Decline in CD4 + Cell Numbers Reflects Increase in HIV-1 Replication

Abstract

Changes in CD4⁺ cell numbers were studied in relation to the presence of HIV-1 antigen (HIV-1-Ag) in serum from homosexual men followed prospectively. During 30 months of follow-up the mean CD4⁺ cell number (x 10⁹ per liter) was stable in 134 at entry HIV-1 antibody (HIV-1-Ab) seropositives, who remained HIV-1-Ag negative (from 0.59 to 0.62) and declined in 38 at entry HIV-1-Ab seropositives who were persistently HIV-1-Ag positive (from 0.43 to 0.34).

In sera of 9 of 65 HIV-1-Ab seroconverters HIV-1-Ag was detected only once, 3 months before or concomitantly with antibody seroconversion. Another 11 men became persistently HIV-1-Ag positive with antibody seroconversion or 2–6 weeks thereafter. A decline in CD4⁺ cell numbers was seen between 6 months before and the moment of HIV-1-Ab seroconversion, independently of duration and level of antigen expression. This indicates initial HIV-1 replication in both HIV-1-Ag negatives and positives.

Following antibody seroconversion, HIV-1-Ag negatives had higher CD4⁺ cell numbers than HIV-1-Ag positives. Similarly to those who were HIV antigenemic from entry of the study, the HIV-1-Ab seroconverters who concomitantly with seroconversion or shortly thereafter became HIV-1 antigenemic showed a steady and significant (^p = 0.01) decline in CD4⁺ cell numbers. In those who remained HIV-1-Ag negative after antibody seroconversion, CD4⁺ cell numbers were stable during follow-up.

At entry, HIV-1-Ab-seropositive individuals who became HIV-1 antigenemic during follow-up had CD4⁺ cell numbers before antigen conversion comparable to those who were antigen positive at entry (0.43 and 0.51, respectively) and subsequently showed a decline (to 0.41).

These results indicate that replication of HIV-1 as well as the proportion of HIV-1-infected cells before virus activation may be reflected in low CD4⁺ cell numbers.