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The long‐term impact on bone health of lifelong HIV infection and prolonged ART in growing and developing children is not yet known. Measures of bone health in youth must be interpreted in the context of expected developmental and physiologic changes in bone mass, size, density and strength that occur from fetal through adult life. Low bone mineral density (BMD) appears to be common in perinatally HIV‐infected youth, especially outside of high‐income settings, but data are limited and interpretation complicated by the need for better pediatric norms. The potential negative effects of tenofovir on BMD and bone mass accrual are of particular concern as this drug may be used more widely in younger children. Emphasizing good nutrition, calcium and vitamin D sufficiency, weight‐bearing exercise and avoidance of alcohol and smoking are effective and available approaches to maintain and improve bone health in all settings. More data are needed to inform therapies and monitoring for HIV‐infected youth with proven bone fragility. While very limited data suggest lack of marked increase in fracture risk for youth with perinatal HIV infection, the looming concern for these children is that they may fail to attain their expected peak bone mass in early adulthood which could increase their risk for fractures and osteoporosis later in adulthood.

The Guidelines for the Prevention and Treatment of Opportunistic Infections (OIs) in HIV-Exposed and HIV-Infected Children in the United States were developed by a panel of specialists in pediatric HIV infection and infectious diseases from the U.S. government and academic institutions, intended for use by clinicians and health care workers providing medical care for HIV-exposed and HIV-infected children in the United States. For each OI, pediatric specialists with subject matter expertise reviewed the literature for new information since the last guidelines were published (2009) and then proposed revised recommendations that were reviewed and approved by the full Panel and endorsing governmental agencies and professional organizations. This executive summary highlights the most important, rated recommendations for each OI from the full Guidelines document.

AbstractIntroductionIncreasing access to multi‐month dispensing (MMD) of antiretroviral therapy (ART) supports treatment continuity and viral load suppression for people living with HIV (PLHIV) and reduces burden on health facilities. During the COVID‐19 response, PEPFAR worked with ministries of health to scale up MMD and expand eligibility to new groups of PLHIV, including children and pregnant/breastfeeding women. We analysed PEPFAR program data to understand the impact of the policy changes on actual practice.MethodsWe conducted a desk review in 21 PEPFAR‐supported countries to identify and collect official documentation released between March and June 2020 addressing changes to MMD guidance during the COVID‐19 response. MMD coverage, the proportion of all ART clients on MMD, was assessed in the calendar quarters preceding the COVID‐19 response (Q4 2019, October–December 2019; and Q1, January–March 2020) and the quarters following the start of the response (Q2 2020, April–June 2020; Q3 2020, July–September, 2020; Q4 2020, October–December 2020). We used the two‐proportion Z‐test to test for differences in MMD coverage pre‐COVID‐19 (Q4 2019) and during implementation of COVID‐19 policy adaptations (Q2 2020).Results and discussionAs of June 2020, 16 of the 21 PEPFAR‐supported countries analysed adapted MMD policy or promoted intensified scale‐up of MMD in response to COVID‐19. MMD coverage for all clients on ART grew from 49% in Q4 2019 pre‐COVID‐19 to 72% in Q2 2020 during COVID‐19; among paediatric clients (< 15), MMD coverage increased from 27% to 51% in the same period. Adaptations to MMD policy were associated with a significantly accelerated growth in the proportion of clients on MMD (p < 0.001) for all populations, irrespective of age and dispensing interval.ConclusionsAccess to MMD markedly expanded during the COVID‐19 pandemic, supporting treatment continuity while mitigating exposure to COVID‐19 at health facilities. This model is beneficial in public health emergencies and during disruptions to the healthcare system. Outside emergency contexts, expanded MMD eligibility extends client‐centred care to previously excluded populations. The success in expanding MMD access during COVID‐19 should motivate countries to recommend broader MMD access as a new standard of care.

