COVID-19 impact on index testing services and programmatic cost in 5 high HIV prevalence Indian districts.

BACKGROUND: Restrictions to curb the first wave of COVID-19 in India resulted in a decline in facility-based HIV testing rates, likely contributing to increased HIV transmission and disease progression. The programmatic and economic impact of COVID-19 on index testing, a standardized contact tracing strategy, remains unknown. METHODS: Retrospective programmatic and costing data were analyzed under a US government-supported program to assess the pandemic's impact on the programmatic outcomes and cost of index testing implemented in two Indian states (Maharashtra and Andhra Pradesh). We compared index testing continuum outcomes during lockdown (April-June 2020) and post-lockdown (July-Sept 2020) relative to pre-lockdown (January-March 2020) by estimating adjusted rate ratios (aRRs) using negative binomial regression. Startup and recurrent programmatic costs were estimated across geographies using a micro-costing approach. Per unit costs were calculated for each index testing continuum outcome. RESULTS: Pre-lockdown, 2431 index clients were offered services, 3858 contacts were elicited, 3191 contacts completed HIV testing, 858 contacts tested positive, and 695 contacts initiated ART. Compared to pre-lockdown, the number of contacts elicited decreased during lockdown (aRR = 0.13; 95% CI: 0.11-0.16) and post-lockdown (aRR = 0.49; 95% CI: 0.43-0.56); and the total contacts newly diagnosed with HIV also decreased during lockdown (aRR = 0.22; 95% CI: 0.18-0.26) and post-lockdown (aRR = 0.52; 95% CI: 0.45-0.59). HIV positivity increased from 27% pre-lockdown to 40% during lockdown and decreased to 26% post-lockdown. Further, ART initiation improved from 81% pre-lockdown to 88% during lockdown and post-lockdown. The overall cost to operate index testing was $193,457 pre-lockdown and decreased during lockdown to $132,177 (32%) and $126,155 (35%) post-lockdown. Post-lockdown unit cost of case identification rose in facility sites ($372) compared to pre-lockdown ($205), however it decreased in community-based sites from pre-lockdown ($277) to post-lockdown ($166). CONCLUSIONS: There was a dramatic decline in the number of index testing clients in the wake of COVID-19 restrictions that resulted in higher unit costs to deliver services; yet, improved linkage to ART suggests that decongesting centres could improve efficiency. Training index testing staff to provide support across services including non-facility-based HIV testing mechanisms (i.e., telemedicine, HIV self-testing, community-based approaches) may help optimize resources during public health emergencies.

Impact of the COVID-19 pandemic on HIV prevention and care services among key populations across 15 cities in India: a longitudinal assessment of clinic-based data.

INTRODUCTION: The COVID-19 pandemic has threatened to diminish gains in HIV epidemic control and impacts are likely most profound among key populations in resource-limited settings. We aimed to understand the pandemic's impact on HIV-related service utilization among men who have sex with men (MSM) and people who inject drugs (PWID) across India. METHODS: Beginning in 2013, we established integrated care centres (ICCs) which provide HIV preventive and treatment services to MSM and PWID across 15 Indian sites. We examined utilization patterns for an 18-month period covering 2 months preceding the pandemic (January-February 2020) and over the first and second COVID-19 waves in India (March 2020-June 2021). We assessed: (1) unique clients accessing any ICC service, (2) ICC services provided, (3) unique clients tested for HIV and (4) HIV diagnoses and test positivity. Among an established cohort of PWID/MSM living with HIV (PLHIV), we administered a survey on the pandemic's impact on HIV care and treatment (June-August 2020). RESULTS: Overall, 13,854 unique clients visited an ICC from January 2020 to June 2021. In January/February 2020, the average monthly number of clients was 3761. Compared to pre-pandemic levels, the number of clients receiving services declined sharply in March 2020, dropping to 25% of pre-pandemic levels in April/May 2020 (first wave), followed by a slow rebound until April/May 2021 (second wave), when there was a 57% decline. HIV testing followed a similar trajectory. HIV test positivity changed over time, declining in the first wave and reaching its nadir around July 2020 at ∼50% of pre-pandemic levels. Positivity then increased steadily, eventually becoming higher than pre-pandemic periods. The second wave was associated with a decline in positivity for MSM but was relatively unchanged for PWID. Among 1650 PLHIV surveyed, 52% of PWID and 45% of MSM reported the pandemic impacted their ability to see an HIV provider. MSM had barriers accessing sexually transmitted infection testing and partner HIV testing. CONCLUSIONS: The COVID-19 pandemic led to significant decreases in HIV-related service utilization among key populations in India. This presents an opportunity for increased transmission and patients presenting with advanced disease among groups already disproportionately impacted by HIV.

