Factors associated with mortality in HIV-TB co-infected patients during and after the course of TB treatment in high-burden settings, Mumbai, India: A cohort analysis.

BACKGROUND: Knowledge of factors associated with TB mortality during treatment and post treatment will help us develop better monitoring and implementation strategies for TB control. We designed the present study to examine the factors associated with mortality in HIV-TB co-infected patients during and after the course of TB treatment. METHODS: This study is a cohort analysis of secondary data collected from 1804 HIV-TB co-infected individuals from 16 anti-retroviral therapy (ART) centres affiliated with the Mumbai Districts AIDS Control Society, Mumbai, India. We used Kaplan Meier survival curves and hazard ratios to estimate the mortality in patients. RESULTS: The overall mortality rate in this cohort was 1.14 per 100 per month. The mortality proportion was 18% (95% CI: 16.1%, 20.1%) during treatment and 10.6% (95% CI: 8.9%, 12.5%) in the post-treatment period. Mortality was significantly higher in those with a CD4 count 0-200 cells/mm3 (HR: 3.04, 95% CI: 2.13, 4.15; p < 0.001), and in patients who were ART naïve and referred to the ART centre with a diagnosis of TB (HR: 1.39, 95% CI: 1.06, 1.82; p = 0.016). Mortality was also significantly higher in the first 6 months after initiation of ART (HR: 1.36, 95% CI: 1.06, 1.75; p = 0.016). A decrease in the CD4 counts from initial levels at start of TB treatment to end of TB treatment was associated with higher mortality in the post-treatment period. DISCUSSION: The overall mortality remains high; early identification of TB and HIV disease, and use of rapid point of care tests for diagnosis of TB are needed across all health care facilities. Post-treatment follow-up and monitoring is important in HIV-TB co-infected patients, and post-treatment mortality should also be considered as one of the indicators for successful TB control programmes.

Implementation of point-of-care testing and prevalence of cryptococcal antigenaemia among patients with advanced HIV disease in Mumbai, India.

OBJECTIVES: To describe the implementation of screening for cryptococcal antigenaemia by point-of-care (POC) serum cryptococcal antigen (CrAg) lateral flow assay, measure the prevalence and factors associated with serum cryptococcal antigenaemia in the routine programmatic setting. DESIGN: Cross-sectional study. SETTING: Seventeen publicly funded antiretroviral therapy (ART) centres in Mumbai, India. PARTICIPANTS: Serum CrAg screening was offered to all adolescents (>10 years of age) and adults with advanced HIV disease (AHD) (CD4 <200 cells/mm3 or with WHO clinical stage III/IV) regardless of symptoms of cryptococcal meningitis. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was to describe the implementation of serum CrAg screening and secondary outcome was to measure the prevalence of serum cryptococcal antigenaemia and its risk factors. RESULTS: A total of 2715 patients with AHD were tested for serum CrAg by POC assay. Of these, 25 (0.9%) had a CrAg positive result. Among CrAg-positive patients, only one had symptoms. Serum CrAg positivity was 3.6% (6/169) and 1.6% (6/520) among those presenting with CD4 <100 cells/mm3 in the treatment naïve and treatment experienced group, respectively. On multivariable analysis, CD4 count <100 cells/mm3 (OR: 2.3, 95% CI 1.01 to 5.3; p=0.05) and people living with HIV who were treatment naïve (OR: 2.5, 95% CI 1.04 to 6.0; p=0.04) were significantly associated with a positive serum CrAg result. Lumbar puncture was obtained in 20/25 patients within 4 days (range: 1-4 days) of positive serum CrAg result and one person was confirmed to have meningitis. All serum CrAg-positive patients who had a negative cerebrospinal fluid CrAg were offered pre-emptive therapy. CONCLUSIONS: Implementation of a POC CrAg assay was possible with existing ART centre staff. Initiation of pre-emptive therapy and management of cryptococcal antigenaemia are operationally feasible at ART centres. The Indian National AIDS Control Programme may consider reflexive CrAg screening of all AHD patients with CD4 <100 cells/mm3.

