Long-term Antiretroviral Therapy and Anogenital Cancer Risk.

BACKGROUND: People with human immunodeficiency virus (HIV) (PWH) experience substantially increased risk of anogenital cancer. Whether long-term antiretroviral therapy (ART) reduces anogenital cancer risk is unknown. METHODS: A target trial emulation using a case-cohort design among Botswana adults aged 30-65, sampled via a probability-based household survey across 30 communities. Cases of cervical, vulvar, anal, and penile cancer were prospectively ascertained at the country's principal treatment centers. We estimated the marginal relative risk (RR) of incident anogenital cancer by ART duration, compared with adults without HIV, using g-computation from weighted models that accounted for shared determinants of human papillomavirus, and HIV infection, access to cancer care, and ART duration. RESULTS: 14 312 participants were enrolled (42% PWH), including 1045 (79% PWH) with incident anogenital cancer-792 cervical, 106 vulvar, 80 anal, and 67 penile cancers. Compared with people without HIV, the marginal RR (95% CI) of anogenital cancer increased with longer durations of ART (P = .001) (no ART: 4.6; 4.3-5.0; <5 years: 4.0; 3.7-4.3; 5-9 years: 4.6; 4.2-5.0; ≥10 years: 7.4; 6.8-8.1). Individuals receiving ART for ≥10 years had the highest RR for each cancer evaluated: cervix, 4.4 (4.0 to 4.8); vulva, 36 (22-57); anus, 15 (11-20); and penis, 102 (42-250). Prior advanced HIV disease was associated with increased risk but this effect diminished on ART and contributed relatively little to overall risk. CONCLUSIONS: Long-term utilization of ART was not associated with a reduction in anogenital cancer risk. Improved prevention strategies are needed for PWH.