Effectiveness and safety of dual therapy with rilpivirine and boosted darunavir in treatment-experienced patients with advanced HIV infection: a preliminary 24 week analysis (RIDAR study)

Juan Pasquau, Samantha E de Jesus, Piedad Arazo, María J Crusells, María J Ríos, Fernando Lozano, Javier de la Torre, María J Galindo, Jorge Carmena, Jesús Santos, Carlos Tornero, Guillermo Verdejo, Gloria Samperiz, Zaira Palacios, Carmen Hidalgo-Tenorio, RIDAR Study Group, Juan Pasquau, Samantha E de Jesus, Piedad Arazo, María J Crusells, María J Ríos, Fernando Lozano, Javier de la Torre, María J Galindo, Jorge Carmena, Jesús Santos, Carlos Tornero, Guillermo Verdejo, Gloria Samperiz, Zaira Palacios, Carmen Hidalgo-Tenorio, Carlos Dueñas, Jose A Terron, Miguel García-Deltoro, María T Rubio, Miguel A Cárdenes, Juan Pasquau, Samantha E de Jesus, Piedad Arazo, María J Crusells, María J Ríos, Fernando Lozano, Javier de la Torre, María J Galindo, Jorge Carmena, Jesús Santos, Carlos Tornero, Guillermo Verdejo, Gloria Samperiz, Zaira Palacios, Carmen Hidalgo-Tenorio, RIDAR Study Group, Juan Pasquau, Samantha E de Jesus, Piedad Arazo, María J Crusells, María J Ríos, Fernando Lozano, Javier de la Torre, María J Galindo, Jorge Carmena, Jesús Santos, Carlos Tornero, Guillermo Verdejo, Gloria Samperiz, Zaira Palacios, Carmen Hidalgo-Tenorio, Carlos Dueñas, Jose A Terron, Miguel García-Deltoro, María T Rubio, Miguel A Cárdenes

Abstract

Background: The objective was to analyze the effectiveness and safety of dual therapy with rilpivirine plus boosted-darunavir (RPV + bDRV) in real-life patients.

Methods: Observational, retrospective, multi-center study in HIV+ patients who had received RPV + bDRV for 24 weeks to optimize/simplify their previous antiretroviral treatment. We determined the percentage of patients without virologic failure (2 consecutive viral loads > 50 copies/mL) at 24 weeks of treatment.

Results: The study included 161 patients from 15 hospitals with median age of 49 years; 29.3% had previous AIDS stage and median CD4+ lymphocyte nadir of 170 cells/uL. They had been diagnosed with HIV for a median of 17 years and had received 14 years of ART, with five previous treatment combinations, and 36.6% had a history of virological failure. The reasons for the switch were simplification/optimization (49.7%), toxicity/intolerance (17.4%), or inadequate effectiveness of previous ART (10.6%). Baseline VL of 50-1000 copies/mL was recorded in 25.5% of the patients. In the"intention-to-treat" analysis at 24 weeks, 87.6% of 161 patients continued the study treatment without virologic failure criteria. In the "on treatment" analysis (excluding patients who discontinued treatment with dual therapy for any reason other than virologic failure) the efficacy was 94.6% (141/149 patients).

Conclusions: Dual therapy with RPV + DRVb proved to be effective and safe in patients with advanced HIV infection, long exposure to ART, low CD4 nadir, previous virologic failure, and/or history of ineffective ART.

Keywords: Darunavir; Dual therapy; HIV; Nuke-sparing regimens; Rilpivirine; Simplification.

