How Long a Life Now?

posted: 26/11/2009

Thanks to the success of HIV treatment, many people with HIV are now living into older age. But how long will HIV+ people live? What can people with HIV reasonably expect?

No-one can predict accurately how long anyone will live, with or without HIV. All we can do is look for people similar to us and use their life spans as a guide.
 

Health harms

HIV is not the only thing that affects how long people live. There are a huge number of things that make a difference, from the genes we inherit from our parents, to our lifestyles – our drinking, eating, exercise habits, our weight, work, where we live, our general health - as well as things outside our control, like our class background and pollution.

Still improving

We know that life expectancy with HIV is still rising. Treatments are improving and there are good new drug prospects in the pipeline. Clinics will become better at managing HIV for older people, with more experience. Whatever life expectancy is now with HIV, we can expect it to continue to stretch nearer towards the length of life for people without HIV.

Making life sense

The information in recent studies seems confusing, but here we try to make better sense of it. We are doing this for two reasons

• people with HIV have a right to know, and
• HIV prevention messages based on a shorter life may discourage risk-taking by some people who are undiagnosed / HIV negative.

Large studies for the answers

Large studies comparing thousands of people with HIV with the rest of the population can tell us part of the answer to the 'how long will people with HIV live?' question.

Into 60s and beyond

One recent large international study found evidence that people taking HIV treatment can now expect to live into their 60s and beyond. The study showed someone starting successful HIV treatment aged 20 would be expected to live to be 63, and that someone starting treatments aged 35 could live to the age of 67.

It also showed the dramatic and continued decline in the risk of early death amongst people with HIV since effective HIV treatment began.

Starting treatment on time makes the difference

Importantly the researchers found that starting treatment with a CD4 cell count above 200 cells/mm3 means a person aged 20 could expect to live to be 70, and that a 35 year-old could survive into their 72nd year. Current treatment guidelines are to start treatment significantly earlier than CD4 200, and start instead at CD4 350.

• Age 20, start treatment at CD4 350  > can expect to reach age 70
• Age 20, start treatment at CD4 200  > can expect to reach age 63
• Age 35, start treatment at CD4 350  > can expect to reach age 72
• Age 35, start treatment at CD4 200  > can expect to reach age 67

10 years less, but earlier treatment adds years

Even in their most optimistic estimates, in this study the life-expectancy of HIV-positive people is about ten years less than for people who are HIV-negative. People who inject drug users and those who start HIV treatment later than recommended have shorter lives than other people with HIV – 20 years shorter for injecting drug users.
 

These results are from the Antiretroviral Cohort Collaboration - 14 large HIV cohort studies in Canada, Europe and the USA, of over 43,000 patients.
 

Late diagnosis and late starting of treatment cuts years from lives. 35 year-olds, starting treatment when the CD4 cell count is below 100 cells/mm3 can expect to reach 62, 67 if they start treatment at CD4 of 200, and by starting when CD4 is 350 (as now recommended) adds 10 years of life - to reach 72 years.

Source for the above 

Over 60s: old age, not HIV, causes deaths
A more recent study looked at people over 60 who live with HIV.

This French study found that over a four-year period, one in seven of the group died – but not a single death was due to an AIDS-defining illness – people died of ordinary diseases of old age.

The COREVIH Cohort is small, and started in 2004 with 149 patients drawn from six HIV clinics in the Paris area. Their average age at the start was 65. About 1 in 10 were in their 80s, the oldest being 86.

The average time since HIV diagnosis was 8.5 years, but this ranged from two months to 19 years.

Source for the above

Not dying soon after infection

A third study looked at deaths within five years of starting treatments. This large European study found no evidence that people died more than normal in the first five years of infection.

The European CASCADE 23 cohort collaboration, compared rates of death amongst HIV-positive people to death rates in the matching general population. It looked at 16,534 HIV-positive people infected with HIV between 1980 and 2006.

Most were infected with HIV via sex with another man (57%), 24% were heterosexual transmissions and 18% through injecting drug use.

They found that early deaths rates have been falling, and are continuing to fall, as treatments have improved. There is now almost no difference in death rates, at least within the first 5 years of infection.

But after the first five years early deaths are still a small risk. About 5 extra deaths in the first ten years of HIV infection can be expected among every 100 people. Extra deaths are more likely if people inject drugs – in the first ten years of infection more than 6 extra deaths can be expected.

