ObjectiveTo examine whether the levels of plasma RNA and DNA provirus predict the rate of CD4 cell decline and patient death.DesignRetrospective analysis of HIV-2 cohort subjects.MethodsFifty-two subjects were recruited between January 1991 and December 1992. HIV-2 RNA levels in plasma and DNA levels in peripheral blood mononuclear cells (PBMC) were measured using in-house quantitative PCR assays. The annual rate of CD4 cell decline was calculated using the least-squares method. The survival data on 31 December 1997 were used.ResultsThe mean percentage of CD4 cells at baseline was 30.7 (SD, 9.5). In a linear regression model, the annual rate of CD4 cell decline was 1.76 CD4% faster for every increase in one log10RNA copies/ml [95% confidence interval (CI), 0.81–2.7;P =0.0006;r= 0.46; n = 52] and 1.76 CD4% faster for every increase in log10DNA copies/105PBMC (95% CI 0.46–3.1;P =0.01;r= 0.33; n = 42). In a multiple linear regression model, RNA load was related to CD4 decline independently of DNA load (P =0.02). The overall mortality rate was 7.29/100 person-years. In a Cox regression model, the hazard rate increased by 2.12 for each log10increase in RNA load (95% CI, 1.3–3.5;P =0.0023) but only by 1.09 for each log10increase in DNA load (95% CI, 0.64–1.87;P =0.8).ConclusionThis longitudinal study shows for the first time that a baseline HIV-2 RNA load predicts the rate of disease progression. HIV-2-infected patients with a high viral load may need to be treated as vigorously as HIV-1 patients.