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).