Programme science: a route to effective coverage and population-level impact for HIV and sexually transmitted infection prevention.

Improvements in context-specific programming are essential to address HIV and other sexually transmitted and blood-borne infection epidemics globally. A programme science approach emphasises the need for context-specific evidence and knowledge, generated on an ongoing basis, to inform timely and appropriate programmatic decisions. We aim to accelerate and improve the use of embedded research, inquiry, and learning to optimise population-level impact of public health programmes and to introduce an effective programme coverage framework as one tool to facilitate this goal. The framework was developed in partnership with public health experts in HIV and sexually transmitted and blood-borne infections through several workshops and meetings. The framework is a practice-based tool that centres on the use of data from iterative cycles of programme-embedded research and learning, as well as routine programme monitoring, to refine the strategy and implementation of a programme. This programme science approach aims to reduce programme coverage gaps, to optimise impact at the population level, and to achieve effective coverage. This framework should facilitate the generation of programme-embedded research and learning agendas to inform resource allocation, optimise population-level impact, and achieve equitable and effective programme coverage.

Reductions in HIV incidence are likely to increase the importance of key population programmes for HIV control in sub-Saharan Africa.

INTRODUCTION: An efficient HIV response requires that resources be focussed on effective interventions for those most at risk of acquiring and transmitting infection. As HIV epidemics evolve the distribution of HIV across key and other populations will change. Here, the epidemiological concepts underpinning these changes are described and the importance of appropriate allocation of effective interventions is discussed. DISCUSSION: In many sub-Saharan African countries HIV epidemics have been categorized as "generalized," and HIV testing, treatment and prevention interventions have focussed on the "general" population. As HIV epidemics are better controlled the relative importance of "key" populations will increase, dominating the ongoing burden of disease and providing the potential for repeated outbreaks of HIV if interventions are relaxed. The basic reproductive number (R0 ) describes the potential for an infectious disease to spread at the boundary of invasion or elimination, whereas the effective reproduction number (Rt ) describes the current potential for spread. Heterogeneity in risk means that while Rt is temporarily below one and prevalence declining, the R0 can remain above one, preventing eventual elimination. Patterns of HIV acquisition are often used to guide interventions but inadequately capture the transmission dynamics of the virus and the most efficient approach to controlling HIV. Risks for HIV acquisition are not identical to risks for HIV transmission and will change depending on the epidemiological context. In addition to the challenges in measuring HIV transmission dynamics, there is a tension between using epidemiology to drive the HIV response and the social and political realities constraining how programmes and providers can practically and appropriately focus on key populations and maintain political support. In addition to being well focussed, interventions need to be effective and cost-effective, which requires a better understanding of packages of interventions rather than specific tools. CONCLUSIONS: Continued control of HIV will increasingly rely on resources, programmes and interventions supporting key populations. Current epidemiological and programmatic approaches for key populations in sub-Saharan Africa are insufficient with a need for an improved understanding of local epidemiology and the effectiveness of interventions.

The potential role of long-acting injectable cabotegravir-rilpivirine in the treatment of HIV in sub-Saharan Africa: a modelling analysis.

