Effect of CD4+ Cell Count Measurement Variability on Staging HIV-1 Infection

A single CD4+ cell count (CD4) measurement is often used to stage HIV-1 infection, decide when to initiate prophylactic therapy and inform patients, and may soon even define AIDS onset. Documentation of the reliability and validity of employing CD4 for the above purposes in a population-based setting is needed. We utilized data from 4.954 homosexual/bisexual men followed over 6 years, with CD4 testing at 6 month intervals, to study the timing of CD4-based staging of HIV-1 disease and quantify and evaluate the potential impact of CD4 measurement error. The median time from seroconversion to first CD4 test below 500 + 106/L or clinical AIDS was 1.70 years, and the first CD4 test below 200 + 106/L or clinical AIDs was 5.29 years. The time from first testing <500 + 106/L to clinical AIDS in untreated men was 5.55 years. With confirmatory retesting, these times were significantly lengthened. The 95% confidence ranges for the true CD4 state in individuals with measured CD4 of 500 and 200 + 106L are at least (297 + 106, 841 + 106/L) and (118 + 106 337 + 106/L), respectively. Without confirmatory retesting. individuals with true CD4 remaining at 700 + 106 and 280 + 106/L have at least a 40% chance for one of five CD4 measurements to fall below guideline limits of 500 + 106 and 200 + 106/L, respectively. Confirmatory retesting can reduce these probabilities to as low as 4% These data suggest the following: (i) initiating antiretroviral therapy when the CD4 cell count is <500 + 106/L and defining AIDS by CD4 < 200 + 106/L in certain circumstances may not be ideal; (ii) confirmatory retesting can significantly influence the timing and duration of therapy, and the time to CD4-defined AIDS; and (iii) confidence intervals should be calculated and reported along with point estimates for CD4 cell levels. This has significant prognostic, clinical, and economic implications.