Long-term efficacy and safety of rilpivirine plus abacavir and lamivudine in HIV-1 infected patients with undetectable viral load

Abstract

IntroductionA regimen with rilpivirine (RPV), abacavir (ABC) and lamivudine (3TC) is simple and may allow the sparing of tenofovir and protease inhibitors. However, data on use of this combination as a strategy of switch are limited. Aims of the study were to assess the long-term efficacy and safety of this regimen.MethodsRetrospective study on HIV-1 infected patients followed at the Infectious Disease Department of the San Raffaele Scientific Institute, HBsAg-negative, HLA B5701-negative, with no documented resistance to RPV, ABC and 3TC, with HIV-RNA<50 copies/mL who started RPV plus ABC/3TC from March 2013 to September 2015.The primary outcome was durability [no treatment failure (TF)]. Secondary objectives were to evaluate changes in immunological, metabolic and other safety parameters.TF was defined as the occurrence of virological failure (VF, 2 consecutive values >50 copies/mL) or discontinuation of any drug in the regimen for any reason.Patients’ follow-up accrued from the date of RPV plus ABC/3TC initiation to the date of TF (VF or discontinuation of any drug in the regimen) or to the date of last available visit.Time to TF was evaluated by use of the Kaplan-Meier curves. Mixed linear models were applied to evaluate changes in immunological, metabolic and other safety parameters.Results and discussionIn this analysis, 100 patients starting RPV plus ABC/3TC were included. By 12, 24 and 36 months after switching to RPV plus ABC/3TC, the proportions of individuals without TF were 88% [95% confidence interval (CI): 79%-93%], 82% (95% CI:73%-89%) and 78% (95% CI:68%-86%), respectively. Time to TF was not significantly influenced by CD4+ nadir (≤200 vs >200 cells/μl; log-rank test: p = 0.311) or pre-ART viral load (<100000 vs ≥100000 copies/mL; log-rank test: p = 0.574) or the type of previous antiretroviral regimen (PI+2NRTIs vs NNRTI+2NRTIs vs Other; log-rank test: p = 0.942).Over a median follow-up of 2.9 years (IQR: 1.9–3.5), 26 subjects discontinued the treatment [10 due to toxicity, 7 for interactions with other drugs, 3 due to cardiovascular risk concern, 2 due to single viral blip, 1 due to VF, 1 for asthma, 1 patient’s decision, 1 due to enrolment in a study protocol].ConclusionsIn this retrospective study, long-term use of RPV plus ABC/3TC regimen is effective and safe. Efficacy of this regimen was not found to be affected by low CD4+ nadir or high pre-ART viral load.

Efficacy and Safety of Rilpivirine-Based Antiretroviral Therapy in Treatment-Naïve and Treatment-Experienced HIV-1-Positive Patients: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

“…Comparator group in the SPIRIT trial: 24 weeks of ongoing ART + 24 weeks of RPV/FTC/TDF. follow-up [15,16,19,21]. These results confirm previous evidence of RPV potency and efficacy in inhibiting a broad spectrum of HIV-1 genotypes and circulating recombinant forms, including K101E-, Y181C-, G190Aand K103N-mutated viruses, and in possessing generally lower half-maximal effective concentration values than those of other NNRTIs against specific HIV-1 isolates [43,44].…”

“…RPV efficacy and safety have been assessed in registrative randomized controlled clinical trials (RCTs) in HIV-positive treatment-naïve [3][4][5][6][7] and treatmentexperienced patients [8][9][10][11][12][13][14] with documented longterm efficacy and tolerability. Real-life data from observational studies [15][16][17][18][19][20][21] eventually confirmed these results. Therefore, current Italian [22], European [23], British [24,25] and DHHS (Department of Health and Human Services) [26] HIV/AIDS guidelines recommend the use of RPV as a first-line third agent coupled with a nucleoside reverse transcriptase inhibitor backbone in people living with HIV (PLWH) with CD4 count > 200 cells/μL and HIV RNA < 100,000 copies/mL starting combination antiretroviral therapy (cART) and in optimization strategies represented by RPV-based single tablet regimens (both standard three-mediated hepatic oxidation, no inhibition or induction of cytochrome P-450 isoenzymes has been reported, and its spectrum of interaction is favorably narrowed [1,2,27].…”

Safety and Effectiveness of Switching to Abacavir/Lamivudine Plus Rilpivirine for Maintenance Therapy in Virologically Suppressed HIV-1 Patients in Singapore (SEALS)

“…Signi cant changes in eCrCl, eGFR and ALTs were rarely noted in other studies on ABC/3TC + RPV, and it is likely that the regimen has no signi cant effect on these laboratory parameters. [11][12][13][14] While no statistically signi cant changes were detected for lipids, fasting blood glucose and HbA1c, the results warrant careful interpretation due to the small number of patients with both baseline and followup values. Remarkably, the SIMRIKI study and the studies by Curran et al and Palacios et al all noted signi cant decreases in total cholesterol and LDL-C, as well as increases in HDL-C. [10][11][12] However, the local study by Ho et al did not lend evidence to any signi cant effect of the regimen on lipids, 14 and there are no studies so far that we know of that have documented signi cant changes in fasting blood glucose and HbA1c.…”

“…In several studies in Spain, 86-88% of HIV patients maintained virologic suppression and avoided therapy discontinuation at 48 weeks or 12 months. [11][12][13] The SIMRIKI study also saw 91.2% of their study population achieving the same outcome at 48 weeks. 10 A local study found that 96% of treatment naïve HIV-1 infected patients achieved virologic suppression at the end of 48 weeks of treatment with ABC/3TC + RPV, 14 which was comparable to that of our study in which 98.0% (197/201) of patients who completed follow-up without therapy discontinuation remained virologically suppressed.…”

“…10 The results of the SIMRIKI study are corroborated by several similar Spanish studies. [11][12][13] A local study has also shown the e cacy and safety of this regimen in treatment naïve HIV-1 infected adults, 14 but to our knowledge, there have not been any studies on the effectiveness and safety of ABC/3TC + RPV as a switch regimen in Singapore.…”