To the Editor: We(1) and others (2,3) have reported that increasing age at time of HIV-1 infection is associated with more rapid progression to AIDS. Later studies have shown that high plasma HIV-1 RNA levels are also correlated with more rapid progression to AIDS(4,5). We have now investigated whether age is associated with viral load. Such an association could explain the accelerating effect of increasing age on HIV-1 disease progression.
We obtained viral load evaluations (AMPLICOR HIV MONITOR Test, Roche Molecular Systems, Inc., Branchburg, NJ, U.S.A.) for a subset of 122 HIV-1-infected individuals(i.e., blood donors and transfusion recipients) described in our earlier study(1). Age at first viral load measurement ranged from 18 years to 80 years. Serum viral RNA level ranged from less than 2.3 to 5.6 log10 copies/ml. Eight persons whose RNA levels were below the manufacturer's recommended quantitation limit of 200 (2.3 log10) copies/ml were assigned a value of 2.3 for this analysis. The correlation coefficient between age and viral load was relatively weak (r = 0.21), but it was statistically significant (p = 0.02) (Fig. 1).
During follow-up, 33 persons developed AIDS. We used Cox regression analysis to investigate time from HIV-1 infection to AIDS diagnosis, with age and viral load as covariates. The date of infection for donors was estimated to be July 1983(1). For recipients, it was the date of transfusion with the known anti-HIV-1 positive component: the range was July 1984 through March 1985.
As seen previously, age was significantly associated with progression to AIDS, with the risk of AIDS increasing by approximately 3% per year of age (relative risk (RR) per year = 1.03, p = 0.005). The first viral load measurement was also significantly associated with rate of progression (RR per log10 copies = 4.27, p = 0.0001). The positive correlation between age and level of viral load, however, made it necessary to include both as covariates in the Cox regression analysis. There remained a relation between age and progression; the relative risk associated with age was reduced only modestly (RR = 1.02) and was marginally significant (p = 0.07). Viral load, however, remained very significant (RR = 3.68, p = 0.0001). When we analyzed time from first viral load measurement instead of time from infection, the results were similar. Viral load and age appear to be partly independent predictors of HIV progression, and viral load seems to account for little of the effect of age.
Because of the generally accepted prognostic importance of the CD4+ count, further analysis investigated the relations among CD4+ level, age, and viral load, using the CD4+ count at the time viral load was measured. There was a strongly significant negative correlation between the CD4+ count and viral load (correlation coefficient = −0.49, p < 0.0001). Adjusting for viral load in the regression analysis, the CD4+ values for subjects younger than 40 years of age were moderately higher than those for subjects 60 years or older at the same levels of viral load (∼18%, p = 0.11). These data suggest that younger persons tend to develop lower levels of viral load and to have less CD4 depletion at given viral loads.
It appears that younger persons may be able to mount a more effective immunologic response to HIV-1 infection, which is manifested by lower levels of viral load, higher levels of CD4+ cells, and less rapid progression to clinical AIDS. The effect of age on HIV-1 progression is complex and must be explained by factors other than a high viral load.
Acknowledgments: This study was supported by National Heart, Lung, and Blood Institute contracts No. HB-4-7002, 4-7003, and 9-7074.
*Eva A. Operskalski;*James W. Mosley;†Michael P. Busch;‡Daniel O. Stram; Transfusion Safety Study Group
*Department of Medicine University of Southern California Los Angeles, California
†Irwin Memorial Blood Centers and Department of Laboratory Medicine University of California San Francisco, California
‡Department of Preventive Medicine University of Southern California Los Angeles, California and other participating U.S. institutions
1. Operskalski EA, Stram DO, Lee H. et al. Human immunodeficiency virus type 1 infection: Relationship of risk group and age to rate of progression to AIDS. J Infect Dis
2. Eyster ME, Gail MH, Ballard JO. Al-Mondhiry H, Goedert JJ. Natural history of human immunodeficiency virus infections in hemophiliacs: effects of T-cell subsets, platelet counts, and age. Ann Intern Med
3. Blaxhult A, Granath F, Lidman K, Giesecke J. The influence of age on the latency period to AIDS in people infected by HIV through blood transfusion. AIDS
4. Mellors JW, Kingsley LA. Rinaldo CR, Todd JA, Hoo BS, Kokka RP, Gupta P. Quantitation of HIV-1 RNA in plasma predicts outcome after seroconversion. Ann Intern Med
5. Henrard DR, Phillips JF, Muenz LR, et al. Natural history of HIV-1 cell-free viremia. JAMA