burden of bacterial infections demonstrating the need for AMR surveillance, and current progress and challenges in AMR surveillance efforts in eight South and Southeast Asian countries

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

Clinical Study Factors Associated with Late Presentation of HIV and Estimation of Antiretroviral Treatment Need according to CD4 Lymphocyte Count in a Resource-Limited Setting: Data from an HIV Cohort Study in India

We describe the CD4 lymphocyte count at HIV presentation in an HIV cohort from a rural district of India. The majority of patients were diagnosed for their HIV-related symptoms, although a sizeable proportion of women were diagnosed because of antenatal screening or for having an HIV-positive partner. Patients diagnosed of HIV for antenatal screening or having an HIV-positive sexual partner had higher CD4 lymphocyte count than patients having tuberculosis or HIV-related symptoms. The proportion of patients diagnosed with CD4 count &lt;200 and &lt;350 cells/mm 3 were 46% and 68.7%, respectively, and these figures did not change during the five years of the study. Factors associated with late presentations were male sex, older age, not having a permanent house, and, in women, lower education and being a widow or separated. With the implementation of 2010 WHO guidelines, the number of newly diagnosed patients who will require HIV treatment will increase 13.8%. If the CD4 count threshold for initiating HIV treatment is increased from 350 to 500 cells/mm 3 , the number of patients in need of treatment would increase 15.7%. Therefore, new strategies for avoiding HIV late presentation are urgently needed in developing countries