Simplification to rilpivirine/emtricitabine/tenofovir disoproxil fumarate from ritonavir-boosted protease inhibitor antiretroviral therapy in a randomized trial of HIV-1 RNA-suppressed participants
ABSTRACT To evaluate the efficacy and safety of antiretroviral simplification from a ritonavir-boosted protease inhibitor-based regimen [protease inhibitor+RTV+two nucleos(t)ide reverse transcriptase inhibitors (NRTIs); ≥6 months of exposure prior to study entry with no prior treatment failure] to the single-tablet regimen (STR) rilpivirine/emtricitabine/tenofovir disoproxil fumarate (RPV/FTC/TDF) in virologically suppressed, HIV-1-infected participants.
Phase 3b, randomized, open-label, international, 48-week switch study.
Participants were randomized 2 : 1 to switch to RPV/FTC/TDF immediately or stay on their baseline protease inhibitor+RTV+2NRTIs regimen with a delayed switch to RPV/FTC/TDF at week 24. The primary endpoint was noninferiority (12% margin) of RPV/FTC/TDF compared with protease inhibitor+RTV+ two NRTIs in maintaining plasma HIV-1 RNA less than 50 copies/ml at week 24 by Snapshot analysis.
A total of 476 participants were randomized and received at least one dose of study drug. Demographics and baseline characteristics were similar between arms. The primary objective of noninferiority at week 24 was met: HIV-1 RNA less than 50 copies/ml by Snapshot analysis, 93.7% of RPV/FTC/TDF versus 89.9% of protease inhibitor+RTV+ two NRTIs (difference 3.8%, 95% confidence interval -1.6 to 9.1%). Through week 48, 89.3% of participants in the immediate switch group maintained virologic suppression. High rates of suppression were maintained with RPV/FTC/TDF regardless of participant's pre-antiretroviral HIV-1 RNA level. Overall development of resistance mutations after switching to RPV/FTC/TDF was low. Decreases in total cholesterol, low-density lipoprotein (LDL), and triglycerides were significantly greater among RPV/FTC/TDF recipients than those in the protease inhibitor+RTV+ two NRTIs group.
Switching to the STR RPV/FTC/TDF from an RTV-boosted protease inhibitor regimen in virologically suppressed, HIV-1-infected participants maintained virologic suppression with a low risk of virologic failure, while improving total cholesterol, LDL, and triglycerides.
SourceAvailable from: Huldrych F Günthard[Show abstract] [Hide abstract]
ABSTRACT: IMPORTANCE New data and antiretroviral regimens expand treatment choices in resource-rich settings and warrant an update of recommendations to treat adults infected with human immunodeficiency virus (HIV). OBJECTIVE To provide updated treatment recommendations for adults with HIV, emphasizing when to start treatment; what treatment to start; the use of laboratory monitoring tools; and managing treatment failure, switches, and simplification. DATA SOURCES, STUDY SELECTION, AND DATA SYNTHESIS An International Antiviral Society–USA panel of experts in HIV research and patient care considered previous data and reviewed new data since the 2012 update with literature searches in PubMed and EMBASE through June 2014. Recommendations and ratings were based on the quality of evidence and consensus. RESULTS Antiretroviral therapy is recommended for all adults with HIV infection. Evidence for benefits of treatment and quality of available data increase at lower CD4 cell counts. Recommended initial regimens include 2 nucleoside reverse transcriptase inhibitors (NRTIs; abacavir/lamivudine or tenofovir disoproxil fumarate/emtricitabine) and a third single or boosted drug, which should be an integrase strand transfer inhibitor (dolutegravir, elvitegravir, or raltegravir), a nonnucleoside reverse transcriptase inhibitor (efavirenz or rilpivirine) or a boosted protease inhibitor (darunavir or atazanavir). Alternative regimens are available. Boosted protease inhibitor monotherapy is generally not recommended, but NRTI-sparing approaches may be considered. New guidance for optimal timing of monitoring of laboratory parameters is provided. Suspected treatment failure warrants rapid confirmation, performance of resistance testing while the patient is receiving the failing regimen, and evaluation of reasons for failure before consideration of switching therapy. Regimen switches for adverse effects, convenience, or to reduce costs should not jeopardize antiretroviral potency. CONCLUSIONS AND RELEVANCE After confirmed diagnosis of HIV infection, antiretroviral therapy should be initiated in all individuals who are willing and ready to start treatment. Regimens should be selected or changed based on resistance test results with consideration of dosing frequency, pill burden, adverse toxic effect profiles, comorbidities, and drug interactions.JAMA The Journal of the American Medical Association 07/2014; 312(4):410-25. DOI:10.1001/jama.2014.8722 · 30.39 Impact Factor
Article: HIV: new drugs, new guidelines[Show abstract] [Hide abstract]
ABSTRACT: Purpose of reviewThis review discusses recent changes in HIV treatment guidelines, focussing on the optimal time for starting antiretroviral therapy (ART) in chronic asymptomatic infection, and treatment options for ART-naive patients.Recent findingsUnderstanding of HIV pathogenesis has progressed significantly, with a growing appreciation of the role of HIV replication in causing inflammation and promoting both AIDS and non-AIDS diseases. Early suppression of HIV replication with ART benefits the individual, and by reducing transmission and promoting engagement with care also brings public health benefits. For years, efavirenz-based ART was favoured by treatment guidelines, reflecting unsurpassed performance in clinical trials. New treatment options show high efficacy and safety and include single-tablet coformulations for once-daily dosing to improve convenience. Recent data have demonstrated superiority over efavirenz of regimens based on rilpivirine in patients with low pre-ART HIV-1 RNA load and raltegravir or dolutegravir regardless of the viral load.SummarySome guidelines now recommend starting ART regardless of CD4 cell counts, whereas others take a more cautious approach pending results from studies that are testing the clinical benefit of early therapy. New treatment options allow therapy to be tailored to the patient's circumstances and are suitable for early ART initiation.Current Opinion in Infectious Diseases 10/2014; 27(6). DOI:10.1097/QCO.0000000000000106 · 5.03 Impact Factor
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ABSTRACT: Objectives Emtricitabine/tenofovir/rilpivirine as a single-tablet regimen (STR) is widely used without licence in treatment-experienced patients. The purpose of this retrospective observational study was to assess viral suppression of ART-experienced patients switching to STR.Methods We assessed 131 pretreated patients switching to STR with HIV RNA < 400 HIV-1 RNA copies/mL. The primary outcome measure was the proportion of patients at week 24 with HIV RNA < 40 copies/mL.ResultsBy week 24, eight patients had stopped STR: four because of adverse events and four for other reasons. Three virological failures were observed; among these, at least one patient developed cross-resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs), in particular with the E138K pattern. In intent-to-treat analysis, 92% of participants (120 of 131) achieved HIV RNA < 40 copies/mL. Only grade 1 to 2 adverse events were observed, mainly consisting of increased liver enzymes (n = 33). Systemic exposure to rilpivirine was above the usually observed steady-state levels for the 18 measurements assessed.Conclusions Efficacy and tolerability are similar to those in treatment-naïve patients.HIV Medicine 09/2014; DOI:10.1111/hiv.12183 · 3.45 Impact Factor