Search

Background: Development of an HIV vaccine might be essential to ending the HIV/AIDS pandemic. However, vaccines can result in the emergence and spread of vaccine-resistant strains. Indeed, analyses of breakthrough infections in the HIV phase 3 vaccine trial RV144 identified HIV genotypes with differential rates of transmission in vaccine and placebo recipients. We hypothesized that, for HIV vaccination programs based on partially effective vaccines similar to RV144, HIV adaptation will rapidly diminish the expected vaccine impact., Methods and Findings: Using two HIV epidemic models, we simulated large-scale vaccination programs and, critically, included HIV strain diversity with respect to the vaccine response. We show here that rapid population-level viral adaptation can lead to decreased overall vaccine efficacy and substantially fewer infections averted by vaccination, when comparing scenarios with and without viral evolution (with outcomes depending on vaccination coverage, vaccine efficacy against the sensitive allele, and the initial resistant allele frequency). Translating this to the epidemic in South Africa, a scenario with 70% vaccination coverage may result in 250,000 infections (non-averted by vaccination) within 10 years of vaccine rollout that are due solely to HIV adaptation, all else being equal., Conclusions: These findings suggest that approaches to HIV vaccine development, program implementation, and epidemic modeling may require attention to viral adaptation in response to vaccination., (Copyright © 2017. Published by Elsevier Ltd.)

Circular migrations are the periodic movement of individuals between multiple locations, observed in parts of sub-Saharan Africa. Relationships between circular migrations and HIV are complex, entailing interactions between migration frequency, partnership structure, and exposure to acute HIV infection. Mathematical modeling is a useful tool for understanding these interactions. Two modeling classes have dominated the HIV epidemiology and policy literature for the last decade: one a form of compartmental models, the other network models. We construct models from each class, using ordinary differential equations and exponential random graph models, respectively. Our analysis suggests that projected HIV prevalence is highly sensitive to the choice of modeling framework. Assuming initial equal HIV prevalence across locations, compartmental models show no association between migration frequency and HIV prevalence or incidence, while network models show that migrations at frequencies shorter than the acute HIV period predict greater HIV incidence and prevalence compared to longer migration periods. These differences are statistically significant when network models are extended to incorporate a requirement for migrant men's multiple partnerships to occur in different locations. In settings with circular migrations, commonly-used forms of compartmental models appear to miss key components of HIV epidemiology stemming from interactions of relational and viral dynamics.

BackgroundWe aim to identify optimal strategies for deploying pre-exposure prophylaxis among men who have sex with men (MSM) in the United States and Peru to maximize population-level effectiveness in an efficient manner. We use epidemic models to simulate the impact of targeting strategies. Most studies have focused on targeting either the general population or high-risk MSM. Alternative strategies, including serodiscordant couples, may better balance effectiveness and efficiency.MethodsWe use dynamic stochastic sexual network models based on exponential-family random graph modeling, parameterized from behavioral surveys of MSM in the United States and Peru. These models represent main partnerships and casual contacts separately, permitting modeling of interventions targeting men whose risk derives from combinations of relational types. We also model varying rates of uptake and adherence to pre-exposure prophylaxis (PrEP). We assess sensitivity of results to risk compensation through increases in condomless casual contacts and condomless sex in main partnerships.ResultsTargeting all men who are not exclusively insertive has the largest impact on HIV incidence, but targeting only those with high levels of casual activity yields comparable results using fewer person-years on PrEP. The effect is robust to risk compensation in the United States, but less so in Peru. Targeting serodiscordant main partnerships does not significantly impact incidence, but requires fewer person-years on PrEP per infection averted than other strategies.ConclusionsPrEP could be effective in reducing new infections at the population level in both settings. Serodiscordant partnerships are an attractive component of a targeting program, but targeting should include other high-risk men.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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. 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%. 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. [ABSTRACT FROM AUTHOR]

