Sentiment Analysis of Twitter Posts Related to a COVID-19 Test & Trace Program in NYC.

As part of a program evaluation of the New York City Test & Trace program (T2)-one of the largest such programs in the USA-we conducted a study to assess how implementing organizations (NYC Health + Hospitals, government agencies, CBOs) communicated information about the T2 program on Twitter. Study aims were as follows: (1) quantify user engagement of posts ("tweets") about T2 by NYC organizations on Twitter and (2) examine the emotional tone of social media users' T2-related tweets in our sample of 1987 T2-related tweets. Celebrities and CBOs generated more user engagement (0.26% and 0.07%, respectively) compared to government agencies (e.g., Mayor's Office, 0.0019%), reinforcing the value of collaborating with celebrities and CBOs in social media public health campaigns. Sentiment analysis revealed that positive tweets (46.5%) had higher user engagement than negative tweets (number of likes: R2 = .095, p < .01), underscoring the importance of positively framing messages for effective public health campaigns.

Meeting Social Needs in a Crisis Context: Lessons Learned from Integrating the 'Take Care Initiative' into New York City's Testing and Contact Tracing Program.

The COVID-19 pandemic highlighted the importance of addressing social needs in a crisis context. Some US jurisdictions integrated a social service component into case investigation and contact tracing (CI/CT) programs, including the New York City (NYC) Test & Trace (T2) Program; the Take Care initiative referred NYC residents who tested positive or were exposed to COVID-19 to services to support isolation and quarantine and meet basic needs. More research is needed to determine effective implementation strategies for integrating social needs provision into CI/CT programs. To identify barriers and facilitators to the implementation of the Take Care initiative, we conducted key informant interviews with program staff, community-based organization partners, and cases and contacts as part of a larger evaluation of the T2 program. Interviews were recorded, transcribed, and analyzed using rapid qualitative methods. Key facilitators to implementation included utilizing a case management software system, employing strategies to encourage service uptake, leveraging cross-agency collaborations, and partnering with community-based organizations for resource navigation. Barriers identified included external management of the software system, challenges reaching and engaging the public, administrative complications due to shifting collaborations, and management of CBO partners' structure and hiring. Based on our findings, we provide recommendations to support effective planning and implementation of social needs service provision in a crisis context. Future research should focus on testing promising implementation strategies highlighted in this study and applying them to varied contexts and crisis situations.

Health impact, budget impact, and price threshold for cost-effectiveness of lenacapavir for HIV pre-exposure prophylaxis in eastern and southern Africa: a modelling analysis.

BACKGROUND: Injectable lenacapavir administered every 6 months is a promising product for HIV pre-exposure prophylaxis (PrEP). We aimed to estimate the health and budget impacts and threshold price at which lenacapavir could be cost-effective in eastern and southern Africa. METHODS: We adapted an agent-based network model, EMOD-HIV, to simulate lenacapavir scale-up in Zimbabwe, South Africa, and western Kenya from 2026 to 2035. Uptake assumptions were informed by a literature review of PrEP product preferences. In the main analysis, we varied lenacapavir coverage by subgroup: female sex workers (40% coverage); male clients of female sex workers (40%); adolescent girls and young women aged 15-24 years with more than one sexual partner (32%); women aged 25 years and older with more than one sexual partner (36%); and males with more than one sexual partner (32%). We also assessed a higher coverage scenario (64-76% across subgroups) and scenarios of expanding lenacapavir use, varying from concentrated among those at highest HIV risk to broader coverage including those at medium HIV risk. We estimated the maximum per-dose lenacapavir price that achieved cost-effectiveness (

Scale-Up of COVID-19 Testing Services in NYC, 2020-2021: Lessons Learned to Maximize Reach, Equity and Timeliness.

