BACKGROUND: Despite the growing adoption of the Family Mid-Upper Arm Circumference (MUAC) approach to empower caregivers in detecting child malnutrition, limited evidence exists on whether caregivers act on identified cases by seeking care and factors influencing their decisions. Most research has focused on the accuracy of caregiver MUAC measurements, leaving a gap in understanding behavioral, social, emotional, and contextual barriers to care-seeking. Addressing this gap is critical for informing interventions to ensure early detection translates into timely treatment. This study aimed to explore the barriers and facilitators influencing care-seeking practices within a Family MUAC program in South Sudan. METHODS: We conducted a mixed-methods, prospective, non-randomized study in Central Equatoria and Warrap States, South Sudan, between March 2022 and January 2023. We enrolled 2,893 children aged 5-53 months and trained their caregivers on using MUAC tapes. Caregivers were followed for 8 months, including three monitoring visits and baseline/endline surveys, capturing self-reported care-seeking practices. Qualitative data were obtained through 20 focus group discussions (FGDs) with caregivers, using the Health Belief Model as a theoretical framework to explore perceptions, barriers, and enablers of care-seeking. A combined deductive and inductive coding approach was used for thematic analysis. RESULTS: Among children identified with wasting using MUAC tapes, 86.5% of caregivers sought care, with significantly higher rates in Warrap (97.6%) than Central Equatoria (79.4%) (p < 0.008). Barriers to care-seeking included distance to health facilities (18.9%), transportation costs (11.3%), and treatment costs (9.4%). Qualitative findings revealed additional challenges such as social stigma, lack of knowledge about where to seek care, and negative experiences with health workers. Despite some caregivers reporting a lack of encouragement, most valued the MUAC tapes, used them weekly, and were confident in their ability to take accurate measurements. CONCLUSIONS: Policies and programmatic interventions should consider integrating Family MUAC programs with community-based financial initiatives like savings groups to address financial barriers. Tailoring interventions to rural and urban contexts through formative research can enhance program effectiveness, while training health workers in compassionate care may improve caregiver trust and increase care-seeking rates. Strengthening these areas can maximize the impact of Family MUAC and improve child health outcomes. TRIAL REGISTRATION: N/A.

Preexposure prophylaxis (PrEP) is highly effective in preventing HIV infections and is recommended for people without HIV who are at ongoing risk of HIV acquisition. In 2019, the U.S. launched the "Ending the HIV Epidemic in the U.S." initiative, which aims to reduce by 90 % the number of annual new HIV infections. To monitor progress towards this goal, several national indicators have been established, one of which is PrEP coverage. Several ways to monitor PrEP use have been developed, each with its own advantages and disadvantages. We developed a method to estimate PrEP "need" in the U.S. that could be used as a denominator to estimate PrEP coverage. The "population need for PrEP" (PPN) is estimated based on the number of people needed to treat (NNT) with PrEP to prevent an additional HIV infection in subpopulations whose annual HIV incidence is ≥ 1 %. This is done in three steps: 1) calculating NNT for each transmission group using 1 % incidence threshold and clinical trial-and cohort-generated evidence of the degree of PrEP effectiveness in each transmission group, 2) estimating the proportion of new HIV infections in subpopulations with incidence at least 1 % from epidemiologic data, 3) multiplying estimates from steps 1 and 2 with the number of new HIV infections for each transmission group from Surveillance. The estimates for each transmission group are then added together, and the number of current PrEP users is finally added to this estimate to produce PPN. This method is relatively easy to calculate and can provide public health authorities at the national, state, or local level with pragmatic estimates of PrEP "need" among different demographic or transmission groups, which can help with planning, resource allocation, and monitoring progress.

OBJECTIVES: To determine the impact of increased long-acting injectable antiretroviral therapy (Cabotegravir-rilpivirine [CAB/RPV]) use among persons with diagnosed HIV (PWDH) with viral suppression (VLS), per 2021 US Food and Drug Administration (FDA) guidelines, on HIV incidence and levels of VLS in the US. METHODS: We used the HOPE compartmental model to simulate CAB/RPV use during 2023-2035. We first simulated a baseline scenario (no CAB/RPV), in which 69% of PWDH had VLS. We then introduced CAB/RPV in 2023 under two scenarios: (1) where CAB/RPV improved the duration of VLS post-cessation of ART use compared to oral ART; (2) where CAB/RPV additionally improved adherence. We compared cumulative 2023-35 incidence and percentage of PWDH with VLS at year-end 2035 to baseline. RESULTS: When CAB/RPV increased the duration of VLS only, cumulative incidence was reduced up to 9%, and VLS increased up to 4%. When CAB/RPV also improved ART adherence, incidence was reduced up to 19.5%, and VLS increased up to 9%. CONCLUSIONS: CAB/RPV, even if only used among PWDH with VLS, may reduce HIV incidence and increase VLS, due to longer-lasting VLS post-cessation of usage. If CAB/RPV also improves ART adherence, incidence is further reduced. Improved clinical efficacy of CAB/RPV may translate to improved population-level outcomes, even in limited use cases.

BACKGROUND: In 2019, there were an estimated 1.2 million persons with HIV (PWH) and 35,100 new infections in the United States. The HIV care continuum has a large influence on transmission dynamics. METHODS: We updated Progression and Transmission of HIV 3.0, an agent-based simulation model, to estimate 2019 HIV transmission rates and distribution of transmissions by the HIV care continuum, race/ethnicity, transmission group, and age group. RESULTS: In 2019, the estimated transmission rate in the United States was 2.94 new infections per 100 person-years (inf /100p-y). Transmission rates decreased along the HIV care continuum; the highest transmission rate was associated with persons with acute HIV infection and unaware of their HIV status at 16.35 inf /100p-y, followed by persons with HIV (non-acute) and unaware of their HIV status (9.52), persons aware of their HIV status and not in care (5.96), persons receiving HIV care (on antiretroviral therapy) but not virally suppressed (4.53), and persons virally suppressed (0). The highest transmission rate by transmission group was among men who have sex with men at 3.68 inf /100p-y. Transmission rates decreased as age increased and are similar by race/ethnicity, after accounting for the HIV care continuum. CONCLUSION: Our results support a continued emphasis on helping PWH move along the care continuum through early diagnosis, linkage to care, and adherence to ART, resulting in viral suppression to reduce HIV transmissions. Further, efforts should focus on reducing disparities in the provision of HIV prevention and care services, particularly for populations disproportionally affected by HIV.

