Background: The purpose of this study was to estimate the health impact of syphilis in the United States in terms of the number of quality-adjusted life years (QALYs) lost attributable to infections in 2018. Method(s): We developed a Markov model which simulates the natural history and long-term sequelae of syphilis. The model was parameterized by sex (men and women), sexual orientation (women who have sex with men, men who have sex with women [MSW], and men who have sex with men [MSM]), and by age at primary infection. We developed a separate decision tree model to account for health losses due to congenital syphilis. We estimated the average lifetime number of QALYs lost per infection, and the total expected lifetime number of QALYs lost due to syphilis acquired in 2018. We performed probabilistic sensitivity analysis to account for uncertainty in the model's estimates. Finding(s): We estimated the average number of discounted lifetime QALYs lost per infection as 0.09 [0.03-0.19 95% uncertainty interval (UI)]. The QALY loss per infection was lower among MSM (0.06) than among MSW (0.15) and women (0.10). The total expected number of QALYs lost due to syphilis acquired in 2018 was 13,349 (5,071-31,360 95%UI). MSM account for 6,373 (47.7%) of the overall burden, compared to MSW (32.1%) and women (20.2%). For each case of congenital syphilis, we estimated 1.79 (1.43-2.16 95%UI) QALYs lost for the child and 0.06 (0.01-0.14 95%UI) QALYs lost for the mother. These per-case estimates correspond to 2,332 (1,871-2,825 95%UI) and 79 (17-177 95%UI) QALYs lost for children and mothers, respectively, due to congenital syphilis in 2018. Conclusion(s): Syphilis causes substantial health losses in adults and children. Quantifying these health losses in terms of QALYs can inform cost-effectiveness analyses and can facilitate comparisons of the burden of syphilis to that of other diseases. 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.

OBJECTIVES: We quantified the quality-adjusted life-years (QALYs) lost attributable to chlamydia, gonorrhea, and trichomoniasis in the US, by sex and age group. METHODS: We adapted a previous probability-tree model to estimate the average number of lifetime QALYs lost due to genital chlamydia, gonorrhea, and trichomoniasis, per incident infection and at the population level, by sex and age group. We conducted multivariate sensitivity analyses to address uncertainty around key parameter values. FINDINGS: The estimated total discounted lifetime QALYs lost for men and women, respectively, due to infections acquired in 2018, were 1,541 (95% uncertainty interval: 186, 6,358) and 111,872 (29,777, 267,404) for chlamydia, 989 (127, 3,720) and 12,112 (2,410, 33,895) for gonorrhea, and 386 (30, 1,851) and 4,576 (13, 30,355) for trichomoniasis. Total QALYs lost were highest among women ages 15-24 years with chlamydia. QALYs lost estimates were highly sensitive to disutilities (health losses) of infections and sequelae, and to duration of infections and chronic sequelae for chlamydia and gonorrhea in women. CONCLUSIONS: The three sexually transmitted infections cause substantial health losses in the US, particularly gonorrhea and chlamydia among women. The estimates of lifetime QALYs lost per infection help to prioritize prevention policies and inform cost-effectiveness analyses of STI interventions.

