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This article discusses the development and implementation of a graphic novel tool called U = U (Undetectable = Untransmittable) in Lesotho to address the unique needs of adolescents and youth living with HIV (AYLHIV). The tool was created by the Elizabeth Glaser Pediatric AIDS Foundation's Committee of African Youth Advisors (CAYA) in partnership with researchers at the University of Cape Town. The tool consists of three stories that explore U = U in the context of romantic partnerships, sero-discordant couples, and pregnant young women. Youth ambassadors in Lesotho have used the tool in peer support groups and individual counseling sessions, finding it useful and relevant in addressing misconceptions and empowering AYLHIV. Suggestions for improvement include translating the stories into Sesotho and adding more diversity in the stories. Overall, the tool shows promise in promoting U = U and supporting AYLHIV in Lesotho. [Extracted from the article]

Introduction: To prevent vertical HIV transmission and ensure healthy mothers and children, pregnant women with HIV must remain on antiretroviral treatment (ART) for life. However, motivation to remain on ART may decline beyond the standard 2‐year breastfeeding/postpartum period. We assessed attrition and retention in ART care among women with HIV up to 6 years since enrolment in vertical transmission prevention services in Dar es Salaam, Tanzania. Methods: A prospective cohort of 22,631 pregnant women with HIV were enrolled in vertical transmission prevention services between January 2015 and December 2017 in routine healthcare settings and followed‐up to July 2021. Kaplan−Meier was used to estimate time to ART attrition (died, stopped ART or was lost to follow‐up [no show ≥90 days since scheduled appointment]) and the proportion retained in care. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHR) of ART attrition in relation to predictors. Results: Participants were followed‐up to 6 years for a median of 3 years (IQR: 0.1–4). The overall ART attrition rate was 13.8 per 100 person‐years (95% CI: 13.5–14.1), highest in the first year of enrolment at 27.1 (26.3–27.9), thereafter declined to 9.5 (8.9–10.1) in year 3 and 2.7 (2.1–3.5) in year 6. The proportion of women retained in care were 78%, 69%, 63%, 60%, 57% and 56% at 1, 2, 3, 4, 5 and 6 years, respectively. ART attrition was higher in young women aged <20 years (aHR 1.63, 95% CI: 1.38–1.92) as compared to 30‐39 year‐olds and women enrolled late in the third versus first trimester (aHR 1.29, 95% CI: 1.16–1.44). In contrast, attrition was lower in older women ≥40 years, women who initiated ART before versus during the index pregnancy and women attending higher‐level health facilities. Conclusions: ART attrition among women with HIV remains highest in the first year of enrolment in vertical transmission prevention services and declines markedly following a transition to chronic HIV care. Targeted interventions to improve ART continuity among women with HIV during and beyond prevention of vertical transmission are vital to ending paediatric HIV and keeping women and children alive and healthy. [ABSTRACT FROM AUTHOR]

Introduction: Pre‐exposure prophylaxis (PrEP) delivery based on user needs can enhance PrEP access and impact. We examined whether telehealth for daily oral PrEP delivery could change the indicators of care related to prophylactic use in five Brazilian public HIV clinics (testing centres, outpatient clinics and infectious disease hospitals). Methods: Between July 2019 and December 2020, clients on PrEP for at least 6 months could transition to telehealth or stay with in‐person follow‐up. Clients were clinically monitored until June 2021. A desktop or mobile application was developed, comprising three asynchronous consultations and one annual in‐person consultation visit. Predictors influencing telehealth preference and care outcomes were examined. The analysis encompassed intent‐to‐treat (first choice) and adjustments for sexual practices, schooling, age, duration of PrEP use and PrEP status during the choice period. Results: Of 470 users, 52% chose telehealth, with the adjusted odds ratio (aOR) increasing over time for PrEP use (aOR for 25–months of use: 4.90; 95% CI: 1.32–18.25), having discontinued PrEP at the time of the choice (aOR: 2.91; 95% CI: 1.40–6.06) and having health insurance (aOR: 1.91; 95% CI: 1.24–2.94) and decreasing for those who reported higher‐risk behaviour (aOR for unprotected anal sex: 0.51; 95% CI: 0.29–0.88). After an average follow‐up period of 1.6 years (95% CI: 1.5–1.7), the risk of discontinuing PrEP (not having the medication for more than 90 days) was 34% lower with telehealth (adjusted hazard ratio: 0.66; 95% CI: 0.45–0.97). When adjusted by mixed linear regression, no differences in adherence (measured by mean medication possession rate) were found between in‐person and telehealth (p = 0.486) or at pre‐ and post‐telehealth follow‐ups (p = 0.245). Sexually transmitted infections increased between the pre‐follow‐up and post‐follow‐up choices and were not associated with in‐person or telehealth (p = 0.528). No HIV infections were observed. Conclusions: Our findings indicate that telehealth for PrEP delivery can enhance service rationalization and reinforce the prevention cascade. This approach reduces prophylaxis interruptions and is mainly preferred by individuals with lower demands for healthcare services. [ABSTRACT FROM AUTHOR]

Introduction: The HIV response has long recognized that certain "key populations" such as individuals in detention, adolescent girls and young women, sex workers, people who use drugs, LGBTQ individuals, migrants and others face higher barriers to access to, uptake of, and retention in HIV prevention and treatment services. One approach to addressing these barriers is the training of community paralegals to advocate for the rights of individuals and to address discrimination in health settings. Discussion: Community paralegal programmes have been able to successfully address rights violations that impact access to health services and underlying determinants of health across a range of countries and populations, focusing upon issues such as discrimination and the denial of health services; unlawful detention of outreach workers, sex workers, persons who use drugs and men who have sex with men; and harmful traditional practices and gender‐based violence. In addition to resolving specific cases, evaluations of paralegal programmes have found that these programmes increased legal literacy among key populations at risk of HIV and increased understanding of human rights among healthcare providers, resulting in improved access to HIV services. Some evaluations have noted challenges related to the sustainability of paralegal programmes similar to those raised with community health worker programmes more broadly. Conclusions: To achieve global HIV goals, funding for legal literacy and paralegal programmes should be increased and interventions should be rigorously evaluated. Efforts should target discrimination in access to HIV prevention and treatment and criminalization of key populations, two key barriers to ensuring access to HIV prevention and treatment services. [ABSTRACT FROM AUTHOR]

Introduction: Data from two randomized controlled trials (RCTs) showed that injectable cabotegravir (CAB) for pre-exposure prophylaxis (PrEP) was efficacious in reducing HIV acquisition. The US Food and Drug Administration approved CAB for PrEP in December 2021; Australia in August 2022; Zimbabwe in October 2022; South Africa in November 2022; Malawi in March 2023; and regulatory approvals are being sought in additional countries. The World Health Organization (WHO) recommended CAB be offered to people at substantial risk of HIV in July 2022. However, implementation experience beyond RCTs is limited. As countries consider CAB implementation, questions remain regarding delivery and involvement of populations excluded from the trials. A coordinated approach is needed to ensure these are addressed and CAB can be introduced in low- and middle-income countries in timely, acceptable and effective ways. Discussion: Beginning in 2018, the Biomedical Prevention Implementation Collaborative (BioPIC) convened over 100 global health experts to develop a comprehensive introduction strategy for CAB. Using this roadmap, country landscaping for CAB introduction and lessons from oral PrEP implementation, AVAC and WHO co-convened 50 researchers, donors, implementers and civil society in September 2021 to: (1) identify questions and evidence gaps related to CAB across contexts and partners; (2) define the implementation science agenda; and (3) agree on mechanism(s) for future coordination. As a result, CAB-related questions were identified, including: defining optimal and feasible HIV testing strategies that expand access; delivery models; integration with a range of services, including family planning and antenatal care; and embedding CAB in demand generation for HIV prevention choices. Through convenings and mapping of implementation research, BioPIC identified gaps in populations, geographies and delivery approaches. Conclusions: The introduction strategy refined by BioPIC lays the groundwork for future HIV prevention products. Ongoing policy and implementation dialogue is critical to accelerate the design of CAB implementation studies that adequately address priority knowledge gaps. Additional long-acting HIV prevention products may be available over the next 5 years, increasing choice, but potentially making delivery and stakeholder engagement more complex. Ongoing coordination with WHO will accelerate the adoption of evidence-based policies and wide-scale implementation, and lessons from BioPIC can inform introduction processes for long-acting HIV prevention products. [ABSTRACT FROM AUTHOR]

Introduction: The burden of HIV in sub-Saharan Africa (SSA) remains unacceptably high, and disproportionately affects girls and women. While the introduction of oral HIV pre-exposure prophylaxis (PrEP) in 2012 revolutionized HIV prevention, its effectiveness is dependent on user adherence and its implementation in SSA has faced numerous challenges. Patient-level, interpersonal and structural barriers, including, for example, daily pill burden, side effects, lack of partner support, testing and disclosure, and costs have been found to reduce adherence to oral PrEP. Discussion: Long-acting extended delivery (LAED) formulations for PrEP, such as injectable long-acting cabotegravir (CAB-LA) and dapivirine vaginal ring (DPV-VR) are critical additions to the HIV prevention toolkit and are especially important for populations such as adolescent girls and young women (AGYW) and other key populations who remain at significant risk of HIV acquisition while facing substantial barriers to preventive services. These LAED formulations have been shown to result in better adherence and fewer side effects, with CAB-LA being superior to oral PrEP in reducing the risk of HIV acquisition. They can be used to overcome user burden and adherence challenges. However, the successful rollout of the DPV-VR and CAB-LA may be hampered by issues such as a shortage of healthcare providers (HCPs), inadequate parenteral medication infrastructure, increased workload for HCPs, patient concerns, the price of the medications and the possibility of drug resistance. Conclusions: SSA must develop laboratory capabilities for monitoring patients on LAED formulations and enhance research on developing more non-injectable LAED formulations. There is a need to train and retain more HCPs, implement task shifting, invest in healthcare infrastructure and integrate healthcare services. To reduce costs and improve availability, the region must advocate for patent license waivers for LAED formulations and procure drugs collectively as a region. [ABSTRACT FROM AUTHOR]

