Overproduction of immunoglobulins due to polyclonal B-cell activation is observed early in the course of HIV infection and levels may be related to outcomes. To assess prognostic significance, we analyzed the relationship of albumin/globulin ratio (AG) in early stage HIV infection with time of progression to AIDS among participants in the U.S. Military Natural History Study (NHS).
NHS, starting in 1986, is a longitudinal study of US military personnel and beneficiaries living with HIV. We retrospectively studied cases diagnosed with HIV from 1986 to 1995. Eligibility criteria included: 1) negative HIV test within 36 mos. preceding HIV diagnosis, 2) initial CD4 cell count ≥500/ul and albumin >3.5 g/dl within 90 days of diagnosis, 3) No evidence of viral hepatitis or liver disease. Cases were categorized by baseline AG quartiles. Outcome was diagnosis of AIDS according to CDC 1993 case definition including CD4 cell count <200 cells/ul. Subjects were censored by the earliest date of last visit, death, or starting combination antiretroviral medications available after 1995. Factors related to AIDS progression were analyzed by Cox regression and Kaplan-Meier methods.
364 participants were included in the analysis. Median follow-up was 7.4 yrs. Median (IQR) age was 26 (23,30) yrs. 94% were male, 52% Caucasian and 41% African-American. Median CD4 cell count was 670 (570, 841) and did not differ by AG quartile. Cases in the lowest quartile of baseline AG (≤1.11) had a shorter time to AIDS (median 8.1 vs. 10.3 yrs, p=0.04) compared to all others (Figure). In a multivariate Cox regression model, time to AIDS was associated with AG ≤1.11 (OR 1.75 [1.18-2.53]), and inversely associated with CD4 count per 100 cells (0.85 [0.78-0.94]) and use of dual NRTI therapy (0.24 [0.13-0.47]). Baseline viral load (VL) determinations were available for 111 subjects. When included in the multivariate model, progression to AIDS was associated with VL per log10 (1.80 [1.34-2.41]), age per 10 yrs (2.87 [1.34-6.17]), and AG<1.11 (1.80 [1.34-2.41]).
These data suggest AG ratio early in HIV infection is a risk factor for disease progression. B-cell dysfunction at this stage may be prognostically significant and independent of viral load.
A. Ganesan, None
J. Okulicz, None
T. Lalani, None
R. Deiss, None
B. Agan, None