Using data from the Danish AIDS Cohort of HIV-infected homosexual men established in the 1980s, the prognostic value of early HIV DNA loads was evaluated. In addition to DNA measurements, concomitant serum HIV RNA levels, CD4 cell counts and CCR5 genotypes were determined. The patients were divided into 3 groups, according to whether their cell-associated HIV DNA load was < or = 100, 500 or > or = 2,500 DNA copies/10(6) peripheral blood mononuclear cells. Clinical progression rates differed significantly between the groups (p < 0.005). Cell-associated HIV DNA load had prognostic value independent of serum HIV RNA (p < 0.02). However, when HIV DNA, HIV RNA and CD4 cell counts were all included in a Cox model, only serum HIV RNA had independent prognostic value. Patients heterozygous for the CCR5 delta 32 allele had significantly lower HIV DNA loads than those homozygous for the normal allele (p < 0.05). The interplay between HIV RNA and DNA levels is discussed, together with the possibility that cell-associated HIV DNA load is a marker of the HIV RNA peak seen shortly after primary HIV infection.