Patterns of Antiretroviral Therapy Use and Immunologic Profiles at Enrollment in the REPRIEVE Trial
Authors: Fichtenbaum Carl J , Ribaudo Heather J , Leon-Cruz Jorge , Overton Edgar T , Zanni Markella V , Malvestutto Carlos D , Aberg Judith A , Kileel Emma M , Fitch Kathleen V , Van Schalkwyk Marije , Kumarasamy Nagalingeswaran , Martinez Esteban , Santos Breno Riegel , Joseph Yvetot , Lo Janet , Siminski Sue , Melbourne Kathleen , Sponseller Craig A , Desvigne-Nickens Patrice , Bloomfield Gerald S , Currier Judith S , Hoffmann Udo , Douglas Pamela S , Grinspoon Steven K ,   REPRIEVE Investigators, Curran Adrian , Baranauskas Adrienne , Wilkin Aimee , Abrams-Downey Alexandra J , Eckard Allison Ross , Wurcel Alysse G , González-Cordón Ana , Paez Armando , Sha Beverly E , Santos Breno , Yoshida Carina Beppu , Rolle Charlotte-Paige , Somboonwit Charurut , Funk Connie , Gómez-Ayerbe Cristina , Frank Cynthia , Nixon Daniel E , Skiest Daniel J , Choi David , Mushatt David M , Rial-Crestelo David , Perez Deborah K , Burke Deirdre J , dos Santos Desirée V G , Jayaweera Dushyantha T , Gardner Edward M , DeJesus Edwin , Connick Elizabeth , Lam Emerline G , Hecker Emily J , Kallas Esper G , Martinez Esteban , Waters Evan , Rhame Frank , Sattler Fred R , Wang Gary P , Enrile Seedhom Helen May , Tavares Isabel C F , Stapleton Jack T , Bennet Jaclyn , Brock James B , Scott James , Forcht Janet , Lama Javier R , Valencia Javier , Brumfield Jennifer K , Brumfield Jennifer K , Portilla Joaquin , Kumar Jonathan , Navarro Jordi , Pinto Jorge A , Castro Jose G , Bernardino Jose I , Casado Jose L , Madruga José Valdez , Baraiaetxaburu Josu , Berenguer Juan , Aberg Judith A , Currier Judith S , Tashima Karen T , Ho Ken , Costa Laura V L , Perez Latorre Leire , Mohapi Lerato , López-González L , Fantry Lori E , Domínguez-Domínguez Lourdes , Martín-Carbonero Luz , Cornelissen Lynne M , Jain Mamta K , Masiá Mar , Lacerda Marcus V G , Saumoy Maria , Van Schalkwyk Marije , Villalobos-Hernández Marina , Mall Mark , Kubat Maureen E , Carreres Melissa , Frank Michael , Kozal Michael J , De la Peña Mireia , Salomon Nadim , Kumarasamy Nagalingeswaran , Kosashunhanan Natapol , Mogashoa Ntebo D , Lance Okeke Nwora , Mukwekwerere Pamela G , Sugandhavesa Patcharaphan , Vizcarra Pilar , Kumar Princy N , Weinman Renee , Novak Richard M , Chaudhary Rina , Dawson Rodney , Bedimo Roger , Chinchay Romina , Pillay Sandy , Bares Sara H , Badal-Faesen Sharlaa , Walmsley Sharon L , Perez-Frontera Sigrid , Middleton Sondra , Mayer Stockton , Adams Suzanne L , Lalloo Umesh G , Estrada Vicente , Watson Vicky , Chiang Victor , Curran Adrian , Baranauskas Adrienne , Wilkin Aimee , Abrams-Downey Alexandra J , Eckard Allison Ross , Wurcel Alysse G , González-Cordón Ana , Paez Armando , Sha Beverly E , Santos Breno , Yoshida Carina Beppu , Rolle Charlotte-Paige , Somboonwit Charurut , Funk Connie , Gómez-Ayerbe Cristina , Frank Cynthia , Nixon Daniel E , Skiest Daniel J , Choi David , Mushatt David M , Rial-Crestelo David , Perez Deborah K , Burke Deirdre J , dos Santos Desirée V G , Jayaweera Dushyantha T , Gardner Edward M , DeJesus Edwin , Connick Elizabeth , Lam Emerline G , Hecker Emily J , Kallas Esper G , Martinez Esteban , Waters Evan , Rhame Frank , Sattler Fred R , Wang Gary P , Enrile Seedhom Helen May , Tavares Isabel C F , Stapleton Jack T , Bennet Jaclyn , Brock James B , Scott James , Forcht Janet , Lama Javier R , Valencia Javier , Brumfield Jennifer K , Brumfield Jennifer K , Portilla Joaquin , Kumar Jonathan , Navarro Jordi , Pinto Jorge A , Castro Jose G , Bernardino Jose I , Casado Jose L , Madruga José Valdez , Baraiaetxaburu Josu , Berenguer Juan , Aberg Judith A , Currier Judith S , Tashima Karen T , Ho Ken , Costa Laura V L , Perez Latorre Leire , Mohapi Lerato , López-González L , Fantry Lori E , Domínguez-Domínguez Lourdes , Martín-Carbonero Luz , Cornelissen Lynne M , Jain Mamta K , Masiá Mar , Lacerda Marcus V G , Saumoy Maria , Van Schalkwyk Marije , Villalobos-Hernández Marina , Mall Mark , Kubat Maureen E , Carreres Melissa , Frank Michael , Kozal Michael J , De la Peña Mireia , Salomon Nadim , Kumarasamy Nagalingeswaran , Kosashunhanan Natapol , Mogashoa Ntebo D , Lance Okeke Nwora , Mukwekwerere Pamela G , Sugandhavesa Patcharaphan , Vizcarra Pilar , Kumar Princy N , Weinman Renee , Novak Richard M , Chaudhary Rina , Dawson Rodney , Bedimo Roger , Chinchay Romina , Pillay Sandy , Bares Sara H , Badal-Faesen Sharlaa , Walmsley Sharon L , Perez-Frontera Sigrid , Middleton Sondra , Mayer Stockton , Adams Suzanne L , Lalloo Umesh G , Estrada Vicente , Watson Vicky , Chiang Victor 
Published: May 2020