Role of geospatial mapping in the planning of HIV programs: A case study from Southern India.

ABSTRACT: Geographic information systems (GIS) tools can be used to understand the spatial distribution of local HIV epidemics but are often underutilized, especially in low-middle income countries. We present characteristics of an HIV epidemic within Hyderabad, a large city in southern India, as a case study to highlight the utility of such data in program planning.Cross-sectional sample recruited using respondent-driven sampling in a cluster-randomized trial.We analyzed data from 2 cross-sectional respondent-driven sampling surveys of MSM in Hyderabad, which were conducted as part of a cluster-randomized trial. All participants were tested for HIV and those positive underwent viral load quantification. ArcGIS was used to create heat maps of MSM distribution using self-reported postal code of residence and combined into larger zones containing at least 200 MSM.Postal code data was available for 661 MSM (66.2%) in the baseline and 978 MSM (97.8%) in the follow-up survey. The proportion of HIV-positive MSM (12.7-15.7%) and prevalence of virally suppressed persons (2.6-8.2%) increased between the 2 surveys. The distribution of all MSM, HIV-positive MSM, and HIV-viremic MSM differed significantly by geographic zone with several zones having higher numbers of HIV-positive and viremic individuals than would be expected based on the distribution of all MSM.The prevalence of HIV and HIV viremia among MSM differed by geographic zones within a city and evolved over time. Such data could be critical to improving program implementation efficiency by accurately targeting resources to population characteristics.

Holiday gatherings, mobility and SARS-CoV-2 transmission: results from 10 US states following Thanksgiving.

Public health officials discouraged travel and non-household gatherings for Thanksgiving, but data suggests that travel increased over the holidays. The objective of this analysis was to assess associations between holiday gatherings and SARS-CoV-2 positivity in the weeks following Thanksgiving. Using an online survey, we sampled 7770 individuals across 10 US states from December 4-18, 2020, about 8-22 days post-Thanksgiving. Participants were asked about Thanksgiving, COVID-19 symptoms, and SARS-CoV-2 testing and positivity in the prior 2 weeks. Logistic regression was used to identify factors associated with SARS-CoV-2 positivity and COVID-19 symptoms in the weeks following Thanksgiving. An activity score measured the total number of non-essential activities an individual participated in the prior 2 weeks. The probability of community transmission was estimated using Markov Chain Monte Carlo (MCMC) methods. While 47.2% had Thanksgiving at home with household members, 26.9% had guests and 25.9% traveled. There was a statistically significant interaction between how people spent Thanksgiving, the frequency of activities, and SARS-CoV-2 test positivity in the prior 2 weeks (p < 0.05). Those who had guests for Thanksgiving or traveled were only more likely to test positive for SARS-CoV-2 if they also had high activity (e.g., participated in > one non-essential activity/day in the prior 2 weeks). Had individuals limited the number and frequency of activities post-Thanksgiving, cases in surveyed individuals would be reduced by > 50%. As travel continues to increase and the more contagious Delta variant starts to dominate transmission, it is critical to promote how to gather in a "low-risk" manner (e.g., minimize other non-essential activities) to mitigate the need for nationwide shelter-at-home orders.

Cost-effectiveness and budgetary impact of HCV treatment with direct-acting antivirals in India including the risk of reinfection.

BACKGROUND: HCV direct-acting antivirals (DAAs) are produced in India at low cost. However, concerns surrounding reinfection and budgetary impact limit treatment scale-up in India. We evaluate the cost-effectiveness and budgetary impact of HCV treatment in India, including reinfection. METHODS: A closed cohort Markov model of HCV disease progression, treatment, and reinfection was parameterized. We compared treatment by fibrosis stage (F2-F4 or F0-F4) to no treatment from a health care payer perspective. Costs (2017 USD$, based on India-specific data) and health utilities (in quality-adjusted life years, QALYs) were attached to each health state. We assumed DAAs with 90% sustained viral response at $900/treatment and 1%/year reinfection, varied in the sensitivity analysis from 0.1-15%. We deemed the intervention cost-effective if the incremental cost-effectiveness ratio (ICER) fell below India's per capita GDP ($1,709). We assessed the budgetary impact of treating all diagnosed individuals. RESULTS: HCV treatment for diagnosed F2-F4 individuals was cost-saving (net costs -$2,881 and net QALYs 3.18/person treated; negative ICER) compared to no treatment. HCV treatment remained cost-saving with reinfection rates of 15%/year. Treating all diagnosed individuals was likely cost-effective compared to delay until F2 (mean ICER $1,586/QALY gained, 67% of simulations falling under the $1,709 threshold) with 1%/year reinfection. For all scenarios, annual retesting for reinfection was more cost-effective than the current policy (one-time retest). Treating all diagnosed individuals and reinfections results in net costs of $445-1,334 million over 5 years (<0.25% of total health care expenditure over 5 years), and cost-savings within 14 years. CONCLUSIONS: HCV treatment was highly cost-effective in India, despite reinfection. Annual retesting for reinfection was cost-effective, supporting a policy change towards more frequent retesting. A comprehensive HCV treatment scale-up plan is warranted in India.

