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 toinitiate 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 fol- lowed over 6 years, with CD4 testing at 6 month intervals, to study the timing of CD4-based staging of HIV-I 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 × ⁶/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 x ⁶/L are at least (297 × ⁶, 841 × ⁶/L) and (118 × ⁶, 337 × ⁶/L), respectively. Without confirmatory retesting, individuals with true CD4 remaining at 700 × ⁶ and 280 × ⁶/L have at least a 40% chance for one of five CD4 measurements to fall below guideline limits of 500 × ⁶ and 200 × ⁶/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 × ⁶/L and defining AIDS by CD4 <200 × ⁶/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.