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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.

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).

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.

Introduction Heterogeneity of sociodemographics and risk behaviours across the HIV treatment cascade could influence the public health impact of universal ART in sub‐Saharan Africa if those not virologically suppressed are more likely to be part of a risk group contributing to onward infections. Sociodemographic and risk heterogeneity across the treatment cascade has not yet been comprehensively described or quantified and we seek to systematically review and synthesize research on this topic among adults in Africa. Methods We conducted a systematic review of peer‐reviewed literature in Embase and MEDLINE databases as well as grey literature sources published in English between 2014 and 2018. We included studies that included people living with HIV (PLHIV) aged ≥15 years, and reported a 90‐90‐90 outcome: awareness of HIV‐positive status, ART use among those diagnosed or viral suppression among those on ART. We summarized measures of association between sociodemographics, within each outcome, and as a composite measure of population‐wide viral suppression. Results and discussion From 3533 screened titles, we extracted data from 92 studies (50 peer‐reviewed, 42 grey sources). Of included studies, 32 reported on awareness, 53 on ART use, 32 on viral suppression and 23 on population‐wide viral suppression. The majority of studies were conducted in South Africa, Uganda, and Malawi and reported data for age and gender. When stratified, PLHIV ages 15 to 24 years had lower median achievement of the treatment cascade (60‐49‐81), as compared to PLHIV ≥25 years (70‐63‐91). Men also had lower median achievement of the treatment cascade (66‐72‐85), compared to women (79‐76‐89). For population‐wide viral suppression, women aged ≥45 years had achieved the 73% target, while the lowest medians were among 15‐ to 24‐year‐old men (37%) and women (49%). Conclusions Considerable heterogeneity exists by age and gender for achieving the HIV 90‐90‐90 treatment goals. These results may inform delivery of HIV testing and treatment in sub‐Saharan Africa, as targeting youth and men could be a strategic way to maximize the population‐level impact of ART.

Mathematical models of sexually transmitted disease (STD) aim to represent sexual contact networks, pathogen characteristics, and intervention activities, helping understand and quantify STD epidemics and their control. Models are, unfortunately, necessary because non-linear infectious disease dynamics combined with many interacting variables undermines intuitive understanding. It is hoped that rational decision makers will include a range of evidence, including the finding of models, in funding, planning, implementing, and evaluating STD interventions and programs. The level of detailed required for informative models that can lead to better decisions, and how models can best be included in the international, national, and local public health ecosystem are areas for attention. Questions to consider are: 1) The pros and cons of focusing resources on sub-groups within a population. This is influenced by the biology and behavior associated with the STD, along with structural context. 2) How to ensure successful implementation of interventions? Here simple cascades are being used to identify gaps in treatment and prevention. 3) What is the relative value of developing, introducing and scaling the use of specific testing, treatment and prevention products in STD programs? The epidemiological context and coverage of other interventions have profound implications here. 4) How do we design a surveillance system that provides timely and actionable data on STD epidemiology? Here again the epidemiological context matters. The history of modeling STDs provides many examples that address such questions, and models are currently influencing policy, particularly in HIV programs. However, the development and validation of models in STD epidemiology has been hampered by our inability to directly measure the sexual network via which STDs spread. Recent efforts to evaluate model performance, and advances in pathogen sequencing and phylogenetic analysis, provide avenues to improve the validity and utility of STD models as their use becomes more systematic. Disclosure No significant relationships.

Background Despite policies for universal HIV testing and treatment (UTT) regardless of CD4 count, there are still 1.8 million new HIV infections and 1 million AIDS-related deaths annually. The UNAIDS 90-90-90 goals target suppression of HIV viral load in 73% of all HIV-infected people worldwide by 2030. However, achieving these targets may not lead to expected reductions in HIV incidence if the remaining 27% (persons with unsuppressed viral load) are the drivers of HIV transmission through high-risk behaviors. We aim to conduct a systematic review and meta-analysis to understand the demographics, mobility, geographic distribution, and risk profile of adults who are not virologically suppressed in sub-Saharan Africa in the era of UTT. Methods We will review the published and grey literature for study sources that contain data on demographic and behavioral strata of virologically suppressed and unsuppressed populations since 2014. We will search PubMed and Embase using four sets of search terms tailored to identify characteristics associated with virological suppression (or lack thereof) and each of the individual 90-90-90 goals. Record screening and data abstraction will be done independently and in duplicate. We will use random effects meta-regression analyses to estimate the distribution of demographic and risk features among groups not virologically suppressed and for each individual 90-90-90 goal. Discussion The results of our review will help elucidate factors associated with failure to achieve virological suppression in sub-Saharan Africa, as well as factors associated with failure to achieve each of the 90-90-90 goals. These data will help quantify the population-level effects of current HIV treatment interventions to improve strategies for maximizing virological suppression and ending the HIV epidemic. Systematic review registration PROSPERO CRD42018089505. Electronic supplementary material The online version of this article (10.1186/s13643-019-1024-6) contains supplementary material, which is available to authorized users.

