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Despite progress in providing antiretroviral therapy to pregnant women living with HIV, a substantial number of vertical transmissions continue to occur. Novel approaches leveraging modern potent, safe, and well-tolerated antiretroviral drugs are urgently needed.

IntroductionMaternal antiretroviral therapy (ART) with viral suppression prior to conception, during pregnancy and throughout the breastfeeding period accompanied by infant postnatal prophylaxis (PNP) forms the foundation of current approaches to preventing vertical HIV transmission. Unfortunately, infants continue to acquire HIV infections, with half of these infections occurring during breastfeeding. A consultative meeting of stakeholders was held to review the current state of PNP globally, including the implementation of WHO PNP guidelines in different settings and identifying the key factors affecting PNP uptake and impact, with an aim to optimize future innovative strategies.DiscussionWHO PNP guidelines have been widely implemented with adaptations to the programme context. Some programmes with low rates of antenatal care attendance, maternal HIV testing, maternal ART coverage and viral load testing capacity have opted against risk-stratification and provide an enhanced PNP regimen for all infants exposed to HIV, while other programmes provide infant daily nevirapine antiretroviral (ARV) prophylaxis for an extended duration to cover transmission risk throughout the breastfeeding period. A simplified risk stratification approach may be more relevant for high-performing vertical transmission prevention programmes, while a simplified non-risk stratified approach may be more appropriate for sub-optimally performing programmes given implementation challenges. In settings with concentrated epidemics, where the epidemic is often driven by key populations, infants who are found to be exposed to HIV should be considered at high risk for HIV acquisition. All settings could benefit from newer technologies that promote retention during pregnancy and throughout the breastfeeding period. There are several challenges in enhanced and extended PNP implementation, including ARV stockouts, lack of appropriate formulations, lack of guidance on alternative ARV options for prophylaxis, poor adherence, poor documentation, inconsistent infant feeding practices and in inadequate retention throughout the duration of breastfeeding.ConclusionsTailoring PNP strategies to a programmatic context may improve access, adherence, retention and HIV-free outcomes of infants exposed to HIV. Newer ARV options and technologies that enable simplification of regimens, non-toxic potent agents and convenient administration, including longer-acting formulations, should be prioritized to optimize the effect of PNP in the prevention of vertical HIV transmission.

Background World Health Organization (WHO) guidelines recommend cotrimoxazole prophylaxis for children who are HIV-exposed until infection is excluded and vertical transmission risk has ended. While cotrimoxazole has benefits for children with HIV, there is no mortality benefit for children who are HIV-exposed but uninfected, prompting a review of global guidelines. Here, we model the potential impact of alternative cotrimoxazole strategies on mortality in children who are HIV-exposed. Methods and findings Using a deterministic compartmental model, we estimated mortality in children who are HIV-exposed from 6 weeks to 2 years of age in 4 high-burden countries: Côte d'Ivoire, Mozambique, Uganda, and Zimbabwe. Vertical transmission rates, testing rates, and antiretroviral therapy (ART) uptake were derived from UNAIDS data, trial evidence, and meta-analyses. We explored 6 programmatic strategies: maintaining current recommendations; shorter cotrimoxazole provision for 3, 6, 9, or 12 months; and starting cotrimoxazole only for children diagnosed with HIV. Modelled alternatives to the current strategy increased mortality to varying degrees; countries with high vertical transmission had the greatest mortality. Compared to current recommendations, starting cotrimoxazole only after a positive HIV test had the greatest predicted increase in mortality: Mozambique (961 excess annual deaths; excess mortality 339 per 100,000 HIV-exposed children; risk ratio (RR) 1.06), Uganda (491; 221; RR 1.04), Zimbabwe (352; 260; RR 1.05), and Côte d'Ivoire (125; 322; RR 1.06). Similar effects were observed for 3-, 6-, 9-, and 12-month strategies. Increased mortality persisted but was attenuated when modelling lower cotrimoxazole uptake, smaller mortality benefits, higher testing coverage, and lower vertical transmission rates. The study is limited by uncertain estimates of cotrimoxazole coverage in programmatic settings; an inability to model increases in mortality arising from antimicrobial resistance due to limited surveillance data in sub-Saharan Africa; and lack of a formal health economic analysis. Conclusions Changing current guidelines from universal cotrimoxazole provision for children who are HIV-exposed increased predicted mortality across the 4 modelled high-burden countries, depending on test-to-treat cascade coverage and vertical transmission rates. These findings can help inform policymaker deliberations on cotrimoxazole strategies, recognising that the risks and benefits differ across settings., Author(s): Shrey Mathur 1,*, Melanie Smuk 1, Ceri Evans 1,2,3, Catherine J. Wedderburn 4,5, Diana M. Gibb 4, Martina Penazzato 6, Andrew J. Prendergast 1,2 Introduction Vertical transmission of HIV [...]

