With all the negativity around this blog lately, thanks to the continued moronic antics of the anti-vaccine contingent, which have irritated me more than they do usually, so much so that I can’t recall a time since Jenny McCarthy’s “Green Our Vaccine” anti-vaccination-fest nearly two months ago that they’ve been so flagrant in their lies, I thought it was time for some good news for a change. Fortunately, by way of the latest issue of The Lancet, some good news showed up in the form of a study. This study, reported late last week by the Antiretroviral Therapy Cohort Collaboration, a multinational collaboration of HIV cohort studies in Europe and North America, is yet one more piece of evidence that science-based medicine works. A press release describing the study sets the stage:
HIV-infected patients in high income countries are living some 13 years longer thanks to improvements in combination antiretroval therapy (cART), according to new research by the University of Bristol published in a HIV Special Issue of The Lancet today.
Improvements in and long-term effectiveness of cART have seen life expectancy increase by some 13 years from 1996-99 to 2003-05, and an accompanying drop in mortality of nearly 40 per cent in the same period.
By any stretch of the imagination, this is good news. The press release continues:
Professor Jonathan Sterne of Bristol University’s Department of Social Medicine and Professor Robert Hogg of British Columbia Centre for Excellence in HIV/AIDS and Simon Fraser University, Vancouver, Canada and colleagues from The Antiretroviral Therapy Cohort Collaboration (ART-CC) compared changes in mortality and life expectancy among HIV-positive individuals on cART.
This collaboration of 14 studies in Europe and North America analysed 18,587, 13,914, and 10,584 patients who started cART in 1996-99, 2000-02, and 2003-05 respectively.
A total of 2,056 patients died during the study period, with mortality decreasing from 16.3 deaths per 1000 person-years in 1996-99 to 10.0 in 2003-05 – a drop of around 40 per cent.
Potential life years lost per 1000 person-years also decreased over the same time, from 366 to 189 — a fall of 48 per cent. Life expectancy increased from 36.1 years in 1996-99 to 49.4 years in 2003-05, an increase of more than 13 years.
I decided to go to the study itself, because that’s usually the best approach in my experience when it comes to evaluating any peer-reviewed literature. This study appeared in the July 26 issue of The Lancet. It has several strengths. For one thing, it uses a concrete and undeniable endpoint as its measure, namely death. If there’s one endpoint that is unmistakeable and concrete, it’s death or, in this case, survival. Another strength of the study is that it looks at huge numbers of patients from multiple cohort studies for a grand total of 43,355 patients with HIV from several developed nations. The large collaborative nature of the study tends to smooth out local variations and statistical quirks, a characteristic which tend to average out highs and lows that can plague smaller studies and particularly single institution studies. On the other hand, one weakness is that the study didn’t take into account prior antiretroviral therapy use, which may be a confounding factor.
Basically, the investigators followed a large cohort of HIV-positive adults undergoing combination antiretroviral therapy from three time periods (1996-99, 2000-02, and 2003-05) and stratified subjects by sex, baseline CD4 cell count, and history of injecting drug use. They then estimated the average remaining life expectancy for those treated with combination antiretroviral therapy at age 20 and 35, as well as potential years of life lost from 20 to 64 years of age. The results were striking. In addition to the striking decreases in mortality reported above, it was found that today the average HIV positive 20 year old starting combination antiretroviral therapy can expect to live another 43 years; a 35 year old, 32 more years.
I was in medical school during the late 1980s, and I did an infectious disease elective in my last year of medical school, 1988. At that time, the diagnosis of an HIV infection was a death sentence. As an accompanying commentary put it:
Before 1996, clinicians who saw patients with HIV had to give bad news almost daily. We tried to restore hope by telling patients the cold hard facts that only 50% would progress to AIDS or death within 10 years, often acknowledging to ourselves that the tell-tale clinical features of immune deficiency had already appeared and the inevitable demise would surely be sooner rather than later.