Conflict of interest statement

Competing interest

JP has received financial grants and/or honoraria from Janssen-Cilag, ViiV Healthcare, Bristol-Myers-Squibb, Merck Sharp & Dohme, Gilead & Abbvie as speaker fees and/or as Advisor fees. PA has received honoraria from Abbvie, Bristol-Myers Squibb, Gilead, Janssen, Merck and ViiV Healthcare as speaker fees and/or advisor fees as well as compensation for writing manuscripts and developing educational presentations. MJC has received honoraria from Abbvie, Gilead, Janssen, Merck and ViiV Healthcare as speaker fees and/or advisor fees. FL has received financial grants and/or honoraria from Gilead, Janssen, Merck and ViiV Healthcare as speaker fees. JdT has received honoraria from Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Janssen, Merck, Boehringer-Ingelheim and ViiV Healthcare as speaker fees and/or advisory fees. JS has received honoraria from Janssen, ViiV Healthcare, Merck and Gilead as speaker fees and/or advisory fees. ZP has received speaker honoraria from Gilead. Rest of authors have no conflicts of interest to declare.

Ethics approval and consent to participate

The study was approved by the regional ethics committee of Andalusia (CCEIBA) on April 25, 2016 and participants provided written informed consent for data from their medical records to be collected.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Flow chart of study patients