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 log10 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 log10 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. Author summary: We used an agent-based model for heterosexual epidemics to evaluate the effects of focusing treatment-as-prevention (TasP) efforts on young people. To keep the focus on age effects, we modeled populations with average risks (i.e., no MSM, no PWIDs, no sex workers). For our baseline model, we found that a long-term TasP program that focuses on HIV+ people under the age of 30 can halve the number of people who need to be treated in order to drive incidence to zero. Within the context of an overall expansion of care, we were able to identify multiple scenarios in which a successful youth-focused TasP campaign also expanded care for older people. Interestingly, we continued to see strong advantages to age-based TasP in sensitivity tests in which we removed key age-related risks (e.g., the tendency for young people to have shorter relationships). Youth-focused TasP succeeds, in large part, because it protects HIV- adolescents entering the sexually active population; i.e., a population that would otherwise be at high risk not only for getting infected but also for spreading the virus to others. This protection of adolescents leads to a steadily expanding AIDS-free generation that drives the virus to extinction. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose Pre-exposure prophylaxis (PrEP) is an effective and safe intervention to prevent human immunodeficiency virus (HIV) transmission in men who have sex with men; current Centers for Disease Control and Prevention guidelines indicate its use among high-risk adults. Adolescent sexual minority males (ASMM) also have significant HIV risk, but implementation strategies are likely to differ for this population. We aimed to estimate impact and efficiency of PrEP for ASMM in higher prevalence US settings, using a variety of implementation strategies and assumptions about coverage, adherence, and background prevalence. Methods We develop a stochastic, dynamic, network-based model, parametrized using numerous ASMM behavioral and clinical data sources. We simulate 10 years with and without PrEP, comparing percent of incident infections averted (impact) and number of person-years on PrEP per infection averted (efficiency). Results Our main scenario (PrEP for 16- to 18-year-old ASMM, initiating PrEP 6 months after first anal intercourse, 40% coverage, adherence profiles from the ATN 113 trial; 2.9% background HIV prevalence among ASMM) prevents 27.8% of infections, with 38 person-years on PrEP per infection averted. Expanding implementation to cover younger ages or earlier initiation has small effects on impact and efficiency. Targeting highest risk ASMM increases efficiency, but requires querying sexual histories. Across levels examined, coverage and adherence do not have major impacts on efficiency, whereas background prevalence does. Conclusions PrEP can have a large impact on HIV incidence among ASMM in the United States, especially in settings with high prevalence. However, willingness of, and support for, providers will be central to achieving the coverage needed to make this a success. [ABSTRACT FROM AUTHOR]

The transformation of HIV from a fatal disease to lifelong disease has resulted in an HIV-infected population that is growing and aging, placing new and increasing demands on public programs and health services. We used National HIV Surveillance System and US census data to project the demographic composition of the population of people living with diagnosed HIV (PLWDH) in the United States through 2045. The input parameters for the projections include: (1) census projections, (2) number of people with an existing HIV diagnosis in 2013, (3) number of new HIV diagnoses in 2013, and (4) death rate within the PLWDH population in 2013. Sex-, risk group-, and race-specific projections were estimated through an adapted Leslie Matrix Model for age-structured populations. Projections for 2013–2045 suggest that the number of PLWDH in the U.S. will consistently grow, from 917,294 to 1,232,054, though the annual growth rate will slow from 1.8% to 0.8%. The number of PLWDH aged 55 years and older will increase from 232,113 to 470,221. The number of non-Hispanic (NH) African Americans/Blacks and Hispanics is projected to consistently grow, shifting the racial/ethnic composition of the US PLWDH population from 32 to 23% NH-White, 42 to 38% NH-Black, and 20–32% Hispanic between 2013 and 2045. Given current trends, the composition of the PLWDH population is projected to change considerably. Public health practitioners should anticipate large shifts in the age and racial/ethnic structure of the PLWDH population in the United States. [ABSTRACT FROM PUBLISHER]