During infectious disease epidemics, accurate diagnostic testing is key to rapidly identify and treat cases, and mitigate transmission. When a novel pathogen is involved, building testing capacity and scaling testing services at the local level can present major challenges to healthcare systems, public health agencies, and laboratories. This mixed methods study examined lessons learned from the scale-up of SARS-CoV-2 testing services in New York City (NYC), as a core part of NYC's Test & Trace program. Using quantitative and geospatial analyses, the authors assessed program success at maximizing reach, equity, and timeliness of SARS-CoV-2 diagnostic testing services across NYC neighborhoods. Qualitative analysis of key informant interviews elucidated key decisions, facilitators, and barriers involved in the scale-up of SARS-CoV-2 testing services. A major early facilitator was the ability to establish working relationships with private sector vendors and contractors to rapidly procure and manufacture necessary supplies locally. NYC residents were, on average, less than 25 min away from free SARS-CoV-2 diagnostic testing services by public transport, and services were successfully directed to most neighborhoods with the highest transmission rates, with only one notable exception. A key feature was to direct mobile testing vans and rapid antigen testing services to areas based on real-time neighborhood transmission data. Municipal leaders should prioritize fortifying supply chains, establish cross-sectoral partnerships to support and extend testing services, plan for continuous testing and validation of assays, ensure open communication feedback loops with CBO partners, and maintain infrastructure to support mobile services during infectious disease emergencies.

Evaluation of the New York City COVID-19 case investigation and contact tracing program: a cascade of care analysis.

BACKGROUND: New York City (NYC) was the first COVID-19 epicenter in the United States and home to one of the country's largest contact tracing programs, NYC Test & Trace (T2). Understanding points of attrition along the stages of program implementation and follow-up can inform contact tracing efforts for future epidemics or pandemics. The objective of this study was to evaluate the completeness and timeliness of T2 case and contact notification and monitoring using a "cascade of care" approach. METHODS: This cross-sectional study included all SARS-CoV-2 cases and contacts reported to T2 from May 31, 2020 to January 1, 2022. Attrition along the "cascade of care" was defined as: (1) attempted, (2) reached, (3) completed intake (main outcome), (4) eligible for monitoring, and (5) successfully monitored. Timeliness was assessed: (1) by median days from a case's date of testing until their positive result was reported to T2, (2) from result until the case was notified by T2, and (3) from a case report of a contact until notification of the contact. RESULTS: A total of 1.45 million cases and 1.38 million contacts were reported to T2 during this period. For cases, attrition occurred evenly across the first three cascade steps (~-12%) and did not change substantially until the Omicron wave in December 2021. During the Omicron wave, the proportion of cases attempted dropped precipitously. For contacts, the largest attrition occurred between attempting and reaching (-27%), and attrition rose with each COVID-19 wave as contact volumes increased. Attempts to reach contacts discontinued entirely during the Omicron wave. Overall, 67% of cases and 49% of contacts completed intake interviews (79% and 57% prior to Omicron). T2 was timely, with a median of 1 day to receive lab results, 2 days to notify cases, and < 1 day to notify contacts. CONCLUSIONS: T2 provided a large volume of NYC residents with timely notification and monitoring. Engagement in the program was lower for contacts than cases, with the largest gap coming from inability to reach individuals during call attempts. To strengthen future test-and-trace efforts, strategies are needed to encourage acceptance of local contact tracer outreach attempts.

Performance analysis of mathematical methods used to forecast the 2022 New York City Mpox outbreak.

In mid-2022, New York City (NYC) became the epicenter of the US mpox outbreak. We provided real-time mpox case forecasts to the NYC Department of Health and Mental Hygiene to aid in outbreak response. Forecasting methodologies evolved as the epidemic progressed. Initially, lacking knowledge of at-risk population size, we used exponential growth models to forecast cases. Once exponential growth slowed, we used a Susceptible-Exposed-Infectious-Recovered (SEIR) model. Retrospectively, we explored if forecasts could have been improved using an SEIR model in place of our early exponential growth model, with or without knowing the case detection rate. Early forecasts from exponential growth models performed poorly, as 2-week mean absolute error (MAE) grew from 53 cases/week (July 1-14) to 457 cases/week (July 15-28). However, when exponential growth slowed, providing insight into susceptible population size, an SEIR model was able to accurately predict the remainder of the outbreak (7-week MAE: 13.4 cases/week). Retrospectively, we found there was not enough known about the epidemiological characteristics of the outbreak to parameterize an SEIR model early on. However, if the at-risk population and case detection rate were known, an SEIR model could have improved accuracy over exponential growth models early in the outbreak.

Lessons Learned from the Launch and Implementation of the COVID-19 Contact Tracing Program in New York City: a Qualitative Study.