Background: Genital herpes (GH), caused by herpes simplex virus type 1 and type 2 (HSV-1, HSV-2), is a common sexually transmitted disease associated with adverse health outcomes. Symptoms associated with GH outbreaks can be reduced by antiviral medications, but the infection is incurable and lifelong. In this study, we estimate the long-term health impacts of GH in the United States using quality-adjusted life years (QALYs) lost. Methods: We used probability trees to model the natural history of GH secondary to infection with HSV-1 and HSV-2 among people aged 18–49 years. We modelled the following outcomes to quantify the major causes of health losses following infection: symptomatic herpes outbreaks, psychosocial impacts associated with diagnosis and recurrences, urinary retention caused by sacral radiculitis, aseptic meningitis, Mollaret's meningitis, and neonatal herpes. The model was parameterized based on published literature on the natural history of GH. We summarized losses of health by computing the lifetime number of QALYs lost per genital HSV-1 and HSV-2 infection, and we combined this information with incidence estimates to compute the total lifetime number of QALYs lost due to infections acquired in 2018 in the United States. Findings: We estimated 0.05 (95% uncertainty interval (UI) 0.02–0.08) lifetime QALYs lost per incident GH infection acquired in 2018, equivalent to losing 0.05 years or about 18 days of life for one person with perfect health. The average number of QALYs lost per GH infection due to genital HSV-1 and HSV-2 was 0.01 (95% UI 0.01–0.02) and 0.05 (95% UI 0.02–0.09), respectively. The burden of genital HSV-1 is higher among women, while the burden of HSV-2 is higher among men. QALYs lost per neonatal herpes infection was estimated to be 7.93 (95% UI 6.63–9.19). At the population level, the total estimated lifetime QALYs lost as a result of GH infections acquired in 2018 was 33,100 (95% UI 12,600–67,900) due to GH in adults and 3,140 (95% UI 2,260–4,140) due to neonatal herpes. Results were most sensitive to assumptions on the magnitude of the disutility associated with post-diagnosis psychosocial distress and symptomatic recurrences. Interpretation: GH is associated with substantial health losses in the United States. Results from this study can be used to compare the burden of GH to other diseases, and it provides inputs that may be used in studies on the health impact and cost-effectiveness of interventions that aim to reduce the burden of GH. Funding: The Center for Disease Control and Prevention © 2023 The Author(s)

Background: Disparities in the health and economic burden of gonorrhoea have not been systematically quantified. We estimated population-level health losses and costs associated with gonococcal infection and sequelae in the United States. Methods: We used probability-tree models to capture gonorrhoea sequelae and to estimate attributable disease burden in terms of the discounted lifetime costs and quality-adjusted life-years (QALYs) lost due to incident infections acquired during 2015 from the healthcare system perspective. Numbers of infections in 2015 were obtained from a published gonorrhoea transmission model. We evaluated population-level disease burden, disaggregated by sex, age, race/ethnicity, and for men who have sex with men (MSM). We conducted a multivariate sensitivity analysis for key parameters. Findings: Discounted lifetime QALYs lost per incident gonococcal infection were estimated as 0.093 (95% uncertainty interval [UI] 0.022-0.22) for women, 0.0020 (0.0015-0.0024) for heterosexual men, and 0.0015 (0.00070-0.0021) for MSM. Discounted lifetime costs per incident infection were USD 261 (109-480), 169 (88-263), and 133 (50-239), respectively. At the population level, total discounted lifetime QALYs lost due to infections acquired during 2015 were 53,293 (12,326-125,366) for women, 621 (430-872) for heterosexual men, and 1,078 (427-1,870) for MSM. Total discounted lifetime costs were USD 150 million (64-277 million), 54 million (25-92 million), and 97 million (34-197 million), respectively. The highest total burden of both QALYs and costs at the population-level was observed in Non-Hispanic Black women, and highest burden per 1,000 person-years was identified in MSM among men and American Indian/Alaska Native among women. Interpretation: Gonorrhoea causes substantial health losses and costs in the United States. These results can inform planning and prioritization of prevention services. Funding: Centers for Disease Control and Prevention, Charles A. King Trust. © 2022 The Author(s)

