Background: The aim of this study was to investigate the effectiveness and tolerability of the combination elvitegravir/cobicistat/tenofovir/emtricitabine plus darunavir (EVG/COB/TFV/FTC + DRV) in treatment-experienced patients from the cohort of the Spanish HIV/AIDS Research Network (CoRIS). Methods: Treatment-experienced patients starting treatment with EVG/COB/TFV/FTC + DRV during the years 2014–2018 and with more than 24 weeks of follow-up were included. TFV could be administered either as tenofovir disoproxil fumarate or tenofovir alafenamide. We evaluated virological response, defined as viral load (VL) < 50 copies/ml and < 200 copies/ml at 24 and 48 weeks after starting this regimen, stratified by baseline VL (< 50 or ≥ 50 copies/ml at the start of the regimen). Results: We included 39 patients (12.8% women). At baseline, 10 (25.6%) patients had VL < 50 copies/ml and 29 (74.4%) had ≥ 50 copies/ml. Among patients with baseline VL < 50 copies/ml, 85.7% and 80.0% had VL < 50 copies/ml at 24 and 48 weeks, respectively, and 100% had VL < 200 copies/ml at 24 and 48 weeks. Among patients with baseline VL ≥ 50 copies/ml, 42.3% and 40.9% had VL < 50 copies/ml and 69.2% and 68.2% had VL < 200 copies/ml at 24 and 48 weeks. During the first 48 weeks, no patients changed their treatment due to toxicity, and 4 patients (all with baseline VL ≥ 50 copies/ml) changed due to virological failure. Conclusions: EVG/COB/TFV/FTC + DRV was well tolerated and effective in treatment-experienced patients with undetectable viral load as a simplification strategy, allowing once-daily, two-pill regimen with three antiretroviral drug classes. Effectiveness was low in patients with detectable viral loads.
Keywords: HIV infection; Highly active antiretroviral therapy; Cohort studies; Darunavir
Treatment adherence is crucial for the effectiveness of antiretroviral therapy (ART) among HIV-infected patients. Adherence could be impaired with antiretroviral regimens that entail multiple pills or more than once-daily dosing [[
The fixed-dose combinations elvitegravir/cobicistat/tenofovir disoproxil fumarate/emtricitabine (EVG/COB/TDF/FTC, Stribild
With these combinations, COB, which boosts EVG, would also allow boosting of DRV [[
The efficacy of EVG/COB/TAF/FTC + DRV in virologically suppressed patients was demonstrated in an open-label clinical trial, which showed that switching to EVG/COB/TAF/FTC + DRV was non-inferior to maintaining the previous ART at 24 weeks and superior at 48 weeks [[
Given the very scarce evidence with the combinations EVG/COB/TDF/FTC + DRV and EVG/COB/TAF/FTC + DRV in clinical practice, the conflicting results of pharmacokinetic studies, and the potential advantages of these combinations as a simplification strategy, we designed a study to describe the use of elvitegravir/cobicistat/tenofovir (administered either as disoproxil fumarate or alafenamide)/emtricitabine plus darunavir 800 mg (EVG/COB/TFV/FTC + DRV) and analyse its effectiveness and tolerability in the multicentre Cohort of the Spanish HIV/AIDS Research Network (CoRIS). The specific objectives of the study were: (
Patients were selected from the Cohort of the Spanish HIV/AIDS Research Network (CoRIS), which has been described in detail elsewhere [[
We included all treatment-experienced patients who started treatment with EVG/COB/TFV/FTC + DRV from January 2014 to November 2018 and who had more than 24 weeks of follow-up. TFV could be administered either as tenofovir disoproxil fumarate or tenofovir alafenamide.
We collected information on the following variables: age, sex, mode of HIV transmission (men who have sex with men [MSM], heterosexual, injecting drug user [IDU], other/unknown), country of origin (Spanish, foreign-born), CD4 count and viral load at the start of EVG/COB/TFV/FTC + DRV and at 24 and 48 weeks after starting this regimen (± 12 weeks), reasons for stopping the previous treatment and EVG/COB/TFV/FTC + DRV (simplification, virological failure, toxicity, interactions, other, unknown) and regimen to which it was switched, previous antiretroviral regimens, number of pills and doses per day with the previous antiretroviral regimen, and time since the start of the first ART.
