In the absence of highly active antiretroviral therapy (HAART), earlier studies showed that faster overall progression to AIDS came with increasing age, an effect noticeable after the age of 40. The rate of disease progression was also faster among younger children, especially newborn HIV-positive babies. The slowest rate of progression to AIDS was seen in teenagers.
In a meta-analysis of data from 38 studies that were done in the pre-HAART era, median survival varied from 12.5 years for those aged between 15 and 24 years at seroconversion to 7.9 years for those aged between 45 and 54 years at seroconversion. Development of AIDS occurred after a median of 11.0 years and 7.7 years respectively.1
One explanation given for this effect is that CD4 T-cells are replaced at a slower rate as age increases, largely because the thymus gland generates fewer new, naive CD4 T-cells. Another possibility is that, with increasing age, there are lower levels of chemokines to interfere with HIV’s ability to infect CD4 T-cells.
Since the introduction of HAART, some disparities in treatment response seem to have dissipated.2 In therapy-naive patients, one US study found that being over 50 years of age (range 50 to 77, median 55) was associated with a higher rate of achieving an undetectable viral load once HAART was initiated. The same level of CD4 cell increase and number of AIDS-defining illnesses were seen in groups under and over age 50.4 One other study reported that when HAART was available, there was no evidence indicating a difference in risk for survival or progression to AIDS according to age group.2
However, one prospective study of nearly 1500 patients did determine that age was the most important baseline predictor of a viral load >50 copies/ml at week 144 and that lower pretreatment viral load level and older age were both important predictors of time to a viral load level of >50 copies/ml.5
The COHERE study group (Collaboration of Observational HIV Epidemiological Research Europe), looked at the issue of age, including data drawn from nearly 50,000 HIV-positive people beginning ARV therapy, ranging in age from four days to 87 years, from 30 different European countries.
Pre-treatment CD4 counts were highest in the youngest patients and decreased steadily with age, in line with the pattern of CD4 count changes seen in non-infected people. Viral load levels started high in patients younger than two years, dropped to a low in patients aged 13 to 17, and rose again in adulthood. After a year of antiretroviral treatment, 54% of all patients experienced a good virologic response (viral load <50 copies/ml) and 59% had a CD4 cell increase of 100 cells/mm3 or greater.
After controlling for baseline disease state and other confounders, age was a predictor of response. The probability of a virologic response was lowest among those aged 6 to 17 years and highest in those aged 50 to 60 years, as compared to a reference group of patients aged 30 to 39 years. Those aged 13 to 29 were less likely than other age groups to have a good virologic response. This was partially attributed to adherence issues. Infants under age two made up a significant proportion of ‘fast progressors’ who experienced an AIDS-defining illness and rapid decline.
The proportion of people showing an improvement in CD4 cell counts was similar across age groups, but people over 40 were less likely than those under 40 to have a CD4 cell count >200 cells/mm3 at one year. The probability of immunological response was higher in those aged 17 years and younger and reduced in those aged 60 years or older. Disease progression, recorded as a new AIDS-defining illness or death, was more common among people over 40 years. After adjusting for most recent CD4 cell count, persons aged 55 or older had poorer clinical outcomes.6
In the reformulated EuroSIDA risk score (used to predict short-term clinical progression of patients on HAART), age is considered a risk factor for disease progression.3
One elegantly designed French study examined the impact of age on antiretroviral treatment response in 600 patients, 15% over the age of 50, diagnosed between 1996 and 2006. Overall, patients over 50 years tended to discontinue their first regimen earlier (6 months vs 14 months) because of side-effects. Older patients also experienced more neuropsychiatric side-effects and blood disorders than those aged under 50.
Patients over 50 were also more likely to be diagnosed late (defined as CD4 count <200 cells/mm3, 56 vs 45%). When this was the case, fewer older patients had an immunological response to treatment (19 vs 75%) and there was an elevated likelihood of clinical progression in the first six months of antiretroviral treatment.
However, in those who were not diagnosed late, after six months of antiretroviral treatment, there was no statistical difference in median CD4 cell count increase, viral load decrease, or clinical progression.7