Age-specific transmission dynamics of SARS-CoV-2 during the first 2 years of the pandemic.

During its first 2 years, the SARS-CoV-2 pandemic manifested as multiple waves shaped by complex interactions between variants of concern, non-pharmaceutical interventions, and the immunological landscape of the population. Understanding how the age-specific epidemiology of SARS-CoV-2 has evolved throughout the pandemic is crucial for informing policy decisions. In this article, we aimed to develop an inference-based modeling approach to reconstruct the burden of true infections and hospital admissions in children, adolescents, and adults over the seven waves of four variants (wild-type, Alpha, Delta, and Omicron BA.1) during the first 2 years of the pandemic, using the Netherlands as the motivating example. We find that reported cases are a considerable underestimate and a generally poor predictor of true infection burden, especially because case reporting differs by age. The contribution of children and adolescents to total infection and hospitalization burden increased with successive variants and was largest during the Omicron BA.1 period. However, the ratio of hospitalizations to infections decreased with each subsequent variant in all age categories. Before the Delta period, almost all infections were primary infections occurring in naive individuals. During the Delta and Omicron BA.1 periods, primary infections were common in children but relatively rare in adults who experienced either reinfections or breakthrough infections. Our approach can be used to understand age-specific epidemiology through successive waves in other countries where random community surveys uncovering true SARS-CoV-2 dynamics are absent but basic surveillance and statistics data are available.

Estimation of introduction and transmission rates of SARS-CoV-2 in a prospective household study.

Household studies provide an efficient means to study transmission of infectious diseases, enabling estimation of susceptibility and infectivity by person-type. A main inclusion criterion in such studies is usually the presence of an infected person. This precludes estimation of the hazards of pathogen introduction into the household. Here we estimate age- and time-dependent household introduction hazards together with within household transmission rates using data from a prospective household-based study in the Netherlands. A total of 307 households containing 1,209 persons were included from August 2020 until March 2021. Follow-up of households took place between August 2020 and August 2021 with maximal follow-up per household mostly limited to 161 days. Almost 1 out of 5 households (59/307) had evidence of an introduction of SARS-CoV-2. We estimate introduction hazards and within-household transmission rates in our study population with penalized splines and stochastic epidemic models, respectively. The estimated hazard of introduction of SARS-CoV-2 in the households was lower for children (0-12 years) than for adults (relative hazard: 0.62; 95%CrI: 0.34-1.0). Estimated introduction hazards peaked in mid October 2020, mid December 2020, and mid April 2021, preceding peaks in hospital admissions by 1-2 weeks. Best fitting transmission models included increased infectivity of children relative to adults and adolescents, such that the estimated child-to-child transmission probability (0.62; 95%CrI: 0.40-0.81) was considerably higher than the adult-to-adult transmission probability (0.12; 95%CrI: 0.057-0.19). Scenario analyses indicate that vaccination of adults can strongly reduce household infection attack rates and that adding adolescent vaccination offers limited added benefit.

Evolutionary implications of SARS-CoV-2 vaccination for the future design of vaccination strategies.

Once the first SARS-CoV-2 vaccine became available, mass vaccination was the main pillar of the public health response to the COVID-19 pandemic. It was very effective in reducing hospitalizations and deaths. Here, we discuss the possibility that mass vaccination might accelerate SARS-CoV-2 evolution in antibody-binding regions compared to natural infection at the population level. Using the evidence of strong genetic variation in antibody-binding regions and taking advantage of the similarity between the envelope proteins of SARS-CoV-2 and influenza, we assume that immune selection pressure acting on these regions of the two viruses is similar. We discuss the consequences of this assumption for SARS-CoV-2 evolution in light of mathematical models developed previously for influenza. We further outline the implications of this phenomenon, if our assumptions are confirmed, for the future design of SARS-CoV-2 vaccination strategies.