Descriptive analyses were carried out using frequency tables for categorical variables and median and interquartile range (IQR) for continuous variables. For the analysis of treatment effectiveness, the primary endpoint was the proportion of patients with virological response, defined as viral load < 50 copies/ml at 24 and 48 weeks after starting EVG/COB/TFV/FTC + DRV. Since the threshold of 200 copies/ml is used in several guidelines to define virologic failure [[
Statistical analyses were performed in Stata software (version 14.0; Stata Corporation, College Station, Texas, USA). All patients signed informed consent forms. The study was approved by the Ethics Committee of Instituto de Salud Carlos III (Madrid).
During the study period, 39 patients from 11 centres switched their ART to the regimen EVG/COB/TFV/FTC + DRV. Patients' demographic and clinical characteristics are shown in Table 1. At the start of the regimen, tenofovir was administered as TDF in 16 and as TAF in 23 patients. During follow-up, eight of the 16 patients who started the regimen with TDF switched TDF to TAF as part of the same regimen.
Patients' characteristics at the start of EVG/COB/TFV/FTC + DRV (n = 39)
Age, median (IQR), years 42 (34–50) Female 5 (12.8) Mode of transmission Men who have sex with men 19 (48.7) Heterosexual 13 (33.3) Injecting drug user 5 (12.8) Other/unknown 2 (5.1) Geographic origin Spanish 14 (33.3) Foreign-born 24 (61.5) Unknown 1 (2.4) Viral load, median (IQR), copies/ml 379 (40–12,000) CD4 count, median (IQR), cells/microl 437 (108–740) Viral load < 50 copies/ml 10 (25.6) ≥ 50 copies/ml 29 (74.4) Years since starting ART, median (IQR) 5.3 (2.5–7.5) Number of prior regimens, median (IQR) 3 (2–6) Previous ART regimen ART daily pill burden, median (IQR) 2 (1–5) At least 3 pills per day 17 (43.6) At least twice daily ART dosing 11 (28.2) Reasons for switching to EVG/COB/TFV/FTC + DRV Virologic failure 14 (35.9) Simplification 10 (25.6) Toxicity 4 (10.3) Non-adherence 2 (5.1) Unknown 9 (23.1)
Values are expressed as n/total (%) unless stated otherwise IQR Interquartile range
At baseline, 10 (25.6%) patients were virologically suppressed and 29 (74.4%) patients had detectable viral load. The most frequent reasons for changing to this regimen were virological failure and treatment simplification (Table 1).
The patients received EVG/COB/TFV/FTC + DRV for a median of 391 (IQR: 205 to 514) days. Outcomes at 24 and 48 weeks are shown in Table 2.
Outcomes of patients at 24 and 48 weeks after starting EVG/COB/TFV/FTC + DRV, stratified by viral load at the start of the regimen
Outcome 24 weeks 48 weeks Virological response < 50 copies/ml Viral load < 50 copies/ml 6/7 (85.7) 4/5 (80.0) Viral load ≥ 50 copies/ml 11/26 (42.3) 9/22 (40.9) Virological response < 200 copies/ml Viral load < 50 copies/ml 7/7 (100.0) 5/5 (100.0) Viral load ≥ 50 copies/ml 18/26 (69.2) 15/22 (68.2) CD4 change, cells/microl: median (IQR) Viral load < 50 copies/ml 29 (14–48) 8 (− 85–50) Viral load ≥ 50 copies/ml − 6 (− 134–107) − 16 (− 116–77) Patients stopping the regimen for any reason Viral load < 50 copies/ml 0/10 (0) 2/10 (20.0) Viral load ≥ 50 copies/ml 8/29 (27.6) 13/29 (44.8) Patients stopping the regimen due to treatment failure Viral load < 50 copies/ml 0/10 (0) 0/10 (0) Viral load ≥ 50 copies/ml 4/29 (13.8) 4/29 (13.8) Patients stopping the regimen due to toxicity Viral load < 50 copies/ml 0/10 (0) 0/10 (0) Viral load ≥ 50 copies/ml 0/29 (0) 0/29 (0)
Values are expressed as n/total (%) unless stated otherwise IQR Interquartile range
Among virologically suppressed patients at baseline, 85.7% and 80.0% of the patients achieved viral load < 50 copies/ml at 24 and 48 weeks, respectively. However, among patients with detectable baseline viral load, only 42.3% and 40.9% achieved these endpoints, respectively. The percentages of patients achieving viral load < 200/ml at 24 and 48 weeks were higher for both groups and reached 100% among the patients who were virologically suppressed at baseline.