IntroductionDespite significant gains in access to early infant diagnosis (EID) over the past decade, most HIV‐exposed infants still do not get tested for HIV in the first two months of life. For those who are tested, the long turnaround time between when the sample is drawn and when the results are returned leads to a high rate of loss to follow‐up, which in turn means that few infected infants start antiretroviral treatment. Consequently, there continues to be high mortality from perinatally acquired HIV, and the ambitious goals of 90% of infected children identified, 90% of identified children treated and 90% of treated children with sustained virologic suppression by 2020 seem far beyond our reach. The objective of this commentary is to review recent advances in the field of HIV diagnosis in infants and describe how these advances may overcome long‐standing barriers to access to testing and treatment.DiscussionSeveral innovative approaches to EID have recently been described. These include point‐of‐care testing, use of SMS printers to connect the central laboratory and the health facility through a mobile phone network, expanding paediatric testing to other entry points where children access the health system and testing HIV‐exposed infants at birth as a rapid way to identify in utero infection. Each of these interventions is discussed here, together with the opportunities and challenges associated with scale‐up. Point‐of‐care testing has the potential to provide immediate results but is less cost‐effective in settings where test volumes are low. Virological testing at birth has been piloted in some countries to identify those infants who need urgent treatment, but a negative test at birth does not obviate the need for additional testing at six weeks. Routine testing of infants in child health settings is a useful strategy to identify exposed and infected children whose mothers were not enrolled in programmes for the prevention of mother‐to‐child transmission. Facility‐based SMS printers speed up the return of laboratory results and may be of value for other testing services apart from HIV infant diagnosis.ConclusionsNew tools and strategies for HIV infant diagnosis could have a significant positive impact on the identification and retention of HIV‐infected infants. In order to be most effective, national programmes should carefully consider which ideas to implement and how best to integrate novel strategies into existing systems. There is no single solution that will work everywhere. Rather, a number of approaches need to be considered and should be linked in order to achieve the greatest impact on the continuum of care from testing to treatment.

AbstractIntroductionThe COVID‐19 pandemic reached the African continent in less than three months from when the first cases were reported from mainland China. As COVID‐19 preparedness and response plans were rapidly instituted across sub‐Saharan Africa, many governments and donor organizations braced themselves for the unknown impact the COVID‐19 pandemic would have in under‐resourced settings with high burdens of PLHIV. The potential negative impact of COVID‐19 in these countries is uncertain, but is estimated to contribute both directly and indirectly to the morbidity and mortality of PLHIV, requiring countries to leverage existing HIV care systems to propel COVID‐19 responses, while safeguarding PLHIV and HIV programme gains. In anticipation of COVID‐19‐related disruptions, PEPFAR promptly established guidance to rapidly adapt HIV programmes to maintain essential HIV services while protecting recipients of care and staff from COVID‐19. This commentary reviews PEPFAR's COVID‐19 technical guidance and provides country‐specific examples of programme adaptions in sub‐Saharan Africa.DiscussionThe COVID‐19 pandemic may pose significant risks to the continuity of HIV services, especially in countries with high HIV prevalence and weak and over‐burdened health systems. Although there is currently limited understanding of how COVID‐19 affects PLHIV, it is imperative that public health systems and academic centres monitor the impact of COVID‐19 on PLHIV. The general principles of the HIV programme adaptation guidance from PEPFAR prioritize protecting the gains in the HIV response while minimizing in‐person home and facility visits and other direct contact when COVID‐19 control measures are in effect. PEPFAR‐supported clinical, laboratory, supply chain, community and data reporting systems can play an important role in mitigating the impact of COVID‐19 in sub‐Saharan Africa.ConclusionsAs community transmission of COVID‐19 continues and the number of country cases rise, fragile health systems may be strained. Utilizing the adaptive, data‐driven programme approaches in facilities and communities established and supported by PEPFAR provides the opportunity to strengthen the COVID‐19 response while protecting the immense gains spanning HIV prevention, testing and treatment reached thus far.

AbstractIntroductionDespite 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.DiscussionThe 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.ConclusionsGAP‐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.