References

    1. Margolis AM, Heverling H, Pham PA, Stolbach A. A review of the toxicity of HIV medications. J Med Toxicol. 2014;10(1):26–39.
    1. Friis-Møller N, Ryom L, Smith C, Weber R, Reiss P, Dabis F, et al. An updated prediction model of the global risk of cardiovascular disease in HIV-positive persons: the data-collection on adverse effects of anti-HIV drugs (D:a:D) study. Eur J Prev Cardiol. 2016;23(2):214–223.
    1. Falcinelli E, Francisci D, Belfiori B, Petito E, Guglielmini G, Malincarne L, et al. In vivo platelet activation and platelet hyperreactivity in abacavir-treated HIV-infected patients. Thromb Haemost. 2013;110(2):349–357.
    1. Scherzer R, Estrella M, Li Y, Choi AI, Deeks SG, Grunfeld C, et al. Association of tenofovir exposure with kidney disease risk in HIV infection. AIDS. 2012;26(7):867–875.
    1. Bedimo R, Maalouf NM, Zhang S, Drechsler H, Tebas P. Osteoporotic fracture risk associated with cumulative exposure to tenofovir and other antiretroviral agents. AIDS. 2012;26(7):825–831.
    1. Mulligan K, Glidden DV, Anderson PL, Liu A, McMahan V, Gonzales P, et al. Effects of Emtricitabine/Tenofovir on bone mineral density in HIV-negative persons in a randomized, double-blind. Placebo-Controlled Trial Clin Infect Dis. 2015;61(4):572–580.
    1. Leeansyah E, Cameron PU, Solomon A, Tennakoon S, Velayudham P, Gouillou M, et al. Inhibition of telomerase activity by human immunodeficiency virus (HIV) nucleos(t) ide reverse transcriptase inhibitors: a potential factor contributing to HIV-associated accelerated aging. J Infect Dis. 2013;207(7):1157–1165.
    1. Kovari H, Sabin CA, Ledergerber B, Ryom L, Reiss P, Law M, et al. Antiretroviral Drugs and Risk of Chronic Alanine Aminotransferase Elevation in Human Immunodeficiency Virus (HIV)-Monoinfected Persons: The Data Collection on Adverse Events of Anti-HIV Drugs Study. Open Forum Infect Dis. 2016;3(1):ofw009.
    1. Carrero-Gras A, Antela A, Muñoz-Rodríguez J, Díaz-Menéndez M, Viciana P, Torrella-Domingo A, et al. Nuke-sparing regimens as a main simplification strategy and high level of toxicity resolution after antiretroviral switch: the SWITCHART study. J Int AIDS Soc. 2014;17(4 Suppl 3):19819.
    1. Rabi SA, Laird GM, Durand CM, Laskey S, Shan L, Bailey JR, et al. Multi-step inhibition explains HIV-1 protease inhibitor pharmacodynamics and resistance. J Clin Invest. 2013;123(9):3848–3860.
    1. Lathouwers E, Gupta S, Haddad M, Paquet A, de Meyer S, Baugh B. Trends in darunavir resistance-associated mutations and phenotypic resistance in commercially tested United States clinical samples between 2006 and 2012. AIDS Res Hum Retrovir. 2015;31(6):628–635.
    1. Pasquau J, Hidalgo-Tenorio C. Nuke-sparing regimens for the long-term care of HIV infection. AIDS Rev. 2015;17(4):220–230.
    1. Arribas JR, Pulido F, Delgado R, Lorenzo A, Miralles P, Arranz A, et al. Lopinavir/ritonavir as single-drug therapy for maintenance of HIV-1 viral suppression: 48-week results of a randomized, controlled, open-label, proof-of-concept pilot clinical trial (OK study) J Acquir Immune Defic Syndr. 2005;40(3):280–287.
    1. Arribas JR, Delgado R, Arranz A, Muñoz R, Portilla J, Pasquau J, et al. Lopinavir-ritonavir monotherapy versus lopinavir-ritonavir and 2 nucleosides for maintenance therapy of HIV: 96-week analysis. J Acquir Immune Defic Syndr. 2009;51(2):147–152.
    1. Arribas JR, Horban A, Gerstoft J, Fätkenheuer G, Nelson M, Clumeck N, et al. The MONET trial: darunavir/ritonavir with or without nucleoside analogues, for patients with HIV RNA below 50 copies/ml. AIDS. 2010;24(2):223–230.
    1. Pasquau J, Hidalgo-Tenorio C, Vergara A, al e. A clinical trail to compare the quality of life of HIV+ patietns who start monotherapy with LPV/r versus continuing triple therapy with a boosted PI. HIV Drug Therapy Congress; Glasgow2012.
