IMMUNOLOGICAL MARKERS OF AIDS PROGRESSION - CONSISTENCY ACROSS 5 HIV-INFECTED COHORTS

Objective: To provide background on five HIV-infected cohorts with doc umented seroconversion times and serum immunoglobulin (Ig) A and beta( 2)-microglobulin (beta(2)M), CD4+ cell count and haemoglobin levels. T o give a relative risks (RR) regression summary of the prognostic valu e of serial CD4+ cell count, IgA, beta(2)M and haemoglobin measurement s for clinical AIDS, and to examine whether cofactors such as current age, sex and exposure category affect these RR. Design: The Multicohor t Analysis Project (MAP) workshop was an international collaboration w hich brought statisticians, immunologists and clinicians from the five cohorts to work together for 10 days. A predefined restricted databas e was made available by each cohort for the workshop. Setting: The Med ical Research Council (MRC) Biostatistics Unit, Cambridge, UK hosted t he MAP workshop from 19 to 30 April 1993. Subjects: MAP workshop datab ase comprised 1744 patients with documented HIV seroconversion times, with 407 women, over 900 injecting drug users (IDU) and over 500 homos exual men; 363 patients had AIDS and there were 308 deaths. Main outco me measures: Descriptive statistics on survival and progression to cli nical AIDS by cohort and exposure category, CD4+ cell count at AIDS di agnosis and pre-AIDS zidovudine therapy. RR summarizing the joint prog nostic significance of serial markers and cofactors such as age, sex a nd exposure category for progression to clinical AIDS. Results: Slower progression to AIDS for IDU [95% confidence interval (CI), 0.35-0.71] and heterosexuals (95% CI, 0.19-0.98) compared with homosexual men wa s confirmed after adjusting for current age-group and serial CD4+ cell counts. CD4+ cell counts at AIDS diagnosis were much higher among hom osexual men before than after 1988 (median, 150 and 90 x 10(6)/l, resp ectively). Little zidovudine use was observed among AIDS cases diagnos ed before 1988 (2%) but increased use was recorded after 1988 and 1989 (24%) and even greater use after 1990 (59%). Low serial CD4+ cell cou nt, haemoglobin levels and high serum IgA and beta(2)M levels were ass ociated with an increased risk of progression to AIDS. CD4+ cell count always provided prognostic information in addition to other markers; IgA and beta(2)M (95% CI, 1.23-1.50 and 105-1.51, respectively) were j ointly prognostic. beta(2)M did not provide significant extra informat ion (95% CI, 0.91-1.47) to the combination of serial CD4+ cell count a nd IgA, although haemoglobin did (95% CI: 0.74-0.91 for 10 g/l increas e in haemoglobin). Interactions between cofactors, particularly exposu re category and serial markers, were used to test for modifications in RR. The association between AIDS risk and serial CD4+ cell count was weaker, and with-elevated IgA stronger, for homosexual men; RR associa ted with high beta(2)M Values were lower for IDU, in whom beta(2)M may be elevated for reasons other than HIV disease. Conclusions: IgA and beta(2)M, which can be measured in small volumes of stored blood, are jointly predictive of progression to AIDS. Results were broadly consis tent between cohorts representing different age-groups, seroconversion periods and exposure categories. Some regression effect modifications by exposure category were noted, however, which merit further indepen dent study.