The number of patients who changed their treatment during the first 24 and 48 weeks, stratified by baseline viral load, is shown in Table 2. Among the two virologically suppressed patients at baseline who changed their treatment during the first 48 weeks, the reasons were simplification in 1 patient and unknown in 1 patient. Among patients with baseline detectable viral load, the reasons for changing the regimen during the first 24 weeks were failure in 4, simplification in 3, and non-adherence in 1 patient, and the reasons for changing the regimen during the first 48 weeks were simplification in 7 patients, failure in 4 patients, nonadherence in 1 patient, and unknown in 1 patient.
This study has analysed the largest cohort published to date showing results from "real-world" clinical practice with the regimen EVG/COB/TFV/FTC + DRV. In our study, EVG/COB/TFV/FTC + DRV was well tolerated and effective in treatment-experienced patients with baseline undetectable viral load as a simplification strategy, allowing a once-daily, two-pill regimen with three antiretroviral drug classes. However, effectiveness was low in patients with baseline detectable viral loads.
There is only one open-label clinical trial that assessed the efficacy of this regimen, which analysed 135 treatment-experienced, virologically suppressed patients who were randomized to continue their previous ART or change to EVG/COB/TAF/FTC + DRV. The study found that this combination had high efficacy (96.6%) and was noninferior to maintaining the previous ART at 24 weeks and superior at 48 weeks [[
Regarding real-world data, the evidence for the effectiveness of this regimen is very limited: only three cohort studies have been published analysing EVG/COB/TDF/FTC + DRV, all from single centres, involving a very low number of patients, and analysing different endpoints. The effectiveness was high in the three studies: Naccarato et al. evaluated 21 treatment-experienced patients (29% of which were virologically suppressed before the switch) who received EVG/COB/TDF/FTC + DRV: at week 48, 14 (67%) patients had undetectable viral load, 1 had virologic failure (> 40 copies/ml) and 6 had stopped the treatment or had no viral load data [[
In our study, the effectiveness of EVG/COB/TFV/FTC + DRV was high in patients who were virologically suppressed at baseline: 85.7% and 80.0% of the patients had viral loads < 50 copies at 24 and 48 weeks, respectively, and 100% of the patients had viral loads < 200 copies/ml at 24 and 48 weeks. These results are comparable to the studies mentioned above. However, the effectiveness was much lower for patients who had detectable viral loads at baseline. These results suggest that this regimen has high effectiveness as a switch strategy for virologically suppressed patients, but it should not be used in patients with virological failure if other alternatives exist. Overall, the treatment was well tolerated in both groups, as none of the patients discontinued their treatment due to toxicity. The treatment also allowed to decrease the pill burden in 43.6% of the patients and the number of doses per day in 28.2%.
For the combination EVG/COB/TFV/FTC + DRV, our patients were receiving tenofovir either as alafenamide or as disoproxil fumarate. Also, as EVG/COB/TAF/FTC was commercialized in Spain in May 2016, many patients who were receiving EVG/COB/TDF/FTC changed their treatment to EVG/COB/TAF/FTC in order to minimize the risk of renal and bone toxicity, as did 8 of our patients. Given that the treatment with EVG/COB/TAF/FTC has shown non-inferiority compared to EVG/COB/TDF/FTC in clinical trials [[
Our study has the limitation of low sample size. Also, since CoRIS does not routinely record resistance testing in pre-treated patients, we could not describe accumulated resistance mutations or those arising after failure with this regimen. Another limitation is that we cannot give information on patients' adherence as CoRIS does not routinely record this variable. However, this is the largest cohort published to date analysing this treatment regimen, with a reasonable follow-up time, and it gives information from routine clinical practice for a combination that could be potentially useful for treatment simplification and has very little published evidence. Our strengths include the use of a multicentre cohort with rigorous quality control and which has clinical and demographic characteristics that are similar to the ones from the general population reported by the National HIV Surveillance System [[
The combination EVG/COB/TFV/FTC + DRV is an effective, well tolerated strategy for treatment simplification in virologically suppressed patients. This treatment is not suitable, however, for treatment-experienced individuals with detectable viral loads, given the low efficacy in this group of patients.
The RIS cohort (CoRIS) is supported by the Instituto de Salud Carlos III through the Red Temática de Investigación Cooperativa en Sida (RD06/006, RD12/0017/0018 and RD16/0002/0006) as part of the Plan Nacional I + D + i and cofinanced by ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER)".
This study would not have been possible without the collaboration of all patients, medical and nursing staff and data managers who have taken part in the Project.
Executive committee: Santiago Moreno, Inma Jarrín, David Dalmau, Maria Luisa Navarro, Maria Isabel González, Federico Garcia, Eva Poveda, Jose Antonio Iribarren, Félix Gutiérrez, Rafael Rubio, Francesc Vidal, Juan Berenguer, Juan González, M Ángeles Muñoz-Fernández.