Introduction: The burden of HIV in sub‐Saharan Africa (SSA) remains unacceptably high, and disproportionately affects girls and women. While the introduction of oral HIV pre‐exposure prophylaxis (PrEP) in 2012 revolutionized HIV prevention, its effectiveness is dependent on user adherence and its implementation in SSA has faced numerous challenges. Patient‐level, interpersonal and structural barriers, including, for example, daily pill burden, side effects, lack of partner support, testing and disclosure, and costs have been found to reduce adherence to oral PrEP. Discussion: Long‐acting extended delivery (LAED) formulations for PrEP, such as injectable long‐acting cabotegravir (CAB‐LA) and dapivirine vaginal ring (DPV‐VR) are critical additions to the HIV prevention toolkit and are especially important for populations such as adolescent girls and young women (AGYW) and other key populations who remain at significant risk of HIV acquisition while facing substantial barriers to preventive services. These LAED formulations have been shown to result in better adherence and fewer side effects, with CAB‐LA being superior to oral PrEP in reducing the risk of HIV acquisition. They can be used to overcome user burden and adherence challenges. However, the successful rollout of the DPV‐VR and CAB‐LA may be hampered by issues such as a shortage of healthcare providers (HCPs), inadequate parenteral medication infrastructure, increased workload for HCPs, patient concerns, the price of the medications and the possibility of drug resistance. Conclusions: SSA must develop laboratory capabilities for monitoring patients on LAED formulations and enhance research on developing more non‐injectable LAED formulations. There is a need to train and retain more HCPs, implement task shifting, invest in healthcare infrastructure and integrate healthcare services. To reduce costs and improve availability, the region must advocate for patent license waivers for LAED formulations and procure drugs collectively as a region. [ABSTRACT FROM AUTHOR]

Introduction: Data from two randomized controlled trials (RCTs) showed that injectable cabotegravir (CAB) for pre‐exposure prophylaxis (PrEP) was efficacious in reducing HIV acquisition. The US Food and Drug Administration approved CAB for PrEP in December 2021; Australia in August 2022; Zimbabwe in October 2022; South Africa in November 2022; Malawi in March 2023; and regulatory approvals are being sought in additional countries. The World Health Organization (WHO) recommended CAB be offered to people at substantial risk of HIV in July 2022. However, implementation experience beyond RCTs is limited. As countries consider CAB implementation, questions remain regarding delivery and involvement of populations excluded from the trials. A coordinated approach is needed to ensure these are addressed and CAB can be introduced in low‐ and middle‐income countries in timely, acceptable and effective ways. Discussion: Beginning in 2018, the Biomedical Prevention Implementation Collaborative (BioPIC) convened over 100 global health experts to develop a comprehensive introduction strategy for CAB. Using this roadmap, country landscaping for CAB introduction and lessons from oral PrEP implementation, AVAC and WHO co‐convened 50 researchers, donors, implementers and civil society in September 2021 to: (1) identify questions and evidence gaps related to CAB across contexts and partners; (2) define the implementation science agenda; and (3) agree on mechanism(s) for future coordination. As a result, CAB‐related questions were identified, including: defining optimal and feasible HIV testing strategies that expand access; delivery models; integration with a range of services, including family planning and antenatal care; and embedding CAB in demand generation for HIV prevention choices. Through convenings and mapping of implementation research, BioPIC identified gaps in populations, geographies and delivery approaches. Conclusions: The introduction strategy refined by BioPIC lays the groundwork for future HIV prevention products. Ongoing policy and implementation dialogue is critical to accelerate the design of CAB implementation studies that adequately address priority knowledge gaps. Additional long‐acting HIV prevention products may be available over the next 5 years, increasing choice, but potentially making delivery and stakeholder engagement more complex. Ongoing coordination with WHO will accelerate the adoption of evidence‐based policies and wide‐scale implementation, and lessons from BioPIC can inform introduction processes for long‐acting HIV prevention products. [ABSTRACT FROM AUTHOR]

Introduction: Human immunodeficiency virus (HIV) continues to rise in young people among low‐ and middle‐income countries (LMIC). The US National Institutes of Health (NIH) supports the largest public investment in HIV research globally. Despite advancements in the last decade, adolescents and young adults (AYA) remain underrepresented in research to improve HIV prevention and care. We undertook a programme analysis of NIH grants and conducted a targeted review of linked publications on international AYA research across the HIV prevention and care continuum (HPCC) to inform new initiatives to address the needs of AYA in these settings. Methods: NIH‐funded grants from 2012 to 2017, pertaining to AYA in LMIC, and evaluating areas of HIV prevention, care and/or treatment were identified. A systematic review of publications limited to funded grants was performed in two waves: 2012–2017 and 2018–2021. The review included a landscape assessment and an evaluation of NIH‐defined clinical trials, respectively. Data on outcomes across the HPCC were abstracted and analysed. Results: Among grant applications, 14% were funded and linked to 103 publications for the analytic database, 76 and 27 from the first and second waves, respectively. Fifteen (15%) wave 1 and 27 (26%) wave 2 publications included an NIH‐defined clinical trial. Among these, 36 (86%) did not target a key population (men who have sex with men, drug users and sex workers) and 37 (88%) were exclusively focused on sub‐Saharan Africa. Thirty (71%) publications addressed at least one HPCC milestone. Specific focus was on milestones in HIV prevention, care or both, for 12 (29%), 13 (31%) and five (12%) of publications, respectively. However, few addressed access to and retention in HIV care (4 [14%]) and none included microbicides or treatment as prevention. More focus is needed in crucial early steps of the HIV care continuum and on biomedical HIV prevention interventions. Discussion and Conclusions: Research gaps remain in this portfolio across the AYA HPCC. To address these, NIH launched an initiative entitled Prevention and Treatment through a Comprehensive Care Continuum for HIV‐affected Adolescents in Resource Constrained Settings (PATC3H) to generate needed scientific innovation for effective public health interventions for AYA affected by HIV in LMIC. [ABSTRACT FROM AUTHOR]

Introduction: Many children and adolescents living with HIV still present with severe immunosuppression with morbidity and mortality remaining high in those starting antiretroviral therapy (ART) when hospitalized. Discussion: The major causes of morbidity and mortality in children living with HIV are pneumonia, tuberculosis, bloodstream infections, diarrhoeal disease and severe acute malnutrition. In contrast to adults, cryptococcal meningitis is rare in children under 5 years of age but increases in adolescence. In 2021, the World Health Organizations (WHO) consolidated guidelines for managing HIV disease and rapid ART included recommendations for children and adolescents. In addition, a WHO technical brief released in 2020 highlighted the various interventions that are specifically related to children and adolescents with advanced HIV disease (AHD). We discuss the common clinical presentations of children and adolescents with AHD with a focus on diagnosis, prevention and treatment, highlight some of the challenges in the implementation of the existing package of care, and emphasize the importance of additional research to address the needs of children and adolescents with AHD. Conclusions: There are limited data informing these recommendations and an urgent need for further research on how to implement optimal strategies to ensure tailored approaches to prevent and treat AHD in children and adolescents. Holistic care that goes beyond a simple choice of ART regimen should be provided to all children and adolescents with AHD. [ABSTRACT FROM AUTHOR]

Introduction: In 2016, South Africa (SA) initiated a national programme to scale‐up pre‐exposure prophylaxis (PrEP) among female sex workers (FSWs), with ∼20,000 PrEP initiations among FSWs (∼14% of FSW) by 2020. We evaluated the impact and cost‐effectiveness of this programme, including future scale‐up scenarios and the potential detrimental impact of the COVID‐19 pandemic. Methods: A compartmental HIV transmission model for SA was adapted to include PrEP. Using estimates on self‐reported PrEP adherence from a national study of FSW (67.7%) and the Treatment and Prevention for FSWs (TAPS) PrEP demonstration study in SA (80.8%), we down‐adjusted TAPS estimates for the proportion of FSWs with detectable drug levels (adjusted range: 38.0–70.4%). The model stratified FSW by low (undetectable drug; 0% efficacy) and high adherence (detectable drug; 79.9%; 95% CI: 67.2–87.6% efficacy). FSWs can transition between adherence levels, with lower loss‐to‐follow‐up among highly adherent FSWs (aHR: 0.58; 95% CI: 0.40–0.85; TAPS data). The model was calibrated to monthly data on the national scale‐up of PrEP among FSWs over 2016–2020, including reductions in PrEP initiations during 2020. The model projected the impact of the current programme (2016–2020) and the future impact (2021–2040) at current coverage or if initiation and/or retention are doubled. Using published cost data, we assessed the cost‐effectiveness (healthcare provider perspective; 3% discount rate; time horizon 2016–2040) of the current PrEP provision. Results: Calibrated to national data, model projections suggest that 2.1% of HIV‐negative FSWs were currently on PrEP in 2020, with PrEP preventing 0.45% (95% credibility interval, 0.35–0.57%) of HIV infections among FSWs over 2016–2020 or 605 (444–840) infections overall. Reductions in PrEP initiations in 2020 possibly reduced infections averted by 18.57% (13.99–23.29). PrEP is cost‐saving, with $1.42 (1.03–1.99) of ART costs saved per dollar spent on PrEP. Going forward, existing coverage of PrEP will avert 5,635 (3,572–9,036) infections by 2040. However, if PrEP initiation and retention doubles, then PrEP coverage increases to 9.9% (8.7–11.6%) and impact increases 4.3 times with 24,114 (15,308–38,107) infections averted by 2040. Conclusions: Our findings advocate for the expansion of PrEP to FSWs throughout SA to maximize its impact. This should include strategies to optimize retention and should target women in contact with FSW services. [ABSTRACT FROM AUTHOR]

Introduction: HIV pre‐exposure prophylaxis (PrEP) has been government subsidized in Australia since April 2018 and while uptake is high among men who have sex with men, rates of discontinuation are also high. The aims of this study were to examine the impact of discontinuation on overall PrEP usage, the proportion of PrEP users who discontinue and the predictors of discontinuation. Methods: We used linked de‐identified dispensing records of all government subsidized PrEP in Australia between April 2018 and September 2021: a whole‐of‐population data set. Defining discontinuation as 180 days or more without PrEP after the final dispensed supply, we calculated the number of people who discontinued at each 6‐month interval during the study period, the proportion who had discontinued 2 years after the first supply and, using Cox regression, predictors of discontinuation. Results: Of 49,164 people dispensed PrEP (98.5% male, median age 34 years), 40.3% (19,815) had discontinued by September 2021. Within 2 years of their first supply, 11,150 (37.7%) of 29,549 PrEP users had discontinued, including 10.0% after a single dispensed supply. Large variations were observed, particularly according to prescriber characteristics: discontinuation was higher among people prescribed PrEP by low caseload (≤10 patients) prescribers (61.2%) than by high caseload (>100 patients) prescribers (31.1%, p<0.001), and by prescribers practising in areas with low estimated prevalence (<1.0%) of gay men (64.1%) than high (>5%) prevalence (36.7%, p<0.001). Women and younger people were more likely to discontinue, while patients receiving a higher level of government subsidy were less likely. The independent predictors of discontinuation with the greatest effect size were female sex (adjusted hazards ratio [aHR] 2.99, p<0.001), low estimated gay prevalence of prescriber location (aHR 1.98, p<0.001) and low prescriber PrEP caseload (aHR 1.79, p<0.001). Conclusions: There are high rates of PrEP discontinuation in Australia and some populations are at increased risk of discontinuation. Strategies are needed to support persistence on PrEP and the re‐starting of PrEP during periods of risk. [ABSTRACT FROM AUTHOR]

