Prospective longitudinal analysis of viral load and surrogate markers in relation to clinical progression in HIV type 1-infected persons.
The temporal relationship between viral and surrogate markers and clinical status was analyzed prospectively every 8 weeks in 34 asymptomatic HIV-1-infected persons. After 3 years, 25 persons remained clinically healthy whereas 9 persons showed clinical progression. In accordance with other reports we found that at study entry HIV-RNA load was predictive of clinical progression. All markers tested evolved significantly in time in both progressors and nonprogressors. The HIV RNA load in plasma and HIV DNA load in T cells were linearly related only in nonprogressors. In addition, the RNA/DNA ratio during follow-up was significantly higher in progressors, indicating a higher replication rate in progressors. The HIV DNA load correlated inversely with CD4+ T cell counts and positively with p24 antigenemia in both nonprogressors and progressors. A significant correlation of HIV DNA load with SI phenotype occurred in progressors only. HIV RNA levels correlated with beta 2-microglobulin level and with p24 antigenemia but not with SI phenotype. These three markers can all routinely be measured in plasma; however, only the HIV RNA levels appear to be informative for clinical progression. Six to 8 months before clinical progression, an SI phenotype switch, increased HIV RNA in plasma, and decreased CD4+ T cell counts were all indicative of an impending clinical event.
Bruisten
S M
SM
Department of Clinical Viro-Immunology, Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, Amsterdam, The Netherlands.
Frissen
P H
PH
Van Swieten
P
P
Harrigan
P R
PR
Kinghorn
I
I
Larder
B
B
Weigel
H M
HM
De Vries
E
E
Regez
R M
RM
Henrichs
J H
JH
Koot
M
M
Huisman
J G
JG
D000328:Adult; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D018450:Disease Progression; D005500:Follow-Up Studies; D016655:HIV Core Protein p24 / Q000097:blood*; D015658:HIV Infections / Q000097:blood / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D006801:Humans; D008137:Longitudinal Studies; D016555:Matched-Pair Analysis; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012367:RNA, Viral; D013997:Time Factors; D001613:beta 2-Microglobulin / Q000032:analysis*
D016655:HIV Core Protein p24; D012367:RNA, Viral; D001613:beta 2-Microglobulin