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Background: Opioid overdose mortality in the US has exceeded one million deaths over the last two decades. A regulated opioid supply may help prevent future overdose deaths by reducing exposure to the unregulated opioid supply. We examined the acceptability, delivery model preference, and anticipated effectiveness of different regulated opioid models among people in the Seattle area who inject opioids., Methods: We enrolled people who inject drugs in the 2022 Seattle-area National HIV Behavior Surveillance (NHBS) survey. Participants were recruited between July and December 2022 using respondent-driven sampling. Participants who reported injecting opioids (N = 453) were asked whether regulated opioids would be acceptable, their preferred model of receiving regulated opioids, and the anticipated change in individual overdose risk from accessing a regulated opioid supply., Results: In total, 369 (81 %) participants who injected opioids reported that a regulated opioid supply would be acceptable to them. Of the 369 who found a regulated opioid supply to be acceptable, the plurality preferred a take-home model where drugs are prescribed (35 %), followed closely by a dispensary model that required no prescription (28 %), and a prescribed model where drugs need to be consumed on site (13 %), a model where no prescription is required and drugs can be accessed in a community setting with a one-time upfront payment was the least preferred model (5 %). Most participants (69 %) indicated that receiving a regulated opioid supply would be "a lot less risky" than their current supply, 20 % said, "a little less risky", 10 % said no difference, and 1 % said a little or a lot more risky., Conclusion: A regulated opioid supply would be acceptable to most participants, and participants reported it would greatly reduce their risk of overdose. As overdose deaths continue to increase in Washington state pragmatic and effective solutions that reduce exposure to unregulated drugs are needed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study measures changes in condomless anal sex (CAS) among HIV-negative men who have sex with men (MSM) who are not taking pre-exposure prophylaxis (PrEP). It considers the 2014-2019 cycles of the American Men's Internet Survey, a serial, cross-sectional web-based survey of US cisgender MSM aged ≥ 15 years, in which ~ 10% of each year's sample is drawn from the previous year. Among those surveyed for 2 years who remained HIV-negative and off PrEP, reports of having any CAS and of CAS partner number were compared across years. We disaggregated by partner HIV status, and considered demographic predictors. The overall population saw a significant 2.2 percentage-point (pp) increase in reports of any CAS year-over-year. Sub-populations with the largest year-on-year increases were 15-24-year-olds (5.0-pp) and Hispanic respondents (5.1-pp), with interaction (young Hispanic respondents = 12.8-pp). On the relative scale, these numbers correspond to 3.2%, 7.2%, 7.3% and 18.7%, respectively. Absolute increases were concentrated among partners reported as HIV-negative. Multivariable analyses for CAS initiation found effects concentrated among Hispanic and White youth and residents of fringe counties of large metropolitan areas. CAS partner number increases were similarly predicted by Hispanic identity and young age. Although condom use remains more common than PrEP use, increasing CAS among MSM not on PrEP suggests potential new HIV transmission pathways. Concentration of increases among 18-24-year-old MSM portends future increases in the proportion of newly diagnosed HIV that occur among youth. Concentration among young Hispanic MSM will likely expand existing disparities. Although reducing barriers to PrEP remains vital, condom promotion for MSM remains a key public health practice and appears to be missing key audiences. LGBTQ+-inclusive sex education is one avenue for enhancing these efforts., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Temporal exponential-family random graph models (TERGMs) are a flexible class of models for network ties that change over time. Separable TERGMs (STERGMs) are a subclass of TERGMs in which the dynamics of tie formation and dissolution can be separated within each discrete time step and may depend on different factors. The Carnegie et al. (2015) approximation improves estimation efficiency for a subclass of STERGMs, allowing them to be reliably estimated from inexpensive cross-sectional study designs. This approximation adapts to cross-sectional data by attempting to construct a STERGM with two specific properties: a cross-sectional equilibrium distribution defined by an exponential-family random graph model (ERGM) for the network structure, and geometric tie duration distributions defined by constant hazards for tie dissolution. In this paper we focus on approaches for improving the behavior of the Carnegie et al. approximation and increasing its scope of application. We begin with Carnegie et al.'s observation that the exact result is tractable when the ERGM is dyad-independent, and then show that taking the sparse limit of the exact result leads to a different approximation than the one they presented. We show that the new approximation outperforms theirs for sparse, dyad-independent models, and observe that the errors tend to increase with the strength of dependence for dyad-dependent models. We then develop theoretical results in the dyad-dependent case, showing that when the ERGM is allowed to have arbitrary dyad-dependent terms and some dyad-dependent constraints, both the old and new approximations are asymptotically exact as the size of the STERGM time step goes to zero. We note that the continuous-time limit of the discrete-time approximations has the desired cross-sectional equilibrium distribution and exponential tie duration distributions with the desired means. We show that our results extend to hypergraphs, and we propose an extension of the Carnegie et al. framework to dissolution hazards that depend on tie age., Competing Interests: 6Declaration of Interest Statement The authors report there are no competing interests to declare.

Background: The "Ending the HIV Epidemic" (EHE) initiative seeks to reduce new HIV infections in the U.S. by prioritizing federal resources towards highly impacted populations. Antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) are essential for reaching EHE goals. Adolescents are often at increased risk for HIV because they may lack agency in negotiating their sexual partnerships and may not have the same access to treatment and prevention as adults. This study estimates the potential contribution of expanded PrEP coverage among adolescents ages 15-17 to achieving the EHE goals in the South., Methods: An HIV-transmission model was built to simulate the HIV epidemic in the South. Increased ART and PrEP uptake were systematically varied with and without PrEP eligibility including individuals age<18., Results: Prioritizing PrEP for adolescents had a negligible impact on incidence. At 50% uptake among eligible adolescents and 90% ART coverage, including adolescents only improved the percentage of infections averted from 80.1% to 80.3%. In 10 of 15 scenarios explored, there was no reduction in new infections when PrEP eligibility was expanded to include adolescents age<18. At 95% ART coverage at the population-level incidence among adolescents declined by over 80%, but PrEP uptake among adolescents did not contribute to additional declines in incidence among adolescents., Conclusions: Prioritizing PrEP for adolescents did not significantly contribute to reaching EHE incidence reductions goal. Focusing resources to specific adolescent populations at risk, such sexual minority males in high incidence settings, will remain an important public health goal outside the context of EHE., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: Oral and anal sex with opposite-sex partners is common and associated with sexually transmitted infection (STI) transmission. Trends in these behaviors over the last decade, during which bacterial STI diagnoses have reached historic highs while HIV diagnoses have decreased, are not well understood. We examined recent trends in oral and anal sex and associated condom use with opposite-sex partners among females and males., Methods: We analyzed data from 16,926 female and 13,533 male respondents aged 15 to 44 years who reported sex with an opposite-sex partner in the past 12 months from the National Survey of Family Growth, 2011-2019. We used survey-weighted linear or logistic regression to evaluate linear temporal trends in oral and anal sex behaviors., Results: From 2011-2013 to 2017-2019, reports of oral sex and number of oral sex partners in the past 12 months increased among females (85.4% in 2011-2013 to 89.4% in 2017-2019; odds ratio [OR], 1.05 [95% confidence interval {CI}, 1.02-1.09], and β = 0.014 [95% CI, 0.005-0.023]; respectively) but not males (ranges, 87.9%-89.1%; 1.27-1.31). Condom use at last oral sex decreased among both females and males (6.3%-4.3%: OR, 0.93 [95% CI, 0.88-0.99]; 5.9%-4.4%: OR, 0.95 [95% CI, 0.91-1.00]). Anal sex (ranges, 21.0%-23.3% [females] and 23.3%-24.6% [males]), number of anal sex partners (females, 0.22-0.25; males, 0.26-0.30), and condom use at last anal sex (females, 15.3%-18.2%; males, 27.0%-28.7%) remained stable., Conclusions: The frequency of oral and anal sex with opposite-sex partners among U.S. 15- to 44-year-olds, paired with limited and-for oral sex-decreasing condom use, demonstrates the need to understand the role of these behaviors in increasing STI diagnosis rates and the potential role of extragenital screening and condoms in reducing STI transmission., Competing Interests: Conflict of Interest and Sources of Funding: None reported., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Sexually Transmitted Diseases Association.)

