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Session 120 Poster Abstracts
Morbidity and Mortality of HIV-1 Infection
Monday, 1:30 - 3:30 pm
Poster Hall


869    
Use of Total Lymphocyte Counts and Hemoglobin Concentration for Monitoring Progression to AIDS
B Lau*1, S Gange1, J Phair2, S Riddler3, R Detels4, J Margolick1, and Multicenter AIDS Cohort Study
1Johns Hopkins Univ., Baltimore, MD, USA; 2Northwestern Med. Sch., Chicago, IL, USA; 3Univ. of Pittsburgh, PA, USA; and 4Univ. of California, Los Angeles, USA

Background: Prognostic markers for HIV disease besides CD4+ lymphocyte counts and plasma viral load are needed for resource-limited regions.  Total lymphocyte counts (TLC) and plasma hemoglobin levels have been shown to decline rapidly prior to AIDS, but the prognostic value of these markers and their declines for predicting AIDS has not been well examined in a prospective, natural history setting.

Methods: Data were examined among 297 seroconverters in the Multicenter AIDS Cohort Study (MACS), a prospective cohort study with semi-annual visits since 1983. Using data prior to 1996, we identified the first time TLC declined by more than 33% per year and, separately, the first time hemoglobin declined by more than 11.6% per year, values previously identified as maximizing sensitivity and specificity for predicting AIDS. The prognostic value of these markers and their declines was evaluated by Cox regression models with time-varying covariates to examine the relative hazard (RH) for progressing to AIDS.

Results:  A TLC <1200 cells/mm3, the WHO recommendation for initiation of therapy when CD4 counts are not available, predicted progression to AIDS (RH = 6.14; 95%CI:  4.33, 8.71).  A rapid decline in either TLC or hemoglobin was also significantly associated with progression to AIDS (RH = 4.70 [3.23, 6.86] and 5.55 [3.69, 8.36], respectively).  When present along with TLC <1200 cells/mm3, a rapid decline in either TLC or hemoglobin was strongly associated with progression to AIDS (RH = 11.30 [7.39, 17.31] and 21.19 [12.43, 36.12], respectively). A faster time to AIDS was seen among those with more rapid marker declines. The relationship of TLC and hemoglobin with the incidence of AIDS remained significant after adjusting for HIV RNA concentration albeit with an attenuated relative hazard. After adjusting for CD4+ count, TLC decline was no longer associated with developing AIDS, but hemoglobin decline remained a significant predictor.

Conclusions: In the MACS, a rapid decline in either total lymphocyte count or hemoglobin concentration indicated an increased likelihood of progression of HIV infection to AIDS.  These results support the utility of these markers for monitoring HIV-infected people in resource-limited regions.

Keywords: Markers of disease progression; Biomarkers; Natural History