Clinical Outcomes of 2-Drug Regimens vs 3-Drug Regimens in Antiretroviral Treatment–Experienced People Living With Human Immunodeficiency Virus
Authors: Greenberg Lauren , Ryom Lene , Neesgaard Bastian , Wandeler Gilles , Staub Therese , Gisinger Martin , Skoll Michael , Günthard Huldrych F , Scherrer Alexandra , Mussini Cristina , Smith Colette , Johnson Margaret , De Wit Stéphane , Necsoi Coca , Pradier Christian , Wit Ferdinand , Lehmann Clara , d’Arminio Monforte Antonella , Miró Jose M , Castagna Antonella , Spagnuolo Vincenzo , Sönnerborg Anders , Law Matthew , Hutchinson Jolie , Chkhartishvili Nikoloz , Bolokadze Natalia , Wasmuth Jan-Christian , Stephan Christoph , Vannappagari Vani , Rogatto Felipe , Llibre Josep M , Duvivier Claudine , Hoy Jennifer , Bloch Mark , Bucher Heiner C , Calmy Alexandra , Volny Anne Alain , Pelchen-Matthews Annegret , Lundgren Jens D , Peters Lars , Bansi-Matharu Loveleen , Mocroft Amanda ,   for the RESPOND (International Cohort Consortium of Infectious Diseases) Study Group, Wit F , Reiss P , Hillebregt M , Law M , Petoumenos K , Rose N , Zangerle R , Appoyer H , De Wit S , Delforge M , Wandeler G , Stephan C , Bucht M , Chkhartishvili N , Chokoshvili O , d’Arminio Monforte A , Rodano A , Tavelli A , Fanti I , Mussini C , Borghi V , Pradier C , Fontas E , Dollet K , Caissotti C , Casabona J , Miro J M , Llibre J M , Riera A , Reyes- Urueña J , Smith C , Lampe F , Castagna A , Lazzarin A , Poli A , Sönnerborg A , Falconer K , Svedhem V , Günthard H , Ledergerber B , Bucher H , Scherrer A , Wasmuth J C , Vehreschild J J , Fätkenheuer G , Mocroft A , Rooney J , Rogatto F , Vannappagari V , Garges H , Wandeler G , Law M , Zangerle R , Smith C , De Wit S , Lundgren J , Günthard H , Lundgren J , Günthard H , Kowalska J , Raben D , Ryom L , Mocroft A , Rockstroh J , Peters L , Volny Anne A , Dedes N , Williams E D , Chkhartishvili N , Zangerle R , Law M , Wit F , Necsoi C , Wandeler G , Stephan C , Pradier C , D’Arminio Monforte A , Mussini C , Bruguera A , Bucher H , Sönnerborg A , Vehreschild J J , Wasmuth J C , Smith C , Castagna A , Rogatto F , Haubrich R , Vannappagari V , Garges H , Ryom L , Mocroft A , Neesgaard B , Greenberg L , Bansi-Matharu L , Svedhem-Johansson V , Wit F , Grabmeier-Pfistershammer K , Zangerle R , Hoy J , Bloch M , Braun D , Calmy A , Schüttfort G , Youle M , De Wit S , Mussini C , Zona S , Castagna A , Antinori A , Chkhartishvili N , Bolokadze N , Fontas E , Dollet K , Pradier C , Miro J M , Llibre J M , Vehreschild J J , Schwarze-Zander C , Wasmuth J -C , Rockstroh J , Petoumenos K , Law M , Duvivier C , Dragovic G , Radoi R , Oprea C , Vasylyev M , Kowalska J , Matulionyte R , Mulabdic V , Marchetti G , Kuzovatova E , Coppola N , Begovac J , Aho I , Martini S , Bucher H , Harxhi A , Wæhre T , Pharris A , Vassilenko A , Fätkenheuer G , Bogner J , Maagaard A , Jablonowska E , Elbirt D , Marrone G , Leen C , Wyen C , Kundro M , Dedes N , Dixon Williams E , Gallant J , Thorpe D , Diaz Cuervo H , Vannappagari V , Garges H , Volny-Anne A , Dedes N , Mendao L , Dixon Williams E , Raben D , Peters L , Ryom L , Neesgaard B , Larsen J F , Jakobsen M L , Bruun T , Bojesen A , Hansen E V , Elsing T W , Kristensen D , Thomsen S , Weide T , Mocroft A , Greenberg L , Mocroft A , Greenberg L , Bansi-Matharu L , Pelchen-Matthews A , Petoumenos K , Rose N , Byonanebye D 
Published: December 2020

Abstract

Background
Limited data exist that compare clinical outcomes of 2-drug regimens (2DRs) and 3-drug regimens (3DRs) in people living with human immunodeficiency virus.

Methods
Antiretroviral treatment–experienced individuals in the International Cohort Consortium of Infectious Diseases (RESPOND) who switched to a new 2DR or 3DR from 1 January 2012–1 October 2018 were included. The incidence of clinical events (AIDS, non-AIDS cancer, cardiovascular disease, end-stage liver and renal disease, death) was compared between regimens using Poisson regression.

Results
Of 9791 individuals included, 1088 (11.1%) started 2DRs and 8703 (88.9%) started 3DRs. The most common 2DRs were dolutegravir plus lamivudine (22.8%) and raltegravir plus boosted darunavir (19.8%); the most common 3DR was dolutegravir plus 2 nucleoside reverse transcriptase inhibitors (46.9%). Individuals on 2DRs were older (median, 52.6 years [interquartile range, 46.7–59.0] vs 47.7 [39.7–54.3]), and a higher proportion had ≥1 comorbidity (81.6% vs 73.9%). There were 619 events during 27 159 person-years of follow-up (PYFU): 540 (incidence rate [IR] 22.5/1000 PYFU; 95% confidence interval [CI]: 20.7–24.5) on 3DRs and 79 (30.9/1000 PYFU; 95% CI: 24.8–38.5) on 2DRs. The most common events were death (7.5/1000 PYFU; 95% CI: 6.5–8.6) and non-AIDS cancer (5.8/1000 PYFU; 95% CI: 4.9–6.8). After adjustment for baseline demographic and clinical characteristics, there was a similar incidence of events on both regimen types (2DRs vs 3DRs IR ratio, 0.92; 95% CI: .72–1.19; P = .53).

Conclusions
This is the first large, international cohort to assess clinical outcomes on 2DRs. After accounting for baseline characteristics, there was a similar incidence of events on 2DRs and 3DRs. 2DRs appear to be a viable treatment option with regard to clinical outcomes. Further research on resistance barriers and long-term durability of 2DRs is needed.