Context

Progress in scale-up and optimization of antiretroviral therapy is key to ending AIDS as a public health threat by 2030 as agreed by the international community. However, despite the dramatic increase in antiretroviral therapy coverage in the last decades, mortality remains unacceptably high amongst adults and children living with HIV. Currently, more than 600,000 AIDS-related deaths still occur per year [1], the majority in low-and middle-income countries (LMICs). If current trends continue, 460,000 people will die of AIDS-related causes in 2025.

Children, who represent only five percent of people living with HIV, are disproportionately affected as they contribute significantly to this death toll. An estimated 110,000 children and adolescents still die from AIDS-related causes annually [1], accounting for fifteen percent of AIDS-related deaths.

Severe loss of immune competence, or AHD, in the absence of effective HIV treatment among adults and children living with HIV puts them at risk of opportunistic infections and remains a persistent challenge for both newly initiating and antiretroviral therapy-experienced patients re-entering care. Thirty percent of people living with HIV still present to care with severe immunosuppression [2].

In an era where rapid screening and diagnostics tools, HIV treatment and effective therapies for preventing and treating coinfections associated with advanced HIV are available, the current rates of AIDS-related deaths are unacceptable. Forty percent of these deaths could be averted by addressing the main drivers of death for those with AHD [3]. Among HIV-opportunistic infections, tuberculosis (TB), cryptococcal meningitis (CM), severe bacterial infections (SBI), and disseminated histoplasmosis (DH) contribute to a substantial proportion of AIDS-related deaths. For children living with HIV, the major causes of morbidity and mortality are pneumonia, TB, bloodstream infections, diarrheal disease, and severe acute malnutrition [4].

Prior Unitaid investments [5] have enabled the generation of evidence on the feasibility of implementation of the AHD care package in adults through hub-and-spoke delivery models in selected countries in sub-Saharan Africa, increasing uptake and significantly improving access to some of the most impactful tools in WHO-recommended AHD package of care (medicines and diagnostics) in Africa and elsewhere. Since 2019, Unitaid has sought to renew the global focus on AHD and accelerate access to lifesaving diagnostics and medicines, with the aim of reducing morbidity and mortality among people with AHD and improving cost efficiencies for health systems to foster sustainable national AHD programs. In alignment with the WHO guidance [6], Unitaid investments have focused on optimizing the package of care including emerging key products for AHD-related infections, across screening (CD4 Advanced Disease lateral flow assay and CD4 count point-of-care, TB urine-Lipoarabinomannan (LAM), CrAg (Cryptoccoccal Antigen) lateral flow assay), prophylaxis (optimized TB preventive treatment), and treatment (fluconazole, Liposomal Amphotericin B and 5-Flucytosine). This initiative, has increased global and national awareness of these products, facilitating their adoption into the AHD package in national guidelines in focus- project countries (Botswana, India, Lesotho, Malawi, Nigeria, South Africa, Tanzania, Uganda, and Zimbabwe) and elsewhere through the expanded partner network. Further implementation and scale-up in countries in need is supported by country governments and donors including Global Fund [7] and PEPFAR [8].

However, significant challenges and opportunities remain for the delivery of simplified, decentralized care for the most vulnerable populations. Diagnosis and treatment of opportunistic infections can be challenging, especially in the rural areas, as the relevant tools are still unavailable for those facing the highest burden of these diseases.

• For SBIs (Severe Bacterial Infections), approaches and tools for enhanced prophylaxis and treatment are not standardized [9], in addition to complex diagnosis pathways. For fungal infections, simplification and decentralization of care are required to enable expanded use of emerging tools. Other developments in the diagnosis, prevention, and treatment of infections, including CM, have the potential to significantly reduce the death toll if they were brought to scale. Examples of tools that could be entering the market soon include the semi-quantitative cryptococcal antigen (CrAg) test and the Histoplasmosis lateral flow assay (LFA), which could allow for rapid and accurate detection of deadly opportunistic infections at lower levels of care, to be used in conjunction with improved treatments and prevention approaches with existing medicines that have become more affordable and accessible.
• Implementation of an optimal care package for children living with AHD is challenged by gaps in health worker knowledge and practice of opportunistic infection screening, diagnosis, prevention, and treatment. In addition, several optimal care package tools exist but are under-used due to these capacity gaps, as well as the absence of guidelines, standard operating procedures, and comprehensive monitoring and evaluation systems. The recent WHO STOP AIDS toolkit [4] provides guidance for a comprehensive package of care for children, that could be very impactful to accomplish the goal of zero AIDS-related deaths by 2030. However, there is very limited access to optimal tools, and limited real-life data regarding optimal strategies for effective prevention, rapid diagnosis, and successful treatment of HIV-associated infections in this population.