Pathogens face a tradeoff with respect to virulence; while more virulent strains often have higher per-contact transmission rates, they are also more likely to kill their hosts earlier. Because virulence is a heritable trait, there is concern that a disease-modifying vaccine, which reduces the disease severity of an infected vaccinee without changing the underlying pathogen genotype, may result in the evolution of higher pathogen virulence. We explored the potential for such virulence evolution with a disease-modifying HIV-1 vaccine in an agent-based stochastic epidemic model of HIV in United States men who have sex with men (MSM). In the model, vaccinated agents received no protection against infection, but experienced lower viral loads and slower disease progression. We compared the genotypic set point viral load (SPVL), a measure of HIV virulence, in populations given vaccines that varied in the degree of SPVL reduction they induce. Sensitivity analyses were conducted under varying vaccine coverage scenarios. With continual vaccination rollout under ideal circumstances of 90 % coverage over thirty years, the genotypic SPVL of vaccinated individuals evolved to become greater than the genotypic SPVL of unvaccinated individuals. This virulence evolution in turn diminished the public health benefit of the vaccine, and in some scenarios resulted in an accelerated epidemic. These findings demonstrate the complexity of viral evolution and have important implications for the design and development of HIV vaccines., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Sexually transmitted infections pose a major public health challenge in the United States and this burden is especially acute in subpopulations like young men who have sex with men (YMSM) and young transgender women (YTW). Yet, the direct behavioral antecedents of these infections are not well understood making it difficult to identify the cause of recent increases in incidence. This study examines how variations in partnership rates and the number of condomless sex acts are associated with STI infections among YMSM-YTW., Method: This study leveraged 3 years of data from a large longitudinal cohort of YMSM-YTW. A series of generalized linear mixed models examined the association between the number of condomless anal sex acts, number of one-time partners, number of casual partners, and number of main partners and chlamydia, gonorrhea, or any STI., Results: Results indicated the number of casual partners was associated with gonorrhea [aOR = 1.17 (95% CI: 1.08, 1.26)], chlamydia [aOR = 1.12 (95% CI: 1.05, 1.20)], and any STI [aOR = 1.14 (95% CI: 1.08, 1.21)] while the number of one-time partners was only associated with gonorrhea [aOR = 1.13 (95% CI: 1.02, 1.26)]. The number of condomless anal sex acts was not associated with any outcome., Conclusion: These findings suggest the number of casual partners is a consistent predictor of STI infection among YMSM-YTW. This may reflect the quick saturation of risk within partnerships making the number of partners, rather than the number of acts, the more relevant factor for STI risk.

Background: Up to 69% of adults who acquire HIV in Kenya seek care for acute retroviral symptoms, providing an important opportunity for early diagnosis and HIV care engagement. The Tambua Mapema Plus (TMP) trial tested a combined HIV-1 nucleic acid testing, linkage, treatment, and partner notification intervention for adults with symptoms of acute HIV infection presenting to health facilities in coastal Kenya. We estimated the potential impact on the Kenyan HIV epidemic of providing PrEP to individuals testing negative in TMP, if scaled up., Methods: We developed an agent-based simulation of HIV-1 transmission using TMP data and current Kenyan statistics. PrEP interventions were layered onto a model of TMP as standard of care, to estimate additional potential population-level impact of enrolling HIV-negative individuals identified through TMP on PrEP over 10 years. Four scenarios were modeled: PrEP for uninfected individuals in disclosed serodiscordant couples; PrEP for individuals with concurrent partnerships; PrEP for all uninfected individuals identified through TMP; and PrEP integrated into the enhanced partner services component of TMP., Findings: Providing PrEP to both individuals with concurrent partnerships and uninfected partners identified through enhanced partner services reduced new HIV infections and was efficient based on numbers needed to treat (NNT). The mean percent of infections averted was 2.79 (95%SI:-10.83, 15.24) and 4.62 (95%SI:-9.5, 16.82) when PrEP uptake was 50% and 100%, respectively, and median NNT was 22.54 (95%SI:not defined, 6.45) and 27.55 (95%SI:not defined, 11.0), respectively. Providing PrEP for all uninfected individuals identified through TMP averted up to 12.68% (95%SI:0.17, 25.19) of new infections but was not efficient based on the NNT: 200.24 (95%SI:523.81, 123.23)., Conclusions: Providing PrEP to individuals testing negative for HIV-1 nucleic acid after presenting to a health facility with symptoms compatible with acute HIV adds value to the TMP intervention, provided PrEP is targeted effectively and efficiently., Funding: National Institutes of Health, Sub-Saharan African Network for TB/HIV Research Excellence., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Antiretroviral medication coverage remains sub-optimal in much of the United States, particularly the Sothern region, and Non-Hispanic Black or African American persons (NHB) continue to be disproportionately impacted by the HIV epidemic. The "Ending the HIV Epidemic in the U.S." (EHE) initiative seeks to reduce HIV incidence nationally by focusing resources towards the most highly impacted localities and populations. This study evaluates the impact of hypothetical improvements in ART and PrEP coverage to estimate the levels of coverage needed to achieve EHE goals in the South., Methods: We developed a stochastic, agent-based network model of 500,000 individuals to simulate the HIV epidemic and hypothetical improvements in ART and PrEP coverage., Results: New infections declined by 78.6% at 90%/40% ART/PrEP and 94.3% at 100%/50% ART/PrEP. Declines in annual incidence rates surpassed 75% by 2025 with 90%/40% ART/PrEP and 90% by 2030 with 100%/50% ART/PrEP coverage. Increased ART coverage among NHB MSM was associated with a linear decline in incidence among all MSM. Declines in incidence among Hispanic/Latino and White/Other MSM were similar regardless of which MSM race group increased their ART coverage, while the benefit to NHB MSM was greatest when their own ART coverage increased. The incidence rate among NHB women declined by over a third when either NHB heterosexual men or NHB MSM increased their ART use respectively. Increased use of PrEP was associated with a decline in incidence for the groups using PrEP. MSM experienced the largest absolute declines in incidence with increasing PrEP coverage, followed by NHB women., Conclusions: Our analysis indicates that it is possible to reach EHE goals. The largest reductions in HIV incidence can be achieved by increasing ART coverage among MSM and all race groups benefit regardless of differences in ART initiation by race. Improving ART coverage to > 90% should be prioritized with a particular emphasis on reaching NHB MSM. Such a focus will reduce the largest number of incident cases, reduce racial HIV incidence disparities among both MSM and women, and reduce racial health disparities among persons with HIV. NHB women should also be prioritized for PrEP outreach., (© 2023. The Author(s).)

The COVID-19 pandemic has disrupted HIV prevention, care, and transmission opportunities. This likely varies by geography, given differences in COVID-19 burden and mandates over time, and by age, given different likelihoods of severe COVID-19 consequences. We consider changes in sexual behavior, HIV testing, pre-exposure prophylaxis (PrEP) use and antiretroviral therapy (ART) use among men who have sex with men (MSM) over the first year of the COVID-19 epidemic, comparing the Atlanta metropolitan area and New York City (NYC). We use two continuous time-series datasets and one panel dataset, assessing changes over time within city and comparing across cities, and disaggregate major findings by age. For clinical results, ART use showed by far the smallest reductions, and testing the largest. Disruptions occurred concurrently between cities, despite the major wave of COVID-19, and government mandates, occurring later in Atlanta. Test positivity increased in NYC only. In both cities, younger MSM saw the greatest reductions in testing and PrEP use, but the smallest in sexual behavior. Reduced clinical service usage would be unconcerning if stemming solely from reductions in exposure; however, the patterns for young MSM suggest that the COVID-19 epidemic likely generated new conditions for increased HIV transmission, especially in this cohort., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Rates of reported gonorrhea and chlamydial infections have increased substantially over the past decade in the USA and disparities persist across age and race/ethnicity. We aimed to understand potential changes in sexual behaviors, sexual network attributes, and sexually transmitted infection (STI) screening that may be contributing to these trends. We analyzed data from 29,423 female and 24,605 male respondents ages 15-44 years from the National Survey of Family Growth, 2008-2019. We used survey-weighted linear or logistic regression to evaluate linear temporal trends in sexual behaviors with opposite-sex partners, network attributes, and STI testing, treatment, and diagnosis. Significant declines were observed in condom use at last vaginal sex, mean number of vaginal sex acts, proportion of condom-protected sex acts in the past 4 weeks, and racial/ethnic homophily with current partners among males and females from 2008-2010 through 2017-2019. Among males, mean number of female partners in the past 12 months and concurrency also declined, while the percent reporting ever having sex with another male increased. Past-year testing for chlamydia and any STI increased among females. Research is needed to understand how these changes interact and potentially contribute to increasing reported gonorrhea and chlamydia diagnoses and identify avenues for future intervention., (© 2022. The Author(s).)