    1. Valantin MA, Lambert-Niclot S, Flandre P, Morand-Joubert L, Cabiè A, Meynard JL, et al. Long-term efficacy of darunavir/ritonavir monotherapy in patients with HIV-1 viral suppression: week 96 results from the MONOI ANRS 136 study. J Antimicrob Chemother. 2012;67(3):691–695.
    1. Antinori A, Clarke A, Svedhem-Johansson V, Arribas JR, Arenas-Pinto A, Fehr J, et al. Week 48 efficacy and central nervous system analysis of darunavir/ritonavir monotherapy versus darunavir/ritonavir with two nucleoside analogues. AIDS. 2015;29(14):1811–1820.
    1. Paton NI, Stöhr W, Arenas-Pinto A, Fisher M, Williams I, Johnson M, et al. Protease inhibitor monotherapy for long-term management of HIV infection: a randomised, controlled, open-label, non-inferiority trial. Lancet HIV. 2015;2(10):e417–e426.
    1. López-Cortés LF, Castaño MA, López-Ruz MA, Rios-Villegas MJ, Hernández-Quero J, Merino D, et al. Effectiveness of ritonavir-boosted protease inhibitor monotherapy in clinical practice even with previous Virological failures to protease inhibitor-based regimens. PLoS One. 2016;11(2):e0148924.
    1. Pasquau J, López-Cortés L, Mayorga MI, Viciana P, Del Mar AM, Ríos MJ, et al. Monotherapy with darunavir/ritonavir is effective and safe in clinical practice. J Int AIDS Soc. 2014;17(4 Suppl 3):19813.
    1. Santos JR, Llibre JM, Berrio-Galan D, Bravo I, Miranda C, Pérez-Alvarez S, et al. Monotherapy with boosted PIs as an ART simplification strategy in clinical practice. J Antimicrob Chemother. 2015;70(4):1124–1129.
    1. Guiguet M, Ghosn J, Duvivier C, Meynard JL, Gras G, Partisani M, et al. Boosted protease inhibitor monotherapy as a maintenance strategy: an observational study. AIDS. 2012;26(18):2345–2350.
    1. Cozzi-Lepri A, Gianotti N, Antorini A, al e. ICONA Foundation Study and Mono PI/r database study cohorts. EACS; Barcelona2015.
    1. Pasquau J, Garcia-Vallecillos C, Cruces-Moreno M, et al. In monotherapy, darunavir/cobicistat demonstrates equivalence to darunavir/ritonavir, and in selected patients is as effective as bitherapies or triple therapies. International congress of drug therapy in HIV infection. J Int AIDS Soc: Glasgow; 2016.
    1. Mathis S, Khanlari B, Pulido F, Schechter M, Negredo E, Nelson M, et al. Effectiveness of protease inhibitor monotherapy versus combination antiretroviral maintenance therapy: a meta-analysis. PLoS One. 2011;6(7):e22003.
    1. Arribas J, Girard PM, Paton N, Winston A, Marcelin AG, Elbirt D, et al. Efficacy of PI monotherapy versus triple therapy for 1964 patients in 10 randomised trials. J Int AIDS Soc. 2014;17(4 Suppl 3):19788.
    1. Arribas JR, Girard PM, Landman R, Pich J, Mallolas J, Martínez-Rebollar M, et al. Dual treatment with lopinavir-ritonavir plus lamivudine versus triple treatment with lopinavir-ritonavir plus lamivudine or emtricitabine and a second nucleos(t) ide reverse transcriptase inhibitor for maintenance of HIV-1 viral suppression (OLE): a randomised, open-label, non-inferiority trial. Lancet Infect Dis. 2015;15(7):785–792.
    1. Mondi A, Fabbiani M, Ciccarelli N, Colafigli M, D'Avino A, Borghetti A, et al. Efficacy and safety of treatment simplification to atazanavir/ritonavir + lamivudine in HIV-infected patients with virological suppression: 144 week follow-up of the AtLaS pilot study. J Antimicrob Chemother. 2015;70(6):1843–1849.
    1. Perez-Molina JA, Rubio R, Rivero A, Pasquau J, Suárez-Lozano I, Riera M, et al. Dual treatment with atazanavir-ritonavir plus lamivudine versus triple treatment with atazanavir-ritonavir plus two nucleos(t) ides in virologically stable patients with HIV-1 (SALT): 48 week results from a randomised, open-label, non-inferiority trial. Lancet Infect Dis. 2015;15(7):775–784.
