Including transgender populations in mathematical models for HIV treatment and prevention: current barriers and policy implications.

INTRODUCTION: Mathematical models of HIV have been uniquely important in directing and evaluating HIV policy. Transgender and nonbinary people are disproportionately impacted by HIV; however, few mathematical models of HIV transmission have been published that are inclusive of transgender and nonbinary populations. This commentary discusses current structural challenges to developing robust and accurate trans-inclusive models and identifies opportunities for future research and policy, with a focus on examples from the United States. DISCUSSION: As of April 2024, only seven published mathematical models of HIV transmission include transgender people. Existing models have several notable limitations and biases that limit their utility for informing public health intervention. Notably, no models include transgender men or nonbinary individuals, despite these populations being disproportionately impacted by HIV relative to cisgender populations. In addition, existing mathematical models of HIV transmission do not accurately represent the sexual network of transgender people. Data availability and quality remain a significant barrier to the development of accurate trans-inclusive mathematical models of HIV. Using a community-engaged approach, we developed a modelling framework that addresses the limitations of existing model and to highlight how data availability and quality limit the utility of mathematical models for transgender populations. CONCLUSIONS: Modelling is an important tool for HIV prevention planning and a key step towards informing public health interventions, programming and policies for transgender populations. Our modelling framework underscores the importance of accurate trans-inclusive data collection methodologies, since the relevance of these analyses for informing public health decision-making is strongly dependent on the validity of the model parameterization and calibration targets. Adopting gender-inclusive and gender-specific approaches starting from the development and data collection stages of research can provide insights into how interventions, programming and policies can distinguish unique health needs across all gender groups. Moreover, in light of the data structure limitations, designing longitudinal surveillance data systems and probability samples will be critical to fill key research gaps, highlight progress and provide additional rigour to the current evidence. Investments and initiatives like Ending the HIV Epidemic in the United States can be further expanded and are highly needed to prioritize and value transgender populations across funding structures, goals and outcome measures.

The influence of operation time for hip hemiarthroplasty on complication rates and mortality in patients with femoral neck fracture: a retrospective data analysis.

BACKGROUND: The aim of the present study was to investigate the influence of various factors, in particular operation time, on mortality and complication rates in patients with femoral neck fractures who have undergone hip hemiarthroplasty (HHA) and to determine a cut-off value above which mortality and complication rates increase significantly. METHODS: Cases of patients with femoral neck fracture treated with HHA between 1 January 2017 and 31 December 2023 were screened for eligibility. Multiple logistic regressions were calculated to determine which factors (patient age, experience of surgeon, patient sex, ASA score, time to surgery, operation time) influenced the incidence of complications and mortality. The exact cut-off value for complications and mortality was determined using the Youden index of the ROC curve (sensitivity vs. specificity) of logistic regression. RESULTS: A total of 552 patients were considered eligible for this study. During the 90-day follow-up period after HHA, 50 deaths and 34 complications were recorded, giving a mortality rate of 9.1%, and a complication rate of 6.2%. Of the 34 complications recorded, 32.3% were infections, 14.7% dislocations, 20.7% trochanteric avulsions, 11.8% periprosthetic fractures, 11.8% nerve injuries, and 8.8% deep vein thrombosis. The odds ratio (OR) of a patient experiencing a complication is 2.2% higher for every minute increase in operation time (Exponential Beta - 1 = 0.022; p = 0.0363). The OR of a patient dying is 8.8% higher for each year increase in age (Exponential Beta - 1 = 0.088; p = 0.0007). When surgery was performed by a certified orthopaedic surgeon the mortality rate lowered by 61.5% in comparison to the surgery performed by a trainee (1 - Exponential Beta = 0.594; p = 0.0120). Male patients have a 168.7% higher OR for mortality than female patients (Exponential Beta - 1 = 1.687; p = 0.0017). Patients with an operation time of ≥ 86 min. have a 111.8% higher OR for mortality than patients with an operation time of < 86 min. (Exponential Beta - 1 = 1.118). CONCLUSION: This retrospective data analysis found that the risk of a patient experiencing a complication was 2.2% higher for every minute increase in operation time. Patients with an operation time above the cut-off of 86 min had a 111.8% higher risk of mortality than those with an operation time below the cut-off. Other influencing factors that operators should be aware of include patient age, male sex, and operator experience.

