Quantification of HIV-1 virus load under zidovudine therapy in patients with symptomatic HIV infection: relation to disease progression.
OBJECTIVE
To measure changes in HIV-1 virus load following zidovudine therapy, and to investigate the relationship between these changes and clinical progression.


METHODS
Prospective study of 18 symptomatic, zidovudine-naive patients, with CD4 count < 350 x 10(6)/l.


METHODS
The following parameters were measured at each visit, before zidovudine therapy, after 1 month of therapy, and every 3 months thereafter. HIV-1 virus load in peripheral blood was determined by serum immune complex-dissociated HIV-1 p24 antigen (ICD-p24 Ag), quantitative plasma and cellular viraemia. A virologic response under zidovudine was defined as > 50% decrease in ICD-p24 Ag levels or > 1 log10 decrease in plasma or cellular viraemia titres from baseline values. CD4 and CD8 cell counts, and beta 2-microglobulin levels were also measured. Disease progression was defined as the time to a new AIDS-defining event or death.


RESULTS
At enrolment, 13 out of 18 (72%) patients had positive ICD-p24 Ag and positive plasma viraemia, with a mean of 44 median tissue culture infective dose (TCID50) per ml; all patients had positive cellular viraemia with a mean TCID50 of 230 per 10(6)/l cells. Median CD4 cell count was 43 x 10(6)/l. Ten patients developed a new AIDS-defining event and eight died during a median follow-up of 15 months on zidovudine. Baseline prognostic markers for development of a new AIDS-defining event included ICD-p24 Ag, CD4 and CD8 cell counts, but only CD4 cell count remained predictive on multivariate analysis (P = 0.003). When each laboratory marker was analysed as a time-dependent covariate, only CD4 (P = 0.002) and CD8 (P = 0.001) cell counts predicted the occurrence of a new AIDS-defining event. Eight out of 13 (61.5%) patients had an ICD-p24 Ag response, and seven out of 13 (54%) a plasma viraemia response, but only cellular viraemia responders (five out of 18; 28%) had a 5.6-fold decrease in their risk of developing an AIDS-defining event (90% confidence interval, 1-33; P = 0.05). None of these markers correlated with survival.


CONCLUSIONS
Plasma viraemia and ICD-p24 Ag, while providing useful short-term markers of zidovudine antiviral activity in vivo, do not correlate with disease progression in patients with advanced HIV infection. CD4 cell count remained the best initial and time-dependent predictor for development of new AIDS-defining events. Interestingly, a high CD8 cell count and a decrease in cellular viraemia titres also appear to be predictive of improved clinical outcome in this population.
Molina
J M
JM
Department of Infectious Diseases, Hôpital Saint-Louis, Paris, France.
Ferchal
F
F
Chevret
S
S
Barateau
V
V
Poirot
C
C
Morinet
F
F
Modai
J
J
D000328:Adult; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes; D005260:Female; D016655:HIV Core Protein p24 / Q000097:blood; D015658:HIV Infections / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology; D015497:HIV-1 / Q000187:drug effects / Q000302:isolation & purification*; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D011446:Prospective Studies; D014766:Viremia; D015215:Zidovudine / Q000627:therapeutic use*
D015415:Biomarkers; D016655:HIV Core Protein p24; D015215:Zidovudine