Introduction: There is robust evidence that stigma negatively impacts both people living with HIV and those who might benefit from HIV prevention interventions. Within healthcare settings, research on HIV stigma has focused on intra‐personal processes (i.e. knowledge or internalization of community‐level stigma that might limit clients' engagement in care) or inter‐personal processes (i.e. stigmatized interactions with service providers). Intersectional approaches to stigma call us to examine the ways that intersecting systems of power and oppression produce stigma not only at the individual and interpersonal levels, but also within healthcare service delivery systems. This commentary argues for the importance of analysing and disrupting the way in which stigma may be (intentionally or unintentionally) enacted and sustained within HIV service implementation, that is the policies, protocols and strategies used to deliver HIV prevention and care. We contend that as HIV researchers and practitioners, we have failed to fully specify or examine the mechanisms through which HIV service implementation itself may reinforce stigma and perpetuate inequity. Discussion: We apply Link and Phelan's five stigma components (labelling, stereotyping, separation, status loss and discrimination) as a framework for analysing the way in which stigma manifests in existing service implementation and for evaluating new HIV implementation strategies. We present three examples of common HIV service implementation strategies and consider their potential to activate stigma components, with particular attention to how our understanding of these dynamics can be enhanced and expanded by the application of intersectional perspectives. We then provide a set of sample questions that can be used to develop and test novel implementation strategies designed to mitigate against HIV‐specific and intersectional stigma. Conclusions: This commentary is a theory‐informed call to action for the assessment of existing HIV service implementation, for the development of new stigma‐reducing implementation strategies and for the explicit inclusion of stigma reduction as a core outcome in implementation research and evaluation. We argue that these strategies have the potential to make critical contributions to our ability to address many system‐level form stigmas that undermine health and wellbeing for people living with HIV and those in need of HIV prevention services. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to evaluate daily oral pre‐exposure prophylaxis (PrEP) uptake, retention, and adherence and predictors of study non‐attendance and low PrEP adherence in a Brazilian trans‐specific 48‐week study (PrEParadas). Methods: We enrolled transgender women (TGW) engaging in high‐risk sexual behaviours between August 2017 and December 2018. PrEP adherence was based on tenofovir diphosphate concentrations in dried blood spots (DBS). We used random effects logistic regression models and ordinal models to estimate the odds of having a missed visit and of low PrEP adherence, respectively. Multivariable models were adjusted for variables with p‐value<0.10 in the univariate analysis. Results: From the 271 eligible, 130 participants were enrolled in the study (PrEP uptake: 48%), out of which 111 (85.4%) were retained at 48 weeks. Multivariable model for study non‐attendance included study visit, age, main sexual partner and stimulant use. The odds of missing a visit increased after the week 24. Participants aged 18–24 (adjusted odds ratio [aOR] = 8.76, 95% CI: 2.09–36.7) and 25–34 years (aOR = 6.79, 95% CI: 1.72–26.8) compared to TGW aged 35+ years had significantly higher odds of having a missed visit. The odds of a missed visit were higher among participants reporting stimulant use (aOR = 4.99, 95% CI: 1.37–18.1) compared to no stimulant use. DBS levels at week 48 showed that 42 (38.5%), 14 (12.8%) and 53 (48.6%) of 109 participants had low, moderate and high PrEP adherence. Multivariable model for low PrEP adherence included study visit, age, schooling, race/colour, housing, binge drinking, stimulant use, feminizing hormone therapy (FHT) use and received text message. Low PrEP adherence was significantly higher among participants with less years of schooling (aOR = 6.71, 95% CI: 1.30–34.5) and had a borderline association with Black colour/race (aOR = 6.72, 95% CI: 0.94–47.8). Participants using the FHT available at the site had decreased odds of low PrEP adherence (aOR = 0.38, 95% CI: 0.16–0.88). No participant seroconverted over the course of the study. Conclusions: Although high PrEP retention can be achieved in a gender‐affirming setting, PrEP adherence may be an important challenge faced among TGW due to social disparities. The scale‐up of prevention tools like PrEP will have to address systemic social determinants as these stand as important barriers for TGW's access to health services. [ABSTRACT FROM AUTHOR]

Introduction: The COVID‐19 pandemic has affected women and children globally, disrupting antiretroviral therapy (ART) services and exacerbating pre‐existing barriers to care for both pregnant women and paediatric populations. Methods: We used the Spectrum modelling package and the CEPAC‐Pediatric model to project the impact of COVID‐19‐associated care disruptions on three key populations in the 21 Global Plan priority countries in sub‐Saharan Africa: (1) pregnant and breastfeeding women living with HIV and their children, (2) all children (aged 0–14 years) living with HIV (CLWH), regardless of their engagement in care and (3) CLWH who were engaged in care and on ART prior to the start of the pandemic. We projected clinical outcomes over the 12‐month period of 1 March 2020 to 1 March 2021. Results: Compared to a scenario with no care disruption, in a 3‐month lockdown with complete service disruption, followed by 3 additional months of partial (50%) service disruption, a projected 755,400 women would have received PMTCT care (a 21% decrease), 187,800 new paediatric HIV infections would have occurred (a 77% increase) and 516,800 children would have received ART (a 35% decrease). For children on ART as of March 2020, we projected 507,200 would have experienced ART failure (an 80% increase). Additionally, a projected 88,400 AIDS‐related deaths would have occurred (a 27% increase) between March 2020 and March 2021, with 51,700 of those deaths occurring among children engaged in care as of March 2020 (a 54% increase). Conclusions: While efforts will continue to curb morbidity and mortality stemming directly from COVID‐19 itself, it is critical that providers also consider the immediate and indirect harms of this pandemic, particularly among vulnerable populations. Well‐informed, timely action is critical to meet the health needs of pregnant women and children if the global community is to maintain momentum towards an AIDS‐free generation. [ABSTRACT FROM AUTHOR]

Introduction: While pregnant people have been an important focus for HIV research, critical evidence gaps remain regarding prevention, co‐infection, and safety and efficacy of new antiretroviral therapies in pregnancy. Such gaps can result in harm: without safety data, drugs used may carry unacceptable risks to the foetus or pregnant person; without pregnancy‐specific dosing data, pregnant people face risks of both toxicity and undertreatment; and delays in gathering evidence can limit access to beneficial next‐generation drugs. Despite recognition of the need, numerous barriers and ethical complexities have limited progress. We describe the process, ethical foundations, recommendations and applications of guidance for advancing responsible inclusion of pregnant people in HIV/co‐infections research. Discussion: The 26‐member international and interdisciplinary Pregnancy and HIV/AIDS: Seeking Equitable Study (PHASES) Working Group was convened to develop ethics‐centred guidance for advancing timely, responsible HIV/co‐infections research with pregnant people. Deliberations over 3 years drew on extensive qualitative research, stakeholder engagement, expert consultation and a series of workshops. The guidance, initially issued in July 2020, highlights conceptual shifts needed in framing research with pregnant people, and articulates three ethical foundations to ground recommendations: equitable protection from drug‐related risks, timely access to biomedical advances and equitable respect for pregnant people's health interests. The guidance advances 12 specific recommendations, actionable within the current regulatory environment, addressing multiple stakeholders across drug development and post‐approval research, and organized around four themes: building capacity, supporting inclusion, achieving priority research and ensuring respect. The recommendations describe strategies towards ethically redressing the evidence gap for pregnant people around HIV and co‐infections. The guidance has informed key efforts of leading organizations working to advance needed research, and identifies further opportunities for impact by a range of stakeholder groups. Conclusions: There are clear pathways towards ethical inclusion of pregnant people in the biomedical research agenda, and strong agreement across the HIV research community about the need for – and the promise of – advancing them. Those who fund, conduct, oversee and advocate for research can use the PHASES guidance to facilitate more, better and earlier evidence to optimize the health and wellbeing of pregnant people and their children. [ABSTRACT FROM AUTHOR]

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

Introduction: Following the implementation of the provision of lifelong antiretroviral therapy to all HIV‐positive pregnant or breastfeeding women for prevention of mother‐to‐child transmission (PMTCT) of HIV by the Kingdom of Lesotho in 2013, we assessed the effectiveness of this approach by evaluating 24‐month HIV‐free survival among HIV‐exposed infants (HEIs). Methods: We conducted a prospective observational cohort study that enrolled HIV‐positive and HIV‐negative pregnant women, with follow‐up of women and their infants for 24 months after delivery. Participant recruitment started in June 2014 and follow‐up ended in September 2018. Trained nurses collected study information through patient interviews and chart abstraction at enrolment and every three to six months thereafter. Maternal HIV testing, infant mortality, HIV transmission and HIV‐free survival rates were computed using Kaplan–Meier estimation. Cox regression hazard models were used to identify factors associated with infant HIV infection and death. Results: Between June 2014 and February 2016, we enrolled 653 HIV‐positive and 941 HIV‐negative pregnant women. Twenty‐seven HIV‐negative women acquired HIV during follow‐up. Ultimately, 634 liveborn HEI (382 (52%) male, 303 (48%) female, 3 missing) and 839 who remained HIV‐unexposed (HUIs) (409 (49.0%) male, 426 (51.0%) female, 4 missing) were followed; 550 HEIs and 701 HUIs completed the 24‐month follow‐up period. Of 607 (95.7%) HEIs who were tested for HIV at least once during follow‐up, 17 were found to be HIV‐positive. Two (9.5%) of 21 infants born to mothers who acquired HIV infection during follow‐up were HIV‐positive compared to 15 (2.4%) of 613 HEI born to women with known HIV infection. The risk of HIV transmission from HIV‐positive mothers to their infants by 24 months of age was 2.9% (95% CI: 1.8 to 4.7). The estimated 24‐month mortality rate among HEIs was 6.0% (95% CI: 4.4 to 8.2) compared to 3.8% (95% CI: 2.6 to 5.3) among HUIs (Log‐rank p = 0.065). HIV‐free survival at 24 months was 91.8% (95% CI: 89.2 to 93.7). Lower maternal age and birth weight were independently associated with increased HIV infection or death of infants. Conclusions: The implementation of lifelong ART for PMTCT in the Lesotho public health system resulted in low HIV transmission, but survival of HEI remains lower than their HIV uninfected counterparts. [ABSTRACT FROM AUTHOR]