BACKGROUND: The OraQuick In-Home HIV self-test represents a fast, inexpensive, and convenient method for users to assess their HIV status. If integrated thoughtfully into existing testing practices, accompanied by efficient pathways to formal diagnosis, self-testing could enhance both HIV awareness and reduce HIV incidence. However, currently available self-tests are less sensitive, particularly for recent infection, when compared to gold-standard laboratory tests. It is important to understand the impact if some portion of standard testing is replaced by self-tests. We used a compartmental model to evaluate the effects of self-testing in diverse scenarios among gay, bisexual and other men who have sex with men (MSM) in the United States for the period 2020-2030, and to understand which scenarios maximize the advantages of self-testing. METHODS: We introduced a novel 4-compartment model for HIV self-testing. We employed the model under different screening rates, self-test proportions, and delays to diagnosis for those identified through self-tests to determine the potential effects of self-testing on HIV incidence and awareness of status when applied to the US MSM population. We studied scenarios in which self-tests supplement laboratory-based tests, with no replacement, and scenarios in which some replacement occurs. We also examined how future improvements in self-test sensitivity may affect our results. RESULTS: When HIV self-tests are supplemental rather than substitutes for laboratory-based testing, self-testing can decrease HIV incidence among MSM in the US by up to 10 % and increase awareness of status among MSM from 85 % to 91 % over a 10-year period, provided linkage to care and formal diagnosis occur promptly following a positive self-test (90 days or less). As self-tests replace a higher percentage laboratory-based testing algorithms, increases in overall testing rates were necessary to ensure reductions in HIV incidence. However, such needed increases were relatively small (under 10 % for prompt engagement in care and moderate levels of replacement). Improvements in self-test sensitivity and/or decreases in the detection period may further reduce any necessary increases in overall testing by up to 40 %. CONCLUSIONS: If properly utilized, self-testing can provide significant long-term reductions to HIV incidence and improve awareness of HIV status. Ensuring that self-testing increases overall testing and that formal diagnosis and engagement in care occur promptly following a positive self-test are necessary to maximize the benefits of self-testing. Future improvements in self-test sensitivity and reductions in the detection period would further reduce HIV incidence and the potential risks associated with replacing laboratory tests with self-tests.

INTRODUCTION: Nutrition program modifications occurred globally in response to the COVID-19 pandemic. Within community management of acute malnutrition (CMAM), community screenings for acute malnutrition were replaced by caregivers monitoring child mid-upper arm circumference (MUAC), but questions remain about different MUAC tapes' performance and acceptability for caregiver use. METHODS: The study was conducted in Central Equatoria and Warrap States, South Sudan, between March 2022 and January 2023. A three-group prospective non-randomized design was used to compare the performance of three MUAC tapes (UNICEF 2009, UNICEF 2020, and GOAL MAMI) used by caregivers. The primary outcome was the false negative rate (i.e., the proportion of children not identified as wasted by the caregiver but classified as wasted by enumerators). Caregivers with children aged 5-53 months were assigned to and trained on the use of 1 of the 3 tapes and followed for 8 months, including three monitoring visits and baseline/endline surveys. RESULTS: Of the 2,893 enrolled children, 2,401 (83.0%) completed baseline, endline, and two or more monitoring visits. Only 3.7% of children were identified as wasted by caregivers and 3.8% by study team measurement. Cumulative measurement agreement between caregivers and enumerators was similar by tape. False negative and false positive rates were both <0.5% overall and similar among the tapes. There were differences in training needs and durability between the tapes, but all three were acceptable and performed equally well. DISCUSSION: Caregiver measurement of child MUAC is feasible in South Sudan. The three MUAC tapes were acceptable, and caregivers could measure accurately with minimal support. All tapes performed similarly and are appropriate for use in Family MUAC programs in South Sudan. There were indications that the UNICEF 2020 tape may be less durable; the GOAL MAMI tape has the added benefit of being suitable for assessments of infants <6 months of age.

BACKGROUND: The COVID-19 pandemic impacted sexual behaviors and the HIV continuum-of-care in the United States, reducing HIV testing and diagnosis, and use of pre-exposure prophylaxis (PrEP) and antiretroviral therapy (ART). We aim to understand the future implications of these effects through a modeling study. METHODS: We first ran our compartmental model of HIV transmission in the US accounting for pandemic-related short-term changes in transmission behavior and HIV prevention and care provision in 2020-2021 only. We then ran a comparison scenario that did not apply pandemic effects but assumed a continuation of past HIV prevention and care trends. We compared results from the two scenarios through 2024. RESULTS: HIV incidence was 4·4% lower in 2020-21 for the pandemic scenario compared with the no-pandemic scenario due to reduced levels of transmission behavior, despite reductions in HIV prevention and care caused by the pandemic. However, reduced care led to less viral load suppression among people with HIV (PWH) in 2020 and, in turn, our model resulted in a slightly greater incidence of 2·0% from 2022-24 in the COVID-19 scenario, as compared to the non-COVID scenario. DISCUSSION: Disruptions in HIV prevention and care services during COVID-19 may lead to somewhat higher post-pandemic HIV incidence, than assuming pre-pandemic trends in HIV care and prevention continued. These results underscore the importance of continuing to increase HIV prevention and care efforts in the coming years.