The impact of variant and vaccination on SARS-CoV-2 symptomatology; three prospective household cohorts.

OBJECTIVES: We compared age-stratified SARS-CoV-2 symptomatology of wild-type/Alpha vs Omicron BA.1/BA.2 variant infected individuals and the impact of COVID-19 booster vaccination on Omicron symptom burden. METHODS: Data from three European prospective household cohorts were used (April 2020 to April 2021 and January to March 2022). Standardized outbreak protocols included (repeated) polymerase chain reaction testing, paired serology, and daily symptom scoring for all household members. Comparative analyses were performed on 346 secondary household cases from both periods. RESULTS: Children <12 years (all unvaccinated) experienced more symptoms and higher severity scores during Omicron compared with wild-type/Alpha period (P ≤0.01). In adults, Omicron disease duration and severity were reduced (P ≤ 0.095). Omicron was associated with lower odds for loss of smell or taste (adjusted odds ratio [aOR]: 0.14; 95% CI 0.03-0.50) and higher but non-significant odds for upper respiratory symptoms, fever, and fatigue (aORs: 1.85-2.23). No differences were observed in disease severity or duration between primary vs booster series vaccinated adults (P ≥0.12). CONCLUSION: The Omicron variant causes higher symptom burden in children compared with wild-type/Alpha and lower in adults, possibly due to previous vaccination. A shift in symptoms occurred with reduction in loss of smell/taste for Omicron. No additional effect of booster vaccination on Omicron symptom burden was observed.

The experienced positive and negative influence of HIV on quality of life of people with HIV and vulnerable to HIV in the Netherlands.

This qualitative study aimed to explore the experienced influence of HIV on the quality of life (QoL) of people with HIV (PHIV) and key populations without but are vulnerable to HIV in the Netherlands. We conducted and thematically analyzed interviews with 29 PHIV and 13 participants from key populations without HIV (i.e., men who have sex with men). PHIV and key populations shared positive meaningful experiences regarding HIV, i.e., feeling grateful for ART, life, and the availability of PrEP, being loved and supported in the light of HIV, and providing support to the community. Negative predominant experiences regarding HIV were described by both PHIV and key populations as the negative effects of ART, challenges with regards to disclosing HIV, social stigmatization, and self-stigma. It remains important to support HIV community organizations in their efforts to reduce social stigmatization and to continue improving biomedical interventions for HIV.

The importance of sustained compliance with physical distancing during COVID-19 vaccination rollout.

BACKGROUND: Increasing vaccination coverage against SARS-CoV-2 enabled relaxation of lockdowns in many countries in Europe. As the vaccination rollouts progressed, the public health authorities were seeking recommendations on the continuation of physical distancing measures during ongoing vaccination rollouts. Compliance with these measures was declining while more transmissible virus variants have emerged. METHODS: We used a SARS-CoV-2 transmission model to investigate the feedback between compliance, infection incidence, and vaccination coverage. We quantified our findings in terms of cumulative number of new hospitalisations three and six months after the start of vaccination. RESULTS: Our results suggest that the combination of fast waning compliance in non-vaccinated individuals, low compliance in vaccinated individuals, low vaccine efficacy against infection and more transmissible virus variants may result in a higher cumulative number of new hospitalisations than in a situation without vaccination. These adverse effects can be alleviated by deploying behavioural interventions that should preferably target both vaccinated and non-vaccinated individuals. The choice of the most appropriate intervention depends on vaccination rate and vaccine efficacy against infection. CONCLUSIONS: Supplementary behavioural interventions aiming to boost compliance to physical distancing measures can improve the outcome of vaccination programmes, until vaccination coverage is sufficiently high. For optimal results, these interventions should be selected based on the vaccine efficacy against infection and expected vaccination rate. While we considered the dynamics of SARS-CoV-2, the qualitative effects of the interplay between infectious disease spread and behavior on the outcomes of a vaccination programme can be used as guidance in a future similar pandemic.

