The eventful journey in tackling the AIDS pandemic ‒ from social stigmas to scientific controversies
Author: Anna Lewicka
Editor: Altay Shaw
Artist: Patrick Marenda
It would be no exaggeration to say that we’ve all had a mandatory and undesired epidemiology crash course during the last 14 months. Our lives were turned upside down, forcing us to think more deeply about our health and hygiene. Whether we will pass this demanding test as a society remains to be seen. Nonetheless, it should serve as a reminder of how dangerous viruses can be.
A formidable opponent
SARS-CoV-2 was not the first virus that caused a pandemic, as we are still in the middle of a draining war against human immunodeficiency virus (HIV). Following the outbreak of HIV in 1980s America, there was widespread panic at the dreadful symptoms of its disease (AIDS) and the absence of a cure. Worst of all, the mysterious illness carried a terrible social stigma because it was frequently diagnosed in gay men and drug users. Various speculations resulted in a campaign of misinformation, for example, the belief that HIV is transmitted by mosquitoes. In the 1990s, the disease was spreading exponentially in developing countries, mainly in Africa, as it encountered extraordinarily favourable conditions for transmission: rapidly growing populations, limited space and sanitary conditions, low awareness of the routes of transmission and the risks. Nowadays, it is estimated that as many as 38 million people in the world live with AIDS, the most affected region being sub-Saharan Africa.
The nature of HIV is nothing like SARS-CoV-2. Contrary to the acute infection caused by circulating coronavirus strains, HIV is a persistent, latent infection. This means that once infected, the virus remains in the cells indefinitely, as its genomic material gets incorporated into the host cell’s DNA. HIV specifically targets CD4+ T cells which play a paramount role in shaping adaptive immune responses. It enters them via CCR5 co-receptors located in their surface membranes.
Once in the cell, HIV uses an enzyme called reverse transcriptase to translate its genome from RNA to DNA, which gets incorporated into the human genome. This is why it is impossible to eliminate the infection, and existing antiretroviral drugs are merely able to stop the virus from reproducing. These drugs target enzymes specific to the virus, for example, by imitating nucleotides and terminating replication. Despite the great success of combination drug therapy at suppressing this rapidly replicating and adapting virus, such treatment has multiple disadvantages, such as the accessibility and cost of medication. Sadly, it also means living with the virus and taking medication indefinitely, thus the battle against HIV cannot be claimed as a victory yet. We’ve developed a way to live with the virus, but are we anywhere near to fully curing AIDS?
Nature to the rescue
In the early 2000s, it was observed that some patients, despite being consistently exposed to the virus, did not become infected with HIV. It turned out that these individuals were homozygous for a particular mutation of the gene encoding the CCR5 receptor, called CCR5-delta 32. As a result, the receptor becomes dysfunctional and the virus cannot enter the host cell. In short, such an individual is naturally immune to HIV.
Some brilliant minds used this discovery to attempt to cure AIDS completely. In 2007, Dr Gero Hutter devised a procedure to administer a bone marrow transplant to a patient suffering from leukaemia and AIDS, known as the Berlin patient. Crucially, he selected a specific donor who was homozygous for the CCR5-delta 32 mutation. Consequently, after the transplant, the patient’s immune system only proliferated T cells that were resistant to HIV infection. The experiment was deemed successful when, despite stopping antiretroviral drug therapy, no HIV particles or HIV-specific antibodies were detected in the patient’s blood, suggesting complete elimination of the virus from the body.
A similar groundbreaking approach was implemented at UCLH in 2018, when the second person in history, called the London patient, was completely cured of HIV. Before getting too optimistic, it is worth noting that both of these cases were highly specific; it is unlikely to be a practical approach for treating the 38 million HIV sufferers around the world. There’s also a significant mortality risk associated with a bone marrow transplant. Moreover, it is believed that without a functional CCR5 receptor, the body may be more sensitive to other infections, such as West Nile virus.
Ways ahead?
In 2018, the battle against HIV became a model example of how science should not be conducted, causing exceptional scientific scandal and contributing to widespread fear and misinformation. Chinese biophysicist He Jiankui announced that he had used CRISPR/Cas9, a revolutionary gene-editing technique, to change the DNA of human embryos that were subsequently implanted in their mother’s womb and developed into twin baby girls. He introduced the famous CCR5-delta 32 mutation, effectively making the babies resistant to HIV. The study was universally condemned by the scientific community, and the rogue researcher was convicted and currently serves a jail sentence.
At first glance, one might be tempted to question the difference between this study and other experimental therapies, among them stem cell transplants described in this article. Importantly, the experiment skipped many steps in the usual careful process of developing innovative treatments. From the studies in animal embryos, we know that CRISPR/Cas9 sometimes changes a gene in unexpected ways, which is potentially dangerous to every cell in the body. Another hugely controversial aspect is the interference in the germline. The altered twins will pass on the edited DNA to their children, thus risking passing potential genetic problems to future generations. Ethically there are still some open questions about the implications of artificially altering the course of human evolution. Regardless, this non-transparent experiment was a terrible strategy for pushing scientific progress, as potential failure could have discouraged public opinion from gene editing in the future when the technique will be better understood. Nevertheless, whether we like it or not, gene-edited humans are no longer science fiction, but live among us, creating a precedent to continue such activities.
It has been a long fight against HIV. Although we have made impressive progress since the start of the AIDS outbreak, HIV is still a major threat in deprived communities. Another pandemic, the infamous COVID-19, is a painful reminder that the viruses are not to be underestimated. Importantly, these dreadful events have triggered extraordinary developments in science, which remains our single greatest hope and weapon in this struggle.
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