BACKGROUND: As part of COVID-19 mitigation strategies, emergency nutrition program adaptations were implemented, but evidence of the effects is limited. Compared to the standard protocol, the full adapted protocol included adapted admissions criteria, simplified dosing, and reduced visit frequency; partially adapted protocols consisting of only some of these modifications were also implemented. To enable evidence-based nutrition program modifications as the context evolved, this study was conducted to characterize how protocol adaptations in South Sudan affected Outpatient Therapeutic Feeding Program outcomes. METHODS: A mixed methods approach consisting of secondary analysis of individual-level nutrition program data and key informant interviews was used. Analyses focused on program implementation and severe acute malnutrition treatment outcomes under the standard, full COVID-19 adapted, and partially adapted treatment protocols from 2019 through 2021. Analyses compared characteristics and outcomes by different admission types under the standard protocol and across four different treatment protocols. Regression models evaluated the odds of recovery and mean length of stay (LoS) under the four protocols. RESULTS: Very few (1.6%; n = 156) children admitted based on low weight-for-height alone under the standard protocol would not have been eligible for admission under the adapted protocol. Compared to the full standard protocol, the partially adapted (admission only) and partially adapted (admission and dosing) protocols had lower LoS of 28.4 days (CI - 30.2, - 26.5) and 5.1 days (CI - 6.2, - 4.0); the full adapted protocol had a decrease of 3.0 (CI - 5.1, - 1.0) days. All adapted protocols had significantly increased adjusted odds ratios (AOR) for recovery compared to the full standard protocol: partially adapted (admission only) AOR = 2.56 (CI 2.18-3.01); partially adapted (admission + dosing) AOR = 1.78 (CI 1.45-2.19); and fully adapted protocol AOR = 2.41 (CI 1.69-3.45). CONCLUSIONS: This study provides evidence that few children were excluded when weight-for-height criteria were suspended. LoS was shortest when only MUAC was used for entry/exit but dosing and visit frequency were unchanged. Significantly shorter LoS with simplified dosing and visit frequency vs. under the standard protocol indicate that protocol adaptations may lead to shorter recovery and program enrollment times. Findings also suggest that good recovery is achievable with reduced visit frequency and simplified dosing.

OBJECTIVE: :COVID-19 and related disruptions led to a significant decline in HIV diagnoses in the US in 2020. A previous analysis estimated 18% fewer diagnoses than expected among persons with HIV (PWH) acquiring infection in 2019 or earlier, suggesting that the decline in overall diagnoses cannot be attributed solely to decreased transmission. This analysis evaluates the progress made towards closing the 2020 diagnosis deficit in 2021. METHODS: :We apply previously developed methods analyzing 2021 diagnosis data from the National HIV Surveillance System to determine whether 2021 diagnosis levels of PWH infected pre2020 are above or below the expected pre-COVID trends. Results are stratified by assigned sex at birth, transmission group, geographic region, and race/ethnicity. RESULTS: :In 2021, HIV diagnoses returned to pre-COVID levels among all PWH acquiring infection 2011-19. Among Hispanic/Latino PWH and males, diagnoses returned to pre-COVID levels. White PWH, men who have sex with men, and PWH living in the south and northeast showed higher-than-expected levels of diagnosis in 2021. For the remaining populations, there were fewer HIV diagnoses in 2021 than expected. CONCLUSIONS: :While overall diagnoses among persons acquiring HIV pre2020 returned to pre-COVID levels, the diagnosis gap observed in 2020 remained unclosed at the end of 2021. Fewer than expected diagnoses among certain populations indicate that COVID-19 related disruptions to HIV diagnosis trends remained in 2021. Although some groups showed higher-than-expected levels of diagnoses, such increases were smaller than corresponding 2020 decreases. Expanded testing programs designed to close these gaps are essential.

BACKGROUND: Whether the COVID-19 pandemic has had a disproportionate impact on mortality among persons with diagnosed HIV (PWDH) in United States is unclear. Through our macro-scale analysis, we seek to better understand how the COVID-19 pandemic affected mortality among PWDH. METHODS: We obtained mortality and population data for the years 2018-2020 from the National HIV Surveillance System (NHSS) for the U.S. PWDH population, and from publicly available data for the general population. We computed mortality rates and excess mortality for both the general and PWDH populations. Stratifications by age, race/ethnicity, and sex were considered. For each group, we determined whether the 2020 mortality rates and mortality risk ratio showed a statistically significant change from 2018-2019. RESULTS: Approximately 1550 excess deaths occurred among PWDH in 2020, with Black, Hispanic/Latino and PWDH 55 and older comprising the majority of excess deaths. Mortality rates increased in 2020 from 2018-2019 across the general population in all groups. Among PWDH, mortality rates either increased, or showed no statistically significant change. These increases were similar to, or smaller than, those observed in the general population, resulting in a 7.7% decrease in the mortality risk ratio between PWDH and the general population. CONCLUSIONS: While mortality rates among PWDH increased in 2020 relative to 2018-2019, the increases were smaller, or of similar magnitude, to those observed in the general population. We thus do not find evidence of elevated mortality risk from the COVID-19 pandemic among PWDH. These findings held across subpopulations stratified by age, sex, and racial/ethnic group.

OBJECTIVE: To estimate prevalent ALS cases in the United States for calendar year 2018. METHODS: The National ALS Registry (Registry) compiled data from national administrative databases (from the Centers for Medicare and Medicaid Services, the Veterans Health Administration, and the Veterans Benefits Administration) and enrollment data voluntarily submitted through a web portal (www.cdc.gov/als). We used log-linear capture-recapture (CRC) model-based methodology to estimate the number of cases not ascertained by the Registry. RESULTS: The Registry identified 21,655 cases of ALS in 2018, with an age-adjusted prevalence of 6.6 per 100,000 U.S. population. When CRC methods were used, an estimated 29,824 cases were identified, for an adjusted prevalence of 9.1 per 100,000 U.S. population. The demographics of cases of ALS did not change from previous year's reports. ALS continues to impact Whites, males, and persons over 50 years of age more so than other comparison groups. The results from the present report suggest case ascertainment for the Registry has improved, with the estimate of missing prevalent cases decreasing from 44% in 2017 to 27% in in 2018. DISCUSSION: Consistent with previous estimates that used CRC, ALS prevalence in the United States is about 29,824 cases per year.