The perceived impact of an HIV cure by people living with HIV and key populations vulnerable to HIV in the Netherlands: A qualitative study.

Introduction: When an HIV cure becomes available, it will have consequences for people living with HIV (PLHIV) and key populations who are vulnerable to HIV. This qualitative study aimed to explore the perceived impact of two HIV cure scenarios (post-treatment control when HIV is suppressed without the need for ongoing antiretroviral treatment (ART) and complete HIV elimination) on the quality of life of PLHIV and key populations living without HIV in the Netherlands. Methods: Participants were purposefully sampled from the Amsterdam Cohort Studies, the AGEhIV Cohort Study, the outpatient clinic of the University Medical Centre Utrecht and the Dutch HIV Association to increase variability. Semi-structured in-depth interviews were conducted between October 2020 and March 2021 and thematically analysed. Results: Of the 42 interviewed participants, 29 were PLHIV and 13 represented key populations (i.e., men who have sex with men and people injecting drugs). Both PLHIV and participants from vulnerable key populations hoped that a cure would result in normalization of their lives by removing the need to disclose HIV, reducing stigma and guilt, increasing independence of ART, and liberating sexual behaviour. Both groups believed only HIV elimination could accomplish this desired impact. Conclusions: While the post-treatment control scenario seems a more plausible outcome of current HIV cure research, our findings highlight that participants may not perceive it as a true cure. Involvement of PLHIV and vulnerable key populations in devising acceptable and feasible experimental approaches to HIV cure is essential to ensure their future successful implementation.

Challenges for modelling interventions for future pandemics.

Mathematical modelling and statistical inference provide a framework to evaluate different non-pharmaceutical and pharmaceutical interventions for the control of epidemics that has been widely used during the COVID-19 pandemic. In this paper, lessons learned from this and previous epidemics are used to highlight the challenges for future pandemic control. We consider the availability and use of data, as well as the need for correct parameterisation and calibration for different model frameworks. We discuss challenges that arise in describing and distinguishing between different interventions, within different modelling structures, and allowing both within and between host dynamics. We also highlight challenges in modelling the health economic and political aspects of interventions. Given the diversity of these challenges, a broad variety of interdisciplinary expertise is needed to address them, combining mathematical knowledge with biological and social insights, and including health economics and communication skills. Addressing these challenges for the future requires strong cross-disciplinary collaboration together with close communication between scientists and policy makers.

Quantifying heterogeneity in sexual behaviour and distribution of STIs before and after pre-exposure prophylaxis among men who have sex with men.

Objectives: Pre-exposure prophylaxis (PrEP) use may influence sexual behaviour and transmission of STIs among men who have sex with men (MSM). We aimed to quantify the distribution of STI diagnoses among MSM in the Netherlands based on their sexual behaviour before and after the introduction of PrEP. Methods: HIV-negative MSM participating in a prospective cohort study (Amsterdam Cohort Studies) completed questionnaires about sexual behaviour and were tested for STI/HIV during biannual visits (2009-2019). We developed a sexual behaviour risk score predictive of STI diagnosis and used it to calculate Gini coefficients for gonorrhoea, chlamydia and syphilis diagnoses in the period before (2009 to mid-2015) and after PrEP (mid-2015 to 2019). Gini coefficients close to zero indicate that STI diagnoses are homogeneously distributed over the population, and close to one indicate that STI diagnoses are concentrated in individuals with a higher risk score. Results: The sexual behaviour risk score (n=630, n visits=10 677) ranged between 0.00 (low risk) and 3.61 (high risk), and the mean risk score increased from 0.70 (SD=0.66) before to 0.93 (SD=0.80) after PrEP. Positivity rates for chlamydia (4%) and syphilis (1%) remained relatively stable, but the positivity rate for gonorrhoea increased from 4% before to 6% after PrEP. Gini coefficients increased from 0.37 (95% CI 0.30 to 0.43) to 0.43 (95% CI 0.36 to 0.49) for chlamydia, and from 0.37 (95% CI 0.19 to 0.52) to 0.50 (95% CI 0.32 to 0.66) for syphilis comparing before to after PrEP. The Gini coefficient for gonorrhoea remained stable at 0.46 (95% CI 0.40 to 0.52) before and after PrEP. Conclusions: MSM engaged in more high-risk sexual behaviour and gonorrhoea diagnoses increased after PrEP was introduced. Chlamydia and syphilis diagnoses have become more concentrated in a high-risk subgroup. Monitoring the impact of increasing PrEP coverage on sexual behaviour and STI incidence is important. Improved STI prevention is needed, especially for high-risk MSM.