Utility of the lateral flow urine lipoarabinomannan tuberculosis assay in patients with advanced HIV disease at antiretroviral therapy centres in Mumbai, India.

BACKGROUND: People with Advanced HIV Disease (AHD) are at higher risk of TB coinfection and mortality. However, there are challenges in TB diagnosis with the currently recommended diagnostic tools. WHO recommends lateral flow urine lipoarabinomannan (LF-LAM) assay to assist TB diagnosis among AHD patients. We assessed the utility and acceptability of using urine LF-LAM assay for TB diagnosis among patients at public Antiretroviral Therapy (ART) Centres in Mumbai. METHODS: The cross-sectional study was conducted among adult AHD patients accessing care from 17 ART centres during November,2020-June, 2021. Urine LF-LAM was offered as routine care for eligible patients in combination with standard diagnostic tests. We calculated the proportion of positive LF-LAM results by CD4 categories and TB symptoms and performed multivariable logistic regression to determine the factors associated with LF-LAM positivity. RESULTS: Among 2,390 patients, the majority (74.5%) had CD4 between 101-200 cells/mm3. The mean age was 43.7 years (SD:10.6), 68.6% were male, 8.4% had TB symptoms and 88.0% were on ART. The overall proportion of patients with urine LF-LAM positive results was 6.4%. Among PLHIV with CD4≤100 cells/mm3, the positivity was 43.0% and 7.7% in symptomatic and asymptomatic patients, respectively. Among PLHIV with a CD4>100 cells/mm3, the positivity was 26.7% and 2.7% in symptomatic and asymptomatic patients respectively. Urine LF-LAM positivity was higher among inpatients, ART naïve, patients on treatment for <6 months, symptomatic and in WHO clinical stage III/IV of HIV disease as compared to the reference categories. We detected an additional 131 TB cases with urine LF-LAM in combination with the standard diagnostic tests. CONCLUSION: The study demonstrated the utility of urine LF-LAM for TB diagnosis among AHD patients and the simple, user-friendly test was acceptable as part of routine care. Inclusion of urine LF-LAM test in the current diagnostic algorithm may facilitate early TB diagnosis among AHD patients.

Barriers for Antiretroviral Therapy Adherence and Viral Suppression in Members of the Key Population in Mumbai, India: Implications for Interventions.

BACKGROUND: Poor adherence to antiretroviral therapy (ART) is associated with poor virologic control and drug resistance in people living with HIV/AIDS. Some barriers to ART adherence are cost, lack of information, stigma, or dissatisfaction with health services. AIMS AND OBJECTIVES: To study the association between barriers for ART adherence and viral suppression, and explore the role of "missing ART dose" as a potential mediator in high-risk groups. MATERIALS AND METHODS: Demographic, clinical, and behavioral data from 50 "virally suppressed" (viral load [VL] <1000 copies/ml) and 48 "not suppressed" (VL > 1000 copies/ml) individuals belonging to the key population in Mumbai were collected. Sociodemographic, behavioral, and other characteristics were compared, and mediation analysis was used to identify the mediator in the pathway to viral suppression. RESULTS: Those who had missed their ART at least once in the past three months (37% versus 60%, P = 0.03) and stayed alone were less likely to be virally suppressed (31% versus 69%, P = 0.002). Individuals who had negative perception about ART (adjusted odds ratio [aOR]: 0.11, 95% confidence interval [CI]: 0.02, 0.47; P = 0.002), poor ART-related knowledge/behaviors (aOR: 0.14, 95% CI: 0.03, 0.60; P = 0.007), and poor pill taking practices (aOR: 0.10, 95% CI: 0.02, 0.61; P = 0.01) were significantly less likely to be virally suppressed. The mediation pathway "adherence theme > missed ART in the past three months > viral suppression" was significant in these themes. CONCLUSIONS: The factors associated with low viral suppression were knowledge/behaviors, perceptions about ART, and poor pill taking practices. Thus, it is important to provide correct information about ART, its effects, side effects, and potential limitations to marginalized population. Involving brothel keepers and Gurus (head of male-to-female transgendered people/Hijras clans), and technology enabled customized counseling sessions will be helpful.

