In the first of a series looking back at the challenges and successes of HIV/AIDS treatments over the past 40 years and potential medical breakthroughs to come, Lenias Hwenda of Medicines for Africa shares her personal meditations on the HIV pandemic, the impact of expanded access to antiretroviral therapy, and the vital importance of immediate treatment to limiting HIV transmission.
“You come from Africa. You have many strange diseases there.” My host was casually making this comment as we sailed off the coast of Greece to escape the oppressive heat on the mainland. I thought “I need better friends.” This would have been a perfect moment to dramatically storm off. However, since my family and I were stuck on this boat some hours away from land, I did what I had to learn to do in such circumstances. Laughed and let the comment pass. Many a time, this stereotype of Africa as a place where people suffer from strange diseases has been lobbed at me. Sometimes in ways that could be rather grotesque. Like when a Chinese woman, my colleague, who wanted to rent a room in my upper East Side Manhattan apartment in New York asked me whether she might catch the human immunodeficiency virus (HIV) from sharing my apartment.
I was genuinely shocked and lost for words. Why would anyone consider themselves at risk of catching a sexually transmitted infection from someone who does not have the infection and from simply sharing a space with them? Then it hit me. She was assuming that I must have HIV. Again, all I could do was laugh. I carried this stigma for merely coming from a continent that experienced the worst of the HIV pandemic. Whether I actually had the infection was irrelevant. Imagine how much worse this stigma must be for people who actually have the infection or those who suffer the resulting illness? HIV Infection can lead to an acquired immunodeficiency syndrome (AIDS), a gradual and persistent deterioration and weakening of immune function and eventual immune failure that leaves the body without immune protection and unable to fend off minor infections or cancers. It is a serious illness that has caused suffering to millions around the world.
The HIV pandemic, a season of darkness
I first became acquainted with HIV at an early age when Harare Central Hospital dispatched my uncle to our home because they could not do anything more for him. His presence in our home meant that I had the occasional task of delivering a glass of water or retrieving an empty one from his bedside. Simple as this task was, the experience was terrifying for a child my age. The skeletal man lying in that bed awaiting the inevitable looked nothing like the tall handsome uncle that I had known. Not so long ago, he had been strong enough to scoop up the cheerful chubby girl that I was and swirl me in the air. I felt sad. The HIV pandemic had that effect on many children. It was a big shadow over the carefree lives of children at its epicentre who experienced the fear of loss, the pain, despair and the trauma of losing some of the most important people in their lives.
Children lost parents, siblings, aunts, uncles, neighbours, teachers, caregivers and more. Mind-boggling millions of them over several decades. On December 1, 2021, the HIV global pandemic reached its forty-year milestone since it began. In those four decades, HIV has infected upwards of 113 million people and counting. AIDS-related illness took upwards of 48 million lives globally, the majority of these deaths on the African continent. Big as these numbers may be, they do not convey the cruel lived reality of those affected by HIV/AIDS, especially during the decade when treatments became available elsewhere but not to the millions at the heart of this pandemic, on the African continent.
Back then, as children, our worst nightmare was not the imaginary monster under our beds. It was the very real possibility of losing one or both parents to HIV/AIDS as many of our peers did. According to UNICEF, an estimated 15.4 million children lost one or both parents to HIV/AIDS between 2000 and 2021 alone. This is not counting the millions more before that. Children did not lose just the grown-ups in their lives. They also lost their friends and playmates. Children learned early just how fragile and fleeting life is. For us, having parents was but a temporary phenomenon. It was never certain that they would be with us tomorrow. Parents fell ill, often suddenly. And they died. Anyone’s parents could be next.
So many died young from HIV causing a dramatic decline in life expectancy in Africa. In our Southern African communities, death was omnipresent. Funerals were endless. This period was our equivalent of the Dickensian “season of darkness” that robbed millions of children of so much and left them feeling like they had nothing before them when they should have had everything, their entire lives, before them. By any measure, the HIV pandemic was the worst of times. How does any community begin to heal from such trauma – a staggering four decades worth of it? They say only time heals a wounded heart when life has been cruel.
Expanding access to antiretroviral therapy (ARV)
To tackle this epic tragedy, scientists rolled up their sleeves and got down to work. Cutting-edge advances would soon unravel our understanding of the basic virology, human immunology, and HIV pathogenesis. Each scientific breakthrough injects a shot of hope into the lives of those on the edge of the precipice. Safe, effective antiretroviral (ARV) medications would quickly transform HIV/AIDS from being a death sentence. However, during that first decade of treatment availability, only a privileged few in wealthy countries enjoyed the hope that the treatments brought. The price tag of saving a life – in the tens of thousands per person per year was beyond the reach of those at the heart of this pandemic. This stage of the HIV crisis revealed the worst of human nature as pharma companies denied treatment to millions in their most desperate hour. People living with HIV alongside activists like Justice Edwin Cameron of the Supreme Court of South Africa and others across the globe demanded social justice. The struggle to have access to treatment extended to all during the HIV pandemic was a confrontation that invoked the biblical David and Goliath.
