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Risk for non-AIDS-defining and AIDS-defining cancer of early versus delayed initiation of antiretroviral therapy: A multinational prospective cohort study

Publicado en:Annals Of Internal Medicine. 174 (6): 768-776 - 2021-06-01 174(6), DOI: 10.7326/M20-5226

Autores: Chammartin F; Lodi S; Logan R; Ryom L; Mocroft A; Kirk O; D'Arminio Monforte A; Reiss P; Phillips A; El-Sadr W; Hatleberg CI; Pradier C; Bonnet F; Law M; De Wit S; Sabin C; Lundgren JD; Bucher HC; Calvo G; Dabis F; Morfeldt L; Weber R; Lind-Thomsen A; Salbøl Brandt R; Hillebreght M; Zaheri S; Wit FWNM; Scherrer A; Schoni-Affolter F; Rickenbach M; Tavelli A; Fanti I; Leleux O; Mourali J; Le Marec F; Boerg E; Thulin E; Sundstrom A; Bartsch G; Thompsen G; Necsoi C; Delforge M; Fontas E; Caissotti C; Dollet K; Mateu S; Torres F; Petoumenos K; Blance A; Huang R; Puhr R; Grønborg Laut K; Kristensen D; Kamara DA; Smith CJ; Raben D; Matthews C; Bojesen A; Grevsen AL; Powderly B; Shortman N; Moecklinghoff C; Reilly G; Smit C; Ross M; Fux CA; Morlat P; Friis-Møller N; Kowalska J; Bohlius J; Bower M; Fatkenheuer G; Grulich A; Sjøl A; Meidahl P; Iversen JS; Hillebregt M; Prins JM; Kuijpers TW; Scherpbier HJ; Van Der Meer JTM; Godfried MH; Van Der Poll T; Nellen FJB; Geerlings SE; Van Vugt M; Pajkrt D; Bos JC; Wiersinga WJ; Van Der Valk M; Goorhuis A; Hovius JW; Van Eden J; Henderiks A; Van Hes AMH; Mutschelknauss M; Nobel HE; Pijnappel FJJ; Jurriaans S; Back NKT

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Background: Immediate initiation of antiretroviral therapy (ART) regardless of CD4 cell count reduces risk for AIDS and non-AIDS-related events in asymptomatic, HIV-positive persons and is the standard of care. However, most HIV-positive persons initiate ART when their CD4 count decreases below 500 × 109 cells/L. Consequences of delayed ART on risk for non-AIDS-defining and AIDS-defining cancer, one of the most common reasons for death in HIV, are unclear. Objective: To estimate the long-term risk difference for cancer with the immediate ART strategy. Design: Multinational prospective cohort study. Setting: The D:A:D (Data collection on Adverse events of anti-HIV Drugs) study, which included HIV-positive persons from Europe, Australia, and the United States. Participants: 8318 HIV-positive persons with at least 1 measurement each of CD4 cell count and viral load while ART-naive (study period, 2006 to 2016). Measurements: The parametric g-formula was used, with adjustment for baseline and time-dependent confounders (CD4 cell count and viral load), to assess the 10-year risk for non-AIDS-defining and AIDS-defining cancer of immediate versus deferred (at CD4 counts < 350 and < 500 × 109 cells/L) ART initiation strategies. Results: During 64 021 person-years of follow-up, 231 cases of non-AIDS-defining cancer and 272 of AIDS-defining cancer occurred among HIV-positive persons with a median age of 36 years (interquartile range, 29 to 43 years). With immediate ART, the 10-year risk for non-AIDS-defining cancer was 2.97% (95% CI, 2.37% to 3.50%) and that for AIDS-defining cancer was 2.50% (CI, 2.37% to 3.38%). Compared with immediate ART initiation, the 10-year absolute risk differences when deferring ART to CD4 counts less than 500 × 109 cells/L and less than 350 × 109 cells/L were 0.12 percentage point (CI, -0.01 to 0.26 percentage point) and 0.29 percentage point (CI, -0.03 to 0.73 percentage point), respectively, for non-AIDS-defining cancer and 0.32 percentage point (CI, 0.21 to 0.44 percentage point) and 1.00 percentage point (CI, 0.67 to 1.44 percentage points), respectively, for AIDS-defining cancer. Limitation: Potential residual confounding due to observational study design. Conclusion: In this young cohort, effects of immediate ART on 10-year risk for cancer were small, and further supportive data are needed for non-AIDS-defining cancer. Primary Funding Source: Highly Active Antiretroviral Therapy Oversight Committee.

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