Fieldwork data management and analysis: Inmaculada Jarrin, Belén Alejos, Cristina Moreno, Carlos Iniesta, Luis Miguel Garcia Sousa, Nieves Sanz Perez, Marta Rava.
BioBanK HIV Hospital General Universitario Gregorio Marañón: M Ángeles Muñoz-Fernández, Irene Consuegra Fernández.
Hospital General Universitario de Alicante (Alicante): Esperanza Merino, Gema García, Irene Portilla, Iván Agea, Joaquín Portilla, José Sánchez-Payá., Juan Carlos Rodríguez, Lina Gimeno, Livia Giner, Marcos Díez, Melissa Carreres, Sergio Reus, Vicente Boix, Diego Torrús.
Hospital Universitario de Canarias (San Cristobal de la Laguna): Ana López Lirola, Dácil García, Felicitas Díaz-Flores, Juan Luis Gómez, María del Mar Alonso, Ricardo Pelazas., Jehovana Hernández, María Remedios Alemán, María Inmaculada Hernández.
Hospital Universitario Central de Asturias (Oviedo): Víctor Asensi, Eulalia Valle, María Eugenia Rivas Carmenado, Tomas Suarez-Zarracina Secades, Laura Pérez Is.
Hospital Universitario 12 de Octubre (Madrid): Rafael Rubio, Federico Pulido, Otilia Bisbal, Asunción Hernando, Lourdes Domínguez, David Rial Crestelo, Laura Bermejo, Mireia Santacreu.
Hospital Universitario de Donostia (Donostia-San Sebastián): José Antonio Iribarren, Julio Arrizabalaga, María José Aramburu, Xabier Camino, Francisco Rodríguez-Arrondo, Miguel Ángel von Wichmann, Lidia Pascual Tomé, Miguel Ángel Goenaga, Mª Jesús Bustinduy, Harkaitz Azkune, Maialen Ibarguren, Aitziber Lizardi, Xabier Kortajarena., Mª Pilar Carmona Oyaga, Maitane Umerez Igartua.
Hospital General Universitario De Elche (Elche): Félix Gutiérrez, Mar Masiá, Sergio Padilla, Andrés Navarro, Fernando Montolio, Catalina Robledano, Joan Gregori Colomé, Araceli Adsuar, Rafael Pascual, Marta Fernández, Elena García., José Alberto García, Xavier Barber.
Hospital Universitari Germans Trias i Pujol (Can Ruti) (Badalona): Roberto Muga, Arantza Sanvisens, Daniel Fuster.
Hospital General Universitario Gregorio Marañón (Madrid): Juan Berenguer, Juan Carlos López Bernaldo de Quirós, Isabel Gutiérrez, Margarita Ramírez, Belén Padilla, Paloma Gijón, Teresa Aldamiz-Echevarría, Francisco Tejerina, Francisco José Parras, Pascual Balsalobre, Cristina Diez, Leire Pérez Latorre., Chiara Fanciulli.
Hospital Universitari de Tarragona Joan XXIII (Tarragona): Francesc Vidal, Joaquín Peraire, Consuelo Viladés, Sergio Veloso, Montserrat Vargas, Montserrat Olona, Anna Rull, Esther Rodríguez-Gallego, Verónica Alba., Alfonso Javier Castellanos, Miguel López-Dupla.
Hospital Universitario y Politécnico de La Fe (Valencia): Marta Montero Alonso, José López Aldeguer, Marino Blanes Juliá, María Tasias Pitarch, Iván Castro Hernández, Eva Calabuig Muñoz, Sandra Cuéllar Tovar, Miguel Salavert Lletí, Juan Fernández Navarro.
Hospital Universitario La Paz/IdiPAZ: Juan González-Garcia, Francisco Arnalich, José Ramón Arribas, Jose Ignacio Bernardino de la Serna, Juan Miguel Castro, Luis Escosa, Pedro Herranz, Victor Hontañón, Silvia García-Bujalance, Milagros García López-Hortelano, Alicia González-Baeza, Maria Luz Martín-Carbonero, Mario Mayoral, Maria Jose Mellado, Rafael Esteban Micán, Rocio Montejano, María Luisa Montes, Victoria Moreno, Ignacio Pérez-Valero, Berta Rodés, Talia Sainz, Elena Sendagorta, Natalia Stella Alcáriz, Eulalia Valencia.