    1. Pulido F, Ribera E, Kagarde M, et al. Non-inferiority of dual-therapy with darunavir/ritonavir plus 3TC vs triple therapy with darunavir/ritonavir plus TDF/FTC or ABC/3TC for maintence of viral suppression: 48-week results of the DUAL-GESIDA 8014-RIS-EST45 trial. International congress of drug therapy in HIV infection; Glasgow: J Int AIDS Soc; 2016.
    1. Pulido F, Pérez-Valero I, Delgado R, Arranz A, Pasquau J, Portilla J, et al. Risk factors for loss of virological suppression in patients receiving lopinavir/ritonavir monotherapy for maintenance of HIV suppression. Antivir Ther. 2009;14(2):195–201.
    1. Stöhr W, Dunn DT, Arenas-Pinto A, Orkin C, Clarke A, Williams I, et al. Factors associated with virological rebound in HIV-infected patients receiving protease inhibitor monotherapy. AIDS. 2016;30(17):2617–2624.
    1. Gianotti N, Cozzi-Lepri A, Antinori A, Castagna A, De Luca A, Celesia BM, et al. Refining criteria for selecting candidates for a safe lopinavir/ritonavir or darunavir/ritonavir monotherapy in HIV-infected virologically suppressed patients. PLoS One. 2017;12(2):e0171611.
    1. Pulido F, Arribas JR, Hill A, Van Delft Y, Moecklinghoff C. Analysis of drug resistance during HIV RNA viraemia in the MONET trial of darunavir/ritonavir monotherapy. Antivir Ther. 2011;16(1):59–65.
    1. Arribas J, Hill A, Xi N, van Delft Y, Moecklinghoff C. Interleukin-6 and C-reactive protein levels after 3 years of treatment with darunavir/ritonavir monotherapy or darunavir/ritonavir + two nucleoside reverse transcriptase inhibitors in the MONET trial. J Antimicrob Chemother. 2012;67(7):1804–1806.
    1. BenMarzouk-Hidalgo OJ, Torres-Cornejo A, Gutiérrez-Valencia A, Ruiz-Valderas R, Viciana P, López-Cortés LF. Differential effects of viremia and microbial translocation on immune activation in HIV-infected patients throughout ritonavir-boosted darunavir monotherapy. Medicine (Baltimore) 2015;94(17):e781.
    1. Estébanez M, Stella-Ascariz N, Mingorance J, Pérez-Valero I, Bernardino JI, Zamora FX, et al. Inflammatory, procoagulant markers and HIV residual viremia in patients receiving protease inhibitor monotherapy or triple drug therapy: a cross-sectional study. BMC Infect Dis. 2014;14:379.
    1. Chun TW, Murray D, Justement JS, Hallahan CW, Moir S, Kovacs C, et al. Relationship between residual plasma viremia and the size of HIV proviral DNA reservoirs in infected individuals receiving effective antiretroviral therapy. J Infect Dis. 2011;204(1):135–138.
    1. Eastburn A, Scherzer R, Zolopa AR, Benson C, Tracy R, Do T, et al. Association of low level viremia with inflammation and mortality in HIV-infected adults. PLoS One. 2011;6(11):e26320.
    1. Gandhi RT, McMahon DK, Bosch RJ, Lalama CM, Cyktor JC, Macatangay BJ, et al. Levels of HIV-1 persistence on antiretroviral therapy are not associated with markers of inflammation or activation. PLoS Pathog. 2017;13(4):e1006285.
    1. Pérez-Valero I, González-Baeza A, Estébanez M, Monge S, Montes-Ramírez ML, Bayón C, et al. A prospective cohort study of neurocognitive function in aviremic HIV-infected patients treated with 1 or 3 antiretrovirals. Clin Infect Dis. 2014;59(11):1627–1634.
    1. Santos JR, Muñoz-Moreno JA, Moltó J, Prats A, Curran A, Domingo P, et al. Virological efficacy in cerebrospinal fluid and neurocognitive status in patients with long-term monotherapy based on lopinavir/ritonavir: an exploratory study. PLoS One. 2013;8(7):e70201.
    1. Torres-Cornejo A, BenMarzouk-Hidalgo OJ, Viciana P, Sánchez B, López-Ruz MA, López-Cortés LF, et al. Protease inhibitor monotherapy is effective in controlling human immunodeficiency virus 1 shedding in the male genital tract. Clin Microbiol Infect. 2016;22(1):98.e7-.e10.
