A retrospective evaluation of highly active antiretroviral therapy simplification in patients with end-stage renal disease receiving hemodialysis

Abstract

Antiretroviral (ARV) therapy in people living with HIV (PLWH) and end-stage renal disease (ESRD) on hemodialysis (HD) is complicated, requiring renally adjusted nucleoside reverse transcriptase inhibitors (NRTIs) and daily administration of non-renally eliminated agents. Recent data in PLWH with ESRD on HD demonstrate maintenance of viral suppression (82% with viral loads (VLs) <50 copies/mL) and favorable safety/tolerability profiles after ARV simplification with a fixed dose combination single tablet [elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF)]. Extrapolation of these data to all F/TAF formulations would allow ARV simplification to most PLWH with ESRD receiving HD. The objective of this retrospective study was to identify if ARV-experienced PLWH with ESRD on HD receiving renally adjusted NRTIs may be simplified to once daily ARV formulations without adverse effects while maintaining viral suppression. This single-center retrospective analysis assessed virologic control (3–12 months) and ARV tolerability post-regimen simplification (primarily NRTI once-daily dose adjustment) in PLWH with ESRD on thrice weekly HD receiving human immunodeficiency virus (HIV) care in an ambulatory clinic. Seventeen PLWH with ESRD on HD were included after documented ARV simplification. At 12 months, 12 patients (71%) remained undetectable (HIV VL <50 copies/mL) with two additional maintaining viral suppression (<200 copies/mL). One patient remained undetectable at month eight but became non-adherent with viral rebound. Two patients did not complete the 6- and 12-month evaluation after documented nonadherence ( N = 1) and an adverse effect (pruritus) ( N = 1). At 12 months, virologic suppression and tolerability resulted after a simplified ARV regimen including once daily F/TAF was initiated in PLWH with ESRD on thrice weekly HD with a reduction in pill burden.

Oxidative stress in hemodialysis patients infected with HIV

“…Some ARV classes are associated with lactic acidosis, hyperlipidemia, glucose intolerance, diabetes mellitus, fat redistribution, wasting, and atherosclerosis. These conditions include the premature onset of cardiovascular disease, neurocognitive disease, bone disease, cancer, and renal disease (Otto & Pecora Fulco, 2021;Sánchez & Gutierrez, 2008). These observations could be related to augmented OS associated with ARV toxicity previously reported and that suggests mitochondria as a toxic target (Lewis, 2003).…”

Managing Modern Antiretroviral Therapy in the Intensive Care Unit: Overcoming Challenges for Critically Ill People With Human Immunodeficiency Virus

“…Additionally, the STR DTG/ABC/3TC has demonstrated safety and efficacy in a small cohort of PWH receiving intermittent hemodialysis for end-stage renal disease [ 62 ]. Extrapolation of these data on safety and efficacy of FTC, 3TC, and TAF in PWH on RRT to all formulations containing these NRTIs is practiced by some HIV clinicians and has been studied in a small cohort of PWH on FTC/TAF-containing STRs [ 78 ]. The primary NRTI requiring renal dose adjustment is tenofovir disoproxil fumarate (TDF) in PWH with creatinine clearance (CrCl) ≤50 mL/minute or in those with CrCl ≤70 mL/minute when used in combination with cobicistat due to the higher risk of renal toxicity from TDF in boosted regimens [ 79–81 ].…”

Renal safety of tenofovir alafenamide-based antiretroviral therapy in people with HIV: A mini-review

“…The safety of TAF-containing regimens in this subgroup of HIV-infected patients requires further validation. Phase 3 clinical trials and real-world studies show that switching to TAF-containing regimens is safe and tolerable for HIV-infected patients with ESRD who receive hemodialysis, and maintains high virologic suppression rates (47)(48)(49)(50)(51). A multicenter Phase 3b study switched 55 HIV-infected patients with virologic suppression and ESRD undergoing hemodialysis to E/c/ F/TAF, and during a 2-year period, only 4 patients (7.3%) discontinued the treatment due to adverse events, with 2 cases related to the study drug.…”

“…At 1 year of treatment, no patients discontinued the treatment due to adverse events, and all patients had virologic suppression (49). Another retrospective study of 17 HIVinfected patients with ESRD undergoing hemodialysis who switched ART regimens, with 15 patients switching to TAF-containing regimens (12 of them to B/F/TAF), showed that only 1 patient discontinued the treatment due to adverse events, and the overall virologic suppression rate was 82% at 1 year (50). Case reports also showed that 6 HIV-infected patients with ESRD undergoing hemodialysis who switched to B/F/TAF had no adverse events, and the virologic suppression rate was 100% at 1 year (51).…”