Study Objectives: Adolescent pregnancies and births in the United States have undergone dramatic declines in recent decades. We aimed to estimate the contribution of changes in 3 proximal behaviors to these declines among 14- to 18-year-olds for 2007-2017: 1) delays in age at first sexual intercourse, 2) declines in number of sexual partners, and 3) changes in contraceptive use, particularly uptake of long-acting reversible contraception (LARC)., Design: We adapted an existing iterative dynamic population model and parameterized it using 6 waves of the Centers for Disease Control and Prevention's Youth Risk Behavior Survey. We compared pregnancies from observed behavioral trends with counterfactual scenarios that assumed constant behaviors over the decade. We calculated outcomes by cause, year, and age., Results: We found that changes in these behaviors could explain pregnancy reductions of 496,200, 78,500, and 40,700 over the decade, respectively, with total medical and societal cost savings of $9.71 billion, $1.54 billion, and $796 million. LARC adoption, particularly among 18-year-olds, could explain much of the improvement from contraception use. The 3 factors together did not fully explain observed birth declines; adding a 50% decline in sex acts per partner did., Conclusions: Delays in first sexual intercourse contributed the most to declining births over this decade, although all behaviors considered had major effects. Differences from earlier models could result from differences in years and ages covered. Evidence-based teen pregnancy prevention programs, including comprehensive sex education, youth-friendly reproductive health services, and parental and community support, can continue to address these drivers and reduce teen pregnancy., (Copyright © 2022. Published by Elsevier Inc.)

Background: Mean active degree is an important proxy measure of cross-sectional network connectivity commonly used in HIV/sexually transmitted infection epidemiology research. No current studies have compared measurement methods of mean degree using a cross-sectional study design for men who have sex with men (MSM) in the United States. We compared mean degree estimates based on reported ongoing main and casual sexual partnerships (current method) against dates of first and last sex (retrospective method)., Methods: We used data from ARTnet, a cross-sectional survey of MSM in the United States (2017-2019). ARTnet collected data on the number and types of sexual partners in the past year, limited to the 5 most recent partners (data truncation). We quantified partnerships for months 0 to 12 before the survey date (retrospective method) and compared that with ongoing partnerships on the day of survey (current method). We used linear regression to understand the impact of truncated partnership data on mean degree estimation., Results: The retrospective method yielded similar degree estimates to the current for months proximate to the day of survey. The retrospective method mean degree systematically decreased as the month increased from 0 to 12 months before survey date. This was driven by data truncation: among participants with >5 partners in the past year compared with those with ≤5, the average change in main partnership degree between 12 and 0 months before survey date was -0.05 (95% confidence interval, -0.08 to -0.03) after adjusting for race/ethnicity, age, and education. The adjusted average change in casual partnership degree was -0.40 (95% confidence interval, -0.45 to -0.35)., Conclusions: The retrospective method underestimates mean degree for MSM in surveys with truncated partnership data, especially for casual partnerships. The current method is less prone to bias from partner truncation when the target population has high rate of partners per year., Competing Interests: Conflict of Interest and Sources of Funding: The authors declare no conflicts of interest., (Copyright © 2022 American Sexually Transmitted Diseases Association. All rights reserved.)

