PROVIRUS LOAD CHANGES IN UNTREATED AND ZIDOVUDINE-TREATED HUMAN-IMMUNODEFICIENCY-VIRUS TYPE 1-INFECTED PATIENTS

Human immunodeficiency virus type 1 (HIV-1) provirus burden was quantified during followup of untreated patients and mathematically analyzed by a parameter called intrinsic rate of increase (r). There was an increase in provirus burden in patients at early stages of the infection, and the increase occurred at a similar rate in later stages of the disease. Antiviral response to zidovudine was evaluated using r. Nearly 50% of patients responded with strong decreases of r, and the rest behaved as nonresponders. Parameter r is valuable in disease prognosis, as the mean r was higher in disease progressors than in nonprogressors, and this difference was significant and more pronounced in treated patients. The zidovudine resistance mutation at codon 215 of reverse transcriptase was associated with a worse response to therapy. Absence of antiviral response and resistance mutations were more frequent in patients with lower CD4(+) cell counts and higher provirus loads. These findings support a more beneficial effect of early than late therapy.