The effect of age on CD4+ T-cell recovery in HIV-suppressed adult participants: a sub-study from AIDS Clinical Trial Group (ACTG) A5321 and the Bone Loss and Immune Reconstitution (BLIR) study

Table 4 Stepwise covariate analysis

Parameter	Covariate	P value		Coefficient
Forward Addition (α = 0.05)
σ [(cell/μL) • year^− 1]	No significant covariates	NA		NA
d_N (year • cell/μL)^− 1	Age	< 0.001		0.0467
d_M (year • cell/μL)^− 1	Sex (Female)	0.0039		−0.510
d_M (year • cell/μL)^− 1	Smoking Status (No prior smoking history)	0.019		0.573
α (year^− 1)	Age	0.046		0.0203
α (year^− 1)	%Activated CD4+ T-cells	0.042		0.228
baseline_N (cell/μL)	Viral load (log₁₀RNA/mL)	< 0.001		−0.636
baseline_N (cell/μL)	%Activated CD4+ T-cells	0.015		−0.446
baseline_M (cell/μL)	Viral load (log₁₀RNA/mL)	< 0.001		−0.388
	%Activated CD4+ T-cells	< 0.001		−0.396
	%Activated CD8+ T-cells	0.0091		0.249
Backward Elimination (α = 0.01)		P value	△IIV (%)
σ [(cell/μL) • year⁻¹]	No significant covariates	< 0.01	NA	NA
d_N (year • cell/μL)⁻¹	Age		−9.6	0.0389
d_M (year • cell/μL)⁻¹	Sex (Female)		−5.0	−0.597
α (year⁻¹)	No significant covariates		NA	NA
baseline_N (cell/μL)	Viral load (log₁₀RNA/mL)		−20	−0.648
baseline_M (cell/μL)	Viral load (log₁₀RNA/mL)		−17.3	−0.422
baseline_M (cell/μL)	%Activated CD4+ T-cells		−8.3	−0.378

σ: production rate of naïve T-cells, α: activation rate constant of naïve T-cells that acquire a memory phenotype, d_N: naïve T-cell death rate constant, d_M: memory T-cell death rate constant, baseline_N: naïve T-cell count at ART initial, baseline_M: memory T-cell count at ART initial, IIV: inter-individual variability, NA: not applicable. Parameter-covariate relations are described using a linear function, e.g. P_i = P • (1+ b * age), with P_i as the individual value, P as the population value and b as the covariate coefficient. Immune activation, presented as %CD38+/HLA-DR+ on the cells, are log-transformed

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