Retrospective cohort analysis of survival of children living with HIV/AIDS in Mumbai, India.

OBJECTIVES: To understand the survival in a cohort of children living with HIV/AIDS (CLHAs) and to study the factors associated with survival in CLHAs in government antiretroviral therapy (ART) centres in Mumbai, India. DESIGN: This is a retrospective cohort analysis. SETTING: Data from electronic ART records of children from 15 ART centres in Mumbai, Maharashtra, India. PARTICIPANTS: 2224 CLHAs registered in one of these ART centres from 2004 until October 2019. CLHAs up to the age of 18 at the time of registration were considered for these analyses. PRIMARY AND SECONDARY OUTCOMES: We accessed the following data: date of test, date of initiation of ART, date of last follow-up, age at the time of registration, gender, potential route of infection, baseline CD4 counts, ART regimen, adherence and presence of co-infection (TB). We estimated the survival probabilities, plotted the Kaplan-Meier survival graphs and estimated HRs for mortality. RESULTS: The mortality rate in our population was 22.75 (95% CI 20.02 to 25.85) per 1000 person-years. The 1-year survival was 0.92 (95% CI 0.91 to 0.93), 0.89 (95% CI 0.88 to 0.91) at 5 years and 0.85 (95% CI 0.83 to 0.87) at 10 years after initiation of ART. Children with adherence less than 80% had lowest survival in the first year (0.54, 95% CI 0.46 to 0.61). It reduced drastically at 5 and 10 years. After adjusting for demographic and clinical parameters, mortality was associated with poor adherence (<80%) (HR 11.70, 95% CI 8.82 to 15.53; p<0.001). However, CD4 counts of greater than 200 and age more than 1 year were protective. CONCLUSIONS: Poor adherence to ART and low CD4 counts were significantly associated with higher mortality. Adherence counselling should be an important component of CLHA monitoring in all ART centres. It is also important to identify children early in the infection and start ART medications appropriately.

Factors associated with survival in adult people living with HIV/AIDS (PLHAs) in Mumbai, India (2004-2019): A retrospective cohort study.

BACKGROUND: Knowledge of factors that affect survival in People living with HIV/AIDS (PLHAs) on anti-retroviral therapy (ART) will help us develop and implement interventions to improve the clinical outcomes and survival in these individuals. The aim of this study was to estimate the survival in PLHAs on ART in the government ART programme in Mumbai, and the factors associated with survival in these individuals. METHODS: It is a retrospective survival analysis of 28,345 adult PLHAs from 18 government ART centres in Mumbai (registration period 2004-2019). We estimated the mortality rates and their 95% confidence intervals [CIs], plotted the Kaplan Meier Survival curves, estimated incidence rate ratios (IRR) and hazard ratios (HR). There were done for the whole cohort and according to various demographic and clinical characteristics. RESULTS: The mortality in PLHAs on ART was 9.04 per 1000 person years. The HR was significantly for those aged 50 years and more at the time of registration (HR: 3.01, 95% CI: 2.37, 3.83; P < 0.001), in those with baseline CD4 count of less than 200 higher hazard (HR: 1.83, 95% CI: 1.47, 2.27; P < 0.001), those with an adherence of 80-95% (HR; 5.58, 95% CI: 4.61, 6.75; P < 0.001) and adherence of <80% (HR: 9.37, 95% CI: 7.74, 11.33; P < 0.001). Furthermore, the hazard was significantly higher in those with TB compared those without TB (HR: 3.28, 95% CI: 2.87, 3.75; P < 0.001). Time from diagnosis (per month increase) to initiation of ART was not significantly associated with mortality. CONCLUSIONS: Increasing awareness about HIV testing and early detection of HIV in those who have high-risk behaviours, prompt diagnosis and management of TB among those infected, and developing and implementing strategies (such as enhanced counselling, telephone-based applications, messages, or reminders) to ensure ART adherence of more than 95% in those on ART will potentially help improve survival in PLHAs in India.