Background: Set-point viral load (SPVL) correlates with the age at which people acquire HIV. Although immunosenescence may seem like a parsimonious explanation for this, it does not easily explain the observation that the relationship between age and SPVL attenuates when accounting for source partner SPVL. Here we propose an alternative explanation that encompasses this latter finding: that decreasing risk of acquisition with older age generates a selection bottleneck that selects for more virulent strains with age., Methods: We adapted a previously published model of HIV transmission and evolution (EvoNetHIV), parameterized here for men who have sex with men (MSM). We conducted a series of simulation experiments that vary seven behavioral or clinical parameters that affect exposure risk as people age. We conducted regressions to determine the mean increase in SPVL per 10-year increase in seroconversion age, with and without source SPVL in the model., Results: All runs generated significant relationships between seroconversion age and SPVL when not including source SPVL. All saw attenuated relationships, most to near 0, with source SPVL included. Four of our behavioral measures (relational duration, age-related homophily, coital frequency, and mean age at relationship formation) had clear effects on this relationship, all in the hypothesized direction. Combining multiple forms of behavioral heterogeneity yielded an increase of 0.056 log10 copies/mL SPVL per 10-year increase in seroconversion age, nearly as large as that seen in two empirical studies of age-SPVL correlations in MSM., Conclusion: The higher virulence of HIV among those infected later in life may be partly explained by a combination of selective bottlenecks and behavioral heterogeneity by age. Variation in the strength of this effect across populations may be in part due to different behavioral, epidemiological and clinical conditions, and not require assumptions about differences in patterns of immunosenescence among populations., Competing Interests: Declaration of Competing Interest GSG has received research grants and research support from the US National Institutes of Health, University of Washington, Bill and Melinda Gates Foundation, Gilead Sciences, Alere Technologies, Merck & Co., Inc., Janssen Pharmaceutica, Cerus Corporation, ViiV Healthcare, Bristol-Myers Squibb, Thera technologies/TAI Med Biologics and Abbott Molecular Diagnostics., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate if community-level HIV PrEP coverage is correlated with individual sexual behaviors., Design: We used demographic, behavioral, and sexual network data from ARTnet, a 2017-2019 study of United States MSM., Methods: Multivariable regression models with a Bayesian modeling framework were used to estimate associations between area-level PrEP coverage and seven sexual behavior outcomes [number of total, main, and casual male partners (network degree); count of one-time partnerships; consistent condom use in one-time partnerships; and frequency of casual partnership anal sex (total and condomless)], controlling for individual PrEP use., Results: PrEP coverage ranged from 10.3% (Philadelphia) to 38.9% (San Francisco). Total degree was highest in Miami (1.35) and lowest in Denver (0.78), while the count of one-time partners was highest in San Francisco (11.7/year) and lowest in Detroit (1.5/year). Adjusting for individual PrEP use and demographics, community PrEP coverage correlated with total degree [adjusted incidence rate ratio (aIRR) = 1.73; 95% credible interval (CrI), 0.92-3.44], casual degree (aIRR = 2.05; 95% CrI, 0.90-5.07), and count of one-time partnerships (aIRR = 1.90; 95% CrI, 0.46-8.54). Without adjustment for individual PrEP use, these associations strengthened. There were weaker or no associations with consistent condom use in one-time partnerships (aIRR = 1.68; 95% CrI, 0.86-3.35), main degree (aIRR = 1.21; 95% CrI, 0.48-3.20), and frequency of casual partnership condomless anal sex (aIRR = 0.23; 95% CrI, 0.01-3.60)., Conclusion: Most correlations between community PrEP coverage and sexual behavior were explained by individual PrEP use. However, some residual associations remained after controlling for individual PrEP use, suggesting that PrEP coverage may partially drive community-level differences in sexual behaviors., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Detection of acute and prevalent HIV infection using point-of-care nucleic acid amplification testing (POC-NAAT) among outpatients with symptoms compatible with acute HIV is critical to HIV prevention, but it is not clear if it is cost-effective compared with existing HIV testing strategies., Methods: We developed and parametrised a decision tree to compare the cost-effectiveness of (1) provider-initiated testing and counselling (PITC) using rapid tests, the standard of care; (2) scaled-up provider-initiated testing and counselling (SU-PITC) in which all patients were tested with rapid tests unless they opted out; and (3) opt-out testing and counselling using POC-NAAT, which detects both acute and prevalent infection. The model-based analysis used data from the Tambua Mapema Plus randomised controlled trial of a POC-NAAT intervention in Kenya, supplemented with results from a stochastic, agent-based network model of HIV-1 transmission and data from published literature. The analysis was conducted from the perspective of the Kenyan government using a primary outcome of cost per disability-adjusted life-year (DALY) averted over a 10-year time horizon., Results: After analysing the decision-analytical model, the average per patient cost of POC-NAAT was $214.9 compared with $173.6 for SU-PITC and $47.3 for PITC. The mean DALYs accumulated per patient for POC-NAAT were 0.160 compared with 0.176 for SU-PITC and 0.214 for PITC. In the incremental analysis, SU-PITC was eliminated due to extended dominance, and the incremental cost-effectiveness ratio (ICER) comparing POC-NAAT to PITC was $3098 per DALY averted. The ICER was sensitive to disability weights for HIV/AIDS and the costs of antiretroviral therapy., Conclusion: POC-NAAT offered to adult outpatients in Kenya who present for care with symptoms compatible with AHI is cost-effective and should be considered for inclusion as the standard of HIV testing in this population., Trial Registration Number: Tambua Mapema ("Discover Early") Plus study (NCT03508908) conducted in Kenya (2017-2020) i.e., Post-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: Up to 69% of adults who acquire HIV in Kenya seek care before seroconversion, providing an important opportunity for early diagnosis and treatment. The Tambua Mapema Plus (TMP) trial tested a combined HIV-1 nucleic acid testing, linkage, treatment, and partner notification intervention for adults aged 18-39 years with symptoms of acute HIV infection presenting to health facilities in coastal Kenya. We estimated the potential impact of TMP on the Kenyan HIV epidemic., Methods: We developed an agent-based network model of HIV-1 transmission using TMP data and Kenyan statistics to estimate potential population-level impact of targeted facility-based testing over 10 years. Three scenarios were modeled: standard care [current use of provider-initiated testing and counseling (PITC)], standard HIV rapid testing scaled to higher coverage obtained in TMP (scaled-up PITC), and the TMP intervention., Results: Standard care resulted in 90.7% of persons living with HIV (PLWH) knowing their status, with 67.5% of those diagnosed on treatment. Scaled-up PITC resulted in 94.4% of PLWH knowing their status and 70.4% of those diagnosed on treatment. The TMP intervention achieved 97.5% of PLWH knowing their status and 80.6% of those diagnosed on treatment. The percentage of infections averted was 1.0% (95% simulation intervals: -19.2% to 19.9%) for scaled-up PITC and 9.4% (95% simulation intervals: -8.1% to 24.5%) for TMP., Conclusion: Our study suggests that leveraging new technologies to identify acute HIV infection among symptomatic outpatients is superior to scaled-up PITC in this population, resulting in >95% knowledge of HIV status, and would reduce new HIV infections in Kenya., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: In sub-Saharan Africa, adult outpatients with symptoms of acute infectious illness are not routinely tested for prevalent or acute HIV infection (AHI) when seeking healthcare., Methods: Adult symptomatic outpatients aged 18-39 years were evaluated by a consensus AHI risk score. Patients with a risk score ≥ 2 and no previous HIV diagnosis were enrolled in a stepped-wedge trial of opt-out delivery of point-of-care (POC) HIV-1 nucleic acid testing (NAAT), compared with standard provider-initiated HIV testing using rapid tests in the observation period. The primary outcome was the number of new diagnoses in each study period. Generalized estimating equations with a log-binomial link and robust variance estimates were used to account for clustering by health facility. The trial is registered with ClinicalTrials.gov NCT03508908., Results: Between 2017 and 2020, 13 (0.9%) out of 1374 participants in the observation period and 37 (2.5%) out of 1500 participants in the intervention period were diagnosed with HIV infection. Of the 37 newly diagnosed cases in the intervention period, two (5.4%) had AHI. Participants in the opt-out intervention had a two-fold greater odds of being diagnosed with HIV (odds ratio = 2.2, 95% confidence interval: 1.39-3.51) after adjustment for factors imbalanced across study periods., Conclusions: Among symptomatic adults aged 18-39 years targeted by our POC NAAT intervention, we identified one chronic HIV infection for every 40 patients and one AHI patient for every 750 patients tested. Although AHI yield was low in this population, routinely offered opt-out testing could diagnose twice as many patients as an approach relying on provider discretion., (© 2021 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Seroadaptive behaviors help reduce HIV risk for some men who have sex with men (MSM), and have been well documented across MSM populations. Advancements in biomedical prevention have changed the contexts in which seroadaptive behaviors occur. We thus sought to estimate and compare the prevalence of four stages of the "seroadaptive cascade" by PrEP use in the recent era: knowledge of own serostatus, knowledge of partner serostatus; serosorting (matching by status), and condomless anal intercourse. Serosorting overall appeared to remain common, especially with casual and one-time partners. Although PrEP use did not impact status discussion, it did impact serosorting and the likelihood of having condomless anal intercourse. For respondents not diagnosed with HIV and not on PrEP, condomless anal intercourse occurred in just over half of relationships with HIV-positive partners who were not on treatment. Biomedical prevention has intertwined with rather than supplanted seroadaptive behaviors, while contexts involving neither persist., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: HIV testing is the gateway to HIV treatment and prevention. HIV self-testing (HIVST) has potential to increase testing; however, the potential population-level impact of HIVST on the HIV epidemic and the best strategies for promoting HIVST are unknown. Our aim is to inform public health approaches for promoting HIVST as part of a comprehensive strategy to reduce HIV incidence., Methods: Stochastic network-based HIV transmission models were used to estimate how different HIVST strategies would affect HIV incidence in Seattle and Atlanta over 10 years. We included four types of HIV testers and implemented nine replacement and eleven supplementation strategies for HIVST., Results: Replacement of clinic-based tests with HIVST increased HIV incidence in Seattle and Atlanta. The benefits of supplementary strategies depended on the tester type using HIVST. Targeting non-testers averted the highest number of cases per test. In Seattle 2.2 (95%SI=-77, 100.4) and 4.7 (95%SI=-35.7, 60.1) infections were averted per 1000 HIVST when non-testers used HIVST once or twice per year respectively. In Atlanta the comparable rates were 8.0 (95%SI=-60.3 to 77.7) and 6.7 (95%SI=-37.7, 41.0). Paradoxically, increasing testing among risk-based testers using HIVST increased incidence., Conclusions: The population-level impact of HIVST depends on who is reached with HIVST, how kits are used, and by characteristics of the underlying epidemic and HIV care infrastructure. Targeted HIVST can be an effective component of a comprehensive HIV testing strategy. More work is needed to understand how to identify and target non-testers for self-testing implementation., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: We examined condom use patterns and potential population-level effects of a hypothetical condom intervention on human immunodeficiency virus (HIV) transmission among adolescent sexual minority males (ASMM)., Methods: Using 3 data sets: national Youth Risk Behavior Survey 2015 to 2017 (YRBS-National), local YRBS data from 8 jurisdictions with sex of partner questions from 2011 to 2017 (YRBS-Trends), and American Men's Internet Survey (AMIS) 2014 to 2017, we assessed associations of condom use with year, age, and race/ethnicity among sexually active ASMM. Using a stochastic agent-based network epidemic model, structured and parameterized based on the above analyses, we calculated the percent of HIV infections averted over 10 years among ASMM ages 13 to 18 years by an intervention that increased condom use by 37% for 5 years and was delivered to 62% of ASMM at age 14 years., Results: In YRBS, 51.8% (95% confidence interval [CI], 41.3-62.3%) and 37.9% (95% CI, 32.7-42.3%) reported condom use at last sexual intercourse in national and trend data sets, respectively. In AMIS, 47.3% (95% CI, 44.6-49.9%) reported condom use at last anal sex with a male partner. Temporal trends were not observed in any data set (P > 0.1). Condom use varied significantly by age in YRBS-National (P < 0.0001) and YRBS-Trends (P = 0.032) with 13- to 15-year-olds reporting the lowest use in both; age differences were not significant in AMIS (P = 0.919). Our hypothetical intervention averted a mean of 9.0% (95% simulation interval, -5.4% to 21.2%) of infections among ASMM., Conclusions: Condom use among ASMM is low and appears to have remained stable during 2011 to 2017. Modeling suggests that condom use increases, consistent with previous interventions, have potential to avert 1 in 11 new HIV infections among ASMM., Competing Interests: Conflict of Interest: None declared., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Sexually Transmitted Diseases Association.)

