Chastening AIDS into submission is surely man’s greatest achievement.
In many ways HIV/AIDS was the classic horror film set up. A community suddenly and inexplicably targeted by a demonic predator. It was Halloween, it was Jaws and it was any number of vampire movies. And it was made all the more terrifying, because this enemy came without a name or a face.
The HIV/AIDS plot began 35 years ago in California. After years of secrecy the gay community had started to find its voice, coming out in a whirlwind of art, music, nightclubs and, understandably, sexual defiance. The new generation of homosexuals were no longer prepared to endure prejudice and, instead, flaunted their physiques, and expressed freedom through promiscuity.
By 1981, however, a mysterious illness threatened to ruin the party. Predominantly young, gay men were dying from a new virus, defined by a period of sudden weight loss, lesions and the shutdown down of a hitherto healthy immune system. The situation triggered panic, and also prompted celestial posturing from those who pronounced it ‘a punishment from God’. The ignorance was almost as harmful as the illness itself.
By the end of that first year, 152 deaths had been recorded, but it was an isolated fatality that most puzzled the scientific community, for one of those infected was not a homosexual, but an intravenous drug user – the first indication that this condition impacted on everyone.
The gay community’s reaction was impressive and they called on an already finely-tuned expertise in activism. Even in the throes of unimaginable suffering they marched, campaigned for accelerated treatment approvals and lent themselves to cohort studies. While some refused to give up their sexual liberation, others wanted to help those they left behind. It was altruism in its purest form.
Meanwhile, in the UK, immunology departments braced themselves as the ‘new disease’ crossed the Atlantic. Amazingly, one of the first diagnosed cases was not a sexually reckless homosexual, but a ‘normal’ housewife, with only one sexual partner (her husband) – this was the moment the ‘gay problem’ became society’s problem.
By 1982/83 the mysterious condition had a name – ‘acquired immune deficiency syndrome’ – and an unforgettable acronym; ‘AIDS’. Experts in the UK attempted to educate the public with a polite letter, printed in national newspapers, but, after it failed to receive attention, a shocking information film was broadcast, which left nothing to chance. The word AIDS was chiselled into a tombstone, lilies were tossed on a grave and a chilling voiceover told you the deal.
There were also a few high profile deaths, but it was Rock Hudson’s, back in the US, that convinced any remaining cynics that this was serious – a symbol of enduring strength was dead, and he had died of AIDS.
In 1987 the first effective treatment – a nucleoside reverse transcriptase Inhibitor (NRTI) – called AZT, began to be widely used and, thereafter, a flurry of anti-retroviral therapies emerged, as pharma’s mission came into sharp focus. While these treatments temporarily fooled the replication system of the virus, patients would eventually be overwhelmed, and die from AIDS-related complications.
The 1990s heralded wider solidarity against a common foe. Freddie Mercury’s death raised awareness further, while the tale of two very different Johnsons – Magic and Holly – proved that there was life after a positive result. The former, a hugely popular basketball star, and the latter, the charismatic lead singer of Frankie Goes to Hollywood, have fought the disease in the public gaze, and are both alive in 2016.
Campaigns continued through a number of female figureheads, notably Princess Diana and Elizabeth Taylor, and the red ribbon became a fashion statement – disease awareness was immersed in pop culture in a way that had never been seen before.
In the second half of the decade indinavir – a protease inhibitor – was combined with two existing NRTIs, and the game changed. It suppressed the virus indefinitely and frequently rendered it undetectable. Thousands of people avoided death, illness and even hospitalisation, as a stranglehold on AIDS was established and it became a long term treatable condition.
The single pill therapy, REZOLSTA, has recently become available for HIV-1 patients, and represents a significant move towards better treatment discipline, in an area which requires at least 95% adherence. Meanwhile, the brilliantly-abbreviated PrEP (from the not quite as sexy, ‘pre-exposure prophylaxis’), is a controversial combination of tenofovir and emtricitabine, which blocks the setting up of an infection, in HIV-negative individuals. It has been argued that people will abuse it in a sexual frenzy, whereas I would suggest that all alternatives to getting AIDS should be celebrated.
Indeed, in the great tapestry of human behaviour history will remember HIV/AIDS, not by mankind’s struggle, but how it reached unchartered heights of humanity. How ‘we’ have dealt with it – as healthcare professionals, as pharma and – most resolutely – as people, has set the template for how all diseases should be approached.
In the final analysis AIDS/HIV has been a most profound study of the human condition but, curiously, it has not been so much about death, as what it is to be alive.
