CD4+ and CD8+ lymphocytes and HIV RNA in HIV infection: high baseline counts and in particular rapid decrease of CD8+ lymphocytes predict AIDS.
OBJECTIVE
To study the progression of HIV infection in relation to immunological and virological variables with emphasis on the role of CD8+ lymphocytes.


METHODS
Prospective follow-up from October 1991 of patients observed for at least 18 months allowing nucleoside analogue monotherapy. Peripheral CD4+ and CD8+ lymphocyte counts, HIV RNA, and soluble CD8 were analysed by statistics allowing the evaluation of serial data, avoiding time points with concurrent infections.


METHODS
Tertiary university clinic.


METHODS
Forty-nine patients were followed for 52.6 months, baseline CD4+ count of 300 x 10(6)/l, sample interval of 5.9 months (medians).


METHODS
AIDS, death, and CDC groups B- or C-related events.


RESULTS
AIDS developed in 28% of patients. Baseline CD8+ counts above the median were significantly associated with AIDS development; the best Cox model included CD8+ cells and the log10RNA/CD4 ratio. A decline in CD8+ counts relative to baseline most significantly predicted AIDS, along with higher baseline RNA and actual CD4+ counts of less than 200 x 10(6)/l. Levels of soluble CD8 in the blood relative to total CD8+ cells significantly increased in patients developing AIDS. Death occurred in 16% of the patients, and was only predicted by high CD8+ cell counts at baseline. CDC B- and C-related events occurred in 35% of the patients and were best predicted by high baseline CD8+ counts and high RNA levels.


CONCLUSIONS
The serial quantitation of CD8+ lymphocytes gave highly significant predictive information on the natural progression of HIV infection in patients with moderate to severe immune deficiency. Our data suggest that the hyperactivation of CD8+ lymphocytes is an important factor leading to a numerical decrease of CD8+ lymphocytes in progressive HIV infection.
Kvale
D
D
Medical Department A and Research Institute for Internal Medicine, The National Hospital, Oslo, Norway. dag.kvale@klinmed.uio.no
Aukrust
P
P
Osnes
K
K
Müller
F
F
Frøland
S S
SS
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000503:physiopathology / Q000821:virology*; D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016827:CD8 Antigens / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood*; D017741:Survivors
D015415:Biomarkers; D016827:CD8 Antigens; D012367:RNA, Viral