Time for change: Transitions between HIV risk levels and determinants of behavior change in men who have sex with men.

As individual sexual behavior is variable over time, the timing of interventions might be vital to reducing HIV transmission. We aimed to investigate transitions between HIV risk levels among men who have sex with men (MSM), and identify determinants associated with behavior change. Participants in a longitudinal cohort study among HIV-negative MSM (Amsterdam Cohort Studies) completed questionnaires about their sexual behavior during biannual visits (2008-2017). Visits were assigned to different HIV risk levels, based on latent classes of behavior. We modelled transitions between risk levels, and identified determinants associated with these transitions at the visit preceding the transition using multi-state Markov models. Based on 7,865 visits of 767 participants, we classified three risk levels: low (73% of visits), medium (22%), and high risk (5%). For MSM at low risk, the six-month probability of increasing risk was 0.11. For MSM at medium risk, the probability of increasing to high risk was 0.08, while the probability of decreasing to low risk was 0.33. For MSM at high risk, the probability of decreasing risk was 0.43. Chemsex, erection stimulants and poppers, high HIV risk perception, and recent STI diagnosis were associated with increased risk at the next visit. High HIV risk perception and young age were associated with decreasing risk. Although the majority of MSM showed no behavior change, a considerable proportion increased HIV risk. Determinants associated with behavior change may help to identify MSM who are likely to increase risk in the near future and target interventions at these individuals, thereby reducing HIV transmission.

Controlling the pandemic during the SARS-CoV-2 vaccination rollout.

There is a consensus that mass vaccination against SARS-CoV-2 will ultimately end the COVID-19 pandemic. However, it is not clear when and which control measures can be relaxed during the rollout of vaccination programmes. We investigate relaxation scenarios using an age-structured transmission model that has been fitted to age-specific seroprevalence data, hospital admissions, and projected vaccination coverage for Portugal. Our analyses suggest that the pressing need to restart socioeconomic activities could lead to new pandemic waves, and that substantial control efforts prove necessary throughout 2021. Using knowledge on control measures introduced in 2020, we anticipate that relaxing measures completely or to the extent as in autumn 2020 could launch a wave starting in April 2021. Additional waves could be prevented altogether if measures are relaxed as in summer 2020 or in a step-wise manner throughout 2021. We discuss at which point the control of COVID-19 would be achieved for each scenario.

Model-based evaluation of school- and non-school-related measures to control the COVID-19 pandemic.

The role of school-based contacts in the epidemiology of SARS-CoV-2 is incompletely understood. We use an age-structured transmission model fitted to age-specific seroprevalence and hospital admission data to assess the effects of school-based measures at different time points during the COVID-19 pandemic in the Netherlands. Our analyses suggest that the impact of measures reducing school-based contacts depends on the remaining opportunities to reduce non-school-based contacts. If opportunities to reduce the effective reproduction number (Re) with non-school-based measures are exhausted or undesired and Re is still close to 1, the additional benefit of school-based measures may be considerable, particularly among older school children. As two examples, we demonstrate that keeping schools closed after the summer holidays in 2020, in the absence of other measures, would not have prevented the second pandemic wave in autumn 2020 but closing schools in November 2020 could have reduced Re below 1, with unchanged non-school-based contacts.