AbstractIntroductionThe COVID‐19 pandemic has impacted global health service delivery, including provision of HIV services. Countries with high HIV burden are balancing the need to minimize interactions with health facilities to reduce the risk of COVID‐19 transmission, while delivering uninterrupted essential HIV prevention, testing and treatment services. Many of these adaptations in resource‐constrained settings have not adequately accounted for the needs of pregnant and breastfeeding women, infants, children and adolescents. We propose whole‐family, tailored programme adaptations along the HIV clinical continuum to protect the programmatic gains made in services.DiscussionEssential HIV case‐finding services for pregnant and breastfeeding women and children should be maintained and include maternal testing, diagnostic testing for infants exposed to HIV, index testing for children whose biological parents or siblings are living with HIV, as well as for children/adolescents presenting with symptoms concerning for HIV and comorbidities. HIV self‐testing for children two years of age and older should be supported with caregiver and provider education. Adaptations include bundling services in the same visit and providing testing outside of facilities to the extent possible to reduce exposure risk to COVID‐19. Virtual platforms can be used to identify vulnerable children at risk of HIV infection, abuse, harm or violence, and link them to necessary clinical and psychosocial support services. HIV treatment service adaptations for families should focus on family based differentiated service delivery models, including community‐based ART initiation and multi‐month ART dispensing. Viral load monitoring should not be a barrier to transitioning children and adolescents experiencing treatment failure to more effective ART regimens, and viral load monitoring for pregnant and breastfeeding women and children should be prioritized and bundled with other essential services.ConclusionsProtecting pregnant and breastfeeding women, infants, children and adolescents from acquiring SARS‐CoV‐2 while sustaining essential HIV services is an immense global health challenge. Tailored, family friendly programme adaptations for case‐finding, ART delivery and viral load monitoring for these populations have the potential to limit SARS‐CoV‐2 transmission while ensuring the continuity of life‐saving HIV case identification and treatment efforts.

AbstractIntroductionWomen who are pregnant or who could become pregnant experience delayed access to or underinformed use of important new antiretroviral (ARV) drugs because of traditional drug development processes that ostensibly aim to reduce potential harm but effectively fail to ensure that timely information about safe and effective use in pregnancy is available.DiscussionThe World Health Organization and International Maternal, Pediatric, Adolescent Antiretroviral Clinical Trials Network convened a year‐long workshop on "Approaches to Enhance and Accelerate Study of New Drugs for HIV and Associated Infections in Pregnant Women." Workshop participants were tasked with defining key principles and optimal approaches to including pregnant women in pre‐ and post‐licensure trials in order to accelerate the availability of pharmacokinetic and safety data for new ARV agents in pregnancy. ARV efficacy in pregnancy and ARV efficacy for prevention of vertical transmission can be extrapolated from proof of efficacy in non‐pregnant adults, provided that drug levels in pregnancy are similar. However, short‐term safety and pharmacokinetics must be studied directly in pregnant women and should be conducted and included in initial licensure for all new ARVs. Accelerating the timeline for completion of pre‐clinical studies is essential for pregnancy short‐term safety and pharmacokinetic studies to be safely completed by the time a drug is licensed. Composite key pregnancy, birth and neonatal outcomes are critical for drugs expected to have broad use, and studies should be initiated at or soon after drug licensure. Teratogenicity risk cannot be feasibly assessed before drug licensure and will depend on robust post‐marketing surveillance systems. With some modifications, these principles will apply to ARVs used for prevention, two‐drug regimens, long‐acting ARVs and ARVs administered through novel delivery systems.ConclusionsImplementation of the proposed principles and framework will enhance and accelerate the study of new ARVs in pregnancy, resulting in more timely, equitable and informed access to new ARVs for pregnant women.

AbstractIntroductionMaternal 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.

AbstractIntroductionThe World Health Organization's (WHO) recommendation of "Treat All" has accelerated the call for differentiated antiretroviral therapy (ART) delivery, a method of care that efficiently uses limited resources to increase access to HIV treatment. WHO has further recommended that stable individuals on ART receive refills every 3 to 6 months and attend clinical visits every 3 to 6 months. However, there is not yet consensus on how to ensure that the quality of services is maintained as countries strive to meet these standards. This commentary responds to this gap by defining a pragmatic approach to the monitoring and evaluation (M&E) of the scale up of differentiated ART delivery for global and national stakeholders.DiscussionProgramme managers need to demonstrate that the scale up of differentiated ART delivery is achieving the desired effectiveness and efficiency outcomes to justify continued support by national and global stakeholders. To achieve this goal, the two existing global WHO HIV treatment indicators of ART retention and viral suppression should be augmented with two broad aggregate measures. The addition of indicators measuring the frequency of (1) clinical and (2) refill visits by PLHIV per year will allow evaluation of the pace of scale up while monitoring its overall effect on the quality and efficiency of services. The combination of these four routinely collected aggregate indicators will also facilitate the comparison of outcomes among facilities, regions or countries implementing different models of ART delivery. Enhanced monitoring or additional assessments will be required to answer other critical questions on the process of implementation, acceptability, effectiveness and efficiency.ConclusionsThese proposed outcomes are useful markers for the effectiveness and efficiency of the health system's attempts to deliver quality treatment to those who need it—and still reserve as much of the available resource pool as possible for other key elements of the HIV response.