Background. Preexposure prophylaxis (PrEP) is highly effective for preventing human immunodeficiency virus (HIV) infection, but risk compensation (RC) in men who have sex with men (MSM) raises concerns about increased sexually transmitted infections (STIs). The Center for Disease Control and Prevention's (CDC's) PrEP guidelines recommend biannual STI screening, which may reduce incidence by treating STIs that would otherwise remain undiagnosed. We investigated these two counteracting phenomena. Methods. With a network-based mathematical model of HIV, Neisseria gonorrhoeae (NG), and Chlamydia trachomatis (CT) transmission dynamics among MSM in the United States, we simulated PrEP uptake following the prescription indications and HIV/STI screening recommendations in the CDC guidelines. Scenarios varied PrEP coverage (the proportion of MSM indicated for PrEP who received it), RC (a reduction in the per-act probability of condom use), and the STI screening interval. Results. In our reference scenario (40% coverage, 40% RC), 42% of NG and 40% of CT infections would be averted over the next decade. A doubling of RC would still result in net STI prevention relative to no PrEP. STIs declined because PrEP-related STI screening resulted in a 17% and 16% absolute increase in the treatment of asymptomatic and rectal STIs, respectively. Screening and timely treatment at quarterly vs biannual intervals would reduce STI incidence an additional 50%. Conclusions. Implementation of the CDC PrEP guidelines while scaling up PrEP coverage could result in a significant decline in STI incidence among MSM. Our study highlights the design of PrEP not only as antiretroviral medication but as combination HIV/STI prevention incorporating STI screening. [ABSTRACT FROM AUTHOR]

Objectives: Risk compensation (RC) could reduce or offset the biological prevention benefits of HIV preexposure prophylaxis (PrEP) among those at substantial risk of infection, including men who have sex with men (MSM). We investigated the potential extent and causal mechanisms through which RC could impact HIV transmission at the population and individual levels. Methods: Using a stochastic network-based mathematical model of HIV transmission dynamics among MSM in the United States, we simulated RC as a reduction in the probability of condom use after initiating PrEP, with heterogeneity by PrEP adherence profiles and partnership type in which RC occurred. Outcomes were changes to population-level HIV incidence and individual-level acquisition risk. Results: When RC was limited to MSM highly/moderately adherent to PrEP, 100% RC (full replacement of condoms) resulted in a 2% relative decline in incidence compared to no RC, but an 8% relative increase in infection risk for MSM on PrEP. This resulted from confounding by indication: RC increased the number of MSM indicated for PrEP as a function of more condomless anal intercourse among men otherwise not indicated for PrEP; this led to an increased PrEP uptake and subsequent decline in incidence. Conclusions: RC is unlikely to decrease the prevention impact of PrEP, and in some cases RC may be counterintuitively beneficial at the population level. This depended on PrEP uptake scaling with behavioral indications. Due to the increased acquisition risk associated with RC, however, clinicians should continue to support PrEP as a supplement rather than replacement of condoms. [ABSTRACT FROM AUTHOR]

Background:  Preexposure prophylaxis (PrEP) is effective for preventing human immunodeficiency virus (HIV) infection among men who have sex with men (MSM) within trial settings. Population impact will depend on clinical indications for PrEP initiation, coverage levels, and drug adherence. No modeling studies have estimated the impact of clinical practice guidelines for PrEP issued by the Centers for Disease Control and Prevention (CDC).Methods:  Mathematical models of HIV transmission among MSM were used to estimate the percentage of infections averted (PIA) and the number needed to treat (NNT) under behavioral indications of the CDC's PrEP guidelines. We modeled the contribution of these indications while varying treatment coverage and adherence.Results:  At 40% coverage of indicated MSM over the next decade, application of CDC guidelines would avert 1162 infections per 100 000 person-years, 33.0% of expected infections. The predicted NNT for the guidelines would be 25. Increasing coverage and adherence jointly raise the PIA, but reductions to the NNT were associated with better adherence only.Conclusions:  Implementation of CDC PrEP guidelines would result in strong and sustained reductions in HIV incidence among MSM in the United States. The guidelines strike a good balance between epidemiological impact (PIA) and efficiency (NNT) at plausible scale-up levels. Adherence counseling could maximize public health investment in PrEP by decreasing the NNT. [ABSTRACT FROM AUTHOR]

