towards an aids-free world for children: a global push to end

Towards an AIDS-free world for children

A global push to end pediatric AIDS

START FREE, STAY FREE, AIDS-FREE

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The response to AIDS continues to make global health history. As of December 2015, 17.0 million people worldwide were receiving antiretroviral therapy(1) – a more than 50-fold increase since 2000. The unprecedented scaling-up of HIV treatment has driven a 26% decline in AIDS-related deaths from 2010 to 2015(1) and contributed to a 35% decline in new HIV infections from 2000 to 2015.

Yet, even as the world celebrates these victories and embarks on a historic effort to end the AIDS epidemic as a public health threat by 2030, the most vulnerable of all populations – children – risks being left behind. Compared to adults, children are less likely to be diagnosed with HIV in a timely manner, and more likely to die of AIDS-related causes. Unless children are linked to timely diagnostic services and life-saving HIV treatment, half of all infants newly infected with HIV will die before age two, with peak mortality occurring 6-8 weeks after birth.

Today, however, the means now exist to make paediatric AIDS a thing of the past. Indeed, striking gains in preventing children from becoming infected with HIV have brought us to the point where the end of paediatric AIDS is now feasible. To travel the last mile to end paediatric AIDS, we must combine continued success in preventing new infections with a renewed determination to provide lifesaving HIV treatment to children living with HIV.

Our goal today must be nothing short of eliminating paediatric AIDS once and for all. In contrast to the broader goal of ending the AIDS epidemic as a public health threat by 2030, we now have the means to end paediatric AIDS even sooner – by 2020 – if we summon the political courage and resources needed to close the paediatric treatment gap.

In 2016, UNAIDS is joining with diverse partners and stakeholders to launch "Start Free, Stay Free, AIDS-Free", a super Fast-Track framework to end AIDS among children, adolescents and young women by 2020. This report -- and the rejuvenated global push it unveils -- aims to support implementation of this new framework, with particular attention to ensuring that children living with HIV are promptly diagnosed and receive life-saving treatment.

Two key steps are immediately needed to address the HIV treatment needs of children. First, growing political commitment and a proliferating array of important initiatives on paediatric HIV treatment need to be effectively leveraged and coordinated. The global push on paediatric HIV treatment needs to be expanded to incorporate additional key stakeholders, including more philanthropic foundations and private industry. By maximizing the visibility, coordination and coherence of these diverse efforts, partners can best translate our aspirations into concrete results for children living with HIV.

In the quest to end the AIDS epidemic, children must not be left behind

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Second, particular attention is needed to quickening progress in countries where gains thus far have lagged. In 2015, Nigeria, where prevention services have yet to be fully scaled up, alone accounted for more than one in four new HIV infections among children worldwide. Ending paediatric AIDS will be impossible unless prevention and treatment gaps for children are closed in all countries, including those where gains thus far have been disappointing.

The 2016 Political Declaration on Ending AIDS calls for urgent efforts to reach 1.6 million children with

antiretroviral therapy by 2018. This will require a near doubling over the 873 000 children estimated to have obtained HIV treatment in 2015.

This report briefly summarizes both the opportunities and challenges the rejuvenated, expanded global push for children confront in efforts to end paediatric AIDS. Specific barriers and emerging opportunities are highlighted with respect to each stage in the HIV treatment continuum for children.

Super Fast-Track Targets for Children, Adolescents and Young Women

START FREE The framework calls for the number of new HIV infections among children to be reduced to less than 40 000 by 2018 and 20 000 by 2020, and for 95% of pregnant women living with HIV to receive lifelong antiretroviral therapy by 2018.

STAY FREE The Super Fast-Track approach aims to reduce the number of new HIV infections among adolescents and young women to less than 100 000 by 2020, and to reach 25 million additional men with voluntary medical male circumcision services by 2020, with a particular focus on young men ages 15-29.

AIDS-FREE The framework calls for antiretroviral treatment services to reach 1.6 million children (ages 0-14) and 1.2 million adolescents (ages 15-19) by 2018, or 95% coverage for children.

The “Start Free Stay Free AIDS Free" framework calls for urgent action to address the HIV-related needs of young people at all stages of their life:

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As a result of the striking success of efforts to prevent new HIV infections among children, a strong foundation now exists to accelerate progress towards the ultimate goal of ending paediatric AIDS altogether. The number of children newly infected with HIV in 2015 was 150 000 [110 000 - 190 000] – was 56% fewer than in 2009 and 70% fewer than in 2000 (Fig. 2). Numerous high-burden countries – including Burundi, South Africa, Swaziland and Uganda – have seen new HIV infections among children decline by at least 60%. (Figure 1 depicts

the countries with the largest number of children living with HIV).

In 2015, 77 [69 - 86]% of pregnant women living with HIV received antiretroviral medicines.Scaled-up provision of antiretroviral medicines to pregnant women living with HIV has substantially cut the rate of mother-to-child HIV transmission. Already, paediatric AIDS has been virtually eliminated in most high-income countries. In 2015 Cuba became the first developing country to have been certified as having eliminated mother-to-child HIV transmission.

