How should APOBEC3-induced resistance mutations be considered in the management of antiretroviral therapy?

Background: Combined antiretroviral therapy (ART) management guided by the cell-associated HIV-DNA genotypic resistance test (GRT) is not standardized, and its interpretation may be difficult in the presence of APOBEC3-induced mutations at drug resistance-associated positions (APOMut). Our objective was to evaluate the virologic outcome of people living with HIV (PLWH) with HIV-DNA provirus carrying APOMuts when switched to or receiving an ART regimen that would theoretically be significantly impacted by those APOMut (potential APOMut-impacted treatment, PAIT).

Methods: PLWH under PAIT and with a cell-associated HIV-DNA GRT containing APOMut between April 2010 and December 2023 were included. Treatment failure was defined as two consecutive plasma viral load values >50 c/mL at least 1 month apart after the switch to PAIT.

Results: We studied 38 PLWH who received 42 distinct PAIT lines. At the time of PAIT introduction, all individuals except one were virally suppressed. Virologic failure occurred in four PLWH; all of these cases were related to either poor ART adherence or ART interruption. Two of them switch to another ART: one for galenic adaptation, and the other due to the emergence of the N155H resistance mutation in integrase. For this individual, virologic suppression was obtained with a PI-containing ART. The two others resumed virologic suppression without any ART switch.

Conclusions: Despite the presence of APOMut in cell-associated HIV-DNA GRTs, virologic suppression was maintained in PLWH switching to PAIT. Virologic failures were unrelated to the presence of APOMut. These results suggest that APOMuts should not be considered in the management of ART.