Background: Whether COVID-19 has had a disproportionate impact on mortality among persons with diagnosed HIV (PWDH) in United States is unclear. Through our macro-scale analysis, we seek to better understand how COVID-19 and subsequent behavioral changes affected mortality among PWDH. Method(s): We obtained mortality and population size data for the years 2018-2020 from the National HIV Surveillance System (NHSS) for the PWDH population aged >=13 years in the United States, and from publicly available data for the general population. We computed mortality rates and excess mortality for both the general and PWDH populations. Stratifications by age, race/ethnicity, and sex-at birth were considered. For each group, we determined whether the 2020 mortality rates and mortality risk ratio showed a statistically significant change from 2018-2019. Result(s): Mortality rates increased in 2020 from 2018-2019 across the general population in all groups. Among PWDH, mortality rates either increased, or showed no statistically significant change. The mortality risk ratio between PWDH and the general population decreased 7.7% in 2020. Approximately 1550 excess deaths occurred among PWDH in 2020, with Black, Hispanic/Latino and PWDH above 55 and older representing the majority of excess deaths. Conclusion(s): While mortality rates among PWDH increased in 2020 relative to 2018-2019, the increases were smaller than those observed in the general population. This suggests that COVID-19 and resulting behavioral changes among PWDH did not result in disproportionate mortality among PWDH. These findings suggest that COVID-19, and any associated indirect effects, do not represent a proportionally greater risk for PWDH compared to the general population. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

Background HIV partner services can accelerate the use of antiretroviral-based HIV prevention tools (ART and PrEP), but its population impact on long-term HIV incidence reduction is challenging to quantify with traditional PS metrics of partner identified or HIV-screened. Understanding the role of partner services within the portfolio of HIV prevention interventions, including using it to efficiently deliver antiretrovirals, is needed to achieve HIV prevention targets. Methods We used a stochastic network model of HIV/STI transmission for men who have sex with men (MSM), calibrated to surveillance-based estimates in the Atlanta area, a jurisdiction with high HIV burden and suboptimal partner services uptake. Model scenarios varied successful delivery of partner services cascade steps (newly diagnosed "index" patient and partner identification, partner HIV screening, and linkage or reengagement of partners in PrEP or ART care) individually and jointly. Results At current levels observed in Atlanta, removal of HIV partner services had minimal impact on 10-year cumulative HIV incidence, as did improving a single partner services step while holding the others constant. These changes did not sufficiently impact overall PrEP or ART coverage to reduce HIV transmission. If all index patients and partners were identified, maximizing partner HIV screening, partner PrEP provision, partner ART linkage, and partner ART reengagement would avert 6%, 11%, 5%, and 18% of infections, respectively. Realistic improvements in partner identification and service delivery were estimated to avert 2-8% of infections, depending on the combination of improvements. Conclusions Achieving optimal HIV prevention with partner services depends on pairing improvements in index patient and partner identification with maximal delivery of HIV screening, ART, and PrEP to partners if indicated. Improving the identification steps without improvement to antiretroviral service delivery steps, or vice versa, is projected to result in negligible population HIV prevention benefit. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

Capture-recapture methods are widely applied in estimating the number (N) of prevalent or cumulatively incident cases in disease surveillance. Here, we focus the bulk of our attention on the common case in which there are two data streams. We propose a sensitivity and uncertainty analysis framework grounded in multinomial distribution-based maximum likelihood, hinging on a key dependence parameter that is typically non-identifiable but is epidemiologically interpretable. Focusing on the epidemiologically meaningful parameter unlocks appealing data visualizations for sensitivity analysis and provides an intuitively accessible framework for uncertainty analysis designed to leverage the practicing epidemiologist's understanding of the implementation of the surveillance streams as the basis for assumptions driving estimation of N. By illustrating the proposed sensitivity analysis using publicly available HIV surveillance data, we emphasize both the need to admit the lack of information in the observed data and the appeal of incorporating expert opinion about the key dependence parameter. The proposed uncertainty analysis is an empirical Bayes-like approach designed to more realistically acknowledge variability in the estimated N associated with uncertainty in an expert's opinion about the non-identifiable parameter, together with the statistical uncertainty. We demonstrate how such an approach can also facilitate an appealing general interval estimation procedure to accompany capture-recapture methods. Simulation studies illustrate the reliable performance of the proposed approach for quantifying uncertainties in estimating N in various contexts. Finally, we demonstrate how the recommended paradigm has the potential to be directly extended for application to data from more than two surveillance streams. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.

Background: Diagnoses of HIV in the US decreased by 17% in 2020 due to COVID-related disruptions. The extent to which this decrease is attributable to changes in HIV testing versus HIV transmission is unclear. We seek to better understand this issue by analyzing the discrepancy in expected versus observed HIV diagnoses in 2020 among persons who acquired HIV between 2010-2019, as changes in diagnosis patterns in this cohort cannot be attributed to changes in transmission. Method(s): We developed three methods based on the CD4-depletion model to estimate excess missed diagnoses in 2020 among persons with HIV (PWH) infected from 2010-2019. We stratified the results by transmission group, sex assigned at birth, race/ethnicity, and region to examine differences by group and confirm the reliability of our estimates. We performed similar analyses projecting diagnoses in 2019 among PWH infected from 2010-2018 to evaluate the accuracy of our methods against surveillance data. Result(s): There were approximately 3100-3300 (approximately 18%) fewer diagnoses than expected in 2020 among PWH infected from 2010-2019. Females (at birth), heterosexuals, persons who inject drugs, and Hispanic/Latino PWH missed diagnoses at higher levels than the overall population. Validation and stratification analyses confirmed the accuracy and reliability of our estimates. Conclusion(s): The substantial drop in number of previously infected PWH diagnosed in 2020, suggests that changes in testing played a substantial role in the observed decrease. Levels of missed diagnoses differed substantially across population subgroups. Increasing testing efforts and innovative strategies to reach undiagnosed PWH are needed to offset this diagnosis gap. These analyses may be used to inform future estimates of HIV transmission during the COVID-19 pandemic. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