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.

Summary 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.

Summary Background Home HIV testing and counselling (HTC) achieves high levels of HIV testing and linkage to care. Periodic home HTC, particularly targeted to those with high HIV viral load, might facilitate expansion of antiretroviral therapy (ART) coverage. We used a mathematical model to assess the effect of periodic home HTC programmes on HIV incidence in KwaZulu-Natal, South Africa. Methods We developed a dynamic HIV transmission model with parameters, primary cost data, and measures of viral suppression collected from a prospective study of home HTC in KwaZulu-Natal. In our model, we assumed home HTC took place every 5 years with ART initiation for people with CD4 counts of 350 cells per μL or less. For individuals with CD4 counts of more than 350 cells per μL, we compared increasing ART coverage for those with 350–500 cells per μL with initiating treatment for those who have viral loads of more than 10 000 copies per mL. Findings Maintaining the presently observed level of 36% viral suppression in HIV-positive people, HIV incidence decreases by 33·8% over 10 years. Home HTC every 5 years with linkage to care with ART initiation at CD4 counts of 350 cells per μL or less reduces HIV incidence by 40·6% over 10 years. Expansion of ART to people with CD4 counts of more than 350 cells per μL who also have a viral load of 10 000 copies per mL or more decreases HIV incidence by 51·6%, and this was the most cost-effective strategy for prevention of HIV infections at US$2960 per infection averted. Expansion of ART eligibility CD4 counts of 350–500 cells per μL is cost-effective at $900 per quality-adjusted life-year gained. Following health economic guidelines, expansion of ART use to individuals who have viral loads of more than 10 000 copies per mL among those with CD4 counts of more than 350 cells per μL was cost-effective to reduce HIV-related morbidity. Interpretation Our results show that province-wide home HTC every 5 years can be a cost-effective strategy to increase ART coverage and reduce HIV burden. Expanded ART initiation criteria that includes individuals with high viral load will improve the effectiveness of home HTC in linking individuals to ART who are at high risk of transmitting HIV, thereby preventing morbidity and onward transmission. Funding National Institutes of Health.