BACKGROUND: The use of a combination of the integrase inhibitor, cabotegravir, and the non-nucleoside reverse transcriptase inhibitor, rilpivirine, in a long-acting injectable form is being considered as an antiretroviral treatment option for people with HIV in sub-Saharan Africa. We aimed to model the effects of injectable cabotegravir-rilpivirine to help to inform its potential effectiveness and cost-effectiveness under different possible policies for its introduction. METHODS: We used an existing individual-based model of HIV to predict the effects of introducing monthly injections of cabotegravir-rilpivirine for people with HIV in low-income settings in sub-Saharan Africa. We evaluated policies in the context of 1000 setting scenarios that reflected characteristics of HIV epidemics and programmes in sub-Saharan Africa. We compared three policies for introduction of injectable cabotegravir-rilpivirine with continued use of dolutegravir-based oral regimens for: all individuals on antiretroviral therapy (ART); individuals with a recently measured viral load of more than 1000 copies per mL (signifying poor adherence to oral drugs, and often associated with drug resistance); and individuals with a recently measured viral load of less than 1000 copies per mL (a group with a lower prevalence of pre-existing drug resistance). We also did cost-effectiveness analysis, taking a health system perspective over a 10 year period, with 3% discounting of disability-adjusted life-years (DALYs) and costs. A cost-effectiveness threshold of US$500 per DALY averted was used to establish if a policy was cost-effective. FINDINGS: In our model, all policies involving the introduction of injectable cabotegravir-rilpivirine were predicted to lead to an increased proportion of people with HIV on ART, increased viral load suppression, and decreased AIDS-related mortality, with lesser benefits in people with a recently measured viral load of less than 1000 copies per mL. Its introduction is also predicted to lead to increases in resistance to integrase inhibitors and non-nucleoside reverse transcriptase inhibitors if introduced in all people with HIV on ART or in those with a recently measured viral load of less than 1000 copies per mL, but to a lesser extent if introduced in people with more than 1000 copies per mL due to concentration of its use in people less adherent to oral therapy. Consistent with the effect on AIDS-related mortality, all approaches to the introduction of injectable cabotegravir-rilpivirine are predicted to avert DALYs. Assuming a cost of $120 per person per year, use of this regimen in people with a recently measured viral load of more than 1000 copies per mL was borderline cost-effective (median cost per DALY averted across setting scenarios $404). The other approaches considered for its use are unlikely to be cost-effective unless the cost per year of injectable cabotegravir-rilpivirine is considerably reduced. INTERPRETATION: Our modelling suggests that injectable cabotegravir-rilpivirine offers potential benefits; however, to be a cost-effective option, its introduction might need to be carefully targeted to individuals with HIV who might otherwise have suboptimal adherence to ART. As data accumulate from trials and implementation studies, such findings can be incorporated into the model to better inform on the full consequences of policy alternatives. FUNDING: Bill & Melinda Gates Foundation, including through the HIV Modelling Consortium (OPP1191655).

Strengthening measurement and performance of HIV prevention programmes.

Indicators for the measurement of programmes for the primary prevention of HIV are less aligned than indicators for HIV treatment, which results in a high burden of data collection, often without a clear vision for its use. As new evidence becomes available, the opportunity arises to critically evaluate the way countries and global bodies monitor HIV prevention programmes by incorporating emerging data on the strength of the evidence linking various factors with HIV acquisition, and by working to streamline indicators across stakeholders to reduce burdens on health-care systems. Programmes are also using new approaches, such as targeting specific sexual networks that might require non-traditional approaches to measurement. Technological advances can support these new directions and provide opportunities to use real-time analytics and new data sources to more effectively understand and adapt HIV prevention programmes to reflect population movement, risks, and an evolving epidemic.

High variability in the measurement of HIV primary prevention activities and outcomes.

INTRODUCTION: While there is a global consensus on monitoring Human Immunodeficiency Virus (HIV) treatment progress, there has been less attention to the degree of consistency of the measurement of HIV prevention programmes-and the global prevention response is not on-track to achieve 2020 goals. In this paper, we assess the degree of variability in primary prevention indicators selected by national strategic plans (NSPs) and global stakeholder monitoring and evaluation (M&E) strategies. METHODS: We obtained the most recent NSPs from low and middle income Joint United Nations Programme on HIV/AIDS (UNAIDS) Fast-Track countries, and M&E documents from The Global Fund to Fight AIDS, Tuberculosis and Malaria (The Global Fund), President's Emergency Plan for AIDS Relief (PEPFAR), UNAIDS, the Global HIV Prevention Coalition and the World Health Organization (WHO). We extracted HIV primary prevention indicators from each document, standardized and aggregated them by age/ sex, categorized indicators by topic, and evaluated the frequency of matched indicators between countries and stakeholders. Data were collected between February and April of 2019. RESULTS: Twenty-one NSPs and five global stakeholder documents were assessed; 736 primary prevention indicators were identified; 284 remained following standardization and aggregation. NSPs contained from 3 to 48 primary prevention indicators, with an average of 23; categories included: HIV education and outreach (17.6%), testing (17.3%) and condom use (16.2%). Of unique national indicators, only 34% was shared between two or more countries. Sixty-nine per cent was applied in a single country only. 56% of NSP indicators did not appear in any global stakeholder document. Conversely, 42% of global indicators did not appear in any surveyed NSPs. Within global indicators, 63% was only measured by one global body, and no single indicator was measured by all five. CONCLUSIONS: These analyses reveal a lack of consensus both between and within countries' and global stakeholders' measurement of HIV prevention. Though some variability is expected, these findings point to a need to refocus attention on achieving greater consensus on a global measurement framework for HIV prevention.

