Lack of consistency between five definitions of nonprogression in cohorts of HIV-infected seroconverters

Objective: To identify appropriate criteria for characterizing HlV-infected nonprogressors. Design: Five definitions were compared as follows: (1) last CD4 count > 500x10(6)/l; (2) two most recent CD4 counts > 500x10(6)/l; (3) calculated CD4 count based on linear regression > 500x10(6)/l; (4) CD4 slope greater than or equal to 0 with no antiretroviral use; (5) all CD4 counts > 500x10(6)/l, decline in CD4 slope < 5 cells per year, no antiretroviral use. Participants: Five prospective cohorts of homosexual men with documented dates of HIV-1 seroconversion. Main outcome measures: Proportions of nonprogressors were calculated 7, 8, 9 and 10 years following seroconversion (n = 285). Definitions were evaluated with respect to consistency over time and across sites. Subjects lacking CD4 counts within 3 years preceding end of follow-up were excluded. Results: Across sites, proportions of nonprogressors ranged from 1% (definition 5) to 17.5% (definition 1) 10 years after seroconversion. Definitions based on absolute CD4 counts (definitions 1-3) had higher proportions and were less consistent than those based on stable slopes (definitions 4 and 5). For each definition, proportions decreased as follow-up increased, but were most stable for definition 4 (3%). Site differences decreased as follow-up increased, but remained nearly threefold for definitions 1-3. None of the definitions classified the same subjects as nonprogressors at any timepoint. Conclusions: Observations regarding nonprogression are highly dependent on the definition and the duration of follow-up. Our findings highlight methodological challenges which will need to be overcome in natural history studies of nonprogression.