TY - JOUR
T1 - Surrogate markers for survival in patients with AIDS and AIDS related complex treated with zidovudine
AU - Jacobson, M. A.
AU - Bacchetti, P.
AU - Kolokathis, A.
AU - Chaisson, R. E.
AU - Szabo, S.
AU - Polsky, B.
AU - Valainis, G. T.
AU - Mildvan, D.
AU - Abrams, D.
AU - Wilber, J.
AU - Winger, E.
AU - Sacks, H. S.
AU - Hendricksen, C.
AU - Moss, A.
PY - 1991
Y1 - 1991
N2 - Objective - To determine whether early effects of zidovudine treatment on CD4+ lymphocyte count and concentrations of β2 microglobulin, neopterin, or HIV p24 antigen or antibody are correlated with survival in patients with AIDS or AIDS related complex. Design - Retrospective study of changes in laboratory markers and survival. Setting - Multicentre trial at university hospital clinics. Subjects - 90 Patients with AIDS or AIDS related complex. Intervention - Patients started zidovudine 200 mg orally every four hours. Fifty six of the patients died a median 17 months after starting zidovudine; the remaining 34 patients were followed up for a median 25.5 months. Main outcome measures - Changes in CD4+ lymphocyte count and serum concentrations of p24 antigen and antibody, β2 microglobulin, and neopterin; survival of the patient. Results - The pretreatment characteristics that independently predicted poor survival were determined using a multivariate proportional hazards model: a diagnosis of AIDS (ν AIDS related complex), age over 45 years, and the logarithm of serum neopterin concentration. When these baseline characteristics were controlled for the logarithm of CD4+ lymphocyte count at weeks 8-12 of treatment (p = 0.007) and an increase in serum β2 microglobulin concentration at weeks 8-12 (p = 0.05) also independently correlated with survival. In the 38 patients with a better pretreatment prognosis, 24 month survival estimated by the product-limit method was 88% for those with a good response on both surrogate markers during early treatment compared with only 50% for those with a poor response on either marker. In the 38 with a worse pretreatment prognosis, 24 month survival was estimated to be 49% for those with a good response on both surrogate markers compared with only 18% for those with a poor response on either. Conclusion - These data suggest that CD4+ lymphocyte count at 8-12 weeks and, perhaps, change in serum β2 microglobulin concentration could be surrogate end points for clinical outcome in trials of antiretroviral drugs for patients with HIV disease.
AB - Objective - To determine whether early effects of zidovudine treatment on CD4+ lymphocyte count and concentrations of β2 microglobulin, neopterin, or HIV p24 antigen or antibody are correlated with survival in patients with AIDS or AIDS related complex. Design - Retrospective study of changes in laboratory markers and survival. Setting - Multicentre trial at university hospital clinics. Subjects - 90 Patients with AIDS or AIDS related complex. Intervention - Patients started zidovudine 200 mg orally every four hours. Fifty six of the patients died a median 17 months after starting zidovudine; the remaining 34 patients were followed up for a median 25.5 months. Main outcome measures - Changes in CD4+ lymphocyte count and serum concentrations of p24 antigen and antibody, β2 microglobulin, and neopterin; survival of the patient. Results - The pretreatment characteristics that independently predicted poor survival were determined using a multivariate proportional hazards model: a diagnosis of AIDS (ν AIDS related complex), age over 45 years, and the logarithm of serum neopterin concentration. When these baseline characteristics were controlled for the logarithm of CD4+ lymphocyte count at weeks 8-12 of treatment (p = 0.007) and an increase in serum β2 microglobulin concentration at weeks 8-12 (p = 0.05) also independently correlated with survival. In the 38 patients with a better pretreatment prognosis, 24 month survival estimated by the product-limit method was 88% for those with a good response on both surrogate markers during early treatment compared with only 50% for those with a poor response on either marker. In the 38 with a worse pretreatment prognosis, 24 month survival was estimated to be 49% for those with a good response on both surrogate markers compared with only 18% for those with a poor response on either. Conclusion - These data suggest that CD4+ lymphocyte count at 8-12 weeks and, perhaps, change in serum β2 microglobulin concentration could be surrogate end points for clinical outcome in trials of antiretroviral drugs for patients with HIV disease.
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U2 - 10.1136/bmj.302.6768.73
DO - 10.1136/bmj.302.6768.73
M3 - Article
C2 - 1671651
AN - SCOPUS:0025959470
SN - 0959-8146
VL - 302
SP - 73
EP - 78
JO - British medical journal
JF - British medical journal
IS - 6768
ER -