Early ART Reduces Risk of Severe Bacterial Infections

According to a recent study, immediate initiation of antiretroviral therapy (ART) reduced the risk of several severe bacterial infections in HIV-positive individuals with high CD4 cell count compared with deferred initiation.

In their study, researchers analyzed data from the of the Strategic Timing of AntiRetroviral Treatment (START) trial to determine if timing of ART initiation influenced the risk of severe bacterial infections.
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START was a multicontinental, randomized trial that included 4685 asymptomatic HIV-positive individuals with CD4 cell counts above 500 μL who were randomly assigned to immediate ART initiation (n=2326) or deferred ART initiation (n=2359) until their CD4 counts fell below 350 cells per μL.

The researchers defined severe bacterial infection as any bacterial pneumonia, pulmonary or extrapulmonary tuberculosis, or any bacterial infectious disorder that was either categorized as a grade 4 severity, required hospitalization, or caused death.

A total of 120 HIV-positive participants in START developed severe bacterial infections, 34 of which occurred in the immediate ART group and 86 occurred in the deferred ART group.

In comparison with deferred ART, immediate ART was associated with a reduced risk of severe bacterial infection (hazard ratio [HR] 0.39, 95% CI 0.26–0·57, p<0.0001).

The average neutrophil count over follow-up for the immediate-initiation group was 321 cells per μL higher than the deferred-initiation group, and the average CD4 cell count was 194 cells per μL higher than the deferred ART group.

In addition, researchers found a higher time-updated CD4 cell count was associated with a reduced risk of severe bacterial infection (0.78, 0.71–0.85, p=0.0001). No association was found between time-updated neutrophil count and reduced risk of severe bacterial infection.

Overall, immediate ART initiation reduced the risk of severe bacterial infection in HIV-positive asymptomatic individuals with high CD4 cell counts by 61%.

“The results of our 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,” the researchers concluded.

—Melissa Weiss

Reference:

O’Connor J, Vjecha MJ, Philips AN, et al. 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 [published online January 4, 2017]. Lancet. doi: dx.doi.org/10.1016/S2352-3018(16)30216-8.