Capture-recapture methods are widely applied in estimating the number (N) of prevalent or cumulatively incident cases in disease surveillance. Here, we focus the bulk of our attention on the common case in which there are two data streams. We propose a sensitivity and uncertainty analysis framework grounded in multinomial distribution-based maximum likelihood, hinging on a key dependence parameter that is typically non-identifiable but is epidemiologically interpretable. Focusing on the epidemiologically meaningful parameter unlocks appealing data visualizations for sensitivity analysis and provides an intuitively accessible framework for uncertainty analysis designed to leverage the practicing epidemiologist's understanding of the implementation of the surveillance streams as the basis for assumptions driving estimation of N. By illustrating the proposed sensitivity analysis using publicly available HIV surveillance data, we emphasize both the need to admit the lack of information in the observed data and the appeal of incorporating expert opinion about the key dependence parameter. The proposed uncertainty analysis is a simulation-based approach designed to more realistically acknowledge variability in the estimated N associated with uncertainty in an expert's opinion about the non-identifiable parameter, together with the statistical uncertainty. We demonstrate how such an approach can also facilitate an appealing general interval estimation procedure to accompany capture-recapture methods. Simulation studies illustrate the reliable performance of the proposed approach for quantifying uncertainties in estimating N in various contexts. Finally, we demonstrate how the recommended paradigm has the potential to be directly extended for application to data from more than two surveillance streams.

We propose a censored quantile regression model for the analysis of relative survival data. We create a hybrid data set consisting of the study observations and counterpart randomly sampled pseudopopulation observations imputed from population life tables that adjust for expected mortality. We then fit a censored quantile regression model to the hybrid data incorporating demographic variables (e.g., age, biologic sex, calendar time) corresponding to the population life tables of demographically-similar individuals, a population versus study covariate, and its interactions with the variables of interest. These latter variables can be interpreted as relative survival parameters that depict the differences in failure quantiles between the study participants and their population counterparts.

BACKGROUND: Globally, emergency nutrition program adaptations were implemented as part of COVID-19 mitigation strategies, but the implications of the adoption of all protocol changes at scale in the context of deteriorating food security are not yet well characterized. With ongoing conflict, widespread floods, and declining food security, the secondary impacts of COVID-19 on child survival in South Sudan is of great concern. In light of this, the present study aimed to characterize the impact of COVID-19 on nutrition programming in South Sudan. METHODS: A mixed methods approach including a desk review and secondary analysis of facility-level program data was used to analyze trends in program indicators over time and compare two 15-month periods prior to the onset of COVID-19 (January 2019 - March 2020; "pre-COVID period") and after the start of the pandemic (April 2020 - June 2021; "COVID" period) in South Sudan. RESULTS: The median number of reporting Community Management of Acute Malnutrition sites increased from 1167 pre-COVID to 1189 during COVID. Admission trends followed historic seasonal patterns in South Sudan; however, compared to pre-COVID, declines were seen during COVID in total admissions (- 8.2%) and median monthly admissions (- 21.8%) for severe acute malnutrition. For moderate acute malnutrition, total admissions increased slightly during COVID (1.1%) while median monthly admissions declined (- 6.7%). Median monthly recovery rates improved for severe (92.0% pre-COVID to 95.7% during COVID) and moderate acute malnutrition (91.5 to 94.3%) with improvements also seen in all states. At the national level, rates also decreased for default (- 2.4% for severe, - 1.7% for moderate acute malnutrition) and non-recovery (- 0.9% for severe, - 1.1% for moderate acute malnutrition), with mortality rates remaining constant at 0.05-0.15%. CONCLUSIONS: Within the context of the ongoing COVID-19 pandemic in South Sudan, improved recovery, default, and non-responder rates were observed following adoption of changes to nutrition protocols. Policymakers in South Sudan and other resource-constrained settings should consider if simplified nutrition treatment protocols adopted during COVID-19 improved performance and should be maintained in lieu of reverting to standard treatment protocols.

BACKGROUND: Diagnoses of HIV in the United States decreased by 17% in 2020 due to COVID-related disruptions. The extent to which this decrease is attributable to changes in HIV testing versus HIV transmission is unclear. We seek to better understand this issue by analyzing the discrepancy in expected versus observed HIV diagnoses in 2020 among persons who acquired HIV between 2010 and 2019 because changes in diagnosis patterns in this cohort cannot be attributed to changes in transmission. METHODS: We developed 3 methods based on the CD4-depletion model to estimate excess missed diagnoses in 2020 among persons with HIV (PWH) infected from 2010 to 2019. We stratified the results by transmission group, sex assigned at birth, race/ethnicity, and region to examine differences by group and confirm the reliability of our estimates. We performed similar analyses projecting diagnoses in 2019 among PWH infected from 2010 to 2018 to evaluate the accuracy of our methods against surveillance data. RESULTS: There were approximately 3100-3300 (approximately 18%) fewer diagnoses than expected in 2020 among PWH infected from 2010 to 2019. Females (at birth), heterosexuals, persons who inject drugs, and Hispanic/Latino PWH missed diagnoses at higher levels than the overall population. Validation and stratification analyses confirmed the accuracy and reliability of our estimates. CONCLUSIONS: The substantial drop in number of previously infected PWH diagnosed in 2020 suggests that changes in testing played a substantial role in the observed decrease. Levels of missed diagnoses differed substantially across population subgroups. Increasing testing efforts and innovative strategies to reach undiagnosed PWH are needed to offset this diagnosis gap. These analyses may be used to inform future estimates of HIV transmission during the COVID-19 pandemic.