Background: Very high coverage human papillomavirus (HPV) vaccination of girls has the potential to eradicate some HPV types but low coverage vaccination does not. The protection of unvaccinated individuals by herd effect (HE) varies by HPV type and vaccination strategy. By combining community-randomized trial data and mathematical modeling we show that gender-neutral vaccination is superior for achieving eradication of oncogenic HPVs. Methods: We randomized 33 communities into gender-neutral HPV16/18 vaccination (A), HPV16/18 vaccination of girls only (B), and hepatitis B-virus vaccination of boys and girls (C). From 2007-2010 11,622/40,852 resident boys and 20,513/39,420 resident girls born 1992-1995 consented to the study. At follow-up in 2010-14, cervicovaginal samples from vaccinated and unvaccinated girls were typed for HPV6/11/16/18/31/33/35/39/45/51/52/56/58/59/66/68. Trial-based vaccine efficacy (VE) and HE, estimated among non-HPV vaccinated arm A/B girls using arm C controls, were weighted for mean protective effectiveness (PE) estimation, and used for modeling eradication. Findings The HPV18/31/33 HE and PE were significant in younger birth cohorts: four years post vaccination HE and PE were 150% and 40% stronger in the gender-neutral than in the girls-only arm. HPV18/31/33 have moderate to fast clearance rates enabling eradication, and corresponding HEs from vaccinated to unvaccinated arose rapidly. HPV18/31/33 eradication in adolescents/young adults is predicted in 20 years with 75% coverage of gender-neutral vaccination, eradication of HPV16 is predicted within 30 years. Interpretation While low coverage with a girls-only vaccination strategy leaves most females unprotected, HPV-disease eradication of oncogenic HPVs is certain with moderate coverage gender-neutral vaccination strategy. Funding: This ancillary study was partially funded by Academy of Finland, Finnish Cancer Organizations and EU FP7 networks PREHDICT and CoheaHR. GlaxoSmithKline Biologicals SA funded the primary study HPV-040 (NCT00534638, data to be published in a separate manuscript) but was not involved in the conduct of this ancillary study. GlaxoSmithKline Biologicals SA was provided the opportunity to review this manuscript for accuracy of primary HPV-040 data but the authors are solely responsible for final content and interpretation. V.N.P. was supported by a personal grant from the Ministry of Health, Government of Catalonia (PERIS SLT002/16/00496). Declaration of Interest: D.A., J.D., G.G., M.L. and J.P. have received grants from Merck & Co. Inc. or the GSK group of companies through their employers [Family Federation Finland (DA), Karolinska Institute (J.D., M.L.), Universities of Tampere (M.L.) or Helsinki (J.P.) or Imperial College London (G.G.)] for HPV vaccination studies. G.D. is currently a full time employee of Takeda Vaccines, but was working for GSK Biologicals at the time the study was planned and conducted. He holds several patents in the HPV field which have been assigned to the GSK groups of companies and has stock shares in both the GSK groups of companies and Takeda. Ethical Approval: The HPV-040 study (Eudra-CT-2007-001731-55, NCT00534638), and parallel ancillary studies on Chlamydia trachomatis screening (Dnro 111/2009) and HPV screening (ETL-code 13149, NCT02149030) were approved by Finnish ethical committees of the Pirkanmaa and PohjoisPohjanmaa hospital districts in 2007, 2009 and 2013, respectively.

Author(s): Bekker, Linda-Gail; Alleyne, George; Baral, Stefan; Cepeda, Javier; Daskalakis, Demetre; Dowdy, David; Dybul, Mark; Eholie, Serge; Esom, Kene; Garnett, Geoff; Grimsrud, Anna; Hakim, James; Havlir, Diane; Isbell, Michael T; Johnson, Leigh; Kamarulzaman, Adeeba; Kasaie, Parastu; Kazatchkine, Michel; Kilonzo, Nduku; Klag, Michael; Klein, Marina; Lewin, Sharon R; Luo, Chewe; Makofane, Keletso; Martin, Natasha K; Mayer, Kenneth; Millett, Gregorio; Ntusi, Ntobeko; Pace, Loyce; Pike, Carey; Piot, Peter; Pozniak, Anton; Quinn, Thomas C; Rockstroh, Jurgen; Ratevosian, Jirair; Ryan, Owen; Sippel, Serra; Spire, Bruno; Soucat, Agnes; Starrs, Ann; Strathdee, Steffanie A; Thomson, Nicholas; Vella, Stefano; Schechter, Mauro; Vickerman, Peter; Weir, Brian; Beyrer, Chris

High-risk human papillomaviruses (hrHPV) cause anogenital and oropharyngeal cancers. HPV-16/18 virus-like particle vaccine formulated with an AS04 adjuvant is very efficacious against hrHPV associated precancers but the herd effects of different vaccination scenarios are not known. Our cluster randomized trial (NCT00534638) assesses the overall and herd effects of vaccinating girls vs. girls and boys. In two school-years (2007–2008 and 2008–2009) we invited 80,272 1992–1995 born early adolescents to a CRT in 33 communities a priori stratified by low, intermediate and high HPV-16/18 seroprevalence. In 11 Arm A communities 90% of participating girls and boys were assigned to receive HPV-16/18 vaccine, in 11 Arm B communities 90% of girls were assigned to receive HPV-16/18 vaccine – boys were assigned to receive hepatitis B-virus (HBV) vaccine, and in 11 Arm C communities all were assigned to receive HBV-vaccine. Prevalence of HPV in vaccinated and unvaccinated girls is studied at age 18.5 years. Recruitment resulted in equal enrolment of four birth cohorts (born 1992–1995) comprising altogether 32,175 (40% response) early adolescents: 20,514 girls (50.5–53.0% response by arm) and 11,661 boys (21.9–31.6%% response by arm). At the age of 15 years, 79.3% of the vaccinees completed a questionnaire. Among them >98% were living at, and during the week-ends 1.3–1.6% stayed outside, the study site communities. Smoking habit and alcohol consumption were similar in the different trial arms, also mean-age of menarche (12.4 years) and 1st ejaculation (12.6 years), and sexual behaviour (among those

