Issues That Divide Expert Opinion: When to Start, HIV and Aging and the Impact of HIV on Life Expectancy
The JAIDS supplement on ageing referred to above, while acknowledging that ART dramatically extends life, also included the following provocative sentence in the opening paragraph of the reports executive summary: "On average, a 20-year old initiating ART may already have lost one-third of the expected remaining years of life compared with demographically similar HIV-uninfected populations,"3 based on a study by the Antiretroviral Therapy Cohort Collaboration (ART-CC) published in 2008.9
The conference in Glasgow included a session on HIV and life expectancy. The first of three presentations was an overview by Caroline Sabin from University College London.8 Given this ultimate outcome is such an important concern, it is notable that this may have been the first time this subject has been given a dedicated session in a conference programme.
Life expectancy, as an important indicator of health, is sometimes referred to from birth, but in the context of HIV is more often presented as additional life years in relation to age at diagnosis/infection. Other measures include:
With the durability of ART, several research groups have reported increasing levels of life expectancy, that now approach that of a similarly matched HIV negative general population. These include models from cohort studies (including ART CC and UK CHIC) estimating an additional 45-49 years of life expectancy for someone diagnosed at age 20 in a Western country with good access to care.9,10
A more recent model, published in AIDS earlier this year, extended life expectancy to 75 years (95%CI: 68-77) for a gay man diagnosed in 2010 at age 30 with a CD4 count of 430, losing approximately 7 years of life due to HIV. Life expectancy dropped to 71, if the CD4 count was 140 on diagnosis, losing approximately 10 years.11
These studies are broadly similar in reporting that the factors associated with longer life expectancy include calendar year, higher CD4 count, suppressed viral load, earlier presentation, fewer coinfections and in non-IDU populations. Adjustment for lifestyle factors may also account for the majority of the differences between HIV positive and general population estimates (approximately 8 out of the 11 year differences in a U.S. study). Gender, race, injecting drug use (IDU), late presentation and stopping treatment were all associated with greater differences.12
An analysis from more than 80,000 HIV positive people in the European COHERE cohort collaboration in 2012 reported that IDU (16% of the cohort) and low CD4 count explained most of the differences in life expectancy between HIV positive and HIV negative groups.13
Mortality rates became similar to those of the general population once CD4 counts reached >500 on treatment in non-IDU men [SMR 0.9; 95% CI 0.7-1.3], and in women after three years at this level (SMR 1.1, 95% CI 0.7-1.7). Of note, although mortality rates increased with age, excess mortality relating to HIV status significantly reduced with older age, with HIV positive MSM older than 60 years who haven't had a previous AIDS diagnosis achieving reduced SMR mortality compared to the matched general population.
However, mortality rates for the whole cohort remained four times higher than the general population (SMR for men: 3.8, for women: 7.4) at 1.2/100 person-years. Mortality for IDU was 13.1 times higher (95% CI 10.5-16.5) than in the general population, and by gender, results were 11.7 higher (95% CI 9.4-14.7) in men and 22.7 times (95% CI 18.0-28.7) higher in women. Mortality also remained elavated in IDU even with CD4 >500 (SMR 5.7; 95% CI 4.2-7.8). Although duration on treatment helped, even after five years, rates remained significantly increased.
Take as a whole, this returns the focus for ageing and life expectancy studies back to the difficulties of finding appropriate general population control groups. Within the UK, for example, average life expectancy can vary by 20 years depending on geographic region and even within London post codes can vary by greater than 10 years. Modifiable lifestyle factors are important, irrespective of HIV status.
Across all these studies, modelled estimates are dependent on extrapolating relatively short-term data. They may underestimate life expectancy by not accounting for future advances in treatment (think of the cure research) and overestimate it by not accounting for currently unknown future complications (whether from ART toxicity, drug resistance or the role of inflammation). Sabin summarised that life expectancy remains poorly explained for children and that the ageing population will clearly having important implications for the global epidemic.
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This article was provided by HIV i-Base. It is a part of the publication HIV Treatment Bulletin. Visit HIV i-Base's website to find out more about their activities, publications and services.
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