The Rhythm of Risk: Sexual Behaviour, PrEP Use and HIV Risk Perception Between 1999 and 2018 Among Men Who Have Sex with Men in Amsterdam, The Netherlands.

HIV risk perception plays a crucial role in the uptake of preventive strategies. We investigated how risk perception and its determinants changed between 1999 and 2018 in an open, prospective cohort of 1323 HIV-negative men who have sex with men (MSM). Risk perception, defined as the perceived likelihood of acquiring HIV in the past 6 months, changed over time: being relatively lower in 2008-2011, higher in 2012-2016, and again lower in 2017-2018. Irrespective of calendar year, condomless anal intercourse (AI) with casual partners and high numbers of partners were associated with higher risk perception. In 2017-2018, condomless receptive AI with a partner living with HIV was no longer associated with risk perception, while PrEP use and condomless AI with a steady partner were associated with lower risk perception. We showed that risk perception has fluctuated among MSM in the past 20 years. The Undetectable equals Untransmittable statement and PrEP coincided with lower perceived risk.

Correction: Antigenic evolution of viruses in host populations.

[This corrects the article DOI: 10.1371/journal.ppat.1007291.].

Impact of delays on effectiveness of contact tracing strategies for COVID-19: a modelling study.

BACKGROUND: In countries with declining numbers of confirmed cases of COVID-19, lockdown measures are gradually being lifted. However, even if most physical distancing measures are continued, other public health measures will be needed to control the epidemic. Contact tracing via conventional methods or mobile app technology is central to control strategies during de-escalation of physical distancing. We aimed to identify key factors for a contact tracing strategy to be successful. METHODS: We evaluated the impact of timeliness and completeness in various steps of a contact tracing strategy using a stochastic mathematical model with explicit time delays between time of infection and symptom onset, and between symptom onset, diagnosis by testing, and isolation (testing delay). The model also includes tracing of close contacts (eg, household members) and casual contacts, followed by testing regardless of symptoms and isolation if testing positive, with different tracing delays and coverages. We computed effective reproduction numbers of a contact tracing strategy (RCTS) for a population with physical distancing measures and various scenarios for isolation of index cases and tracing and quarantine of their contacts. FINDINGS: For the most optimistic scenario (testing and tracing delays of 0 days and tracing coverage of 100%), and assuming that around 40% of transmissions occur before symptom onset, the model predicts that the estimated effective reproduction number of 1·2 (with physical distancing only) will be reduced to 0·8 (95% CI 0·7-0·9) by adding contact tracing. The model also shows that a similar reduction can be achieved when testing and tracing coverage is reduced to 80% (RCTS 0·8, 95% CI 0·7-1·0). A testing delay of more than 1 day requires the tracing delay to be at most 1 day or tracing coverage to be at least 80% to keep RCTS below 1. With a testing delay of 3 days or longer, even the most efficient strategy cannot reach RCTS values below 1. The effect of minimising tracing delay (eg, with app-based technology) declines with decreasing coverage of app use, but app-based tracing alone remains more effective than conventional tracing alone even with 20% coverage, reducing the reproduction number by 17·6% compared with 2·5%. The proportion of onward transmissions per index case that can be prevented depends on testing and tracing delays, and given a 0-day tracing delay, ranges from up to 79·9% with a 0-day testing delay to 41·8% with a 3-day testing delay and 4·9% with a 7-day testing delay. INTERPRETATION: In our model, minimising testing delay had the largest impact on reducing onward transmissions. Optimising testing and tracing coverage and minimising tracing delays, for instance with app-based technology, further enhanced contact tracing effectiveness, with the potential to prevent up to 80% of all transmissions. Access to testing should therefore be optimised, and mobile app technology might reduce delays in the contact tracing process and optimise contact tracing coverage. FUNDING: ZonMw, Fundação para a Ciência e a Tecnologia, and EU Horizon 2020 RECOVER.

