Cancer risk and use of protease inhibitor or nonnucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy: the D: A: D study.

Abstract

BACKGROUND:

The association between combination antiretroviral therapy (cART) and cancer risk, especially regimens containing protease inhibitors (PIs) or nonnucleoside reverse transcriptase inhibitors (NNRTIs), is unclear.

METHODS:

Participants were followed from the latest of D:A:D study entry or January 1, 2004, until the earliest of a first cancer diagnosis, February 1, 2012, death, or 6 months after the last visit. Multivariable Poisson regression models assessed associations between cumulative (per year) use of either any cART or PI/NNRTI, and the incidence of any cancer, non-AIDS-defining cancers (NADC), AIDS-defining cancers (ADC), and the most frequently occurring ADC (Kaposi sarcoma, non-Hodgkin lymphoma) and NADC (lung, invasive anal, head/neck cancers, and Hodgkin lymphoma).

RESULTS:

A total of 41,762 persons contributed 241,556 person-years (PY). A total of 1832 cancers were diagnosed [incidence rate: 0.76/100 PY (95% confidence interval: 0.72 to 0.79)], 718 ADC [0.30/100 PY (0.28-0.32)], and 1114 NADC [0.46/100 PY (0.43-0.49)]. Longer exposure to cART was associated with a lower ADC risk [adjusted rate ratio: 0.88/year (0.85-0.92)] but a higher NADC risk [1.02/year (1.00-1.03)]. Both PI and NNRTI use were associated with a lower ADC risk [PI: 0.96/year (0.92-1.00); NNRTI: 0.86/year (0.81-0.91)]. PI use was associated with a higher NADC risk [1.03/year (1.01-1.05)]. Although this was largely driven by an association with anal cancer [1.08/year (1.04-1.13)], the association remained after excluding anal cancers from the end point [1.02/year (1.01-1.04)]. No association was seen between NNRTI use and NADC [1.00/year (0.98-1.02)].

CONCLUSIONS:

Cumulative use of PIs may be associated with a higher risk of anal cancer and possibly other NADC. Further investigation of biological mechanisms is warranted.

• Authors: Mathias Bruyand, Lene Ryom, Leah Shepherd, Gerd Fatkenheuer, Andrew Grulich, Peter Reiss, Stéphane de Wit, Antonella D Arminio Monforte, Hansjakob Furrer, Christian Pradier, Jens Lundgren, Caroline Sabin, D:A:D study group
• Journal: Journal of acquired immune deficiency syndromes (1999) (J Acquir Immune Defic Syndr) Vol. 68 Issue 5 Pg. 568-77 (Apr 15 2015) ISSN: 1944-7884 [Electronic] United States
• PMID: 25763785 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Protease Inhibitors
• Reverse Transcriptase Inhibitors

Topics

• Adult
• Antiretroviral Therapy, Highly Active (adverse effects, methods)
• Female
• Follow-Up Studies
• HIV Infections (drug therapy)
• Humans
• Incidence
• Male
• Middle Aged
• Neoplasms (epidemiology)
• Prospective Studies
• Protease Inhibitors (adverse effects)
• Reverse Transcriptase Inhibitors (adverse effects)
• Risk Assessment