Information on the extent of drug exposure to mothers and infants during pregnancy and lactation normally becomes available years after regulatory approval of a drug. Clinicians face knowledge gaps on drug selection and dosing in pregnancy and infant exposure during breastfeeding. Physiological changes during pregnancy often result in lower drug exposures of antiretrovirals, and in some cases a risk of reduced virologic efficacy. The International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) network and the World Health Organization (WHO)-convened Pediatric Antiretrovirals Working Group collaboratively organized a workshop of key stakeholders in June 2019 to define key standards to generate pharmacology data for antiretrovirals to be used among pregnant and lactating women; review the antiretroviral product pipeline; describe key gaps for use in low-income and middle-income countries; and identify opportunities to undertake optimal studies allowing for rapid implementation in the clinical field. We discussed ethical and regulatory principles, systemic approaches to obtaining data for pregnancy pharmacokinetic/pharmacodynamic (PK/PD) studies, control groups, optimal sampling times during pregnancy, and pharmacokinetic parameters to be considered as primary end points in pregnancy PK/PD studies. For lactation studies, the type of milk to collect, ascertainment of maternal adherence, and optimal PK methods to estimate exposure were discussed. Participants strongly recommended completion of preclinical reproductive toxicology studies prior to phase III, to allow study protocols to include pregnant women or to allow women who become pregnant after enrolment to continue in the trial. The meeting concluded by developing an algorithm for design and interpretation of results and noted that recruitment of pregnant and lactating women into clinical trials is critical.

IntroductionManagement of concomitant use of ART and TB drugs is difficult because of the many drug-drug interactions (DDIs) between the medications. This systematic review provides an overview of the current state of knowledge about the pharmacokinetics (PK) of ART and TB treatment in children with HIV/TB co-infection, and identifies knowledge gaps.MethodsWe searched Embase and PubMed, and systematically searched abstract books of relevant conferences, following PRISMA guidelines. Studies not reporting PK parameters, investigating medicines that are not available any longer or not including children with HIV/TB co-infection were excluded. All studies were assessed for quality.ResultsIn total, 47 studies met the inclusion criteria. No dose adjustments are necessary for efavirenz during concomitant first-line TB treatment use, but intersubject PK variability was high, especially in children 4 weeks old as well as twice-daily dolutegravir (instead of once daily) in children older than 6 years. Exposure to some TB drugs (ethambutol and rifampicin) was reduced in the setting of HIV infection, regardless of ART use. Only limited PK data of second-line TB drugs with ART in children who are HIV infected have been published.ConclusionsWhereas integrase inhibitors seem favourable in older children, there are limited options for ART in young children (

Medication use during pregnancy in the absence of pharmacokinetic and safety data is common, particularly for antiretrovirals, as pregnant women are not usually included in clinical trials leading to drug licensure. To date, data are typically generated through opportunistic pregnancy studies performed in the postmarketing setting, leading to a substantial time-lag between initial regulatory approval of a drug and availability of essential pregnancy-specific pharmacokinetic and safety data. During this period, health care providers lack key information on human placental transfer, fetal exposure, optimal maternal dosing in pregnancy, and maternal and fetal drug toxicity, including teratogenicity risk. We discuss new approaches that could facilitate the acquisition of these critical data earlier in the drug development process, aiding clinicians and patients in making informed decisions on drug selection and dosing during pregnancy. An integrated approach utilizing multiple novel methodologies (in vitro, ex vivo, in silico and in vivo) is needed to accelerate the availability of pharmacology data in pregnancy and lactation.

