Declines in mortality rates and changes in causes of death in HIV-1-infected children during the HAART era.
BACKGROUND
Introduction of highly active antiretroviral therapy has significantly decreased mortality in HIV-1-infected adults and children. Although an increase in non-HIV-related mortality has been noted in adults, data in children are limited.


OBJECTIVE
To evaluate changes in causes and risk factors for death among HIV-1-infected children in Pediatric AIDS Clinical Trials Group 219/219C.


METHODS
Multicenter, prospective cohort study designed to evaluate long-term outcomes in HIV-1-exposed and infected US children. There were 3553 HIV-1-infected children enrolled and followed up between April 1993 and December 2006, with primary cause of mortality identified in the 298 observed deaths.


METHODS
Mortality rates per 100 child-years overall and by demographic factors; survival estimates by birth cohort; and hazard ratios for mortality by various demographic, health, and antiretroviral treatment factors were determined.


RESULTS
Among 3553 HIV-1-infected children followed up for a median of 5.3 years, 298 deaths occurred. Death rates significantly decreased between 1994 and 2000, from 7.2 to 0.8 per 100 person-years, and remained relatively stable through 2006. After adjustment for other covariates, increased risk of death was identified for those with low CD4 and AIDS-defining illness at entry. Decreased risks of mortality were identified for later birth cohorts, and for time-dependent initiation of highly active antiretroviral therapy (hazard ratio 0.54, P < 0.001). The most common causes of death were "End-stage AIDS" (N = 48, 16%) and pneumonia (N = 41, 14%). The proportion of deaths due to opportunistic infections (OIs) declined from 37% in 1994-1996 to 24% after 2000. All OI mortality declined during the study period. However, a greater decline was noted for deaths due to Mycobacterium avium complex and cryptosporidium. Deaths from "End-stage AIDS," sepsis and renal failure increased.


CONCLUSIONS
Overall death rates declined from 1993 to 2000 but have since stabilized at rates about 30 times higher than for the general US pediatric population. Deaths due to OIs have declined, but non-AIDS-defining infections and multiorgan failure remain major causes of mortality in HIV-1-infected children.
Brady
Michael T
MT
Nationwide Children's Hospital, Columbus, OH, USA. michael.Brady@nationalwidechildren's.org
Oleske
James M
JM
Williams
Paige L
PL
Elgie
Carol
C
Mofenson
Lynne M
LM
Dankner
Wayne M
WM
Van Dyke
Russell B
RB
D000293:Adolescent; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000401:mortality*; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy / Q000401:mortality*; D015497:HIV-1; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011446:Prospective Studies; D014481:United States / Q000453:epidemiology
D019380:Anti-HIV Agents