Accelerated adoption and preparing for further scale-up of simplified packages of care to reduce morbidity and mortality from AHD in decentralized settings represents a near-term opportunity that would support efforts to progress toward HIV-related mortality global targets for children, adolescents, and adults in high-burden countries. 

By using innovative service delivery models that include optimal tools suitable for the most vulnerable populations, Unitaid will contribute to the global goal of zero pediatric AIDS-related deaths by 2030, and the target to reduce the number of people dying from HIV-related causes to less than 240 000 by 2030, and, in general, ending AIDS as a public health threat by 2030.

Call scope

Building on prior Unitaid-supported work to introduce accessible optimal tools for screening and diagnosis, prevention, and treatment of AHD in LMICs, and to further improve global efficiencies as national programs, with support from scale-up donors, engage in scaling up AHD management, Unitaid seeks to further support the simplification of the AHD management, including for children.

Specifically, the objective of this call for proposals is to identify interventions that can support the expanded use of optimized AHD packages of care (catalyzing their introduction into simplified packages of care) and provide robust operational evidence on innovative delivery models to manage AHD for people living with HIV, and with particular attention to children living with HIV, enabling further simplification and decentralization of AHD management.

Under this call, Unitaid is soliciting proposals that can support the objective of reducing mortality by:

• Supporting innovative approaches to improve implementation and enable increased utilization of the STOP-AIDS toolkit to prevent, diagnose, and treat AHD-associated opportunistic infections in pediatric populations through:
  • supporting introduction of the toolkit in selected early-adopter countries to enable and accelerate expanded access conditions to life-saving tools,
  • and generating operational evidence on the implementation of the toolkit, to optimize and demonstrate the effective use of existing under-used and new tools in real-life high-burden settings.

• Supporting introduction of emerging tools that could complement the current care package recommended by WHO for adults and adolescents living with HIV to enable further simplification in selected early-adopter countries and early management of main drivers of death that remain unaddressed (DH, SBIs) and/or that can be further optimized with recent products entering the market (CM).

Newly recommended tools will need to be adopted as part of an integrated package of care. Proposals should therefore clearly indicate how the proposed activities will integrate with existing programs and planned efforts to support a holistic approach to AHD care. While comprehensive packages of AHD care should include TB-related tools, complementary efforts supporting optimizing TB diagnosis, prevention and treatment are ongoing and are not the focus of this call for proposals.

Implementation pilots that can demonstrate the impact, cost-effectiveness, and operational feasibility of delivery as a means of supporting onwards scale-up are encouraged.  To maximize impact, implementation models should include delivery at the lowest-level health facilities and should be transferrable to other high-burden settings to enable scale-up potential in non-project countries.

Implementation in countries will be catalytic in nature and time-bound, and transition to scale-up funding should be secured. Applicants are encouraged to consider settings where there is a high prevalence of AHD among people living with HIV, and for which the enabling environment and the programmatic support exist. We are soliciting multi-country project proposals, and project countries may include countries where prior Unitaid Advanced HIV Disease projects were implemented if adequately justified.

Areas out of scope for this call include proposals:

a) focusing on the development of products still in the pipeline or large clinical trials,

b) aiming to deliver services without a focus on optimizing and supporting expanded access to under-used and/or new commodities referred to above for the diagnosis, prevention, and treatment of opportunistic infections,

c) aiming for full-scale implementation and/or delivery of products.

Proposals submitted should clearly demonstrate the fit with the objective(s) set out above, the expected impact and value for money as well as the complementarity and added value to similar projects in this area.

Engagement with affected communities is a critical determinant for project/program success. All proposals are required to clearly indicate the role of affected communities and planned collaborations with other relevant groups including grassroots community organizations and Civil Society Organizations. Meaningful engagement with these important groups should be included at all stages of proposed activities, for example, integration of both community and civil society engagement into project design, development, and implementation.

Impact we are seeking

Through this Call for Proposals, Unitaid aims to increase equitable access to optimal products for AHD management in adults and children in the following ways:

• Further demonstrating decentralized delivery models for AHD care to prevent loss to follow-up along the care cascade.
• Generating real-world evidence regarding optimal strategies and delivery models for rapid diagnosis, prevention, and treatment of HIV-associated infections in children.
• Facilitating adoption and implementation of WHO Advanced HIV Disease guidance (including recent cryptococcal meningitis [10] and histoplasmosis guidelines [11] and STOP AIDS toolkit [4] and expanding access to and use of optimized components of such packages of care, to enable further scale up.

The objectives outlined above to catalyze access to an optimal package for AHD care will lead to (i) an increase in the number of adults and children screened, diagnosed, and treated for HIV-associated infections and (ii) a reduction in HIV-related morbidity and mortality by reducing the number of undetected AHD cases, increasing the speed of treatment initiation, and reducing loss to follow-up. The goal is to significantly contribute to progress against the global goal of zero AIDS-related deaths by 2030.

