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Roselyne Sachiti Features, Health & Society Editor
Sickle cell disease (SCD) and HIV are major burdens on health in low-resource communities around the world. In most Third World countries, especially in sub-Saharan Africa, HIV/AIDS has had a negative impact on human development.

Stories and facts on how it has shredded health and demographic indicators that include life expectancy at birth, health care assistance, age and sex distribution, economic indicators like income, workforce, and economic growth, education and knowledge, among others, are there for all to see.

Approximately 95 percent of the 38 million people living with HIV globally are in the developing world, with 67 percent in sub-Saharan Africa, half of whom are living untreated.

Sickle cell disease — a group of disorders that affects haemoglobin, the molecule in red blood cells that delivers oxygen to cells throughout the body — is also wreaking a havoc of its own.

The sad reality is that 15 million babies will be born with SCD globally over the next 30 years, with about 75 percent of those births occurring in sub-Saharan Africa.

Of concern is that an estimated 50-90 percent of infants born with SCD in low-income countries will die before their fifth birthday and SCD is identified as the underlying cause of about one in 12 newborn deaths in sub-Saharan Africa.

This calls for urgent attention.

Last week, the United States-based National Institutes of Health (NIH) announced that it would invest at least US$100 million over the next four years towards an audacious goal: develop affordable, gene-based cures for SCD and HIV.

On the same day, the Bill & Melinda Gates Foundation also disclosed that they would invest US$100 million towards the same goal.

The NIH is a medical research agency which includes 27 institutes and centres, conducts and supports basic clinical and translational medical research, and is investigating the causes, treatments and cures for both common and rare diseases.

In announcing the new funding, NHI said the intention of the latest development was for the cures to be made globally available, including in low-resource settings, sub Saharan Africa included.

Ultimately, the goal is to scale up and implement these treatments globally in areas hardest hit by these diseases.

NIH director Francis S. Collins said: “This unprecedented collaboration focuses from the get-go on access, scalability and affordability of advanced gene-based strategies for sickle cell disease and HIV to make sure everybody, everywhere has the opportunity to be cured, not just those in high-income countries. We aim to go big or go home.”

Dramatic advances in genetics over the last decade have made effective gene-based treatments a reality, including new treatments for blindness and certain types of leukaemia.

Yet, accessibility of these breakthroughs by most of the world  — by virtue of the complexity and cost of treatment requirements, which currently limit their administration to hospitals in wealthy countries — remains a distant dream.

To reduce the gaps, and make these treatments effective and available for SCD and HIV, which disproportionately affect populations living in Africa or of African descent, new investment is needed to focus research on the development of curative therapies that can be delivered safely, effectively and affordably in low-resource settings.

The collaboration between the NIH and the Gates Foundation sets out a bold goal of advancing safe, effective and durable gene-based cures to clinical trials in the United States and relevant countries in sub-Saharan Africa within the next seven to 10 years.

It will also align aggressive, high-reward research efforts to accelerate progress on shared gene-based strategies to cure SCD and HIV.

Both organisations will continue to invest in other parallel research efforts on cures for SCD and HIV outside of this collaboration.

“In recent years, gene-based treatments have been ground breaking for rare genetic disorders and infectious diseases,” said Trevor Mundel, president, Global Health Programme, Bill & Melinda Gates Foundation.

“While these treatments are exciting, people in low and middle-income countries do not have access to these breakthroughs. By working with the NIH and scientists across Africa, we aim to ensure these approaches will improve the lives of those most in need and bring the incredible promise of gene therapy to the world of public health.”

First, the collaboration will identify potential candidate cures for SCD and HIV for pre-clinical and clinical evaluation, co-funded by the NIH and Gates Foundation

Second, it will define long-term opportunities to work together and with African partners on advancing promising candidates to late-phase clinical trials, with funding to be determined as candidates progress

Though SCD, a genetically inherited disease, and HIV, an acquired infectious disease, present significantly different scientific challenges, gene-based treatments hold promise for both, and many of the technical challenges for gene-based cures are expected to be common to both diseases.

