HIV-1 pol replication capacity predicts disease progression.
OBJECTIVE
To determine the influence of pol replication capacity on the natural history of HIV-1 infection.


METHODS
Pol replication capacity was measured using a recombinant virus single cycle assay on baseline plasma specimens from subjects enrolled in the Hemophilia Growth and Development Study.


METHODS
Children and adolescents with hemophilia and HIV-1 infection were enrolled at multiple sites across the USA into a natural history study.


METHODS
The Hemophilia Growth and Development Study enrolled 207 HIV-1-infected hemophiliacs between 6 and 19 years of age in 1989 and 1990. Subjects were followed every 6 months through 1997 with pol replication capacity measurements available from 128 of the subjects.


METHODS
A univariate model defined the relationship between pol replication capacity and HIV-1 RNA and CD4 T-cell number. A random effects model assessed the ability of this measure to predict CD4 T-cell decline over time and a Cox proportional hazards model and Kaplan-Meier analyses defined how it predicts clinical progression.


RESULTS
Pol replication capacity measures correlated with baseline HIV-1 RNA, R = 0.189 (P = 0.03) and CD4 T-cell number, -0.197 (P = 0.03). It also independently predicted CD4 T-cell decline over time and progression to AIDS.


CONCLUSIONS
This study demonstrates that pol replication capacity independently influences the natural history of HIV-1 infection.
Daar
Eric S
ES
Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center and the David Geffen School of Medicine at UCLA, Torrance, California 90502, USA. EDaar@LABioMed.org
Kesler
Karen L
KL
Wrin
Terri
T
Petropoulo
Christos J
CJ
Bates
Michael
M
Lail
Alice
A
Hellmann
Nicholas S
NS
Gomperts
Edward
E
Donfield
Sharyne
S
D000293:Adolescent; D000328:Adult; D018791:CD4 Lymphocyte Count; D002648:Child; D018450:Disease Progression; D004812:Epidemiologic Methods; D015751:Genes, pol; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D006467:Hemophilia A / Q000150:complications; D006801:Humans; D008297:Male; D012367:RNA, Viral / Q000235:genetics; D019562:Viral Load; D014779:Virus Replication
D012367:RNA, Viral