We can end paediatric AIDS

Fig. 1 Children ages 0-14 living with HIV, 2015

Nigeria (15%)

South Africa (13%)

India (8%)

Mozambique (6%)

Kenya (5%)

Uganda (5%)

United Republic of Tanzania (5%)

Zambia (5%)

Malawi (5%)

Zimbabwe (4%)

Remaining countries (29%)

Sources: UNAIDS 2015 estimates.

Fig. 2 Number of new HIV infections in children, global, 2000-2015

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Many low- and middle-income countries, including several with heavy HIV burdens, are also making notable progress towards eliminating new HIV infections among women. In Malawi, which pioneered the Option B+ approach that provides lifelong antiretroviral therapy to all pregnant women living with HIV, regardless of their CD4 count, the overall rate of mother-to-child transmission among women receiving prevention services has fallen to 3.9% (and to 2.8% among those receiving antiretroviral therapy).(5) In South Africa, the percentage of children testing HIV-positive on virologic tests at six months of age fell from 7.7% in 2009 to 1.4% in 2015.

The sustained success of prevention efforts, combined with the fact that older children will continue transitioning out of the paediatric cohort and into adult care, means that the total number of children living with HIV will further decline in future years.

By combining continued emphasis on HIV prevention with scaled-up HIV diagnostic and treatment services, we can effectively end paediatric AIDS. Towards ending AIDS as a public health threat, the world has embraced a new target in the AIDS response. By 2020: (a) 90% of all people living with HIV will know their HIV status; (b) 90% of people with an HIV diagnosis will receive sustained antiretroviral therapy; and

(c) 90% of all people receiving antiretroviral therapy will achieve viral suppression. Achieving 90-90-90, combined with strengthened HIV prevention and non-discrimination efforts, will reduce new HIV infections 90% and AIDS-related deaths by 79% by 2030.

The 90-90-90 target is universal in scope, applying to all settings and all populations affected by the HIV epidemic, including children. Indeed, health ministry officials and other global stakeholders who attended a major global consultation on paediatric HIV treatment in 2014, including health ministry leaders from diverse regions, unanimously endorsed the 90-90-90 target for children living with HIV.

But with such extraordinary progress having been made towards eliminating new HIV infections among children, the world is raising its ambitions even higher when it comes to HIV treatment scale-up for children. By rapidly scaling up to reach 1.6 million children with HIV treatment by 2018 -- by achieving 95% coverage of HIV treatment and prevention of mother-to-child transmission -- modeling indicates that it will be possible to end paediatric AIDS by 2020 -- a full decade before the Fast-Track target for ending the epidemic as a whole. It is around this goal that a rejuvenated, expanded global push must unite.

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Political attention to the paediatric HIV treatment gap is growing, and the global community has now formally committed to intensify action to make paediatric AIDS a thing of the past.

In the 2016 Political Declaration on HIV and AIDS: On the Fast Track to Accelerate the Fight Against HIV and to End the AIDS Epidemic by 2030, countries unanimously committed to reach 1.6 million children with HIV treatment by 2018. In part, renewed political commitment regarding children living with HIV builds on optimism stemming from important developments in the field. New tools have emerged for quicker diagnosis of HIV in children; the spectrum of paediatric antiretroviral medicines has expanded, and new license agreements suggest that this expansion is poised to continue; and important lessons have been learned regarding the best strategies for reaching and treating children living with HIV.

With the goal of leveraging these trends to eliminate paediatric AIDS worldwide, the UNAIDS Programme Coordinating Board encouraged UNAIDS to work with partners to establish a platform to optimize coordination and help drive action on paediatric HIV treatment at country, regional and global levels. Recently, UNAIDS and PEPFAR launched the Start Free Stay Free AIDS Free framework or action on paediatric AIDS as a part of the AIDS free commitment for children and youth. In December 2016, the UNAIDS Programme Coordinating Board will review an updated analysis of the paediatric HIV treatment gap.

Over the last several years, a number of important new initiatives have emerged to close the paediatric HIV treatment gap:

• In 2014, the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) joined with the Children’s Investment Fund Foundation (CIFF) to launch the Accelerating Children’s HIV/AIDS Treatment (ACT) initiative, a two-year effort that aims to double the number of children receiving antiretroviral therapy in nine high-burden countries.

• The Clinton Health Access Initiative (CHAI), the Drugs for Neglected Diseases initiative (DNDi) and the Medicines Patent Pool (MPP) are collaborating with UNITAID to accelerate the development of paediatric antiretroviral formulations, and UNITAID is supporting efforts by the Elizabeth Glaser Pediatric AIDS Foundation (EGPAF) to accelerate uptake of early infant diagnostic testing.

• The World Organization (WHO) is leading global efforts to develop treatment recommendations and to optimize treatment options for children.

• Jointly launched by UNICEF, WHO and EGPAF, the Double Dividend initiative seeks to better align paediatric HIV treatment with maternal, neonatal and child health (MNCH) by encouraging ‘smart’ joint investments that generate synergies and improve child survival.

