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M94A2376.TXT
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1994-10-25
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Document 2376
DOCN M94A2376
TI Quantitative measures of p24/gp41 and p24 HIV antibody as predictors of
progression to AIDS: evidence for effect modification by zidovudine.
DT 9412
AU Strathdee SA; Frank J; Leblanc M; McLaughlin J; Major C; Le TN; Read SE;
Dept. Prev. Med. & Biostat, U of Toronto, Canada.
SO Int Conf AIDS. 1994 Aug 7-12;10(1):318 (abstract no. PC0204). Unique
Identifier : AIDSLINE ICA10/94370199
AB OBJECTIVE: To date, the manner in which HIV-specific antibody (Ab)
levels are treated in statistical models has been generally
non-quantitative. This study determined the potential of serial
quantitative measures of HIV Ab as predictors of progression to AIDS in
a cohort of homosexual men. METHODS: Reflectance densitometry was used
to provide quantitative measures of HIV Ab from Western Blotting of
serial serum specimens provided at quarterly intervals from 159 HIV+ men
in the Toronto Sexual Contact Study, which observed 50 AIDS cases from
'84-'91. Cox relative risk (RR) regression was used to predict risk of
progression to AIDS, where HIV Ab and other laboratory markers were
either fixed values at enrollment, or time-dependent covariates (TDC)
which were continuously updated. Zidovudine (ZDV) and the presence of
OIs were treated as binary TDC. Since the clinical relevance of HIV Ab
was of primary interest, time was measured from enrollment. Ab levels
were expressed in terms of optical density (OD x mm), as a ratio
relative to the corresponding standard positive control, per 0.1 unit
decline. RESULTS: Quantitative measures of p24 and p24/gp41 Ab ratio
were independent predictors of progression. Both markers remained highly
significant in multivariate models which treated Ab levels as fixed or
TDC and controlled for the effects of other markers listed below. Final
models considering TDC included either p24/gp41 Ab ratio (RR = 2.27, 95%
CI: 1.01, 5.26) or p24 Ab (RR = 1.12, 95% CI: 1.01, 1.21), while
controlling for CD4/CD8 ratio, age, OIs, and ZDV use (RR = 0.28, 95% CI:
0.11, 0.71). However, a significant time-dependent interaction was
observed between ZDV use and p24 Ab, or ZDV and p24/gp41 Ab ratio,
rendering the main effects non-significant. CONCLUSIONS: These data
demonstrate that quantitative measures of p24 Ab and p24/gp41 Ab may be
useful markers of future risk of progression to AIDS. Although these
data are observational and should be interpreted with caution due to
selection factors associated with ZDV use, these data suggest that the
benefits provided by ZDV use are modest if levels of p24 Ab or p24/gp41
Ab ratio are already declining. Such data could potentially be of use in
clinical decision-making regarding ZDV therapy.
DE Acquired Immunodeficiency Syndrome/DRUG THERAPY/*IMMUNOLOGY
AIDS-Related Opportunistic Infections/IMMUNOLOGY Cohort Studies
CD4-CD8 Ratio Homosexuality Human HIV Antibodies/*ANALYSIS HIV Core
Protein p24/*IMMUNOLOGY HIV Envelope Protein gp41/*IMMUNOLOGY Male
Zidovudine/*THERAPEUTIC USE MEETING ABSTRACT
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).