BACKGROUND: As part of New York State's Ending the Epidemic (EtE) initiative, Sexual Health Clinics (SHCs) in New York City (NYC) invested in clinic enhancements and expanded their HIV-related services to increase access to HIV prevention interventions and treatment. The objective of this study was to estimate and describe the change in SHC operating costs related to clinic enhancements and expanded patient services implemented as part of the EtE initiative. METHODS: A comprehensive micro-costing approach was used to collect retrospective cost information from SHCs, broken down by category and programmatic activity. Cost information was collected from eight clinics across NYC during two 6-month time periods before (2015) and during (2018 - 2019) EtE. RESULTS: Eight SHCs reported comprehensive cost data. Costs increased by $800,000 on average per clinic during the 6-month EtE period. The cost per visit at a SHC increased by $120 on average to $381 (ranging from $302-$464) during the EtE period. Personnel costs accounted for 69.9% of EtE costs and HIV-related medications accounted for 8.9% of costs. Employment of social workers and patient navigators increased costs by approximately $150,000 on average per clinic. Post-exposure prophylaxis was the costliest medication with average expenditures of $103,800 per clinic. CONCLUSIONS: This study demonstrates the key drivers of cost increases when offering enhanced HIV services in SHCs. Documenting the changes in resources necessary to implement these services and their costs can inform other health departments on the viability of offering enhanced HIV services within their own clinics.

BACKGROUND: The purpose of this study was to estimate the health impact of syphilis in the United States in terms of the number of quality-adjusted life years (QALYs) lost attributable to infections in 2018. METHODS: We developed a Markov model which simulates the natural history and management of syphilis. The model was parameterized by sex and sexual orientation (women who have sex with men, men who have sex with women[MSW], and men who have sex with men[MSM]), and by age at primary infection. We developed a separate decision tree model to quantify health losses due to congenital syphilis. We estimated the average lifetime number of QALYs lost per infection, and the total expected lifetime number of QALYs lost due to syphilis acquired in 2018. RESULTS: We estimated the average number of discounted lifetime QALYs lost per infection as 0.09 [0.03-0.19 95% uncertainty interval (UI)]. The total expected number of QALYs lost due to syphilis acquired in 2018 was 13,349[5,071-31,360]. While per-case loss was the lowest among MSM(0.06), MSM accounted for 47.7% of the overall burden. For each case of congenital syphilis, we estimated 1.79[1.43-2.16] and 0.06[0.01-0.14] QALYs lost in the child and the mother, respectively. We projected 2,332[1,871-2,825] and 79[17-177] QALYs lost for children and mothers, respectively, due to congenital syphilis in 2018. CONCLUSIONS: Syphilis causes substantial health losses in adults and children. Quantifying these health losses in terms of QALYs can inform cost-effectiveness analyses and can facilitate comparisons of the burden of syphilis to that of other diseases.

Network approaches can be used to study sociosexual partnerships and identify individuals at high risk of infection. Little is known about the cost structure of these services and their association with STD diagnoses. METHOD: We collected costs associated with using a peer network strategy to recruit MSM and transwomen of color in 4 counties in North Carolina: Guilford, Forsyth, Durham, and Wake from February through October 2019. We used a comprehensive costing approach to gather detailed retrospective information on the intervention cost, broken down by category and programmatic activity. RESULTS: The sociosexual networks collected consisted of 31 initial seeds (index cases) and 49 peers of those seeds. In peers, 5 cases of HIV and 10 cases of syphilis were identified. The cost per case (HIV or syphilis) identified was $7,325. Personnel costs accounted for 80% of total expenditures, followed by laboratory expenses (12%). Personnel cost was distributed between DIS patient navigators (51%), non-clinical (37%), and management (12%) staff. General administration was the costliest programmatic activity (37%), followed by case management and field services (37%), and study activities (11%). The estimated average cost per patient tested was $2,242. CONCLUSIONS: Finding positive peer cases in non-clinical settings is costly but may be crucial for limiting the spread of sexually transmitted diseases. The cost of staff was the major driver. This study demonstrates that using a network strategy can be a cost-effective way to identify, test, and refer patients at high-risk of syphilis and HIV infections to care.