Introduction: People who inject drugs (PWID) in Ukraine have high prevalences of HIV and hepatitis C (HCV). Since the turn of the century, various organizations have funded non‐governmental organizations (NGOs) in Ukraine to provide PWID with needles and syringes, condoms, HIV and HCV testing, and improve linkage to opioid agonist therapy (OAT) and HIV treatment. We investigated whether contact with these NGOs was associated with improved HIV prevention and treatment outcomes among PWID. Methods: Five rounds of respondent‐driven sampled integrated bio‐behavioural survey data (2009 [N = 3962], 2011 [N = 9069], 2013 [N = 9502], 2015 [N = 9405], and 2017 [N = 10076]) among PWID in Ukraine (including HIV/HCV testing and questionnaires) were analysed using mixed‐effect logistic regression models (mixed‐effects: city, year). These regression models assessed associations between being an NGO client and various behavioural, OAT, HIV testing and HIV treatment outcomes, adjusting for demographic characteristics (age, gender, lifetime imprisonment, registration in a drug abuse clinic, education level). We also assessed associations between being an NGO client and being HIV positive or HCV positive, likewise adjusting for demographic characteristics (as above). Results: NGO clients were more likely to have received HIV testing ever (adjusted odds ratio [aOR] 5.37, 95% confidence interval [95% CI]: 4.97 to 5.80) or in the last year (aOR 3.37, 95% CI: 3.20 to 3.54), to have used condoms at last sexual intercourse (aOR 1.37, 95% CI: 1.30 to 1.44) and sterile needles at last injection (aOR 1.37, 95% CI: 1.20 to 1.56), to be currently (aOR 4.19, 95% CI: 3.48 to 5.05) or ever (aOR 2.52, 95% CI: 2.32 to 2.74) on OAT, and to have received syringes (aOR 109.89, 95% CI: 99.26 to 121.66) or condoms (aOR 54.39, 95% CI: 50.17 to 58.96) in the last year. PWID who were HIV positive (aOR 1.40, 95% CI: 1.33 to 1.48) or HCV positive (aOR 1.57, 95% CI: 1.49 to 1.65) were more likely to have contact with NGOs, with HIV positive PWID in contact with NGOs being more likely to be registered at AIDS centres (aOR 2.34, 95% CI: 1.88 to 2.92) and to be on antiretroviral therapy (aOR 1.60, 95% CI: 1.40 to 1.83). Conclusions: Contact with PWID targeted NGOs in Ukraine is associated with consistently better preventive, HIV testing and HIV treatment outcomes, suggesting a beneficial impact of harm reduction NGO programming. [ABSTRACT FROM AUTHOR]

Introduction: Over one hundred implementation studies of HIV pre‐exposure prophylaxis (PrEP) are completed, underway or planned. We synthesized evidence from these studies to inform mathematical modelling of the prevention cascade for oral and long‐acting PrEP in the setting of western Kenya, one of the world's most heavily HIV‐affected regions. Methods: We incorporated steps of the PrEP prevention cascade – uptake, adherence, retention and re‐engagement after discontinuation – into EMOD‐HIV, an open‐source transmission model calibrated to the demography and HIV epidemic patterns of western Kenya. Early PrEP implementation research from East Africa was used to parameterize prevention cascades for oral PrEP as currently implemented, delivery innovations for oral PrEP, and future long‐acting PrEP. We compared infections averted by PrEP at the population level for different cascade assumptions and sub‐populations on PrEP. Analyses were conducted over the 2020 to 2040 time horizon, with additional sensitivity analyses for the time horizon of analysis and the time when long‐acting PrEP becomes available. Results: The maximum impact of oral PrEP diminished by over 98% across all prevention cascades, with the exception of long‐acting PrEP under optimistic assumptions about uptake and re‐engagement after discontinuation. Long‐acting PrEP had the highest population‐level impact, even after accounting for possible delays in product availability, primarily because its effectiveness does not depend on drug adherence. Retention was the most significant cascade step reducing the potential impact of long‐acting PrEP. These results were robust to assumptions about the sub‐populations receiving PrEP, but were highly influenced by assumptions about re‐initiation of PrEP after discontinuation, about which evidence was sparse. Conclusions: Implementation challenges along the prevention cascade compound to diminish the population‐level impact of oral PrEP. Long‐acting PrEP is expected to be less impacted by user uptake and adherence, but it is instead dependent on product availability in the short term and retention in the long term. To maximize the impact of long‐acting PrEP, ensuring timely product approval and rollout is critical. Research is needed on strategies to improve retention and patterns of PrEP re‐initiation. [ABSTRACT FROM AUTHOR]

Introduction: Surveillance of recent HIV infections in national testing services has the potential to inform primary prevention programming activities. Focusing on procedures required to accurately determine recent infection, and the potential for recent infection surveillance to inform prevention efforts, we present the results of three independent but linked pilots of recency testing. Methods: To distinguish recently acquired HIV infection from long‐standing infection, in 2018 we applied a Recent Infection Testing Algorithm that combined a laboratory‐based Limiting Antigen Avidity Enzyme Immunoassay with clinical information (viral‐load; history of prior HIV diagnosis; antiretroviral therapy‐exposure). We explored potential misclassification of test results and analysed the characteristics of participants with recent infection. We applied the algorithm in antenatal clinics providing prevention of mother‐to‐child transmission services in Siaya County, Kenya, outreach sites serving female sex workers in Zimbabwe, and routine HIV testing and counselling facilities in Nairobi, Kenya. In Nairobi, we also conducted recency testing among partners of HIV‐positive participants. Results: In Siaya County, 2.3% (10/426) of HIV‐positive pregnant women were classified as recent. A risk factor analysis comparing women testing recent with those testing HIV‐negative found women in their first trimester were significantly more likely to test recent than those in their second or third trimester. In Zimbabwe, 10.5% (33/313) of female sex workers testing HIV‐positive through the outreach programme were classified recent. A risk factor analysis of women testing recent versus those testing HIV‐negative, found no strong evidence of an association with recent infection. In Nairobi, among 532 HIV‐positive women and men, 8.6% (46) were classified recent. Among partners of participants, almost a quarter of those who tested HIV‐positive were classified as recent (23.8%; 5/21). In all three settings, the inclusion of clinical information helped improve the positive predictive value of recent infection testing by removing cases that were likely misclassified. Conclusions: We successfully identified recently acquired infections among persons testing HIV‐positive in routine testing settings and highlight the importance of incorporating additional information to accurately classify recent infection. We identified a number of groups with a significantly higher proportion of recent infection, suggesting recent infection surveillance, when rolled‐out nationally, may help in further targeting primary prevention efforts. [ABSTRACT FROM AUTHOR]

Introduction: In settings where both daily and event-driven pre-exposure prophylaxis (PrEP) are offered to men who have sex with men (MSM), a clear understanding of the motives to choose between the different dosing-regimens can facilitate more effective PrEP implementation. We therefore studied the motives for choosing for, switching between, and stopping daily or event-driven PrEP. Methods: We used data (August 2015-June 2017) from the prospective, longitudinal, open-label Amsterdam PrEP demonstration study, in which daily (dPrEP) and event-driven PrEP (edPrEP) were offered to 374 HIV-negative MSM and two transgender persons. Participants self-selected the preferred PrEP-regimen at baseline and could switch regimens at three-monthly follow-up visits. We measured motives for choosing PrEP-regimen at baseline and for switching and stopping PrEP at follow-up visits. Open- and closed-end items were combined and qualitatively analysed. Results: Choices of PrEP-regimens were determined by personal and contextual factors, involving the perceived self-efficacy concerning adherence, the risk-context, and the anticipated impact of PrEP on physical and sexual wellbeing. dPrEP was preferred because of the anticipated better adherence and the fear of side-effects relating to edPrEP re-initiations. Moreover, dPrEP was perceived to be more effective than edPrEP. Motives to choose edPrEP were the expected physical burden of dPrEP, anticipated side-effects of dPrEP, and fear to forget daily doses. Regarding the risk-context: dPrEP was preferred for unplanned and/or frequent sex, while edPrEP was chosen when risk was predictable and/or less frequent. While some chose for dPrEP to gain more sexual freedom, others chose for edPrEP to minimize sexual risk episodes. Changes in the above factors, such as changing risk patterns, changing relationships or changing physical conditions, resulted in switching regimens. Choices to stop PrEP were related to lower sexual risk, adherence issues and side-effects. Conclusions: The great diversity of motives illustrates the importance of offering a choice of PrEP-regimens. In counselling of MSM starting PrEP, choices for PrEP-regimens may be addressed as a continuum of flexible and changeable options over time. This may help individuals choose the PrEP-regimen that best fits their current sexual context, priorities and personal capabilities and therefore will be more easily adhered to. [ABSTRACT FROM AUTHOR]

Introduction: The World Health Organization, while recommending pre‐exposure prophylaxis (PrEP) for HIV‐negative pregnant and postpartum women in HIV high‐burden settings, advocates for continued safety evaluation of PrEP in this population. Methods: The PrEP Implementation in Young Women and Adolescents (PrIYA) program delivered PrEP to pregnant and postpartum women integrated within routine maternal and child health clinics (MCH) at 16 sites in Western Kenya. PrEP exposure and perinatal outcome data were collected among women obtaining postnatal services during programme evaluation. PrEP use was self‐reported and confirmed with clinical records. Perinatal outcomes including gestational age at birth, birthweight, congenital malformations and infant growth outcomes were abstracted from clinical records for mother‐infant pairs attending the six week visit. Associations between infant outcomes and maternal prenatal PrEP use were assessed using univariate and multivariate logistic and linear regression. Results: The PrIYA evaluation identified 1530 postpartum mother‐infant pairs with data on prenatal PrEP exposure: 206 with prenatal PrEP use, 1324 without. Median maternal age was 24 years in both groups. PrEP users (any reported PrEP use) were significantly more likely to report HIV risk factors such as: intimate partner violence, sexually transmitted infections and having a partner with positive or unknown HIV status. Most mothers initiated PrEP during the second trimester (n = 116, 57%) and used PrEP for more than one month (n = 110, 58%). The mean birthweight was 3.3 kg and gestational age at birth was 38.5 weeks in both groups. There were no major differences between PrEP exposed and unexposed infants in rates of preterm birth and low birthweight. There were no congenital malformations identified in the PrEP‐exposed group and five reported in the PrEP unexposed group. At six weeks postpartum, infants in both groups had similar growth. No differences in infant outcomes were found by duration PrEP exposure, trimester of PrEP initiation, a subset analysis of women 15 to 24 years old or in multivariate analyses. This analysis demonstrates that monitoring of infant outcomes is feasible within large‐scale programmatic implementation of PrEP among pregnant and postpartum populations. Conclusions: Pregnancy outcomes and early infant growth did not differ by PrEP exposure. [ABSTRACT FROM AUTHOR]

