Background:  HIV disease progression is associated with the appearance of 2 distinct populations of B cells:  immature/transitional B cells that arise as a result of CD4⁺ T-cell lymphopenia, and mature/activated B cells that arise as a result of HIV-induced immune activation. Both populations were previously shown to be unresponsive to various B-cell stimuli. The effect of ART on B-cell counts and population dynamics was investigated in the setting of chronic HIV disease.

Methods:  B cells of 13 HIV chronically infected ART-naïve individuals were evaluated before and after initiation of ART. Lymphocyte counts and HIV plasma viremia were monitored for 1 year, along with changes in sub-populations of B cells. The subpopulations of B cells were evaluated in terms of phenotype, cell turnover, expression of survival factors, and susceptibility to apoptosis.

Results:  After initiation of ART, HIV plasma viremia declined to undetectable levels within 3 to 4 months while CD4⁺ T-cell counts increased by 30%, reaching 42% recovery by 1 year. Unexpectedly, the rise in B-cell counts was not significantly different than that of CD4⁺ T-cell counts, 32% after 3 to 4 months and 34% by 1 year. Prior to the initiation of ART, >50% of the B cells were comprised of immature/transitional and mature/activated B cells, compared to <15% in uninfected individuals. After 1 year on ART, profiles of B-cell populations were similar to those of uninfected individuals. Functional characterization revealed that immature/transitional B cells were highly susceptible to intrinsic apoptosis associated with reduced expression of pro-survival members of the Bcl-2 family, whereas mature/activated B cells expressed increased levels of Ki-67 and were highly susceptible to extrinsic apoptosis associated with increased expression of CD95.

Conclusions:  We provide evidence of increases in B-cell counts in chronically infected HIV-infected individuals following reduction of HIV plasma viremia by ART that paralleled increases in CD4⁺ T-cell counts. Given that the increases in total B-cell counts were associated with the disappearance of apoptosis-prone B-cell populations, these data suggest that loss of B cells during ongoing HIV replication may in part be due to increased B-cell death.