Maximising HIV prevention by balancing the opportunities of today with the promises of tomorrow: a modelling study.

BACKGROUND: Many ways of preventing HIV infection have been proposed and more are being developed. We sought to construct a strategic approach to HIV prevention that would use limited resources to achieve the greatest possible prevention impact through the use of interventions available today and in the coming years. METHODS: We developed a deterministic compartmental model of heterosexual HIV transmission in South Africa and formed assumptions about the costs and effects of a range of interventions, encompassing the further scale-up of existing interventions (promoting condom use, male circumcision, early antiretroviral therapy [ART] initiation for all [including increased HIV testing and counselling activities], and oral pre-exposure prophylaxis [PrEP]), the introduction of new interventions in the medium term (offering intravaginal rings, long-acting injectable antiretroviral drugs) and long term (vaccine, broadly neutralising antibodies [bNAbs]). We examined how available resources could be allocated across these interventions to achieve maximum impact, and assessed how this would be affected by the failure of the interventions to be developed or scaled up. FINDINGS: If all interventions are available, the optimum mix would place great emphasis on the following: scale-up of male circumcision and early ART initiation with outreach testing, as these are available immediately and assumed to be low cost and highly efficacious; intravaginal rings targeted to sex workers; and vaccines, as these can achieve a large effect if scaled up even if imperfectly efficacious. The optimum mix would rely less on longer term developments, such as long-acting antiretroviral drugs and bNAbs, unless the costs of these reduced. However, if impossible to scale up existing interventions to the extent assumed, emphasis on oral PrEP, intravaginal rings, and long-acting antiretroviral drugs would increase. The long-term effect on the epidemic is most affected by scale-up of existing interventions and the successful development of a vaccine. INTERPRETATION: With current information, a strategic approach in which limited resources are used to maximise prevention impact would focus on strengthening the scale-up of existing interventions, while pursuing a workable vaccine and developing other approaches that can be used if further scale-up of existing interventions is limited. FUNDING: Bill & Melinda Gates Foundation.

The HIV prevention cascade: integrating theories of epidemiological, behavioural, and social science into programme design and monitoring.

Theories of epidemiology, health behaviour, and social science have changed the understanding of HIV prevention in the past three decades. The HIV prevention cascade is emerging as a new approach to guide the design and monitoring of HIV prevention programmes in a way that integrates these multiple perspectives. This approach recognises that translating the efficacy of direct mechanisms that mediate HIV prevention (including prevention products, procedures, and risk-reduction behaviours) into population-level effects requires interventions that increase coverage. An HIV prevention cascade approach suggests that high coverage can be achieved by targeting three key components: demand-side interventions that improve risk perception and awareness and acceptability of prevention approaches; supply-side interventions that make prevention products and procedures more accessible and available; and adherence interventions that support ongoing adoption of prevention behaviours, including those that do and do not involve prevention products. Programmes need to develop delivery platforms that ensure these interventions reach target populations, to shape the policy environment so that it facilitates implementation at scale with high quality and intensity, and to monitor the programme with indicators along the cascade.

HIV Prevention 2020: a framework for delivery and a call for action.

Although effective programmes are available and several countries have seen substantial declines in new HIV infections, progress in the reduction of adult HIV incidence has been slower than expected worldwide and many countries have not had large decreases in new infections in adults despite large reductions in paediatric infections. Reasons for slow progress include inadequate commitment, investment, focus, scale, and quality of implementation of prevention and treatment interventions. The UNAIDS-Lancet Commission on Defeating AIDS-Advancing Global Health reported that the provision of large-scale, effective HIV prevention programmes has failed and called on stakeholders to "get serious about HIV prevention". An ambitious worldwide target has been set by UNAIDS to reduce new infections below 500 000 by 2020-a 75% reduction from 2010. Models show that such a reduction requires a combination of primary prevention interventions and preventative effects of treatment. Achievement of the target will require more effective delivery of HIV prevention for sufficient coverage in populations at greatest risk of infection ensuring that interventions that have proved effective are made available, barriers to their uptake are overcome, demand is created, and use is consistent and occurs at the right scale with high coverage. This paper discusses how programmatic targets for prevention in a worldwide plan could be used to re-energise the HIV prevention approach. A management framework is proposed outlining global, regional, national, and subnational actions and is summarised in a call for action on HIV prevention for 2020.