Abstract

Background
Patterns of antiretroviral therapy (ART) use and immunologic correlates vary globally, and contemporary trends are not well described.

Methods
The REPRIEVE trial (Randomized Trial to Prevent Vascular Events in HIV) enrolled persons with human immunodeficiency virus (HIV) who were aged 40–75 years, receiving ART, and had low-to-moderate cardiovascular disease risk. ART use was summarized within Global Burden of Disease (GBD) super-regions, with adjusted linear and logistic regression analyses examining associations with immune parameters and key demographics.

Results
A total of 7770 participants were enrolled, with a median age of 50 years (interquartile range, 45–55 years); 31% were female, 43% were black or African American, 15% were Asian, 56% had a body mass index &gt;25 (calculated as weight in kilograms divided by height in meters squared), and 49% were current or former smokers. The median CD4 T-cell count was 620/µL (interquartile range, 447–826/ µ L), and the median duration of prior ART use, 9.5 years (5.3–14.8) years. The most common ART regimens were nucleoside/nucleotide reverse-transcriptase inhibitor (NRTI) plus nonnucleoside reverse-transcriptase inhibitor (43%), NRTI plus integrase strand transfer inhibitor (25%), and NRTI plus protease inhibitor (19%). Entry ART varied by GBD region, with shifts during the trial enrollment period. In adjusted analyses, entry CD4 cell count and CD4/CD8 ratio were associated with GBD region, sex, entry regimen, duration of ART, and nadir CD4 cell count; CD4 and CD8 cell counts were also associated with body mass index and smoking status.

Conclusions
There were substantial variations in ART use by geographic region and over time, likely reflecting the local availability of specific medications, changes in treatment guidelines and provider/patient preferences. The analyses of CD4 cell counts and CD4/CD8 ratios may provide valuable insights regarding immune correlates and outcomes in people living with HIV.

Clinical Trials Registration
NCT02344290.