TD-9 Exploring the use of darunavir boosted plus dolutegravir in highly treatment-experienced HIV population: a retrospective Cohort study

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Introduction The combination of darunavir boosted (DRV/b) and dolutegravir (DTG) has a high genetic barrier to resistance, crucial for treatment-experienced people with HIV (PWH) for whom options may be limited. However, there is no clinical trial data and limited real-life evidence supporting its use. This study aims to fill this gap by exploring the demographic, clinical, and genotypic profiles of patients initiating this regimen. Methods This was an observational, retrospective study from the ARCA database, including PWH starting treatment with DRV/cobicistat(c) or DRV/ritonavir(r) plus DTG, who had at least one Genotypic Resistance Test (GRT). The analysis focuses on evaluating the participants’ demographic, clinical, and historical genotypic characteristics. Statistical methodologies include descriptive statistics for demographic and clinical variables. Results A total of 500 PWH were included in the study, with a median age of 53 (IQR 48–58) years and a long history of HIV and antiretroviral treatment. The median number of previous regimens was 10 (IQR 5–14). Most initiated treatment with an undetectable viral load (60.8%). Among those with a detectable viral load, the median HIV-RNA level was 596 (IQR 131–6674) copies/mL. The characteristics of the population are detailed in table 1. The variety of previous regimens was extensive, encompassing more than 100 different regimens, as depicted in figure 1. Among the 500 PWH, 270 (54%) started treatment with DRV/c, while 230 (46%) started with DRV/r. The median number of previous GRTs was 3 (IQR 1–4). Considering the historic genotype, 211 (42.2%) exhibited no resistance, 150 (30.0%) had resistance to one class, and 113 (22.6%) to two classes; among these, 88 (17.6%) had only protease inhibitors (PI) and integrase inhibitors (INSTI) as available treatment. A smaller group, 23 (4.6%), had resistance to three classes, and 3 (0.6%) were resistant to four classes. Focusing on resistance within individual drug classes (figure 2), for nucleoside reverse transcriptase inhibitor (NRTI), only 112 (22.4%) had no mutations, while 362 (72.4%) exhibited resistance to at least one drug; notably, 319 (63.8%) were resistant to lamivudine. Regarding non-NRTI, 157 (31.4%) had no mutations for this class, while 280 (56%) exhibited resistance to rilpivirine or doravirine. For PIs, 50 (10%) were resistant to DRV/b. Finally, for INSTI, only 53 (10.6%) carried a mutation; however, among these, only 10 (2%) were resistant to DTG or bictegravir (figure 3). Conclusion Our analysis of a highly experienced PWH cohort highlighted how DRV/b + DTG is often preserved. Thus, approximately 60% of our population initiating the PI/b + INSTI regimen showed evidence of prior resistance. The selection of this regimen for the remaining portion may relate to factors of tolerability or other clinical considerations rather than resistance. However, further studies are essential to fully elucidate the regimen’s efficacy, safety, and durability.

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