Up to 50% of those diagnosed with HIV in the U.S. are not retained in medical care. Care retention provides opportunity to monitor benefits of HIV therapy and enable viral suppression. To increase retention, there is a need to prioritize best practices appropriate for translation and dissemination for real-world implementation. Eighteen interventions from CDC's Compendium of Evidence-Based Interventions were scored using the RE-AIM framework to determine those most suitable for dissemination. A CDC Division of HIV Prevention workgroup developed a RE-AIM scale with emphasis on the Implementation and Maintenance dimensions and less emphasis on the Efficacy dimension since all 18 interventions were already identified as evidence-based or evidence-informed. Raters referenced primary efficacy publications and scores were averaged for a ranked RE-AIM score for interventions. Of 18 interventions, four included care linkage and 7 included viral suppression outcomes. Interventions received between 20.6 and 35.3 points (45 maximum). Scores were converted into a percentage of the total possible with ranges between 45.8 and 78.4%. Top four interventions were ARTAS (78.4%); Routine Screening for HIV (RUSH) (73.2%); Optn4Life (67.4%) and Virology Fast Track (65.9%). All four scored high on Implementation and Maintenance dimensions. Select items within the scale were applicable to health equity, covering topics such as reaching under-served focus populations and acceptability to that population. Navigation-enhanced Case Management (NAV) scored highest on the health equity subscale. RE-AIM prioritization scores will inform dissemination and translation efforts, help clinical staff select feasible interventions for implementation, and support sustainability for those interventions.

BACKGROUND: Detection of malaria parasitaemia in samples that are negative by rapid diagnostic tests (RDTs) requires resource-intensive molecular tools. While pooled testing using a two-step strategy provides a cost-saving alternative to the gold standard of individual sample testing, statistical adjustments are needed to improve accuracy of prevalence estimates for a single step pooled testing strategy. METHODS: A random sample of 4670 malaria RDT negative dried blood spot samples were selected from a mass testing and treatment trial in Asembo, Gem, and Karemo, western Kenya. Samples were tested for malaria individually and in pools of five, 934 pools, by one-step quantitative polymerase chain reaction (qPCR). Maximum likelihood approaches were used to estimate subpatent parasitaemia (RDT-negative, qPCR-positive) prevalence by pooling, assuming poolwise sensitivity and specificity was either 100% (strategy A) or imperfect (strategy B). To improve and illustrate the practicality of this estimation approach, a validation study was constructed from pools allocated at random into main (734 pools) and validation (200 pools) subsets. Prevalence was estimated using strategies A and B and an inverse-variance weighted estimator and estimates were weighted to account for differential sampling rates by area. RESULTS: The prevalence of subpatent parasitaemia was 14.5% (95% CI 13.6-15.3%) by individual qPCR, 9.5% (95% CI (8.5-10.5%) by strategy A, and 13.9% (95% CI 12.6-15.2%) by strategy B. In the validation study, the prevalence by individual qPCR was 13.5% (95% CI 12.4-14.7%) in the main subset, 8.9% (95% CI 7.9-9.9%) by strategy A, 11.4% (95% CI 9.9-12.9%) by strategy B, and 12.8% (95% CI 11.2-14.3%) using inverse-variance weighted estimator from poolwise validation. Pooling, including a 20% validation subset, reduced costs by 52% compared to individual testing. CONCLUSIONS: Compared to individual testing, a one-step pooled testing strategy with an internal validation subset can provide accurate prevalence estimates of PCR-positivity among RDT-negatives at a lower cost.

BACKGROUND: HIV partner services can accelerate the use of antiretroviral-based HIV prevention tools (ART and PrEP), but its population impact on long-term HIV incidence reduction is challenging to quantify with traditional PS metrics of partner identified or HIV-screened. Understanding the role of partner services within the portfolio of HIV prevention interventions, including using it to efficiently deliver antiretrovirals, is needed to achieve HIV prevention targets. METHODS: We used a stochastic network model of HIV/STI transmission for men who have sex with men (MSM), calibrated to surveillance-based estimates in the Atlanta area, a jurisdiction with high HIV burden and suboptimal partner services uptake. Model scenarios varied successful delivery of partner services cascade steps (newly diagnosed "index" patient and partner identification, partner HIV screening, and linkage or reengagement of partners in PrEP or ART care) individually and jointly. RESULTS: At current levels observed in Atlanta, removal of HIV partner services had minimal impact on 10-year cumulative HIV incidence, as did improving a single partner services step while holding the others constant. These changes did not sufficiently impact overall PrEP or ART coverage to reduce HIV transmission. If all index patients and partners were identified, maximizing partner HIV screening, partner PrEP provision, partner ART linkage, and partner ART reengagement would avert 6%, 11%, 5%, and 18% of infections, respectively. Realistic improvements in partner identification and service delivery were estimated to avert 2-8% of infections, depending on the combination of improvements. CONCLUSIONS: Achieving optimal HIV prevention with partner services depends on pairing improvements in index patient and partner identification with maximal delivery of HIV screening, ART, and PrEP to partners if indicated. Improving the identification steps without improvement to antiretroviral service delivery steps, or vice versa, is projected to result in negligible population HIV prevention benefit.

