Surrogate markers for disease progression in treated HIV infection.
OBJECTIVE
To characterize the relationships among highly active antiretroviral therapy (HAART), HIV-1 RNA levels, immune system markers, and clinical outcome in a cohort of HIV-1-infected homosexual men.


METHODS
A total of 123 men enrolled in the Amsterdam cohort study of HIV-1 infection and AIDS with a documented seroconversion for HIV-1 antibodies and known date of seroconversion were included in this study.


METHODS
CD4 + /CD8 + T-cell counts and HIV-1 RNA levels in plasma were measured approximately every 6 months. Dates of starting and stopping antiretroviral therapy were also recorded. The relationship between HIV-1 RNA in plasma, CD4 + /CD8 + T-cell counts and HAART and their influence on clinical outcome were examined using a graphical chain modeling approach. Generalized estimating equations were used to examine correlations among the three disease markers. Hazards models with time-dependent covariates were used to examine the influence of HAART and the disease markers on progression to AIDS.


RESULTS
HAART was significantly associated with reduced disease progression (relative hazard [RH] of AIDS, 0.20;, 95% confidence interval [CI], 0.05-0.85). The most recent HIV-1 RNA measurement and CD4 + T-cell count are independently associated with disease progression (adjusted RH for HIV-1 RNA 1.8 per log 10 increase; 95% CI, 1.2-2.6, p =.002; adjusted RH for CD4 + 0.48 per 100 x 10(6)/L increase; 95% CI, 0.40-0.58; p <.001). Depending on these measurements, HAART was no longer significantly associated with AIDS (adjusted RH, 0.81; 95% CI, 0.18-3.6; p =.78).


CONCLUSIONS
HIV-1 RNA levels in plasma and CD4 + T-cell counts are currently considered as effective surrogate markers for the effect of HAART on disease progression in this cohort.
Ghani
A C
AC
Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College School of Science, Technology, and Medicine, London, UK. a.ghani@ic.ac.uk
de Wolf
F
F
Ferguson
N M
NM
Donnelly
C A
CA
Coutinho
R
R
Miedema
F
F
Goudsmit
J
J
Anderson
R M
RM
D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers / Q000097:blood*; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D015331:Cohort Studies; D018450:Disease Progression; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D006801:Humans; D008297:Male; D011379:Prognosis; D012367:RNA, Viral / Q000097:blood*; D019562:Viral Load
D015415:Biomarkers; D012367:RNA, Viral