Real-life use of Doravirine in treatment-experienced people living with HIV: A multicenter Italian study

Abstract

Use of doravirine (DOR), a new nonnucleoside reverse-transcriptase inhibitors recently approved for HIV treatment, is still unclear in clinical practice and real-life data are scarce.We retrospectively investigated the rationale for switching people with HIV to DOR-containing/-based regimens in a real-life cohort. Among 132 patients (68.9% males, median age 56 years), the main reasons to start DOR were prevention of toxicities (39.4%) and dyslipidemia (18.2%). DOR was combined with integrase inhibitors in 40.9% cases, and in 25.7% of patients, DOR was prescribed without availability of a genotypic resistance test.Twenty-four weeks after the switch to DOR-containing/-based regimens, no significant changes in CD4+ T-cell count, CD4/ CD8 ratio, detectable HIV-RNA, serum creatinine levels, and body weight were detected. By contrast, a significant reduction in lipids (both cholesterol and triglycerides) was observed in 52 patients for whom a follow-up assessment was available (P = .008 and .01, respectively).Our data confirmed that switching to DOR-containing/-based regimens may have a favorable impact on lipid profile and a neutral impact on weight gain. However, more data are needed to support its use in patients who do not have a genotypic test available or have an extensive nonnucleoside reverse-transcriptase inhibitors-associated resistance, as well as its use in a dual regimen, especially in combination with second-generation integrase inhibitors.

Efficacy and safety of dolutegravir/rilpivirine in real‐world clinical practice. GeSIDA study 1119

“…Compared to other 2DR, similar results have been reported with DTG/RPV and DTG/3TC [17,18], although for patients with extensive experience with ART and prior virological failures, DTG/RPV would be a better option. Data with 2DR with the last available NNRTI doravirine (DOR) are scanty, showing a favourable impact on lipid profile [19], similar to that reported in our cohort with DTG/RPV. No trials have yet explored DOR combined with second-generation INSTI, so although this regimen may be attractive, caution is advised.…”

Doravirine/lamivudine/tenofovir disoproxil fumarate in virologically suppressed people living with HIV: A real-life experience

“…After 24-weeks follow-up, no significant changes were reported regarding the proportion of subjects with virological suppression (94.2%), CD4+ T lymphocyte count, body weight and serum creatinine level, while a significant decrease was observed in both total cholesterol and triglycerides. 14 In a retrospective cohort of 40 virologically suppressed PLWHIV switched to a regimen with doravirine plus two NRTIs, a significant decrease in median values of total cholesterol, LDL cholesterol and triglycerides were reported, in association with a reduction in median predicted 10-years risk of cardiovascular disease. 15 The coformulation of doravirine with tenofovir disoproxil fumarate (TDF) and lamivudine in a single-tablet regimen raised some concerns following the documented risk of renal toxicity and treatment discontinuation associated with TDF exposure.…”

“…After 24-weeks follow-up, no significant changes were reported regarding the proportion of subjects with virological suppression (94.2%), CD4+ T lymphocyte count, body weight and serum creatinine level, while a significant decrease was observed in both total cholesterol and triglycerides. 14…”

Doravirine Plus Integrase Strand Transfer Inhibitors as a 2-Drug Treatment–Switch Strategy in People Living with HIV: The Real-Life DORINI Multicentric Cohort Study

“…Specifically, data from clinical practice testify that the two-drug combination of DOR + INI (mostly the second-generation INI DTG) has preferentially been chosen as the regimen of switch among other DOR-containing regimens and has allowed the persistence of virological suppression even in subjects with no resistance test available in medical history, even if these data deserve to be interpreted cautiously. 7…”