Does ART Intensification Prevent Residual HIV Replication?

Residual replication is rare in HIV-infected individuals who undergo antiretroviral therapy (ART) intensification with dolutegravir, according to a recent study.

In order to determine whether residual virus replication occurs in HIV-infected individuals on ART, and whether this replication could be a barrier to achieving an HIV cure, researchers conducted a randomized, placebo-controlled, double-blind trial involving 40 individuals with HIV who had been receiving combination ART for at least 3 years. All participants had fewer than 50 copies per mL HIV-1 plasma RNA for more than 3 years, fewer than 20 copies at screening, and 2 CD4 counts higher than 350 cells per μL in the previous 24 months.
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The participants were randomly assigned to receive either 50 mg oral dolutegravir or placebo once-daily for 56 days in addition to their ART. Follow-up was conducted on days 1, 3, 7, 14, 28, 56, and 84.

Overall, median 2-LTR circles fold-change from baseline to day 7 was −0·17 (IQR −0·90 to 0·90) in the dolutegravir group and −0·26 (−1·00 to 1·17) in the placebo group (p=0·17). No treatment discontinuations or treatment-related adverse events occurred in either group.

“Our findings show that in HIV-infected individuals on modern suppressive ART regimens, residual replication is rare, if at all present, and was not recorded in blood after dolutegravir intensification,” the researchers concluded. 

“Because tissue biopsies were not done we cannot exclude the possibility of residual virus replication in tissue. Strategies other than ART alone are needed to eliminate HIV persistence on treatment.”

—Michael Potts

Reference:

The effect of antiretroviral intensification with dolutegravir on residual virus replication in HIV-infected individuals: a randomised, placebo-controlled, double-blind trial [published online April 8, 2018]. Lancet HIV. doi:https://doi.org/10.1016/S2352-3018(18)30040-7