The third and final piece in Lenias Hwenda of Medicines for Africa’s series looking back at the challenges and successes of HIV/AIDS treatments over the past 40 years and potential medical breakthroughs to come (read part one here and part two here). Here, Hwenda examines the persistent challenge of HIV/AIDS survivors losing their lives to noncommunicable diseases (NCDs), calls for a new public health approach in what is now the fifth decade of battling HIV/AIDS, and finishes with her optimism about the breakthrough that a safe and effective HIV vaccine would represent.
The fifth Decade of HIV/AIDS – losing lives saved from HIV/AIDS to NCDs
Billions of dollars have been invested in saving millions of lives from HIV/AIDS. The success is however clouded by the fact that long-term HIV/AIDS survivors are increasingly losing their lives to unmanaged non-communicable diseases like cancer, diabetes, and cardiovascular diseases (CVD). Few health systems in low- and middle-income countries (LMICs) have adequate programs and infrastructure for non-communicable disease management for national populations. Yes, HIV/AIDS has had a disproportionate impact on the young economically productive demographic. Those affected individuals carry it for life and they have a heightened vulnerability to other chronic conditions affecting the general population. And so whilst AIDS has become a medically manageable chronic condition that is no longer among the 10 leading causes of death globally, at a population level, HIV gains are not being fully realised because health systems neglect NCDs which subsequently take the lives saved by HIV/AIDS programs.
What is clear is that HIV programs are no longer meeting the medical needs that people living with HIV have today. Meeting those needs requires that public health do something differently in the fifth decade of HIV/AIDS. Firstly, it is necessary to evaluate whether investing billions of dollars to save lives from a single disease whilst several other chronic conditions that are equally likely to take the lives saved are left unaddressed is still a compelling value proposition. Secondly, countries need to decide whether health systems built around service provision for single diseases are tenable. The WHO anticipates an increase in the frequency of disease outbreaks in the African region over the next decade. Can the health systems of vulnerable countries be adequately prepared without investing in wider healthcare needs? Ultimately, high-burden countries must decide whether they would be best served by prioritizing investment in developing health systems capable of meeting the broader health needs of life-long survivors of HIV? Does it make sense for organisations like UNAIDS to continue advocating for overall increased spending only on HIV/AIDS and nothing else?
HIV programs are no longer meeting the medical needs that people living with HIV have today. Meeting those needs requires that public health do something differently in the fifth decade of HIV/AIDS.
What countries chose to invest in public health will significantly impact how well countries are able to respond to multiple anticipated health challenges driven by the climate crisis amidst existing unmet medical needs. Then there is the question of how countries will pay for the multiple crises amidst multiple challenges and whether it is realistic or desirable for the world to continue to maintain a singular focus on HIV/AIDS at the expense of all else? The dominant trend in the last decade is that of declining donor funding, even though development assistance may have increased by 15 percent to reach USD 40.6 billion in 2019 relative to 2010. When sustainable development goals (SDGs) come to an end in 2030, it may be necessary to re-evaluate the justification for maintaining single-disease organizations such as UNAIDS in the context of the needs of people living with HIV/AIDS.
What countries chose to prioritise when investing in healthcare will determine whether healthcare and economies can be effectively secured. The COVID-19 pandemic service disruptions significantly reversed decades worth of HIV progress. The WHO projected that a six-month disruption of antiretroviral therapy could lead to more than half a million additional deaths from AIDS-related illnesses. Widespread global supply chain disruptions resulting from export bans imposed by many countries that are major suppliers of medical products to African countries made it difficult to ensure an uninterrupted supply of essential medications to high-burden countries. This is why it is a big problem that Africa, the region with the heaviest burden of HIV/AIDS on the planet, does not manufacture rapid HIV diagnostics, for example. Dr John Nkengasong, who leads PEPFAR and is the former Director of the Africa Center for Disease Control (CDC) often lamented how damaging this has been for the continent of Africa. He constantly highlighted the need to provide some level of supply security with local production of some of the essential medical products needed for an effective HIV/AIDS response. It is a wonder that given its outsized burden of disease, investing in local production of essential HIV care products like ARVs and diagnostics was never made a part of a smart investment strategy made by governments, international institutions like the WHO, UNAIDS and the Global Fund straight from the beginning. Even more surprising is that all these decades, these institutions have sourced medical products in a way that does not promote supply chain security, sometimes concentrating supply risk in a limited number of countries like India and very few manufacturers like the Serum Institute of India.