Patient-related Predictors for the Functional Outcome of SuperPATH Hemiarthroplasty versus Conventional Approach Hemiarthroplasty: A Systematic Review and Meta-regression Analysis of Randomized Controlled Trials.

Specialist literature lacks evidence that explores associations between patient characteristics and the beneficial treatment effect of SuperPATH hemiarthroplasty (HA) compared with conventional approach (CA) HA. To investigate and identify patient-related predictors of the effect size of the short-term functional outcome of SuperPATH HA and CA HA by performing a systematic review and meta-regression analysis of randomized controlled trials (RCTs). A systematic search of literature was performed in PubMed, CNKI, CENTRAL of The Cochrane Library, Clinical trials, and Google Scholar until August 25, 2023. For the continuous outcome parameter Harris hip score (HHS) ≤1 week and 3 months postoperatively, mean differences (MDs) with 95% confidence intervals (CIs) were calculated. A meta-regression analysis was based on random-effects meta-analysis using the Hartung-Knapp-Sidik-Jonkman method for continuous covariates. A total of five RCTs with 404 patients were found. The following predictors of HHS ≤1 week postoperatively were identified: patient age (predictor estimate = 1.29; p < 0.01), patient age groups (predictor estimate = 14.07; p < 0.01), time to mobilization (predictor estimate = 5.51; p < 0.01). The following predictors of HHS 3 months postoperatively were identified: incision length (predictor estimate = -2.12; p < 0.01); intraoperative blood loss (predictor estimate = 0.02; p < 0.01). Patient age, time to mobilization, incision length, and intraoperative blood loss were identified as predictors of the effect size of early postoperative functional outcome as measured by HHS. Elderly patients, particularly those over 70 years of age, appear to benefit from SuperPATH HA. Based on these findings, and taking into account our limitations, we recommend that the use of minimally invasive SuperPATH HA in elderly patients should be more widely considered and not limited to elective THA patients.

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.

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.

US-guided high-intensity focused ultrasound in pancreatic cancer treatment: a consensus initiative between Chinese and European HIFU centers.

Purpose: Ultrasound-guided high-intensity focused ultrasound (USgHIFU) represents a safe and effective non-invasive thermoablative technique for managing inoperable pancreatic cancer. This treatment method significantly alleviates disease-related symptoms and reduces pancreatic tumor volume. However, the current body of evidence is constrained by a lack of randomized controlled trials. The utilization of USgHIFU is primarily indicated for patients with unresectable, locally advanced, or metastatic pancreatic cancer, particularly those experiencing symptoms due to a locally advanced primary tumor.Methods: This collaborative consensus paper, involving European and Chinese HIFU centers treating pancreatic cancer, delineates criteria for patient selection, focusing on those most likely to benefit from USgHIFU treatment. Consideration is given to endpoints encompassing symptom alleviation, local response rates, other oncological outcomes, as well as overall and progression-free survival. Additionally, this paper defines relevant contraindications, side effects, and complications associated with USgHIFU. The publication also explores the feasibility and role of USgHIFU within the context of palliative care, including standard systemic chemotherapy.Results: The non-invasive local treatment of advanced pancreatic cancer using HIFU should be regarded as an adjunctive option alongside systemic chemotherapy or best supportive care for managing this aggressive disease. Based on the ability of USgHIFU therapy to mitigate pain and reduce primary tumor volume, it should be considered as a complementary therapy for symptomatic patients with inoperable pancreatic cancer and as a potential means of tumor debulking. The underutilized yet promising USgHIFU exhibits the potential to enhance patients' quality of life by alleviating cancer-related pain. Experts in the field should evaluate this treatment option be evaluated by experts in this field, with this consensus paper potentially serving as a guiding resource for the medical community.Conclusions: US-guided HIFU for advanced pancreatic cancer addresses treatment goals, available options, success rates, and limitations. As a non-invasive, effective local therapy, complementary to chemotherapy and best supportive care, it plays a pivotal role in pain relief, reducing of tumor volume, and potentially improving survival rates.

Hemiarthroplasty through SuperPATH versus hemiarthroplasty through conventional approaches in patients with femoral neck fractures: a systematic review and meta-analysis of randomized controlled trials.

