Response to combination antiretroviral therapy: variation by age.
OBJECTIVE
To provide information on responses to combination antiretroviral therapy in children, adolescents and older HIV-infected persons.


METHODS
Multicohort collaboration of 33 European cohorts.


METHODS
: Forty-nine thousand nine hundred and twenty-one antiretroviral-naive individuals starting combination antiretroviral therapy from 1998 to 2006.


METHODS
Time from combination antiretroviral therapy initiation to HIV RNA less than 50 copies/ml (virological response), CD4 increase of more than 100 cells/microl (immunological response) and new AIDS/death were analysed using survival methods. Ten age strata were chosen: less than 2, 2-5, 6-12, 13-17, 18-29, 30-39 (reference group), 40-49, 50-54, 55-59 and 60 years or older; those aged 6 years or more were included in multivariable analyses.


RESULTS
The four youngest age groups had 223, 184, 219 and 201 individuals and the three oldest age groups had 2693, 1656 and 1613 individuals. Precombination antiretroviral therapy CD4 cell counts were highest in young children and declined with age. By 12 months, 53.7% (95% confidence interval: 53.2-54.1%) and 59.2% (58.7-59.6%) had experienced a virological and immunological response. The probability of virological response was lower in those aged 6-12 (adjusted hazard ratio: 0.87) and 13-17 (0.78) years, but was higher in those aged 50-54 (1.24), 55-59 (1.24) and at least 60 (1.18) years. The probability of immunological response was higher in children and younger adults and reduced in those 60 years or older. Those aged 55-59 and 60 years or older had poorer clinical outcomes after adjusting for the latest CD4 cell count.


CONCLUSIONS
Better virological responses but poorer immunological responses in older individuals, together with low precombination antiretroviral therapy CD4 cell counts, may place this group at increased clinical risk. The poorer virological responses in children may increase the likelihood of emergence of resistance.
Sabin
Caroline A
CA
Smith
Colette J
CJ
d'Arminio Monforte
Antonella
A
Battegay
Manuel
M
Gabiano
Clara
C
Galli
Luisa
L
Geelen
Sibyl
S
Gibb
Diana
D
Guiguet
Marguerite
M
Judd
Ali
A
Leport
Catherine
C
Dabis
François
F
Pantazis
Nikos
N
Porter
Kholoud
K
Raffi
Francois
F
Thorne
Claire
C
Torti
Carlo
C
Walker
Sarah
S
Warszawski
Josiane
J
Wintergerst
Uwe
U
Chene
Genevieve
G
Lundgren
Jens
J
D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005060:Europe / Q000453:epidemiology; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000821:virology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D016019:Survival Analysis; D016896:Treatment Outcome; D019562:Viral Load
D019380:Anti-HIV Agents; D012367:RNA, Viral