On June 1, 2020, NYC Health + Hospitals, in partnership with the NYC Department of Health and Mental Hygiene, other city agencies, and a large network of community partners, launched the New York City Test & Trace (T2) COVID-19 response program to identify and isolate cases, reduce transmission through contact tracing, and provide support to residents during isolation or quarantine periods. In this paper, we describe lessons learned with respect to planning and implementation of case notification and contact tracing. Our findings are based on extensive document review and analysis of 74 key informant interviews with T2 leadership and frontline staff, cases, and contacts conducted between January and September 2022. Interviews elicited respondent background, history of program development, program leadership and structure, goals of the program, program evolution, staffing, data systems, elements of community engagement, trust with community, program reach, timeliness, equity, general barriers and challenges, general facilitators and best practices, and recommendations/improvement for the program. Facilitators and barriers revealed in the interviews primarily revolved around hiring and managing staff, data and technology, and quality of interactions with the public. Based on these facilitators and barriers, we identify suggestions to support effective planning and response for future case notification and contact tracing programs, including recommendations for planning during latent periods, case management and data systems, and processes for outreach to cases and contacts.

Moving beyond hotspots of HIV prevalence to geospatial hotspots of UNAIDS 95-95-95 targets in sub-Saharan Africa.

The HIV epidemic in sub-Saharan Africa displays a varied geographical distribution, with particular regions termed as HIV hotspots due to a higher prevalence of infection. Addressing these hotspots is essential for controlling the epidemic. However, these regions, influenced by historical factors, challenge standard interventions. Legacy effects-the lasting impact of past events-play a substantial role in the persistence of these hotspots. To address this challenge of the standard interventions, we propose a shift towards the UNAIDS 95-95-95 targets. Spatial analysis of HIV viral load and antiretroviral therapy coverage can provide a more comprehensive perspective on the epidemic's dynamics. Studies in Zambia and Zimbabwe, using this approach, have revealed disparities in HIV care metrics across regions. By focusing on the UNAIDS 95-95-95 targets, more effective control strategies can be designed, with consideration of both historical and current factors. This approach would offer a solution-oriented strategy, emphasising tailored interventions based on specific regional needs.

Measuring HIV Acquisitions Among Partners of Key Populations: Estimates From HIV Transmission Dynamic Models.

BACKGROUND: Key populations (KPs), including female sex workers (FSWs), gay men and other men who have sex with men (MSM), people who inject drugs (PWID), and transgender women (TGW) experience disproportionate risks of HIV acquisition. The UNAIDS Global AIDS 2022 Update reported that one-quarter of all new HIV infections occurred among their non-KP sexual partners. However, this fraction relied on heuristics regarding the ratio of new infections that KPs transmitted to their non-KP partners to the new infections acquired among KPs (herein referred to as "infection ratios"). We recalculated these ratios using dynamic transmission models. SETTING: One hundred seventy-eight settings (106 countries). METHODS: Infection ratios for FSW, MSM, PWID, TGW, and clients of FSW were estimated from 12 models for 2020. RESULTS: Median model estimates of infection ratios were 0.7 (interquartile range: 0.5-1.0; n = 172 estimates) and 1.2 (0.8-1.8; n = 127) for acquisitions from FSW clients and transmissions from FSW to all their non-KP partners, respectively, which were comparable with the previous UNAIDS assumptions (0.2-1.5 across regions). Model estimates for female partners of MSM were 0.5 (0.2-0.8; n = 20) and 0.3 (0.2-0.4; n = 10) for partners of PWID across settings in Eastern and Southern Africa, lower than the corresponding UNAIDS assumptions (0.9 and 0.8, respectively). The few available model estimates for TGW were higher [5.1 (1.2-7.0; n = 8)] than the UNAIDS assumptions (0.1-0.3). Model estimates for non-FSW partners of FSW clients in Western and Central Africa were high (1.7; 1.0-2.3; n = 29). CONCLUSIONS: Ratios of new infections among non-KP partners relative to KP were high, confirming the importance of better addressing prevention and treatment needs among KP as central to reducing overall HIV incidence.

Comparison of Empirically Derived and Model-Based Estimates of Key Population HIV Incidence and the Distribution of New Infections by Population Group in Sub-Saharan Africa.