Source for the above

USA: 21 years less - compare with 10 years less in European study
A recent USA study estimates people with HIV will die 21 years earlier than someone without HIV. This is very different to the best estimate from the study that included Europeans that we started this article with - which suggested 10 years less life with HIV.

Over 22,000 newly diagnosed people, from 25 of the 50 USA States (but not the major HIV states of New York and California) were included in the study.

They worked out how many years of life are lost, compared with someone of the same age, sex and ethnicity in the general population.

On average, life expectancy after diagnosis increased from 10.5 years in 1996 to 22.5 years in 2005.

HIV-positive women, had a longer life expectancy than men (23.6 years for women in 2005, compared to 21.8 years for men).
 

Among men, white men had the greatest improvement in life expectancy. USA black men diagnosed in 2005 could expect to live five years less than white men.

HIV+ white men’s life expectancy in 2005 = 25.5 years after infection (up from 10.3 years in 1996).
HIV+ black men’s life expectancy in 2005 = 19.9 years after infection (was 9.5 years in 1996).
USA gay men do best - life-expectancy for gay and bisexual men was for 28.3 years after infection in 2005. 
 

Injecting drug users have the shortest life expectancy (15.2 years for men, and 15.9 years for women in 2005).
 

Black women in USA in the early 2000s had a 20.6 year life expectancy after infection, and white women could expect 22.6 years.

The headline from this is that HIV appears to cut a USA person with HIV’s life by 21 years. This is very different to the best estimate from the study including Europeans we started this article with - which offers 10 years less life with HIV.

21 years is not as bad as it looks at first. Perhaps a significant part of the 21 less years is due to lifestyle differences between the people in the two studies, not HIV.

People who get HIV in the USA are far more likely to have a history of drink and drug use, have hepatitis C, and significant socio-economic problems, than the general population.

And many people with HIV in the USA don’t get all the HIV healthcare and treatment they need – there is no free NHS.

This means in the UK people with HIV on average would not lose so many years life as in the USA.
 

In this USA study, men could expect to die an average of 19.1 years before similar HIV-negative men, but this varies with your age. A man diagnosed aged 20 would die 25 years early, a 40-year old 18 years early, and a 60-year old 10 years early.

HIV-positive women lived an average 22.7 years less than women in the general population, but again this varies with your age. A woman diagnosed aged 20 would die 31 years early, a 40-year old 21 years early, and a 60-year old 11 years early.

Source for the above

What's this all mean?

We began by saying life-span prediction is not exact. We have a choice of two large studies looking at the years HIV cuts from life.

The first study suggests a loss of 10 years life is the best we can expect at present, but the last study, from USA, suggests you might lose 21 years of life. 

The two studies in the middle looked at slightly different things - would HIV kill you within the first few years after infection (answer: very unlikely) and the second looked at the causes of deaths in over 60s with HIV (answer: caused by old age, not HIV).

We think the truth, for most people diagnosed in the UK, is near to a loss of 10 years life. But this loss will shrink even more, with better treatments and better care for older people with HIV.

Treat early for a longer, better life with HIV

The biggest lesson is that once you have HIV, starting treatment as early as is recommended (at a CD4 count of 350) and taking HIV treatments properly will make the biggest difference to life length.

After HIV treatment, make your lifestyle healthier to reduce the risks of age-related ill-health damage (from smoking, drinking, drugs, lack of exercise, inadequate diet etc).

image credit - Caution Life Ahead 

image credit - 10 years ArtsMark

image credit -  Lifespan

Further information - prognosis factsheet from aidsmap

Hepatitis C and HIV - Treatment Urgency

posted: 17/08/2009

The key importance of starting HIV treatment at CD4 count of 350 is emphasised in a new study into how AIDS illnesses follow hepatitis C infection when you also have HIV. Some people with HIV also have hepatitis C, particularly gay men, people with haemophilia, and people who have ever injected drugs. Hepatitis C virus causes serious liver damage in many people, and liver disease is now an important cause of illness and earlier death in people with both HIV and hepatitis C.
 

Now researchers have found that having both HIV and hepatitis C doubles the risk of developing AIDS-defining illnesses as well. People who have cirrhosis of the liver (whether this is caused by hepatitis, or drinking alcohol) are even more likely to get an AIDS condition. Hepatitis C makes having HIV significantly more risky and worse for people.