With optimal strategy, human papillomavirus (HPV) vaccines have the potential to control HPV. We have assessed vaccine efficacy (VE), herd effect (HE) of HPV vaccination and overall protective effectiveness (PE) against high-risk HPV infections by HPV type and vaccination strategy in a community-randomized trial using the bivalent HPV16/18 vaccine. We randomized 33 communities to gender-neutral HPV vaccination (Arm A), HPV vaccination of girls and hepatitis B-virus (HBV) vaccination of boys (Arm B) and gender-neutral HBV vaccination (Arm C). Entire 1992-1995 male (40,852) and female (39,420) birth cohorts were invited, and 11,662 males and 20,513 females vaccinated with 20-30% and 45% coverage in 2007-2010. During 2010-2014, 11,396 cervicovaginal samples were collected from 13,545 18.5-year-old attendees. HPV typing was performed by a high-throughput PCR. VE was calculated for HPV vaccinated women and HE for non-HPV-vaccinated women, using the HBV vaccinated, for HE all non-HPV vaccinated, Arm C women as controls. PE was calculated as coverage rate-weighted mean of VE + HE. HPV16/18/45 and 31/33/35 VEs varied between 86-94% and 30-66%, respectively. Only the gender-neutral vaccination provided significant HEs against HPV18 (61%) and HPV31 (72%) in the 1995 birth cohort-increased HEs against HPV33 (39%) and HPV35 (42%) were also observed. Due to the increased HEs, PEs for HPV16/18/45 and HPV31/33/35 were comparable in the gender-neutral arm 1995 birth cohort. High vaccine efficacy against HPV16/18/45 and, gender-neutral vaccination-enforced, herd effect against HPV18/31/33/35 by the bivalent vaccine rapidly provides comparable overall protective effectiveness against six oncogenic HPV types: 16/18/31/33/35/45.

There are inefficiencies in current approaches to monitoring patients on antiretroviral therapy in sub-Saharan Africa. Patients typically attend clinics every 1 to 3 months for clinical assessment. The clinic costs are comparable with the costs of the drugs themselves and CD4 counts are measured every 6 months, but patients are rarely switched to second-line therapies. To ensure sustainability of treatment programmes, a transition to more cost-effective delivery of antiretroviral therapy is needed. In contrast to the CD4 count, measurement of the level of HIV RNA in plasma (the viral load) provides a direct measure of the current treatment effect. Viral-load-informed differentiated care is a means of tailoring care so that those with suppressed viral load visit the clinic less frequently and attention is focussed on those with unsuppressed viral load to promote adherence and timely switching to a second-line regimen. The most feasible approach to measuring viral load in many countries is to collect dried blood spot samples for testing in regional laboratories; however, there have been concerns over the sensitivity and specificity of this approach to define treatment failure and the delay in returning results to the clinic. We use modelling to synthesize evidence and evaluate the cost-effectiveness of viral-load-informed differentiated care, accounting for limitations of dried blood sample testing. We find that viral-load-informed differentiated care using dried blood sample testing is cost-effective and is a recommended strategy for patient monitoring, although further empirical evidence as the approach is rolled out would be of value. We also explore the potential benefits of point-of-care viral load tests that may become available in the future.