Introduction: Pre‐exposure prophylaxis (PrEP) to prevent HIV infection is being rolled out in Africa. The uptake of PrEP to date has varied across populations and locations. We seek to understand the drivers of demand for PrEP through analysis of qualitative data collected in conjunction with a PrEP demonstration project involving East African HIV serodiscordant couples. Our goal was to inform demand creation by understanding what PrEP means – beyond HIV prevention – for the lives of users. Methods: The Partners Demonstration Project evaluated an integrated strategy of PrEP and antiretroviral therapy (ART) delivery in which time‐limited PrEP served as a "bridge" to long‐term ART. Uninfected partners in HIV serodiscordant couples were offered PrEP at baseline and encouraged to discontinue once infected partners had taken ART for six months. We conducted 274 open‐ended interviews with 93 couples at two Ugandan research sites. Interviews took place one month after enrolment and at later points in the follow‐up period. Topics included are as follows: (1) discovery of serodiscordance; (2) decisions to accept/decline PrEP and/or ART; (3) PrEP and ART initiation; (4) experiences of using PrEP and ART; (5) PrEP discontinuation; (6) impact of PrEP and ART on the partnered relationship. Interviews were audio‐recorded and transcribed. We used an inductive, content analytic approach to characterize meanings of PrEP stemming from its effectiveness for HIV prevention. Relevant content was represented as descriptive categories. Results: Discovery of HIV serodiscordance resulted in fear of HIV transmission for couples, which led to loss of sexual intimacy in committed relationships, and to abandonment of plans for children. As a result, partners became alienated from each other. PrEP countered the threat to the relationship by reducing fear and reinstating hopes of having children together. Condom use worked against the re‐establishment of intimacy and closeness. By increasing couples' sense of protection against HIV infection and raising the prospect of a return to "live sex" (sex without condoms), PrEP was perceived by couples as solving the problem of serodiscordance and preserving committed relationships. Conclusions: The most effective demand creation strategies for PrEP may be those that address the everyday life priorities of potential users in addition to HIV prevention. Clinical Trial Number: NCT02775929 [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Fast‐dissolving vaginal film formulations release antiretroviral drugs directly into vaginal fluid and may be as efficient at drug delivery yet more acceptable to women than gels. In this Phase 1 vaginal film study, the safety, acceptability, pharmacokinetics and pharmacodynamics of two doses of tenofovir (TFV) film and TFV 1% gel were compared to corresponding placebo formulations. Methods: Seventy‐eight healthy HIV negative women were randomized to self‐insert daily vaginal film (10 mg TFV, 40 mg TFV or placebo) or 4 mL of vaginal gel (TFV 1% [40 mg] or placebo) for seven days. Grade 2 and higher adverse events (AEs) related to study product were compared across study arms using Fisher's exact test. Plasma TFV concentrations were measured before and 2 hours after last product use. Paired cervical and vaginal tissue biopsies obtained 2 hours after the last dose were measured to determine tenofovir diphosphate (TFV‐DP) concentrations and exposed to HIV in an ex vivo challenge assay. Acceptability was assessed through questionnaire. Results: There was only one grade 2 or higher related AE, the primary endpoint; it occurred in the placebo gel arm. AEs occurred in 90% of participants; the majority (91%) were grade 1. AEs were similar across study arms. TFV concentrations in plasma and TFV‐DP concentrations in cervical and vaginal tissues were comparable between 40 mg TFV film and the TFV gel groups. There was a significant relationship between reduced viral replication and TFV‐DP concentrations in cervical tissues. Film users were less likely to report product leakage than gel users (66% vs. 100%, p < 0.001). Conclusions: Films were safe and well tolerated. Furthermore, films delivered TFV to mucosal tissues at concentrations similar to gel and were sufficient to block HIV infection of genital tissue ex vivo. [ABSTRACT FROM AUTHOR]

The article provides information on the role of population mobility for achieving HIV infections treatment, transmission and prevention in African countries. Topics discussed include antiretroviral therapy for HIV infections, engagement in the medical care and viral suppression through various randomized controlled trials.

Abstract: Introduction: Population‐level improvements in knowledge about HIV may reduce the stigma attached to HIV and ensure maximal uptake of HIV prevention initiatives. The extent to which levels of HIV knowledge in the general population of sub‐Saharan Africa have changed in the current era of antiretroviral therapy (ART) scale‐up remains unknown. Methods: Data on HIV knowledge in the general population were drawn from the 2003 to 2015 Demographic and Health Surveys (DHS) and AIDS Indicator Surveys (AIS) of 33 countries in sub‐Saharan Africa. The DHS/AIS contain five questions on HIV prevention and transmission that have been used by the Joint United Nations Programme on HIV/AIDS (UNAIDS) as a core indicator of HIV knowledge. We created a composite HIV knowledge variable equal to the number of correct responses to these five questions; a participant was considered to have comprehensive knowledge of HIV (yes/no) if he/she answered all five questions correctly. We fitted negative binomial regression models with cluster‐correlated robust standard errors and country fixed effects, adjusted for socio‐demographic variables, specifying HIV knowledge as the dependent variable and year as the explanatory variable. As an alternative parameterization, we also fitted a multivariable linear probability model with cluster‐correlated robust standard errors and country fixed effects specifying comprehensive knowledge of HIV as the dependent variable. Results: A total of 791,186 women and 395,891 men participating in 75 DHS/AIS were included in the analyses. The mean HIV knowledge score was 3.7 among women and 3.9 among men (p < 0.001). Only 35% of women and 41% of men (p < 0.001) had a comprehensive knowledge of HIV. We estimated a modest but statistically significant positive association between year of DHS/AIS and HIV knowledge (adjusted b = 0.005; 95% confidence interval (CI), 0.001 to 0.009). Similarly, we estimated a statistically significant positive association between year of DHS/AIS and comprehensive knowledge of HIV (adjusted b = 0.011; 95% CI, 0.005 to 0.017), suggesting an approximately 1% relative increase per year in the percentage of the general population who possess a comprehensive knowledge of HIV. Conclusions: There have been minimal improvements over time in HIV knowledge across sub‐Saharan Africa. [ABSTRACT FROM AUTHOR]

Keywords: tuberculosis; prevention; pregnant; HIV; isoniazid; postpartum EN tuberculosis prevention pregnant HIV isoniazid postpartum 1 3 3 04/01/20 20200301 NES 200301 To end the tuberculosis (TB) epidemic, the World Health Organization (WHO) recommends improving access to testing and treatment of latent TB infection (LTBI) [[1]]. Because few TB studies include pregnant and lactating women, many questions remain, from TB epidemiology in pregnancy to optimal testing and treatment. Once active TB is excluded, WHO recommends providing isoniazid preventive therapy (IPT) for people living with HIV, including pregnant women to prevent TB disease [[1]]. [Extracted from the article]

Keywords: women; HIV; prevention; treatment; transgender women; ageing EN women HIV prevention treatment transgender women ageing 1 3 3 04/01/20 20200301 NES 200301 As we celebrate International Women's Day and the many successes that women have, and continue to achieve globally, we are also reminded of the many challenges that remain. Sub-Saharan Africa bears a disproportionate 70% of the global burden of HIV that is spread predominantly through sex with a concomitant epidemic in infants born to mothers living with HIV. A unique characteristic of this generalized epidemic is the high rate of HIV in AGYW, who are up to six times more likely to have HIV compared to their male peers. [Extracted from the article]