• The Inter-Agency Task Team (IATT) on the Prevention and Treatment of HIV Infection in Pregnant Women, Mothers and Children has played an important role in harmonizing and improving treatment for children living with HIV.

Commitment to ending paediatric AIDS is increasing

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• In July 2014, UNAIDS Secretariat joined with CHAI, WHO, the African Society of Laboratory Medicine (ASLM), UNICEF and PEPFAR to launch the global Diagnostics Access Initiative, which has prioritized efforts to catalyse the development and uptake of tools to diagnose HIV infection in children.

• The Global Fund to Fight AIDS, Tuberculosis and Malaria has assumed leadership of the Paediatric ARV Procurement Working Group and Procurement Consortium, managing a project initiated by CHAI with UNITAID funding.

These important initiatives now need to be coordinated and fully leveraged to ensure that scaled-up HIV treatment can be combined with prevention efforts to speed progress towards the elimination of paediatric AIDS.

To fully leverage improved global coordination, programmes at the national and sub-national level must be adequately resourced and driven by locally developed targets and strategies and regular reporting of results.

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A push to end paediatric AIDS

To achieve the Super Fast-Track treatment target for children by the end of 2018, partners will need to work even more closely to drive progress. A new, more inclusive and focused push will be needed to ensure that the world reaches 1.6 million children with antiretroviral therapy by 2018.

New momentum to address the treatment needs of children living with HIV was an important outcome of a historic meeting of 11 African ministers, numerous deputy ministers and senior national government officials, and representatives of key international bodies, programme implementers and civil society in May 2016 in Abidjan, Côte d’Ivoire. Organized by the Government of Côte d’Ivoire, UNAIDS, ELMA Philanthropies, Funders Concerned About AIDS, Children’s Investment Fund Foundation (CIFF), Johnson & Johnson and the Grand Duchy

of Luxembourg, the gathering focused on key actions required to end paediatric AIDS, taking into account both challenges and opportunities.

After reviewing extensive evidence regarding both the feasibility of ending paediatric AIDS and the critical importance of HIV treatment towards this goal, the meeting generated broad support for urgent action to close the paediatric treatment gap. Ministers recommended that the international community recognize ending paediatric AIDS as a global obligation, including a commitment in the 2016 Political Declaration from the High Level Meeting on Ending AIDS to fast-track the AIDS response for children.

Ministers and other stakeholders attending the Abidjan meeting placed particular emphasis on immediate action to close paediatric treatment gaps in Africa. “Almost 90 percent of children

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While the combination of scaled-up antiretroviral therapy and further expansion of services to prevent mother-to-child transmission has the potential to end paediatric AIDS as a public health threat, it will not eliminate all child health challenges associated with HIV infection.

Children who are exposed to HIV but do not become infected experience notably poorer health outcomes than HIV-unexposed children. In Botswana, the risk that an HIV-exposed but uninfected child will die before the age of 2 is 2.9 times greater than for HIV-unexposed children(8). Altogether, HIV-exposed children (including both infected and uninfected

children) now account for roughly half of all children in Botswana who die before age 2(9). According to recent studies, exposure to maternal antiretroviral therapy does not confer protection against premature mortality for HIV-exposed but uninfected infants.

Even if paediatric AIDS is technically eliminated, health problems experienced by HIV-exposed but uninfected infants are likely to persist. With 17.8 million women living with HIV in 2015, many children will continue to born exposed to HIV, underscoring the importance of intensified health monitoring of HIV-exposed children and their mothers.

Addressing the needs of HIV-exposed, but uninfected, children

who are living with HIV are living in Africa,” said Mr Michel Sidibé. “It is not acceptable that in 2016 we have 90% of the world’s children living with HIV in Africa when we have come close to eliminating paediatric AIDS outside Africa.”

In formal decision points from the meeting that were forwarded to the President of the United Nations General Assembly in advance of the High Level Meeting on Ending AIDS, ministers attending the Abidjan meeting noted the need for increases in domestic and international resources for paediatric HIV treatment. Ministers also emphasized the need for further innovation in the paediatric HIV treatment field, including through development and roll-out of more child-friendly diagnostic and therapeutic technologies and through expansion of proven service delivery strategies for children.

In Abidjan, ministers stressed the critical importance of a broad partnership to end paediatric AIDS. Ministers called for efforts to engage additional philanthropic, industry and private sector partners and for concerted efforts to strengthen the coordination and coherence of the many initiatives that have emerged to address various aspects of the paediatric HIV treatment agenda.

The momentum and decision points resulting from the Abidjan meeting also support the decision by the UNAIDS Programme Coordinating Board to prioritize coordination, leadership and action on paediatric HIV treatment issues, towards the goal of ending paediatric AIDS. In December 2016, the UNAIDS Secretariat will report back to the Programme Coordinating Board regarding progress in closing the HIV treatment gap for children and in assembling an expanded global push for children living with HIV.