References

[1] Global HIV &AIDS Statistics 2022.

[2] Alexandra Calmy, Nathan Ford, Graeme Meintjes, The Persistent Challenge of Advanced HIV Disease and AIDS in the Era of Antiretroviral Therapy, Clinical Infectious Diseases, Volume 66, Issue suppl_2, 1 April 2018, Pages S103–SS105, Link

[3] Unitaid, Stopping preventable deaths among people with advanced HIV disease. Accessed June 13, 2022. Link

[4] WHO, Package of care for children and adolescents with advanced HIV disease: Stop AIDS, Technical briefing, July 2020.

[5] Clinton Health Access Initiative/Unitaid. The Road to Zero. Report on the Implementation of the Advanced HIV Disease Package of Care in Low- and Middle-Income Countries, 2022.

[6] The Global Fund to Fight HIV, TB and Malaria 2022. HIV Information Note for allocation period 2023-2025.

[7] PEPFAR 2022 Country Operational Plan Guidance.

[8] WHO, Guidelines for managing advanced HIV disease and rapid initiation of antiretroviral therapy, July 2017

[9] WHO, Report from the scoping consultation on severe bacterial infections among people with advanced HIV disease, November 2021.

[10] WHO, Guidelines for diagnosing, preventing, and managing cryptococcal disease among adults, adolescents and children living with HIV. June 2022.

[11] WHO, Guidelines for diagnosing and managing disseminated histoplasmosis among people living with HIV, April 2020.

Process for proposal submission

When developing a proposal, please note the following resources:

• For answers to frequently asked questions relevant to proposal development (this document is regularly updated), please click here [PDF: 400 KB];

• Further background reading about Unitaid’s preliminary rationale and prior work in this area:
  • Clinton Health Access Initiative (with support from Unitaid). The Road to Zero. Report on the Implementation of the Advanced HIV Disease Package of Care in Low- and Middle-Income Countries. 2022.
  • Clinton Health Access Initiative (with support from Unitaid). HIV Market Report: The state of the HIV market in low- and middle-income countries. 2021.

• Global Advanced HIV Disease Toolkit available here, developed through strong collaboration of partners (WHO, Centers for Disease Control & Prevention, St George’s University of London, USAID, Médecins Sans Frontières, Elizabeth Glaser Pediatric AIDS Foundation, International AIDS Society, National Institute for Communicable Diseases South Africa, National Institute for Medical Research Tanzania, Joint United Nations Program on HIV/AIDS, Infectious Disease Institute Uganda, PEPFAR, The Global Fund, Bill & Melinda Gates Foundation, Global Health Impact Group, Coalition Plus, Medical Mycology Society of Nigeria and Lighthouse Malawi)  under the AHD Implementation Steering Committee (ISC) of the Unitaid/ Clinton Health Access Initiative AHD Initiative.

Applicants should be clear about the underlying assumptions made in their proposed approach and should highlight any major risks or other factors that may affect the delivery of results. Finally, proposals are expected to outline a lean, concrete, and clear pathway to results and impact.

After assessment of the proposals and endorsement by the Unitaid Board, all applicants will be officially notified as to whether they will be invited to develop a full grant agreement for Unitaid funding.

Important dates

Submission and format of proposals

Proposals, including all annexes, should be submitted electronically to proposalsUnitaid@who.int. A full proposal consists of the following documents:

• Proposal form with scanned version of signed Front page template, [DOC: 570 KB]
• Annex 1: Log frame and GANTT chart template, [XLS: 278 KB]
• Annex 2: Budget details template, [XLS: 24 KB]
• Annex 3: Organizational details and CVs of key team members [no template]
• Annex 4: Country engagement support Letters [no template]
• Annex 5: Declaration of relevant interest template, [DOC: 21 KB]
• Annex 6: Applicable ethics, anti-discrimination and environmental policies template, [DOC: 21 KB]
• Annex 7: Declaration regarding tobacco entities template, [DOC: 24 KB]
• Annex 8: Anti-Terrorism Declaration template, [DOC: 30 KB]
• Annex 9: Audited financial statements for the past 3 years [no template]
• Guidance on Impact Assessment [PDF: 160 KB]
• Financial Guidelines for Unitaid Grantees [PDF: 1,2 MB]
• Unitaid Results Framework [PDF: 1.3 MB]
• Unitaid Scalability Framework [PDF: 466 KB]

If you have any questions about the application processes throughout any stage of the application review process, please send your queries to the Grant Application Manager:  proposalsUnitaid@who.int

You will find further guidance in the Unitaid proposal process document [PDF: 530 KB].

Webinar on this Call for Proposals: