[32] PREDICTORS OF IMMUNOLOGIC LONG-TERM NON-PROGRESSION IN HIV-INFECTED CHILDREN IN A PROSPECTIVE BIRTH COHORT

2nd International AIDS Society Conference on HIV Pathogenesis and Treatment

Paris, France - July 13 - 16, 2003

[TITLE:] PREDICTORS OF IMMUNOLOGIC LONG-TERM NON-PROGRESSION IN HIV-INFECTED CHILDREN IN A PROSPECTIVE BIRTH COHORT

[AUTHOR(S):] K McIntosh¹, C Mao¹, M Paul², M Charurat³ and W Shearer² for the Women and Infants Transmission Study (WITS)
¹Children's Hospital, Boston, MA, USA; ²Baylor College of Medicine, Houston, TX, USA; and ³Institute of Human Virology, Baltimore, MD, USA

IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 32
Antiviral Therapy 2003; 8(Suppl. 1):S192

[ABSTRACT:] Background: The identification of early markers that predict longterm nonprogression may help identify HIV-infected infants in whom antiretroviral therapy (ART) may be deferred. There are no comprehensive reports of long-term nonprogression in prospective paediatric cohorts followed from birth. In the WITS cohort, we defined immunologic intermediate- and long-term nonprogressors (IITNP and ILTNP) and then examined immunologic and virologic predictors.

Design and Methods: Changes in lymphocyte (L) phenotypes (CD3+CD4+, CD3+CD8+, CD8+HLA-DR+, CD8+CD38+, CD3-CD16+CD56+, CD19+, and CD3+) over the first 18 months of life were compared between 14 ILTNP, 27 IITNP, and 41 rapid progressors (RP). ILTNP were those who survived to ≥8 yrs with CD4 ≥25% or ≥500 without receiving HAART. IITNP survived to ≥5 yrs with CD4 ≥25% or ≥500 without receiving HAART, and no longer met criteria for ILTNP at 8 years. RP were children who died or showed severe immunosuppression (CD4 <15% or <500) by 18 months of age. Rates of change in L were estimated by repeated-measure regression taking into account correlation between individuals. All children were born before 1995.

Results: Differences in the distribution of L subpopulations occurred by 4 months of age for all phenotypes except CD19+. The most striking predictors of ILTNP were CD3+CD4+, CD8+CD38+, CD8+HLA-DR+, and CD16+CD56+. CD8+HLA-DR+ increased less rapidly after birth in ILTNP (1.1% per month) than RP (4.6% per month). CD16+CD56+ decreased markedly in ILTNP compared with RP (¨C0.9% vs +0.3% per month, P=0.001). Plasma HIV-1 RNA peaked at 2 months and decreased thereafter in all groups, but the rate of decline was 3-fold greater for ILTNP than RP (0.06 log vs 0.02 log per month, P<0.01).

Conclusions: The levels of L phenotypic markers, particularly activation markers, in the first 4 months of life may predict rapid progression in infants and allow identification of slow immunologic progressors who may not need immediate ART.

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