PMID- 35399147 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220716 IS - 2193-8229 (Print) IS - 2193-6382 (Electronic) IS - 2193-6382 (Linking) VI - 11 IP - 3 DP - 2022 Jun TI - Shorter Time to Discontinuation Due to Treatment Failure in People Living with HIV Switched to Dolutegravir Plus Either Rilpivirine or Lamivudine Compared with Integrase Inhibitor-Based Triple Therapy in a Large Spanish Cohort. PG - 1177-1192 LID - 10.1007/s40121-022-00630-y [doi] AB - INTRODUCTION: Standard therapy for HIV treatment has consisted of two nucleoside analogue reverse transcriptase inhibitors (NRTI) paired with a third agent. Use of two-drug regimens (2DR) has been considered for selected patients in part to avoid toxicities associated with the use of NRTIs. This study aimed to compare the real-world outcomes of integrase inhibitor (INSTI)-based three-drug regimens (3DR) versus 2DR of dolutegravir (DTG) + rilpivirine (RPV) or DTG + lamivudine (3TC). METHODS: All patients in the Spanish VACH cohort switching to INSTI-based 3DR or a 2DR consisting of DTG + RPV or DTG + 3TC between May 2, 2016 and May 15, 2019 were included. Kaplan-Meier curves and Cox proportional hazard models were used to assess time to/risk of discontinuation due to treatment failure (TF) (defined as virologic failure [VF], immunologic failure, or disease progression) and adverse events (AEs). Three secondary analyses were performed: (1) in restricting the analysis to patients who were virologically suppressed (HIV RNA < 50 copies/mL) at switch; (2) matched analysis (2:1, matched by age, sex, number of previous VFs, and line of regimen), and (3) using VF as the primary endpoint in all patients. RESULTS: Overall, 5047 3DR and 617 2DR patients were analyzed. Baseline characteristics differed between groups; 2DR patients were older, more treatment experienced, and more likely to be virologically suppressed at switch. Time to discontinuation due to TF was significantly shorter for 2DR (P = 0.002). The hazard ratio (HR) for discontinuation due to TF on 2DR vs 3DR was 2.33 (P = 0.003). No difference was observed for time to discontinuation (P = 0.908) or risk of discontinuation due to AEs (HR = 0.80; P = 0.488). Results were qualitatively similar in virologically suppressed patients, matched analysis, and for VF. CONCLUSION: In the real world, the risks of discontinuation due to TF and VF were more than two times higher in patients switching to DTG-based 2DR than INSTI-based 3DR, with no difference in discontinuation due to AEs. CI - (c) 2022. The Author(s). FAU - Teira, Ramon AU - Teira R AD - Service of Internal Medicine, Hospital de Sierrallana, 39300, Torrelavega, Spain. ramon.teira1@gmail.com. FAU - Diaz-Cuervo, Helena AU - Diaz-Cuervo H AD - Gilead Sciences, MAOR, London, UK. FAU - Aragao, Filipa AU - Aragao F AD - Maple Health Group, New York City, NY, USA. AD - NOVA National School of Public Health, Public Health Research Centre, Unversidade NOVA de Lisboa, Lisboa, Portugal. FAU - Castano, Manuel AU - Castano M AD - Hospital Regional Universitario de Malaga, Malaga, Spain. FAU - Romero, Alberto AU - Romero A AD - Hospital Universitario de Puerto Real, Puerto Real, Spain. FAU - Roca, Bernardino AU - Roca B AD - Hospital General de Castellon, Castellon, Spain. FAU - Montero, Marta AU - Montero M AD - Hospital Universitario Y Politecnico La Fe, Valencia, Spain. FAU - Galindo, Maria Jose AU - Galindo MJ AD - Hospital Clinico Universitario de Valencia, Valencia, Spain. FAU - Munoz-Sanchez, Maria Jose AU - Munoz-Sanchez MJ AD - Hospital Universitario de Basurto, Bilbao, Spain. FAU - Espinosa, Nuria AU - Espinosa N AD - Hospital Universitario Virgen del Rocio, Sevilla, Spain. FAU - Peraire, Joaquim AU - Peraire J AD - Hospital Universitario Joan XXIII, Tarragona, Spain. FAU - Martinez, Elisa AU - Martinez E AD - Complejo Hospitalario de Albacete, Albacete, Spain. FAU - de la Fuente, Belen AU - de la Fuente B AD - Hospital Universitario de Cabuenes, Gijon, Spain. FAU - Domingo, Pere AU - Domingo P AD - Hospital de Al Santa Pau, Barcelona, Spain. FAU - Deig, Elisabeth AU - Deig E AD - Hospital General de Granollers, Granollers, Spain. FAU - Merino, Maria Dolores AU - Merino MD AD - Hospital Juan Ramon Jimenez, Huelva, Spain. FAU - Geijo, Paloma AU - Geijo P AD - Hospital Virgen de La Luz, Cuenca, Spain. FAU - Estrada, Vicente AU - Estrada V AD - Hospital Clinico de San Carlos, Madrid, Spain. FAU - Sepulveda, Maria Antonia AU - Sepulveda MA AD - Hospital Virgen de La Salud, Toledo, Spain. FAU - Garcia, Josefina AU - Garcia J AD - Hospital de Santa Lucia, Cartagena, Spain. FAU - Berenguer, Juan AU - Berenguer J AD - Hospital Gregorio Maranon, Madrid, Spain. FAU - Curran, Adria AU - Curran A AD - Hospital Universitari Vall d Hebron, Barcelona, Spain. LA - eng PT - Journal Article DEP - 20220411 PL - New Zealand TA - Infect Dis Ther JT - Infectious diseases and therapy JID - 101634499 PMC - PMC9124284 OAB - People living with HIV (PLHIV) need lifelong treatment to prevent progression to AIDS. Standard HIV treatments use three different drugs in combination, but these can potentially cause unwanted side effects. Treatments using just two drugs have been developed. These aim to reduce side effects and treat HIV effectively. This study included 5664 participants in Spain who were split into two groups: 5047 participants switched from their old treatment to a three-drug regimen (3DR), and 617 participants switched to a two-drug regimen (2DR). The researchers measured how long it took for the participants to stop taking their treatment because it was not working, or it caused too many side effects. At the end of the study, more than 70% of participants in either group were still taking the same treatment. Of the 30% of participants who stopped treatment because it stopped working, those taking a 2DR stopped sooner than those taking a 3DR. This difference started to appear at about 18 months and got bigger until the study ended, which was 3 years after starting treatment. Participants taking a 2DR were twice as likely to stop treatment because it was not working than those taking a 3DR. There was no difference between the groups for how long it took for participants to stop their treatment because of side effects. These results show that for some PLHIV, the 2DR stopped working sooner than 3DR, without the benefit of fewer side effects. OABL- eng OTO - NOTNLM OT - Adverse events OT - Effectiveness OT - HIV OT - Time to discontinuation OT - Triple therapy OT - Two-drug combinations OT - Virologic failure EDAT- 2022/04/12 06:00 MHDA- 2022/04/12 06:01 PMCR- 2022/04/11 CRDT- 2022/04/11 05:09 PHST- 2021/12/12 00:00 [received] PHST- 2022/03/18 00:00 [accepted] PHST- 2022/04/12 06:00 [pubmed] PHST- 2022/04/12 06:01 [medline] PHST- 2022/04/11 05:09 [entrez] PHST- 2022/04/11 00:00 [pmc-release] AID - 10.1007/s40121-022-00630-y [pii] AID - 630 [pii] AID - 10.1007/s40121-022-00630-y [doi] PST - ppublish SO - Infect Dis Ther. 2022 Jun;11(3):1177-1192. doi: 10.1007/s40121-022-00630-y. Epub 2022 Apr 11.