Burden of chronic health conditions (CHCs) among people with HIV (PWH) and non-AIDS defining cancers (NADC): A report from the center for AIDS research (CFAR) network of integrated clinical systems (CNICS).
Authors: Goyal Gaurav , Richman Joshua , Enogela Ene Mercy , Burkholder Greer , Kitahata Mari M , Crane Heidi , Achenbach Chad , Farel Claire , Hunt Peter , Jacobsen Jeffery M , Fleming Julia , Cachay Edward R , Saag Michael , Bhatia Smita 
Published: June 2023

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Background: Advances in anti-retroviral therapy (ART) have led to improved life expectancy of PWH and a growing population of PWH who are at an increased risk of NADC. While the risk of CHCs in HIV uninfected cancer survivors is well known, the burden of morbidity (CHCs) borne by PWH-NADC remains unstudied and can adversely influence long-term survival. Methods: We utilized CNICS data for PWH ≥18y from 1995- 2018. CNICS data are harmonized across 8 academic sites, comprising patient-level clinical, morbidity, and outcomes data in the ART era. We included individuals with the five most common NADCs: anal squamous cell cancer, non-small cell lung cancer (NSCLC), prostate cancer, classic Hodgkin lymphoma (cHL), and hepatocellular cancer (HCC). For controls, we conducted a 1:2 matching (age at CNICS entry, year of CNICS entry, sex) for each NADC subgroup to select PWH and no NADC at last follow-up. Comorbidities diagnosed after cohort entry are validated in CNICS and were graded using the Common Terminology Criteria for Adverse Events into grade 1 (mild) through grade 4 (severe/life-threatening). Results: We included 693 PWH-NADC and 1,345 non-cancer PWH controls in this study. The NADC distribution was anal cancer (n = 195, 28%), NSCLC (n = 155, 22%), prostate cancer (n = 144, 21%), cHL (n = 124, 18%), and HCC (n = 75, 11%). Mean age at CNICS entry was 45y for cases and controls (SD: 10.4). At a median follow-up of 12.5y for cases and 9.5y for controls, the prevalence of all-grade and grade ≥3 CHCs was higher in PWH-NADC compared with controls (94% vs. 88%, and 25% vs. 14%, respectively [p < 0.01]). PWH-NADC had a higher prevalence of all-grade HTN (87% vs. 80%), CKD (49% vs. 46%), hyperlipidemia (56% vs. 50%), DM (26% vs. 18%), VTE (4% vs. 1%), MI (12% vs. 5%), and CHF (7% vs. 3%) compared with controls (p-value for all < 0.01). In Cox regression including type of NADC, age at CNICS cohort entry, ART use, race/ethnicity, NADCs were associated with increased risk of new-onset grade 3 or 4 CHCs (HR 2.94, p < 0.01). When examining specific CHCs, all NADCs were associated with increased risk of new-onset grade 3 DM ([anal cancer HR 2.34, HCC HR 5.02, NSCLC HR 3.89, cHL HR 2.77, and prostate cancer HR 1.88], p-value for all < 0.01). Additionally, NSCLC was associated with increased risk of G3-4 MI (HR 2.79, p = 0.04), and prostate cancer with G3-4 CHF (HR 6.19, p < 0.01). Conclusions: In this large multi-institutional study, 25% of PWH-NADC had developed severe/life-threatening CHCs at last follow up. Occurrence of NADC among PWH was associated with increased hazards of developing grade ≥3 morbidities. The specific types of CHCs observed in PWH with NADC subtypes could be used to inform risk-based anticipatory surveillance and risk reduction strategies.