Despite considerable progress in paediatric HIV treatment and timely revision of global policies recommending the use of more effective and tolerable antiretroviral regimens, optimal antiretroviral formulations for infants, children, and adolescents remain limited. The Paediatric Antiretroviral Drug Optimization group reviews medium-term and long-term priorities for antiretroviral drug development to guide industry and other stakeholders on formulations most needed for low-income and middle-income countries. The group convened in December, 2018, to assess progress since the previous meeting and update the list of priority formulations. Issues relating to drug optimisation for neonatal prophylaxis and paediatric treatment, and those relating to the investigation of novel antiretrovirals in adolescents and pregnant and lactating women were also discussed. Continued focus on identifying, prioritising, and providing access to optimal antiretroviral formulations suitable for infants, children, and adolescents is key to ensuring that global HIV treatment targets can be met.

Introduction: Adolescents living with HIV are subject to multiple co-morbidities, including growth retardation and immunodeficiency. We describe growth and CD4 evolution during adolescence using data from the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) globalproject. Methods: Data were collected between 1994 and 2015 from 11 CIPHER networks worldwide. Adolescents with perinatally acquired HIV infection (APH) who initiated antiretroviral therapy (ART) before age 10 years, with at least one height or CD4 count measurement while aged 10-17 years, were included. Growth was measured using height-for-age Z-scores (HAZ, stunting if Results: A total of 20,939 and 19,557 APH were included for the growth and CD4 analyses, respectively. Half were females, two-thirds lived in East and Southern Africa, and median age at ART initiation ranged from 7 years in sub-Saharan African regions. At age 10, stunting ranged from 6% in North America and Europe to 39% in the Asia-Pacific; 19% overall had CD4 counts Conclusions: Growth patterns during adolescence differed substantially by sex and region, while CD4 patterns were similar, with an observed CD4 decline that needs further investigation. Early diagnosis and timely initiation of treatment in early childhood to prevent growth retardation and immunodeficiency are critical to improving APH growth and CD4 outcomes by the time they reach adulthood. Keywords: adolescent; CD4; cohort studies; growth; HIV; perinatally acquired Additional information may be found under the Supporting Information tab of this article., 1 | INTRODUCTION In 2019, an estimated 1.7 million adolescents aged 10-19 years were living with HIV worldwide, with 90% of them in sub-Saharan Africa, and 8% in Asia and [...]

Objectives To develop a pragmatic twice daily lamivudine dosing strategy for preterm infants from 24 to 37 completed weeks of gestation. Methods Data were combined from eight pharmacokinetic studies in neonates and infants receiving lamivudine oral solution. A population pharmacokinetic model was developed using non-linear mixed effects regression. Different lamivudine dosing strategies, stratified by gestational age at birth (GA) bands, were simulated in a virtual population of preterm infants, aimed at maintaining lamivudine drug exposures (AUC0-12) within a reference target range of 2.95 to 13.25 µg·h/mL, prior to switching to WHO-weight band doses when ≥4 weeks of age and weighing ≥3 kg. Results A total of 154 infants (59% female) contributed 858 lamivudine plasma concentrations. Median (range) GA at birth was 38 (27–41) weeks. At the time of first pharmacokinetic sampling infants were older with median postnatal age (PNA) of 6.3 (0.52–26.6) weeks. Lamivudine concentrations were described by a one-compartment model, with CL/F and V /F allometrically scaled to weight. Maturation of CL/F was described using an Emax model based on PNA. CL/F was also adjusted on GA to allow extrapolation for extreme prematurity. Simulations predicted an optimal lamivudine dosing for infants GA ≥24 to <30 weeks of 2 mg/kg twice daily from birth until weighing 3 kg; and for GA ≥30 to <37 weeks, 2 mg/kg twice daily for the first 4 weeks of life, followed by 4 mg/kg twice daily until weighing 3 kg. Conclusions Model-based predictions support twice daily pragmatic GA band dosing of lamivudine for preterm infants, but clinical validation is warranted. [ABSTRACT FROM AUTHOR]

