How old you are determines, in part, how you respond to HIV therapy, according to the results of a vast cohort study including almost 50,000 HIV-positive people. The results, published in the July 31st issue of the journal AIDS, confirms that older people generally have better viral suppression than their younger counterparts, but often show a poorer immune response. Young people with HIV face different challenges, from rapid disease progression during infancy to relatively poor adherence during adolescence.
Evidence of the impact of age on response to antiretroviral therapy is inconsistent and scarce. Studies comparing younger and older adults show contradictory effects on virologic and immunologic response. And no study has compared the effect of antiretroviral treatment on children versus adults.
One reason for the paucity of data is the difficulty in obtaining sufficient numbers of participants at different ages to provide statistically sound results. In 2005, in response to a need for large cohorts for epidemiological studies, researchers formed the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) study group, a collaboration of 33 observational cohort studies in 30 European countries.
The COHERE database includes over 250,000 HIV-positive people of ages spanning over eight decades and so provides an ideal resource for studying the effects of age on response to HIV treatment. For the current study, investigators searched the database for records of patients starting anti-HIV drugs for the first time. They grouped the records by age and then assessed virologic response, immune response and clinical progression within each group.
Children and adolescents were divided as under two years, two to five years, six to twelve years and 13 to 17 years. Adults were divided as 18 to 29 years, 30 to 39 years (the reference group) and 40 to 49 years. Older adults were divided as 50 to 54 years, 55 to 59 and 60 and older.
The final study cohort included 49,921 records, with patients ranging in age from four days to 87 years. 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 age 13 to 17 and rose again in adulthood.
By 12 months after starting treatment, 54% of all patients had experienced a virologic response, measured as a viral load below 50 copies/ml, and 59% had experienced an immunologic response, seen as an increase in CD4 counts of at least 100 cells/mm3. “Although responses to [combination antiretroviral therapy] were reasonable across all age groups,” the investigators write, “age was a predictor of many of the outcomes considered, even after controlling for [pre-treatment] disease stage and other known confounders.”
Advancing age had a clear impact on both virologic and immunologic response. Among people aged 40 and older, virologic response was higher than among younger people. This group was between 18% and 24% more likely to have an undetectable viral load at one year, compared with the reference age 30 to 39. However, improved virologic response did not translate into improved immunologic responses. In fact, the proportion of people showing an improvement in CD4 cell counts was similar across age groups. What is more, people over 40 were less likely than their younger counterparts to have a CD4 cell count above 200 cells/mm3 at one year.
A poorer immunologic response might leave older people more vulnerable to other infections. “These poorer responses,” the investigators write, “coupled with lower [pre-treatment] CD4 cell counts, suggest that older individuals are at greater risk of experiencing clinical events, a hypothesis that was confirmed in our study.” Disease progression, recorded as a new AIDS-defining infection or death, was more common among people over 40 years.
In contrast with their older counterparts, younger people had a weak virologic response and a stronger immunologic response. Only 34 to 40% of children younger than six years had a virologic response to treatment. That same group showed a good immunologic response, with 72 to 82% showing an increase of at least 100 CD4 cells/mm3, though the investigators highlight proper analysis was hampered by the naturally high level of CD4 cells and subsequent decline seen in childhood.
Despite the immunologic response, the very youngest in this group, infants less than two years, also showed significant disease progression. The investigators note that a significant proportion of infants were ‘fast progressers’ who had an AIDS-defining event before age two and that these infants may have a rapid decline even while receiving antiretroviral therapy.
Investigators noted that older children, adolescents and young adults were also less likely to show a virologic response. This, they suggest, may be due to the instability seen in the lives of people of this age. Approximately 15% of those aged 13 to 29 years stopped taking all medications during the first twelve months, a rate twice as high as that among younger children and older adults. A lack of virologic response may lead to the development of drug resistance, which is of particular concern among these young people, who face a lifetime of HIV therapy.
Investigators see great potential for the study’s findings. HIV affects people of all ages, and knowing how best to care for people at different stages of life would represent a significant advance. “These findings are of clinical importance,” the investigators conclude, “as they may permit treatment guidelines (particularly relating to the timing of initiation of HAART and frequency of subsequent patient monitoring) to be targeted to specific age groups.”
The COHERE Study Group. Response to combination antiretroviral therapy: variation by age. AIDS 22:1463 – 1473, 2008.