Hospital San Pedro Centro de Investigación Biomédica de La Rioja (CIBIR) (Logroño): José Ramón Blanco, José Antonio Oteo, Valvanera Ibarra, Luis Metola, Mercedes Sanz, Laura Pérez-Martínez.
Hospital Universitario Miguel Servet (Zaragoza): Piedad Arazo, Gloria Sampériz.
Hospital Universitari MutuaTerrassa (Terrasa): David Dalmau, Angels Jaén, Montse Sanmartí, Mireia Cairó, Javier Martinez-Lacasa, Pablo Velli, Roser Font, Mariona Xercavins, Noemí Alonso.
Complejo Hospitalario de Navarra (Pamplona): Maria Rivero Marcotegui, Jesús Repáraz, María Gracia Ruiz de Alda, María Teresa de León Cano, Beatriz Pierola Ruiz de Galarreta
Corporació Sanitària Parc Taulí (Sabadell): María José Amengual, Gemma Navarro, Manel Cervantes Garcia, Sonia Calzado Isbert, Marta Navarro Vilasaro.
Hospital Universitario de La Princesa (Madrid): Ignacio de los Santos, Jesus Sanz Sanz, Ana Salas Aparicio, Cristina Sarria Cepeda, Lucio Garcia-Fraile Fraile, Enrique Martín Gayo.
Hospital Universitario Ramón y Cajal (Madrid): Santiago Moreno, José Luis Casado Osorio, Fernando Dronda Nuñez, Ana Moreno Zamora, Maria Jesús Pérez Elías, Carolina Gutiérrez, Nadia Madrid, Santos del Campo Terrón, Sergio Serrano Villar, Maria Jesús Vivancos Gallego, Javier Martínez Sanz, Usua Anxa Urroz, Tamara Velasco
Hospital General Universitario Reina Sofía (Murcia): Enrique Bernal, Alfredo Cano Sanchez, Antonia Alcaraz García, Joaquín Bravo Urbieta, Angeles Muñoz Perez, Maria Jose Alcaraz, Maria del Carmen Villalba.
Hospital Nuevo San Cecilio (Granada): Federico García, José Hernández Quero, Leopoldo Muñoz Medina , Marta Alvarez, Natalia Chueca, David Vinuesa García , Clara Martinez-Montes., Carlos Guerrero Beltran, Adolfo de Salazar Gonzalerz, Ana Fuentes Lopez.
Centro Sanitario Sandoval (Madrid): Montserrat Raposo Utrilla, Jorge Del Romero, Carmen Rodríguez, Teresa Puerta, Juan Carlos Carrió, Mar Vera, Juan Ballesteros, Oskar Ayerdi.
Hospital Clínico Universitario de Santiago (Santiago de Compostela): Antonio Antela, Elena Losada.
Hospital Universitario Son Espases (Palma de Mallorca): Melchor Riera, María Peñaranda, María Leyes, Mª Angels Ribas, Antoni A Campins, Carmen Vidal, Francisco Fanjul, Javier Murillas, Francisco Homar.
Hospital Universitario Virgen de la Victoria (Málaga): Jesús Santos, Crisitina Gómez Ayerbe, Isabel Viciana, Rosario Palacios, Carmen Pérez López, Carmen Maria Gonzalez-Domenec.
Hospital Universitario Virgen del Rocío (Sevilla): Pompeyo Viciana, Nuria Espinosa, Luis Fernando López-Cortés.
Hospital Universitario de Bellvitge (Hospitalet de Llobregat): Daniel Podzamczer, Arkaitz Imaz, Juan Tiraboschi, Ana Silva, María Saumoy, Paula Prieto.
Hospital Universitario Valle de Hebrón (Barcelona): Esteban Ribera, Adrian Curran.
Hospital Costa del Sol (Marbella): Julián Olalla Sierra, Javier Pérez Stachowski., Alfonso del Arco, Javier de la torre, José Luis Prada, José María García de Lomas Guerrero.
Hospital General Universitario Santa Lucía (Cartagena): Onofre Juan Martínez, Francisco Jesús Vera, Lorena Martínez, Josefina García, Begoña Alcaraz, Amaya Jimeno.
Complejo Hospitalario Universitario a Coruña (Chuac) (A Coruña): Angeles Castro Iglesias, Berta Pernas Souto, Alvaro Mena de Cea.
Hospital Universitario Basurto (Bilbao): Josefa Muñoz, Miren Zuriñe Zubero, Josu Mirena Baraia-Etxaburu, Sofía Ibarra Ugarte, Oscar Luis Ferrero Beneitez, Josefina López de Munain, Mª Mar Cámara López, Mireia de la Peña, Miriam Lopez., Iñigo Lopez Azkarreta.