: Introduction: Co‐trimoxazole prophylaxis is recommended for children born to women with HIV to protect those who acquire HIV from opportunistic infections, severe bacterial infections and malaria. With scale‐up of maternal antiretroviral therapy, most children remain HIV‐exposed uninfected (HEU) and the benefits of universal co‐trimoxazole are uncertain. We assessed the effect of co‐trimoxazole on mortality and morbidity of children who are HEU. Methods: We performed a systematic review (PROSPERO number: CRD42021215059). We systematically searched MEDLINE, Embase, Cochrane CENTRAL, Global Health, CINAHL Plus, Africa‐Wide Information, SciELO and WHO Global Index Medicus for peer‐reviewed articles from inception to 4th January 2022 without limits. Ongoing randomized controlled trials (RCTs) were identified through registries. We included RCTs reporting mortality or morbidity in children who are HEU receiving co‐trimoxazole versus no prophylaxis/placebo. The risk of bias was assessed using the Cochrane 2.0 tool. Data were summarized using narrative synthesis and findings were stratified by malaria endemicity. Results: We screened 1257 records and included seven reports from four RCTs. Two trials from Botswana and South Africa of 4067 children who are HEU found no difference in mortality or infectious morbidity in children randomized to co‐trimoxazole prophylaxis started at 2–6 weeks of age compared to those randomized to placebo or no treatment, although event rates were low. Sub‐studies found that antimicrobial resistance was higher in infants receiving co‐trimoxazole. Two trials in Uganda investigating prolonged co‐trimoxazole after breastfeeding cessation showed protection against malaria but no other morbidity or mortality differences. All trials had some concerns or a high risk of bias, which limited the certainty of evidence. Discussion: Studies show no clinical benefit of co‐trimoxazole prophylaxis in children who are HEU, except to prevent malaria. Potential harms were identified for co‐trimoxazole prophylaxis leading to antimicrobial resistance. The trials in non‐malarial regions were conducted in populations with low mortality potentially reducing generalizability to other settings. Conclusions: In low‐mortality settings with few HIV transmissions and well‐performing early infant diagnosis and treatment programmes, universal co‐trimoxazole may not be required., INTRODUCTION Vertical transmission of HIV has declined enormously over recent years due to the widespread scale‐up of antiretroviral therapy (ART) among pregnant and breastfeeding women. However, despite this marked progress, [...]

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 well being of pregnant people and their children. Keywords: co-infections; ethics; HIV; pregnancy; prevention; research, 1 | INTRODUCTION Since the early 1990s, the management of pregnancy has been an important focus for HIV research. The urgent need to identify interventions to prevent perinatal transmission led [...]

Introduction: Adolescents and young people comprise a growing proportion of new HIV infections globally yet current approaches do not effectively engage this group, and adolescent HIV-related outcomes are the poorest among all age groups. Providing psychosocial interventions incorporating psychological, social, and/or behavioural approaches offer a potential pathway to improve engagement in care and health and behavioural outcomes among adolescents and young people living with HIV (AYPLHIV). Methods: A systematic search of all peer-reviewed papers published between January 2000 and July 2020 was conducted through four electronic databases (Cochrane Library, PsycINFO, PubMed and Scopus). We included randomized controlled trials evaluating psychosocial interventions aimed at improving engagement in care and health and behavioural outcomes of AYPLHIV aged 10 to 24 years. Results and discussion: Thirty relevant studies were identified. Studies took place in the United States (n = 18, 60%), sub-Saharan Africa (Nigeria, South Africa, Uganda, Zambia, Zimbabwe) and Southeast Asia (Thailand). Outcomes of interest included adherence to antiretroviral therapy (ART), ART knowledge, viral load data, sexual risk behaviours, sexual risk knowledge, retention in care and linkage to care. Overall, psychosocial interventions for AYPLHIV showed important, small-to-moderate effects on adherence to ART (SMD = 0.3907, 95% CI: 0.1059 to 0.6754, 21 studies, n = 2647) and viral load (SMD = -0.2607, 95% CI -04518 to -0.0696, 12 studies, n = 1566). The psychosocial interventions reviewed did not demonstrate significant impacts on retention in care (n = 8), sexual risk behaviours and knowledge (n = 13), viral suppression (n = 4), undetectable viral load (n = 5) or linkage to care (n = 1) among AYPLHIV. No studies measured transition to adult services. Effective interventions employed various approaches, including digital and lay health worker delivery which hold promise for scaling interventions in the context of COVID-19. Conclusions: This review highlights the potential of psychosocial interventions in improving health outcomes in AYPLHIV. However, more research needs to be conducted on interventions that can effectively reduce sexual risk behaviours of AYPL-HIV, as well as those that can strengthen engagement in care. Further investment is needed to ensure that these interventions are cost-effective, sustainable and resilient in the face of resource constraints and global challenges such as the COVID-19 pandemic. Keywords: adolescent HIV; adolescents and young people; psychosocial interventions; adherence to ART; viral load; vira suppression; sexual risk behaviour; engagement in care, 1 | INTRODUCTION Adolescents living with HIV are unlikely to meet the necessary milestones to end the AIDS epidemic by 2030. In 2019, an estimated 1.7 million (1.1 to 2.4 [...]