Abstract: Introduction: The Amsterdam PrEP project is a prospective, open‐label demonstration study at a large sexually transmitted infection (STI) clinic. We examined the uptake of PrEP; the baseline characteristics of men who have sex with men (MSM) and transgender persons initiating PrEP; their choices of daily versus event‐driven PrEP and the determinants of these choices. Methods: From August 2015 through May 2016, enrolment took place at the STI clinic of the Public Health Service of Amsterdam, the Netherlands. MSM or transgender persons were eligible if they had at least one risk factor for HIV infection within the preceding six months. Participants were offered a choice between daily or event‐driven use of tenofovir/emtricitabine. Baseline data were analysed using descriptive statistics and multivariable analysis was employed to determine variables associated with daily versus event‐driven PrEP. Results: Online applications were submitted by 870 persons, of whom 587 were invited for a screening visit. Of them, 415 were screened for eligibility and 376 initiated PrEP. One quarter (103/376, 27%) chose event‐driven PrEP. Prevalence of bacterial STI was 19.0% and mean condomless anal sex (CAS) episodes in the preceding three months were 11. In multivariable analysis, older age (≥45 vs. ≤34, aOR 2.1, 95% CI 1.2 to 3.9), being involved in a steady relationship (aOR 1.7, 95% CI 1.0 to 2.7), no other daily medication use (aOR 0.6, 95% CI 0.3 to 0.9), and fewer episodes of CAS (per log increase aOR 0.7, 95% CI 0.6 to 0.9) were determinants for choosing event‐driven PrEP. Discussion: PrEP programmes are becoming one of the more important intervention strategies with the goal of reducing incident HIV‐infection and we were unable to accommodate many of the persons applying for this study. Offering a choice of dosing regimen to PrEP users may enable further personalization of HIV prevention strategies and enhance up‐take, adherence and cost‐effectiveness. Conclusions: The majority of participants preferred daily versus event‐driven use. Within this majority, a high number of CAS episodes before PrEP initiation was reported and we observed a high prevalence of STI. Determinants of choosing event‐driven PrEP were older age, fewer CAS episodes, no other daily medication use, and involved in a steady relationship. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Black men who have sex with men and transgender women are at high risk for HIV infection, but are more likely to be unaware of their infection or not in care for diagnosed HIV compared to other races. Respondent driven sampling has been advanced as a method to reach stigmatized and hidden populations for HIV testing. We compared strategies to recruit black, substance‐using men who have sex with men and transgender women to identify newly diagnosed HIV infection, or those previously diagnosed but not in care. Methods: The STAR (Seek, Test, and Retain) study (ClinicalTrials.gov NCT01790360) used several recruitment strategies to identify black, substance‐using men who have sex with men and transgender women with undiagnosed HIV infection or with previously diagnosed HIV infection but who were not in HIV care. Respondent‐driven sampling, community‐based recruitment and online advertising were used to recruit participants. Incentivized peer referral was integrated into all recruitment strategies. Participants completed interviewer‐administered questionnaires and HIV testing. Demographic and HIV risk‐related characteristics and recruitment strategy were summarized and stratified by HIV status. Associations were tested using Pearson's chi‐squared, Fisher's exact, and Wilcoxon rank sum tests. Factors associated with HIV‐positive diagnosis at p < 0.1 were included in a multivariable logistic regression model. Results: From July 2012 through October 2015, the study enrolled 1929 participants; 96.3% men who have sex with men and 3.7% transgender women. Behavioural risk factors included recent condomless anal sex (55.6%) and recent substance use during sex (73.1%). HIV prevalence was 8.7%. In multivariable analysis, significant associations with HIV infection included being transgender; non‐Hispanic black; gay/homosexual orientation; not homeless; and less likely to have insufficient income for necessities. Among recruitment strategies, respondent driven sampling was least effective in identifying HIV‐positive participants. Conclusions: Integrating multiple recruitment strategies yielded a large sample of black men who have sex with men and transgender women at substantial risk for HIV. Respondent‐driven sampling was less effective than other strategies at identifying men who have sex with men and transgender women with HIV. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: A number of antiretroviral HIV prevention products are efficacious in preventing HIV infection. However, the sexual and reproductive health needs of many women extend beyond HIV prevention, and research is ongoing to develop multi‐purpose prevention technologies (MPTs) that offer dual HIV and pregnancy protection. We do not yet know if these products will be an efficient use of constrained health resources. In this paper, we estimate the cost‐effectiveness of combinations of candidate multi‐purpose prevention technologies (MPTs), in South Africa among general population women and female sex workers (FSWs). Methods: We combined a cost model with a static model of product impact based on incidence data in South Africa to estimate the cost‐effectiveness of five candidate co‐formulated or co‐provided MPTs: oral PrEP, intravaginal ring, injectable ARV, microbicide gel and SILCS diaphragm used in concert with gel. We accounted for the preferences of end‐users by predicting uptake using a discrete choice experiment (DCE). Product availability and protection were systematically varied in five potential rollout scenarios. The impact model estimated the number of infections averted through decreased incidence due to product use over one year. The comparator for each scenario was current levels of male condom use, while a health system perspective was used to estimate discounted lifetime treatment costs averted per HIV infection. Product benefit was estimated in disability‐adjusted life years (DALYs) averted. Benefits from contraception were incorporated through adjusting the uptake of these products based on the DCE and through estimating the costs averted from avoiding unwanted pregnancies. We explore the additional impact of STI protection through increased uptake in a sensitivity analysis. Results: At central incidence rates, all single‐ and multi‐purpose scenarios modelled were cost‐effective among FSWs and women aged 16–24, at a governmental willingness‐to‐pay threshold of $1175/DALY averted (range: $214–$810/DALY averted among non‐dominant scenarios), however, none were cost‐effective among women aged 25–49 (minimum $1706/DALY averted). The cost‐effectiveness of products improved with additional protection from pregnancy. Estimates were sensitive to variation in incidence assumptions, but robust to other parameters. Conclusions: To the best of our knowledge, this is the first study to estimate the cost‐effectiveness of a range of potential MPTs; suggesting that MPTs will be cost‐effective among higher incidence FSWs or young women, but not among lower incidence older women. More work is needed to make attractive MPTs available to potential users who could use them effectively. [ABSTRACT FROM AUTHOR]

INTRODUCTION: With the rapid scale-up of antiretroviral treatment (ART) in the "Treat All" era, there has been increasing emphasis on using differentiated models of HIV service delivery. The gaps within the clinical cascade for mothers and their infants suggest that current service delivery models are not meeting families' needs and prompt re-consideration of how services are provided. This article will explore considerations for differentiated care and encourage the ongoing increase of ART coverage through innovative strategies while also addressing the unique needs of mothers and infants. DISCUSSION: Service delivery models should recognize that the timing of the mother's HIV diagnosis is a critical aspect of determining eligibility. Women newly diagnosed with HIV require a more intensive approach so that adequate counselling and monitoring of ART initiation and response can be provided. Women already on ART with evidence of virologic failure are also at high risk of transmitting HIV to their infants and require close follow-up. However, women stable on ART with a suppressed viral load before conception have a very low likelihood of HIV transmission and thus are strong candidates for multi-month ART dispensing, community-based distribution of ART, adherence clubs, community adherence support groups and longer intervals between clinical visits. A number of other factors should be considered when defining eligibility of mothers and infants for differentiated care, including location of services, viral load monitoring and duration on ART. To provide differentiated care that is client-centred and driven while encompassing a family-based approach, it will be critical to engage mothers, families and communities in models that will optimize client satisfaction, retention in care and quality of services. CONCLUSIONS: Differentiated care for mothers and infants represents an opportunity to provide client-centred care that reduces the burden on clients and health systems while improving the quality and uptake of services for families. However, with decreasing funding, stable HIV incidence, and aspirations for sustainability, it is critical to consider efficient, customized and cost-effective models of care for these populations as we aspire to eliminate mother-to-child transmission of HIV. [ABSTRACT FROM AUTHOR]

Introduction: The science presented at the 21st International AIDS Conference in Durban, South Africa, in July 2016, addressed the state of the field across basic, clinical, prevention, law and policy and implementation science. Methods and Results: The AIDS response has seen remarkable achievements in scientific advances, in translation of those advances into prevention, treatment and care for affected individuals and communities, and in large scale implementation - reaching 18 million people with antiviral therapy by mid-year 2016. Yet incident HIV infections in adults remain stubbornly stable and are increasing in some regions and among adolescents and adults in some key populations, challenging current science, policy and programming. There have been important advances in both preventive vaccines and in cure research, but both areas require ongoing investment and innovation. Clinical research has flourished with new agents, regimens, delivery modes and diagnostics but has been challenged by aging and increasingly complex patient populations, long-term adherence challenges, co-infections and co-morbidities, and unresolved issues in TB management and epidemic control. It is an extraordinary period of innovation in prevention, yet the promise of new tools and combination approaches have yet to deliver epidemic HIV control. [ABSTRACT FROM AUTHOR]

Introduction: The science presented at the 21st International AIDS Conference in Durban, South Africa, in July 2016, addressed the state of the field across basic, clinical, prevention, law and policy and implementation science. Methods and Results: The AIDS response has seen remarkable achievements in scientific advances, in translation of those advances into prevention, treatment and care for affected individuals and communities, and in large scale implementation - reaching 18 million people with antiviral therapy by mid-year 2016. Yet incident HIV infections in adults remain stubbornly stable and are increasing in some regions and among adolescents and adults in some key populations, challenging current science, policy and programming. There have been important advances in both preventive vaccines and in cure research, but both areas require ongoing investment and innovation. Clinical research has flourished with new agents, regimens, delivery modes and diagnostics but has been challenged by aging and increasingly complex patient populations, long-term adherence challenges, co-infections and co-morbidities, and unresolved issues in TB management and epidemic control. It is an extraordinary period of innovation in prevention, yet the promise of new tools and combination approaches have yet to deliver epidemic HIV control. Conclusions: Proven interventions, most notably pre-exposure prophylaxis, PrEP, have been limited in rollout and impact. Treatment as prevention has the promise to improve clinical outcomes but remains uncertain as a prevention tool to reduce population-level HIV incidence. The improvement of legal, policy and human rights environments for those most at risk for HIV acquisition and most at risk for lack of access to essential services; sexual and gender minorities, sex workers of all genders, people who inject drugs, and prisoners and detainees remain among the greatest unmet needs in HIV/AIDS. Failure to do better for these individuals and communities could undermine the HIV response. [ABSTRACT FROM AUTHOR]

Introduction: Despite the rollout of antiretroviral therapy (ART), challenges remain in ensuring timely access to care and treatment for people living with HIV. As part of a multi-country study to investigate HIV mortality, we conducted health facility surveys within 10 health and demographic surveillance system sites across six countries in Eastern and Southern Africa to investigate clinic-level factors influencing (i) use of HIV testing services, (ii) use of HIV care and treatment and (iii) patient retention on ART. Methods: Health facilities (n = 156) were sampled within 10 surveillance sites: Nairobi and Kisumu (Kenya), Karonga (Malawi), Agincourt and uMkhanyakude (South Africa), Ifakara and Kisesa (Tanzania), Kyamulibwa and Rakai (Uganda) and Manicaland (Zimbabwe). Structured questionnaires were administered to in-charge staff members of HIV testing, prevention of mother-to-child transmission (PMTCT) and ART units within the facilities. Forty-one indicators influencing uptake and patient retention along the continuum of HIV care were compared across sites using descriptive statistics. Results: The number of facilities surveyed ranged from six in Malawi to 36 in Zimbabwe. Eighty percent were government-run; 73% were lower-level facilities and 17% were district/referral hospitals. Client load varied widely, from less than one up to 65 HIV testing clients per provider per week. Most facilities (>80%) delivered services or interventions that would support patient retention in care such as delivering free services, offering PMTCT within antenatal care, pre-ART monitoring and adherence counselling. Many facilities under-delivered in several areas, however, such as targeted testing for high-risk groups (21%) and mobile testing (36%). There were also intra-site and inter-site differences, including in the delivery of Option B+ (ranging from 6% in Kisumu to 93% in Kyamulibwa), and nurse-led ART initiation (ranging from 50% in Kisesa to 100% in Karonga and Agincourt). Only facilities in Malawi did not require additional lab tests for ART initiation. Stock-outs of HIV test kits and antiretroviral drugs were particularly common in Tanzania. Conclusions: We identified a high standard of health facility performance in delivering strategies that may support progression through the continuum of HIV care. HIV testing policy and practice was particularly weak. Inter- and intracountry differences in quality and coverage represent opportunities to improve the delivery of comprehensive services to people living with HIV. [ABSTRACT FROM AUTHOR]