BACKGROUND: Despite declining HIV infection rates, persistent racial and ethnic disparities remain. Appropriate calculations of diagnosis rates by HIV transmission category, race and ethnicity, and geography are needed to monitor progress towards reducing systematic disparities in health outcomes. We estimated the number of heterosexually active adults (HAAs) by sex and state to calculate appropriate HIV diagnosis rates and disparity measures within subnational regions. METHODS: The analysis included all HIV diagnoses attributed to heterosexual transmission in 2018 in the United States, in 50 states and the District of Columbia. Logistic regression models estimated the probability of past-year heterosexual activity among adults in three national health surveys, by sex, age group, race and ethnicity, education category, and marital status. Model-based probabilities were applied to estimated counts of HAAs by state, which were synthesized through meta-analysis. HIV diagnoses were overlaid to calculate racial- and ethnic-specific rates, rate differences (RDs), and rate ratios (RRs) among HAAs by sex and state. RESULTS: Nationally, HAA women have a two-fold higher HIV diagnosis rate than HAA men (rate per 100,000 HAAs, women: 6.57; men: 3.09). Compared to White non-Hispanic HAAs, Black HAAs have a 20-fold higher HIV diagnosis rate (RR, men: 21.28, women: 19.55; RD, men: 15.40, women: 31.78) and Hispanic HAAs have a 4-fold higher HIV diagnosis rate (RR, men: 4.68, RD, women: 4.15; RD, men: 2.79, RD, women: 5.39). Disparities were ubiquitous across regions, with >75% of states in each region having Black-to-White RR ≥10. CONCLUSION: The racial and ethnic disparities across regions suggests a system-wide failure particularly with respect to preventing HIV among Black and Hispanic women. Pervasive disparities emphasize the role for coordinated federal responses such as the current Ending the HIV Epidemic (EHE) initiative.

BACKGROUND: Men who have sex with men (MSM) experience high rates of gonococcal infection at extragenital (rectal and pharyngeal) anatomic sites, which often are missed without asymptomatic screening and may be important for onward transmission. Implementing an express pathway for asymptomatic MSM seeking routine screening at their clinic may be a cost-effective way to improve extragenital screening by allowing patients to be screened at more anatomic sites through a streamlined, less costly process. METHODS: We modified an agent-based model of anatomic site-specific gonococcal infection in U.S. MSM to assess the cost-effectiveness of an express screening pathway in which all asymptomatic MSM presenting at their clinic were screened at the urogenital, rectal, and pharyngeal sites but forewent a provider consultation and physical exam and self-collected their own samples. We calculated the cumulative health effects expressed as gonococcal infections and cases averted over five years, labor and material costs, and incremental cost effectiveness ratios (ICER) for express versus traditional scenarios. RESULTS: The express scenario averted more infections and cases in each intervention year. The increased diagnostic costs of triple-site screening were largely offset by the lowered visit costs of the express pathway and, from the end of year 3 onward, this pathway generated small cost savings. However, in a sensitivity analysis of assumed overhead costs, cost savings under the express scenario disappeared in the majority of simulations once overhead costs exceeded 7% of total annual costs. CONCLUSIONS: Express screening may be a cost-effective option for improving multi-site anatomic screening among U.S. MSM.

BACKGROUND: Outreach screening is a common strategy for detecting cases of syphilis in high-risk populations. New rapid syphilis tests allow for quicker response times and may alter the costs of detecting and treating syphilis in non-clinical settings. METHODS: Between May and October of 2017, we collected detailed retrospective cost data from two outreach screening programs engaging people experiencing homelessness and LGBTQ populations. Comprehensive and retrospective cost information, disaggregated by cost category, programmatic activity, and source of support, was collected during and after the testing period. RESULTS: Across all sites, rapid syphilis tests were conducted on 595 people at an average cost of $213 per person. Twenty-three cases of syphilis were confirmed and treated for an average cost of $5,517 per case, ranging from $3,604 at a rehabilitation facility to $13,140 at LGBTQ venues served by a mobile clinic. Personnel contributed the most to total costs (56.4%), followed by supplies (12.8%) and the use of buildings (10.4%). Expenditures by programmatic activity varied substantially across sites. CONCLUSIONS: Testing costs varied between venues, reflecting differences in the models used and intensity of services provided. While staff costs are the major driver, buildings and supplies costs are also significant. Our findings suggest that outreach screenings using rapid syphilis tests may be a feasible and cost-effective tool for health departments when targeting known high-prevalence areas and hard to reach populations.