The aim was to conduct a systematic review of literature and meta-analysis of randomized controlled trials (RCTs) comparing short-term outcomes of bipolar hemiarthroplasty (HA) through SuperPATH and bipolar HA through conventional approaches (CAs) in patients with femoral neck fractures. The following PICO question was formulated: In human participants with femoral neck fractures, are the short-term outcomes of SuperPATH HA better than the short-term outcomes of CAs HA? The following databases were searched until 25 August 2023: PubMed, CNKI, CENTRAL of The Cochrane Library, Clinical trials, and Google Scholar. Quality assessment of the RCTs was performed, according to the Cochrane's Risk of Bias 2 tool and the recommendations of the GRADE system. Furthermore, we evaluated publication bias with funnel plots. Mean differences (MDs) with 95% confidence intervals (CIs) were calculated for continuous variables using the Hartung-Knapp-Sidik-Jonkman method and a random effects model. Nine RCTs with overall 762 patients were included in this meta-analysis. All 9 RCTs were rated with a moderate risk of bias. The quality of evidence of the outcome parameters was rated moderate to very low. The funnel plots were overall broadly symmetrical, possibly indicating low to moderate publication bias. SuperPATH had a longer operation time compared to CAs (MD = 21.79, 95% CI 12.57 to 31.02). SuperPATH decreased incision length (MD = - 4.50; 95% CI - 5.80 to - 3.20), intraoperative blood loss (MD = - 103.96, 95% CI - 150.27 to - 55.66), postoperative drainage volume (MD = - 137.30, 95% CI - 178.74 to - 95.86), time to mobilization (MD = - 3.86; 95% CI - 5.96 to - 1.76), pain VAS ≤ 1 week postoperatively (MD = - 1.81; 95% CI - 2.17 to - 1.45), and hospitalization time (MD = - 4.05; 95% CI - 4.96 to - 3.15). SuperPATH improved HHS ≤ 1 week postoperatively (MD = 11.10; 95% CI 1.65 to 20.54) and HHS 3 months postoperatively (MD = 6.33; 95% CI 3.97 to 8.69). There was no difference in pain VAS 1-3 months postoperatively (MD = - 0.08; 95% CI - 0.22 to 0.05) and HHS 6 months postoperatively (MD = 0.44; 95% CI - 0.11 to 1.00). This is the first meta-analysis comparing SuperPATH HA with CAs HA in patients with femoral neck fractures. SuperPATH HA was superior in the early short-term functional outcome (HHS) compared to CAs HA, reaching minimal clinically important differences. Furthermore, SuperPATH HA showed significantly better results in incision length, blood loss, time to mobilization, pain intensity (VAS), and hospitalization time than CAs HA.

Efficacy estimates of oral pre-exposure prophylaxis for HIV prevention in cisgender women with partial adherence.

Pre-exposure prophylaxis (PrEP) with tenofovir (TFV) disoproxil fumarate and emtricitabine administered orally daily is effective in preventing human immunodeficiency virus (HIV) acquisition in both men and women with sufficient adherence; however, the adherence-efficacy relationship in cisgender women has not been well established. We calculated the adherence-efficacy curve for cisgender women by using HIV incidence and plasma TFV concentration data from three trials (FEM-PrEP, VOICE and Partners PrEP). We imputed TFV diphosphate (TFV-DP) concentrations, a measure of long-term adherence, from TFV quantification by using data from the HIV Prevention Trials Network 082 study, which measured both TFV-DP and TFV concentrations. Two, four and seven pills per week reduced HIV incidence by 59.3% (95% credible interval (CrI) 29.9-95.8%), 83.8% (95% CI 51.7-99.8%) and 95.9% (95% CI 72.6-100%), respectively. Our adherence-efficacy curve can be validated and updated by HIV prevention studies that directly measure TFV-DP concentrations. The curve suggests that high adherence confers high protection in cisgender women. However, the lower efficacy with partial adherence highlights the need for new PrEP products and interventions to increase adherence.

Success rate and safety of totally implantable access ports placed by the cephalic vein cutdown technique in oncological patients - a single-center study.

INTRODUCTION: Totally implantable access ports (TIAPs) are commonly used in oncologic patients undergoing ongoing chemotherapy. The methods of choice for implantation are the subclavian vein puncture approach and the cephalic vein cutdown technique, followed by internal jugular vein access and external jugular vein access.

Risk Factors and Predictors for Functional Outcome and Complication Rate in Total Hip Arthroplasty through Minimally Invasive and Conventional Approaches: A Systematic Review and Meta-Regression Analysis of 41 Randomized Controlled Trials.