So now that the world has seen just how harmful the exclusion of the African continent from the global medical supply chains, including of things that it needs at all times like HIV commodities, is there a willingness to change and create structures that are more equitable? PEPFAR recently announced its intention to support the regional production of essential HIV medical products in Africa. The World Bank and others have made similar indications but whether this will amount to anything is anyone’s guess given these institutions’ long history of broken promises and the reticence of development partners to support industrial development in Africa. For instance, each year, the United States government buys health commodities (diagnostics, therapeutics, vaccines, equipment) worth over USD 1 billion, most of them destined for Africa. Less than 1 percent of the value of those commodities is bought from Africa. Then there is also a question of how funding contributions from low- and middle-income countries (LMICs) governments themselves are invested. For instance, LMICs contributed more than half of the approximately USD 20.2 billion annual spend on HIV/AIDS in 2021. Donor funding constituted about USD 9.5 billion. About half of the annual sum is spent on procuring medical commodities in a way that supports the economic interests of donors.
A very negligible portion of it is spent investing in health and pharmaceutical industrial development of countries with a high HIV/AIDS burden. For too long, governments and international institutions have invested in a way that fortifies excessive dependency of high-burden countries on importing critical and essential medical products needed for an effective HIV response. Can this change in the fifth decade of HIV/AIDS? At a minimum, the substantial routine funding contributions made by high HIV-burden countries towards international HIV/AIDS programs like the USD 10.5 billion spend in 2021 that are rarely mentioned should be used to support a sustainable approach to providing treatments to affected populations beyond donation. Smart investment means investing some of these funds to bring supply chains closer to HIV high-burden countries so that people can continue to get treated even during international health emergencies. Leaders should spend the fifth decade of HIV integrating the most committed LMICs on the African continent into the global supply chain. This will benefit all of humanity during global health emergency situations. Failure to make these adjustments would be a waste of a good opportunity.
An HIV vaccine breakthrough would bring a spring of hope
Even though antiretroviral treatments have significantly improved the life expectancy and quality of life for people living with HIV, without a cure for HIV, preventing infection remains our best public health tool for limiting this epidemic. Of all the possible ways of preventing infection, a vaccine remains the best approach. However, the scientific hurdles to developing an effective HIV vaccine are immense. Firstly, the virus rapidly establishes a persistent lifelong infection. Once infected, individuals are not able to clear the infection on their own and here is why this is a problem. If no individual with a confirmed infection is ever able to naturally clear the virus, we can never know what protection from HIV should look like. If one considers what happens when individuals are infected with viruses causing diseases like measles and chickenpox, generally, they can recover from their infection. Once they recover, the immune response to the natural infection is usually enough to prevent further future re-infection for a lifetime or for a limited amount of time like a few years. Scientists are then able to use this naturally-acquired immunity to model what a vaccine must do in order to be effective. Scientists can study natural immunity and extrapolate the specific characteristics and magnitude of protective immunity an effective vaccine must provide.
In contrast, when individuals are infected with HIV, they never recover from it naturally. This makes it difficult to answer the most important question. What is the specific type of immune response associated with protection against HIV infection, disease or reduced disease severity? In immunological parlance, we call this the correlates of protection. Scientists are unable to precisely understand the nature, type and magnitude of immune responses necessary to effectively protect the population against HIV infection. In order to answer this important question, scientists would need to determine whether protection requires a specific type of immune response say for instance the type and magnitude of antibody response or a certain type of memory T cell. Without knowing these correlates of protective immunity against HIV infection, vaccine development against HIV is like shooting in the dark. It is difficult to design and validate an effective vaccine.
