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.

Targeted interventions of the Avahan program and their association with intermediate outcomes among female sex workers in Maharashtra, India.

BACKGROUND: Avahan, the India AIDS Initiative has been a partner supporting targeted interventions of high risk populations under India's National AIDS Control Organisation (NACO) since 2004 in the state of Maharashtra. This paper presents an assessment of the Avahan program among female sex workers (FSWs) in Maharashtra, its coverage, outcomes achieved and their association with Avahan program. METHODS: An analytical framework based on the Avahan evaluation design was used, addressing assessment questions on program implementation, intermediate outcomes and association of outcomes with Avahan. Data from routine program monitoring, two rounds of cross-sectional Integrated Behavioural and Biological Assessments (IBBAs) conducted in 2006 (Round 1- R1) and 2009 (Round 2 - R2) and quality assessments of program clinics were used. Bi-variate and multivariate analysis were conducted using the complex samples module in SPSS 15 (IBM, Somers NY). RESULTS: The Avahan program achieved coverage of over 66% of FSWs within four years of implementation. The IBBA data showed increased contact by peers in R2 compared to R1 (AOR:2.34; p=0.001). Reported condom use with clients increased in R2 and number of FSWs reporting zero unprotected sex acts increased from 76.2% (R1) to 94.6% (R2) [AOR: 5.1, p=0.001].Significant declines were observed in prevalence of syphilis (RPR) (15.8% to 10.8%; AOR:0.54; p=0.001), chlamydia (8% to 6.2%; AOR:.0.65; p=0.010) and gonorrohoea (7.4% to 3.9; AOR:.0.60; p=0.026) between R1 and R2. HIV prevalence increased (25.8% to 27.5%; AOR:1.29; p=0.04). District-wise analysis showed decline in three districts and increase in Mumbai and Thane districts.FSWs exposed to Avahan had higher consistent condom use with occasional (94.3% vs. 90.6%; AOR: 1.55; p=0.04) and regular clients (92.5% vs. 86.0%; AOR: 1.95, p=0.001) compared to FSWs unexposed to Avahan. Decline in high titre syphilis was associated with Avahan exposure. CONCLUSION: The Avahan program was scaled up and achieved high coverage of FSWs in Maharashtra amidst multiple intervention players. Avahan coverage of FSWs was associated with improved safe sexual practices and declines in STIs. Prevalence of HIV increased requiring more detailed understanding of the data and, if confirmed, new approaches for HIV control.

Condom use and prevalence of syphilis and HIV among female sex workers in Andhra Pradesh, India - following a large-scale HIV prevention intervention.

BACKGROUND: Avahan, the India AIDS initiative began HIV prevention interventions in 2003 in Andhra Pradesh (AP) among high-risk groups including female sex workers (FSWs), to help contain the HIV epidemic. This manuscript describes an assessment of this intervention using the published Avahan evaluation framework and assesses the coverage, outcomes and changes in STI and HIV prevalence among FSWs. METHODOLOGY: Multiple data sources were utilized including Avahan routine program monitoring data, two rounds of cross-sectional survey data (in 2006 and 2009) and STI clinical quality monitoring assessments. Bi-variate and multivariate analyses, Wald Chi-square tests and multivariate logistic regressions were used to measure changes in behavioural and biological outcomes over time and their association. RESULTS: Avahan scaled up in conjunction with the Government program to operate in all districts in AP by March 2009. By March 2009, 80% of the FSWs were being contacted monthly and 21% were coming to STI services monthly. Survey data confirmed an increase in peer educator contacts with the mean number increasing from 2.9 in 2006 to 5.3 in 2009. By 2008 free and Avahan-supported socially marketed condoms were adequate to cover the estimated number of commercial sex acts, at 45 condoms/FSW/month. Consistent condom use was reported to increase with regular (63.6% to 83.4%; AOR=2.98; p<0.001) and occasional clients (70.8% to 83.7%; AOR=2.20; p<0.001). The prevalence of lifetime syphilis decreased (10.8% to 6.1%; AOR=0.39; p<0.001) and HIV prevalence decreased in all districts combined (17.7% to 13.2%; AOR 0.68; p<0.01). Prevalence of HIV among younger FSWs (aged 18 to 20 years) decreased (17.7% to 8.2%, p=0.008). A significant increase in condom use at last sex with occasional and regular clients and consistent condom use with occasional clients was observed among FSWs exposed to the Avahan program. There was no association between exposure and HIV or STIs, although numbers were small. CONCLUSIONS: The absence of control groups is a limitation of this study and does not allow attribution of changes in outcomes and declines in HIV and STI to the Avahan program. However, the large scale implementation, high coverage, intermediate outcomes and association of these outcomes to the Avahan program provide plausible evidence that the declines were likely associated with Avahan. Declining HIV prevalence among the general population in Andhra Pradesh points towards a combined impact of Avahan and government interventions.

Baseline integrated behavioural and biological assessment among most at-risk populations in six high-prevalence states of India: design and implementation challenges.

OBJECTIVE: This paper presents key methodological approaches and challenges in implementing and analysing the first round of the integrated biobehavioural assessment of most-at-risk populations, conducted in conjunction with evaluation of Avahan, the India AIDS initiative. METHODS: The survey collected data on HIV risk behaviours, sexually transmitted infections and HIV prevalence in 29 districts in six high-prevalence states of India. Groups included female sex workers and clients, men who have sex with men, injecting drug users and truck drivers. Strategies for overcoming some challenges of the large-scale surveys among vulnerable populations, including sampling hidden populations, involvement of the communities targeted by the survey, laboratory and quality control in remote, non-clinic field settings, and data analysis and data use are presented. DISCUSSION: Satisfying the need for protocols, guidelines and tools that allowed for sufficient standardization, while being tailored enough to fit diverse local situations on such a large scale, with so many implementing partners, emerged as a major management challenge. A major lesson from the first round is the vital importance of investing upfront time in tailoring the sampling methods, data collection instruments, and analysis plan to match measurement objectives. CONCLUSION: Despite the challenges, the integrated biobehavioural assessment was a huge achievement, and was largely successful in providing previously unavailable information about the HIV situation among populations that are critical to the curtailment of HIV spread in India. Lessons from the first round will be used to evolve the second round into an exercise with increased evaluative capability for Avahan.