The effect of zidovudine treatment on serum neopterin and β2- microglobulin levels in mildly symptomatic, HIV type 1 seropositive individuals

H. Z. Bass, W. D. Hardy, R. T. Mitsuyasu, J. M G Taylor, Xiao Wang Yong Xiao Wang, Margaret A Fischl, S. A. Spector, D. D. Richman, J. L. Fahey

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Abstract

Sixty-one subjects with mildly symptomatic human immunodeficiency virus (HIV) infection were included in a double-blind, randomized, placebo- controlled trial of zidovudine (part of AIDS Clinical Trials Group protocol 016, ACTG 016) to evaluate changes in the serum immune activation markers neopterin and β2-microglobulin (β2M) as early markers of the antiviral effect of zidovudine on HIV type 1 (HIV-1) infection. The mean values of serum neopterin and β2M levels in 27 placebo-treated subjects tended to increase with time. The mean value of neopterin in 34 subjects receiving zidovudine decreased at 4 weeks (15.76 nmol/L before treatment to 12.73 nmol/L, p = 0.001). The maximum reduction was seen at 8 weeks of treatment (10.78 nmol/L, p < 0.0001). Subsequently, the mean value of serum neopterin increased but remained below the pretreatment value for more than a year. Serum β2M levels decreased (from 3.01 to 2.69 mg/L at 4 weeks, p = 0.01) and reached the lowest level at 8 weeks (2.45 mg/L, p = 0.0002) in zidovudine recipients. The mean β2M level returned to pretreatment value at approximately 24 weeks of the treatment. There was a close correlation between changes from baseline in serum neopterin and β2M during the first 16 weeks of the zidovudine therapy, but not later. Subjects with greater reductions of serum neopterin or β2M tended to maintain lower levels of these markers with continued zidovudine administration. There was no statistical significance in the changes of CD4 lymphocyte numbers in this limited number of subjects, and the maximum neopterin and β2M changes were independent of the maximum CD4 T-cell changes. Thus, the serum activation markers provide independent measures of zidovudine effects. We conclude that measurement of serum immune activation markers (neopterin and β2M) can rapidly and sensitively reflect effects of zidovudine treatment. Zidovudine, on average, substantially (but only partially) reduced the immune activation caused by HIV infection.

Original languageEnglish
Pages (from-to)215-221
Number of pages7
JournalJournal of Acquired Immune Deficiency Syndromes
Volume5
Issue number3
StatePublished - Jan 1 1992

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Neopterin
Zidovudine
HIV-1
Serum
Virus Diseases
Therapeutics
Biomarkers
Placebos
HIV
Lymphocyte Count
Clinical Protocols
Antiviral Agents
Acquired Immunodeficiency Syndrome
Randomized Controlled Trials
Clinical Trials
T-Lymphocytes

ASJC Scopus subject areas

  • Virology
  • Immunology and Allergy

Cite this

The effect of zidovudine treatment on serum neopterin and β2- microglobulin levels in mildly symptomatic, HIV type 1 seropositive individuals. / Bass, H. Z.; Hardy, W. D.; Mitsuyasu, R. T.; Taylor, J. M G; Yong Xiao Wang, Xiao Wang; Fischl, Margaret A; Spector, S. A.; Richman, D. D.; Fahey, J. L.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 5, No. 3, 01.01.1992, p. 215-221.

Research output: Contribution to journalArticle

Bass, HZ, Hardy, WD, Mitsuyasu, RT, Taylor, JMG, Yong Xiao Wang, XW, Fischl, MA, Spector, SA, Richman, DD & Fahey, JL 1992, 'The effect of zidovudine treatment on serum neopterin and β2- microglobulin levels in mildly symptomatic, HIV type 1 seropositive individuals', Journal of Acquired Immune Deficiency Syndromes, vol. 5, no. 3, pp. 215-221.
Bass, H. Z. ; Hardy, W. D. ; Mitsuyasu, R. T. ; Taylor, J. M G ; Yong Xiao Wang, Xiao Wang ; Fischl, Margaret A ; Spector, S. A. ; Richman, D. D. ; Fahey, J. L. / The effect of zidovudine treatment on serum neopterin and β2- microglobulin levels in mildly symptomatic, HIV type 1 seropositive individuals. In: Journal of Acquired Immune Deficiency Syndromes. 1992 ; Vol. 5, No. 3. pp. 215-221.
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abstract = "Sixty-one subjects with mildly symptomatic human immunodeficiency virus (HIV) infection were included in a double-blind, randomized, placebo- controlled trial of zidovudine (part of AIDS Clinical Trials Group protocol 016, ACTG 016) to evaluate changes in the serum immune activation markers neopterin and β2-microglobulin (β2M) as early markers of the antiviral effect of zidovudine on HIV type 1 (HIV-1) infection. The mean values of serum neopterin and β2M levels in 27 placebo-treated subjects tended to increase with time. The mean value of neopterin in 34 subjects receiving zidovudine decreased at 4 weeks (15.76 nmol/L before treatment to 12.73 nmol/L, p = 0.001). The maximum reduction was seen at 8 weeks of treatment (10.78 nmol/L, p < 0.0001). Subsequently, the mean value of serum neopterin increased but remained below the pretreatment value for more than a year. Serum β2M levels decreased (from 3.01 to 2.69 mg/L at 4 weeks, p = 0.01) and reached the lowest level at 8 weeks (2.45 mg/L, p = 0.0002) in zidovudine recipients. The mean β2M level returned to pretreatment value at approximately 24 weeks of the treatment. There was a close correlation between changes from baseline in serum neopterin and β2M during the first 16 weeks of the zidovudine therapy, but not later. Subjects with greater reductions of serum neopterin or β2M tended to maintain lower levels of these markers with continued zidovudine administration. There was no statistical significance in the changes of CD4 lymphocyte numbers in this limited number of subjects, and the maximum neopterin and β2M changes were independent of the maximum CD4 T-cell changes. Thus, the serum activation markers provide independent measures of zidovudine effects. We conclude that measurement of serum immune activation markers (neopterin and β2M) can rapidly and sensitively reflect effects of zidovudine treatment. Zidovudine, on average, substantially (but only partially) reduced the immune activation caused by HIV infection.",
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