Introduction: HIV pre-exposure prophylaxis (PrEP) is effective in preventing HIV transmission. United States Public Health Service (USPHS) clinical practice guidelines define biobehavioral indications for initiation. To assess guideline implementation, it is critical to quantify PrEP nonusers who are indicated and PrEP users who are not indicated. We sought to estimate current PrEP use among US men who have sex with men (MSM), characterize whether their PrEP use aligned with their current indications for PrEP, and assess whether the association between PrEP indications and PrEP use differed by demography or geography., Methods: Using data from a US web-based sexual network study of MSM between 2017 and 2019, we measured PrEP usage and assessed whether respondents met indications for PrEP. Log-binomial regression was used to estimate the relationship between PrEP indications and PrEP use, with adjustment for geography, age and race/ethnicity., Results: Of 3508 sexually active, HIV-negative MSM, 34% met indications for PrEP. The proportion with current PrEP use was 32% among MSM meeting indications and 11% among those without indications. Nearly 40% of those currently using PrEP did not meet indications for PrEP, and 68% of MSM with indications for PrEP were not currently using PrEP. After adjusting for geography and demographics, MSM with PrEP indications were about three times as likely to be currently using PrEP. This association varied slightly, but not significantly, by geographic region, age and race/ethnicity., Conclusions: Indications for PrEP strongly predicted current PrEP use among US MSM. However, we identified substantial misalignment between indications and use in both directions (indicated MSM who were not benefitting from PrEP, and MSM taking PrEP while not presently being indicated). PrEP underuse by those at greatest risk for HIV acquisition may limit the projected impact of PrEP implementation, despite reported increases in PrEP provision. This calls for further implementation efforts to improve PrEP delivery to those most in need during periods of elevated sexual risk and to close the gap between indications and uptake., (© 2021 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: Rates of adolescent sexual activity have long been declining in the United States. We sought to estimate the number of cases of gonorrhea and chlamydia averted over 1 decade associated with these declines and associated costs saved., Methods: We analyzed data from the Centers for Disease Control and Prevention's Youth Risk Behavior Survey of US high school students from 2007 to 2017 and combined it with epidemiological estimates drawn from the literature to parameterize a dynamic population transmission model. We compared transmissions from observed behavioral trends with a counterfactual scenario that assumed sexual behaviors from 2007 remained constant for 10 years. We calculated outcomes by age and for 3 racial/ethnic groups (Hispanic, non-Hispanic Black, and non-Hispanic White adolescents) who vary on underlying burden and amount of behavioral change., Results: We estimated 1,118,483 cases of chlamydia and 214,762 cases of gonorrhea were averted (19.5% of burden across all ages). This yielded $474 million (2017 dollars) savings in medical costs over the decade. The largest number of averted cases (767,543) was among Black adolescents, but the largest proportion (28.7%) was among Hispanic adolescents., Conclusions: Whatever its origins, changing sexual behavior among adolescents results in large estimated reductions in STI burden and medical costs relative to previous cohorts. Although diagnoses among adolescents have not declined at this rate, multiple explanations could make these apparently divergent trends consistent. Efforts to continue supporting effective sex education in and out of school along with STI screening for adolescents should reinforce these gains., Competing Interests: Conflict of Interest and Sources of Funding: The authors have no conflicts of interest to declare that are relevant to the content of this article., (Copyright © 2021 American Sexually Transmitted Diseases Association. All rights reserved.)

Mathematical models of sexually transmitted disease (STI) are increasingly relied on to inform policy, practice, and resource allocation. Because STI transmission requires sexual contact between two or more people, a model's ability to represent the dynamics of sexual partnerships can influence the validity of findings. This ability is to a large extent constrained by the model type, as different modeling frameworks vary in their capability to capture patterns of sexual contact at individual, partnership, and network levels. In this paper, we classify models into three groups: compartmental, individual-based, and statistical network models. For each framework, we describe the basic model structure and discuss key aspects of sexual partnership dynamics: how and with whom partnerships are formed, partnership duration and dissolution, and temporal overlap in partnerships (concurrency). We illustrate the potential implications of accurately accounting for partnership dynamics, but these effects depend on characteristics of both the population and pathogen; the combined impact of these partnership and epidemiologic dynamics can be difficult to predict. While each of the reviewed model frameworks may be appropriate to inform certain research or policy questions, modelers and consumers of models should carefully consider the implications of sexual partnership dynamics for the questions under study., (Copyright © 2021. Published by Elsevier Inc.)

Background: Volatility in sexual contact rates has been recognized as an important factor influencing HIV transmission dynamics. One-time partnerships may be particularly important given the potential to quickly accumulate large number of contacts. Yet, empirical data documenting individual variation in contact rates remain rare. This study provides much needed data on temporal variation in one-time partners to better understand behavioral dynamics and improve the accuracy of transmission models., Methods: Data for this study were obtained from a longitudinal cohort study of young men who have sex with men and transgender women in Chicago. Participants provided sexual network data every 6 months for 2 years. A series of random effects models examined variation in one-time partnership rates and disaggregated within and between associations of exposure variables. Exposure variables included prior number of one-time partners, number of casual partners, and having a main partner., Results: Results indicated substantial between-person and within-person variation in one-time partners. Casual partnerships were positively associated and main partnerships negatively associated with one-time partnership rates. There remained a small positive association between prior one-time partnerships and the current number of one-time partnerships., Conclusions: Despite the preponderance of a low number of one-time partners, substantial variation in one-time partnership rates exists among young men who have sex with men and transgender women. Accordingly, focusing on high contact rate individuals alone may be insufficient to identify periods of highest risk. Future studies should use these estimates to more accurately model how volatility impacts HIV transmission and better understand how this variation influences intervention effectiveness., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Pathogen populations can evolve in response to selective pressure from vaccine-induced immune responses. For HIV, models predict that viral adaptation, either via strain replacement or selection on de novo mutation, may rapidly reduce the effectiveness of an HIV vaccine. We hypothesized that behavioral risk compensation after vaccination may accelerate the transmission of vaccine resistant strains, increasing the rate of viral adaptation and leading to a more rapid decline in vaccine effectiveness. To test our hypothesis, we modeled: (a) the impact of risk compensation on rates of HIV adaptation via strain replacement in response to a partially effective vaccine; and (b) the combined impact of risk compensation and viral adaptation on vaccine-mediated epidemic control. We used an agent-based epidemic model that was calibrated to HIV-1 trends in South Africa, and includes demographics, sexual network structure and behavior, and within-host disease dynamics. Our model predicts that risk compensation can increase the rate of HIV viral adaptation in response to a vaccine. In combination, risk compensation and viral adaptation can, under certain scenarios, reverse initial declines in prevalence due to vaccination, and result in HIV prevalence at 15 years equal to or greater than prevalence without a vaccine.

Purpose: Pre-exposure prophylaxis (PrEP)-an effective and safe intervention to prevent HIV transmission-was recently approved by the Food and Drug Administration for use by adolescents. Informed by studies of sexual behavior and PrEP adherence, retention, and promotion, we model the potential impact of PrEP use among at-risk adolescent sexual minority males., Methods: We simulate an HIV epidemic among men who have sex with men (MSM) aged 13-39. We assume adult MSM ages 19-39 have had PrEP available for 3 years with 20% coverage among eligible MSM based on the Centers for Disease Control and Prevention guidelines. PrEP interventions for ages 16-18 are then simulated using adherence and retention profiles drawn from the ATN113 and Enhancing Preexposure Prophylaxis in Community studies across a range of uptake parameters (10%-100%). Partnerships across age groups were modeled using parameterizations from the RADAR study. We compare the percent of incident infections averted (impact), person-years on PrEP per infection averted (efficiency), and changes in prevalence over 10 years., Results: As compared to no PrEP use, baseline PrEP adherence and retention among adolescent sexual minority males drawn from the ATN113 and Enhancing Preexposure Prophylaxis in Community studies averted from 2.8% to 41.0% of HIV infections depending on the fraction of eligible adolescent sexual minority males that initiated PrEP at their annual health-care visit. Improved adherence and retention achieved with an array of focused interventions from real-world settings increased the percent of infections averted by as much as 26%-70%., Conclusions: Empirically demonstrated improvements in the PrEP continuum of care in response to existing interventions can substantially reduce incident HIV infections among adolescent sexual minority males., (Copyright © 2020 Society for Adolescent Health and Medicine. All rights reserved.)

