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Non-AIDS Cancer Rate Higher With Longer PI (But Not NNRTI) Therapy in D:A:D
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20th Conference on Retroviruses and Opportunistic Infections, March 3-6, 2013, Atlanta
Mark Mascolini
Every year of treatment with protease inhibitors (PIs) boosted the risk of non-AIDS cancers 3%, according to results of a 41,762-person D:A:D Study analysis [1]. In contrast, longer treatment with nonnucleoside reverse transcriptase inhibitors (NNRTIs) did not affect risk of non-AIDS cancers. Longer treatment with either PIs or NNRTIs cut the risk of AIDS cancers. (The poster is linked in the reference below.)
Because the cumulative impact of combination antiretroviral therapy (cART) with PIs and NNRTIs remains unclear, D:A:D Study investigators conducted this analysis of participants monitored for new cancer diagnoses since January 1, 2004 until the first new cancer, January 2, 2012, death, or 6 months after the last study visit. The D:A:D team separately considered the impact of cumulative therapy on any cancer, AIDS cancers, non-AIDS cancers, three individual AIDS cancers (cervical cancer, Kaposi sarcoma, non-Hodgkin lymphoma), and four individual non-AIDS cancers (lung cancer, invasive anal cancer, Hodgkin lymphoma, head and neck cancer). To assess associations between each additional year of cART use and cancer incidence, the researchers used Poisson regression models adjusted for age, sex, cohort, HIV acquisition mode, ethnic group, calendar year, body mass index, any prior cancer, prior AIDS cancer, prior AIDS diagnosis, hepatitis B or C status, and smoking status.
The analysis included 41,762 HIV-positive people, 73% of them men, 44% infected during sex between men, and 35% infected during sex between men and women. Median age stood at 39 years, median CD4 count at 433, and median viral load at 200 copies. While 39.8% of the study group currently smoked, 10.5% were positive for HCV and 4.2% for HBV; 7% had a prior cancer diagnosis.
Over a median follow-up of 6.4 years (interquartile range 3.7 to 8.1), clinicians diagnosed 2242 new cancers to yield an incidence of 0.93 per 100 person-years, meaning almost 1 in 100 people got diagnosed with cancer every year. There were 1151 AIDS cancers (incidence 0.48 per 100 person-years), 1091 non-AIDS cancers (0.45 per 100 person-years), 496 cervical cancers (0.21 per 100 person-years), and 194 lung cancers (0.081 per 100 person-years).
Non-AIDS cancer incidence rose from 0.24 per 100 person-years before cART use to 0.73 after more than 12 years of therapy. In contrast, AIDS cancer risk dropped from 0.81 per 100 person-years before cART to 0.11 after more than 12 years of treatment. Every year of cART cut the overall cancer risk 2% (adjusted rate ratio [aRR] 0.98 per year, 95% confidence interval [CI] 0.97 to 1.00, P = 0.009). Every year of NNRTI therapy trimmed overall cancer risk 3% (aRR 0.97 per year, 95% CI 0.95 to 0.99, P = 0.0009). But longer PI use was not associated with overall cancer risk.
Every year of PI therapy lowered the risk of AIDS cancers 7% (aRR 0.93 per year, 95% CI 0.90 to 0.97, P = 0.0001), while every year of NNRTI therapy cut the AIDS cancer risk 16% (aRR 0.84 per year, 95% CI 0.80 to 0.88, P = 0.0001). These associations held true for cervical cancer and Kaposi sarcoma, but longer PI use was not linked to lower non-Hodgkin lymphoma risk.
Each year of PI therapy boosted the risk of non-AIDS cancers 3% (aRR 1.03 per year, 95% CI 1.01 to 1.05, P = 0.0003). But longer NNRTI use was not associated with non-AIDS cancer risk (aRR 1.00 per year, 95% CI 0.98 to 1.02). Among non-AIDS cancers, longer PI therapy inflated the risk of anal cancer, but not Hodgkin lymphoma, lung cancer, or head and neck cancers. In an analysis adjusted for mode of HIV acquisition, longer PI use raised the risk of anal cancer regardless of gender.
In a recent 12,872-person analysis of HIV-positive people in the US Kaiser healthcare system, every year of PI therapy was associated with a 16% higher anal cancer rate and a 13% lower prostate cancer rate [2].
References
1. Bruyand M, Ryom L, Shepherd L, et al. Cancer risk and use of protease inhibitor- or NNRTI-based cART: the D:A:D study. 20th Conference on Retroviruses and Opportunistic Infections. March 3-6, 2013. Atlanta. Abstract 742b. http://www.retroconference.org/2013b/PDFs/742b.pdf
2. Chao C, Leyden WA, Xu L, et al. Exposure to antiretroviral therapy and risk of cancer in HIV-infected persons. AIDS. 2012;26:2223-2231.
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