BACKGROUND: Men who have sex with men (MSM) are disproportionately burdened by gonorrhea and face high rates of extragenital (rectal and pharyngeal) infection, which is mostly asymptomatic and often missed by urogenital-only screening. Extragenital screening likely remains below CDC-recommended levels. Since increasing screening coverage is often resource-intensive, we assessed whether improved extragenital screening among men already presenting at clinics could lead to substantial reductions in prevalence and incidence. METHODS: We calibrated an agent-based model of site- and race-specific gonorrhea infection in MSM to explicitly model multi-site infection within an individual and transmission via anal, orogenital, and ororectal sex. Compared to current screening levels, we assessed the impact of increasing screening at 1) both extragenital sites, 2) only the rectal site, and 3) only the pharyngeal site among men already being urogenitally screened. RESULTS: All scenarios reduced prevalence and incidence, with improved screening at both extragenital sites having the largest effect across outcomes. Extragenitally screening 100% of men being urogenitally screened reduced site-specific prevalence by an average of 42% (black MSM) and 50% (white MSM), with these values dropping by approximately 10% and 20% for each race group when targeting only the rectum and only the pharynx, respectively. However, increasing only rectal screening was more efficient in terms of the number of screens needed to avert an infection as this avoided duplicative screens due to rectum/pharynx multi-site infection. CONCLUSIONS: Improved extragenital screening substantially reduced site-specific gonorrhea prevalence and incidence, with strategies aimed at increasing rectal screening proving the most efficient.

BACKGROUND: The purpose of this article was to describe methods that sexually transmitted disease (STD) programs can use to estimate the potential effects of changes in their budgets in terms of disease burden and direct medical costs. METHODS: We proposed 2 distinct approaches to estimate the potential effect of changes in funding on subsequent STD burden, one based on an analysis of state-level STD prevention funding and gonorrhea case rates and one based on analyses of the effect of Disease Intervention Specialist (DIS) activities on gonorrhea case rates. We also illustrated how programs can estimate the impact of budget changes on intermediate outcomes, such as partner services. Finally, we provided an example of the application of these methods for a hypothetical state STD prevention program. RESULTS: The methods we proposed can provide general approximations of how a change in STD prevention funding might affect the level of STD prevention services provided, STD incidence rates, and the direct medical cost burden of STDs. In applying these methods to a hypothetical state, a reduction in annual funding of US $200,000 was estimated to lead to subsequent increases in STDs of 1.6% to 3.6%. Over 10 years, the reduction in funding totaled US $2.0 million, whereas the cumulative, additional direct medical costs of the increase in STDs totaled US $3.7 to US $8.4 million. CONCLUSIONS: The methods we proposed, though subject to important limitations, can allow STD prevention personnel to calculate evidence-based estimates of the effects of changes in their budget.