: Introduction: Globally about 1.7 million children were living with HIV in 2020. Two integrase strand transfer inhibitors, dolutegravir and raltegravir, are increasingly used in children. We conducted a systematic review to assess the effectiveness and safety of dolutegravir and raltegravir in children and adolescents living with HIV, aged 0–19 years. Methods: Sources included MEDLINE, Embase, the Cochrane Library, clinical trial registries, abstracts from key conferences and reference list searching. Observational studies and clinical trials published January 2009–March 2021 were eligible. Outcomes included efficacy/effectiveness (CD4 counts and viral load) and/or safety outcomes (mortality, grade 3/4 adverse events and treatment discontinuation) through 6 months or more post‐treatment initiation. Risk of bias was assessed using previously published tools appropriate for the study design. Narrative syntheses were conducted. Results and discussion: In total, 3626 abstracts and 371 papers were screened. Eleven studies, including 2330 children/adolescents, reported data on dolutegravir: one randomized controlled trial (RCT; low risk of bias), one single‐arm trial (unclear risk of bias) and nine cohort studies (three low risk of bias, two unclear risk and four high risk). Ten studies, including 649 children/adolescents receiving raltegravir, were identified: one RCT (low risk of bias), one single‐arm trial (low risk of bias) and eight cohort studies (four low risk of bias, three unclear risk and one high risk). Viral suppression levels in children/adolescents at 12 months were high (>70%) in most studies assessing dolutegravir (mostly second‐ or subsequent‐line, or mixed treatment lines), and varied from 42% (5/12) to 83% (44/53) at 12 months in studies assessing raltegravir (mostly second‐ or subsequent‐line). Across all studies assessing dolutegravir or raltegravir, grade 3/4 adverse events (clinical and/or laboratory) were reported in 0–50% of subjects, few resulted in discontinuation, few were drug related and no deaths were attributed to either drug. Conclusions: These reassuring findings suggest that dolutegravir and raltegravir are effective and safe as preferred regimens in children and adolescents living with HIV. With the rollout of dolutegravir in paediatric populations already underway, it is critical that data are collected on safety and effectiveness in infants, children and adolescents, including on longer‐term outcomes, such as weight and metabolic changes., INTRODUCTION In 2020, approximately 1.7 million children aged 0–14 years were living with HIV worldwide [1]. The World Health Organization (WHO) recommends that all children and adolescents living with HIV [...]