BACKGROUND: The distribution of new HIV infections among key populations, including female sex workers (FSWs), gay men and other men who have sex with men (MSM), and people who inject drugs (PWID) are essential information to guide an HIV response, but data are limited in sub-Saharan Africa (SSA). We analyzed empirically derived and mathematical model-based estimates of HIV incidence among key populations and compared with the Joint United Nations Programme on HIV/AIDS (UNAIDS) estimates. METHODS: We estimated HIV incidence among FSW and MSM in SSA by combining meta-analyses of empirical key population HIV incidence relative to the total population incidence with key population size estimates (KPSE) and HIV prevalence. Dynamic HIV transmission model estimates of HIV incidence and percentage of new infections among key populations were extracted from 94 country applications of 9 mathematical models. We compared these with UNAIDS-reported distribution of new infections, implied key population HIV incidence and incidence-to-prevalence ratios. RESULTS: Across SSA, empirical FSW HIV incidence was 8.6-fold (95% confidence interval: 5.7 to 12.9) higher than total population female 15-39 year incidence, and MSM HIV incidence was 41.8-fold (95% confidence interval: 21.9 to 79.6) male 15-29 year incidence. Combined with KPSE, these implied 12% of new HIV infections in 2021 were among FSW and MSM (5% and 7% respectively). In sensitivity analysis varying KPSE proportions within 95% uncertainty range, the proportion of new infections among FSW and MSM was between 9% and 19%. Insufficient data were available to estimate PWID incidence rate ratios. Across 94 models, median proportion of new infections among FSW, MSM, and PWID was 6.4% (interquartile range 3.2%-11.7%), both much lower than the 25% reported by UNAIDS. CONCLUSION: Empirically derived and model-based estimates of HIV incidence confirm dramatically higher HIV risk among key populations in SSA. Estimated proportions of new infections among key populations in 2021 were sensitive to population size assumptions and were substantially lower than estimates reported by UNAIDS.

Impact of Decarceration Plus Alcohol, Substance Use, and Mental Health Screening on Life Expectancies of Black Sexual Minority Men and Black Transgender Women Living With HIV in the United States: A Simulation Study Based on HPTN 061.

BACKGROUND: Given the disproportionate rates of incarceration and lower life expectancy (LE) among Black sexual minority men (BSMM) and Black transgender women (BTW) with HIV, we modeled the impact of decarceration and screening for psychiatric conditions and substance use on LE of US BSMM/BTW with HIV. METHODS: We augmented a microsimulation model previously validated to predict LE and leading causes of death in the US with estimates from the HPTN 061 cohort and the Veteran's Aging Cohort Studies. We estimated independent associations among psychiatric and substance use disorders, to simulate the influence of treatment of one condition on improvement on others. We used this augmented simulation to estimate LE for BSMM/BTW with HIV with a history of incarceration under alternative policies of decarceration (ie, reducing the fraction exposed to incarceration), screening for psychiatric conditions and substance use, or both. RESULTS: Baseline LE was 61.3 years. Reducing incarceration by 25%, 33%, 50%, and 100% increased LE by 0.29, 0.31, 0.53, and 1.08 years, respectively, versus no reductions in incarceration. When reducing incarceration by 33% and implementing screening for alcohol, tobacco, substance use, and depression, in which a positive screen triggers diagnostic assessment for all psychiatric and substance use conditions and linkage to treatment, LE increased by 1.52 years compared with no screening or decarceration. DISCUSSION: LE among BSMM/BTW with HIV is short compared with other people with HIV. Reducing incarceration and improving screening and treatment of psychiatric conditions and substance use could substantially increase LE in this population.

Geospatial patterns of progress towards UNAIDS '95-95-95' targets and community vulnerability in Zambia: insights from population-based HIV impact assessments.

INTRODUCTION: In sub-Saharan Africa, HIV/AIDS remains a leading cause of death. The UNAIDS established the '95-95-95' targets to improve HIV care continuum outcomes. Using geospatial data from the Zambia Population-based HIV Impact Assessment (ZAMPHIA), this study aims to investigate geospatial patterns in the '95-95-95' indicators and individual-level determinants that impede HIV care continuum in vulnerable communities, providing insights into the factors associated with gaps. METHODS: This study used data from the 2016 ZAMPHIA to investigate the geospatial distribution and individual-level determinants of engagement across the HIV care continuum in Zambia. Gaussian kernel interpolation and optimised hotspot analysis were used to identify geospatial patterns in the HIV care continuum, while geospatial k-means clustering was used to partition areas into clusters. The study also assessed healthcare availability, access and social determinants of healthcare utilisation. Multiple logistic regression models were used to examine the association between selected sociodemographic and behavioural covariates and the three main outcomes of study. RESULTS: Varied progress towards the '95-95-95' targets were observed in different regions of Zambia. Each '95' displayed a unique geographical pattern, independent of HIV prevalence, resulting in four distinct geographical clusters. Factors associated with gaps in the '95s' include younger age, male sex, and low wealth, with younger individuals having higher odds of not being on antiretroviral therapy and having detectable viral loads. CONCLUSIONS: Our study revealed significant spatial heterogeneity in the HIV care continuum in Zambia, with different regions exhibiting unique geographical patterns and levels of performance in the '95-95-95' targets, highlighting the need for geospatial tailored interventions to address the specific needs of different subnational regions. These findings underscore the importance of addressing differential regional gaps in HIV diagnosis, enhancing community-level factors and developing innovative strategies to improve local HIV care continuum outcomes.