OBJECTIVE: To investigate and identify risk factors and predictors for the difference in functional outcome and complications between total hip arthroplasty (THA) through minimally invasive and conventional approaches, using a meta-regression analysis of randomized controlled trials (RCTs). METHODS: A systematic review of the literature up to 31 July 2022 was performed. A meta-regression was conducted based on a random effects meta-analysis using the Hartung-Knapp-Sidik-Jonkman method. RESULTS: A total of 41 RCTs with 3607 patients were found. The following predictors of HHS ≥ 6 months postoperatively were identified: patient age (predictor estimate = 0.14; p < 0.01), avascular necrosis of the femoral head (predictor estimate = -0.03; p = 0.04); incision length (predictor estimate = -0.82; p < 0.01). The following predictors of complication rate were identified: osteoarthritis (predictor estimate = 0.02; p = 0.02); femoral neck fracture (predictor estimate = -0.02; p = 0.02); SuperPATH (predictor estimate = -1.72; p < 0.01). CONCLUSIONS: Patient age, avascular necrosis of the femoral head, and incision length were identified as predictors of the effect size of the HHS ≥ 6 months postoperatively; and osteoarthritis, femoral neck fracture, and SuperPATH as predictors of the effect size of the complication rate. Based on these findings, we recommend that more frequent use of minimally invasive THA in elderly patients should be considered. LEVEL OF EVIDENCE I: a systematic review of all relevant randomized controlled trials. Registered in PROSPERO on 10 August 2022 (CRD42022350287).

Retrospective analysis of equity-based optimization for COVID-19 vaccine allocation.

Marginalized racial and ethnic groups in the United States were disproportionally affected by the COVID-19 pandemic. To study these disparities, we construct an age-and-race-stratified mathematical model of SARS-CoV-2 transmission fitted to age-and-race-stratified data from 2020 in Oregon and analyze counterfactual vaccination strategies in early 2021. We consider two racial groups: non-Hispanic White persons and persons belonging to BIPOC groups (including non-Hispanic Black persons, non-Hispanic Asian persons, non-Hispanic American-Indian or Alaska-Native persons, and Hispanic or Latino persons). We allocate a limited amount of vaccine to minimize overall disease burden (deaths or years of life lost), inequity in disease outcomes between racial groups (measured with five different metrics), or both. We find that, when allocating small amounts of vaccine (10% coverage), there is a trade-off between minimizing disease burden and minimizing inequity. Older age groups, who are at a greater risk of severe disease and death, are prioritized when minimizing measures of disease burden, and younger BIPOC groups, who face the most inequities, are prioritized when minimizing measures of inequity. The allocation strategies that minimize combinations of measures can produce middle-ground solutions that similarly improve both disease burden and inequity, but the trade-off can only be mitigated by increasing the vaccine supply. With enough resources to vaccinate 20% of the population the trade-off lessens, and with 30% coverage, we can optimize both equity and mortality. Our goal is to provide a race-conscious framework to quantify and minimize inequity that can be used for future pandemics and other public health interventions.

Cannulated screws versus dynamic hip screw versus hemiarthroplasty versus total hip arthroplasty in patients with displaced and non-displaced femoral neck fractures: a systematic review and frequentist network meta-analysis of 5703 patients.