Efficacy of human papillomavirus (HPV) vaccines promises to control HPV infections. However, HPV vaccination programs may lay bare an ecological niche for non-vaccine HPV types. We evaluated type-replacement by HPV type and vaccination strategy in a community-randomized trial executed in HPV vaccination naïve population. Thirty-three communities were randomized to gender-neutral vaccination with AS04-adjuvanted HPV16/18 vaccine (Arm A), HPV vaccination of girls and hepatitis B-virus (HBV) vaccination of boys (Arm B) and gender-neutral HBV vaccination (Arm C). Resident 1992-95 born boys (40,852) and girls (39,420) were invited. 11,662 boys and 20,513 girls were vaccinated with 20-30% and 45-48% coverage, respectively. HPV typing of 11,396 cervicovaginal samples was performed by high throughput PCR. Prevalence ratios (PR) between arms and ranked order of HPV types and odds ratio (OR) for having multiple HPV types in HPV16 or 18/45 positive individuals were calculated. The ranked order of HPV types did not significantly differ between arms or birth cohorts. For the non-HPV vaccinated 1992-1993 birth cohorts increased PR, between the gender-neutral intervention versus control arms for HPV39 (PR

BACKGROUND: It is unknown what properties would be required to make an intervention in low income countries that can eradicate or control human immunodeficiency virus (HIV) without antiretroviral therapy (ART) cost-effective.METHODS: We used a model of HIV and ART to investigate the effect of introducing an ART-free viral suppression intervention in 2022 using Zimbabwe as an example country. We assumed that the intervention (cost: $500) would be accessible for 90% of the population, be given to those receiving effective ART, have sufficient efficacy to allow ART interruption in 95%, with a rate of viral rebound of 5% per year in the first 3 months, and a 50% decline in rate with each successive year.RESULTS: An ART-free viral suppression intervention with these properties would result in >0.53 million disability-adjusted-life-years averted over 2022-2042, with a reduction in HIV program costs of $300 million (8.7% saving). An intervention of this efficacy costing anything up to $1400 is likely to be cost-effective in this setting.CONCLUSIONS: Interventions aimed at curing HIV infection have the potential to improve overall disease burden and to reduce costs. Given the effectiveness and cost of ART, such interventions would have to be inexpensive and highly effective.

The delivery of HIV care in the initial rapid scale-up of HIV care and treatment was based on existing clinic-based models, which are common in highly resourced settings and largely undifferentiated for individual needs. A new framework for treatment based on variable intensities of care tailored to the specific needs of different groups of individuals across the cascade of care is proposed here. Service intensity is characterised by four delivery components: (i) types of services delivered, (ii) location of service delivery, (iii) provider of health services and (iv) frequency of health services. How these components are developed into a service delivery framework will vary across countries and populations, with the intention being to improve acceptability and care outcomes. The goal of getting more people on treatment before they become ill will necessitate innovative models of delivering both testing and care. As HIV programmes expand treatment eligibility, many people entering care will not be ‘patients’ but healthy, active and productive members of society 1. To take the framework to scale, it will be important to: (i) define which individuals can be served by an alternative delivery framework; (ii) strengthen health systems that support decentralisation, integration and task shifting; (iii) make the supply chain more robust; and (iv) invest in data systems for patient tracking and for programme monitoring and evaluation. La delivrance des soins du VIH dans le deploiement initial rapide des soins et du traitement du VIH a ete basee sur des modeles existants dans les cliniques, qui sont courants dans les regions beneficiant d’importantes ressources et largement indifferenciees pour les besoins individuels. Un nouveau cadre est propose ici pour le traitement base selon les intensites variables de soins, adaptes aux besoins specifiques des differents groupes de personnes a travers la cascade de soins. L’intensite des services est caracterisee par quatre elements de delivrance: (1) les types de services delivres, (2) l’emplacement de la delivrance des services, (3) Les prestataires des services de sante et (4) la frequence des services de sante. La facon dont ces elements sont developpes dans un cadre de prestation de services peut varier selon les pays et les populations, l’intention etant d’ameliorer les resultats d’acceptabilite et des soins. Le but d’obtenir plus de personnes sous traitement avant qu’ils ne tombent malades necessitera des modeles innovateurs de prestation a la fois pour depistage et pour les soins. Comme les programmes VIH etendent l’eligibilite au traitement, beaucoup de gens qui entrent dans les soins ne seront pas des “malades- mais des elements sains de la societe, actifs et productifs. Afin de tenir le cadre a l’echelle, il sera important de: (1) definir les individus qui peuvent etre traites par un cadre alternatif de prestation, (2) renforcer les systemes de sante qui soutiennent la decentralisation, l’integration et le transfert des tâches; (3) rendre la chaine d’approvisionnement plus robuste et (4) investir dans des systemes de donnees pour le suivi des patients et pour le suivi et l’evaluation du programme. Los servicios de atencion del VIH durante el inicio de la primera etapa de rapida expansion del tratamiento y cuidados del VIH estaban basados en modelos clinicos existentes, comunes en lugares con abundancia de recursos y poco diferenciados en cuanto a necesidades individuales. Aqui se propone un nuevo marco para el tratamiento basado en intensidades variables de cuidados, hecho a medida segun las necesidades especificas de los diferentes grupos de individuos a lo largo del tratamiento. La intensidad del servicio se caracteriza por cuatro componentes de entrega: (1) tipologia de los servicios ofrecidos, (2) lugar de entrega de los servicios, (3) proveedor de los servicios sanitarios, y (4) frecuencia de los servicios sanitarios. El como estos componentes conforman un marco de entrega de servicios variara segun el pais y la poblacion, con la intencion de mejorar la aceptabilidad y los resultados de los cuidados. El objetivo de conseguir que mas personas reciban tratamiento antes de que enfermen requerira de modelos innovadores en la oferta tanto de pruebas para deteccion como de los cuidados. A medida que los programas para el VIH expandan los criterios de elegibilidad para el tratamiento, muchas de las personas que comiencen a recibir cuidados no seran “pacientes- sino miembros sanos, activos y productivos de la sociedad. Con el fin de expandir la escala de esta estructura, seria importante: (1) definir cuales individuos pueden ser atendidos dentro de un marco de entrega de servicios alternativo; (2) fortalecer los sistemas sanitarios que apoyan la descentralizacion, integracion y delegacion de funciones; (3) robustecer la cadena de proveedores; e (4) invertir en sistemas de datos para el seguimiento de pacientes y para la monitorizacion y evaluacion de programas.

