Cancer following combination antiretroviral therapy initiation: Incidence patterns and effects of antiretroviral response

Among HIV-infected patients, cancer is a leading cause of morbidity and mortality. While combination antiretroviral therapy (ART) has reduced the incidence of Kaposi sarcoma (KS) and non-Hodgkin lymphomas, the burden of non-AIDS-defining cancers (NADCs) is increasing. However, the patterns and predictors of cancer incidence following ART initiation remain poorly characterized.;The Centers for AIDS Research Network of Integrated Clinical Systems, a collaboration of 8 United States HIV clinical cohorts, was used to evaluate the incidence and timing of cancer among patients initiating first ART, defined as ≥3 antiretrovirals, between 1996 and 2011. Poisson regression was used to estimate incidence rates. Cox regression was used to estimate adjusted hazard ratios to identify patient characteristics at ART initiation associated with subsequent cancer incidence.;Associations between immunologic ART response and NADC incidence were also evaluated among patients with ≥1 CD4 count and HIV RNA measurement by six months after ART initiation. Six month CD4, latest CD4, and CD4 count-years, a cumulative measure of CD4 lymphopenia, were used as measures of immunologic ART response and were considered with 0, 6, and 12-month exposure lags. Inverse probability weights were applied to Cox regression to account for time-varying confounding from the coincident virologic ART response.;Incidence for KS and lymphoma (Hodgkin, non-Hodgkin) were highest in the first six months post-ART start and plateaued thereafter, while incidence for all other cancers combined increased with time from ART initiation. A lower CD4 count at ART initiation was associated with greater incidence of KS, lymphomas, and human papillomavirus-related cancers. Calendar year of ART initiation was not associated with cancer incidence. All measures of immunologic response were associated with virus-related NADC incidence independent of CD4 count at ART initiation, but none were associated with virus-unrelated NADC incidence. These associations persisted when measures were assessed with 6 and 12-month exposure lags.;Our results underscore recommendations for earlier HIV diagnosis followed by prompt ART initiation. They also highlight the need for cancer prevention and screening efforts throughout the course of HIV care, particularly among patients with poor immunologic response to ART.