BACKGROUND: Our aim was to determine the best operative procedure in human participants with a displaced or non-displaced femoral neck fracture comparing cannulated screw (CS) fixation, dynamic hip screw (DHS) fixation, hemiarthroplasty (HA), and total hip arthroplasty (THA) in terms of surgical and functional outcomes, reoperation and postoperative complications. METHODS: We searched PubMed, The Cochrane Library, Clinical trials, CINAHL, and Embase for randomized controlled trials (RCTs) or quasi-RCTs up to 31 July 2022. A frequentist network meta-analysis was performed to assess the comparative effects of the four operative procedures, using fixed-effects and random-effects models. Mean differences (MDs) with 95% confidence intervals (CIs) were estimated for continuous variables and odds ratios (ORs) with 95% CIs were estimated for binary variables. RESULTS: A total of 33 RCTs with 5703 patients were included in our network meta-analysis. CS fixation was best in terms of operation time (CS: MD = - 57.70, 95% CI - 72.78; - 42.62; DHS: MD = - 53.56, 95% CI - 76.17; - 30.95; HA: MD = - 20.90, 95% CI - 30.65; - 11.15; THA: MD = 1.00 reference) and intraoperative blood loss (CS: MD = - 3.67, 95% CI - 4.44; - 2.90; DHS: MD = - 3.20, 95% CI - 4.97; - 1.43; HA: MD = - 1.20, 95% CI - 1.73; - 0.67; THA: MD = 1.00 reference). In life quality and functional outcome, measured at different time points with EQ-5D and the Harris Hip Score (HHS), THA ranked first and HA second (e.g. EQ-5D 2 years postoperatively: CS: MD = - 0.20, 95% CI - 0.29; - 0.11; HA: MD = - 0.09, 95% CI - 0.17; - 0.02; THA: MD = 1.00 reference; HHS 2 years postoperatively: CS: MD = - 5.50, 95% CI - 9.98; - 1.03; DHS: MD = - 8.93, 95% CI - 15.08; - 2.78; HA: MD = - 3.65, 95% CI - 6.74; - 0.57; THA: MD = 1.00 reference). CS fixation had the highest reoperation risk, followed by DHS fixation, HA, and THA (CS: OR = 9.98, 95% CI 4.60; 21.63; DHS: OR = 5.07, 95% CI 2.15; 11.96; HA: OR = 1.60, 95% CI 0.89; 2.89; THA: OR = 1.00 reference). CONCLUSION: In our cohort of patients with displaced and non-displaced femoral neck fractures, HHS, EQ-5D, and reoperation risk showed an advantage of THA and HA compared with CS and DHS fixation. Based on these findings, we recommend that hip arthroplasty should be preferred and internal fixation of femoral neck fractures should only be considered in individual cases. LEVEL OF EVIDENCE I: a systematic review of randomized controlled trials. TRIAL REGISTRATION: PROSPERO on 10 August 2022 (CRD42022350293).

Population-level impact of expanding PrEP coverage by offering long-acting injectable PrEP to MSM in three high-resource settings: a model comparison analysis.

INTRODUCTION: Long-acting injectable cabotegravir (CAB-LA) demonstrated superiority to daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for HIV pre-exposure prophylaxis (PrEP) in the HPTN 083/084 trials. We compared the potential impact of expanding PrEP coverage by offering CAB-LA to men who have sex with men (MSM) in Atlanta (US), Montreal (Canada) and the Netherlands, settings with different HIV epidemics. METHODS: Three risk-stratified HIV transmission models were independently parameterized and calibrated to local data. In Atlanta, Montreal and the Netherlands, the models, respectively, estimated mean TDF/FTC coverage starting at 29%, 7% and 4% in 2022, and projected HIV incidence per 100 person-years (PY), respectively, decreasing from 2.06 to 1.62, 0.08 to 0.03 and 0.07 to 0.001 by 2042. Expansion of PrEP coverage was simulated by recruiting new CAB-LA users and by switching different proportions of TDF/FTC users to CAB-LA. Population effectiveness and efficiency of PrEP expansions were evaluated over 20 years in comparison to baseline scenarios with TDF/FTC only. RESULTS: Increasing PrEP coverage by 11 percentage points (pp) from 29% to 40% by 2032 was expected to avert a median 36% of new HIV acquisitions in Atlanta. Substantially larger increases (by 33 or 26 pp) in PrEP coverage (to 40% or 30%) were needed to achieve comparable reductions in Montreal and the Netherlands, respectively. A median 17 additional PYs on PrEP were needed to prevent one acquisition in Atlanta with 40% PrEP coverage, compared to 1000+ in Montreal and 4000+ in the Netherlands. Reaching 50% PrEP coverage by 2032 by recruiting CAB-LA users among PrEP-eligible MSM could avert >45% of new HIV acquisitions in all settings. Achieving targeted coverage 5 years earlier increased the impact by 5-10 pp. In the Atlanta model, PrEP expansions achieving 40% and 50% coverage reduced differences in PrEP access between PrEP-indicated White and Black MSM from 23 to 9 pp and 4 pp, respectively. CONCLUSIONS: Achieving high PrEP coverage by offering CAB-LA can impact the HIV epidemic substantially if rolled out without delays. These PrEP expansions may be efficient in settings with high HIV incidence (like Atlanta) but not in settings with low HIV incidence (like Montreal and the Netherlands).

The Association Between Heterosexual anal Intercourse and HIV Acquisition in Three Prospective Cohorts of Women.