Hospital Universitario Virgen de la Arrixaca (El Palmar): Carlos Galera, Helena Albendin, Aurora Pérez, Asunción Iborra, Antonio Moreno, Maria Angustias Merlos, Asunción Vidal, Marisa Meca.
Hospital de la Marina Baixa (La Vila Joiosa): Concha Amador, Francisco Pasquau, Javier Ena, Concha Benito, Vicenta Fenoll., Concepcion Gil Anguita, Jose Tomas Algado Rabasa.
Hospital Universitario Infanta Sofia (San Sebastian de los Reyes): Inés Suárez-García, Eduardo Malmierca, Patricia González-Ruano, Dolores Martín Rodrigo, Mª Pilar Ruiz Seco.,
Hospital Universitario de Jaén (Jaén): Mohamed Omar Mohamed-Balghata, María Amparo Gómez Vidal.
Hospital San Agustín (Avilés): Miguel Alberto de Zarraga.
Hospital Clínico San Carlos (Madrid): Vicente Estrada Pérez, Maria Jesus Téllez Molina, Jorge Vergas García, Juncal Pérez-Somarriba Moreno.
Hospital Universitario Fundación Jiménez Díaz (Madrid): Miguel Górgolas, Alfonso Cabello, Beatriz Álvarez, Laura Prieto.
Hospital Universitario Príncipe de Asturias (Alcalá de Henares): José Sanz Moreno, Alberto Arranz Caso, Cristina Hernández Gutiérrez, María Novella Mena.
Hospital Clínico Universitario de Valencia (València): María José Galindo Puerto, Ramón Fernando Vilalta, Ana Ferrer Ribera.
Hospital Reina Sofía (Córdoba): Antonio Rivero Román, Antonio Rivero Juárez, Pedro López López, Isabel Machuca Sánchez, Mario Frias Casas, Angela Camacho Espejo.
Hospital Universitario Severo Ochoa (Leganés): Miguel Cervero Jiménez, Rafael Torres Perea.
Nuestra Señora de Valme (Sevilla): Juan A Pineda, Pilar Rincón Mayo, Juan Macias Sanchez, Nicolas Merchante Gutierrez, Luis Miguel Real, Anais Corma Gomez, Marta Fernandez Fuertes, Alejandro Gonzalez-Serna.
Hospital Álvaro Cunqueiro (Vigo): Eva Poveda, Alexandre Pérez, Manuel Crespo, Luis Morano, Celia Miralles, Antonio Ocampo, Guillermo Pousada.
All authors were involved in the setting up of the cohort and contributed to its design. All authors were involved in data collection. ISG asked the research question presented in this paper and designed the study. ISG and CM performed the statistical analyses. ISG wrote the first draft of the paper which was supervised by IJ. All authors were involved in interpretation of the data and commented on interim drafts. All authors read and approved the final manuscript.
The authors confirm that, for approved reasons, some access restrictions apply to the data underlying the findings. Data cannot be made publicly available because they are owned by a third party, the HIV/AIDS Research Network (RIS), and because participants agreed that data would only be used for research projects by RIS or those projects approved by its Executive and Scientific Committee. Interested readers may send requests for the data to proyectoscoris@gmail.com. Requests will be assessed by the Executive and Scientific Committee.
Ethics approval was obtained from all hospitals' Ethics Committees and every patient provided written informed consent to participate in the cohort. This study was approved by the Ethics Committee of Instituto de Salud Carlos III, Madrid, Spain.
Not applicable.
ISG has received conference grants or speaker fees from BMS, ViiV Healthcare and Gilead. IJ has received teaching fees from ViiV Healthcare. All other authors declare that they have no conflict of interest related to this work.
