Jul 30 2008
People with HIV are living longer on the latest anti-retroviral therapy. This is something any infectious disease specialist knows from their own clinical experience – but it’s reassuring (I would even argue necessary) to have objective data to support experience. A study published in the latest issue of Lancet provides this objective data. (Lancet. 2008 Jul 26;372(9635):293-9.)
The press release from Bristol University, academic home of the lead author, says:
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 to 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.
That’s very impressive – both the study and the data. Large collaborative studies are inherently more powerful and reliable than studies conducted at a single location by a single team. Methodological errors and statistical flukes tend to average out in larger studies with multiple centers.
Also – survival is a very hard (meaning objective and concrete) outcome, which is why it is preferred as a primary outcome measure whenever possible. Again this adds to reliability, more so than subjective symptoms dependent upon patient reporting.
The size of the result is also impressive, making it unlikely that small unanticipated confounding factors are responsible for the measured effect. Small effect sizes, even when highly statistically significant, are always suspect because it is difficult to account for everything that could potentially cause a small effect. Large effect sizes require a significant factor that is harder (but not impossible) to miss.
The weakness of the study is that it is a retrospective study, not a controlled prospective study. This opens the door for confounding factors. The authors accounted for known factors by stratifying subjects – making sure that known variables, such as age and sex, were accounted for. But unanticipated factors can always skew the results.
There are several important bottom-line implications of this study. The first is that the current cocktail of combination anti-retrovial therapy (cART) works. It correlated with decreased mortality every way it was measured. A newly diagnosed 20 year old can expect to live 49 years on current therapy. This is not a normal life expectancy, which is closer to 60 years from age 20, but it’s very good considering that in the 1980′s, prior to available treatments, life expectancy was about 12 years from time of infection.
While current treatments are very good, there is still room for improvement.
The data also show that the benefits of treatment diminish if they are delayed. Those with early treatment survived longer than those who started later. It is estimated that about 1/3 of people with HIV do not know it, and therefore are not being treated. The data therefore support continued efforts at public awareness to ensure early diagnosis and treatment.
As those with HIV are living longer we are also discovering new complications of chronic HIV infection, such as organ damage and cancer. Essentially, people with HIV are now surviving long enough to get more complications from long term HIV infection. Recognition of the later effects of HIV is prompting reevaluation of treatment recommendations and research. With continued research we will therefore likely improve survival further.
Being optimistic it is therefore likely that a newly diagnosed young HIV patient today will live long enough on current treatments to benefit from future treatments not yet developed. A normal life expectancy may therefore already be within reach, assuming continued research efforts.
This study also has great significance for the pseudoscientific denial that HIV is the cause of AIDS. Back in the late 1980′s and early 1990′s, prior to the development of the protease inhibitors and anti-retroviral drugs that make up the current cART, one of the main points of the HIV deniers was that treating HIV did not prolong survival with AIDS. For example, Peter Duesberg said in an interview:
“I could understand them saying I am so horrible and irresponsible if they were showing any results with their theory, but so far they haven’t saved a single life. After ten years there is still no vaccine, and the only therapy is AZT, which is, in my view, making people sicker.”
If the HIV theory of AIDS is correct, deniers argued, then why are HIV treatments not prolonging survival. Even in the early 1990′s the claim was not accurate, but treatments were only mildly effective. Now the efficacy of anti-HIV treatments for AIDS are undeniable. Interestingly, even though they once used this as an argument against the HIV theory, deniers are not willing to admit that increased survival is now an argument for the HIV theory.
Prominent denier Christine Maggiore on her website Alive and Well, wrote:
Government officials, AIDS organizations and the media unanimously agree that the recent decline in AIDS cases and deaths is an unprecedented occurrence due to a new combination of drugs that include protease inhibitors, chemicals said to block the replication of HIV. However, a careful look behind the headlines reveals that there is no medical evidence to support these popular claims about the protease inhibitor “combo cocktails.”
She then argues that increased survival is due solely to expanding the diagnostic criteria so that more mild cases qualify as AIDS. This is a real concern in any epidemiological data, such as the current study. But the criticism is not fair and accurate because changing diagnostic patterns is a known and often controlled for factor. For example, in the current study the methods indicate that populations were stratified by baseline CD4 count. The CD4 cells are those T-cells that are primarily affected by HIV infection, and CD4 count is widely used as an estimate of disease severity. This ensures that populations with similar severity are being compared, so that prolonged survival is likely to be due to treatment, rather than just changes in diagnostic behavior.
Maggiore also makes the rather dubious argument that decreases in AIDS cases preceded the introduction of modern treatments by several years. But treatment is not primarily about preventing new cases, but prolonging survival of existing cases. It can decrease viral load and therefore reduce the risk of spread – but it does not eliminate it. Most cases are spread from those who do not yet know they are HIV positive, before they would be treated, in any case. The changes in the rate of spread of HIV has to do with changing behavior, not treatment.
Maggiore and other HIV deniers are desperate to cast doubt on this now undeniable fact that treatments targeting HIV significantly prolong survival with HIV and AIDS. This is a major prediction of the HIV theory, and its confirmation is another nail in the coffin of HIV denial.
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