As HIV incidence among people who inject drugs grows in the context of an escalating drug overdose epidemic in North America, investigating how network structure may affect vulnerability to rapid HIV transmission is necessary for preventing outbreaks. We compared the characteristics of the observed contact tracing network from the 2015 outbreak in rural Indiana with 1000 networks generated by an agent-based network model with approximately the same number of individuals (n = 420) and ties between them (n = 913). We introduced an initial HIV infection into the simulated networks and compared the subsequent epidemic behavior (e.g., cumulative HIV infections over 5 years). The model was able to produce networks with largely comparable characteristics and total numbers of incident HIV infections. Although the model was unable to produce networks with comparable cohesiveness (where the observed network had a transitivity value 35.7 standard deviations from the mean of the simulated networks), the structural variability of the simulated networks allowed for investigation into their potential facilitation of HIV transmission. These findings emphasize the need for continued development of injection network simulation studies in tandem with empirical data collection to further investigate how network characteristics played a role in this and future outbreaks., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

HIV set point viral load (SPVL), the viral load established shortly after initial infection, is a proxy for HIV virulence: higher SPVLs lead to higher risk of transmission and faster disease progression. Three models of test-and-treat scenarios, mainly in heterosexual populations, found that increasing treatment coverage selected for more virulent viruses. We modeled virulence evolution in a population of men who have sex with men (MSM) with increasing test-and-treat coverage. We extended a stochastic, dynamic network model (EvoNetHIV). We varied relationship patterns (MSM vs. heterosexual), HIV transmission models (increasing vs. plateauing probability of transmission at very high viral loads), and treatment roll-out (with explicit testing or fixed intervals between infection and treatment). In scenarios most similar to previous models (longer relational durations and the plateauing transmission function), we replicated trends previously found: increasing treatment coverage led to increased virulence (0.12 log 10 increase in mean population SPVL between 20% and 100% treatment coverage). In scenarios reflecting MSM behavioral data using the increasing transmission function, increasing treatment coverage selected for viruses with lower virulence (0.16 log 10 decrease in mean population SPVL between 20% and 100% treatment coverage). These findings emphasize the impact of sexual network conditions and transmission function details on predicted epidemiological and evolutionary outcomes. Varying these features creates very different evolutionary environments, which in turn lead to opposite effects in mean population SPVL evolution. Our results suggest that, under some realistic conditions, effective test-and-treat strategies may not face the previously reported tradeoff in which increasing coverage leads to evolution of greater virulence. This suggests instead that a virtuous cycle of increasing treatment coverage and diminishing virulence is possible., (© The Author(s) 2021. Published by Oxford University Press.)

Background: Detection and management of acute HIV infection (AHI) is a clinical and public health priority, and HIV infections diagnosed among young adults aged 18 to 39 years are usually recent. Young adults with recent HIV acquisition frequently seek care for symptoms and could potentially be diagnosed through the health care system. Early recognition of HIV infection provides considerable individual and public health benefits, including linkage to treatment as prevention, access to risk reduction counseling and treatment, and notification of partners in need of HIV testing., Objective: The Tambua Mapema Plus study aims to (1) test 1500 young adults (aged 18-39 years) identified by an AHI screening algorithm for acute and prevalent (ie, seropositive) HIV, linking all newly diagnosed HIV-infected patients to care and offering immediate treatment; (2) offer assisted HIV partner notification services to all patients with HIV, testing partners for acute and prevalent HIV infection and identifying local sexual networks; and (3) model the potential impact of these two interventions on the Kenyan HIV epidemic, estimating incremental costs per HIV infection averted, death averted, and disability-adjusted life year averted using data on study outcomes., Methods: A modified stepped-wedge design is evaluating the yield of this HIV testing intervention at 4 public and 2 private health facilities in coastal Kenya before and after intervention delivery. The intervention uses point-of-care HIV-1 RNA testing combined with standard rapid antibody tests to diagnose AHI and prevalent HIV among young adults presenting for care, employs HIV partner notification services to identify linked acute and prevalent infections, and follows all newly diagnosed patients and their partners for 12 months to ascertain clinical outcomes, including linkage to care, antiretroviral therapy (ART) initiation and virologic suppression in HIV-infected patients, and pre-exposure prophylaxis uptake in uninfected individuals in discordant partnerships., Results: Enrollment started in December 2017. As of April 2020, 1374 participants have been enrolled in the observation period and 1500 participants have been enrolled in the intervention period, with 13 new diagnoses (0.95%) in the observation period and 37 new diagnoses (2.47%), including 2 AHI diagnoses, in the intervention period. Analysis is ongoing and will include adjusted comparisons of the odds of the following outcomes in the observation and intervention periods: being tested for HIV infection, newly diagnosed with prevalent or acute HIV infection, linked to care, and starting ART by week 6 following HIV diagnosis. Participants newly diagnosed with acute or prevalent HIV infection in the intervention period are being followed for outcomes, including viral suppression by month 6 and month 12 following ART initiation and partner testing outcomes., Conclusions: The Tambua Mapema Plus study will provide foundational data on the potential of this novel combination HIV prevention intervention to reduce ongoing HIV transmission in Kenya and other high-prevalence African settings., Trial Registration: ClinicalTrials.gov NCT03508908; https://clinicaltrials.gov/ct2/show/NCT03508908., International Registered Report Identifier (irrid): DERR1-10.2196/16198., (©Susan M Graham, Clara Agutu, Elise van der Elst, Amin S Hassan, Evanson Gichuru, Peter M Mugo, Carey Farquhar, Joseph B Babigumira, Steven M Goodreau, Deven T Hamilton, Thumbi Ndung'u, Martin Sirengo, Wairimu Chege, Eduard J Sanders. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 07.08.2020.)

Purpose: Adolescents aged 13-18 years bear a large burden of sexually transmitted infections (STIs) and changing adolescent sexual risk behavior is a key component of reducing this burden. We demonstrate a novel publicly available modeling tool (teen-SPARC) to help state and local health departments predict the impact of behavioral change on gonorrhea, chlamydia, and HIV burden among adolescents., Methods: Teen-SPARC is built in Excel for familiarity and ease and parameterized using data from CDC's Youth Risk Behavior Surveillance System. We present teen-SPARC's methods, including derivation of national parameters and instructions to obtain local parameters. We model multiple scenarios of increasing condom use and estimate the impact on gonorrhea, chlamydia, and HIV incidence, comparing national and New York State (NYS) results., Results: A 1% annual increase in condom use (consistent with Healthy People 2020 goals) could prevent nearly 10,000 cases of STIs nationwide. Increases in condom use of 17.1%, 2.2%, and 25.5% in NYS would be necessary to avert 1000 cases of gonorrhea, 1000 cases of chlamydia, and 10 cases of HIV infection, respectively. Additional results disaggregate outcomes by age, sex, partner sex, jurisdiction, and pathogen., Conclusion: Teen-SPARC may be able to assist health departments aiming to tailor behavioral interventions for STI prevention among adolescents., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Respondent-driven sampling (RDS) is widely used for collecting data on hard-to-reach populations, including information about the structure of the networks connecting the individuals. Characterizing network features can be important for designing and evaluating health programs, particularly those that involve infectious disease transmission. While the validity of population proportions estimated from RDS-based datasets has been well studied, little is known about potential biases in inference about network structure from RDS. We developed a mathematical and statistical platform to simulate network structures with exponential random graph models, and to mimic the data generation mechanisms produced by RDS. We used this framework to characterize biases in three important network statistics - density/mean degree, homophily, and transitivity. Generalized linear models were used to predict the network statistics of the original network from the network statistics of the sample network and observable sample design features. We found that RDS may introduce significant biases in the estimation of density/mean degree and transitivity, and may exaggerate homophily when preferential recruitment occurs. Adjustments to network-generating statistics derived from the prediction models could substantially improve validity of simulated networks in terms of density, and could reduce bias in replicating mean degree, homophily, and transitivity from the original network.