A quantitative assessment of the consistency of projections from five mathematical models of the HIV epidemic in South Africa: a model comparison study.

BACKGROUND: Mathematical models are increasingly used to inform HIV policy and planning. Comparing estimates obtained using different mathematical models can test the robustness of estimates and highlight research gaps. As part of a larger project aiming to determine the optimal allocation of funding for HIV services, in this study we compare projections from five mathematical models of the HIV epidemic in South Africa: EMOD-HIV, Goals, HIV-Synthesis, Optima, and Thembisa. METHODS: The five modelling groups produced estimates of the total population, HIV incidence, HIV prevalence, proportion of people living with HIV who are diagnosed, ART coverage, proportion of those on ART who are virally suppressed, AIDS-related deaths, total deaths, and the proportion of adult males who are circumcised. Estimates were made under a "status quo" scenario for the period 1990 to 2040. For each output variable we assessed the consistency of model estimates by calculating the coefficient of variation and examining the trend over time. RESULTS: For most outputs there was significant inter-model variability between 1990 and 2005, when limited data was available for calibration, good consistency from 2005 to 2025, and increasing variability towards the end of the projection period. Estimates of HIV incidence, deaths in people living with HIV, and total deaths displayed the largest long-term variability, with standard deviations between 35 and 65% of the cross-model means. Despite this variability, all models predicted a gradual decline in HIV incidence in the long-term. Projections related to the UNAIDS 95-95-95 targets were more consistent, with the coefficients of variation below 0.1 for all groups except children. CONCLUSIONS: While models produced consistent estimates for several outputs, there are areas of variability that should be investigated. This is important if projections are to be used in subsequent cost-effectiveness studies.

Progress Towards UNAIDS's 95-95-95 Targets in Zimbabwe: Sociodemographic Constraints and Geospatial Heterogeneity.

The HIV/AIDS epidemic remains critical in sub-Saharan Africa, with UNAIDS establishing "95-95-95" targets to optimize HIV care. Using the Zimbabwe Population-based HIV Impact Assessment (ZIMPHIA) geospatial data, this study aimed to identify patterns in these targets and determinants impacting the HIV care continuum in underserved Zimbabwean communities. Analysis techniques, including Gaussian kernel interpolation, optimized hotspot, and multivariate geospatial k-means clustering, were utilized to establish spatial patterns and cluster regional HIV care continuum needs. Further, we investigated healthcare availability, access, and social determinants and scrutinized the association between socio-demographic and behavioral covariates with HIV care outcomes. Disparities in progress toward the "95-95-95" targets were noted across different regions, with each target demonstrating unique geographic patterns, resulting in four distinct clusters with specific HIV care needs. Key factors associated with gaps in achieving targets included younger age, male sex, employment, and minority or no religious affiliation. Our study uncovers significant spatial heterogeneity in the HIV care continuum in Zimbabwe, with unique regional patterns in "95-95-95" targets. The spatial analysis of the UNAIDS targets presented here could prove instrumental in designing effective control strategies by identifying vulnerable communities that are falling short of these targets and require intensified efforts. Our result provides insights for designing region-specific interventions and enhancing community-level factors, emphasizing the need to address regional gaps and improve HIV care outcomes in vulnerable communities lagging behind.

Optimizing the pipeline of multipurpose prevention technologies: opportunities across women's reproductive lifespans.