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Life-saving HIV treatment is essential if we hope to end paediatric AIDS. Yet, even as the number of children living with HIV declines as a result of prevention successes, the world has yet to fully leverage antiretroviral therapy to accelerate progress towards ending paediatric AIDS. Data through 2015 indicate that national treatment access gaps for children vary by country (Fig. 3).

Since the expansion of access to antiretroviral therapy began in low- and middle-income countries about 15 years ago, adults living with HIV have historically enjoyed higher treatment coverage than children living with HIV. In recent years, however, that has begun to change. Indeed, in 2015, antiretroviral treatment coverage for children (ages 0 -14) globally was actually higher than among adults (Fig. 4).

To end paediatric AIDS, we must close children's HIV treatment gap

Fig. 3 Gap in ART coverage among children ages 0-14, 2015

Indonesia

Chad

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Angola

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Democratic Republic of the Congo

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Children living with HIV not receiving ART

Children receiving ART

Source: UNAIDS 2016 estimates.

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Fig. 4 Antiretroviral therapy coverage (%) among people living with HIV: adults and children

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Source: UNAIDS 2016 estimates.

Yet, while strides have clearly been made in closing the HIV treatment gap for children, coverage figures alone can be deceiving as a measure of children’s access to treatment. Due to the steady decline in the total population of children living with HIV – resulting from the combination of very high mortality rates among children living with HIV, the reduced number of children newly infected with HIV, and the “aging out” of older children into the adult cohort – paediatric treatment coverage would rise over time even were the number of children receiving antiretroviral therapy to remain unchanged.

In reality, a severe treatment gap persists for children living with HIV, and the consequences are unacceptable. In 2015, while children accounted for

only 5% of all people living with HIV, they made up 10% of all AIDS-related deaths. At the same time that we work to eliminate new HIV infections among children, we must eliminate AIDS-related mortality among children by closing the paediatric treatment gaps.

Going the last mile to eliminate paediatric AIDS will demand increased political commitment and more focused resources and action for HIV testing and treatment programmes for children. The tragic reality is that while the global push to eliminate new HIV infections among children has appropriately attracted global attention and robust political support, the needs of children living with HIV have largely been neglected by the AIDS response.

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The 90-90-90 target and the paediatric fast-track agenda it has inspired represent a paradigm shift in the global response. In the place of earlier treatment targets, which focused exclusively on the number of people receiving antiretroviral therapy, both 90-90-90 and the new super-fast-track agenda for children demand improved outcomes across the treatment cascade. As country-level data reveal (see Fig. 5, which focuses on outcomes among children

living with HIV in Kenya), gaps at each stage of the treatment cascade worsen outcomes for children.

Enhancing the health and well-being of children will demand improved results at each stage of the HIV treatment cascade. Closing gaps at each stage of the paediatric HIV treatment cascade must now become the primary work of the renewed, expanded global push to end paediatric AIDS.

Fig. 5 Plugging the gaps in the cascade requires innovative solutions

Number of children 18 month-14 years old on treatment in Kenya

TOTAL HIV POSITIVE

KNOWN HIV POSITIVE

REMAIN ON ART

REACHING VIRAL

SUPPRESSION

The roadmap: Plugging the gaps in the cascade

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The expanded global push to end paediatric AIDS must work to increase political commitment, strategically focus reosurces and implement smart programming to ensure prompt diagnosis of all children exposed to HIV. Late diagnosis of HIV infection is perhaps the greatest single obstacle to improved health outcomes for children living with HIV. In 2015, only 51% of HIV-exposed children received early infant diagnostic services within the first two months

of life, as recommended by WHO. This coverage for early infant diagnostic services is effectively unchanged from 2014.

The challenge of early infant diagnosis

As children born to mothers living with HIV carry maternal HIV antibodies for up to 18 months, more sophisticated tests that identify the presence of viral DNA or RNA are required to diagnose HIV in very young children. As

The First 90: Ensuring early diagnosis of HIV infection

2012 2013 2014 2015

TARGET

2020

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Source: 2016 Global AIDS Response Reporting.

Fig. 6 Percentage of HIV-exposed children receiving early infant diagnostic testing in first two months

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such testing primarily relies on centralized laboratories, health settings typically use dried blood spots, which are then transferred to laboratories for analysis.

WHO recommends virologic testing at 4-6 weeks or at the earliest opportunity thereafter.Because services for the prevention of mother-to-child transmission do not reach all HIV-exposed children – and also because breastfeeding may also lead to HIV transmission, including in older children – case-finding and serological testing services are also needed for children older than 18 months.Centralized early infant diagnostic services necessarily involve important logistical and financial challenges, requiring the transport of dried specimens to the laboratory and the return of test results to the clinical site. Delays are common, which can be life-threatening for HIV-exposed infants, given the peak in mortality that occurs at 6-8 weeks for children infected in utero. A multi-country study indicates that up to 51% of infants who test positive on these virologic tests never receive their test results(13).

