Integrase Strand Transfer Inhibitor Use and Cancer Incidence in a Large Cohort Setting

Abstract

Background: Limited data exist examining the association between incident cancer and cumulative integrase inhibitor (INSTI) exposure.

Methods: Participants were followed from baseline (latest of local cohort enrollment or January 1, 2012) until the earliest of first cancer, final follow-up, or December 31, 2019. Negative binomial regression was used to assess associations between cancer incidence and time-updated cumulative INSTI exposure, lagged by 6 months.

Results: Of 29 340 individuals, 74% were male, 24% were antiretroviral treatment (ART)-naive, and median baseline age was 44 years (interquartile range [IQR], 36-51). Overall, 13 950 (48%) individuals started an INSTI during follow-up. During 160 657 person-years of follow-up ([PYFU] median 6.2; IQR, 3.9-7.5), there were 1078 cancers (incidence rate [IR] 6.7/1000 PYFU; 95% confidence interval [CI], 6.3-7.1). The commonest cancers were non-Hodgkin lymphoma (n = 113), lung cancer (112), Kaposi's sarcoma (106), and anal cancer (103). After adjusting for potential confounders, there was no association between cancer risk and INSTI exposure (≤6 months vs no exposure IR ratio: 1.15 [95% CI, 0.89-1.49], >6-12 months; 0.97 [95% CI, 0.71-1.32], >12-24 months; 0.84 [95% CI, 0.64-1.11], >24-36 months; 1.10 [95% CI, 0.82-1.47], >36 months; 0.90 [95% CI, 0.65-1.26] [P = .60]). In ART-naive participants, cancer incidence decreased with increasing INSTI exposure, mainly driven by a decreasing incidence of acquired immune deficiency syndrome cancers; however, there was no association between INSTI exposure and cancer for those ART-experienced (interaction P < .0001).

Conclusions: Cancer incidence in each INSTI exposure group was similar, despite relatively wide CIs, providing reassuring early findings that increasing INSTI exposure is unlikely to be associated with an increased cancer risk, although longer follow-up is needed to confirm this finding.

Keywords: HIV; antiretroviral treatment; cancer; cohort; integrase inhibitors.

Figure 1.

Study flow. ∗More than 1 reason can apply. INSTI, integrase inhibitor; VL, viral load.

Figure 2.

Association between any cancer risk and cumulative exposure to integrase strand transfer inhibitors (INSTIs), adjusted for potential confounders. Incidence rate ratio (IRR) adjusted for age, sex, ethnicity, human immunodeficiency virus risk group, antiretroviral treatment experience, CD4 cell count, CD4 nadir, body mass index, geographical region, hepatitis B, prior diabetes, prior acquired immune deficiency syndrome, prior cancer, prior chronic kidney disease, prior cardiovascular disease, prior end-stage liver disease (all fixed at baseline), smoking status (time updated). Note, INSTI exposure is lagged by 6 months. CI, confidence interval; PYFU, person years of follow-up.

Figure 3.

Adjusted incidence of cancer, by integrase inhibitor (INSTI) exposure compared to no exposure, stratified by antiretroviral treatment (ART)-experience at baseline. Incidence rate ratio (IRR) calculated from a negative binomial regression model, adjusted for the same confounders as the main analysis, and including an interaction term between INSTI exposure and ART-experience at baseline. ADC, acquired immune deficiency syndrome (AIDS)-defining cancers; NADC, non-AIDS-defining cancers; VL, viral load.