The extent to which receptive anal intercourse (RAI) increases the HIV acquisition risk of women compared to receptive vaginal intercourse (RVI) is poorly understood. We evaluated RAI practice over time and its association with HIV incidence during three prospective HIV cohorts of women: RV217, MTN-003 (VOICE), and HVTN 907. At baseline, 16% (RV 217), 18% (VOICE) of women reported RAI in the past 3 months and 27% (HVTN 907) in the past 6 months, with RAI declining during follow-up by around 3-fold. HIV incidence in the three cohorts was positively associated with reporting RAI at baseline, albeit not always significantly. The adjusted hazard rate ratios for potential confounders (aHR) were 1.1 (95% Confidence interval: 0.8-1.5) for VOICE and 3.3 (1.6-6.8) for RV 217, whereas the ratio of cumulative HIV incidence by RAI practice was 1.9 (0.6-6.0) for HVTN 907. For VOICE, the estimated magnitude of association increased slightly when using a time-varying RAI exposure definition (aHR = 1.2; 0.9-1.6), and for women reporting RAI at every follow-up survey (aHR = 2.0 (1.3-3.1)), though not for women reporting higher RAI frequency (> 30% acts being RAI vs. no RAI in the past 3 months; aHR = 0.7 (0.4-1.1)). Findings indicated precise estimation of the RAI/HIV association, following multiple RVI/RAI exposures, is sensitive to RAI exposure definition, which remain imperfectly measured. Information on RAI practices, RAI/RVI frequency, and condom use should be more systematically and precisely recorded and reported in studies looking at sexual behaviors and HIV seroconversions; standardized measures would aid comparability across geographies and over time.

Evaluation of mpox vaccine dose-sparing strategies.

The spring-summer 2022 mpox outbreak had over 50,000 cases globally, most of them in gay, bisexual, and other men who have sex with men (MSM). In response to vaccine shortages, several countries implemented dose-sparing vaccination strategies, stretching a full-dose vaccine vial into up to five fractional-dose vaccines. Recent studies have found mixed results regarding the effectiveness of the mpox vaccine, raising the question of the utility of dose-sparing strategies. We used an age- and risk-stratified mathematical model of an urban MSM population in the United States with ∼12% high-risk MSM to evaluate potential benefits from implementing dose-sparing vaccination strategies in which a full dose is divided into 3.5 fractional doses. We found that results strongly depend on the fractional-dose vaccine effectiveness (VE) and vaccine supply. With very limited vaccines available, enough to protect with a full dose approximately one-third of the high-risk population, dose-sparing strategies are more beneficial provided that fractional doses preserved at least 40% of full-dose effectiveness (34% absolute VE), projecting 13% (34% VE) to 70% (68% absolute VE) fewer infections than full-dose strategies. In contrast, if vaccine supply is enough to cover the majority of the high-risk population, dose-sparing strategies can be outperformed by full-dose strategies. Scenarios in which fractional dosing was 34% efficacious resulted in almost three times more infections than full dosing. Our analysis suggests that when mpox vaccine supply is limited and fractional-dose vaccination retains moderate effectiveness, there are meaningful health benefits from providing a smaller dose to a larger number of people in the high-risk population. These findings should inform the public-health response to future mpox outbreaks.

Retrospective Analysis of Equity-Based Optimization for COVID-19 Vaccine Allocation.

Marginalized racial and ethnic groups in the United States were disproportionally affected by the COVID-19 pandemic. To study these disparities, we construct an age-and-race-stratified mathematical model of SARS-CoV-2 transmission fitted to age-and-race-stratified data from 2020 in Oregon and analyze counter-factual vaccination strategies in early 2021. We consider two racial groups: non-Hispanic White persons and persons belonging to BIPOC groups (including non-Hispanic Black persons, non-Hispanic Asian persons, non-Hispanic American Indian or Alaska Native persons, and Hispanic or Latino persons). We allocate a limited amount of vaccine to minimize overall disease burden (deaths or years of life lost), inequity in disease outcomes between racial groups (measured with five different metrics), or both. We find that, when allocating small amounts of vaccine (10% coverage), there is a trade-off between minimizing disease burden and minimizing inequity. Older age groups, who are at a greater risk of severe disease and death, are prioritized when minimizing measures of disease burden, and younger BIPOC groups, who face the most inequities, are prioritized when minimizing measures of inequity. The allocation strategies that minimize combinations of measures can produce middle-ground solutions that similarly improve both disease burden and inequity, but the trade-off can only be mitigated by increasing the vaccine supply. With enough resources to vaccinate 20% of the population the trade-off lessens, and with 30% coverage, we can optimize both equity and mortality. Our goal is to provide a race-conscious framework to quantify and minimize inequity that can be used for future pandemics and other public health interventions.