Several service delivery and technological innovations have emerged to reduce delays in diagnosing infants with HIV. Text messaging has successfully been used to speed the return of test results for infants(14). In 2016, the Government of Malawi joined with UNICEF to pilot the use of unmanned aerial drones to deliver specimens to laboratories and cut waiting times for test results(15). In September 2014, Roche, the maker of a leading platform for early infant diagnosis, announced a global programme capping the per-test costs of reagents and consumables, although building capacity for early infant diagnosis still requires up-front costs for the purchase of equipment and the training of personnel(16).

By expanding diagnostic sites and by intensifying programme management and monitoring, some countries are reporting important progress in increasing coverage of early infant diagnosis. In Zimbabwe, for example, the proportion of HIV-exposed infants who receive early infant diagnostic testing rose from 37% in 2012 to 54% in 2015(1).

Likewise, coverage of early infant diagnostic services rose in Mozambique from 32% in 2012 to 47% in 2015.

In the quest to reach the first 90 for children, the emergence of point-of-care diagnostic technologies is especially promising. Two primary platforms – the Alere™ q HIV-1/2 Detect and the GeneXpert® system – have been approved for point-of-care early infant diagnosis, prequalified by WHO and are on the market. Other products are in the pipeline, including some that are inexpensive, battery-operated and able to be used in decentralized service settings.

For many of the point-of-care platforms for early infant diagnosis, associated training requirements are modest. The characteristics of products in the pipeline vary(16). Some provide only qualitative results (i.e., indicating the presence or absence of infection), while others also provide quantitative (i.e., numerical viral load reading) results. Some platforms only diagnose HIV infection, while others are multiplex platforms that are able to diagnose other conditions (e.g., tuberculosis).

Uptake of these point-of-care platforms has been limited to date, although CHAI, EGPAF and UNICEF are working to aid 13 countries in introducing these platforms. Preparatory activities – including training, negotiations and planning – are underway, with the hope of beginning roll-out of point-of-care technologies beginning in September 2016. At the global level, a consortium of organizations is negotiating with the makers of point-of-care tools to optimize public health pricing of these tools.

In addition to service delivery and technological innovations to promote early infant diagnosis, there is growing interest in changing diagnostic policies in order to encourage routine virological testing of infants at birth, which may now be more feasible as a result of declines in the cost of virological assays. WHO has yet to endorse routine birth testing, citing insufficient evidence, but WHO says the approach appears promising(17). In June 2015, South Africa introduced birth testing of all HIV-exposed

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infants, with early results indicating a successful roll-out of this new national policy(18).

WHO emphasizes the continued importance of strengthening and expanding early infant diagnostic testing even in settings where birth testing is routine(17). A recent analysis of South African data suggests that nearly 30% of infants testing positive at birth and initiating antiretroviral therapy might actually be HIV-uninfected in settings where the rate of mother-to-child HIV transmission is low, underscoring the need for confirmatory testing(19). In South Africa, while birth testing has led to a sharp increase in the number of infants tested for HIV, utilization of postpartum early infant diagnostic services in the early phase of the country’s new infant testing approach has been sub-optimal, raising questions as to whether routine birth testing might undermine the traditional system for early infant diagnosis(20).

Reaching older children

Children who are no longer infants are seldom offered HIV testing in many settings. As noted, testing of older children is needed to reach those missed by prevention programmes or exposed

to HIV as a result of breastfeeding. In 32 rural communities in Kenya and Uganda, integration of HIV testing for children in mobile, community-centred, multi-disease health promotion campaign resulted in 81% HIV testing coverage of at-risk children(21).

Under the ACT initiative, PEPFAR has intensified testing and outreach efforts to identify older children with undiagnosed HIV infection1 and numerous other partners, including CHAI, have also expanded outreach to older children. Routinizing provider-initiated HIV testing services in health service delivery for children is a critical priority. Specific efforts have been made to integrate HIV testing into in-patient health delivery settings, although PEPFAR reports that under the ACT initiative to date the yield from such efforts (in terms of the number of HIV-infected children identified) has been lower than anticipated. Outpatient settings are likely to be an excellent venue for identifying undiagnosed children living with HIV, although integrating HIV testing in such settings is challenging due to health workforce shortages and lack of space. PEPFAR is currently working to identify strategies to incorporate testing in outpatient settings.

1 G. Siberry, personal communication, 24 April 2016.

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Timely access to antiretroviral therapy is the difference between life and death for many children. Towards ending paediatric AIDS once and for all, the renewed global push for children living with HIV must intensify efforts to ensure that all children receive timely access to child-appropriate antiretroviral therapy.

Aligning national policy with international guidelines

WHO recommends initiation of antiretroviral therapy in all children with confirmed HIV infection, regardless of CD4 count(22). In revising its 2013 guidance, which called for treatment initiation regardless of CD4 count in children younger than 5, WHO in its 2015 guidance cited evidence that early treatment is associated with improved health and developmental outcomes for children(22).