Introduction: Uptake of early infant HIV diagnosis (EID) varies widely across sub-Saharan African settings. We evaluated the potential clinical impact and cost-effectiveness of universal maternal HIV screening at infant immunization visits, with referra to EID and maternal antiretroviral therapy (ART) initiation. Methods: Using the CEPAC-Pediatric model, we compared two strategies for infants born in 2017 in Cote d'Ivoire (CI), South Africa (SA), and Zimbabwe: (1) existing EID programmes offering six-week nucleic acid testing (NAT) for infants with known HIV exposure (EID), and (2) EID plus universal maternal HIV screening at six-week infant immunization visits, leading to referral for infant NAT and maternal ART initiation (screen-and-test). Model inputs included published Ivoirian/South African/Zimbabwean data: maternal HIV prevalence (4.8/30.8/16.1%), current uptake of EID (40/95/65%) and six-week immunization attendance (99/74/94%). Referral rates for infant NAT and maternal ART initiation after screen-and-test were 80%. Costs included NAT ($24/infant), maternal screening ($10/mother-infant pair), ART ($5 to 31/month) and HIV care ($15 to 190/month). Model outcomes included mother-to-child transmission of HIV (MTCT) among HIV-exposed infants, and life expectancy (LE) and mean lifetime per-person costs for children with HIV (CWH) and all children born in 2017. We calculated incremental cost-effectiveness ratios (ICERs) using discounted (3%/year) lifetime costs and LE for all children. We considered two cost-effectiveness thresholds in each country: (1) the per-capita GDP ($1720/6380/2150) per year-of-life saved (YLS), and (2) the CEPAC-generated ICER of offering 2 versus 1 lifetime ART regimens (e.g. offering second-line ART; $520/500/580/YLS). Results: With EID, projected six-week MTCT was 9.3% (CI), 4.2% (SA) and 5.2% (Zimbabwe). Screen-and-test decreased total MTCT by 0.2% to 0.5%, improved LE by 2.0 to 3.5 years for CWH and 0.03 to 0.07 years for all children, and increased discounted costs by $17 to 22/child (all children). The ICER of screen-and-test compared to EID was $1340/YLS (CI), $650/YLS (SA) and $670/YLS (Zimbabwe), below the per-capita GDP but above the ICER of 2 versus 1 lifetime ART regimens in all countries. Conclusions: Universal maternal HIV screening at immunization visits with referral to EID and maternal ART initiation may reduce MTCT, improve paediatric LE, and be of comparable value to current HIV-related interventions in high maternal HIV prevalence settings like SA and Zimbabwe. Keywords: Early infant diagnosis; HIV; paediatric HIV testing; HIV-exposed infants; immunization; prevention of mother-to-child HIV transmission, 1 | INTRODUCTION In 2019, more than 1.2 million infants were born to women with HIV worldwide and 150,000 acquired HIV [1]. Prompt diagnosis and treatment are critical to the [...]

In 2021, long‐acting cabotegravir (LA CAB) was approved by the United States Food and Drug Administration for an indication of pre‐exposure prophylaxis in women [1]. This is a first in [...]

: Introduction: Historical approaches to clinical development of novel therapeutics for treatment and prevention of HIV have led to unacceptable delays in the generation of data to support optimal antiretroviral drug use in pregnancy. Over the last 5 years, multiple stakeholders have voiced their concerns around the exclusion of pregnant women from drug trials, and some progress has been made to consolidate principles and forge consensus. Building on ongoing efforts, the World Health Organization (WHO) and the International Maternal Paediatric Adolescent AIDS Clinical Trials Network (IMPAACT) convened a technical consultation designed to move the discussion from theory to practice. Discussion: Accelerating the inclusion of pregnant women in pre‐licensure clinical trials, with a goal to have pharmacokinetics (PK) and preliminary safety data for all new HIV agents in pregnancy available at the time of drug approval, requires: (1) performing non‐clinical developmental and reproductive toxicology studies early in drug development for all new HIV agents; (2) recognizing and acting on the central role of women of childbearing potential affected by HIV through the research being conducted and the dissemination of associated results; (3) enrolling pregnant women in studies to specifically determine pregnancy PK and preliminary safety, as soon as late non‐clinical studies are completed with no negative signals, for all new HIV agents that have demonstrated preliminary evidence of safety and efficacy from phase 2 trials; (4) investigating adverse pregnancy and birth outcomes through dedicated pregnancy safety studies for all new priority HIV agents; and (5) expanding active surveillance of drug safety in pregnancy for rare events, such as birth defects. Strategic actions to pursue include developing tools and resources to support designing and implementing studies among pregnant and breastfeeding women, identifying and promoting modifications of the regulatory framework that are supportive of systematic ethical investigation of new drugs in pregnancy, coordinating surveillance efforts, mobilizing key stakeholders and promoting transparency and accountability for all involved. Conclusions: With more than 19 million women living with HIV worldwide, ensuring greater inclusion of pregnant women in research on novel therapeutics is a priority to support drug optimization and effective introduction of innovations for treatment and prevention of HIV., INTRODUCTION Despite tremendous work by the research community in exploring effective strategies to prevent HIV vertical transmission, historical approaches to clinical development of novel therapeutics for treatment and prevention of [...]

