Background:  The hemoglobin (Hg) level was consistently found to be associated with advanced HIV disease (both AIDS-defining illness and mortality) in multiple studies prior to the use of HAART, and in several studies in patients receiving HAART. We sought to determine its significance as a prognostic factor compared to CD4, CD4%, and HIV-1 RNA in HAART-treated patients.

Methods:  We conducted our analysis using laboratory and clinical data collected in HIV-infected patients from a cohort of HIV-infected patients in longitudinal HIV care at Johns Hopkins in Baltimore, Maryland. We determined all Hg-CD4-CD4%-HIV-1 RNA values obtained in all patients who started their first HAART regimen. Using negative binomial regression, we assessed the incidence rate ratio (IRR) of AIDS-defining illness and death for each Hg-CD4-CD4%-HIV-1 RNA value over a maximum of 6 months or until the next set of values was obtained. For each set of laboratory values, the median time until the next set of values was 95 days (range 14 to 181 days).

Results:  We analyzed 2168 Hg-CD4-CD4%-HIV-RNA sets from 1718 patients. There were 164 AIDS-defining illnesses and 399 deaths. The IRR for developing an AIDS-defining illness by Hg was 8.62 (95% confidence interval [CI]: 5.52, 13.3) events/100 person-years for < 10 g/dL, 7.31 (95% CI: 4.52, 11.7) for 10 to 11 g/dL, and 3.93 (95% CI: 2.44, 6.35) for 11 to 12 g/dL, compared with the reference group of >12 g/dL. The IRR for death by Hg was 15.6 (95% CI: 9, 96, 24.0) events/100 person-years for <10 g/dl, 8.41 (95% CI: 5.10, 13.9) for 10 to 11 g/dL, and 4.30 (95% CI: 2.61, 7.09) for 11 to 12 g/dL, compared with >12 g/dL. The Hg level was associated independently with a higher IRR for death and AIDS-defining illness when the CD4 was concurrently <50, 50 to 200, or >200 cells and for AIDS-defining illness when the CD4 was concurrently <50 and 50 to 200 cells. In a multivariable analysis adjusting for absolute CD4, CD4%, HIV-RNA, use of HAART, age, sex, race, injecting drug use status, Hg level was associated with an IRR of AIDS-defining illness/death of 4.8 (1.3, 6,.2) for Hg <10 g, 3.4 (2.3, 5.1) for Hg 10 to 11 g , 2.4 (1.6, 3.6) for Hg 11 to 12 g, compared with Hg >12 g.

Conclusions:  Our results indicate that Hg has a significant association with AIDS-defining illness and death over the subsequent 6 months. A low Hg appears to be as useful as the CD4 and other established prognostic factors for the short-term risk of developing an AIDS-defining illness or death. Hg may be a surrogate marker of immune-activation or cytokine-mediated processes not fully accounted for by the CD4, HIV-1 RNA level, and other measures.

Keywords: hemoglobin; prognostic factors; outcomes