    1. Lopez-Ruz MA, Navas P, López-Zúñiga MA, Gonzalvo MC, Sampedro A, Pasquau J, et al. Effect of monotherapy with Darunavir/ritonavir on viral load in seminal fluid, and quality parameters of semen in HIV-1-positive patients. PLoS One. 2016;11(7):e0159305.
    1. Vinuesa D, Parra-Ruiz J, Chueca N, Alvarez M, Muñoz-Medina L, Garcia F, et al. Protease inhibitor monotherapy is not associated with increased viral replication in lymph nodes. AIDS. 2014;28(12):1835–1837.
    1. Pasquau Liaño J. Penetración en reservorios. En: Lopinavir potenciado con ritonavir en monoterapia para el tratamiento del virus de la inmunodeficiencia humana. Enf Infecc Microb Clin. 2008;26(Supl 16):41–6.
    1. Fletcher CV, Staskus K, Wietgrefe SW, Rothenberger M, Reilly C, Chipman JG, et al. Persistent HIV-1 replication is associated with lower antiretroviral drug concentrations in lymphatic tissues. Proc Natl Acad Sci U S A. 2014;111(6):2307–2312.
    1. Ciaffi L, Koulla-Siro S, Sawadogo A, et al. Dual therapy with a boosted protease inhibitor plus lamivudine is an effective maitenance strategy in patients on second-line antiretroviral therapy in Africa: the ANRS 12286/MOBIDIP trial. International congress of drug therapy in HIV infection. J Int AIDS Soc: Glasgow, UK; 2016.
    1. Baril JG, Angel JB, Gill MJ, Gathe J, Cahn P, van Wyk J, et al. Dual therapy treatment strategies for the Management of Patients Infected with HIV: a systematic review of current evidence in ARV-naive or ARV-experienced. Virologically Suppressed Patients PLoS One. 2016;11(2):e0148231.
    1. Collins SE, Grant PM, Shafer RW. Modifying antiretroviral therapy in Virologically suppressed HIV-1-infected patients. Drugs. 2016;76(1):75–98.
    1. Pasquau J, Gostkorzewicz J, Ledesma F, Anceau A, Hill A, Moecklinghoff C. Budget impact analysis of switching to darunavir/ritonavir monotherapy for HIV-infected people in Spain. Appl Health Econ Health Policy. 2012;10(2):139–141.
    1. Oddershede L, Walker S, Paton N, Stöhr W, Dunn D, Sculpher M. Cost-effectiveness analysis of protease inhibitor monotherapy vs. ongoing triple-therapy in the long-term management of HIV patients. J Int AIDS Soc. 2014;17(4 Suppl 3):19498.
    1. Ribera E, Martínez-Sesmero JM, Sánchez-Rubio J, Rubio R, Pasquau J, Poveda JL, et al. [Economic impact of optimising antiretroviral treatment in human immunodeficiency virus-infected adults with suppressed viral load in Spain, by implementing the grade A-1 evidence recommendations of the 2015 GESIDA/national AIDS plan]. Enferm Infecc Microbiol Clin 2017.
    1. van Lunzen J, Pozniak A, Gatell JM, Antinori A, Klauck I, Serrano O, et al. Brief report: switch to ritonavir-boosted Atazanavir plus Raltegravir in Virologically suppressed patients with HIV-1 infection: a randomized pilot study. J Acquir Immune Defic Syndr. 2016;71(5):538–543.
    1. Amin J, Boyd MA, Kumarasamy N, Moore CL, Losso MH, Nwizu CA, et al. Raltegravir non-inferior to nucleoside based regimens in second-line therapy with lopinavir/ritonavir over 96 weeks: a randomised open label study for the treatment of HIV-1 infection. PLoS One. 2015;10(2):e0118228.
    1. Ruane PJ, Brinson C, Ramgopal M, Ryan R, Coate B, Cho M, et al. The Intelence aNd pRezista once a day study (INROADS): a multicentre, single-arm, open-label study of etravirine and darunavir/ritonavir as dual therapy in HIV-1-infected early treatment-experienced subjects. HIV Med. 2015;16(5):288–296.
    1. Gazzola L, Cicconi P, Ripamonti D, Di Filippo E, Gustinetti G, Di Biagio A, et al. Efficacy and safety of darunavir/ritonavir plus etravirine dual regimen in antiretroviral therapy-experienced patients: a multicenter clinical experience. HIV Clin Trials. 2014;15(4):140–150.
    1. Portilla J, Arazo P, Crusells J, Pérez-Martínez L, Martínez-Madrid O, Boix V, et al. Dual therapy with darunavir/r plus etravirine is safe and effective as switching therapy in antiretroviral experienced HIV-patients. The BITER Study. J Int AIDS Soc. 2014;17(4 Suppl 3):19803.