This stage of the HIV crisis revealed the worst of human nature as pharma companies denied treatment to millions in their most desperate hour
The sad irony was that leaders of an industry whose business model is premised on saving lives were the least willing to cede an inch and become part of the solution. When South African President Nelson Mandela sought a humane solution to his nation’s tragedy through legislative changes in South Africa, the industry simply sued him. Over an entire decade, the denial of treatment haemorrhaged twelve million lives on the African continent. Solutions could have been found much sooner, but there weren’t many men and women of reason and besides, these lives were expendable. This decade-long stand-off would eventually take a positive turn when some leaders decided they would not continue to avert their gaze from the unspeakable tragedy of this deadly virus ravaging African communities. The United Nations (UN) Secretary-General Kofi Annan rallied the UN to establish a Global Fund. President George W. Bush created PEPFAR committing the United States government to tackle HIV/AIDS as health development support. Acquiescence meant that millions would no longer be denied life-saving medicines. Generic medicines produced in India and China would play a central role in making treatment accessible to the masses. Leaders swore that the world must stand together because no one was safe until everyone was safe. It took them a decade to realise this.
This dark period would become history as the world built international institutions that would progressively put tens of millions on treatment significantly improving the survival of people with HIV. At the end of 2021, a total of 28.7 million people were receiving antiretroviral therapy worldwide- 7.8 million more than in 2010. That constituted an estimated seventy-five percent of people living with HIV. Global averages like this can however mislead by hiding regional and demographic differences. Depending on geography and demography, a range of sixty-six to eighty-five percent of people with HIV were receiving treatment in 2021. The pandemic’s epicentre in East and Southern Africa still accounted for fifty-four percent of all HIV-infected persons. Amongst those receiving treatment, children were the fewest. An estimated fifty-two percent of children between 0–14 years were receiving treatment compared to seventy-six percent of people fifteen years or older. The biggest group on treatment was pregnant women. About eighty-one percent of them were receiving treatment to prevent the transmission of HIV to their unborn babies.
This excellent progress made in improving access to HIV medicines is however facing a major threat from HIV drug resistance. Constant changes in the genetic structure of HIV that affect the ability of HIV medications to block the replication of the virus are making the virus resistant to medications. Widespread HIV drug resistance can eventually reduce the efficacy of medicines used to treat HIV. This would again increase the numbers of HIV infections and death. All ARV medications, including new classes, are at risk of becoming partially or fully inactive as a result of the virus’ drug resistance. People with prior exposure to ARVs have an increased likelihood of developing resistance especially to non-nucleoside reverse transcriptase inhibitors (NNRTI) class of medications, up to three times greater. An estimated 50 percent of neonates born to HIV infected mothers show resistance to treatment with one or more NNRTI class of ARVs. Consequently, the WHO now recommends rapid transition to the newer dolutegravir-based treatment regimens to minimize resistance. We can however take steps to minimize resistance. One is to ensure that patients receive the most optimal HIV treatments available and adhere to their treatment. It is also important to keep people on treatment and to frequently verify that treatment is still working by performing regular viral load testing. As soon as treatment failure is detected, treatment changes must be rapidly made in order to minimize opportunities for the virus to develop resistance.
Immediate treatment is key to limiting HIV transmission
HIV resistance to treatment is also detrimental to global efforts to limit onward transmission of HIV within the population. Putting more people on treatment helped to decrease overall HIV incidence and mortality. For example, in 2021, there were 54 percent fewer infections than at the peak of the pandemic in 1996. Amongst children, new infections decreased by 52 percent. The combination of biomedical, social and economic interventions has significantly increased maternal and child survival in the most heavily affected countries. Treatment reduces the prevalence of unsuppressed viraemia and this in turn limits viral transmission. Individuals with viremia transmit the virus sexually and when viraemia is not suppressed, it is the biggest driver of HIV transmission. Evidence shows that when viremia is undetectable, the virus is also untransmittable. HIV resistance to treatment undermines the use of treatment as prevention.
Regular HIV testing and immediate initiation of treatment helps to suppress and eventually prevent HIV transmission
For more than 2 decades, public health experts bickered about when was the best to initiate treatment. A decline in CD4+ immune cell numbers in the body signals worsening disease. CD4+ cells are the immune cell that coordinate immune responses. HIV infects them and in the absence of treatment, HIV replication causes the progressive loss of CD4+ T cell. This loss precipitates a wide range of immunological abnormalities that increases the risk of infectious and oncological complications The fall of these cell numbers below a certain threshold was used to signal when to initiate treatment. The need to reduce the economic cost of treatment justified delaying the initiation of treatment in order to shorten treatment, so treatment would commence when CD4 levels had dropped significantly. The public health need to save the maximum number of lives argued for the initiation of treatment as soon as possible regardless of CD4 cell counts.
Modeling studies and clinical trials resolved this question by showing that regular HIV testing and immediate initiation of treatment helps to suppress and eventually prevent HIV transmission. Subsequent clinical trials confirmed that immediate treatment regardless of the levels of CD4+ cell count in the blood reduced the incidence of HIV-associated disease and death. Today there is a substantive body of evidence that supports universal early treatment regardless of CD4 cell counts as the best way to extend the life of people infected with HIV. This is the most compelling argument why public health recommends actively identifying infected individuals through frequent testing and notification of partners in order to rapidly initiate early treatment.
Stay tuned for part two of this article in the coming weeks…