Is there synergy in syndemics? Psychosocial conditions and sexual risk among men who have sex with men in India.

Syndemic theory describes the clustering and synergistic interaction of disease driven by contextual and social factors, which worsen health outcomes for a population, and has been applied to men who have sex with men (MSM) and their risk for HIV and other sexually transmitted infections. Recent reviews, however, have critiqued prevailing approaches in syndemic studies that assess only additive associations without evaluation of synergy. Following these suggestions, we compared the traditional additive approach with a test for synergistic association of 5 syndemic conditions (alcohol dependence, illicit drug use, depression, intimate partner violence (IPV), and childhood sexual abuse (CSA)) with unprotected anal intercourse (UAI) and active syphilis infection among 11,771 MSM recruited through respondent driven sampling from 12 cities in India. UAI was assessed via self-report and active syphilis infection was diagnosed by RPR and THPA tests. An additive association was explored using a condition count (range 0-5), and synergy was tested using relative excess risk due to interactions (RERIs) calculated from all 2-way and common 3-way interactions between conditions in adjusted regression models. There was a significant dose response associated with the syndemic count and UAI, and a similar pattern for syphilis, though not statistically significant. RERIs showed synergy for only one pair of conditions for UAI and syphilis, respectively: IPV + depression and alcohol dependence + illicit drug use. In this study, we found an additive association between syndemic conditions and UAI with evidence of synergistic interaction between a pair of psychosocial conditions, and no significant additive association, but a synergistic interaction between another pair of psychosocial conditions for syphilis. Our results lend further support to a critical reassessment of syndemic analyses. Closer attention to the cumulative development, underlying causal pathways, and possible synergistic interaction of co-occurring epidemics through combined qualitative and quantitative methodologies may yield more effective interventions for vulnerable, marginalized populations.

HIV viral load monitoring among key populations in low- and middle-income countries: challenges and opportunities.

INTRODUCTION: Key populations bear a disproportionate HIV burden and have substantial unmet treatment needs. Routine viral load monitoring represents the gold standard for assessing treatment response at the individual and programme levels; at the population-level, community viral load is a metric of HIV programme effectiveness and can identify "hotspots" of HIV transmission. Nevertheless, there are specific implementation and ethical challenges to effectively operationalize and meaningfully interpret viral load data at the community level among these often marginalized populations. DISCUSSION: Viral load monitoring enhances HIV treatment, and programme evaluation, and offers a better understanding of HIV surveillance and epidemic trends. Programmatically, viral load monitoring can provide data related to HIV service delivery coverage and quality, as well as inequities in treatment access and uptake. From a population perspective, community viral load data provides information on HIV transmission risk. Furthermore, viral load data can be used as an advocacy tool to demonstrate differences in service delivery and to promote allocation of resources to disproportionately affected key populations and communities with suboptimal health outcomes. However, in order to perform viral load monitoring for individual and programme benefit, health surveillance and advocacy purposes, careful consideration must be given to how such key population programmes are designed and implemented. For example, HIV risk factors, such as particular sex practices, sex work and drug use, are stigmatized or even criminalized in many contexts. Consequently, efforts must be taken so that routine viral load monitoring among marginalized populations does not cause inadvertent harm. Furthermore, given the challenges of reaching representative samples of key populations, significant attention to meaningful recruitment, decentralization of care and interpretation of results is needed. Finally, improving the interoperability of health systems through judicious use of biometrics or identifiers when confidentiality can be maintained is important to generate more valuable data to inform monitoring programmes. CONCLUSIONS: Opportunities for expanded viral load monitoring could and should benefit all those affected by HIV, including key populations. The promise of the increasing routinization of viral load monitoring as a tool to advance HIV treatment equity is great and should be prioritized and appropriately implemented within key population programmatic and research agendas.

Impact of generic antiretroviral therapy (ART) and free ART programs on time to initiation of ART at a tertiary HIV care center in Chennai, India.

