A Mixture Model for Estimating SARS-CoV-2 Seroprevalence in Chennai, India.

Serological assays used to estimate the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) often rely on manufacturers' cutoffs established on the basis of severe cases. We conducted a household-based serosurvey of 4,677 individuals in Chennai, India, from January to May 2021. Samples were tested for SARS-CoV-2 immunoglobulin G (IgG) antibodies to the spike (S) and nucleocapsid (N) proteins. We calculated seroprevalence, defining seropositivity using manufacturer cutoffs and using a mixture model based on measured IgG level. Using manufacturer cutoffs, there was a 5-fold difference in seroprevalence estimated by each assay. This difference was largely reconciled using the mixture model, with estimated anti-S and anti-N IgG seroprevalence of 64.9% (95% credible interval (CrI): 63.8, 66.0) and 51.5% (95% CrI: 50.2, 52.9), respectively. Age and socioeconomic factors showed inconsistent relationships with anti-S and anti-N IgG seropositivity using manufacturer cutoffs. In the mixture model, age was not associated with seropositivity, and improved household ventilation was associated with lower seropositivity odds. With global vaccine scale-up, the utility of the more stable anti-S IgG assay may be limited due to the inclusion of the S protein in several vaccines. Estimates of SARS-CoV-2 seroprevalence using alternative targets must consider heterogeneity in seroresponse to ensure that seroprevalence is not underestimated and correlates are not misinterpreted.

Integrating HCV testing with HIV programs improves hepatitis C outcomes in people who inject drugs: A cluster-randomized trial.

BACKGROUND & AIMS: There have been calls to integrate HCV testing into existing services, including harm reduction and HIV prevention and treatment, but there are few empirical trials to date. We evaluated the impact of integrating HCV testing/education into integrated care centers (ICCs) delivering HIV services to people who inject drugs (PWID) across India, using a cluster-randomized trial. METHODS: We compared ICCs with usual care in the PWID stratum (12 sites) of a 22-site cluster-randomized trial. In 6 sites, ICCs delivering HIV testing, harm reduction, other preventive services and linkage to HIV treatment were scaled from opioid agonist therapy centers and operated for 2 years. On-site rapid HCV antibody testing was integrated after 1 year. To assess impact, we conducted baseline and evaluation surveys using respondent-driven sampling (RDS) across the 12 sites (n = 11,993 recruited at baseline; n = 11,721 recruited at evaluation). The primary outcome was population-level self-reported HCV testing history. RESULTS: At evaluation, HCV antibody prevalence ranged from 7.2-76.6%. Across 6 ICCs, 5,263 ICC clients underwent HCV testing, of whom 2,278 were newly diagnosed. At evaluation, PWID in ICC clusters were 4-fold more likely to report being tested for HCV than in usual care clusters, adjusting for baseline testing (adjusted prevalence ratio [aPR] 3.69; 95% CI 1.34-10.2). PWID in ICC clusters were also 7-fold more likely to be aware of their HCV status (aPR 7.11; 95% CI 1.14-44.3) and significantly more likely to initiate treatment (aPR 9.86; 95% CI 1.52-63.8). CONCLUSIONS: We provide among the first empirical data supporting the integration of HCV testing into HIV/harm reduction services. To achieve elimination targets, programs will need to scale-up such venues to deliver comprehensive HCV services. CLINICALTRIALS. GOV IDENTIFIER: NCT01686750. LAY SUMMARY: Delivering hepatitis C virus (HCV) testing to people who inject drugs (PWID) in places where they also have access to HIV prevention and treatment services is an effective way to improve uptake of HCV testing among communities of PWID. To achieve the World Health Organization's ambitious elimination targets, integrated programs will need to be scaled up to deliver comprehensive HCV services.

Temporal change in population-level prevalence of detectable HIV viraemia and its association with HIV incidence in key populations in India: a serial cross-sectional study.

