by Carolyn Chu, MD, MSc, AAHIVS, AAHIVM Chief Medical Officer
January 31, 2023
Harris TN and Buscemi LR. Evaluation of treatment simplification strategies in patients living with HIV with multi-drug resistance. Ther Adv Infect Dis. 2023 Jan 19; 10:20499361221149869. doi:10.1177/20499361221149869. PMID 36699503.
This observational, retrospective cohort study described virologic outcomes of a single-center initiative evaluating ART simplification among PWH with a history of multi-drug resistance and treatment failure. Patients received medical services at a non-urban, Ryan White funded clinic and were on ‘salvage’ therapy (defined as ≥ 3 agents from at least 3 classes) between July 2016 and July 2021. Clinical information for 50 adults was extracted from health records including data on prior and current regimens and genotypes. Cumulative resistance profiles were constructed and genotypic sensitivity scores were calculated for current regimens and also for new simplified regimens, if applicable. 28/50 patients underwent simplification (defined as a pill burden reduction by at least 1 pill/day); 5 of these 28 patients were viremic prior to the change. Baseline characteristics were generally similar between patients who underwent simplification (median baseline GSS 3) and those who did not (median baseline GSS 2.5), although there were more patients with darunavir-specific mutations in the non-simplified group. Patients in the simplified group had their regimen reduced by a median of 6 pills/day to a median of 2 pills/day: most were simplified to a single-tablet or two-tablet regimen. 24/28 (85.7%) in the simplified group achieved or maintained virologic suppression at their most recent clinic visit, versus 16/22 (72.7%) in the non-simplified group. 23/28 (82.1%) in the simplified group were suppressed ≥ 80% of the time over the past 2 years, versus 16/22 (72.7%) in the non-simplified group. 3 patients in the simplified group and 5 in the non-simplified group experienced virologic failure, however no emergence of new resistance mutations was observed.
Although this small, “real world” study did not observe significantly different virologic outcomes among comparison groups, median ARV pill burden decreased from 6 to 2 pills/day for patients undergoing simplification and > 85% who underwent simplification achieved or maintained virologic suppression at study endpoint. In the simplification group, 75% had anticipated high-level NRTI resistance, 78.6% had anticipated high-level NNRTI resistance, 7.1% had anticipated DRV-specific mutations, and 0 had anticipated high-level INSTI resistance. The three most common simplification regimens utilized were BIC/FTC/TAF plus DRV/cobi, BIC/FTC/TAF, and DTG/RPV plus DRV/cobi. These findings may be of interest not only for general ART switch decision-making, but could also potentially help inform construction of streamlined “optimized background regimens” for patients who are being considered for newer ARV agents such as fostemsavir and lenacapavir. The multidisciplinary approach utilized in this effort also highlights the important role pharmacists hold in helping to construct effective and well-tolerated regimens, drug interaction assessments, and adherence support through interventions such as regular medication reviews and pill box fills.
The author has no conflicts of interest to disclose.
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