Sexually transmitted infection screening uptake and knowledge of sexually transmitted infection symptoms among female sex workers participating in a community randomised trial in Peru.

This study aims to evaluate condom use, sexually transmitted infection (STI) screening, and knowledge of STI symptoms among female sex workers in Peru associated with sex work venues and a community randomised trial of STI control. One component of the Peru PREVEN intervention conducted mobile-team outreach to female sex workers to reduce STIs and increase condom use and access to government clinics for STI screening and evaluation. Prevalence ratios were calculated using multivariate Poisson regression models with robust standard errors, clustering by city. As-treated analyses were conducted to assess outcomes associated with reported exposure to the intervention. Care-seeking was more frequent in intervention communities, but differences were not statistically significant. Female sex workers reporting exposure to the intervention had a significantly higher likelihood of condom use, STI screening at public health clinics, and symptom recognition compared to those not exposed. Compared with street- or bar-based female sex workers, brothel-based female sex workers reported significantly higher rates of condom use with last client, recent screening exams for STIs, and HIV testing. Brothel-based female sex workers also more often reported knowledge of STIs and recognition of STI symptoms in women and in men. Interventions to promote STI detection and prevention among female sex workers in Peru should consider structural or regulatory factors related to sex work venues.

Heterogeneity in risk of pelvic inflammatory diseases after chlamydia infection: a population-based study in Manitoba, Canada.

BACKGROUND: The association between chlamydia infection and pelvic inflammatory disease (PID) is a key parameter for models evaluating the impact of chlamydia control programs. We quantified this association using a retrospective population-based cohort. METHODS: We used administrative health data sets to construct a retrospective population-based cohort of women and girls aged 12-24 years who were resident in Manitoba, Canada, between 1992 and 1996. We performed survival analysis on a subcohort of individuals who were tested for chlamydia to estimate the risk of PID diagnosed in a primary care, outpatient, or inpatient setting after ≥ 1 positive chlamydia test. RESULTS: A total of 73 883 individuals contributed 625 621 person years of follow-up. Those with a diagnosis of chlamydia had an increased risk of PID over their reproductive lifetime compared with those who tested negative (adjusted hazard ratio [AHR], 1.55; 95% confidence interval [CI], 1.43-1.70). This risk increased with each subsequent infection: the AHR was 1.17 for first reinfection (95% CI, 1.06-1.30) and 1.35 for the second (95% CI, 1.04-1.75). The increased risk of PID from reinfection was highest in younger individuals (AHR, 4.55 (95% CI, 3.59-5.78) in individuals aged 12-15 years at the time of their second reinfection, compared with individuals older than 30 years). CONCLUSIONS: There is heterogeneity in the risk of PID after a chlamydia infection. Describing the progression to PID in mathematical models as an average rate may be an oversimplification; more accurate estimates of the cost-effectiveness of screening may be obtained by using an individual-based measure of risk. Health inequalities may be reduced by targeting health promotion interventions at sexually active girls younger than 16 years and those with a history of chlamydia.

The theoretical impact and cost-effectiveness of vaccines that protect against sexually transmitted infections and disease.

Sexually transmitted diseases, a source of widespread morbidity and sometimes mortality, are caused by a diverse group of infections with a common route of transmission. Existing vaccines against hepatitis B virus (HBV) and human papilloma virus 16, 18, 6 and 11 are highly efficacious and cost effective. In reviewing the potential role for other vaccines against sexually transmitted infections (STIs) a series of questions needs to be addressed about the burden of disease, the potential characteristics of a new vaccine, and the impact of other interventions. These questions can be viewed in the light of the population dynamics of sexually transmitted infections as a group and how a vaccine can impact these dynamics. Mathematical models show the potential for substantial impact, especially if vaccines are widely used. To better make the case for sexually transmitted infection vaccines we need better data and analyses of the burden of disease, especially severe disease. However, cost effectiveness analyses using a wide range of assumptions show that STI vaccines would be cost effective and their development a worthwhile investment.

Reaching the unreachable: providing STI control services to female sex workers via mobile team outreach.

