Nucleoside reverse transcriptase inhibitors (NRTIs) may contribute to or exacerbate cardiovascular risk, bone loss, and renal dysfunction. Darunavir (DRV) and dolutegravir (DTG) have a high barrier to resistance and proven tolerability profile, but have not been well studied as part of a NRTI sparing regimen. The purpose of this study is to determine the real-world efficacy and safety of a NRTI-sparing regimen of boosted DRV and DTG.
We conducted a retrospective chart review (NCT03198884) of approximately 400 HIV+ patients at an urban Federally Qualified Health Center to identify those who started a NRTI-sparing regimen of ritonavir(r) boosted DRV and DTG once-daily (QD). Included subjects were ³ 18 years of age, receiving DRV/r QD + DTG QD for ³ 24 weeks, and had 48 weeks of laboratory data available. Subjects were excluded if they, missed >5 doses over two weeks prior study visit, or had missing laboratory data for ³2 study time points. The primary endpoints were the percent of patients with HIV-1 RNA <50 copies/mL at 48 weeks and the change in mean serum creatinine (SCr) from baseline to 48 weeks. Analysis used was the Snapshot algorithm and Wilcoxon signed rank testing, respectively. Additional secondary endpoints included changes in CD4+ cell counts, and incidence and severity of adverse events.
Twenty subjects were identified for inclusion. The mean age of the cohort was 51 years with an average of 12.5 years of HIV seropositivity. The mean baseline CD4+ was 485 cells/mm3 with an HIV-1 RNA of 20,000 copies/mL. The percentage of subjects with HIV-1 RNA < 50 copies increased from 45% at baseline to 95% at week 48 (P-value=0.002), 95% CI [2.24; NA], with one subject not having data in the 48 week window. There were no significant differences in SCr from baseline to 48 weeks (p = 0.5753) and no significant changes in CD4+ cell count from baseline at time points 24, 36 or 48 weeks. No subjects experienced virologic failure during the study period, or required genotypic resistance testing. No patients reported adverse events that led to discontinuation of the study regimen.
The once daily regimen of boosted DRV and DTG was effective at achieving or maintaining virologic suppression with no significant adverse events. This regimen offers another viable option for patients unable to tolerate NRTIs.
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