BACKGROUND: Governments and international donors have partnered to provide free HIV treatment to over 6 million individuals in low and middle-income countries. Understanding the determinants of HIV treatment costs will help improve efficiency and provide greater certainty about future resource needs. METHODS AND FINDINGS: We collected data on HIV treatment costs from 54 clinical sites in Botswana, Ethiopia, Mozambique, Nigeria, Uganda, and Vietnam. Sites provided free HIV treatment funded by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), national governments, and other partners. Service delivery costs were categorized into successive six-month periods from the date when each site began HIV treatment scale-up. A generalized linear mixed model was used to investigate relationships between site characteristics and per-patient costs, excluding ARV expenses. With predictors at their mean values, average annual per-patient costs were $177 (95% CI: 127-235) for pre-ART patients, $353 (255-468) for adult patients in the first 6 months of ART, and $222 (161-296) for adult patients on ART for >6 months (excludes ARV costs). Patient volume (no. patients receiving treatment) and site maturity (months since clinic began providing treatment services) were both strong independent predictors of per-patient costs. Controlling for other factors, costs declined by 43% (18-63) as patient volume increased from 500 to 5,000 patients, and by 28% (6-47) from 5,000 to 10,000 patients. For site maturity, costs dropped 41% (28-52) between months 0-12 and 25% (15-35) between months 12-24. Price levels (proxied by per-capita GDP) were also influential, with costs increasing by 22% (4-41) for each doubling in per-capita GDP. Additionally, the frequency of clinical follow-up, frequency of laboratory monitoring, and clinician-patient ratio were significant independent predictors of per-patient costs. CONCLUSIONS: Substantial reductions in per-patient service delivery costs occur as sites mature and patient cohorts increase in size. Other predictors suggest possible strategies to reduce per-patient costs.

PEPFAR, national governments, and other stakeholders are investing unprecedented resources to provide HIV treatment in developing countries. This study reports empirical data on costs and cost trends in a large sample of HIV treatment sites.In 2006-2007, we conducted cost analyses at 43 PEPFAR-supported outpatient clinics providing free comprehensive HIV treatment in Botswana, Ethiopia, Nigeria, Uganda, and Vietnam.We collected data on HIV treatment costs over consecutive 6-month periods from scale-up of dedicated HIV treatment services at each site. The study included all patients receiving HIV treatment and care at study sites (62,512 ART and 44,394 pre-ART patients). Outcomes were costs per-patient and total program costs, subdivided by major cost categories.Median annual economic costs were $202 (2009 USD) for pre-ART patients and $880 for ART patients. Excluding ARVs, per-patient ART costs were $298. Care for newly initiated ART patients cost 15-20% more than for established patients. Per-patient costs dropped rapidly as sites matured, with per-patient ART costs dropping 46.8% between first and second 6-month periods after the beginning of scale-up, and an additional 29.5% the following year. PEPFAR provided 79.4% of funding for service delivery, and national governments provided 15.2%.Treatment costs vary widely between sites, and high early costs drop rapidly as sites mature. Treatment costs vary between countries and respond to changes in ARV regimen costs and the package of services. While cost reductions may allow near-term program growth, programs need to weigh the trade-off between improving services for current patients and expanding coverage to new patients.

BACKGROUND: The U.S. President's Emergency Plan for AIDS Relief (PEPFAR) has supported the extension of HIV care and treatment to 2.4 million individuals as of September 2009. With increasing resources targeted toward rapid scale-up, it is important to understand the characteristics of current PEPFAR-supported HIV care and treatment sites. METHODS: Forty-five sites in Botswana, Ethiopia, Nigeria, Uganda, and Vietnam were sampled. Data were collected retrospectively from successive 6-month periods through reviews of facility records and interviews with site personnel between April 2006 and March 2007. Facility size and scale-up rate, patient characteristics, staffing models, clinical and laboratory monitoring, and intervention mix were compared. RESULTS: Sites added a median of 293 patients per quarter. By the evaluation's end, sites supported a median of 1,649 HIV patients, 922 of them receiving antiretroviral therapy (ART). Patients were predominantly adult (97.4%) and the majority (96.5%) were receiving regimens based on nonnucleoside reverse transcriptase inhibitors (NNRTIs). The ratios of physicians to patients dropped substantially as sites matured. ART patients were commonly seen monthly or quarterly for clinical and laboratory monitoring, with CD4 counts being taken at 6-month intervals. One-third of sites provided viral load testing. Cotrimoxazole prophylaxis was the most prevalent supportive service. CONCLUSIONS: HIV treatment sites scaled up rapidly with the influx of resources and technical support through PEPFAR, providing complex health services to progressively expanding patient cohorts. Human resources are stretched thin, and delivery models and intervention mix differ widely between sites. Ongoing research is needed to identify best-practice service delivery models.