• ART
- Antiretroviral therapy
• CoRIS
- Cohort of the Spanish HIV/AIDS Research Network
• DRV
- Darunavir
- EVG/COB/TAF/FTC
- Elvitegravir/cobicistat/tenofovir alafenamide/emtricitabine
- EVG/COB/TDF/FTC
- Elvitegravir/cobicistat/tenofovir disoproxil fumarate/emtricitabine
- EVG/COB/TFV/FTC
- Elvitegravir/cobicistat/tenofovir/emtricitabine
• IDU
- Injecting drug user
• IQR
- Interquartile range
• MSM
- Men who have sex with men
• VL
- Viral load
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
By Inés Suárez-García; Cristina Moreno; Marta Ruiz-Algueró; María Jesús Pérez-Elías; Marta Navarro; Marcos Díez Martínez; Pompeyo Viciana; Laura Pérez-Martínez; Miguel Górgolas; Concha Amador; Miguel Alberto de Zárraga; Inma Jarrín; the Cohort of the Spanish HIV/AIDS Research Network (CoRIS); Santiago Moreno; David Dalmau; Maria Luisa Navarro; Maria Isabel González; Federico Garcia; Eva Poveda; Jose Antonio Iribarren; Félix Gutiérrez; Rafael Rubio; Francesc Vidal; Juan Berenguer; Juan González; M Ángeles Muñoz-Fernández; Inmaculada Jarrin; Belén Alejos; Carlos Iniesta; Luis Miguel Garcia Sousa; Nieves Sanz Perez; Marta Rava; Irene Consuegra Fernández; Esperanza Merino; Gema García; Irene Portilla; Iván Agea; Joaquín Portilla; José Sánchez-Payá; Juan Carlos Rodríguez; Lina Gimeno; Livia Giner; Marcos Díez; Melissa Carreres; Sergio Reus; Vicente Boix; Diego Torrús; Ana López Lirola; Dácil García; Felicitas Díaz-Flores; Juan Luis Gómez; María del Mar Alonso; Ricardo Pelazas; Jehovana Hernández; María Remedios Alemán; María Inmaculada Hernández; Víctor Asensi; Eulalia Valle; María Eugenia Rivas Carmenado; Tomas Suarez-Zarracina Secades; Laura Pérez Is; Federico Pulido; Otilia Bisbal; Asunción Hernando; Lourdes Domínguez; David Rial Crestelo; Laura Bermejo; Mireia Santacreu; José Antonio Iribarren; Julio Arrizabalaga; María José Aramburu; Xabier Camino; Francisco Rodríguez-Arrondo; Miguel Ángel von Wichmann; Lidia Pascual Tomé; Miguel Ángel Goenaga; Mª Jesús Bustinduy; Harkaitz Azkune; Maialen Ibarguren; Aitziber Lizardi; Xabier Kortajarena; Mª Pilar Carmona Oyaga; Maitane Umerez Igartua; Mar Masiá; Sergio Padilla; Andrés Navarro; Fernando Montolio; Catalina Robledano; Joan Gregori Colomé; Araceli Adsuar; Rafael Pascual; Marta Fernández; Elena García; José Alberto García; Xavier Barber; Roberto Muga; Arantza Sanvisens; Daniel Fuster; Juan Carlos López Bernaldo de Quirós; Isabel Gutiérrez; Margarita Ramírez; Belén Padilla; Paloma Gijón; Teresa Aldamiz-Echevarría; Francisco Tejerina; Francisco José Parras; Pascual Balsalobre; Cristina Diez; Leire Pérez Latorre; Chiara Fanciulli; Joaquín Peraire; Consuelo Viladés; Sergio Veloso; Montserrat Vargas; Montserrat Olona; Anna Rull; Esther Rodríguez-Gallego; Verónica Alba; Alfonso Javier Castellanos; Miguel López-Dupla; Marta Montero Alonso; José López Aldeguer; Marino Blanes Juliá; María Tasias Pitarch; Iván Castro Hernández; Eva Calabuig Muñoz; Sandra Cuéllar Tovar; Miguel Salavert Lletí; Juan Fernández Navarro; Juan González-Garcia; Francisco Arnalich; José Ramón Arribas; Jose Ignacio Bernardino de la Serna; Juan Miguel Castro; Luis Escosa; Pedro Herranz; Victor Hontañón; Silvia García-Bujalance; Milagros García López-Hortelano; Alicia González-Baeza; Maria Luz Martín-Carbonero; Mario Mayoral; Maria Jose Mellado; Rafael Esteban Micán; Rocio Montejano; María Luisa Montes; Victoria Moreno; Ignacio Pérez-Valero; Berta Rodés; Talia Sainz; Elena Sendagorta; Natalia Stella Alcáriz; Eulalia Valencia; José Ramón Blanco; José Antonio Oteo; Valvanera Ibarra; Luis