I would note that a 50% ten year “progression-free” survival would not be so hot for many cancers. Also, I note that it is exactly this slow and variable progression of HIV to full blown AIDS is exactly the characteristic that gives HIV/AIDS denialists the opening to claim that HIV doesn’t cause AIDS and that antiretroviral therapy does more harm than good (for instance, when outliers go 15 or more years with HIV and do not progress or when the small subset of “nonprogressors” is examined). In any event, from my perspective, having dealt with AIDS patients in the era when there was nothing much that could be offered besides AZT, I find the prospect of patients being able to expect to live to an average age in their 60s while on antiretroviral therapy to be one of the most amazing successes of scientific medicine ever. In less than 25 years after having identified the virus that causes AIDS, we’ve gone from a disease that was a death sentence to a disease that can be managed on a chronic basis, with the expectation of patients living to a decent, if not ripe old, age. By any measure, this is an amazing, even unprecedented achievement and evidence that science works.
This study isn’t all sweetness and light, unfortunately. Although 20 and 35 year olds can expect to live into their 60s on antiretroviral therapy, it’s not clear why their life expectancy is not normal, which would be a life expectancy to around 80. Even with the new drug cocktails, these patients tend to die younger than patients without HIV. One thing this study shows is that starting treatment early is imperative if patients are to survive even this long. Starting treatment after patients have already become immunosuppressed shaves 10-20 years off of their anticipated time left. Being an IV drug abuser is good for the loss of around 10 years. It’s unclear exactly why, although it’s been speculated that the difference between IV drug abusers and those who do not abuse IV drugs may be due to poorer compliance with therapy in the former group. In the latter group, it is not clear why life expectancy has not yet been moved to normal, although it has been speculated that the effects of uncontrolled replication of HIV before treatment begins may produce long-term damage. Indeed, it’s speculated in the editorial:
Death is now increasingly due to serious non-AIDS illnesses, such as cardiovascular disease, cancers, and end-stage liver and renal disease….The most reasonable explanation for the 10-20-year gap in life expectancy so well documented by the ART-CC study is the previously unrealised clinical mischief of untreated HIV infection. The prevention of CD4 loss and perhaps immune activation by early treatment above a CD4 T-cell count of 500 cells per μL, a band which contains the lowest rates of serious HIV-related clinical events, is perhaps the most important clinical trial that should be done in the post-cART era. Hopefully, the START study, which compares starting cART with a CD4 cell count above 500 cells per μL versus deferring to a CD4 cell count of less than 350 cells per μL, will provide the evidence base to bridge the gap so elegantly defined by the ART-CC group.
Scientific medicine has done amazingly well in developing better treatments for HIV/AIDS. If someone had predicted to me in 1988 that in 2008 HIV would be in essence a chronic disease that shortened lifespans by 10-20 years if treated but still allowed a fairly normal life, I’d never have believed it given the death toll from this disease 20 years ago. For all intents and purposes, HIV has now become more like coronary artery disease or severe diabetes, a chronic disease that can be managed, than like cancer. However, clearly what scientific medicine has accomplished is not enough. HIV is still deadly if not treated soon enough, before serious damage to the immune system is done by the virus, and even perfectly treated patients do not live as long as uninfected patients. More importantly, the antiretroviral regimens are both expensive and onerous to follow, producing a major gap between results in developed nations (which were examined in this study) and Third World or developing nations, where HIV is such an enormous problem. Much has been accomplished, but much is still required if this scourge is to be vanquished, not the least of which is the development of far more inexpensive and less difficult combination drug regimens that poorer nations can actually afford.
The bottom line from this study is that it is yet another in a long line of studies that indicate that our current treatments for HIV infection are making a difference in the lives of patients. They are prolonging lives far beyond what was thought possible. That such advances occurred within my professional lifetime still astonishes me. What astonishes me even more is how people who for apparently ideological reasons simply can’t accept the copious science demonstrating that HIV infection ultimately results in AIDS in the vast majority of people infected and that treatments targeted at HIV work. They may not work as well as we would like yet, and their many drawbacks leave an opening for the denialists to obfuscate, but on balance the benefits they bring far outweigh the risks. Indeed, that combination antiretroviral therapy has improved the life expectancy of patients with HIV infection is a powerful refutation of the pseudoscience of the HIV/AIDS denialists.
The Antiretroviral Therapy Cohort Collaboration (2008). Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies. The Lancet, 372(9635), 293-299. DOI: 10.1016/S0140-6736(08)61113-7