Predictors of Progression in Long-Term Nonprogressors

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Abstract
It is now apparent that a proportion of individuals (5–8%) remains clinically free of HIV-1 disease with normal levels of CD4+ lymphocytes (≥500/μl) for more than 8 years following infection. However, the proportion of these individuals who ultimately progress to AIDS remains to be established. We determined the virological and immunological characteristics of a cohort of long-term nonprogressors in Australia and examined the role of these factors in predicting disease progression. Individuals with documented asymptomatic HI V-1 infection for at least 8 years with CD4+ lymphocyte counts >500 cells/μl were recruited from hospital clinics and general practices serving the eastern area of Australia. CD4+ lymphocyte count, rate of CD4+ lymphocyte change, CD8+ lymphocyte count, β2-microglobulin, immune complex dissociated (ICD) HIV-1 p24 antigen, and plasma HIV-1 RNA were measured at baseline and multiple visits at 6-month intervals over an average period of 2 years. Up to November 1996, 67 study participants were recruited, of whom 72% had been infected with HIV-1 for at least 10 years. HIV-1 RNA correlated with β2-microglobulin, ICD p24 antigen, and the ability to isolate virus in culture but not with levels of CD4+ or CD8+ lymphocytes. Serum β2-microglobulin was a stronger predictor of CD4+ lymphocyte decline than HIV-1 RNA and the only factor significantly associated with CD4+ lymphocyte decline. These findings show that the serum concentration of β2-microglobulin is a strong predictor of immunological progression in people with long-term asymptomatic HIV-1 infection and provides additional prognostic information to HIV-1 RNA in determining the risk of disease progression.