Development of a composite indicator to prioritize districts for implementation of human immunodeficiency virus programmes in Maharashtra, India.

A key recommendation of the National AIDS Control Programme-IV of India was to develop new strategies for geo-prioritization of the human immunodeficiency virus (HIV) epidemic. We conducted this study to categorize the districts in Maharashtra (India) based on a multidimensional framework for geo-prioritization of services. Programmatic data on trends of HIV prevalence, coverage of marginalized populations and vulnerability factors were included. A composite indicator based on these was developed, and the cumulative score was calculated for each district. HIV prevalence among general population has declined steadily from 0.60% in 2007 to 0.33% in 2017. The programme coverage was stable but inadequate for men who have sex with men (MSM). The coverage for female sex workers (FSWs) was inadequate and reduced over time. Nine districts were categorized as high priority, 13 as moderate priority and 11 were classified as low-priority districts based on burden and vulnerability for HIV. The high-priority districts were Pune, Solapur and Yavatmal for FSW interventions and Pune, Thane and Latur for MSM interventions. This multidimensional indicator is based on existing programmatic data, dynamic and can be made state-specific. It is useful to categorize and prioritize districts for allocation of resources and geo-prioritization of services in resource limited settings.

Findings from the 2017 HIV estimation round & trend analysis of key indicators 2010-2017: Evidence for prioritising HIV/AIDS programme in India.

Background & objectives: The National AIDS Control Organisation (NACO) and the ICMR-National Institute of Medical Statistics, the nodal agency for conducting HIV estimations in India, have been generating HIV estimates regularly since 2003. The objective of this study was to describe India's biennial HIV estimation 2017 process, data inputs, tool, methodology and epidemiological assumptions used to generate the HIV estimates and trends of key indicators for 2010-2017 at national and State/Union Territory levels. Methods: Demographic Projection (DemProj) and AIDS Impact Modules (AIM) of Spectrum 5.63 software recommended by the United Nations Programme on HIV and AIDS Global Reference Group on HIV Estimates, Modelling and Projections, were used for generating HIV estimations on key indicators. HIV sentinel surveillance, epidemiological and programme data were entered into Estimation Projection Package (EPP), and curve fitting was done using EPP classic model. Finally, calibration was done using the State HIV prevalence of two rounds of National Family Health Survey (NFHS) -3 and -4 and Integrated Biological and Behavioural Surveillance (IBBS), 2014-2015. Results: The national adult prevalence of HIV was estimated to be 0.22 per cent in 2017. Mizoram, Manipur and Nagaland had the highest prevalence over one per cent. An estimated 2.1 million people were living with HIV in 2017, with Maharashtra estimated to have the highest number. Of the 88 thousand annual new HIV infections estimated nationally in 2017, Telangana accounted for the largest share. HIV incidence was found to be higher among key population groups, especially people who inject drugs. The annual AIDS-related deaths were estimated to be 69 thousand nationally. For all indicators, geographic variation in levels and trends between States existed. Interpretation & conclusions: With a slow decline in annual new HIV infections by only 27 per cent from 2010 to 2017 against the national target of 75 per cent by 2020, the national target to end AIDS by 2030 may be missed; although at the sub-national level some States have made better progress to reduce new HIV infection. It calls for reinforcement of HIV prevention, diagnosis and treatment efforts by geographical regions and population groups.