HIV/AIDS and maternal mortality are the two leading causes of death among women of reproductive age in sub-Saharan Africa. A growing body of research investigates opportunities for multipurpose prevention technologies (MPTs) that prevent unintended pregnancy, HIV, and/or other sexually transmitted infections (STIs) with a single product. More than two dozen MPTs are currently in development, most of them combining contraception with HIV pre-exposure prophylaxis, with or without protection from other STIs. If successful, such MPTs could offer women benefits at multiple levels: greater motivation for effective use; lower product administration burden; accelerated integration of HIV, STI, and reproductive health services; and opportunities to circumvent stigma by using contraception as a "fig leaf" for HIV and/or STI prevention. However, even if women find respite from product burden, lack of motivation, and/or stigma in contraceptive-containing MPTs, their use of MPTs will be interrupted, often multiple times, over the reproductive lifecourse due to desire for pregnancy, pregnancy and breastfeeding, menopause, and changes in risk. Interruptions to the benefits of MPTs could be avoided by combining HIV/STI prevention with other life-stage-appropriate reproductive health products. New product concepts could include combining prenatal supplements with HIV and STI prevention, emergency contraception with HIV post-exposure prophylaxis, or hormone replacement therapies for menopause with HIV and STI prevention. Research is needed to optimize the MPT pipeline based on the populations underserved by available options and the capacity of resource-constrained health systems to deliver novel preventative healthcare products.

Cost-effectiveness of the dual prevention pill for contraception and HIV pre-exposure prophylaxis.

Introduction: Women in sub-Saharan Africa (SSA) experience the world's highest rates of both HIV infection and unintended pregnancy. The Dual Prevention Pill (DPP) is a novel multipurpose prevention technology (MPT) that co-formulates HIV pre-exposure prophylaxis (PrEP) and combined hormonal oral contraception into a single daily pill. As a dual indication product, the DPP may be preferred by women facing these overlapping health risks. However, most SSA countries face severe healthcare resource constraints. Research is needed to assess whether, in what populations, and in what use cases the DPP would be cost-effective. Methods: We augmented an agent-based SSA HIV model with maternal health parameters including unintended pregnancy, abortion, and maternal mortality. Based on a previous market analysis, we assumed a primary DPP user population of current oral contraceptive users ages 25-49, and alternative user populations in different risk groups (age 15-24, sex workers, HIV-serodiscordant couples) and baseline product use profiles (unmet need for contraception, oral PrEP use, condom use). In three geographies (western Kenya, Zimbabwe, South Africa), we estimated HIV infections averted, pregnancies averted, disability-adjusted life-years (DALYs) averted, and the incremental cost-effectiveness ratio (ICER) over a 30-year time horizon, assuming equivalent adherence to the DPP as to oral contraceptives, higher adherence, or lower adherence. Results: The DPP is likely to be a cost-effective alternative to oral PrEP among users in need of contraception. Among women not already using PrEP, the DPP is likely to be cost-saving in sex workers and serodiscordant couples. The DPP is unlikely to be cost-effective in oral contraceptive users in the general population. Switching from oral contraception to the DPP could be net harmful in some settings and populations if it were to substantially reduces adherence to oral contraception. Results were robust to a range of time horizons or discount rates. Conclusion: The DPP has the potential to be cost-effective and cost-saving in populations at substantial HIV risk. Outcomes are sensitive to adherence, implying that effective counseling and decision-making tools for users considering the DPP will be essential. More research is needed to understand real-life adherence patterns and ensure health benefits achieved from contraception alone are not lost.

Geospatial Patterns of Progress towards UNAIDS "95-95-95" Targets and Community Vulnerability in Zambia.

In sub-Saharan Africa, HIV/AIDS remains a leading cause of death. The UNAIDS established the "95-95-95" targets to improve HIV care continuum outcomes. Using geospatial data from the Zambia Population-based HIV Impact Assessment (ZAMPHIA), this study aims to investigate geospatial patterns in the "95-95-95" indicators and individual-level determinants that impede HIV care continuum in vulnerable communities, providing insights into the factors associated with gaps. This study used data from the 2016 ZAMPHIA to investigate the geospatial distribution and individual-level determinants of engagement across the HIV care continuum in Zambia. Gaussian kernel interpolation and optimized hotspot analysis were used to identify geospatial patterns in the HIV care continuum, while geospatial k-means clustering was used to partition areas into clusters. The study also assessed healthcare availability, access, and social determinants of healthcare utilization. Multiple logistic regression models were used to examine the association between selected sociodemographic and behavioral covariates and the three main outcomes of study. Varied progress towards the "95-95-95" targets were observed in different regions of Zambia. Each "95" displayed a unique geographic pattern, independent of HIV prevalence, resulting in four distinct geographic clusters. Factors associated with gaps in the "95s" include younger age, male sex, and low wealth, with younger individuals having higher odds of not being on ART and having detectable viral loads. Our study revealed significant spatial heterogeneity in the HIV care continuum in Zambia, with different regions exhibiting unique geographic patterns and levels of performance in the "95-95-95" targets, highlighting the need for geospatial tailored interventions to address the specific needs of different subnational regions. These findings underscore the importance of addressing differential regional gaps in HIV diagnosis, enhancing community-level factors, and developing innovative strategies to improve local HIV care continuum outcomes.

