Reduction in mortality with availability of antiretroviral therapy for children with perinatal HIV-1 infection. Italian Register for HIV Infection in Children and the Italian National AIDS Registry.
BACKGROUND
Since the introduction of combined antiretroviral therapy, mortality rates in adults with human immunodeficiency virus type 1 (HIV-1) infection have decreased. However, little information is available outside the setting of controlled trials on survival of perinatally HIV-infected children treated with antiretroviral therapy.


OBJECTIVE
To assess effect of availability of antiretroviral therapy on decreasing mortality in perinatally HIV-infected children.


METHODS
Population-based, multicenter longitudinal study involving data collected by the Italian Register for HIV Infection in Children.


METHODS
A network of 106 pediatric clinical centers.


METHODS
A total of 1142 children born between November 1980 and December 1997 with perinatally acquired HIV infection with a median follow-up of 5.9 years.


METHODS
Time to HIV-related death calculated for birth cohort and calendar period and grouped by distribution of predominant type of antiretroviral therapy administered over time.


RESULTS
Survival was longer in the 1996-1997 birth cohort (crude relative hazard [RH] of death, 0.39; 95% confidence interval [CI], 0.15-0.96) and 1996-1998 calendar period (crude RH of death, 0.65; 95% CI, 0.45-0.95) than in birth cohort and calendar period 1980-1995, but not when adjusted for maternal antiretroviral treatment during pregnancy and clinical condition at time of delivery, gestational age, and birth weight (adjusted RH of death, 0.55; 95% CI, 0.20-1.50, for birth cohort; and adjusted RH of death, 0.71, 95% CI, 0.43-1.16, for calendar period). In a multivariate model with 1980-1995 as comparison, the 1996-1997 birth cohort had an RH of 0.57 (95% CI, 0.22-1.47; P=.27) but RH for calendar period 1996-1998 was 0.63 (95% CI, 0.47-0.85; P<. 01). When the effects of birth cohort, calendar period, and type of antiretroviral therapy were evaluated simultaneously in the same model, the RH of death was not significantly different from 1.0 for the 1996-1997 birth cohort (P=.19) and calendar period 1996-1998 (P=. 83) suggesting a causal relationship between decreased risk of death and use of combination therapy. The RH of death in children receiving monotherapy or double or triple combination therapy was 0. 77 (95% CI, 0.55-1.08), 0.70 (95% CI, 0.42-1.17), and 0.29 (95% CI, 0.13-0.67), respectively, vs no antiretroviral therapy.


CONCLUSIONS
Survival of perinatally HIV-infected children improved in 1996-1998 as a result of the introduction of combined antiretroviral therapies. JAMA. 2000;284:190-197
de Martino
M
M
Department of Pediatrics, University of Florence, via Luca Giordano 13, I-50132 Florence, Italy. mdm@ao-meyer.toscana.it
Tovo
P A
PA
Balducci
M
M
Galli
L
L
Gabiano
C
C
Rezza
G
G
Pezzotti
P
P
D000293:Adolescent; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality* / Q000635:transmission; D006679:HIV Seropositivity; D015497:HIV-1; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D007558:Italy / Q000453:epidemiology; D008137:Longitudinal Studies; D008297:Male; D015999:Multivariate Analysis; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D016016:Proportional Hazards Models; D012042:Registries; D016019:Survival Analysis
D019380:Anti-HIV Agents