Introduction: Men who have sex with men (MSM) are suboptimally engaged in efficacious HIV interventions, due in part to stigma., Aim: We sought to validate the Anal Health Stigma Model, developed based on theory and prior qualitative data, by testing the magnitude of associations between measures of anal sex stigma and engagement in HIV prevention practices, while adjusting for covariates., Methods: We conducted a cross-sectional online survey of 1,263 cisgender MSM living in the United States and analyzed data with structural equation modeling. We tested a direct path from Anal Sex Stigma to Engagement in HIV Prevention alongside 2 indirect paths, 1 through Anal Sex Concerns and another through Comfort Discussing Anal Sexuality with Health Workers. The model adjusted for Social Support, Everyday Discrimination, and Sociodemographics., Main Outcome Measure: Engagement in HIV Prevention comprised an ad hoc measure of (i) lifetime exposure to a behavioral intervention, (ii) current adherence to biomedical intervention, and (iii) consistent use of a prevention strategy during recent penile-anal intercourse., Results: In the final model, anal sex stigma was associated with less engagement (β = -0.22, P < .001), mediated by participants' comfort talking about anal sex practices with health workers (β = -0.52; β = 0.44; both P < .001), adjusting for covariates (R 2  = 67%; χ 2 /df = 2.98, root mean square error of approximation = 0.040, comparative fit index = 0.99 and Tucker-Lewis index = 0.99). Sex-related concerns partially mediated the association between stigma and comfort (β = 0.55; β = 0.14, both P < .001). Modification indices also supported total effects of social support on increased comfort discussing anal sex (β = 0.35, P < .001) and, to a lesser degree, on decreased sex-related concerns (β = -0.10; P < .001)., Clinical Implications: Higher stigma toward anal sexuality is associated with less engagement in HIV prevention, largely due to discomfort discussing anal sex practices with health workers., Strength & Limitations: Adjustment for mediation in a cross-sectional design cannot establish temporal causality. Self-report is vulnerable to social desirability and recall bias. Online samples may not represent cisgender MSM in general. However, findings place HIV- and health-related behaviors within a social and relational context and may suggest points for intervention in health-care settings., Conclusion: Providers' willingness to engage in discussion about anal sexuality, for example, by responding to questions related to sexual well-being, may function as social support and thereby bolster comfort and improve engagement in HIV prevention. Kutner BA, Simoni JM, King KM, et al. Does Stigma Toward Anal Sexuality Impede HIV Prevention Among Men Who Have Sex With Men in the United States? A Structural Equation Modeling Assessment. J Sex Med 2020;17:477-490., (Copyright © 2019 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Sexual network degree, a count of ongoing partnerships, plays a critical role in the transmission dynamics of human immunodeficiency virus and other sexually transmitted infections. Researchers often quantify degree using self-reported cross-sectional data on the day of survey, which may result in bias because of uncertainty about future sexual activity., Methods: We evaluated the bias of a cross-sectional degree measure with a prospective cohort study of men who have sex with men (MSM). At baseline, we asked men about whether recent sexual partnerships were ongoing. We confirmed the true, ongoing status of those partnerships at baseline at follow-up. With logistic regression, we estimated the partnership-level predictors of baseline measure accuracy. With Poisson regression, we estimated the longitudinally confirmed degree as a function of baseline predicted degree., Results: Across partnership types, the baseline ongoing status measure was 70% accurate, with higher negative predictive value (91%) than positive predictive value (39%). Partnership exclusivity and racial pairing were associated with higher accuracy. Baseline degree generally overestimated confirmed degree. Bias, or number of ongoing partners different than predicted at baseline, was -0.28 overall, ranging from -1.91 to -0.41 for MSM with any ongoing partnerships at baseline. Comparing MSM of the same baseline degree, the level of bias was stronger for black compared with white MSM, and for younger compared with older MSM., Conclusions: Research studies may overestimate degree when it is quantified cross-sectionally. Adjustment and structured sensitivity analyses may account for bias in studies of human immunodeficiency virus or sexually transmitted infection prevention interventions.

In this paper, we present an overview and descriptive results from one of the first egocentric network studies of men who have sex with men (MSM) from across the United States: the ARTnet study. ARTnet was designed to support prevention research for human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs) that are transmitted across partnership networks. ARTnet implemented a population-based egocentric network study design that sampled egos from the target population and asked them to report on the number, attributes, and timing of their sexual partnerships. Such data provide the foundation needed for parameterizing stochastic network models that are used for disease projection and intervention planning. ARTnet collected data online from 2017 to 2019, with a final sample of 4904 participants who reported on 16198 sexual partnerships. The aims of this paper were to characterize the joint distribution of three network parameters needed for modeling: degree distributions, assortative mixing, and partnership age, with heterogeneity by partnership type (main, casual and one-time), demography, and geography. Participants had an average of 1.19 currently active partnerships ("mean degree"), which was higher for casual partnerships (0.74) than main partnerships (0.45). The mean rate of one-time partnership acquisition was 0.16 per week (8.5 partners per year). Main partnerships lasted 272.5 weeks on average, while casual partnerships lasted 133.0 weeks. There was strong but heterogenous assortative mixing by race/ethnicity for all groups. The mean absolute age difference for all partnership types was 9.5 years, with main partners differing by 6.3 years compared to 10.8 years for casual partners. Our analysis suggests that MSM may be at sustained risk for HIV/STI acquisition and transmission through high network degree of sexual partnerships. The ARTnet network study provides a robust and reproducible foundation for understanding the dynamics of HIV/STI epidemiology among U.S. MSM and supporting the implementation science that seeks to address persistent challenges in HIV/STI prevention., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Pre-exposure prophylaxis (PrEP) has been proven safe and effective in preventing HIV among adolescent sexual minority males (ASMM), but the cost-effectiveness of PrEP in ASMM remains unknown. Building on a recent epidemiological network modeling study of PrEP among ASMM, we estimated the cost-effectiveness of PrEP use in a high prevalence U.S. setting with significant disparities in HIV between black and white ASMM., Methods: Based on the estimated number of infections averted and the number of ASMM on PrEP from the previous model and published estimates of PrEP costs, HIV treatment costs, and quality-adjusted life years (QALYs) gained per infection prevented, we estimated the cost-effectiveness of PrEP use in black and white ASMM over 10 years using a societal perspective and lifetime horizon. Effectiveness was measured as lifetime QALYs gained. Cost estimates included 10-year PrEP costs and lifetime HIV treatment costs saved. Cost-effectiveness was measured as cost/QALY gained. Multiple sensitivity analyses were performed on key model input parameters and assumptions used., Results: Under base-case assumptions, PrEP use yielded an incremental cost-effectiveness ratio of $33,064 per QALY in black ASMM and $427,788 per QALY in white ASMM. In all sensitivity analyses, the cost-effectiveness ratio of PrEP use remained <$100,000 per QALY in black ASMM and >$100,000 per QALY in white ASMM., Conclusions: We found favorable cost-effectiveness ratios for PrEP use among black ASMM or other ASMM in communities with high HIV burden at current PrEP costs. Clinicians providing services in high-prevalence communities, and particularly those serving high-prevalence communities of color, should consider including PrEP services., (Published by Elsevier Inc.)

Predominantly heterosexual HIV-1 epidemics like those in sub-Saharan Africa continue to have high HIV incidence in young people. We used a stochastic, agent-based model for age-disparate networks to test the hypothesis that focusing uptake and retention of ART among youth could enhance the efficiency of treatment as prevention (TasP) campaigns. We used the model to identify strategies that reduce incidence to negligible levels (i.e., < 0.1 cases/100 person-years) 20-25 years after initiation of a targeted TasP campaign. The model was parameterized using behavioral, demographic, and clinical data from published papers and national reports. To keep a focus on the underlying age effects we model a generalized heterosexual population with average risks (i.e., no MSM, no PWIDs, no sex workers) and no entry of HIV+ people from other regions. The model assumes that most people (default 95%, range in variant simulations 60-95%) are "linkable"; i.e., could get linked to effective care given sufficient resources. To simplify the accounting, we assume a rapid jump in the number of people receiving treatment at the start of the TasP campaign, followed by a 2% annual increase that continues until all linkable HIV+ people have been treated. Under historical scenarios of CD4-based targeted ART allocation and current policies of untargeted (random) ART allocation, our model predicts that viral replication would need to be suppressed in 60-85% of infected people at the start of the TasP campaign to drive incidence to negligible levels. Under age-based strategies, by contrast, this percentage dropped by 18-54%, depending on the strength of the epidemic and the age target. For our baseline model, targeting those under age 30 halved the number of people who need to be treated. Age-based targeting also minimized total and time-discounted AIDS deaths over 25 years. Age-based targeting yielded benefits without being highly exclusive; in a model in which 60% of infected people were treated, ~87% and ~58% of those initiating therapy during a campaign targeting those <25 and <30 years, respectively, fell outside the target group. Sensitivity analyses revealed that youth-focused TasP is beneficial due to age-related risk factors (e.g. shorter relationship durations), and an age-specific herd immunity (ASHI) effect that protects uninfected adolescents entering the sexually active population. As testing rates increase in response to UNAIDS 90-90-90 goals, efforts to link all young people to care and treatment could contribute enormously to ending the HIV epidemic., Competing Interests: GSG has received support from Gilead Sciences, Alere Technologies, Merck & Co., Inc., Janssen Pharmaceutica, Cerus Corporation, ViiV Healthcare, Bristol-Myers Squibb, and Abbott Molecular Diagnostics.

