Surrogate markers for survival in patients with AIDS and AIDS related complex treated with zidovudine

Mark A. Jacobson, Peter Bacchetti, Antonia Kolokathis, Richard E Chaisson, Susan Szabo, Bruce Polsky, Gregory T. Valainis, Donna Mildvan, Donald Abrams, Judith Wilber, Edward Winger, Henry S. Sacks, Carol Hendricksen, Andrew Moss

Research output: Contribution to journalArticle

Abstract

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 (υ 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.

Original languageEnglish (US)
Pages (from-to)73-78
Number of pages6
JournalBMJ (Online)
Volume302
Issue number6768
StatePublished - Jan 12 1991

Fingerprint

AIDS-Related Complex
Zidovudine
Acquired Immunodeficiency Syndrome
Biomarkers
Survival
CD4 Lymphocyte Count
Neopterin
Serum
HIV Core Protein p24
HIV Antibodies
Kaplan-Meier Estimate
Proportional Hazards Models
Multicenter Studies
Therapeutics
Retrospective Studies
Outcome Assessment (Health Care)
HIV
Antigens
Antibodies

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Jacobson, M. A., Bacchetti, P., Kolokathis, A., Chaisson, R. E., Szabo, S., Polsky, B., ... Moss, A. (1991). Surrogate markers for survival in patients with AIDS and AIDS related complex treated with zidovudine. BMJ (Online), 302(6768), 73-78.

Surrogate markers for survival in patients with AIDS and AIDS related complex treated with zidovudine. / Jacobson, Mark A.; Bacchetti, Peter; Kolokathis, Antonia; Chaisson, Richard E; Szabo, Susan; Polsky, Bruce; Valainis, Gregory T.; Mildvan, Donna; Abrams, Donald; Wilber, Judith; Winger, Edward; Sacks, Henry S.; Hendricksen, Carol; Moss, Andrew.

In: BMJ (Online), Vol. 302, No. 6768, 12.01.1991, p. 73-78.

Research output: Contribution to journalArticle

Jacobson, MA, Bacchetti, P, Kolokathis, A, Chaisson, RE, Szabo, S, Polsky, B, Valainis, GT, Mildvan, D, Abrams, D, Wilber, J, Winger, E, Sacks, HS, Hendricksen, C & Moss, A 1991, 'Surrogate markers for survival in patients with AIDS and AIDS related complex treated with zidovudine', BMJ (Online), vol. 302, no. 6768, pp. 73-78.
Jacobson MA, Bacchetti P, Kolokathis A, Chaisson RE, Szabo S, Polsky B et al. Surrogate markers for survival in patients with AIDS and AIDS related complex treated with zidovudine. BMJ (Online). 1991 Jan 12;302(6768):73-78.
Jacobson, Mark A. ; Bacchetti, Peter ; Kolokathis, Antonia ; Chaisson, Richard E ; Szabo, Susan ; Polsky, Bruce ; Valainis, Gregory T. ; Mildvan, Donna ; Abrams, Donald ; Wilber, Judith ; Winger, Edward ; Sacks, Henry S. ; Hendricksen, Carol ; Moss, Andrew. / Surrogate markers for survival in patients with AIDS and AIDS related complex treated with zidovudine. In: BMJ (Online). 1991 ; Vol. 302, No. 6768. pp. 73-78.
@article{5b8aac39f88043c094c357eb7cda27c3,
title = "Surrogate markers for survival in patients with AIDS and AIDS related complex treated with zidovudine",
abstract = "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 (υ 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.",
author = "Jacobson, {Mark A.} and Peter Bacchetti and Antonia Kolokathis and Chaisson, {Richard E} and Susan Szabo and Bruce Polsky and Valainis, {Gregory T.} and Donna Mildvan and Donald Abrams and Judith Wilber and Edward Winger and Sacks, {Henry S.} and Carol Hendricksen and Andrew Moss",
year = "1991",
month = "1",
day = "12",
language = "English (US)",
volume = "302",
pages = "73--78",
journal = "British Medical Journal",
issn = "0959-8146",
publisher = "BMJ Publishing Group",
number = "6768",

}

TY - JOUR

T1 - Surrogate markers for survival in patients with AIDS and AIDS related complex treated with zidovudine

AU - Jacobson, Mark A.

AU - Bacchetti, Peter

AU - Kolokathis, Antonia

AU - Chaisson, Richard E

AU - Szabo, Susan

AU - Polsky, Bruce

AU - Valainis, Gregory T.

AU - Mildvan, Donna

AU - Abrams, Donald

AU - Wilber, Judith

AU - Winger, Edward

AU - Sacks, Henry S.

AU - Hendricksen, Carol

AU - Moss, Andrew

PY - 1991/1/12

Y1 - 1991/1/12

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 (υ 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 (υ 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.

UR - http://www.scopus.com/inward/record.url?scp=0025959470&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025959470&partnerID=8YFLogxK

M3 - Article

C2 - 1671651

AN - SCOPUS:0025959470

VL - 302

SP - 73

EP - 78

JO - British Medical Journal

JF - British Medical Journal

SN - 0959-8146

IS - 6768

ER -