Antiretroviral therapy (ART) access in the developing world has improved, but whether increased access has translated to more rapid treatment initiation among those who need it is unknown. We characterize time to ART initiation across three eras of ART availability in Chennai, India (1996-1999: pregeneric; 2000-2003: generic; 2004-2007: free rollout). Between 1996 and 2007, 11,171 patients registered for care at the YR Gaitonde Centre for AIDS Research and Education (YRGCARE), a tertiary HIV referral center in southern India. Of these, 5726 patients became eligible for ART during this period as per Indian guidelines for initiation of ART. Generalized gamma survival models were used to estimate relative times (RT) to ART initiation by calendar periods of eligibility. Time to initiation of ART among patients in Chennai, India was also compared to an HIV clinical cohort in Baltimore, USA. Median age of the YRGCARE patients was 34 years; 77% were male. The median CD4 at presentation was 140 cells/µl. After adjustment for demographics, CD4 and WHO stage, persons in the pregeneric era took 3.25 times longer (95% confidence interval [CI]: 2.53-4.17) to initiate ART versus the generic era and persons in the free rollout era initiated ART more rapidly than the generic era (RT: 0.73; 95% CI: 0.63-0.83). Adjusting for differences across centers, patients at YRGCARE took longer than patients in the Johns Hopkins Clinical Cohort (JHCC) to initiate ART in the pregeneric era (RT: 4.90; 95% CI: 3.37-7.13) but in the free rollout era, YRGCARE patients took only about a quarter of the time (RT: 0.31; 95% CI: 0.22-0.44). These data demonstrate the benefits of generic ART and government rollouts on time to initiation of ART in one developing country setting and suggests that access to ART may be comparable to developed country settings.

Low-cost assays for monitoring HIV infected individuals in resource-limited settings.

Use of a combination of CD4 counts and HIV viral load testing in the management of antiretroviral therapy (ART) provides higher prognostic estimation of the risk of disease progression than does the use of either test alone. The standard methods to monitor HIV infection are flow cytometry based for CD4+ T cell count and molecular assays to quantify plasma viral load of HIV. Commercial assays have been routinely used in developed countries to monitor ART. However, these assays require expensive equipment and reagents, well trained operators, and established laboratory infrastructure. These requirements restrict their use in resource-limited settings where people are most afflicted with the HIV-1 epidemic. With the advent of low-cost and/or low-tech alternatives, the possibility of implementing CD4 count and viral load testing in the management of ART in resource-limited settings is increasing. However, an appropriate validation should have been done before putting them to use for patient testing.

Evaluation of two human immunodeficiency virus-1 genotyping systems: ViroSeq 2.0 and an in-house method.

Commercial HIV-1 genotypic resistance assays are very expensive, particularly for use in resource-constrained settings like India. Hence a cost effective in-house assay for drug resistance was validated against the standard ViroSeq HIV-1 Genotyping System 2.0 (Celera Diagnostics, CA, USA). A total of 50 samples were used for this evaluation (21 proficiency panels and 29 clinical isolates). Known resistance positions within HIV-1 protease (PR) region (1-99 codons) and HIV-1 reverse-transcriptase (RT) region (1-240 codons) were included. The results were analysed for each codon as follows: (i) concordant; (ii) partially concordant; (iii) indeterminate and (iv) discordant. A total of 2750 codons (55 codons per patient samplex50 samples) associated with drug resistance (1050 PR and 1700 RT) were analysed. For PR, 99% of the codon results were concordant and 1% were partially concordant. For RT, 99% of the codon results were concordant, 0.9% were partially concordant and 0.1% were discordant. No indeterminate results were observed and the results were reproducible. Overall, the in-house assay provided comparable results to those of US FDA approved ViroSeq, which costs about a half of the commercial assay ($ 100 vs. $ 230), making it suitable for resource-limited settings.

A reliable and inexpensive EasyCD4 assay for monitoring HIV-infected individuals in resource-limited settings.

Serial measurements of absolute CD4+ T-lymphocyte counts are required to initiate and gauge response to therapy and monitor disease progression. Hence, there is an urgent need to evaluate the accuracy and validity of low-cost CD4+ T-cell count assays. Tripotassium EDTA blood specimens from HIV-infected individuals were studied using a novel flow cytometric assay (EasyCD4 assay; Guava Technologies, Hayward, CA) in comparison with standard flow cytometry (FACSCount; Becton Dickinson Immunocytometry Systems, San Jose, CA). The sensitivity, specificity value by EasyCD4 assay in enumerating absolute CD4+ T-cell counts of less than 200 cells/microL were 95% and 100%, respectively. Bland-Altman analysis showed close agreement, with the EasyCD4 assay yielding CD4+ T-cell counts a mean difference of -26 cells/microL (95% confidence interval, -96 to 44 cells/microL) higher than by flow cytometry. Our data suggest that EasyCD4 assay could be a useful alternative assay to conventional flow cytometry, may be appropriate for use in resource-limited settings.