BACKGROUND: As part of a community-randomized trial of a multicomponent intervention to prevent sexually transmitted infections, we created Mobile Teams (MTs) in ten intervention cities across Peru to improve outreach to female sex workers (FSW) for strengthened STI prevention services. METHODS: Throughout 20 two-month cycles, MTs provided counseling; condoms; screening and specific treatment for Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), and vaginal Trichomonas vaginalis (TV) infections; and periodic presumptive metronidazole treatment for vaginal infections. RESULTS: MTs had 48,207 separate encounters with 24,814 FSW; numbers of sex work venues and of FSW reached increased steadily over several cycles. Approximately 50% of FSW reached per cycle were new. Reported condom use with last client increased from 73% to 93%. Presumptive metronidazole treatment was accepted 83% of times offered. Over 38 months, CT prevalence declined from 15.4% to 8.2%, and TV prevalence from 7.3% to 2.6%. Among participants in ≥ 9 cycles, CT prevalence decreased from 12.9% to 6.0% (p <0.001); TV from 4.6% to 1.5% (p <0.001); and NG from 0.8% to 0.4% (p = 0.07). CONCLUSIONS: Mobile outreach to FSW reached many FSW not utilizing government clinics. Self-reported condom use substantially increased; CT and TV prevalences declined significantly. The community-randomized trial, reported separately, demonstrated significantly greater reductions in composite prevalence of CT, NG, TV, or high-titer syphilis serology in FSW in these ten intervention cities than in ten matched control cities.

Vaccinating women previously exposed to human papillomavirus: a cost-effectiveness analysis of the bivalent vaccine.

Recent trials have indicated that women with prior exposure to Human papillomavirus (HPV) subtypes 16/18 receive protection against reinfection from the HPV vaccines. However, many of the original models investigating the cost effectiveness of different vaccination strategies for the protection of cervical cancer assumed, based on the trial results at that time, that these women received no protection. We developed a deterministic, dynamic transmission model that incorporates the vaccine-induced protection of women with prior exposure to HPV. The model was used to estimate the cost effectiveness of progressively extending a vaccination programme using the bivalent vaccine to older age groups both with and without protection of women with prior exposure. We did this under a range of assumptions on the level of natural immunity. Our modelling projections indicate that including the protection of women with prior HPV exposure can have a profound effect on the cost effectiveness of vaccinating adults. The impact of this protection is inversely related to the level of natural immunity. Our results indicate that adult vaccination strategies should potentially be reassessed, and that it is important to include the protection of non-naive women previously infected with HPV in future studies. Furthermore, they also highlight the need for a more thorough investigation of this protection.

Transmission dynamics of the four dengue serotypes in southern Vietnam and the potential impact of vaccination.

BACKGROUND: With approximately 2.5 billion people at risk, dengue is a major international public health concern. Dengue vaccines currently in development should help reduce the burden associated with this disease but the most efficient way of using future dengue vaccines remains to be defined. Mathematical models of transmission can provide insight into the expected impact of different vaccination strategies at a population level and contribute to this definition. METHODS AND FINDINGS: We developed and analyzed an age-structured, host-vector and serotype-specific compartmental model, including seasonality. We first used this transmission model to identify the immunological interactions between serotypes that affect the risks and consequences of secondary infections (cross-protection, increased susceptibility, increased severity, and increased infectiousness) and reproduce the observed epidemiology of dengue. For populating this model, we used routine surveillance data from Southern Vietnam and the results of a prospective cohort study conducted in the same area. The model provided a good fit to the observed data for age, severity of cases, serotype distribution, and dynamics over time, using two scenarios of immunological interaction : short term cross-protection alone (6-17 months) or a combination of short term cross-protection with cross-enhancement (increased susceptibility, severity and infectiousness in the case of secondary infections). Finally, we explored the potential impact of vaccination for these two scenarios. Both highlighted that vaccination can substantially decrease dengue burden by reducing the magnitude and frequency of outbreaks. CONCLUSION: Our model suggests that seasonality and short term cross-protection are key factors for explaining dengue dynamics in Southern Vietnam. Vaccination was predicted to significantly reduce the disease burden, even in the situation where immunological cross-enhancement affects the risks and consequences of secondary infections.

The potential impact of pre-exposure prophylaxis for HIV prevention among men who have sex with men and transwomen in Lima, Peru: a mathematical modelling study.

