Effect of immediate initiation of antiretroviral therapy on risk of severe bacterial infections in HIV-positive people with CD4 cell counts of more than 500 cells per μL: secondary outcome results from a randomised controlled trial. Lancet HIV
O’Connor et al. for the INSIGHT START study group aimed to quantify the effects of immediate versus deferred antiretroviral therapy (ART) on the risk of severe bacterial infection in people with high CD4 cell counts in a preplanned analysis of the START trial. The START trial was a randomised controlled trial in ART-naive HIV-positive patients with CD4 cell count of more than 500 cells per μL assigned to immediate ART or deferral until their CD4 cell counts were lower than 350 cells per μL.
Of 4685 HIV-positive people enrolled, 120 had severe bacterial infections (immediate-initiation group n=34, deferred initiation group n=86). Of the 120 people with a severe bacterial infection, 50 had a bacterial infectious disorder (e.g. pyelonephritis, cellulitis, syphilis), 48 developed bacterial pneumonia, and 26 developed tuberculosis. Immediate ART was associated with a reduced risk of severe bacterial infection compared with deferred ART (hazard ratio [HR] 0·39, p<0·0001). In the immediate-initiation group, average neutrophil count over follow-up was 321 cells per μL higher, and average CD4 cell count 194 cells per μL higher than the deferred-initiation group (p<0·0001). In univariable analysis, higher time updated CD4 cell count was associated with reduced risk of severe bacterial infection. Time-updated neutrophil count was not associated with severe bacterial infection.
In summary, the results of the study show the protective effect of immediate ART in reducing the risk of a broad spectrum of severe bacterial infections in HIV-positive people. The effect of immediate ART appears to be mediated in part by ART-induced increases in CD4 cell count, but not by the ART-induced increases in neutrophil count.