TY - JOUR
T1 - HIV replication capacity is an independent predictor of disease progression in persons with untreated chronic HIV infection
AU - Goetz, Matthew Bidwell
AU - Leduc, Robert
AU - Wyman, Nicole
AU - Kostman, Jay R.
AU - Labriola, Ann M.
AU - Lie, Yolanda
AU - Weidler, Jodi
AU - Coakley, Eoin
AU - Bates, Michael
AU - Luskin-Hawk, Roberta
PY - 2010/4
Y1 - 2010/4
N2 - 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 ≥450 CD4+ cells per microliter and ≥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 ≤350 cells per microliter, treatment initiation, or death.
AB - 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 ≥450 CD4+ cells per microliter and ≥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 ≤350 cells per microliter, treatment initiation, or death.
KW - Disease progression
KW - HIV infections
KW - Natural history
KW - Replication
UR - http://www.scopus.com/inward/record.url?scp=77949402350&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77949402350&partnerID=8YFLogxK
U2 - 10.1097/QAI.0b013e3181cae480
DO - 10.1097/QAI.0b013e3181cae480
M3 - Article
C2 - 20032783
AN - SCOPUS:77949402350
SN - 1525-4135
VL - 53
SP - 472
EP - 479
JO - Journal of Acquired Immune Deficiency Syndromes
JF - Journal of Acquired Immune Deficiency Syndromes
IS - 4
ER -