After release of the 2013 guidelines, most high-burden countries swiftly adopted WHO’s earlier recommendation to initiate HIV treatment in all children living with HIV under the age of 5(22). As of December 2015 – roughly three months after WHO revised its guidance to call for treatment initiation for all children with HIV infection – five high-burden countries had adopted national guidelines aligned with the WHO’s new approach(23). All countries need to ensure that their national guidelines reflect the very best scientific evidence, as summarized in the 2015 WHO guidelines.

Complexities associated with treating HIV in children have declined over time, as evidence

has grown regarding the most effective regimens for different age groups. WHO’s most recent antiretroviral guidelines reflect a notable simplification and streamlining of treatment recommendations for paediatric HIV infection.

Linking children living with HIV to antiretroviral therapy

To end paediatric AIDS by 2020, the number of children receiving antiretroviral therapy will need to rise from 872 500 in 2015 to 1.6 million by 2018, an increase of roughly 83%. This will demand substantially greater success in linking children who are confirmed to be HIV-infected to paediatric treatment services. Currently, only 30% of perinatally infected infants start antiretroviral therapy in a timely manner, primarily due to the above-described deficiencies in diagnosing HIV in infants(13). A study in Botswana found that median time from birth until initiation of HIV treatment was 23 weeks – substantially beyond the period of peak mortality – with an average three-week interval between receipt of test results and treatment initiation; of 79 children in the study who died, 56 died before receiving HIV treatment(24).

Service delivery weaknesses often impede swift, effective linkage to care for children living with HIV. Some health care workers are reluctant to recommend HIV testing or referral to care for children, due in many cases to lack of knowledge regarding the importance of early infant diagnosis and treatment initiation for children or fears that antiretroviral administration for children is especially complex(25).

The Second 90:Ensuring prompt initiation of antiretroviral therapy

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Antiretroviral medicine stockouts occur more frequently for paediatric formulations than for adult medicines(26). Treatment and care services for children living with HIV need to be comprehensive, as HIV-infected children who receive antiretroviral therapy still remain vulnerable to other health problems, such as pneumonia, diarrhea, malaria and measles, as well as malnutrition and failure to thrive.

The need to improve service linkage and treatment uptake among children has given rise to important programmatic innovations. Numerous high-burden countries have taken steps to expand the number of facilities equipped to administer antiretroviral therapy for children. To improve antiretroviral access for children, Kenya has prioritized caregiver education, decentralizating services and strengthening monitoring systems. In a multi-facility programme in Uganda, roll-out of a family-centred model resulted in a 40-fold increase in paediatric HIV treatment uptake over 84 months(27).

As noted, paediatric HIV treatment requires proper dosing of antiretroviral medicines based on the child’s weight. An audit of a public sector paediatric HIV outpatient clinic in Zimbabwe found that 59% of infants were overdosed with at least one antiretroviral medicine, while 46% of children ages 4-10 were either overdosed or underdosed(28). Health worker training and improved methods for weight-based dosing of antiretroviral medicines are needed to ensure administration of the appropriate dose.

Expanding the spectrum of child-appropriate antiretroviral regimens

Due to differences in medicine delivery needs, changing metabolism and difficulties swallowing pills, children require medicine formulations that differ from those prescribed for adults. For children living with HIV, WHO recommends different regimens depending on the child’s age. With respect to infants and young children, WHO recommends formulations based on ritonavir-boosted lopinavir (LPV/r), a protease inhibitor. For children younger than four weeks, the only available formulation is a combination

of nevirapine (NVP), lamivudine (3TC) and zidovudine (AZT)(29).

Administering antiretroviral therapy in young children can be more complicated than for adults (although, as previously noted, these complexities have diminished somewhat over time). Currently, only one paediatric regimen is available as a fixed-dose combination(29). For very young infants, antiretroviral therapy previously relied on a foul-tasting syrup, although the emergence of LPV/r pellets (approved by the U.S. Food and Drug Administration in 2015) represents a potentially important step forward, obviating many transport and storage challenges and enabling caregivers to sprinkle the pellets on soft food(29). Evidence indicates that first-line LPV/r regimens are clearly superior to the NVP-based regimens on which paediatric HIV treatment programmes relied earlier, yielding significantly greater life expectancy and lower lifetime costs(29).

There are several reasons why the spectrum of antiretroviral formulations is more limited for children than for adults. Historically, initial clinical trials of antiretroviral compounds have focused on adults, resulting in considerable delays in the development of paediatric versions of medicines that are approved for adults. Regulatory pathways can also be more complicated for paediatric medicines, and observers have questioned whether the diminishing size of the paediatric HIV treatment market will be sufficient to attract sustained investments in research and development by pharmaceutical companies.

However, while progress still remains too slow, there is some good news on the research front for children living with HIV. As of July 2015, HIV i-Base and the Treatment Action Group reported that 19 paediatric antiretroviral compounds or combinations were in the research pipeline(29). In addition, regulatory agencies have strengthened incentives and penalties to ensure that promising compounds are evaluated in children(29). Currently, paediatric development efforts adopt a staged approach based on age cohorts, evaluating experimental compounds first in adults and

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adolescents and subsequently in younger age groups, eventually reaching children under six months; some have suggested that this process could be accelerated by studying age groups simultaneously(29). The success of the Medicines Patent Pool in obtaining licenses for numerous paediatric antiretroviral compounds – including raltegravir, lopinavir and ritonavir – will increase access to affordable medicines for the treatment of paediatric HIV.