Introduction: We assessed mortality and losses to follow-up (LTFU) during adolescence in routine care settings in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. Methods: Cohorts in the Asia-Pacific, the Caribbean, Central, and South America, and sub-Saharan Africa (Central, East, Southern, West) contributed data, and included adolescents living with HIV (ALHIV) enrolled from January 2003 and aged 10 to 19 years (period of adolescence) while under care up to database closure (June 2016). Follow-up started at age 10 years or the first clinic visit, whichever was later. Entering care at Results: Of the 61,242 ALHIV from 270 clinics in 34 countries included in the analysis, 69% (n = 42,138) entered care Conclusions: Both mortality and LTFU were worse among those entering care at [greater than or equal to]15 years. ALHIV should be evaluated apart from younger children and adults to identify population-specific reasons for death and LTFU. Keywords: adolescents; mortality; lost to follow-up; retention; global; HIV, 1 | INTRODUCTION UNAIDS estimates that there were 1.0 million female and 770,000 male adolescents living with HIV in 2017 (aidsinfo.unaids. org). The adolescent age group (10 to 19 years) [...]

Keywords: HIV; children; antiretroviral therapy; paediatric HIV, There is no doubt about the exceptional progress made by the global community to date in preventing vertical transmission of HIV, halving the number of new infections in children and [...]

Introduction: Despite the coordinated efforts by several stakeholders to speed up access to HIV treatment for children, development of optimal paediatric formulations still lags 8 to 10 years behind that of adults, due mainly to lack of market incentives and technical complexities in manufacturing. The small and fragmented paediatric market also hinders launch and uptake of new formulations. Moreover, the problems affecting HIV similarly affect other disease areas where development and introduction of optimal paediatric formulations is even slower. Therefore, accelerating processes for developing and commercializing optimal paediatric drug formulations for HIV and other disease areas is urgently needed. Discussion: The Global Accelerator for Paediatric Formulations (GAP-f) is an innovative collaborative model that will accelerate availability of optimized treatment options for infectious diseases, such as HIV, tuberculosis and viral hepatitis, affecting children in low- and middle-income countries (LMICs). It builds on the HIV experience and existing efforts in paediatric drug development, formalizing collaboration between normative bodies, research networks, regulatory agencies, industry, supply and procurement organizations and funding bodies. Upstream, the GAP-f will coordinate technical support to companies to design and study optimal paediatric formulations, harmonize efforts with regulators and incentivize manufacturers to conduct formulation development. Downstream, the GAP-f will reinforce coordinated procurement and communication with suppliers. The GAP-f will be implemented in a three-stage process: (1) development of a strategic framework and promotion of key regulatory efficiencies; (2) testing of feasibility and results, building on the work of existing platforms such as the Paediatric HIV Treatment Initiative (PHTI) including innovative approaches to incentivize generic development and (3) launch as a fully functioning structure. Conclusions: GAP-f is a key partnership example enhancing North-South and international cooperation on and access to science and technology and capacity building, responding to Sustainable Development Goal (SDG) 17.6 (technology) and 17.9. (capacity-building). By promoting access to the most needed paediatric formulations for HIV and high-burden infectious diseases in low-and middle-income countries, GAP-f will support achievement of SDG 3.2 (infant mortality), 3.3 (end of AIDS and combat other communicable diseases) and 3.8 (access to essential medicines), and be an essential component of meeting the global Start Free, Stay Free, AIDS Free super-fast-track targets. Keywords: paediatric drugs; drug development; drug formulations; regulatory approval; Global Accelerator for Paediatric Formulations; HIV; tuberculosis; viral hepatitis Received 22 May 2017; Accepted 18 December 2017; Published 27 February 2018, 1 | INTRODUCTION Prompt treatment of people living with HIV (PLHIV) with appropriate antiretroviral drugs (ARVs) saves lives and improves health, but the 43% ARV treatment (ART) coverage of children [...]