Estimating the impact of HIV PrEP regimens containing long-acting injectable cabotegravir or daily oral tenofovir disoproxil fumarate/emtricitabine among men who have sex with men in the United States: a mathematical modelling study for HPTN 083.

Background: The HPTN 083 trial demonstrated superiority of HIV pre-exposure prophylaxis (PrEP) containing long-acting injectable cabotegravir (CAB) to daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) among men who have sex with men (MSM). We compared the potential population-level impact of TDF/FTC and CAB among MSM in Atlanta, Georgia. Methods: An MSM HIV transmission model was calibrated to Atlanta-specific data on HIV prevalence and PrEP usage (percentage of uninfected MSM on PrEP), assuming only PrEP-indicated MSM used PrEP. CAB effectiveness (efficacy × adherence) of 91% was estimated using data from HPTN 083 and previous TDF/FTC trials. We estimated HIV infections averted over 5/10 years if TDF/FTC use were maintained, or if all TDF/FTC users switched to CAB in January 2022 (vs. no PrEP or continued TDF/FTC use). CAB scenarios with 10%/20% more users were also considered. Progress towards Ending the HIV Epidemic (EHE) goals (75%/90% fewer HIV infections in 2025/2030 vs. 2017) was estimated. Findings: We predicted TDF/FTC at current usage (∼28%) would avert 36.3% of new HIV infections (95% credible interval 25.6-48.7%) among all Atlanta MSM over 2022-2026 vs. no PrEP. Switching to CAB with similar usage may prevent 44.6% (33.2-56.6%) infections vs. no PrEP and 11.9% (5.2-20.2%) infections vs. continued TDF/FTC. Increasing CAB usage 20% could increase the incremental impact over TDF/FTC to 30.0% over 2022-2026, getting ∼60% towards reaching EHE goals (47%/54% fewer infections in 2025/2030). Reaching the 2030 EHE goal would require 93% CAB usage. Interpretation: If CAB effectiveness were like HPTN 083, CAB could prevent more infections than TDF/FTC at similar usage. Increased CAB usage could contribute substantially towards reaching EHE goals, but the usage required to meet EHE goals is unrealistic. Funding: NIH, MRC.

Estimating benefits of using on-demand oral prep by MSM: A comparative modeling study of the US and Thailand.

Background: Daily and on-demand pre-exposure prophylaxis (PrEP) are effective at preventing HIV acquisition among men who have sex with men (MSM), but only daily PrEP is approved in the US. On-demand PrEP may improve uptake and adherence. We identify sub-groups of MSM who would benefit from on-demand PrEP and determine effectiveness achieved if individuals used their optimal regimens. Methods: Using data from the HPTN 067 study (study period 2012-2014), we created an individual-based stochastic model of HIV risk in two synthetic MSM populations with parameters separately estimated using data from Harlem, US, and Bangkok, Thailand. Agents were assigned daily and on-demand PrEP for six months each. Two personalized PrEP assignments: optimal, based on improved predicted effectiveness and reduced pill burden, and adherence-based, using daily PrEP adherence, were simulated for another six months. Findings: Simulated on-demand PrEP was optimal for approximately one-third of MSM. It was assigned mainly to those with low daily PrEP adherence (88% (Harlem), 95% (Bangkok) of MSM with daily PrEP adherence <40%). Mean effectiveness was slightly higher in the full synthetic population with optimal PrEP assignment compared to universal daily PrEP. Among MSM for whom on-demand PrEP was optimal, mean effectiveness improved by 18 (Harlem) and 7 percentage points (Bangkok). Comparable predicted effectiveness was achieved if on-demand PrEP was assigned to the population with daily PrEP adherence <50%. There was no advantage in assigning on-demand PrEP by sex act frequency. Interpretation: On-demand PrEP could benefit many MSM by increasing effectiveness or decreasing pill burden with similar effectiveness. On-demand PrEP may be an effective alternative to daily PrEP for individuals with difficulty taking daily PrEP consistently. Results were similar for Harlem and Bangkok, indicating that these conclusions were robust in populations with different overall adherence levels and may inform future public-health policies. Funding: US NIH grant UM1 AI068617.