Further simplification of antiretroviral regimens for children is urgently needed. In particular, priority should be given to the development of additional fixed-dose combinations for children in order to reduce pill burden and improve treatment adherence.

As noted, WHO spearheads global efforts to optimize paediatric antiretroviral drugs. At the second Paediatric ARV Drug Optimization (PADO) meeting in December 2014, stakeholders outlined a roadmap for forecasting demand for paediatric antiretroviral drugs, generating the strategic information needed to permit antiretroviral indications for neonates, accelerating approval processes for new drugs, implementing patent-sharing agreements for priority paediatric compounds, and promoting financial innovation to sustain the diminishing paediatric HIV treatment market(30). The PADO 2 meeting also identified key research gaps.

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Viral suppression is the ultimate aim of antiretroviral therapy, and maximizing rates of viral suppression among children living with HIV must be an urgent focus for the global push for ending paediatric AIDS. Sub-optimal adherence to prescribed regimens – through missed doses or discontinuation or interruption of treatment – is the primary cause of HIV-related treatment failure. In the case of children, the ability of caregivers to ensure strong treatment adherence is of paramount importance.

Ensuring robust adherence and viral suppression

PEPFAR reports that the ACT initiative, while sharply increasing HIV testing and treatment uptake among children in the nine focus countries, has encountered very high rates (30-40%) of virologic failure among children receiving paediatric antiretroviral therapy. Among children in Mozambique starting first-line antiretroviral therapy, with a median time on treatment of 8.5 years, 35.9% experienced virologic

failure(31). According to PEPFAR, continued use in many settings of NVP-based regimens contribute to sub-optimal clinical outcomes for children, underscoring the need for national programmes to bring their treatment guidelines into line with WHO recommendations.

Smart service approaches can improve rates of adherence and viral suppression. Use of a nurse-driven, patient-centred, streamlined paediatric treatment model in 16 rural Kenyan and Ugandan clinics yielded a retention rate of 94% at 48 weeks, with 91% of children achieving viral suppression(32). In a separate study in Uganda, a facility-based, family-centred appointment scheduling and health education intervention significantly improved adherence, with researchers citing the health education and peer support elements as key factors (Fig. 7)(33). In Kenya, health facilities are incorporating mothers living with HIV, providing a monthly stipend to support their efforts to increase retention in care and treatment adherence(34).

The Third 90:Achieving viral suppression

1999 2010

Num

ber

of

child

ren

and

ad

ole

scen

ts (

0-1

7)

Source: Luyirika et al., PloS ONE, 2013.

Fig. 7 Treatment access to entire family increases likelihood of children receiving diagnosis and HIV treatment

0

5000

50x RISE IN FAMILY ENROLMENT IN CARE

40x INCREASE IN ENROLMENT IN PAEDIATRIC HIV TREATMENT

UNIVERSAL ACCESS TO PAEDIATRIC COTRIMOXAZOLE PROPHYLAXIS

21


Among children who have initiated antiretroviral therapy during the first year of PEPFAR/CIFF ACT initiative, there is still substantial mortality, especially among children under 52. The primary reason for such high mortality, PEPFAR reports, is that far too many children start HIV treatment too late. A recent study in four Kenyan hospitals found that provision of urgent antiretroviral therapy to hospitalized HIV-infected children did not reduce mortality, further underscoring the need to identify and begin treating children living with HIV before they become sick(35).

Preventing loss to follow-up

Many children who initiate antiretroviral therapy do not remain engaged in care. According to a study involving 17 000 children receiving antiretroviral therapy in four African countries, 51% of children who were enrolled in HIV treatment before their

first birthday were lost to follow-up within 24 months(36). Poorly run clinics may contribute to loss to follow-up, with sub-optimal retention of children living with HIV associated with long wait times, understaffing and loss of early infant diagnostic tests results(27). The lack of standardized, well-developed patient information systems – compounded by the fact that mothers and their infants may commonly be followed through separate register systems, rather than as a mother-baby pair – also contributes to high rates of loss to follow-up among HIV-exposed children.

An important strategy for improving retention in care is to bring services closer to the children who need them through decentralization. Experience in multiple countries indicates that bringing services closer to families cuts rates of loss-to-follow-up by at least half (Fig. 8).

2 G. Siberry, personal communication, 24 April 2016.

Fig. 8 Increased retention in care when service delivery is decentralized Loss to follow-up/100 person years on ART

Source: http://www.emtct-iatt.org/wp-content/uploads/2013/03/Decentralization-of-Pediatric-HIV-Care-and-Treatment-in-Five-SS-African-Countries2.pdf.

