Relations among CD4 lymphocyte count nadir, antiretroviral therapy, and HIV-1 disease progression: results from the EuroSIDA study.
BACKGROUND
The effect of previous CD4 cell count nadir on clinical progression in patients with increases in CD4 cell counts has not been investigated.


OBJECTIVE
To assess risk for progression of HIV disease in patients with CD4 counts of at least 200 cells/mm3 (stratified by the lowest previous CD4 count) and compare the rate of progression in patients with CD4 counts less than 50 cells/mm3 with that in patients whose CD4 counts rebounded from less than 50 cells/mm3 to at least 200 cells/mm3.


METHODS
Prospective, observational multicenter study.


METHODS
52 HIV outpatient clinics in Europe.


METHODS
Two groups were identified: those with CD4 counts of at least 200 cells/mm3 (group A) and those with CD4 counts less than 50 cells/mm3 (group B). Group A was stratified according to the lowest previous CD4 count: at least 150 cells/mm3 (stratum 1), 100 to 149 cells/mm3 (stratum 2), 50 to 99 cells/mm3 (stratum 3), and 1 to 50 cells/mm3 (stratum 4).


METHODS
Patients were followed until a progression event occurred (first AIDS-defining event, new AIDS-defining event, or death) or until the CD4 count decreased to less than 200 cells/mm3 (group A) or increased to more than 50 cells/mm3 (group B). Incidence rates were based on a patient-years analysis and reported as events per 100 patient-years of follow-up; the relative hazards for progression were based on Cox proportional hazards models.


RESULTS
The overall rate of disease progression in group A was 3.9 per 100 patient-years (95% CI, 3.5 to 4.3 per 100 patient-years), whereas in group B it was much higher (72.9 per 100 patient-years [CI, 69.0 to 76.8 per 100 patient-years]). In group A, the rate increased in patients with previous low CD4 cell count nadirs, resulting in a significant increase in the relative hazard for progression. The relative hazards for strata 2, 3, and 4 were 2.29 (CI, 1.30 to 4.03), 3.65 (CI, 1.94 to 6.85), and 2.94 (CI, 1.44 to 6.00), respectively.


CONCLUSIONS
Increases in CD4 counts from very low levels to at least 200 cells/mm3 are associated with a much reduced rate of disease progression. However, a previously low CD4 cell count nadir remains associated with a moderately higher risk for disease progression among patients with CD4 counts of at least 200 cells/mm3.
Miller
V
V
J.W. Goethe-Universität, Zentrum der Inneren Medizin, Frankfurt, Germany. miller@em.uni-frankfurt.de
Mocroft
A
A
Reiss
P
P
Katlama
C
C
Papadopoulos
A I
AI
Katzenstein
T
T
van Lunzen
J
J
Antunes
F
F
Phillips
A N
AN
Lundgren
J D
JD
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D016867:Immunocompromised Host; D008297:Male; D016016:Proportional Hazards Models; D011446:Prospective Studies
D019380:Anti-HIV Agents