Impact of self-imposed prevention measures and short-term government-imposed social distancing on mitigating and delaying a COVID-19 epidemic: A modelling study.

BACKGROUND: The coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to nearly every country in the world since it first emerged in China in December 2019. Many countries have implemented social distancing as a measure to "flatten the curve" of the ongoing epidemics. Evaluation of the impact of government-imposed social distancing and of other measures to control further spread of COVID-19 is urgent, especially because of the large societal and economic impact of the former. The aim of this study was to compare the individual and combined effectiveness of self-imposed prevention measures and of short-term government-imposed social distancing in mitigating, delaying, or preventing a COVID-19 epidemic. METHODS AND FINDINGS: We developed a deterministic compartmental transmission model of SARS-CoV-2 in a population stratified by disease status (susceptible, exposed, infectious with mild or severe disease, diagnosed, and recovered) and disease awareness status (aware and unaware) due to the spread of COVID-19. Self-imposed measures were assumed to be taken by disease-aware individuals and included handwashing, mask-wearing, and social distancing. Government-imposed social distancing reduced the contact rate of individuals irrespective of their disease or awareness status. The model was parameterized using current best estimates of key epidemiological parameters from COVID-19 clinical studies. The model outcomes included the peak number of diagnoses, attack rate, and time until the peak number of diagnoses. For fast awareness spread in the population, self-imposed measures can significantly reduce the attack rate and diminish and postpone the peak number of diagnoses. We estimate that a large epidemic can be prevented if the efficacy of these measures exceeds 50%. For slow awareness spread, self-imposed measures reduce the peak number of diagnoses and attack rate but do not affect the timing of the peak. Early implementation of short-term government-imposed social distancing alone is estimated to delay (by at most 7 months for a 3-month intervention) but not to reduce the peak. The delay can be even longer and the height of the peak can be additionally reduced if this intervention is combined with self-imposed measures that are continued after government-imposed social distancing has been lifted. Our analyses are limited in that they do not account for stochasticity, demographics, heterogeneities in contact patterns or mixing, spatial effects, imperfect isolation of individuals with severe disease, and reinfection with COVID-19. CONCLUSIONS: Our results suggest that information dissemination about COVID-19, which causes individual adoption of handwashing, mask-wearing, and social distancing, can be an effective strategy to mitigate and delay the epidemic. Early initiated short-term government-imposed social distancing can buy time for healthcare systems to prepare for an increasing COVID-19 burden. We stress the importance of disease awareness in controlling the ongoing epidemic and recommend that, in addition to policies on social distancing, governments and public health institutions mobilize people to adopt self-imposed measures with proven efficacy in order to successfully tackle COVID-19.

Short- and long-term impact of vaccination against cytomegalovirus: a modeling study.

BACKGROUND: Infection with cytomegalovirus (CMV) is highly prevalent worldwide and can cause severe disease in immunocompromised persons and congenitally infected infants. The disease burden caused by congenital CMV infection is high, especially in resource-limited countries. Vaccines are currently under development for various target groups. METHODS: We evaluated the impact of vaccination strategies and hygiene intervention using transmission models. Model parameters were estimated from a cross-sectional serological population study (n=5179) and a retrospective birth cohort (n=31,484), providing information on the age- and sex-specific CMV prevalence and on the birth prevalence of congenital CMV (cCMV). RESULTS: The analyses show that vertical transmission and infectious reactivation are the main drivers of transmission. Vaccination strategies aimed at reducing transmission from mother to child (vaccinating pregnant women or women of reproductive age) can yield substantial reductions of cCMV in 20 years (31.7-71.4% if 70% of women are effectively vaccinated). Alternatively, hygiene intervention aimed at preventing CMV infection and re-infection of women of reproductive age from young children is expected to reduce cCMV by less than 2%. The effects of large-scale vaccination on CMV prevalence can be substantial, owing to the moderate transmissibility of CMV at the population level. However, as CMV causes lifelong infection, the timescale on which reductions in CMV prevalence are expected is in the order of several decades. Elimination of CMV infection in the long run is only feasible for a vaccine with a long duration of protection and high vaccination coverage. CONCLUSIONS: Vaccination is an effective intervention to reduce the birth prevalence of cCMV. Population-level reductions in CMV prevalence can only be achieved on a long timescale. Our results stress the value of vaccinating pregnant women and women of childbearing age and provide support for the development of CMV vaccines and early planning of vaccination scenarios and rollouts.