Introduction: The science presented at the 21st International AIDS Conference in Durban, South Africa, in July 2016, addressed the state of the field across basic, clinical, prevention, law and policy and implementation science. Methods and Results: The AIDS response has seen remarkable achievements in scientific advances, in translation of those advances into prevention, treatment and care for affected individuals and communities, and in large scale implementation – reaching 18 million people with antiviral therapy by mid-year 2016. Yet incident HIV infections in adults remain stubbornly stable and are increasing in some regions and among adolescents and adults in some key populations, challenging current science, policy and programming. There have been important advances in both preventive vaccines and in cure research, but both areas require ongoing investment and innovation. Clinical research has flourished with new agents, regimens, delivery modes and diagnostics but has been challenged by aging and increasingly complex patient populations, long-term adherence challenges, co-infections and co-morbidities, and unresolved issues in TB management and epidemic control. It is an extraordinary period of innovation in prevention, yet the promise of new tools and combination approaches have yet to deliver epidemic HIV control. Conclusions: Proven interventions, most notably pre-exposure prophylaxis, PrEP, have been limited in rollout and impact. Treatment as prevention has the promise to improve clinical outcomes but remains uncertain as a prevention tool to reduce population-level HIV incidence. The improvement of legal, policy and human rights environments for those most at risk for HIV acquisition and most at risk for lack of access to essential services; sexual and gender minorities, sex workers of all genders, people who inject drugs, and prisoners and detainees remain among the greatest unmet needs in HIV/AIDS. Failure to do better for these individuals and communities could undermine the HIV response. [ABSTRACT FROM AUTHOR]

Introduction Of the two million new HIV infections in adults in 2014, 70% occurred in sub-Saharan Africa. Several African countries have already approved guidelines for pre-exposure prophylaxis (PrEP) for individuals at substantial risk of HIV as part of combination HIV prevention but key questions remain about how to identify and deliver PrEP to those at greatest need. Throughout the continent, individuals in sero-discordant relationships, and members of key populations (sex workers, men who have sex with men (MSM), transgender women and injection drug users) are likely to benefit from the availability of PrEP. In addition, adolescent girls and young women (AGYW) are at substantial risk in some parts of the continent. It has been estimated that at least three million individuals in Africa are likely to be eligible for PrEP according to WHO's criteria. Tens of demonstration projects are planned or underway across the continent among a range of countries, populations and delivery settings. Discussion In each of the target populations, there are overarching issues related to (i) creating demand for PrEP, (ii) addressing supply-side issues and (iii) providing appropriate and tailored adherence support. Critical for creating demand for PrEP is the normalization of HIV prevention. Community-level interventions which engage opinion leaders as well as empowerment interventions for those at highest risk will be key. Critical to supply of PrEP is that services are accessible for all, including for stigmatized populations. Establishing accessible integrated services provides the opportunity to address other public health priorities including the unmet need for HIV testing, contraception and sexually transmitted infections treatment. National policies need to include minimum standards for training and quality assurance for PrEP implementation and to address supply chain issues. Adherence support needs to recognize that social and structural factors are likely to have an important influence. Combining interventions that build self-efficacy, empowerment and social cohesion, with evidence-based individualized adherence support for PrEP, are most likely to be effective. Conclusions Efficacy of tenfovir-based PrEP is proven but many issues related to implementation remain unclear. Here, we have summarized some of the important implementation questions that need to be assessed as PrEP is rolled out across Africa. [ABSTRACT FROM AUTHOR]

Introduction Despite progress in scaling up antiretroviral treatment, HIV prevention strategies have not been successful in significantly curbing HIV incidence in Latin America. HIV prevention interventions need to be expanded to target the most affected key populations with a combination approach, including new high impact technologies. Oral pre-exposure prophylaxis (PrEP) is recommended as additional prevention choice for individuals at higher risk of infection and could become a cost-effective prevention tool. We discuss the barriers and solutions for a fair consideration of PrEP as part of combination HIV prevention strategies in Latin America. Discussion Although demonstration projects are ongoing or being planned in a number of countries, to date no Latin American country has implemented a public PrEP programme. The knowledge of policymakers about PrEP implementation needs to be strengthened, and programmatic guidance and cost estimate tools need to be developed to support adequate planning. Despite high levels of awareness among health providers, especially if engaged in HIV or key population care, willingness to prescribe PrEP is still low due to the lack of national policies and guidelines. Key populations, especially men who have sex with men, transgender women and sex workers, have been engaged in demonstration projects, and qualitative research shows high awareness and willingness to use PrEP, especially if accessible in the public sector for free or at affordable price. Concerns of safety, adherence, effectiveness and risk compensation need to be addressed through targeted social communication strategies to improve PrEP knowledge and stimulate demand. Alliance among policymakers, civil society and representatives from key populations, healthcare providers and researchers will be critical for the design and successful implementation of PrEP demonstration projects of locally adapted delivery models. The use of mechanisms of joint negotiation and procurement of antiretrovirals could reduce costs and significantly increase the cost-effectiveness of PrEP. Conclusions PrEP is an additional prevention tool and should be implemented in combination and synergy with other prevention interventions. PrEP programmes should target high-risk individuals from key populations for higher cost-effectiveness. Demonstration projects may generate strategic information for and lead to the implementation of full-scale PrEP programmes. [ABSTRACT FROM AUTHOR]

Introduction: Despite progress in scaling up antiretroviral treatment, HIV prevention strategies have not been successful in significantly curbing HIV incidence in Latin America. HIV prevention interventions need to be expanded to target the most affected key populations with a combination approach, including new high impact technologies. Oral pre-exposure prophylaxis (PrEP) is recommended as additional prevention choice for individuals at higher risk of infection and could become a costeffective prevention tool. We discuss the barriers and solutions for a fair consideration of PrEP as part of combination HIV prevention strategies in Latin America. Discussion: Although demonstration projects are ongoing or being planned in a number of countries, to date no Latin American country has implemented a public PrEP programme. The knowledge of policymakers about PrEP implementation needs to be strengthened, and programmatic guidance and cost estimate tools need to be developed to support adequate planning. Despite high levels of awareness among health providers, especially if engaged in HIV or key population care, willingness to prescribe PrEP is still low due to the lack of national policies and guidelines. Key populations, especially men who have sex with men, transgender women and sex workers, have been engaged in demonstration projects, and qualitative research shows high awareness and willingness to use PrEP, especially if accessible in the public sector for free or at affordable price. Concerns of safety, adherence, effectiveness and risk compensation need to be addressed through targeted social communication strategies to improve PrEP knowledge and stimulate demand. Alliance among policymakers, civil society and representatives from key populations, healthcare providers and researchers will be critical for the design and successful implementation of PrEP demonstration projects of locally adapted delivery models. The use of mechanisms of joint negotiation and procurement of antiretrovirals could reduce costs and significantly increase the cost-effectiveness of PrEP. Conclusions: PrEP is an additional prevention tool and should be implemented in combination and synergy with other prevention interventions. PrEP programmes should target high-risk individuals from key populations for higher cost-effectiveness. Demonstration projects may generate strategic information for and lead to the implementation of full-scale PrEP programmes. [ABSTRACT FROM AUTHOR]

Introduction: Of the two million new HIV infections in adults in 2014, 70% occurred in sub-Saharan Africa. Several African countries have already approved guidelines for pre-exposure prophylaxis (PrEP) for individuals at substantial risk of HIV as part of combination HIV prevention but key questions remain about how to identify and deliver PrEP to those at greatest need. Throughout the continent, individuals in sero-discordant relationships, and members of key populations (sex workers, men who have sex with men (MSM), transgender women and injection drug users) are likely to benefit from the availability of PrEP. In addition, adolescent girls and young women (AGYW) are at substantial risk in some parts of the continent. It has been estimated that at least three million individuals in Africa are likely to be eligible for PrEP according to WHO’s criteria. Tens of demonstration projects are planned or underway across the continent among a range of countries, populations and delivery settings. Discussion: In each of the target populations, there are overarching issues related to (i) creating demand for PrEP, (ii) addressing supply-side issues and (iii) providing appropriate and tailored adherence support. Critical for creating demand for PrEP is the normalization of HIV prevention. Community-level interventions which engage opinion leaders as well as empowerment interventions for those at highest risk will be key. Critical to supply of PrEP is that services are accessible for all, including for stigmatized populations. Establishing accessible integrated services provides the opportunity to address other public health priorities including the unmet need for HIV testing, contraception and sexually transmitted infections treatment. National policies need to include minimum standards for training and quality assurance for PrEP implementation and to address supply chain issues. Adherence support needs to recognize that social and structural factors are likely to have an important influence. Combining interventions that build self-efficacy, empowerment and social cohesion, with evidence-based individualized adherence support for PrEP, are most likely to be effective. Conclusions: Efficacy of tenfovir-based PrEP is proven but many issues related to implementation remain unclear. Here, we have summarized some of the important implementation questions that need to be assessed as PrEP is rolled out across Africa. [ABSTRACT FROM AUTHOR]

Introduction Transgender women are the population most vulnerable to HIV in Latin America, with prevalence between 18 and 38%. Although the region has improved antiretroviral coverage, there is an urgent need to strengthen HIV prevention for key populations to meet regional targets set by governments. We conducted an assessment on the state of HIV prevention among transgender women in Latin America. Methods We conducted a desk review of Global AIDS Response Progress Reports, national strategic plans, technical reports and peer-reviewed articles from 17 Latin American countries published through January 2015. The review was preceded by 12 semi-structured interviews with UNAIDS and Pan American Health Organization officers and a discussion group with transgender women regional leaders, to guide the identification of documents. We assessed access to, implementation and coverage of programmes; legal frameworks; community participation; inclusion of new strategies; and alignment with international recommendations. Results and discussion Overall, prevention activities in the region focus on condom distribution, diagnosis of sexually transmitted infections and peer education, mostly delivered at health facilities, with limited community involvement. Argentina and Uruguay have implemented structural interventions to address social inclusion. Argentina, Brazil and Mexico have adopted early initiation of antiretroviral therapy and treatment as prevention strategies. The other countries do not have substantial tailored interventions and consider the trans population a sub-population of men who have sex with men in data collection and programme implementation. Limited coverage of services, discrimination and a deep-seated mistrust of the health system among transgender women are the main barriers to accessing HIV prevention services. Promising interventions include health services adapted to transgender women in Mexico; LGBT-friendly clinics in Argentina that incorporate community and health workers in mixed teams; task-shifting to community-based organizations; mobile HIV testing; and gender identity laws. Conclusions Transgender women in Latin America continue to have limited access to HIV prevention services, which presents a bottleneck for reaching prevention goals and incorporating new prevention interventions. Prevention programmes should be rights-based; offer tailored, holistic interventions; and involve transgender women in their design and implementation. [ABSTRACT FROM AUTHOR]

