Incidence and timing of cancer in HIV-infected individuals following initiation of combination antiretroviral therapy

Abstract

Background: Cancer is an important cause of morbidity and mortality in individuals infected with human immunodeficiency virus (HIV), but patterns of cancer incidence after combination antiretroviral therapy (ART) initiation remain poorly characterized.

Methods: We evaluated the incidence and timing of cancer diagnoses among patients initiating ART between 1996 and 2011 in a collaboration of 8 US clinical HIV cohorts. Poisson regression was used to estimate incidence rates. Cox regression was used to identify demographic and clinical characteristics associated with cancer incidence after ART initiation.

Results: At initiation of first combination ART among 11 485 patients, median year was 2004 (interquartile range [IQR], 2000-2007) and median CD4 count was 202 cells/mm(3) (IQR, 61-338). Incidence rates for Kaposi sarcoma (KS) and lymphomas were highest in the first 6 months after ART initiation (P < .001) and plateaued thereafter, while incidence rates for all other cancers combined increased from 416 to 615 cases per 100 000 person-years from 1 to 10 years after ART initiation (average 7% increase per year; 95% confidence interval, 2%-13%). Lower CD4 count at ART initiation was associated with greater risk of KS, lymphoma, and human papillomavirus-related cancer. Calendar year of ART initiation was not associated with cancer incidence.

Conclusions: KS and lymphoma rates were highest immediately following ART initiation, particularly among patients with low CD4 cell counts, whereas other cancers increased with time on ART, likely reflecting increased cancer risk with aging. Our results underscore recommendations for earlier HIV diagnosis followed by prompt ART initiation along with ongoing aggressive cancer screening and prevention efforts throughout the course of HIV care.

Keywords: AIDS-defining cancer; HIV-associated malignancies; combination antiretroviral therapy; non-AIDS-defining cancer.

Figure 1.

Incidence of first cancer across time following initiation of combination antiretroviral therapy (ART), Centers for AIDS Research Network of Integrated Clinical Systems, 1996–2011. After ART initiation, incidence rates were estimated in the first 6 months, the second 6 months, and every year thereafter. The vertical lines extending from each incidence rate estimate represent the 95% confidence interval. Listed below the x-axis are the total numbers of patients remaining in follow-up at the end of each year. Solid line with circles, Kaposi sarcoma incidence; dashed line with squares, lymphoma incidence; dotted line with triangles, incidence of non-Kaposi sarcoma, nonlymphoma cancers. Abbreviations: ART, combination antiretroviral therapy; KS, Kaposi sarcoma.

Figure 2.

Cancer incidence across time following initiation of combination antiretroviral therapy (ART) stratified by CD4 count at ART initiation, Centers for AIDS Research Network of Integrated Clinical Systems, 1996–2011. Graphs divided by cancer type: A, Kaposi sarcoma; B, lymphoma; C, human papillomavirus–related cancer; D, other cancers. Dotted lines with diamonds, incidence rates among those with CD4 counts <200 cells/mm³ at ART initiation; dashed lines with squares, incidence rates among those with CD4 counts ≥200 cells/mm³ at ART initiation. *Other cancer includes lung, liver, prostate, breast, melanoma, colorectal, kidney, bladder, brain, esophagus, larynx, leukemia, multiple myeloma, ovary, pancreas, peritoneum, small intestine, soft tissue, stomach, testicular, uterus, or non–squamous cell oral cavity/pharynx. Abbreviations: ART, combination antiretroviral therapy; HPV, human papillomavirus.

Figure 3.

Cancer incidence across time following initiation of combination antiretroviral therapy (ART) stratified by antiretroviral history at ART initiation, Centers for AIDS Research Network of Integrated Clinical Systems, 1996–2011. Graphs divided by cancer type: A, Kaposi sarcoma; B, lymphoma; C, human papillomavirus–related cancer; D, other cancers. Dotted lines with diamonds, incidence rates among those who were antiretroviral naive at ART initiation; dashed lines with squares, incidence rates among those with prior exposure to mono- or dual therapy or an unknown antiretroviral history at ART initiation. *Other cancer includes lung, liver, prostate, breast, melanoma, colorectal, kidney, bladder, brain, esophagus, larynx, leukemia, multiple myeloma, ovary, pancreas, peritoneum, small intestine, soft tissue, stomach, testicular, uterus, or non–squamous cell oral cavity/pharynx. Abbreviations: ART, combination antiretroviral therapy; ARV, antiretroviral; HPV, human papillomavirus.