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.

Summary 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.

The HIV treatment cascade has been a powerful illustrative tool used to explore the performance of HIV treatment programs. The cascade steps through the recruitment of HIV-infected individuals into treatment programs and the effectiveness of those programs, and despite its conceptual flaws provides an intuitively appealing snapshot of performance. Because of its advocacy potential attempts have been made to generate a prevention cascade, covering those HIV positive and negative or to integrate prevention into the treatment cascade generating a ‘prevention, treatment and care cascade’. However, these tend to diminish the focus on prevention, confuse different interventions and do not provide a simple scheme through which to measure performance. Here we explore the required elements for prevention cascades for HIV and other sexually transmitted infections and identify the steps linking the delivery of interventions with their use in populations. Starting from the susceptible population at risk we can consider whether the intervention is available to them, whether they uptake the intervention, whether they adhere to the intervention and what the efficacy of the intervention is. Cascades for the delivery, use and effectiveness of prevention products should be able to identify who has been protected, what the key failures in protection are and the relative importance of system and product characteristics. In explaining theoretically how we might think about prevention programs we hope that empirical studies will consider adopting this framework, which has guided some thinking about voluntary medical male circumcision programs and HIV pre-exposure prophylaxis programs. In HIV treatment global targets and indicators have been set based on the treatment cascade and without similar targets for other prevention interventions they are likely to be neglected.

In the welter of official statistics, many can naively assume that numbers are based on actual counts. However, because of the effort required to collect and collate often rare or hidden events in difficult circumstances this is often not the case and estimates are required. In the case of HIV, infections are often asymptomatic, symptoms often untreated and people living with HIV often undiagnosed and unreported. Thus, estimates of the numbers of infections and cases of disease have to be built from partial data the representativeness of which has to be considered. Over the course of the HIV pandemic a continuous process of updating and improving the quality of data, our understanding of that data and the tools used to analyse the data has been undertaken, led by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and with input from many scientists and technical experts. This effort should increase our confidence in the estimates of numbers of HIV infections and AIDS deaths, which are generated in partnership with national epidemiologists. Along the way the methods developed have been published in the peer review literature to allow critical scrutiny and to share our improving understanding of HIV epidemiology. We believe that the continued reassessment of methods and the transparency of their use have been important in establishing the validity of HIV estimates and facilitating their use in advocacy. HIV estimates are used to understand the burden of disease and death caused by the virus, to understand trends in incidence and the impact of interventions. The distribution of infections and numbers of people needing treatment should act as a guide to the global, national and local efforts to prevent and treat infections. HIV-associated mortality should show us …

Summary 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.