Incidence of Non-AIDS-Defining Cancer in Antiretroviral Treatment-Naïve Subjects after Antiretroviral Treatment Initiation: An ACTG Longitudinal Linked Randomized Trials Analysis

Abstract

Background: Prospective data on factors associated with the non-AIDS-defining cancer (NADC) incidence in HIV-infected individuals are limited. Methods: We examined the NADC incidence in 3,158 antiretroviral treatment (ART)-naïve subjects after ART initiation in AIDS Clinical Trials Group trials; extended follow-up was available for 2,122 subjects. Poisson regression was used to examine the associations between covariates and incident NADC. Results: At ART initiation, subjects (median age 37 years) were 40% non-Hispanic whites, and 82% were male; 23% had CD4+ T cell count ≤50 cells/mm³ and 25% had CD4 >350 cells/mm³. Median follow-up was 3.8 years. Among 64 incident NADCs, the most common were 8 anal cancers, 8 basal cell carcinomas, 8 Hodgkin’s disease, and 6 lung cancers. In univariate models, age, smoking and recent (time-updated) CD4 were associated with incident NADC. There was no association between initial ART drug class (protease inhibitor, nucleoside reverse transcriptase inhibitor and nonnucleoside reverse transcriptase inhibitor) and NADC. After adjusting for age, race and sex: smoking [relative risk = 2.12 (95% CI = 1.1–4.08)] and recent CD4 (≤50 cells/mm³: 3.58, 1.22–10.45; 51–200 cells/mm³: 2.54, 1.30–5.0; 201–350 cells/mm³: 2.37, 1.32–4.26 vs. >350 cells/mm³) were associated with NADC. Conclusion: Smoking and lower recent CD4 levels, but not initial ART drug class, were associated with NADC. Strategies for maintaining higher CD4 cell counts and successful smoking cessation may reduce the NADC incidence in the HIV-infected population.

HIV Infection, Immunodeficiency, Viral Replication, and the Risk of Cancer

“…Similar observations for NADC and immunodeficiency are inconsistent likely due to the small numbers of cancer events, requiring analysis of grouped cancer types only (30–32), or often insensitive, static measures of CD4 count, such as CD4 count at AIDS diagnosis or at enrollment (1, 4, 6, 17, 24, 33–37). Several recent studies have evaluated time-dependent measures of CD4 count for specific cancers (14–16).…”

Increased non‐AIDS mortality among persons with AIDS‐defining events after antiretroviral therapy initiation

“…With this, there has been a shift in distribution of causes of death toward non‐AIDS‐defining events (NADEs) 8, 9, 10, 11, 12. Factors contributing to non‐AIDS mortality include immunodeficiency 13, 14, ART toxicity 15, 16, increasing age 17, 18, 19, 20, 21, 22, and lifestyle factors such as tobacco use and obesity 18, 21, 23. However, chronic inflammation and immune activation produced by chronic HIV infection as well as many AIDS‐defining events (ADEs) are now recognized as significant drivers in the pathogenesis of non‐AIDS‐related deaths 14, 24, 25, 26, 27, 28.…”

Tobacco Use Among Adults Initiating Treatment for HIV Infection in Rural Uganda

“…Managing traditional risk factors for cardiovascular disease [44] and malignancy [45], like tobacco use, could greatly impact morbidity and mortality among people infected with HIV. Therefore, even in this low prevalence setting, tobacco use is an important risk factor that should be assessed among every patient.…”