Switching protease inhibitors to rilpivirine in HIV-positive individuals with complete viral suppression and without prior HIV drug resistance in a resource-limited setting: a randomized controlled trial

Abstract

Introduction: Prior to the availability of rilpivirine (RPV), patients who could not tolerate efavirenz and nevirapine (NVP) were treated with protease inhibitor (PI)-based antiretroviral therapy (ART). Dyslipidaemia and other metabolic complications are commonly associated with PI use. This study aimed to compare the efficacy and adverse events between switching from PI-based to RPV-based regimen, versus continuing PI-based regimens in HIV-positive individuals with complete viral suppression.

Methods: A randomized controlled trial was conducted in HIV-positive individuals receiving PI-based regimens with undetectable HIV RNA and without prior HIV drug resistance. Patients were enrolled between July and December 2017 in a university medical centre in Bangkok, Thailand. They were randomized to switch from PIs to RPV (switch group) or continue ritonavir-boosted PI (control group). Primary endpoint was the proportion of patients with undetectable HIV RNA at 48 weeks. Changes in CD4 cell counts, lipid profiles and adverse events were also analysed.

Results and discussion: A total of 84 patients were enrolled, 42 in each group. Mean age was 47.7 years and 53.6% were males. At 48 weeks, 95.2% of patients in the switch group and 92.9% of control group had maintained undetectable HIV RNA (difference rate 2.4%; 95% CI, -9.6 to 14.7). Means of CD4 cell counts were 611 and 641 cells/mm³ in switch and control groups respectively (p = 0.632). Mean changes in lipid profiles (switch vs. control groups) were: total cholesterol, -12.5 versus + 12.2 (p = 0.024); LDL, -3.4 versus + 6.2 (p = 0.040); HDL, +1.6 versus + 1.9 (p = 0.887); and triglycerides, -82.6 versus - 24.4 mg/dL (p = 0.031). The mean changes of glucose and eGFR were similar (p > 0.05) between the two groups. The mean change of ALT was significantly greater in switch group (18.2 vs. 4.0 U/L, p = 0.017). One patient in switch group had anorexia and elevated ALT at 14 weeks and completely recovered after RPV discontinuation.

Conclusions: Switching PIs to RPV, in patients with complete viral suppression and without prior HIV drug resistance, sustains viral suppression and yields better lipid profiles. This finding supports its use as switching therapy in patients receiving PI-based regimens due to intolerance to efavirenz and NVP and previous alternatives limited to PI in resource-limited settings.

Keywords: antiretroviral therapy; protease inhibitor; randomized controlled trial; rilpivirine; switching.