A linked physiologically based pharmacokinetic model for hydroxychloroquine and metabolite desethylhydroxychloroquine in SARS-CoV-2(-)/(+) populations.

Hydroxychloroquine (HCQ) is Food and Drug Administration (FDA)-approved for malaria, systemic and chronic discoid lupus erythematosus, and rheumatoid arthritis. Because HCQ has a proposed multimodal mechanism of action and a well-established safety profile, it is often investigated as a repurposed therapeutic for a range of indications. There is a large degree of uncertainty in HCQ pharmacokinetic (PK) parameters which complicates dose selection when investigating its use in new disease states. Complications with HCQ dose selection emerged as multiple clinical trials investigated HCQ as a potential therapeutic in the early stages of the COVID-19 pandemic. In addition to uncertainty in baseline HCQ PK parameters, it was not clear if disease-related consequences of SARS-CoV-2 infection/COVID-19 would be expected to impact the PK of HCQ and its primary metabolite desethylhydroxychloroquine (DHCQ). To address the question whether SARS-CoV-2 infection/COVID-19 impacted HCQ and DHCQ PK, dried blood spot samples were collected from SARS-CoV-2(-)/(+) participants administered HCQ. When a previously published physiologically based pharmacokinetic (PBPK) model was used to fit the data, the variability in exposure of HCQ and DHCQ was not adequately captured and DHCQ concentrations were overestimated. Improvements to the previous PBPK model were made by incorporating the known range of blood to plasma concentration ratios (B/P) for each compound, adjusting HCQ and DHCQ distribution settings, and optimizing DHCQ clearance. The final PBPK model adequately captured the HCQ and DHCQ concentrations observed in SARS-CoV-2(-)/(+)participants, and incorporating COVID-19-associated changes in cytochrome P450 activity did not further improve model performance for the SARS-CoV-2(+) population.

Potential health benefits of integrated screening strategies for alcohol, tobacco, other substance use, depression, anxiety, and chronic pain among people living with HIV in the USA: a mathematical modelling study.

BACKGROUND: Alcohol use, tobacco use, and other substance use often co-occur with depression, anxiety, and chronic pain, forming a constellation of alcohol, substance, and mood-related (CASM) conditions that disproportionately affects people with HIV in the USA. We used a microsimulation model to evaluate how alternative screening strategies accounting for CASM interdependence could affect life expectancy in people with HIV in the USA. METHODS: We augmented a microsimulation model previously validated to predict US adult life expectancy, including in people with HIV. Using data from the Veterans Aging Cohort Study, we incorporated CASM co-occurrence, inferred causal relationships between CASM conditions, and assessed the effects of CASM on HIV treatment and preventive care. We simulated an in-care HIV cohort exposed to alternative CASM screening and diagnostic assessment strategies, ranging from currently recommended screenings (alcohol, tobacco, and depression, with diagnostic assessments for conditions screening positive) to a series of integrated strategies (screening for alcohol, tobacco, or depression with additional diagnostic assessments if any screened positive) to a maximal saturation strategy (diagnostic assessments for all CASM conditions). FINDINGS: The saturation strategy increased life expectancy by 0·95 years (95% CI 0·93-0·98) compared with no screening. Recommended screenings provided much less benefit: 0·06 years (0·03-0·09) gained from alcohol screening, 0·08 years (0·06-0·11) from tobacco screening, 0·10 years (0·08-0·11) from depression screening, and 0·25 years (0·22-0·27) from all three screenings together. One integrated strategy (screening alcohol, tobacco, and depression with diagnostic assessment for all CASM conditions if any screened positive) produced near-maximal benefit (0·82 years [0·80-0·84]) without adding substantial screening burden, albeit requiring additional diagnostic assessments. INTERPRETATION: Primary care providers for people with HIV should consider comprehensive diagnostic assessment of CASM conditions if one or more conditions screen positive. FUNDING: US National Institute on Alcohol Abuse and Alcoholism.