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. 2024 Aug;96(4):393-398.
doi: 10.1097/QAI.0000000000003436.

Brief Report: Protease Inhibitors Versus Nonnucleoside Reverse Transcriptase Inhibitors and the Risk of Cancer Among People With HIV

Sally B Coburn  1 , Noel Pimentel  2 , Wendy Leyden  2 , Mari M Kitahata  3 , Richard D Moore  4 , Keri N Althoff  1 , M John Gill  5 , Raynell Lang  5 , Michael A Horberg  6 , GypsyAmber D'Souza  1 , Shehnaz K Hussain  7 , Robert Dubrow  8 , Richard M Novak  9 , Charles S Rabkin  10 , Lesley S Park  11 , Timothy R Sterling  12 , Romain S Neugebauer  2   13 , Michael J Silverberg  2   13   14 ; North American AIDS Cohort Collaboration on Research and Design of the International Epidemiologic Databases to Evaluate AIDS
Collaborators, Affiliations

Brief Report: Protease Inhibitors Versus Nonnucleoside Reverse Transcriptase Inhibitors and the Risk of Cancer Among People With HIV

Sally B Coburn et al. J Acquir Immune Defic Syndr. 2024 Aug.

Abstract

Background: The effect of initial antiretroviral therapy (ART) class on cancer risk in people with HIV (PWH) remains unclear.

Setting: Cohort study of 36,322 PWH enrolled (1996-2014) in the North American AIDS Cohort Collaboration on Research and Design.

Methods: We followed individuals from ART initiation (protease inhibitor [PI]-, non-nucleoside reverse transcriptase inhibitor [NNRTI]-, or integrase strand transfer inhibitor [INSTI]-based) until incident cancer, death, loss-to-follow-up, 12/31/2014, 85 months (intention-to-treat analyses [ITT]), or 30 months (per-protocol [PP] analyses). Cancers were grouped (non-mutually exclusive) as: any cancer, AIDS-defining cancers (ADC), non-AIDS-defining cancers (NADC), any infection-related cancer, and common individual cancer types. We estimated adjusted hazard ratios (aHR) comparing cancer risk by ART class using marginal structural models emulating ITT and PP trials.

Results: We observed 17,004 PWH (954 cancers) with PI-based (median 6 years follow-up), 17,536 (770 cancers) with NNRTI-based (median 5 years follow-up) and 1,782 (29 cancers) with INSTI-based ART (median 2 years follow-up). Analyses with 85 months follow-up indicated no cancer risk differences. In truncated analyses, risk of ADCs (aHR 1.33; 95% CI 1.00, 1.77 [PP-analysis]) and NADCs (aHR 1.23; 95% CI 1.00, 1.51[ITT-analysis]) were higher comparing PIs vs. NNRTIs.

Conclusions: Results with longer-term follow-up suggest being on a PI- versus NNRTI-based ART regimen does not affect cancer risk. We observed shorter-term associations that should be interpreted cautiously and warrant further study. Further research with longer duration of follow-up that can evaluate INSTIs, the current first-line recommended therapy, is needed to comprehensively characterize the association between ART class and cancer risk.

Keywords: ART class; HIV; NNRTI; PI; cancer.

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Conflict of interest statement

Conflicts of Interest: KN Althoff serves on the advisory board for TrioHealth. MJ Gill has received honoraria as an ad hoc member of Canadian National HIV Advisory Boards to Merck Gilead and ViiV.

Figures

Figure 1.
Figure 1.
Adjusted hazard ratios (95% CI) for cancer risk comparing PI-based versus NNRTI-based ART1,2 ADC, AIDS-defming cancer; ITT, intention-to-treat; NADC, non-AIDS-defining cancer; PI, pro tease inhibitor; PP, per-protocol; NNRTI, non-nucleoside reverse transcriptase inhibitor 1Results from marginal structural working models, with weights for right-censoring due to death and loss to follow-up in ITT models, and switching/discontinuing original ART in PP models. Proportional hazards assumed to estimate one hazard ratio across the month-level discrete-time intervals. Confidence intervals derived utilizing the influence curve of the IPW estimator of the coefficients of the marginal structural model and the delta method. 2ADCs: Kaposi sarcoma, non-Hodgkin lymphoma and cervical cancer; NADCs; all other cancers; virus-related NADCs: anal, liver, human papillomavirus-related oropharyngeal, penile, vaginal, vulvar cancers and Hodgkin lymphoma; virus-unrelated NADCs: all other NADCs
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References

    1. Blum L, Pellet C, Agbalika F, et al. Complete remission of AIDS-related Kaposi’s sarcoma associated with undetectable human herpesvirus-8 sequences during anti-HIV protease therapy. AIDS. Nov 1997;11(13):1653–5. - PubMed
    1. Kennedy AR. Chemopreventive agents: protease inhibitors. Pharmacol Ther. Jun 1998;78(3):167–209. doi: 10.1016/s0163-7258(98)00010-2 - DOI - PubMed
    1. Lebbe C, Blum L, Pellet C, et al. Clinical and biological impact of antiretroviral therapy with protease inhibitors on HIV-related Kaposi’s sarcoma. AIDS. May 7 1998;12(7):F45–9. doi: 10.1097/00002030-199807000-00002 - DOI - PubMed
    1. Monini P, Sgadari C, Toschi E, Barillari G, Ensoli B. Antitumour effects of antiretroviral therapy. Nat Rev Cancer. Nov 2004;4(11):861–75. doi: 10.1038/nrc1479 - DOI - PubMed
    1. Monini P, Toschi E, Sgadari C, et al. The use of HAART for biological tumour therapy. J HIV Ther. Sep 2006;11(3):53–6. - PubMed

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