BACKGROUND: HIV pre-exposure prophylaxis (PrEP), the use of antiretroviral drugs by uninfected individuals to prevent HIV infection, has demonstrated effectiveness in preventing acquisition in a high-risk population of men who have sex with men (MSM). Consequently, there is a need to understand if and how PrEP can be used cost-effectively to prevent HIV infection in such populations. METHODS AND FINDINGS: We developed a mathematical model representing the HIV epidemic among MSM and transwomen (male-to-female transgender individuals) in Lima, Peru, as a test case. PrEP effectiveness in the model is assumed to result from the combination of a "conditional efficacy" parameter and an adherence parameter. Annual operating costs from a health provider perspective were based on the US Centers for Disease Control and Prevention interim guidelines for PrEP use. The model was used to investigate the population-level impact, cost, and cost-effectiveness of PrEP under a range of implementation scenarios. The epidemiological impact of PrEP is largely driven by programme characteristics. For a modest PrEP coverage of 5%, over 8% of infections could be averted in a programme prioritising those at higher risk and attaining the adherence levels of the Pre-Exposure Prophylaxis Initiative study. Across all scenarios, the highest estimated cost per disability-adjusted life year averted (uniform strategy for a coverage level of 20%, US$1,036-US$4,254) is below the World Health Organization recommended threshold for cost-effective interventions, while only certain optimistic scenarios (low coverage of 5% and some or high prioritisation) are likely to be cost-effective using the World Bank threshold. The impact of PrEP is reduced if those on PrEP decrease condom use, but only extreme behaviour changes among non-adherers (over 80% reduction in condom use) and a low PrEP conditional efficacy (40%) would adversely impact the epidemic. However, PrEP will not arrest HIV transmission in isolation because of its incomplete effectiveness and dependence on adherence, and because the high cost of programmes limits the coverage levels that could potentially be attained. CONCLUSIONS: A strategic PrEP intervention could be a cost-effective addition to existing HIV prevention strategies for MSM populations. However, despite being cost-effective, a substantial expenditure would be required to generate significant reductions in incidence. Please see later in the article for the Editors' Summary.

Improved STD syndrome management by a network of clinicians and pharmacy workers in Peru: The PREVEN Network.

BACKGROUND: Sexually Transmitted diseases (STD) syndrome management has been one cornerstone of STD treatment. Persons with STD symptoms in many countries, especially those with limited resources, often initially seek care in pharmacies. The objective of the study was to develop and evaluate an integrated network of physicians, midwives and pharmacy workers trained in STD syndromic management (The PREVEN Network) as part of a national urban community-randomized trial of sexually transmitted infection prevention in Peru. METHODS AND FINDINGS: After a comprehensive census of physicians, midwives, and pharmacies in ten intervention and ten control cities, we introduced seminars and workshops for pharmacy workers, and continuing education for physicians and midwives in intervention cities and invited graduates to join the PREVEN Network. "Prevention Salespersons" visited pharmacies, boticas and clinicians regularly for educational support and collection of information on numbers of cases of STD syndromes seen at pharmacies and by clinicians in intervention cities. Simulated patients evaluated outcomes of training of pharmacy workers with respect to adequate STD syndrome management, recommendations for condom use and for treatment of partners. In intervention cities we trained, certified, and incorporated into the PREVEN Network the workers at 623 (80.6%) of 773 pharmacies and 701 (69.6%) of 1007 physicians and midwives in private practice. Extremely high clinician and pharmacy worker turnover, 13.4% and 44% respectively in the first year, dictated continued training of new pharmacy workers and clinicians. By the end of the intervention the Network included 792 pharmacies and 597 clinicians. Pharmacies reported more cases of STDs than did clinicians. Evaluations by simulated patients showed significant and substantial improvements in the management of STD syndromes at pharmacies in intervention cities but not in control cities. CONCLUSIONS: Training pharmacy workers linked to a referral network of clinicians proved feasible and acceptable. High turn-over was challenging but over come.

Prevalences of sexually transmitted infections in young adults and female sex workers in Peru: a national population-based survey.