Background: Three trials have demonstrated the prophylactic effect of male circumcision (MC) for HIV acquisition among heterosexuals, and MC interventions are underway throughout sub-Saharan Africa. Similar efforts for men who have sex with men (MSM) are stymied by the potential for circumcised MSM to acquire HIV easily through receptive sex and transmit easily through insertive sex. Existing work suggests that MC for MSM should reach its maximum potential in settings where sexual role segregation is historically high and relatively stable across the lifecourse; HIV incidence among MSM is high; reported willingness for prophylactic circumcision is high; and pre-existing circumcision rates are low. We aim to identify the likely public health impact that MC interventions among MSM would have in one setting that fulfills these conditions—Peru—as a theoretical upper bound for their effectiveness among MSM generally. Methods and Findings: We use a dynamic, stochastic sexual network model based in exponential-family random graph modeling and parameterized from multiple behavioral surveys of Peruvian MSM. We consider three enrollment criteria (insertive during 100%, >80% or >60% of UAI) and two levels of uptake (25% and 50% of eligible men); we explore sexual role proportions from two studies and different frequencies of switching among role categories. Each scenario is simulated 10 times. We estimate that efficiency could reach one case averted per 6 circumcisions. However, the population-level impact of an optimistic MSM-MC intervention in this setting would likely be at most ∼5–10% incidence and prevalence reductions over 25 years. Conclusions: Roll-out of MC for MSM in Peru would not result in a substantial reduction in new HIV infections, despite characteristics in this population that could maximize such effects. Additional studies are needed to confirm these results for other MSM populations, and providers may consider the individual health benefits of offering MC to their MSM patients. [ABSTRACT FROM AUTHOR]

In this work, we estimate the proportions of transmissions occurring in main vs. casual partnerships, and by the sexual role, infection stage, and testing and treatment history of the infected partner, for men who have sex with men (MSM) in the US and Peru. We use dynamic, stochastic models based in exponential random graph models (ERGMs), obtaining inputs from multiple large-scale MSM surveys. Parallel main partnership and casual sexual networks are simulated. Each man is characterized by age, race, circumcision status, sexual role behavior, and propensity for unprotected anal intercourse (UAI); his history is modeled from entry into the adult population, with potential transitions including HIV infection, detection, treatment, AIDS diagnosis, and death. We implemented two model variants differing in assumptions about acute infectiousness, and assessed sensitivity to other key inputs. Our two models suggested that only 4-5% (Model 1) or 22-29% (Model 2) of HIV transmission results from contacts with acute-stage partners; the plurality (80-81% and 49%, respectively) stem from chronic-stage partners and the remainder (14-16% and 27-35%, respectively) from AIDS-stage partners. Similar proportions of infections stem from partners whose infection is undiagnosed (24-31%), diagnosed but untreated (36-46%), and currently being treated (30-36%). Roughly one-third of infections (32-39%) occur within main partnerships. Results by country were qualitatively similar, despite key behavioral differences; one exception was that transmission from the receptive to insertive partner appears more important in Peru (34%) than the US (21%). The broad balance in transmission contexts suggests that education about risk, careful assessment, pre-exposure prophylaxis, more frequent testing, earlier treatment, and risk-reduction, disclosure, and adherence counseling may all contribute substantially to reducing the HIV incidence among MSM in the US and Peru. [ABSTRACT FROM AUTHOR]