BACKGROUND: Population-level prevalence of detectable HIV viraemia (PDV) has been proposed as a metric for monitoring the population-level effectiveness of HIV treatment as prevention. We aimed to characterise temporal changes in PDV in people who inject drugs (PWID) and men who have sex with men (MSM) in India and evaluate community-level and individual-level associations with cross-sectional HIV incidence. METHODS: We did a serial cross-sectional study in which baseline (from Oct 1, 2012, to Dec 19, 2013) and follow-up (from Aug 1, 2016, to May 28, 2017) respondent-driven sampling (RDS) surveys were done in MSM (ten community sites) and PWID (12 community sites) across 21 cities in India. Eligible participants were those aged 18 years or older who provided informed consent and possessed a valid RDS referral coupon. Annualised HIV incidence was estimated with validated multiple-assay algorithms. PDV was calculated as the percentage of people with detectable HIV RNA (>150 copies per mL) in a community site. Community-level associations were determined by linear regression. Multivariable, multilevel Poisson regression was used to assess associations with recent HIV infection. FINDINGS: We recruited 21 990 individuals in the baseline survey and 21 726 individuals in the follow-up survey. The median community-level HIV incidence estimate increased from 0·9% (range 0·0-2·2) at baseline to 1·5% (0·5-3·0) at follow-up in MSM and from 1·6% (0·5-12·4) to 3·6% (0·0-18·4) in PWID. At the community-level, every 1 percentage point increase in baseline PDV and temporal change in PDV between surveys was associated with higher annualised HIV incidence at follow-up: for baseline PDV ß=0·41 (95% CI 0·18-0·63) and for change in PDV ß=0·52 (0·38-0·66). After accounting for individual-level risk factors, every 10 percentage point increase in baseline PDV and temporal change in PDV was associated with higher individual-level risk of recent HIV infection at follow-up: adjusted risk ratio 1·85 (95% CI 1·44-2·37) for baseline PDV and 1·81 (1·43-2·29) for change in PDV. INTERPRETATION: PDV was temporally associated with community-level and individual-level HIV incidence. These data support scale-up of treatment as prevention programmes to reduce HIV incidence and the programmatic use of PDV to monitor community HIV risk potential. FUNDING: US National Institutes of Health, Elton John AIDS Foundation.

Low incidences of human immunodeficiency virus and hepatitis C virus infection and declining risk behaviors in a cohort of injection drug users in Chennai, India.

The authors characterized human immunodeficiency virus (HIV) and hepatitis C virus (HCV) incidence and prospective changes in self-reported risk behavior over 2 years among 1,158 injection drug users (IDUs) recruited in Chennai, India, in 2005-2006. At baseline, HIV prevalence was 25.3%, and HCV prevalence was 54.5%. Seropositive persons with prevalent HIV infection were used to estimate baseline HIV incidence by means of the Calypte HIV-1 BED Incidence EIA (Calypte Biomedical Corporation, Portland, Oregon). Longitudinal HIV and HCV incidence were measured among 865 HIV-negative IDUs and 519 HCV antibody-negative IDUs followed semiannually for 2 years. Participants received pre- and posttest risk reduction counseling at each visit. Estimated HIV incidence at baseline was 2.95 per 100 person-years (95% confidence interval (CI): 1.21, 4.69) by BED assay; observed HIV incidence over 1,262 person-years was 0.48 per 100 person-years (95% CI: 0.17, 1.03). HCV incidence over 645 person-years was 1.71 per 100 person-years (95% CI: 0.85, 3.03). Self-reported risk behaviors declined significantly over time, from 100% of participants reporting drug injection at baseline to 11% at 24 months. In this cohort with high HIV and HCV prevalence at enrollment, the authors observed low incidence and declining self-reported risk behavior over time. While no formal intervention was administered, these findings highlight the potential impact of voluntary counseling and testing in a high-risk cohort.

The Hidden Burden of Dengue and Chikungunya in Chennai, India.