BACKGROUND: Previous models have estimated the total population attributable fraction of NG/CT on HIV incidence among men who have sex with men (MSM), but this does not represent realistic intervention effects. We estimated the potential impact of screening for NG/CT on downstream incidence of HIV among MSM. METHODS: Using a network model, we estimated the effects of varying coverage levels for STI screening among different priority populations: all sexually active MSM regardless of HIV serostatus, MSM with multiple recent (past 6 months) sex partners regardless of serostatus, MSM without HIV, and MSM with HIV. Under the assumption that all screening events included a urethral test, we also examined the effect of increasing of the proportion of screening events that include rectal screening for NG/CT on HIV incidence. RESULTS: Increasing annual NG/CT screening among sexually active MSM by 60% averted 4.7% of HIV infections over a 10-year period (interquartile range (IQR): 2.3, 7.3). More HIV infections were averted when screening was focused on MSM with multiple recent sex partners: 60% coverage among MSM with multiple recent sex partners averted 9.8% of HIV infections (IQR: 8.1, 11.6). Increased STI screening among MSM without HIV averted more new HIV infections compared to the transmissions averted due to screening MSM with HIV, but fewer NG/CT tests were needed among MSM with HIV to avert a single new HIV infection. CONCLUSIONS: NG/CT screening among MSM is expected to lead to modest but clinically relevant reductions in HIV incidence among MSM.

BACKGROUND: Nonviral sexually transmitted infections (STIs) increase risk of sexually-acquired HIV infection. Updated risk estimates carefully scrutinizing temporality bias of studies are needed. METHODS: We conducted a systematic review (PROSPERO # CRD42018084299) of peer-reviewed studies evaluating variation in risk of HIV infection among high-risk heterosexuals diagnosed with any of: Chlamydia trachomatis, Mycoplasma genitalium, Neisseria gonorrhoeae, Treponema pallidum, and/or Trichomonas vaginalis. We searched PubMed, Web of Science, and Embase databases through December 2017 and included studies where STIs and HIV were assessed using laboratory tests or medical exams and where STI was diagnosed before HIV. After dual screening, data extraction, and risk of bias assessment, we meta-analytically pooled risk ratios (RR). RESULTS: We found 32 eligible studies reporting k = 97 effect size estimates of HIV acquisition risk due to infection with one of the above STIs. Most data were based on females engaged in sex work or other high-risk occupations in developing countries. Many studies did not measure or adjust for known confounders including drug injection and condom use and most were at medium or high risk of bias due to potential for undetected HIV infection to have occurred prior to STI infection. HIV acquisition risk increased among females infected with any pathogen; the effect was greatest for females infected with Mycoplasma genitalium (RR = 3.10; 95% CI 1.63, 5.92; k = 2) and gonorrhea (RR = 2.81; 95% CI 2.25, 3.50; k = 16) but also statistically significant for females infected with syphilis (RR = 1.67; 95% CI 1.23, 2.27; k = 17), trichomonas (RR = 1.54; 95% CI 1.31, 1.82; k = 17) and chlamydia (RR = 1.49; 95% CI 1.08, 2.04; k = 14). For males, data were space except for syphilis (RR = 1.77; 95% CI 1.22, 2.58; k = 5). CONCLUSION: Nonviral STI increases risk of heterosexual HIV acquisition, although uncertainty remains due to risk of bias in primary studies.

BACKGROUND: Men who have sex with men (MSM) who have bacterial sexually transmitted infections (STIs) are at increased risk for HIV infection. We enhanced and updated past summary risk estimates. METHODS: We systematically reviewed (PROSPERO No. CRD42018084299) peer-reviewed studies assessing the risk of HIV infection among MSM attributable to Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), Neisseria gonorrhoeae (NG), Treponema pallidum (TP), and/or Trichomonas vaginalis (TV). We searched 3 databases through December 2017. We excluded studies with self-reported data or simultaneous STI and HIV assessment. We conducted dual screening and data extraction, meta-analytically pooled risk ratios (RRs), and assessed potential risk of bias. RESULTS: We included 26 studies yielding 39 RR (k) for HIV acquisition due to one of TP, NG, or CT. We did not identify eligible data for MG or TV, or for HIV transmission. HIV acquisition risk increased among MSM infected with TP (k = 21; RR, 2.68, 95% confidence interval [CI], 2.00-3.58), NG (k = 11; RR, 2.38; 95% CI, 1.56-3.61), and CT (k = 7; RR, 1.99; 95% CI, 1.59-2.48). Subanalysis RRs for all 3 pathogens were ≥1.66 and remained statistically significant across geography and methodological characteristics. Pooled RR increased for data with the lowest risk of bias for NG (k = 3; RR, 5.49; 95% CI, 1.11-27.05) and TP (k = 4; RR, 4.32; 95% CI, 2.20-8.51). We observed mostly moderate to high heterogeneity and moderate to high risk of bias. CONCLUSIONS: Men who have sex with men infected with TP, NG, or CT have twice or greater risk of HIV acquisition, although uncertainties exist because of data heterogeneity and risk of bias.

OBJECTIVE: Research synthesis, through qualitative or quantitative systematic reviews, allows for integrating results of primary research to improve public health. We examined more than 2 decades of work in HIV prevention by the Centers for Disease Control and Prevention's (CDC's) HIV/AIDS Prevention Research Synthesis (PRS) Project. We describe the context and contributions of research synthesis, including systematic reviews and meta-analyses, through the experience of the PRS Project. METHODS: We reviewed PRS Project publications and products and summarized PRS contributions from 1996 to July 2020 in 4 areas: synthesis of interventions and epidemiologic studies, synthesis methods, prevention programs, and prevention policy. RESULTS: PRS Project publications summarized risk behaviors and effects of prevention interventions (eg, changing one's perception of risk, teaching condom negotiation skills) across populations at risk for HIV infection and intervention approaches (eg, one-on-one or group meetings) as the HIV/AIDS epidemic and science evolved. We used the PRS Project cumulative database and intervention efficacy reviews to contribute to prevention programs and policies through identification of evidence-based interventions and development of program guidance. Subject matter experts and scientific evidence informed PRS Project products and contributions, which were implemented through strategic programmatic partnerships. CONCLUSIONS: The contributions of the PRS Project to HIV prevention and public health efforts in the United States can be credited to CDC's long-standing support of the project and its context within a federal prevention agency, where HIV programs and policies were developed and implemented. The effect of the PRS Project was likely facilitated by opportunities to directly influence program and policy because of connections with other research translation activities and program and policy decision making within CDC.