AIDS illnesses become more likely

Liver disease, often due to hepatitis C or drinking, is now an important cause of illness and death in people with HIV. Hepatitis C infection has been linked with an increased risk of non-Hodgkin’s lymphoma, which is an AIDS-defining illness. However, does hepatitis C increase the likelihood of other AIDS-defining illnesses?. Italian researchers decided to investigate hepatitis C and links with other AIDS conditions. They found the risk was doubled, and is even worse for people whose liver shows cirrhosis damage.

Starting HIV treatment at 350 CD4 is a key guide

They say the best time to start HIV treatment needs to consider this doubled risk of developing AIDS illnesses. British HIV treatment guidelines recommend that HIV treatment should be started when a person’s CD4 cell count is around 350. People with HIV and hepatitis C co-infection are especially encouraged to start taking anti-HIV drugs at this time. Treatment delay can damage people's life expectancy and health prospects quite quickly.

The editorial in the journal says the study “highlights and strengthens the need for careful follow-up of hepatitis C-HIV-co-infected patients, including preventative methods (screening, prophylaxis, and vaccination of preventable diseases), effective management of co-morbidities…and early and effective therapies against HIV and hepatitis C virus.”

NamLife has a useful section on HIV and hepatitis C and treatment.

NAM produces an information booklet called HIV & Hepatitis.

i-Base also have a new Hepatitis C guide for people living with HIV

Source
 

CD4 Counts in Ugandan Rainforest

posted: 14/04/2009

"When I arrived here, I saw people with HIV being carried all day to get to the clinic," Paul Williams recalls. There were no testing services, no education, no treatment and certainly no monitoring of treatment. People just died."
 

That was the situation in Bwindi, Uganda, three years ago. Dr Williams, formerly a GP in North-East England, has since transformed a tiny and very basic health centre on the edge of the rainforest into an efficient community hospital.

And for the past five months, thanks to a small but important piece of equipment, Dr Williams' medical team has been able to monitor the health of patients with HIV from a clinic that fits into the back of their four-wheel-drive "community ambulance".

Bwindi Community Hospital now provides health care for about 40,000 people.
It has a dedicated maternity programme and a children's ward that deals with many cases of malnutrition, as well as other common diseases including malaria and HIV. In total, the hospital takes care of 1,000 HIV positive patients.
 

Treating HIV in the rainforest
Dr Williams describes the environment in which he works: "We're a mile away from the rainforest where there are mountain gorillas, right on the border between Uganda and the Democratic Republic of Congo. "There aren't any tarmac roads here, there isn't any public transport, and lots of the patients live a day's walk from the hospital. Many of them live a subsistence existence and they can't afford to get here."

So his team packs an "HIV outreach clinic" into its vehicle, and takes it out to remote communities.Along with the rest of the equipment loaded into the back and strapped on to the roof of the ambulance, there is one modest-looking grey box.
 

Portable and practical fast CD4 testing machine vital
This piece of equipment is a PointCare NOW machine. It was donated to the hospital last year, and has since transformed the care Dr Williams can offer HIV patients. The machine is a portable blood-testing device - pop in a blood sample and, within 10 minutes, it gives a print-out detailing the condition of a patient's immune system. It counts CD4 positive T cells. These are the white blood cells that the HIV virus latches on to - attacking and destroying them.
 

"When we say someone has a weak immune system because of HIV, we mean their number of CD4 cells is low," explains Dr Williams. "During the course of infection, the number of these cells gets less and less - so you have to count them to see how advanced the HIV is."
 

The quest for practical, cheap, quick, easy CD4 counts
The machine was developed by PointCare, a USA company that specialises in diagnostic equipment for the developing world. It's an organisation with an sound pedigree. Petra Krauledat, and her long-time business partner Peter Hansen, founded the company in 2003, having both already had long and successful careers in HIV research.

"Peter invented the first automated CD4 test in the late 1970s, and I led the group in 1982, in Germany, that launched the first HIV screening test in Europe," explains Dr Krauledat.
In the 1990s they were approached by former colleagues who asked them to turn their attention to developing a much-needed, cheap CD4 test for the developing world.
 

"So we went to Southern Africa to talk to the [medics] actually working there," she says.
What they found surprised them both. "People showed us tonnes of donated instruments just sat in storage. The reagents [or chemicals needed to run the tests] had simply perished in the heat," she relates. "So 'cheap' wasn't people's biggest concern. What they needed was a test that could be used in a little shack of a clinic, transported to remote areas, and that could withstand the high temperatures. We've fulfilled that quest."
 

Surviving the heat
Dr Hansen invented a test that uses chemical reagent that can be freeze-dried and stored in temperatures of over 40C. CD4 screening tests use antibodies - molecular tags that recognise and latch onto a chemical marker on the surface of the cell. By attaching to the cells, they act as flags distinguishing CD4 cells from other white blood cells. But these antibodies need to be "labelled", so they can be detected by a machine.
 

Traditionally, antibodies are labelled using fluorescent markers, but these fluorescent chemicals perish if they are not kept refrigerated. So they're useless for a medical team operating from a temporary clinic in the heat of an African summer.
 

Nanotechnology gold
Dr Hansen developed a new “label”. "We use colloidal gold," explains Dr Krauledat. "It's true nanotechnology - extremely tiny gold particles attached to the anti-CD4 antibody."
The gold-bound antibodies are very heat-stable - they can be stored at over 42C for an entire year.
 

Immediate result
Inside the PointCare machine, the freeze-dried, gold-labelled antibody is liquefied and combined with the blood sample, and with a chemical accelerator that speeds up the attachment of the antibody to the cells. "How the accelerator works is a trade secret, but it allows us to complete the test within eight minutes," says Dr Krauledat.

"Before we had this machine, we'd see somebody in the clinic, then we'd have to see them on another day to collect a blood sample," recalls Dr Williams. We had a system of motorcycle riders that went round all of our outreach sites on a particular day to collect samples. They would have to ride for four hours along a muddy road through the rainforest, to a laboratory on the other side, where we could get them tested. It took us three days to get the result, and we couldn't get it back to the patient until we saw them again two weeks later. Now, with this simple piece of technology, we can deal with problems immediately."
 

The machine is also far cheaper to run than traditional instruments. It is powered by a battery pack. "Because we use colloidal gold, we have an instrument that doesn't consume a lot of power," explains Dr Krauledat. The standard technology [which uses fluorescently labelled antibodies] means they have to be detected with a laser, and those systems are quite fragile and consume more power. We use a [light-emitting diode] detector. It's technology with a lifetime of 180,000 days, doesn't break and it uses almost no power."
 

Complete picture given with 5 other blood counts
As well as a CD4 count, the device also counts five other subtypes of white blood cell. This gives a complete picture of the patient's immune system.
 

The results provide a physician with a good indication of whether an HIV positive patient might have tuberculosis, give a warning sign of other opportunistic infections, and find out if the patient has anaemia - a debilitating condition that is fairly common in the latter stages of HIV.
It also means that a patient's treatment can be monitored. "HIV treatment is great - anti-retroviral drugs can add up to 30 years to a person's life," says Dr Williams. But there are some people who develop resistance to the drugs, or in whom the drugs fail, and we can spot that early on to take action to be able to stop them from getting sick."
 

3 years has changed community's life prospects

In three years, Dr Williams and his team have transformed the lives of their HIV positive patients.
"I started a testing centre in the hospital, then the mobile testing services, and then, once we had access to drugs, developed a treatment programme. Now our death rates from HIV are very low. We're able to diagnose it early, manage it early and keep people living with HIV fit and well. Over a reasonably short period of time, we've been able to change HIV from being a death sentence into something that people can live with and lead productive lives."

Source

Report on the development of an easier and cheaper system for CD4 checks 
 

Start Treatment Earlier - USA Study

posted: 07/04/2009

A major USA study is recommending people should start treatment even earlier than now. The evidence indicates treatment should be started at a CD4 count of 500. Current UK guidleines are for treatment to start at about 350; the USA also has this start point.

A study showing improved survival of starting antiretroviral treatment earlier than current U.S. recommendations is being reported in the April 30 issue of the New England Journal of Medicine. The study found that not starting HIV patients at a CD4 count greater than 500 cells per cubic millimeter increased risk of death by 94 percent.

George House comment: Figures like this can look rather scary - the risk of death is almost doubled if the start of treatment is delayed to a CD4 level of 350, compared with starting at 500. But remember that the current start point for treatment in the UK is exactly this already, 350. And we see very few early deaths among people in this country who started treatment at 350 - the death rate from HIV has instead plummeted. A death rate twice as high doesn't much matter when the number of early deaths is already low, as it is for people who start treatment at the recommended time and reach an undetectable viral load. The chance of being killed by shark attack is very low. Even if the death rates for shark attacks double, it is still really unlikely. The same principle applies to HIV deaths in this country.

"The question of when to start antiretroviral therapy has been one of the key controversies in HIV care for over a decade" said University of Washington's Dr. Mari Kitahata, the lead researcher on the study. "Our study adds weight to the growing body of evidence that starting treatment earlier in HIV disease saves lives."

Current U.S. guidelines recommend treatment for asymptomatic patients who have a CD4 count of less than 350. However, these guidelines lack data from randomized clinical trials regarding the timing of antiretroviral therapy.

Since 1996, when potent antiretroviral therapy was introduced and recommended for asymptomatic HIV patients with a CD4 count less than 500 cells per cubic millimeter, there has been uncertainty about when to start treatment.

Almost 18,000 people studied

The article reports on two analyses of 17,517 asymptomatic patients with HIV infection receiving care between 1996 and 2006. The data were gathered through a recent collaboration of 22 research groups in more than 60 sites in the United States and Canada -- the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).

In order to study the impact of earlier initiation of therapy, researchers needed such a large number of patients at high CD4+ counts who are observed for a long period of time to a definitive endpoint of death. Because of the combined effort of one of the largest collaborations of HIV cohorts in the world, researchers had enough data to examine the effect of early HIV treatment.

study 1 - wait until CD4 falls below 350

Results from the first analysis were announced Oct. 2008 . Among the 8,632 patients with a CD4+ count+ 351 to 500, those who deferred antiretroviral therapy until the CD4+ count was below 350 had an increase of 69% in the risk of death.

study 2 - wait until CD4 falls below 500

Results from the second analysis were announced Feb 2009. Among the 9,155 patients with a CD4+ count above 500, those who deferred antiretroviral therapy until the CD4+ count was below 500 had an increase of 94% in the risk of death.

Recommendations for when to start antiretroviral therapy from around ten years ago used to delay the start of treatment until much later (a CD4 of 200) to avoid the development of drug resistance and because of significant side effects. Now treatment is much easier, drug resistance is of less concern, side effects are much reduced and better managed, and the evidence is that it makes much more sense to start therapy even earlier.

Benefits of earlier therapy are that immune system functioning is far better preserved, and you are more likely to get close to a normal CD4 count again, you become barely infectious and you can expect a near normal lifespan.

Mari Kitahata says "For years, we have started patients on HIV therapy when their immune systems were already compromised. It is becoming clear that early institution of antiretroviral therapy, before the immune system is heavily damaged, saves lives."

New England Journal of Medicine article

NEJM Editorial  

Source

Right Start for HIV Treatment

posted: 09/03/2009

British HIV treatment guidelines now say HIV treatment should start when the CD4 count of immune cells falls to about 350. Over recent years the time to start has been getting earlier and earlier - the first guidelines said treatment should start at CD4 200. Studies are now looking at whether HIV treatment should be started even sooner, perhaps when CD4 count is around 500.

Treatment starting sooner means people's immune system is left stronger and people are less likely to develop serious illnesses and poor health as a result of HIV in later years.

Mixed results

The first results from studies about starting treatment before the CD4 count falls below 350 are mixed.

A North American study found that people who started treatment with a CD4 count below 500 cells/mm3 had a 60% higher risk of death than people who started treatment above this level, but a collaborative study by European and North American cohorts failed to find any extra benefit of starting above 400 cells/mm3.

The second study found that while there was a clear benefit to starting treatment at a CD4 count in the range 350-450 cells/mm3 when compared with a lower count, starting treatment at CD4 count in the range 450-550 cells/mm3 did not provide a further benefit in terms of reducing the risk of AIDS or death.

Treatment guidelines in the developed world all agree that antiretroviral treatment should start around the time the CD4 cell count falls to 350 cells/mm3, although some groups of people, such as those with high viral load or with HIV/hepatitis C co-infection, should consider starting treatment before this point is reached.

However some physicians now believe that treatment should start considerably earlier, when the CD4 count is above 500 cells/mm3, in order to minimise the time during which individuals with HIV are immunosuppressed (the normal CD4 count in healthy adults is in the range of 700-1200 cells/mm3). Immunosuppression might increase the risk of some non-AIDS-defining cancers, which occur more frequently in people with HIV, and might also exacerbate the damage caused by hepatitis C infection, which appears to be more virulent and damaging to the liver in people with lower CD4 cell counts.

At last year’s ICAAC meeting US researchers presented an analysis of US and Canadian patient cohorts which showed a significant advantage to starting treatment before the CD4 count fell below 350 cells/mm3 (a 70% higher risk of death was identified in those who started treatment at a CD4 count below 350 cells/mm3 when compared to above 350 cells/mm3), but that study was not designed to determine whether starting treatment with a CD4 count above 500 cells/mm3 conferred additional benefit.

Does starting treatment at about 500 help?

In order to answer that question Mari Kitahata and colleagues from the North American AIDS Cohort Collaboration looked again at the 9174-patient cohort, and identified 2620 patients who had started treatment at a CD4 count above 500 cells/mm3, and compared their risk of death to those who started treatment later.

Their observational study attempted to mimic the conditions of a randomised trial by only including people who had been diagnosed with HIV at a CD4 count above 500 cells/mm3, in order to take into account the potential biasing effect of missing people who might die with a CD4 count below 500 cells/mm3 before starting treatment. Some previous studies have only looked at people who actually started treatment, and would thus have missed those most likely to die.

They found a 60% higher risk of death for those who deferred treatment (relative hazard 1.60, p<0.001), a highly significant effect, after controlling for potential confounding factors such as age and baseline viral load. They also found that older age was a significant predictor of death, independent of the CD4 count at which treatment was started.

After six years 10% of those who deferred treatment had died, and 15% by eight years, indicating that although the absolute risk of death was small, it was not negligible.

Maybe worthwhile

However, this study is still not able to answer the question of whether there is a significant difference between starting treatment in the CD4 count range of 350 to 500 cells/mm3, or starting at a CD4 count above 500 cells/mm3.

A second analysis, using data from 21,247 patients in seven cohorts, yielding 68,256 person-years of follow-up was carried out by the When to Start Consortium, led by Jonathan Sterne at Bristol University in the United Kingdom. That group compared the effects of deferring treatment across a range of CD4 cell bands below 550 cells/mm3, and found that while there was no significant difference in the risk of AIDS or death between those who started in the range 451-550 cells/mm3 and those who started in the range 351 to 450 cells/mm3 (HR 0.99, 95% CI 0.76 – 1.29), nor in the range 401-500 cells/mm3 compared to 301-400 cells/mm3 (HR 1.09, 95% CI 0.85 – 1.38), a significant difference was apparent in the range 351-450 cells/mm3 when compared to 251-350 cells/mm3 (HR 1.28, 95% CI 1.04 – 1.57).

This study also attempted to deal with the problem of deaths that might not be detected by a straightforward comparison of immediate versus deferred treatment, by estimating the rate of events seen at the CD4 counts being studied prior to the adoption of antiretroviral therapy, and then using the observed trends to fill in gaps where follow-up data were missing due to late diagnosis.

Different methods

It should be noted that the two analyses are not strictly comparable. The North American analysis measured only the risk of death, while the When to Start Consortium measured the risk of death or AIDS. Neither analysis was able to capture the risk of non-AIDS-defining serious illnesses, such as non-AIDS-defining cancers or cardiovascular events, which were detected at a higher frequency in individuals with CD4 counts below 350 cells/mm3 off treatment in the SMART treatment interruption study. Determining the relative risk of these serious illnesses is likely to be a factor in measuring the risk/benefit of earlier treatment, and in particular in determining whether the number needed to treat in order to avoid one event is sufficient to be cost-effective.

The findings sparked a lively debate at the conference about the feasibility of conducting a large 'when to start' trial. In particular, there was concern that the observational analyses might not be able to capture the effect of confounding factors.

As Andrew Zolopa of Stanford University noted, referring to the North American analysis: “Patients who choose to defer [antiretroviral treatment] have different health-seeking behaviours than those who start treatment earlier, who probably wear seat-belts, don’t smoke, etc.”.

However, said Mari Kitahata, the North American cohort analyses had attempted to determine the size of unknown confounding effect that would be necessary in order to affect the result. Any confounding factor would have to reduce the risk of death fourfold to change the result of the analysis, she said – a far greater effect than detected in this study.

Professor Doug Richman of the University of California San Diego questioned whether a 'when to start' trial was worth the expense. “Rather than spend millions on a trial, given that most people aren’t diagnosed until much later, why not use all that money to identify people who have the higher risk?”, he asked.

source and references