BACKGROUND: Dengue and chikungunya are rapidly expanding viruses transmitted by mosquitoes of the genus Aedes. Few epidemiological studies have examined the extent of transmission of these infections in South India despite an increase in the number of reported cases, and a high suitability for transmission. METHODS AND FINDINGS: We conducted a household-based seroprevalence survey among 1010 individuals aged 5-40 years living in fifty randomly selected spatial locations in Chennai, Tamil Nadu. Participants were asked to provide a venous blood sample and to complete a brief questionnaire with basic demographic and daily activity information. Previous exposure to dengue and chikungunya was determined using IgG indirect ELISA (Panbio) and IgG ELISA (Novatec), respectively. We used this data to estimate key transmission parameters (force of infection and basic reproductive number) and to explore factors associated with seropositivity. While only 1% of participants reported history of dengue and 20% of chikungunya, we found that 93% (95%CI 89-95%) of participants were seropositive to dengue virus, and 44% (95%CI 37-50%) to chikungunya. Age-specific seroprevalence was consistent with long-tem, endemic circulation of dengue and suggestive of epidemic chikungunya transmission. Seropositivity to dengue and chikungunya were significantly correlated, even after adjusting for individual and household factors. We estimate that 23% of the susceptible population gets infected by dengue each year, corresponding to approximately 228,000 infections. This transmission intensity is significantly higher than that estimated in known hyperendemic settings in Southeast Asia and the Americas. CONCLUSIONS: These results provide unprecedented insight into the very high transmission potential of dengue and chikungunya in Chennai and underscore the need for enhanced surveillance and control methods.

Burden of hepatitis C virus disease and access to hepatitis C virus services in people who inject drugs in India: a cross-sectional study.

BACKGROUND: 90% of individuals infected with hepatitis C virus (HCV) worldwide reside in resource-limited settings. We aimed to characterise the prevalence of HCV, HIV/HCV co-infection, and the HCV care continuum in people who inject drugs in India. METHODS: 14 481 people (including 31 seeds--individuals selected as the starting point for sampling because they were well connected in the drug using community) who inject drugs were sampled from 15 cities throughout India using respondent-driven sampling from Jan 2, 2013 to Dec 19, 2013. Data from seeds were excluded from all analyses. HCV prevalence was estimated by the presence of anti-HCV antibodies incorporating respondent-driven sampling weights. HCV care continuum outcomes were self-reported except for viral clearance in treatment-experienced participants. FINDINGS: The median age of participants was 30 years (IQR 24-36) and 13 608 (92·4%) of 14 449 were men (data were missing for some variables). Weighted HCV prevalence was 5777 (37·2%) of 14 447; HIV/HCV co-infection prevalence was 2085 (13·2%) of 14 435. Correlates of HCV infection included high lifetime injection frequency, HIV positivity, and a high prevalence of people with HIV RNA (more than 1000 copies per mL) in the community. Of the 5777 people who inject drugs that were HCV antibody positive, 440 (5·5%) were aware of their status, 225 (3·0%) had seen a doctor for their HCV, 79 (1·4%) had taken HCV treatment, and 18 (0·4%) had undetectable HCV RNA. Of 12 128 participants who had not previously been tested for HCV, 6138 (50·5%) did not get tested because they had not heard of HCV. In the 5777 people who were HCV antibody positive, 2086 (34·4%) reported harmful or hazardous alcohol use, of whom 1082 (50·4%) were dependent, and 3821 (65·3%) reported needle sharing. Awareness of HCV positive status was significantly associated with higher education, HIV testing history, awareness of HIV positive status, and higher community antiretroviral therapy coverage. INTERPRETATION: The high burden of HCV and HIV/HCV co-infection coupled with low-access to HCV services emphasises an urgent need to include resource-limited settings in the global HCV agenda. Although new treatments will become available worldwide in the near future, programmes to improve awareness and reduce disease progression and transmission need to be scaled up without further delay. Failure to do so could result in patterns of rising mortality, undermining advances in survival attributed to widespread HIV treatment. FUNDING: US National Institutes of Health.