Let’s suppose that scientists were able to crack the nature and magnitude of protective immunity, the frequent mutation of the virus throws a spanner in the works. HIV shows unprecedented genetic variability. It is so complex that understanding the best way to stimulate protective immunity against it is hard to crack. This complexity has made the traditional approaches used for developing vaccines against other diseases like measles ineffective. The virus is constantly changing. Developing a vaccine against a virus that is constantly changing its genetic makeup is like trying to hit a moving target with a dart. Constant mutation generates multiple variants of HIV that are genetically unique such that a vaccine that protects against one subtype may not protect against the others.
It is not all dome and gloom, however. Studies with limited success provide hope that an effective HIV vaccine is scientifically possible
Vaccine development efforts are also hindered by the limitations of the scientific tools available to us. For instance, when doing vaccine research, animal models are an essential tool for understanding the basic path of infection and immune response in any disease. There is no reliable animal model for modelling an effective immune system response against HIV infection. Testing HIV vaccines in animals does not provide accurate predictions of how the vaccine might behave in humans. Scientists test vaccines against HIV’s cousin, the monkey virus called the Simian Immunodeficiency Virus (SIV) and hybrids of SIV and HIV in efforts to adapt the observed responses to HIV. These models, however, have their limitations.
It is not all dome and gloom, however. Studies with limited success provide hope that an effective HIV vaccine is scientifically possible. For instance, a large-scale Thai HIV vaccine trial in 2009 showed limited efficacy providing a glimmer of hope that the design of a protective vaccine against HIV may yet be possible. Trial participants were given a recombinant vaccine as a prime, followed by a genetically engineered vaccine boost expressing HIV surface proteins designed to stimulate antibody responses. Participants who received the prime-boost combination had 31 percent fewer HIV infections compared to the placebo. However, because HIV is such a serious disease, 31 percent efficacy is considered much too low to allow the vaccine to be licensed for routine use. Nevertheless, this was the first time an HIV vaccine efficacy trial showed evidence of some protection against the virus. Understanding precisely how the prime-boost combination protected against HIV infection will enable other vaccine technologies to efficiently and effectively deliver HIV immunogens into the body to stimulate strong protective immunity. Amongst the most promising technology platforms being tested today are messenger RNA (mRNA) and viral vector vaccines. Both were successfully used in licensed COVID-19 vaccines to stimulate protective immunity and they hold great promise.
Conclusion
Success in the development of an HIV vaccine may have been limited but critical lessons from four decades of HIV/AIDS have informed the global response to subsequent outbreaks like Zika, Ebola and COVID-19. The HIV pandemic is likely to remain a major reference point against which to evaluate global responses in terms of funding, coordination, and access to life-saving interventions. Though different biological agents may be involved in future outbreaks, they will share a common challenge. They have a potential for international spread and international cooperation is the best way to limit their spread. The expected heightened risk of future disease outbreaks requires that a future public health strategy for maintaining progress with HIV/AIDS must be considered in the context of enhanced outbreak preparedness and capacity to respond to international health threats. The dissemination of pathogens will continue to be amplified by global connectedness, but our biggest future challenge is how the world can effectively tackle international health challenges when countries are becoming increasingly inward-looking.
When the COVID-19 pandemic broke out, we hoped that we would not see a repetition of the early history of ART. What we witnessed, however, was pure unapologetic vaccine nationalism. Wealthy countries hoarded vaccines and prioritized vaccinating their low-risk groups whilst frontline healthcare workers in low-income settings went unprotected. They did this whilst repeating ad nauseum, that “no one is safe until everyone is safe” echoing the HIV pandemic. One wonders whether this dynamic will ever change and whether it can. We know for certain that the COVID-19 pandemic showed that wealthy countries simply refuse to defer to the authority of multilateral agencies and international accords which is necessary to a coordinated global response. So if multilateral cooperation can no longer provide the answers to humanity’s shared challenges, then the only hope for LMICs may lie in regional cooperation. The HIV pandemic journey has been a difficult one. It showed the world the worst and the best of humanity. Difficult as it was for millions around the world, much that is good came out of it. Just like for the COVID-19 pandemic, an effective HIV vaccine remains humanity’s fountain of hope – the best tool we could have for one day eradicating HIV. We must remain hopeful that when this tool becomes available on the next part of the AIDS pandemic journey, it will take nations into a “season of light and a spring of hope” for all.
