HIV replication capacity is an independent predictor of disease progression in persons with untreated chronic HIV infection.
OBJECTIVE
To assess the effect of pol replication capacity (RC) on the hazard ratio of progression to a composite endpoint of time to progression to <350 CD4+ cells per microliter, initiation of therapy, or death.


METHODS
pol RC assays were performed after study closure in baseline samples obtained from 316 enrollees in a prospectively monitored cohort of treatment-naive adults with >or=450 CD4+ cells per microliter and >or=1000 HIV-1 RNA copies per milliliter.


RESULTS
The median RC was 79%. Patients with a lower RC had a lower median viral load (4.0 vs 4.2 Log HIV-1 RNA copies/mL, P = 0.026) and a lower rate of protease inhibitor resistance 2% vs 8%, P = 0.03). Otherwise, baseline demographic and laboratory characteristics were similar. The hazard ratio of progression to the composite endpoint was 0.73 (P = 0.041) for persons with lower RC, 2.07 per 1.0 log10 higher viral load (P < 0.001), and 0.86 per 50 cells per microliter higher CD4+ cell count (P < 0.001). The effect of lower RC was also significant in a separate analysis of time to initiation of therapy (P = 0.04).


CONCLUSIONS
These results show that untreated patients with lower vs higher RC had a slower rate of progression as assessed by a composite outcome of time to CD4+ count <or=350 cells per microliter, treatment initiation, or death.
Goetz
Matthew Bidwell
MB
Department of Medicine, Veterans Affairs Greater Los Angeles Healthcare System and David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. matthew.goetz@va.gov
Leduc
Robert
R
Wyman
Nicole
N
Kostman
Jay R
JR
Labriola
Ann M
AM
Lie
Yolanda
Y
Weidler
Jodi
J
Coakley
Eoin
E
Bates
Michael
M
Luskin-Hawk
Roberta
R
D000328:Adult; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000201:enzymology* / Q000502:physiology*; D006801:Humans; D008297:Male; D014779:Virus Replication; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
D054302:pol Gene Products, Human Immunodeficiency Virus