Longitudinal analysis of quantitative virologic measures in human immunodeficiency virus-infected subjects with ≤400 CD4 lymphocytes: Implications for applying measurements to individual patients

Abstract

The natural variability of quantitative virologic measures among human immunodeficiency virus (HIV) type 1-infected persons was prospectively studied in 29 untreated persons with >600 CD4 cells/μL and in 15 persons receiving zidovudine monotherapy who had 400-550 CD4 cells/μL at study entry. Cell- and plasma-associated infectious HIV-1, provirus, and virion RNA were determined monthly as were numbers of CD4 and CD8 cells. HIV-1 replication varied widely among subjects with similar CD4 cell counts. The within-individual variability was significantly less than the variability between subjects for all virologic measures. Plasma virion HIV-1 RNA levels had the least variability. A mathematical model was devised to assess whether a potential therapeutic intervention significantly alters peripheral HIV-1 load. The model indicated that three measurements of plasma RNA would be outside the 95th percentile for the expected change in an individual due to natural variability. This approach can be used to accurately assess a therapeutic intervention among persons with low plasma HIV-1 titers.