Impact of sexual trajectories of men who have sex with men on the reduction in HIV transmission by pre-exposure prophylaxis.

Changes in sexual risk behavior over the life course in men who have sex with men (MSM) can influence population-level intervention efficacy. Our objective was to investigate the impact of incorporating sexual trajectories describing long-term changes in risk levels on the reduction in HIV prevalence by pre-exposure prophylaxis (PrEP) among MSM. Based on the Amsterdam Cohort Study data, we developed two models of HIV transmission in a population stratified by sexual behavior. In the first model, individuals were stratified into low, medium and high risk levels and did not change their risk levels. The second model had the same stratification but incorporated additionally three types of sexual behavior trajectories. The models assumed universal antiretroviral treatment of HIV+ MSM, and PrEP use by high risk HIV- MSM. We computed the relative reduction in HIV prevalence in both models for annual PrEP uptakes of 10% to 80% at different time points after PrEP introduction. We then investigated the impact of sexual trajectories on the effectiveness of PrEP intervention. The impact of sexual trajectories on the overall prevalence and prevalence in individuals at low, medium and high risk levels varied with PrEP uptake and time after PrEP introduction. Compared to the model without sexual trajectories, the model with trajectories predicted a higher impact of PrEP on the overall prevalence, and on the prevalence among the medium and high risk individuals. In low risk individuals, there was more reduction in prevalence during the first 15 years of PrEP intervention if sexual trajectories were not incorporated in the model. After that point, at low risk level there was more reduction in the model with trajectories. In conclusion, our study predicts that sexual trajectories increase the estimated impact of PrEP on reducing HIV prevalence when compared to a population where risk levels do not change.

Elimination prospects of the Dutch HIV epidemic among men who have sex with men in the era of preexposure prophylaxis.

OBJECTIVE: Preexposure prophylaxis (PrEP) is a promising intervention to help end the HIV epidemic among men who have sex with men (MSM) in the Netherlands. We aimed to assess the impact of PrEP on HIV prevalence in this population and to determine the levels of PrEP coverage necessary for HIV elimination. DESIGN AND METHODS: We developed a mathematical model of HIV transmission in a population stratified by sexual risk behavior with universal antiretroviral treatment (ART) and daily PrEP use depending on an individual's risk behavior. We computed the effective reproduction number, HIV prevalence, ART and PrEP coverage for increasing ART and PrEP uptake levels, and examined how these were affected by PrEP effectiveness and duration of PrEP use. RESULTS: At current levels of ART coverage of 80%, PrEP effectiveness of 86% and PrEP duration of 5 years, HIV elimination required 82% PrEP coverage in the highest risk group (12 000 MSM with more than 18 partners per year). If ART coverage increased by 9%, the elimination threshold was at 70% PrEP coverage. For shorter PrEP duration and lower effectiveness elimination prospects were less favorable. For the same number of PrEP users distributed among two groups with highest risk behavior, prevalence dropped from the current 8 to 4.6%. CONCLUSION: PrEP for HIV prevention among MSM could, in principle, eliminate HIV from this population in the Netherlands. The highest impact of PrEP on prevalence was predicted when ART and PrEP coverage increased simultaneously and PrEP was used by the highest risk individuals.