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Timing of Antiretroviral Therapy Initiation and Risk of Cancer Among Persons Living With Human Immunodeficiency Virus.
Silverberg MJ, Leyden W, Hernández-Ramírez RU, Qin L, Lin H, Justice AC, Hessol NA, Achenbach CJ, D'Souza G, Engels EA, Althoff KN, Mayor AM, Sterling TR, Kitahata MM, Bosch RJ, Saag MS, Rabkin CS, Horberg MA, Gill MJ, Grover S, Mathews WC, Li J, Crane HM, Gange SJ, Lau B, Moore RD, Dubrow R, Neugebauer RS. Timing of Antiretroviral Therapy Initiation and Risk of Cancer Among Persons Living With Human Immunodeficiency Virus. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2021 Jun 1; 72(11):1900-1909.
Persons living with human immunodeficiency virus (HIV; PLWH) experience a high burden of cancer. It remains unknown which cancer types are reduced in PLWH with earlier initiation of antiretroviral therapy (ART).
We evaluated AIDS-free, ART-naive PLWH during 1996-2014 from 22 cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. PLWH were followed from first observed CD4 of 350-500 cells/µL (baseline) until incident cancer, death, lost-to-follow-up, or December 2014. Outcomes included 6 cancer groups and 5 individual cancers that were confirmed by chart review or cancer registry linkage. We evaluated the effect of earlier (in the first 6 months after baseline) versus deferred ART initiation on cancer risk. Marginal structural models were used with inverse probability weighting to account for time-dependent confounding and informative right-censoring, with weights informed by subject's age, sex, cohort, baseline year, race/ethnicity, HIV transmission risk, smoking, viral hepatitis, CD4, and AIDS diagnoses.
Protective results for earlier ART were found for any cancer (adjusted hazard ratio [HR] 0.57; 95% confidence interval [CI], .37-.86), AIDS-defining cancers (HR 0.23; 95% CI, .11-.49), any virus-related cancer (HR 0.30; 95% CI, .16-.54), Kaposi sarcoma (HR 0.25; 95% CI, .10-.61), and non-Hodgkin lymphoma (HR 0.22; 95% CI, .06-.73). By 15 years, there was also an observed reduced risk with earlier ART for virus-related NADCs (0.6% vs 2.3%; adjusted risk difference -1.6; 95% CI, -2.8, -.5).
Earlier ART initiation has potential to reduce the burden of virus-related cancers in PLWH but not non-AIDS-defining cancers (NADCs) without known or suspected viral etiology.