Somatic growth and laboratory markers of HIV disease progression in children in the Women and Infants Transmission Study (WITS)

Jack Moye, MD, CRMC, PAMAB, NIH, NICHD, Bldg 6100 Rm 4B11H MSC 7510, 9000 Rockville Pike, Bethesda, MD 20892-7510, 301-496-7339, moyej@exchange.nih.gov, Margaret Frederick, PhD, Clinical Trials & Surveys Corp., 2 Hamill Rd, Ste 350, West Quadrangle, Baltimore, MD 21210-1874, Caroline Chantry, MD, Medical Center, University of California Davis, Ticon II, Room 338, 2516 Stockton Boulevard, Sacramento, CA 95817, Edward Handelsman, MD, DAIDS, TRP, NIH, NIAID, Bldg 6700B, Rm 5107 MSC 7624, 9000 Rockville Pike, Bethesda, MD 20892-7624, Delmyra Turpin, MSN, Dept. of Pediatrics -- M/C 856, Univ. of Illinois -- Chicago, 840 South Wood St, Rm 1410 CSB, Chicago, IL 60612, Mary Paul, MD, Texas Children's Hospital - M/C FC330.01, Baylor College of Medicine, 6621 Fannin St, Houston, TX 77030-2600, and Samuel Adeniyi-Jones, MD, PhD, DAIDS, PSB, NIH, NIAID, Bldg 6700B, Rm 4133, MSC 7628, 9000 Rockville Pike, Bethesda, MD 20892-7626.

BACKGROUND: With expanding antiretroviral (ARV) access worldwide, efforts are ongoing to identify surrogates for HIV-specific disease progression markers in areas of limited resources. OBJECTIVES: To evaluate the relation of readily obtained anthropometric measurements to CD4+ T-lymphocyte and viral load (VL) measures in HIV infected children. METHODS: 132 infected children were studied. Routine anthropometric measurements were made by trained examiners every 6 months through age 10. CD4+ T-lymphocytes and HIV RNA were measured by laboratories with approved performance in the NIAID/DAIDS QA program. Prediction equations were generated by generalized estimating equation and spline modeling. Growth failure was defined as z-score <-2 or change <-1.4. ARV treatment was categorized as HAART (>2 drugs of >1 class), combination (>1 drug not HAART), monotherapy, or none. RESULTS: Values of selected parameter estimates are shown below.

Weight .

Height .

%CD4

Log₁₀RNA

%CD4

Log₁₀RNA

Intercept

34.2

5.69

36.6

5.37

Growth velocity (g or cm/d)

0.155#

-0.005

29.3#

1.52

Growth failure

-2.81+

0.113

-3.29#

0.272#

HAART

4.10*

-1.20*

4.56*

-1.21*

Combination

-0.518

-0.166

0.201

-0.180

Monotherapy

1.32

-0.092

1.037

-0.120

*p<=0.001; #0.001<p<=0.01; +0.01<p<0.05

The model predicts, for example, that %CD4=26 in a 54 mo child on no ARV with height growth velocity 0.0357 cm/d and no growth failure; actual measured %CD4=25. CONCLUSIONS: Velocity of growth in weight or height may predict relative CD4 count but not VL when treatment is accounted for. Easily obtained growth measures may be useful proxies in pediatric treatment decisions where ready and reliable CD4 or VL measurements are not available yet.

Learning Objectives: At the conclusion of the session, the participant (learner) in this session will be able to

	Weight .		Height .
	%CD4	Log₁₀RNA	%CD4	Log₁₀RNA
Intercept	34.2	5.69	36.6	5.37
Growth velocity (g or cm/d)	0.155#	-0.005	29.3#	1.52
Growth failure	-2.81+	0.113	-3.29#	0.272#
HAART	4.10*	-1.20*	4.56*	-1.21*
Combination	-0.518	-0.166	0.201	-0.180
Monotherapy	1.32	-0.092	1.037	-0.120

*p<=0.001; #0.001<p<=0.01; +0.01<p<0.05