The Child Health and Mortality Prevention Surveillance (CHAMPS) Network is designed to elucidate and track causes of under-5 child mortality and stillbirth in multiple sites in sub-Saharan Africa and South Asia using advanced surveillance, laboratory and pathology methods. Expert panels provide an arguable gold standard determination of underlying cause of death (CoD) on a subset of child deaths, in part through examining tissue obtained via minimally invasive tissue sampling (MITS) procedures. We consider estimating a population-level distribution of CoDs based on this sparse but precise data, in conjunction with data on subgrouping characteristics that are measured on the broader population of cases and are potentially associated with selection for MITS and with cause-specific mortality. We illustrate how estimation of each underlying CoD proportion using all available data can be addressed equivalently in terms of a Horvitz-Thompson adjustment or a direct standardization, uncovering insights relevant to the designation of appropriate subgroups to adjust for non-representative sampling. Taking advantage of the functional form of the result when expressed as a multinomial distribution-based maximum likelihood estimator, we propose small-sample adjustments to Bayesian credible intervals based on Jeffreys or related weakly informative Dirichlet prior distributions. Our analyses of early data from CHAMPS sites in Kenya and Mozambique and accompanying simulation studies demonstrate the validity of the adjustment approach under attendant assumptions, together with marked performance improvements associated with the proposed adjusted Bayesian credible intervals. Adjustment for non-representative sampling of those validated via gold standard diagnostic methods is a critical endeavor for epidemiologic studies like CHAMPS that seek extrapolation of CoD proportion estimates.

This paper describes the development of a formula to determine which evidence-based behavioral interventions (EBIs) targeting HIV-negative persons would be cost-saving in comparison to the lifetime cost of HIV treatment and the process by which this formula was used to prioritize those with greatest potential impact for continued dissemination. We developed a prevention benefit index (PBI) to rank risk-reduction EBIs for HIV-negative persons based on their estimated cost for achieving the behavior change per one would-be incident infection of HIV. Inputs for calculating the PBI included the mean estimated cost-per-client served, EBI effect size for the behavior change, and the HIV incidence per 100,000 persons in the target population. EBIs for which the PBI was </= $402,000, the estimated lifetime cost of HIV care, were considered cost-saving. We were able to calculate a PBI for 35 EBI and target population combinations. Ten EBIs were cost-saving having a PBI below $402,000. One EBI did not move forward for dissemination due to high start-up dissemination costs. DHAP now supports the dissemination of 9 unique EBIs targeting 13 populations of HIV-negative persons. The application of a process, such as the PBI, may assist other health-field policymakers when making decisions about how to select and fund implementation of EBIs.

BACKGROUND: Sexually transmitted infections (STIs) are associated with an increased risk of HIV acquisition and transmission. We estimated the proportion of HIV incidence among men who have sex with men attributable to infection with the two most common bacterial STIs, Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT). METHODS: We used a stochastic, agent-based model of a sexual network of MSM with co-circulating HIV, NG, and CT infections. Relative risk (RR) multipliers, specific to anatomic site of infection, modified the risk of HIV transmission and acquisition based on STI status. We estimated the effect of NG and CT on HIV incidence overall and on HIV acquisition and HIV transmission separately. Each scenario was simulated for ten years. The population attributable fraction (PAF) was determined for each combination of RRs by comparing the incidence in the final year of a scenario to a scenario in which the RRs associated with NG and CT were set to 1.0. RESULTS: Overall, 10.4% (IQR: 7.9,12.4) of HIV infections were attributable to NG/CT infection. Then in sensitivity analyses, the PAF for HIV transmission ranged from 3.1% (IQR: 0.5, 5.2) to 20.4% (IQR: 17.8, 22.5) and the PAF for HIV acquisition ranged from 2.0% (IQR: -0.7, 4.3) to 13.8% (IQR: 11.7, 16.0). CONCLUSIONS: Despite challenges in estimating the causal impact of NG/CT on HIV risk, modeling is an alternative approach to quantifying plausible ranges of effects given uncertainty in the biological co-factors. Our estimates represent idealized public health interventions in which STI could be maximally prevented, setting targets for real-world STI interventions that seek to reduce HIV incidence. SUMMARY: Approximately 10% of incident HIV infections among MSM in the US are caused by prevalent gonorrhea or chlamydia infection.

BACKGROUND: Sexually transmitted infections (STIs) are associated with an increased risk of HIV acquisition and transmission. We estimated the proportion of HIV incidence among men who have sex with men attributable to infection with the two most common bacterial STIs, Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT). METHODS: We used a stochastic, agent-based model of a sexual network of MSM with co-circulating HIV, NG, and CT infections. Relative risk (RR) multipliers, specific to anatomic site of infection, modified the risk of HIV transmission and acquisition based on STI status. We estimated the effect of NG and CT on HIV incidence overall and on HIV acquisition and HIV transmission separately. Each scenario was simulated for ten years. The population attributable fraction (PAF) was determined for each combination of RRs by comparing the incidence in the final year of a scenario to a scenario in which the RRs associated with NG and CT were set to 1.0. RESULTS: Overall, 10.4% (IQR: 7.9,12.4) of HIV infections were attributable to NG/CT infection. Then in sensitivity analyses, the PAF for HIV transmission ranged from 3.1% (IQR: 0.5, 5.2) to 20.4% (IQR: 17.8, 22.5) and the PAF for HIV acquisition ranged from 2.0% (IQR: -0.7, 4.3) to 13.8% (IQR: 11.7, 16.0). CONCLUSIONS: Despite challenges in estimating the causal impact of NG/CT on HIV risk, modeling is an alternative approach to quantifying plausible ranges of effects given uncertainty in the biological co-factors. Our estimates represent idealized public health interventions in which STI could be maximally prevented, setting targets for real-world STI interventions that seek to reduce HIV incidence. SUMMARY: Approximately 10% of incident HIV infections among MSM in the US are caused by prevalent gonorrhea or chlamydia infection.