Background: In Peru, there is an ongoing high-incidence HIV epidemic among men who have sex with men (MSM) and transgender women (TW). Sexual concurrency, or having sex with a partner in between two acts of sex with another partner, may be a key factor in onward HIV transmission. In this study, we quantify concurrency, evaluate factors associated with concurrency, and assess condom use with concurrent partners among MSM and TW in Peru., Methods: We conducted a secondary analysis of data from the 2011 Peruvian Biobehavioral Survey. Pearson's Chi-squared test was used to identify individual-level characteristics associated with concurrency. We estimated the association between participant characteristics, concurrent partnerships, partnership type (stable vs. non-stable), and CLAI within the context of concurrent partnerships using multivariate and repeated-measure Poisson regression., Results: 3-month cumulative prevalence of concurrency was higher among TW compared to MSM (30.7% vs 25.2%, p = 0.014). Among those with concurrent stable and non-stable partners, 45% used condoms with both partners (95% CI: 40%-50%) and 30% preferentially had CLAI with the stable partner only (95%CI: 26%-35%). Factors associated with CLAI within the context of concurrent partnerships varied between MSM and TW., Conclusions: Although concurrency is common among TW and MSM in Peru, patterns of concurrency and differential condom use may vary between TW and MSM. Future research may explore differential condom use with stable and non-stable partners to better understand behavioral factors that may alter vulnerability to HIV in TW compared to MSM., Competing Interests: The authors have declared that no competing interests exist.

Pathogen evolution is a potential threat to the long-term benefits provided by public health vaccination campaigns. Mathematical modeling can be a powerful tool to examine the forces responsible for the development of vaccine resistance and to predict its public health implications. We conducted a systematic review of existing literature to understand the construction and application of vaccine resistance models. We identified 26 studies that modeled the public health impact of vaccine resistance for 12 different pathogens. Most models predicted that vaccines would reduce overall disease burden in spite of evolution of vaccine resistance. Relatively few pathogens and populations for which vaccine resistance may be problematic were covered in the reviewed studies, with low- and middle-income countries particularly under-represented. We discuss the key components of model design, as well as patterns of model predictions., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Pre-exposure prophylaxis (PrEP) is an effective and safe intervention approved for use to prevent HIV transmission. PrEP scale-up strategies and clinical practice are currently being informed by modeling studies, which have estimated the impact of PrEP in adult and adolescent MSM populations separately. This partitioning may miss important effects or yield biased estimates by excluding dependencies between populations., Methods: We combined two published models of HIV transmission among adults and adolescent MSM. We simulated an HIV epidemic among MSM aged 13-39 without PrEP, with PrEP for adult MSM ages (19-39) and with the addition of PrEP for adolescents ages (16-18), comparing percent of incident infections averted (impact), the number of person-years on PrEP per infection averted (efficiency), and changes in prevalence., Results: PrEP use among eligible 19-39 year old MSM averted 29.0% of infections and reduced HIV prevalence from 23.2% to 17.0% over ten years in the population as a whole. Despite being ineligible for PrEP in this scenario, prevalence among sexually active 18 year-olds declined from 6.0% to 4.3% due to reduced transmissions across age cohorts. The addition of PrEP for adolescents ages 16-18 had a small impact on the overall epidemic, further reducing overall prevalence from 17.0% to 16.8%; however prevalence among the sexually active 18 year-olds further declined from 4.3% to 3.8%., Conclusions: PrEP use among adults may significantly reduce HIV prevalence among MSM and may also have significant downstream effects on HIV incidence among adolescents; PrEP targeting adolescents remains an important intervention for HIV prevention., Competing Interests: The authors have declared that no competing interests exist.

Background: Many state and local health departments now promote and support the use of HIV preexposure prophylaxis (PrEP), yet monitoring use of the intervention at the population level remains challenging., Methods: We report the results of an online survey designed to measure PrEP use among men who have sex with men (MSM) in Washington State. Data on the proportion of men with indications for PrEP based on state guidelines and levels of awareness, interest, and use of PrEP are presented for 1080 cisgender male respondents who completed the survey between January 1 and February 28, 2017. We conducted bivariate and multivariable logistic regression to identify factors associated with current PrEP use. To examine patterns of discontinuation, we conducted Cox proportional hazards regression and fit a Kaplan-Meier curve to reported data on time on PrEP., Results: Eighty percent of respondents had heard of PrEP, 19% reported current use, and 36% of men who had never used PrEP wanted to start taking it. Among MSM for whom state guidelines recommend PrEP, 31% were taking it. In multivariable analysis, current PrEP use was associated with older age, higher education, and meeting indications for PrEP use. Our data suggest that 20% of PrEP users discontinue within 12 months, and men with lower educational attainment were more likely to discontinue., Conclusions: Despite high levels of use, there is significant unmet need for PrEP in Washington. Our experience indicates that Internet surveys are feasible and informative for monitoring PrEP use in MSM.

The potential for human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) to reduce the racial disparities in HIV incidence in the United States might be limited by racial gaps in PrEP care. We used a network-based mathematical model of HIV transmission for younger black and white men who have sex with men (BMSM and WMSM) in the Atlanta, Georgia, area to evaluate how race-stratified transitions through the PrEP care continuum from initiation to adherence and retention could affect HIV incidence overall and disparities in incidence between races, using current empirical estimates of BMSM continuum parameters. Relative to a no-PrEP scenario, implementing PrEP according to observed BMSM parameters was projected to yield a 23% decline in HIV incidence (hazard ratio = 0.77) among BMSM at year 10. The racial disparity in incidence in this observed scenario was 4.95 per 100 person-years at risk (PYAR), a 19% decline from the 6.08 per 100 PYAR disparity in the no-PrEP scenario. If BMSM parameters were increased to WMSM values, incidence would decline by 47% (hazard ratio = 0.53), with an associated disparity of 3.30 per 100 PYAR (a 46% decline in the disparity). PrEP could simultaneously lower HIV incidence overall and reduce racial disparities despite current gaps in PrEP care. Interventions addressing these gaps will be needed to substantially decrease disparities., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2019.)

Background: HIV-1 set point viral load (SPVL) is a highly variable trait that influences disease progression and transmission risk. Men who are exclusively insertive (EI) during anal intercourse require more sexual contacts to become infected than exclusively receptive (ER) men. Thus, we hypothesize that EIs are more likely to acquire their viruses from highly infectious partners (i.e., with high SPVLs) and to have higher SPVLs than infected ERs., Methods: We used a one-generation Bernoulli model, a dynamic network model, and data from the Multicenter AIDS Cohort Study (MACS) to examine whether and under what circumstances MSM differ in SPVL by sexual role., Results: Both models predicted higher SPVLs in EIs than role versatile (RV) or ER men, but only in scenarios where longer-term relationships predominated. ER and RV men displayed similar SPVLs. EI men remained far less likely than ER men to become infected, however. When the MACS data were limited by some estimates of lower sex partner counts (a proxy for longer relationships), EI men had higher SPVLs; these differences were clinically relevant (>0.3 log 10 copies/mL) and statistically significant (p < 0.05)., Conclusions: Mode of acquisition may be an important aspect of SPVL evolution in MSM, with clinical implications., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

HIV viral load (VL) predicts both transmission potential and rate of disease progression. For reasons that are still not fully understood, the set point viral load (SPVL) established after acute infection varies across individuals and populations. Previous studies have suggested that population mean SPVL (MSPVL) has evolved near an optimum that reflects a trade-off between transmissibility and host survival. Sexual network structures affect rates of potential exposure during different within-host phases of infection marked by different transmission probabilities, and thus affect the number and timing of transmission events. These structures include relational concurrency , which has been argued to explain key differences in HIV burden across populations. We hypothesize that concurrency will alter the fitness landscape for SPVL in ways that differ from other network features whose impacts accrue at other times during infection. To quantitatively test this hypothesis, we developed a dynamic, stochastic, data-driven network model of HIV transmission, and evolution to assess the impact of key sexual network phenomena on MSPVL evolution. Experiments were repeated in sensitivity runs that made different assumptions about transmissibility during acute infection, SPVL heritability, and the functional form of the relationship between VL and transmissibility. For our main transmission model, scenarios yielded MSPVLs ranging from 4.4 to 4.75 log 10 copies/ml, covering much of the observed empirical range. MSPVL evolved to be higher in populations with high concurrency and shorter relational durations, with values varying over a clinically significant range. In linear regression analyses on these and other predictors, main effects were significant ( P < 0.05), as were interaction terms, indicating that effects are interdependent. We also noted a strong correlation between two key emergent properties measured at the end of the simulations-MSPVL and HIV prevalence-most clearly for phenomena that affect transmission networks early in infection. Controlling for prevalence, high concurrency yielded higher MSPVL than other network phenomena. Interestingly, we observed lower prevalence in runs in which SPVL heritability was zero, indicating the potential for viral evolution to exacerbate disease burden over time. Future efforts to understand empirical variation in MSPVL should consider local HIV burden and basic sexual behavioral and network structure.