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

M A Jacobson, P Bacchetti, A Kolokathis, R E Chaisson, S Szabo, B Polsky, G T Valainis, D Mildvan, D Abrams, J Wilber, M A Jacobson, P Bacchetti, A Kolokathis, R E Chaisson, S Szabo, B Polsky, G T Valainis, D Mildvan, D Abrams, J Wilber

Abstract

Objective: To determine whether early effects of zidovudine treatment on CD4+ lymphocyte count and concentrations of beta 2 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, beta 2 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 (v 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 beta 2 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 beta 2 microglobulin concentration could be surrogate end points for clinical outcome in trials of antiretroviral drugs for patients with HIV disease.

References

    1. N Engl J Med. 1989 Oct 26;321(17):1141-8
    1. J Exp Med. 1984 Jul 1;160(1):310-6
    1. J Infect Dis. 1988 May;157(5):1044-7
    1. J Acquir Immune Defic Syndr. 1989;2(3):291-6
    1. N Engl J Med. 1987 Jul 23;317(4):185-91
    1. N Engl J Med. 1987 Nov 19;317(21):1297-302
    1. Lancet. 1986 Jul 26;2(8500):177-80
    1. Br Med J (Clin Res Ed). 1988 Mar 12;296(6624):745-50
    1. J Infect Dis. 1989 Jun;159(6):1029-36
    1. J Acquir Immune Defic Syndr. 1989;2(3):229-34
    1. J Acquir Immune Defic Syndr. 1989;2(2):114-24
    1. N Engl J Med. 1989 Sep 14;321(11):726-38
    1. Science. 1989 Jul 21;245(4915):305-8
    1. N Engl J Med. 1989 Dec 14;321(24):1621-5
    1. Lancet. 1988 Feb 6;1(8580):298
    1. Arch Intern Med. 1988 Oct;148(10):2151-3
    1. JAMA. 1988 Nov 25;260(20):3009-15
    1. N Engl J Med. 1990 Jan 18;322(3):166-72
    1. Ann Intern Med. 1990 May 15;112(10):727-37
    1. Arch Intern Med. 1990 Jan;150(1):73-7

Source: PubMed

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

3
Abonner