To achieve the goals of the collaboration, both projects will require new delivery systems that can get prospective therapies to the right places in the body and optimise treatments to target the cells involved in the respective diseases efficiently and specifically.

For SCD, that would mean repairing or compensating for the mutations in haemoglobin that cause SCD in hematopoietic stem cells. For HIV, that would mean targeting the reservoir of proviral DNA that continues to lurk inside a small number of cells, even after many years of effective antiviral treatment.

Such treatments that happen entirely within the body, known as in vivo treatments, would be a major step forward from current treatments, which apply genetic therapies to cells taken outside the body (ex-vivo) and then re-infused.

World Health Organisation regional director for Africa Dr Matshidiso Moeti said too much of Africa’s future is being lost to sickle cell disease and HIV.

“Beating these diseases will take new thinking and long-term commitment,” she said. “I’m very pleased to see the innovative collaboration announced today, which has a chance to help tackle two of Africa’s greatest public health challenges.”

SCD
The collaboration’s goal for SCD, according to NHI, is to develop an easy-to-administer gene-based intervention to either correct the SCD gene mutations or promote fetal hemoglobin gene expression to achieve normal haemoglobin function. The path to a cure will rely in part on the development of gene-based delivery systems capable of selectively targeting hematopoietic stem cells.

This will result in the precise correction of gene mutations or addition of a gene to promote sufficient levels of normal haemoglobin expression and function.

Director, National Heart, Lung and Blood Institute (NHLBI), part of the NIH, Gary H. Gibbons, said a person’s health should not be limited by their geographic location, whether rural America or sub-Saharan Africa; harnessing the power of science is needed to transcend borders to improve health for all.

“Our excitement around this partnership rests not only in its ability to leverage the expertise in two organisations to reduce childhood mortality rates in low-resource countries, but to bring curative therapies for sickle cell disease and HIV to communities that have been severely burdened by these diseases for generations,” he said.

In addition, more needs to be done to understand the burden of SCD in sub-Saharan Africa and to screen newborns for SCD in high-risk geographic areas.

NHLBI has already begun to establish a clinical research infrastructure in sub-Saharan Africa.

However, additional clinical research and capacity-building efforts are needed to deliver point-of-care screening, such as at the time of infant vaccinations, and to initiate a standard of care.

These activities will be undertaken by NIH and Gates Foundation outside of the collaboration, but will support collaboration efforts.

HIV
Nearly 38 million people worldwide are living with HIV, with 770 000 deaths due to AIDS in 2018 alone. Like SCD, people in sub-Saharan Africa face a disproportionate risk of HIV.

Antiretroviral therapy is highly effective and has made it possible for people with HIV to live long, healthy lives without transmitting the disease to sexual partners.

However, treatment must be maintained for a lifetime. A low-cost, safe, effective and durable cure that also prevents reinfection upon sexual exposure has long been a goal to curb the HIV global pandemic.

A number of approaches will be considered to meet the goal of a scalable HIV cure.

Both the Gates Foundation and National Institute of Allergy and Infectious Diseases (NIAID), part of NIH, are already funding cure research, exploring gene-based treatments in concert with long-acting therapeutics, monoclonal antibodies and other immune-based targets.

This collaboration will allow the partners to intensify and better coordinate ongoing research efforts on these strategies, accelerating studies into early phase clinical trials to safely test promising tools and interventions.

A particularly appealing approach is to identify the location of the reservoir of infected cells that still harbour integrated HIV genomes after treatment and target those DNA sequences with gene editing technology.

“This collaboration is an ambitious step forward, harnessing the most cutting-edge scientific tools and NIH’s sizeable global HIV research infrastructure to one day deliver a cure and end the global HIV pandemic.” said NIAID director Anthony S. Fauci.

“We are taking into account those with the greatest need at the foundation of this effort, to ensure that, if realised, this exceptional public health achievement will be made accessible to all.”