Introduction: Transgender women are the population most vulnerable to HIV in Latin America, with prevalence between 18 and 38%. Although the region has improved antiretroviral coverage, there is an urgent need to strengthen HIV prevention for key populations to meet regional targets set by governments. We conducted an assessment on the state of HIV prevention among transgender women in Latin America. Methods: We conducted a desk review of Global AIDS Response Progress Reports, national strategic plans, technical reports and peer-reviewed articles from 17 Latin American countries published through January 2015. The review was preceded by 12 semistructured interviews with UNAIDS and Pan American Health Organization officers and a discussion group with transgender women regional leaders, to guide the identification of documents.We assessed access to, implementation and coverage of programmes; legal frameworks; community participation; inclusion of new strategies; and alignment with international recommendations. Results and discussion: Overall, prevention activities in the region focus on condom distribution, diagnosis of sexually transmitted infections and peer education, mostly delivered at health facilities, with limited community involvement. Argentina and Uruguay have implemented structural interventions to address social inclusion. Argentina, Brazil and Mexico have adopted early initiation of antiretroviral therapy and treatment as prevention strategies. The other countries do not have substantial tailored interventions and consider the trans population a sub-population of men who have sex with men in data collection and programme implementation. Limited coverage of services, discrimination and a deep-seated mistrust of the health system among transgender women are the main barriers to accessing HIV prevention services. Promising interventions include health services adapted to transgender women in Mexico; LGBT-friendly clinics in Argentina that incorporate community and health workers in mixed teams; task-shifting to community-based organizations; mobile HIV testing; and gender identity laws. Conclusions: Transgender women in Latin America continue to have limited access to HIV prevention services, which presents a bottleneck for reaching prevention goals and incorporating new prevention interventions. Prevention programmes should be rights-based; offer tailored, holistic interventions; and involve transgender women in their design and implementation. [ABSTRACT FROM AUTHOR]

Introduction: Vaginal tenofovir (TFV) 1% gel may reduce incident HIV-1 and herpes simplex virus 2 infection. Pregnancy may increase risk of HIV acquisition, and incident HIV in pregnancy potentiates perinatal HIV transmission. Our objective was to investigate the safety and pharmacokinetics of seven days of TFV 1% vaginal gel in term and near-term pregnancy.Methods: Ninety-eight healthy pregnant women, stratified to a term cohort followed by a near-term cohort, were enrolled into a 2:1 randomized, double-blinded, placebo-controlled trial. Women received TFV or placebo gel for seven consecutive days with pharmacokinetic sampling on days 0 and 6. Maternal and cord blood were collected at delivery. Primary end points included laboratory and genital adverse events, adverse pregnancy and neonatal outcomes, and maternal TFV levels.Results: Most adverse events were grade 1 and none of the grade 3 or 4 adverse events were related to study product. There was no significant difference in safety end points between the two pregnancy cohorts (p=0.18); therefore, their data were combined. Primary safety end point rates were similar for mothers randomized to the TFV gel vs placebo arm (72.7 and 68.8%, p=0.81). The same was true for newborns in the TFV gel vs placebo arms (4.5% vs 6.3%, p=0.66). All women randomized to TFV had quantifiable serum levels within eight hours of dosing, with low overall median (interquartile range) day 0 and day 6 peak values (3.8 (2.0 to 7.0) and 5.8 (2.6 to 9.4) ng/mL, respectively).Conclusions: Daily TFV 1% vaginal gel use in term and near-term pregnancy appears to be safe and produces low serum drug levels. [ABSTRACT FROM AUTHOR]

Introduction: Once-daily tenofovir/emtricitabine-based pre-exposure prophylaxis (PrEP) can reduce HIV acquisition in men who have sex with men (MSM), by 44% in the iPrEx trial, and reaching up to 99% with high adherence. We examined the potential population-level impact and cost-effectiveness of different PrEP implementation strategies.Methods: We developed a dynamic, stochastic compartmental model of HIV transmission among the estimated 57,400 MSM in Toronto, Canada. Parameterization was performed using local epidemiologic data. Strategies examined included (1) uniform PrEP delivery versus targeting the highest risk decile of MSM (with varying coverage proportions); (2) increasing PrEP efficacy as a surrogate of adherence (44% to 99%); and (3) varying HIV test frequency (once monthly to once yearly). Outcomes included HIV infections averted and the incremental cost ($CAD) per incremental quality-adjusted-life-year (QALY) gained over 20 years.Results: Use of PrEP among all HIV-uninfected MSM at 25, 50, 75 and 100% coverage prevented 1970, 3427, 4317, and 4581 infections, respectively, with cost/QALY increasing from $500,000 to $800,000 CAD. Targeted PrEP for the highest risk MSM at 25, 50, 75 and 100% coverage prevented 1166, 2154, 2816, and 3012 infections, respectively, with cost/QALY ranging from $35,000 to $70,000 CAD. Maximizing PrEP efficacy, in a scenario of 25% coverage of high-risk MSM with PrEP, prevented 1540 infections with a cost/QALY of $15,000 CAD. HIV testing alone (Q3 months) averted 898 of infections with a cost savings of $4,000 CAD per QALY.Conclusions: The optimal implementation strategy for PrEP over the next 20 years at this urban centre is to target high-risk MSM and to maximize efficacy by supporting PrEP adherence. A large health benefit of PrEP implementation could come from engaging undiagnosed HIV-infected individuals into care. [ABSTRACT FROM AUTHOR]

Introduction: Every new HIV infection is preventable and every HIV-related death is avoidable. As many jurisdictions around the world endeavour to end HIV as an epidemic, missed HIV prevention and treatment opportunities must be regarded as public health emergencies, and efforts to quickly fill gaps in service provision for all people living with and vulnerable to HIV infection must be prioritized.Discussion: We present a novel, comprehensive, primary and secondary HIV prevention continuum model for the United States as a conceptual framework to identify key steps in reducing HIV incidence and improving health outcomes among those vulnerable to, as well as those living with, HIV infection. We further discuss potential approaches to address gaps in data required for programme planning, implementation and evaluation across the elements of the HIV prevention continuum.Conclusions: Our model conceptualizes opportunities to monitor and quantify primary HIV prevention efforts and, importantly, illustrates the interplay between an outcomes-oriented primary HIV prevention process and the HIV care continuum to move aggressively forward in reaching ambitious reductions in HIV incidence. To optimize the utility of this outcomes-oriented HIV prevention continuum, a key gap to be addressed includes the creation and increased coordination of data relevant to HIV prevention across sectors. [ABSTRACT FROM AUTHOR]

Introduction: In Bangalore, new HIV infections of female sex workers and men who have sex with men continue to occur, despite high condom use. Pre-exposure prophylaxis (PrEP) has high anti-HIV efficacy for men who have sex with men. PrEP demonstration projects are underway amongst Indian female sex workers.We estimated the impact and efficiency of prioritizing PrEP to female sex workers and/or men who have sex with men in Bangalore. Methods: A mathematical model of HIV transmission and treatment for female sex workers, clients, men who have sex with men and low-risk groups was parameterized and fitted to Bangalore data. The proportion of transmission attributable (population attributable fraction) to commercial sex and sex between men was calculated. PrEP impact (infections averted, life-years gained) and efficiency (life-years gained/infections averted per 100 person-years on PrEP) were estimated for different levels of PrEP adherence, coverage and prioritization strategies (female sex workers, high-risk men who have sex with men, both female sex workers and high-risk men who have sex with men, or female sex workers with lower condom use), under current conditions and in a scenario with lower baseline condom use amongst key populations. Results: Population attributable fractions for commercial sex and sex between men have declined over time, and they are predicted to account for 19% of all new infections between 2016 and 2025. PrEP could prevent a substantial proportion of infections amongst female sex workers and men who have sex with men in this setting (23%/27% over 5/10 years, with 60% coverage and 50% adherence), which could avert 2.9%/4.3% of infections over 5/10 years in the whole Bangalore population. Impact and efficiency in the whole population was greater if female sex workers were prioritized. Efficiency increased, but impact decreased, if only female sex workers with lower condom use were given PrEP. Greater impact and efficiency was predicted for the scenario with lower condom use. Conclusions: PrEP could be beneficial for female sex workers and men who have sex with men in Bangalore, and give some benefits in the general population, especially in similar settings with lower condom use levels. [ABSTRACT FROM AUTHOR]

Introduction: Poor adherence to product use has been observed in recent trials of antiretroviral (ARV)-based oral and vaginal gel HIV prevention products, resulting in an inability to determine product efficacy. The delivery of microbicides through vaginal rings is widely perceived as a way to achieve better adherence but vaginal rings do not eliminate the adherence challenges exhibited in clinical trials. Improved objective measures of adherence are needed as new ARV-based vaginal ring products enter the clinical trial stage. Methods: To identify technologies that have potential future application for vaginal ring adherence measurement, a comprehensive literature search was conducted that covered a number of biomedical and public health databases, including PubMed, Embase, POPLINE and the Web of Science. Published patents and patent applications were also searched. Technical experts were also consulted to gather more information and help evaluate identified technologies. Approaches were evaluated as to feasibility of development and clinical trial implementation, cost and technical strength. Results: Numerous approaches were identified through our landscape analysis and classified as either point measures or cumulative measures of vaginal ring adherence. Point measurements are those that give a measure of adherence at a particular point in time. Cumulative measures attempt to measure ring adherence over a period of time. Discussion: Approaches that require modifications to an existing ring product are at a significant disadvantage, as this will likely introduce additional regulatory barriers to the development process and increase manufacturing costs. From the point of view of clinical trial implementation, desirable attributes would be high acceptance by trial participants, and little or no additional time or training requirements on the part of participants or clinic staff. We have identified four promising approaches as being high priority for further development based on the following measurements: intracellular drug levels, drug levels in hair, the accumulation of a vaginal analyte that diffuses into the ring, and the depletion of an intrinsic ring constituent. Conclusions: While some approaches show significant promise over others, it is recommended that a strategy of using complementary biometric and behavioural approaches be adopted to best understand participants’ adherence to ARV-based ring products in clinical trials. [ABSTRACT FROM AUTHOR]