How to RESPOND to Modern Challenges for People Living with HIV: A Profile for a New Cohort Consortium

Abstract

Background: the International Cohort Consortium of Infectious Disease (RESPOND) is a collaboration dedicated to research on HIV and other infectious diseases.

Methods: RESPOND is a flexible organization, with several independent substudies operating under one shared governance. HIV-related variables, including full antiretroviral therapy (ART) history, are collected annually for all participants and merged with substudy specific data into a shared data pool. Incident clinical events are reported using standardized forms. Prospective follow-up started 1/10/17 (enrolment) with retrospective data collected back to 01/01/12.

Results: Overall, 17 cohorts from Europe and Australia provided data on 26,258 people living with HIV (PLWH). The majority (43.3%) of the population were white, with men-sex-with-men accounting for 43.3% of the risk for HIV acquisition. The median age was 48 years (IQR 40-56) and 5.2% and 25.5% were known to be co-infected with hepatitis B or C. While 5.3% were ART-naïve, the median duration on ART was 10.1 years (4.8-17.6), with 89.5% having a VL <200 copies/mL and the median CD4 count being 621 cells/µL (438-830). Malignancies (n = 361) and cardiovascular disease (n = 168) were the predominant reported clinical events.

Conclusion: RESPOND's large, diverse study population and standardized clinical endpoints puts the consortium in a unique position to respond to the diverse modern challenges for PLWH.

Keywords: HIV; cohort; hepatitis; observational study; pharmacovigilance; public health; tuberculosis.

Figure 1

Flowchart of the International Cohort Consortium of Infectious Disease (RESPOND) inclusion and exclusion criteria.

Figure 2

Organization of RESPOND. The executive committee oversee the overall financial wellbeing and scientific progression, while the scientific steering committee supervises the scientific integrity and research conducted. Research agendas are developed in the sub studies/scientific interest groups: Public Health, Outcomes with Antiretroviral Treatment, Hepatitis and Tuberculosis (the latter under development). Each SIG may have multiple underlying working groups (WG) dedicated to developing specific subtopics. All the participating cohorts supply core RESPOND data to the data pool. In addition, study-specific data can be collected by a subset of cohorts involved in specific SIGs which are also merged into the data pool. All the data can be utilized by the different SIGs upon permission from the cohorts.

Figure 3

(A) Antiretroviral exposures at RESPOND enrolment; (B) number of validated clinical; (C) number of deaths in the study period events, after the 1st RESPOND data merger. Abbreviations: INSTI: Integrase strand transfer inhibitor; EVG/c: cobicistat boosted elvitegravir; RAL: Raltegravir; DTG: dolutegravir; PI/b: boosted protease inhibitor; DRV: darunavir; ATV: atazanavir; NNRTI: non-nucleotide reverse transcriptase inhibitor; RPV: rilpivirin; EFV: efavirenz; NRTI: nucleos(t)ide reverse transcriptase inhibitor; TAF: tenofovir alafenamide; ABC: abacavir; FTC: emtricitabine; TDF: tenofovir disoproxil; 3TC: lamivudine; ESLD: end-stage liver disease; ESRD: end-stage renal disease. Cardiovascular disease includes myocardial infarctions, strokes, and invasive cardiovascular procedures. Bubble size reflects the person-years of follow-up (PYFU) exposed to the specific antiretroviral drug, calculated from last clinical visit, with the number above each bubble indicating the number of individuals exposed. Clinical events refer to validated events after the first data merger. Deaths are all deaths occurring in the period between 01/01/12 and 01/10/2017.