Metola; Mercedes Sanz; Piedad Arazo; Gloria Sampériz; Angels Jaén; Montse Sanmartí; Mireia Cairó; Javier Martinez-Lacasa; Pablo Velli; Roser Font; Mariona Xercavins; Noemí Alonso; Maria Rivero Marcotegui; Jesús Repáraz; María Gracia Ruiz de Alda; María Teresa de León Cano; Beatriz Pierola Ruiz de Galarreta; María José Amengual; Gemma Navarro; Manel Cervantes Garcia; Sonia Calzado Isbert; Marta Navarro Vilasaro; Ignacio de los Santos; Jesus Sanz Sanz; Ana Salas Aparicio; Cristina Sarria Cepeda; Lucio Garcia-Fraile Fraile; Enrique Martín Gayo; José Luis Casado Osorio; Fernando Dronda Nuñez; Ana Moreno Zamora; Maria Jesús Pérez Elías; Carolina Gutiérrez; Nadia Madrid; Santos del Campo Terrón; Sergio Serrano Villar; Maria Jesús Vivancos Gallego; Javier Martínez Sanz; Usua Anxa Urroz; Tamara Velasco; Enrique Bernal; Alfredo Cano Sanchez; Antonia Alcaraz García; Joaquín Bravo Urbieta; Angeles Muñoz Perez; Maria Jose Alcaraz; Maria del Carmen Villalba; Federico García; José Hernández Quero; Leopoldo Muñoz Medina; Marta Alvarez; Natalia Chueca; David Vinuesa García; Clara Martinez-Montes; Carlos Guerrero Beltran; Adolfo de Salazar Gonzalerz; Ana Fuentes Lopez; Montserrat Raposo Utrilla; Jorge Del Romero; Carmen Rodríguez; Teresa Puerta; Juan Carlos Carrió; Mar Vera; Juan Ballesteros; Oskar Ayerdi; Antonio Antela; Elena Losada; Melchor Riera; María Peñaranda; María Leyes; Mª Angels Ribas; Antoni A Campins; Carmen Vidal; Francisco Fanjul; Javier Murillas; Francisco Homar; Jesús Santos; Crisitina Gómez Ayerbe; Isabel Viciana; Rosario Palacios; Carmen Pérez López; Carmen Maria Gonzalez-Domenec; Nuria Espinosa; Luis Fernando López-Cortés; Daniel Podzamczer; Arkaitz Imaz; Juan Tiraboschi; Ana Silva; María Saumoy; Paula Prieto; Esteban Ribera; Adrian Curran; Julián Olalla Sierra; Javier Pérez Stachowski; Alfonso del Arco; Javier de la torre; José Luis Prada; José María García de Lomas Guerrero; Onofre Juan Martínez; Francisco Jesús Vera; Lorena Martínez; Josefina García; Begoña Alcaraz; Amaya Jimeno; Angeles Castro Iglesias; Berta Pernas Souto; Alvaro Mena de Cea; Josefa Muñoz; Miren Zuriñe Zubero; Josu Mirena Baraia-Etxaburu; Sofía Ibarra Ugarte; Oscar Luis Ferrero Beneitez; Josefina López de Munain; Mª Mar Cámara López; Mireia de la Peña; Miriam Lopez; Iñigo Lopez Azkarreta; Carlos Galera; Helena Albendin; Aurora Pérez; Asunción Iborra; Antonio Moreno; Maria Angustias Merlos; Asunción Vidal; Marisa Meca; Francisco Pasquau; Javier Ena; Concha Benito; Vicenta Fenoll; Concepcion Gil Anguita; Jose Tomas Algado Rabasa; Eduardo Malmierca; Patricia González-Ruano; Dolores Martín Rodrigo; Mª Pilar Ruiz Seco; Mohamed Omar Mohamed-Balghata; María Amparo Gómez Vidal; Miguel Alberto de Zarraga; Vicente Estrada Pérez; Maria Jesus Téllez Molina; Jorge Vergas García; Juncal Pérez-Somarriba Moreno; Alfonso Cabello; Beatriz Álvarez; Laura Prieto; José Sanz Moreno; Alberto Arranz Caso; Cristina Hernández Gutiérrez; María Novella Mena; María José Galindo Puerto; Ramón Fernando Vilalta; Ana Ferrer Ribera; Antonio Rivero Román; Antonio Rivero Juárez; Pedro López López; Isabel Machuca Sánchez; Mario Frias Casas; Angela Camacho Espejo; Miguel Cervero Jiménez; Rafael Torres Perea; Juan A Pineda; Pilar Rincón Mayo; Juan Macias Sanchez; Nicolas Merchante Gutierrez; Luis Miguel Real; Anais Corma Gomez; Marta Fernandez Fuertes; Alejandro Gonzalez-Serna; Alexandre Pérez; Manuel Crespo; Luis Morano; Celia Miralles; Antonio Ocampo and Guillermo Pousada
Reported by Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author