Background: Although many men who have sex with men (MSM) in Peru are unaware of their HIV status, they are frequent users of the Internet, and can be approached by that medium for promotion of HIV testing. Methods: We conducted an online randomized controlled trial to compare the effect of HIV-testing motivational videos versus standard public health text, both offered through a gay website. The videos were customized for two audiences based on self-identification: either gay or non-gay men. The outcomes evaluated were 'intention to get tested' and 'HIV testing at the clinic.' Findings: In the non-gay identified group, 97 men were randomly assigned to the video-based intervention and 90 to the text-based intervention. Non-gay identified participants randomized to the video-based intervention were more likely to report their intention of getting tested for HIV within the next 30 days (62.5% vs. 15.4%, Relative Risk (RR): 2.77, 95% Confidence Interval (CI): 1.42-5.39). After a mean of 125.5 days of observation (range 42-209 days), 11 participants randomized to the video and none of the participants randomized to text attended our clinic requesting HIV testing (p = 0.001). In the gay-identified group, 142 men were randomized to the video-based intervention and 130 to the textbased intervention. Gay-identified participants randomized to the video were more likely to report intentions of getting an HIV test within 30 days, although not significantly (50% vs. 21.6%, RR: 1.54, 95% CI: 0.74-3.20). At the end of follow up, 8 participants who watched the video and 10 who read the text visited our clinic for HIV testing (Hazard Ratio: 1.07, 95% CI: 0.40-2.85). Conclusion: This study provides some evidence of the efficacy of a video-based online intervention in improving HIV testing among non-gay-identified MSM in Peru. This intervention may be adopted by institutions with websites oriented to motivate HIV testing among similar MSM populations. Trial registration: Clinicaltrials.gov NCT00751192. [ABSTRACT FROM AUTHOR]

Geneticists seeking to understand HIV-1 evolution among human hosts generally assume that hosts represent a panmictic population. Social science research demonstrates that the network patterns over which HIV-1 spreads are highly nonrandom, but the effect of these patterns on the genetic diversity of HIV-1 and other sexually transmitted pathogens has yet to be thoroughly examined. In addition, interhost phylogenetic models rarely account explicitly for genetic diversity arising from intrahost dynamics. This study outlines a graph-theoretic framework (exponential random graph modeling, ERGM) for the estimation, inference, and simulation of dynamic partnership networks. This approach is used to simulate HIV-1 transmission and evolution under eight mixing patterns resembling those observed in empirical human populations, while simultaneously incorporating intrahost viral diversity. Models of parametric growth fit panmictic populations well, yielding estimates of total viral effective population on the order of the product of infected host size and intrahost effective viral population size. Populations exhibiting patterns of nonrandom mixing differ more widely in estimates of effective population size they yield, however, and reconstructions of population dynamics can exhibit severe errors if panmixis is assumed. I discuss implications for HIV-1 phylogenetics and the potential for ERGM to provide a general framework for addressing these issues. [ABSTRACT FROM AUTHOR]

In Latin America, men who have sex with men (MSM) have traditionally practiced role segregation—that is, the adoption of a fixed role (insertive or receptive) rather than a versatile role (both practices) during anal sex. Previous modeling has shown that role segregation may yield a lower incidence of human immunodeficiency virus (HIV) type 1 infection, compared with role versatility; however, the modeling assumed no risk of acquiring HIV-1 during insertive sex, which is now recognized as unlikely. We reexamine the issue by use of a deterministic model incorporating bidirectional transmission and data from a cohort study of MSM in Lima, Peru, to demonstrate the potential effects of role segregation on the trajectory of the HIV-1 epidemic. In Lima, 67% of MSM reported segregated roles in their recent male partnerships. A population of MSM with identical contact rates but complete role versatility would have twice the prevalence of HIV-1 infection throughout the epidemic's first 3 decades. Preferential mixing among versatile MSM does not change overall prevalence but affects which individuals become infected. [ABSTRACT FROM AUTHOR]

• Compared modeled networks to that observed in an HIV outbreak among PWID in Indiana. • Our model was comparable to the observed with respect to several network metrics. • Our model was able to reproduce outbreaks of comparable size to the observed data. • Our simulated networks had incomparable values of transitivity. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]