9.820.8

OVERALL

18.1

29.4

KENYA

12.9

47.3

LESOTHO

14.423

MOZAMBIQUE

2.5

16.8

TANZANIA

Decentralized primary care facilities

Secondary and tertiary facilities

22

UNAIDS

Ensuring sufficient access to second- and third-line regimens

WHO projects that 6-20% of children needing antiretroviral therapy by 2020 will experience virologic failure(30). As a result, the ready availability of affordable second- and third-line antiretroviral regimens will be essential to long-term sustainability of paediatric HIV treatment programmes. WHO’s guidelines identify preferred second- and third-line regimens, and the WHO-convened PADO process is working to optimize the alternative regimens available to children who fail on first-line therapy.

Even when affordable second- and third-line options are available, clinicians need to be prepared to promptly identify treatment failure and switch patients to an effective alternative regimen. However, WHO reports that the “growing but still very limited experience with

2nd/3rd line paediatric [antiretroviral] provision in resource-limited settings is characterized by delays in switching from failing regimens, drug unavailability and a general lack of national treatment guidelines(30)."

To guide HIV-related clinical decision-making, WHO recommends the use of viral load monitoring. Coverage of viral load testing has until recently been quite limited in most low- and middle-income countries, although negotiations between Roche and partners in the Diagnostics Access Initiative substantially lowered the price of a leading viral load testing platform, making expansion of viral load testing more feasible. A number of high-burden countries have taken steps to scale up viral load testing, although a recent survey of seven sub-Saharan African countries found that most have fallen short of their 2015 scale-up targets(37).

Although surveys indicate that stigmatizing attitudes regarding HIV are on the decline, stigma remains stubbornly persistent in many settings, undermining efforts to address the HIV-related needs of children and other populations(38). In one study of children living with HIV who were lost to follow-up, 30% of caregivers cited fear of disapproval among families or communities as the reason their children were no longer engaged in care(39). Mothers living with HIV may be especially hesitant to enroll their children in HIV

treatment programmes if they have previously experienced stigmatizing attitudes in health care settings(40).

The persistence of harmful stigma highlights the need for additional investments in anti-stigma programming. In addition, as surveys have found that HIV-related stigma declines as treatment coverage increases(38), among the most potent anti-stigma measures may be further investments in scaling up HIV testing and treatment programmes.

Stigma and paediatric HIV treatment

23


From a global standpoint, the philanthropic contribution to the AIDS response may appear rather modest, accounting for only 2% of total resources for HIV-related programmes and activities in low- and middle-income countries(41). However, the influence of private foundations often easily outstrips their nominal share of funding as a result of the ability of the philanthropic sector to strategically

focus its support on priority issues. This is especially evident with respect to paediatric HIV treatment; ELMA Philanthropies supported paediatric HIV treatment programmes long before most other funders focused on this area of work, and the alliance of CIFF and PEPFAR is driving transformative progress on paediatric HIV treatment in high-burden African countries through the ACT initiative.

Philanthropy: A key partner in the global effort to end paediatric AIDS

24

UNAIDS

Although the challenge is considerable, the opportunity to end paediatric AIDS is real. The stars are aligned to make paediatric AIDS a thing of the past, but to seize this historic moment of opportunity, we must act, using the tools and resources available to us to meet the needs of the most vulnerable of all groups affected by HIV. Diverse stakeholders must now unite to reach the global target of providing antiretroviral therapy to 1.6 million children by December 2018.

Ending paediatric AIDS must become a clear global and regional political priority. National leaders have a pivotal role to play, building political support to prevent new infections and address the needs of children living with HIV, aligning national approaches with international normative guidance, focusing increased domestic resources on paediatric testing and treatment programmes, and ensuring preparedness to scale up new technologies and innovative practices.

Moving forward: Seizing the opportunity to end paediatric AIDS

INCREASE AWARENESS OF PAEDIATRIC AIDS IN HEALTH CARE

SETTINGS

FAMILY CENTRED

CARE

CHILD HEALTH SERVICE

CLOSER TO HOME

SECURE SUPPLY CHAIN MANAGEMENT

PROVINDER-INITIATED TESTING

FOR CHILDREN

MAKE FORMULATIONS CHILD FRIENDLY

IMPROVED INFANT

DIAGNOSIS

PRIMARY PREVENTION OF NEW HIV INFECTIONS

AMONG CHILDREN

REDUCE STIGMA AND

DISCRIMINATION

Fig. 9 Innovations to close the gap in access to treatment

25


The international community must also remain engaged, continuing and increasing financial assistance for paediatric treatment programmes and helping build strong national capacity to drive gains for children living with HIV.

Innovation must be the hallmark of our efforts to end paediatric AIDS. Across the treatment cascade, creative approaches are needed to close gaps and improve outcomes for children (Fig. 9). All partners

in the response – national governments, donors, the United Nations system, programme implementers, communities and civil society, and the private sector – must join together to leverage innovation to drive progress towards eliminating paediatric AIDS.The opportunity to end paediatric AIDS is real, and the time to act is now. Only by urgently using the tools and knowledge at our disposal can we end paediatric AIDS once and for all and protect the health and well being of future generations.

26

UNAIDS

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