BACKGROUND: We assessed prevalences of seven sexually transmitted infections (STIs) in Peru, stratified by risk behaviours, to help to define care and prevention priorities. METHODS: In a 2002 household-based survey of the general population, we enrolled randomly selected 18-29-year-old residents of 24 cities with populations greater than 50 000 people. We then surveyed female sex workers (FSWs) in these cities. We gathered data for sexual behaviour; vaginal specimens or urine for nucleic acid amplification tests for Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis; and blood for serological tests for syphilis, HIV, and (in subsamples) herpes simplex virus 2 (HSV2) and human T-lymphotropic virus. This study is a registered component of the PREVEN trial, number ISRCTN43722548. FINDINGS: 15 261 individuals from the general population and 4485 FSWs agreed to participate in our survey. Overall prevalence of infection with HSV2, weighted for city size, was 13·5% in men, 13·6% in women, and 60·6% in FSWs (all values in FSWs standardised to age composition of women in the general population). The prevalence of C trachomatis infection was 4·2% in men, 6·5% in women, and 16·4% in FSWs; of T vaginalis infection was 0·3% in men, 4·9% in women, and 7·9% in FSWs; and of syphilis was 0·5% in men, 0·4% in women, and 0·8% in FSWs. N gonorrhoeae infection had a prevalence of 0·1% in men and women, and of 1·6% in FSWs. Prevalence of HIV infection was 0·5% in men and FSWs, and 0·1% in women. Four (0·3%) of 1535 specimens were positive for human T-lymphotropic virus 1. In men, 65·0% of infections with HIV, 71·5% of N gonorrhoeae, and 41·4% of HSV2 and 60·9% of cases of syphilis were in the 13·3% who had sex with men or unprotected sex with FSWs in the past year. In women from the general population, 66·7% of infections with HIV and 16·7% of cases of syphilis were accounted for by the 4·4% who had been paid for sex by any of their past three partners. INTERPRETATION: Defining of high-risk groups could guide targeting of interventions for communicable diseases-including STIs-in the general Peruvian population. FUNDING: Wellcome Trust-Burroughs Wellcome Fund Infectious Disease Initiative and US National Institutes of Health.

Prevention of sexually transmitted infections in urban communities (Peru PREVEN): a multicomponent community-randomised controlled trial.

BACKGROUND: Previous community-randomised trials of interventions to control sexually transmitted infections (STIs) have involved rural settings, were rarely multicomponent, and had varying results. We aimed to assess the effect of a multicomponent intervention on curable STIs in urban young adults and female sex workers (FSWs). METHODS: In this community-randomised trial, baseline STI screening was done between August, and November, 2002, in random household samples of young adults (aged 18-29 years) and in FSWs in Peruvian cities with more than 50,000 inhabitants. Geographically separate cities were selected, matched into pairs, and randomly allocated to intervention or control groups with an S-PLUS program. Follow-up surveys of random samples were done after 2 years and 3 years. The intervention comprised four modalities: strengthened STI syndromic management by pharmacy workers and clinicians; mobile-team outreach to FSWs for STI screening and pathogen-specific treatment; periodic presumptive treatment of FSWs for trichomoniasis; and condom promotion for FSWs and the general population. Individuals in control cities received standard care. The composite primary endpoint was infection of young adults with Chlamydia trachomatis, Trichomonas vaginalis, or Neisseria gonorrhoeae, or syphilis seroreactivity. Laboratory workers and the data analyst were masked, but fieldworkers, the Peruvian study team, and participants in the outcome surveys were not. All analyses were done by intention to treat. This trial is registered, ISRCTN43722548. FINDINGS: We did baseline surveys of 15,261 young adults in 24 Peruvian cities. Of those, 20 geographically separate cities were matched into pairs, in each of which one city was assigned to intervention and the other to standard of care. In the 2006 follow-up survey, data for the composite primary outcome were available for 12,930 young adults. We report a non-significant reduction in prevalence of STIs in young adults, adjusted for baseline prevalence, in intervention cities compared with control cities (relative risk 0·84, 95% CI 0·69-1·02; p=0·096). In subgroup analyses, significant reductions were noted in intervention cities in young adult women and FSWs. INTERPRETATION: Syndromic management of STIs, mobile-team outreach to FSWs, presumptive treatment for trichomoniasis in FSWs, and condom promotion might reduce the composite prevalence of any of the four curable STIs investigated in this trial. FUNDING: Wellcome Trust and Burroughs Wellcome Fund, National Institutes of Health, Center for AIDS Research, CIPRA, and USAID-Peru.