John Pinching talks to Professor of Clinical Immunology Professor Anthony Pinching about his reflections on HIV/AIDS.
Prof. Anthony Pinching, witnessed the arrival of AIDS, treated its earliest patients and saw at first-hand how the story unfolded.
1. How satisfying is it to you personally that HIV/AIDS is now a treatable long term condition rather than a death sentence?
In the early 1980s, when we started to see this condition in the UK, a patient being diagnosed as having AIDS had an average life expectancy of some nine months. While some died sooner from their first presenting illness, others lived quite a bit longer – I remember some living for as long as three years. Once we were able to identify people with HIV infection, before they were ill, we recognised that they could remain well, and without immunodeficiency for many years, although there was a steady and relatively high rate of progression to AIDS over 5-10 years of follow-up.
Initial treatments were based on treating presenting opportunist infections and tumours, and maximising health and well-being, together with adjustment to the condition and its prognosis amongst a generally young group of people. This could achieve a certain amount in treating acute events, and maximising health inbetween bouts of illness, but the underlying condition would continue to progress.
We then saw single-agent anti-retroviral therapy (zidovudine) making a small, but useful, difference in life expectancy, initially demonstrated in those with AIDS, where it almost doubled. It was later shown to help people with HIV infection and adverse prognostic markers, leading to lower rates of progression.
The breakthrough – and it really was that – came with the clinical trials, demonstrating the impact of combination anti-retroviral therapy in the mid-1990s. While the theoretical concept was logical and attractive, the actual impact was unexpectedly massive. It transformed life expectancy, and indeed the whole landscape of HIV/AIDS treatment. We were surprised and delighted to see the extent to which the immune system could recover when HIV was effectively suppressed. What had been, in effect, a terminal illness, became a chronic treatable disease, with life expectancy increased by more than an order of magnitude. The impact on individuals and on populations were remarkable for those of us at the front-line.
Studies subsequently have consolidated this impact, refining the approach, and optimal timing of intervention, monitoring treatment impact, minimising side-effects and maximising convenience and adherence, as well as showing reductions in HIV transmission from effectively treated HIV-infected persons – most strikingly in mother-to-infant transmission.
As someone involved in treating patients from the outset of the pandemic, this change was truly extraordinary to witness. It was a very satisfying outcome to all the enormous investment of ideas and money, by many people and organisations across the world. As a clinical researcher, it was great to see how the systematic pursuit of clinical research had achieved such results in such a relatively short time. As someone involved in public policy, as well as helping in addressing the challenge of HIV in Africa, it was immense, and heartening. It was especially good to see these treatments made available in Africa and other developing regions, contrary to early predictions.
2. Are you surprised at the relative speed at which it has happened?
The pace of the improvements in HIV/AIDS treatment – in real time – seemed frustratingly slow because, as clinicians, we saw the immediacy of need in our patients, and yet we had to do our best with more limited tools, while the necessary research was done. From a wider perspective, however, the speed with which we went from first recognition of the disease (1981), to first HIV tests (1985), to first effective treatment (1987), through to combination anti-retroviral therapy (1996), was unprecedented.
It required massive investment, great focus, and tremendous collaboration between scientists, clinicians, the pharmaceutical industry, governments and – above all – patients. It showed what could be done with that sort of focus and collaboration. It wasn’t easy – indeed it was quite ‘bumpy’ at times, but we got there!
3. Do you think the social stigma regarding HIV/AIDS has lifted in recent years?
Yes, to a substantial degree, although there is more to be done. Extraordinary work across many sectors, important community advocacy, valuable public policy changes, and cumulative shifts in society have all played a part in reducing stigma. But problems remain in a number of respects in the UK, and even more so in other parts of the world. It will take a generation or two to get to where we need to be, but there has undoubtedly been change for the good, and some came surprisingly soon. The response to HIV/AIDS has also had a positive impact in reducing stigma and discrimination for people with a wide range of other health problems.
4. Do you think it's possible that a cure could emerge in the next decade?
‘Cure’ is not a helpful word for most diseases – it has a very particular meaning, signifying something that is very rarely achieved with chronic disease. I do think that what has already been achieved for HIV/AIDS, however, represents something of the same order: an eminently treatable chronic condition that may be compatible with near-normal life expectancy. I wouldn’t have imagined much of what has transpired!
Professor Anthony J Pinching, DPhil, FRCP, Emeritus Professor of Clinical Immunology, PCMD
Illustration by Alex Buccheri