    1. Calin R, Paris L, Simon A, Peytavin G, Wirden M, Schneider L, et al. Dual raltegravir/etravirine combination in virologically suppressed HIV-1-infected patients on antiretroviral therapy. Antivir Ther. 2012;17(8):1601–1604.
    1. Calza L, Magistrelli E, Colangeli V, Borderi M, Conti M, Mancini R, et al. Improvement in renal function and bone mineral density after a switch from tenofovir/emtricitabine plus ritonavir-boosted protease inhibitor to raltegravir plus nevirapine: a pilot study. Antivir Ther. 2016;21(3):217–224.
    1. Bernardino JI, Mocroft A, Mallon PW, Wallet C, Gerstoft J, Russell C, et al. Bone mineral density and inflammatory and bone biomarkers after darunavir-ritonavir combined with either raltegravir or tenofovir-emtricitabine in antiretroviral-naive adults with HIV-1: a substudy of the NEAT001/ANRS143 randomised trial. Lancet HIV. 2015;2(11):e464–e473.
    1. Maggiolo F, Di Filippo E, Valenti D, Serna Ortega PA, Callegaro A. NRTI sparing therapy in Virologically controlled HIV-1 infected subjects: results of a controlled, randomized trial (Probe) J Acquir Immune Defic Syndr. 2016;72(1):46–51.
    1. Molina JM, Clotet B, van Lunzen J, Lazzarin A, Cavassini M, Henry K, et al. Once-daily dolutegravir versus darunavir plus ritonavir for treatment-naive adults with HIV-1 infection (FLAMINGO): 96 week results from a randomised, open-label, phase 3b study. Lancet HIV. 2015;2(4):e127–e136.
    1. Cevik M. Orkin C. Curr Opin HIV AIDS: Fixed dose darunavir boosted with cobicistat combined with emtricitabine and tenofovir alafenamide fumarate; 2018.
    1. Kanters S, Socias ME, Paton NI, Vitoria M, Doherty M, Ayers D, et al. Comparative efficacy and safety of second-line antiretroviral therapy for treatment of HIV/AIDS: a systematic review and network meta-analysis. Lancet HIV. 2017;4(10):e433–ee41.
    1. DHHS. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV 2018 [Available from: .
    1. FDA. Human Immunodeficiency Virus-1 Infection: Developing Antiretroviral Drugs for Treatment [Available from: .
    1. Arribas JR, Clumeck N, Nelson M, Hill A, van Delft Y, Moecklinghoff C. The MONET trial: week 144 analysis of the efficacy of darunavir/ritonavir (DRV/r) monotherapy versus DRV/r plus two nucleoside reverse transcriptase inhibitors, for patients with viral load < 50 HIV-1 RNA copies/mL at baseline. HIV Med. 2012;13(7):398–405.
    1. Perez-Molina JA, Rubio R, Rivero A, Pasquau J, Suárez-Lozano I, Riera M, et al. Simplification to dual therapy (atazanavir/ritonavir + lamivudine) versus standard triple therapy [atazanavir/ritonavir + two nucleos(t)ides] in virologically stable patients on antiretroviral therapy: 96 week results from an open-label, non-inferiority, randomized clinical trial (SALT study). J Antimicrob Chemother. 2016.
    1. Ananworanich J, Eller LA, Pinyakorn S, Kroon E, Sriplenchan S, Fletcher JL, et al. Viral kinetics in untreated versus treated acute HIV infection in prospective cohort studies in Thailand. J Int AIDS Soc. 2017;20(1):21652.
    1. Paton NI, Stöhr W, Oddershede L, Arenas-Pinto A, Walker S, Sculpher M, et al. The protease inhibitor monotherapy versus ongoing triple therapy (PIVOT) trial: a randomised controlled trial of a protease inhibitor monotherapy strategy for long-term management of human immunodeficiency virus infection. Health Technol Assess. 2016;20(21):1–158.
    1. Margolis DA, Gonzalez-Garcia J, Stellbrink HJ, Eron JJ, Yazdanpanah Y, Podzamczer D, et al. Long-acting intramuscular cabotegravir and rilpivirine in adults with HIV-1 infection (LATTE-2): 96-week results of a randomised, open-label, phase 2b, non-inferiority trial. Lancet. 2017;390(10101):1499–1510.

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren