Two studies presented at the 17th Conference on Retroviruses and Opportunistic Infections (CROI) show that some groups of patients – those diagnosed recently, or some of those with high CD4 counts when they begin treatment – will have normal or near-normal life expectancies.
These are not the first studies to calculate normal life expectancies for some groups of patients, but they are based on larger cohorts and extend the expectation of a normal lifespan to a broader group of patients.
Dutch patients not diagnosed late should live near-normal lifespans
The first study, from the Dutch ATHENA Cohort, took a sample of 4612 patients, newly diagnosed between 1998 and 2007, and measured their death rate for, on average, the next 3.3 years. The only patients excluded from the cohort were those who had to start antiretroviral therapy (ART) less than six months after diagnosis or who had an AIDS-defining illness in the first six months. Patents in the study could start ART after six months.
This study, therefore, includes a large proportion of the newly diagnosed patients in the Netherlands over a nine-year period, except the sickest, which makes its findings even more surprising.
The average CD4 count 24 weeks after diagnosis was 480 cells/mm3, with 75% of patients having a CD4 count over 350 cells/mm3.
During the study 118 patients died, indicating an annual mortality rate of 0.67% a year (one death in 150 patients a year). The only predictors, at 24 weeks, of death in the next few years were HIV-related but not AIDS-defining symptoms, coming from somewhere other than developed countries or sub-Saharan Africa, and age – there was a doubling in the risk of death for every 14 years older at diagnosis.
This mortality rate enabled the researchers to compute life expectancies. For a patient diagnosed at the age of 25 the life expectancy came out at 52.7 years – in other words they would die, on average, at the age of 77.7. This was scarcely different to the life expectancy for 25 year olds in the general Dutch population – 53.1 years.
Men and women diagnosed aged 25 could expect to live just five months less than HIV-negative people and men diagnosed at age 55 would live 1.3 years less (women 1.5 years less). For patients diagnosed with HIV (but not AIDS) symptoms the figure was two years shorter for men and women diagnosed at 25, and six and 7.5 years shorter for men and women respectively diagnosed at 55.
The researchers comment: “The life expectancy of asymptomatic HIV-infected patients who are still treatment-naive and have not experienced [an HIV or AIDS-defining symptom] at 24 weeks after diagnosis approaches that of age and gender-matched uninfected individuals.”
They note that the follow-up time was short and that the predictions depend on ARV treatment continuing to work, and it is again worth emphasising that this study excludes the large proportion of patients who are late-diagnosed.
…and so will European men achieving CD4 counts over 500 and not using drugs
The second study involved a much bigger group of 80,642 patients from 30 European countries and was a study, not of the newly diagnosed, but of all patients in the group initiating ART after 1998. It found that men who were not injecting drug users and who had a current CD4 count over 500 were no more likely to die during the follow-up period than their HIV-negative equivalents.
A study of the French Aquitaine Cohort reported a similar finding in 2005, but in this study Aquitaine is only one of 25 patient cohorts that combined to make a new European ‘super-cohort’ called COHERE. It’s important to note that the geographical spread was very uneven, ranging from only 19 patients in Ireland to 30,000 in France (and 11,000 in the UK).
The median age at ART initiation was 37, at which point the average CD4 count was 225 cells/mm3. During a median follow-up time of 3.5 years, 3813 patients died.
The study computed the annual mortality rate for patients with CD4 counts under 200 cells/mm3; between 200 and 350; between 350 and 500; and over 500.
These were 3.9%, 0.8%, 0.5% and 0.4% respectively.
The researchers then computed the Standard Mortality Ratio (SMR). This measures how much higher the mortality rate in each group is compared with HIV-negative people of the same sex and age.
The SMR for all patients with a CD4 count under 200 was 13.0, and for the other CD4 strata it was 3,0, 1.8 and 1.5.
So for the patient group as a whole, being HIV positive raised the risk of death by 50%, even in those who had CD4 counts over 500 cells/mm3.
However, for men, in those who maintained a CD4 count over 500 cells/mm3 for at least three years, the SMR was 1.0 and it was also 1.0 if current or ex-injecting drug users (IDUs) were excluded. These groups had the same life expectancy as their HIV-negative peers.
In IDUs the SMR for those with high CD4 counts was 4.5, within a wide margin of uncertainty, but this declined to 3.0 after five years maintaining high counts.
The absolute annual death rate for women was actually lower than for men. For instance it was 4.2% in men with CD4 counts under 300 cells/mm3 and 3.0% in women, and 0.4% and 0.2% respectively in men and women with counts over 500 cells/mm3.
But because the death rate in HIV-negative women is lower than in men, the SMRs for HIV-positive women were higher: it was 2.2 for women with CD4 counts over 500 cells/mm3 (1.5 excluding IDUs). This excess 50% SMR rate in women probably reflects that women with HIV have relatively lower socioeconomic status than HIV-negative women, whereas in positive men the wealth gap is not so large.