Burden of Non-AIDS-Defining and Non-Virus-Related Cancers Among HIV-Infected Patients in the Combined Antiretroviral Therapy Era

Abstract

The risk of cancer is substantially increased in HIV-infected patients. However, little is known about non-AIDS-defining cancers (NADCs) without an infectious etiology. A total of 5,090 HIV-infected patients registered in the Local Health Authority (LHA) of Brescia and receiving primary care at our clinic were included in a retrospective (1999-2009) analysis. The cancer diagnoses were obtained through a record-linkage procedure between our database and the LHA general database and population-based Cancer Registry of LHA. We compared risks of these malignancies with those of the general population living in the same health area by using age-standardized incidence ratios (SIRs). Poisson regression analysis was used to assess factors associated with non-virus-related NADCs. We recorded an increase in the SIR of non-virus-related NADCs over time, with 138 cancers diagnosed in 131 patients. The mean incidence rate was 42.6/10,000 person years and the median age at the diagnosis was 49 (range, 28-78) years old. Stratifying for gender, only HIV-infected males had an increased risk of non-virus-related NADCs [SIR=1.86; 95% confidence interval (CI), 1.55-2.26]. Risk was higher for lung (SIR=3.59; 95% CI, 2.36-5.45) and testis cancer (SIR=3.11; 95% CI, 1.48-6.52). However,, cancers of the prostate and breast in HIV-positive men and women were null (SIR=1.10; 95% CI, 0.53-2.32 and SIR=0.91; 95% CI, 0.47-1.74, respectively). The only predictors of non-virus-related NADCs included older age [incidence rate ratio (IRR)=1.10; 95% CI, 1.08-1.12 per each additional year, p<0.001] and a shorter or no exposition to combined antiretroviral therapy (cART) (IRR=2.31; 95% CI, 1.38-3.89, p=0.002). A CD4⁺ count lower than 50/mm³ was significantly associated with cancers only in the univariate model (IRR=1.40; 95% CI, 0.99-1.98, p=0.057). HIV-infected men showed a 2-fold increased risk of non-virus-related NADCs compared to the general population. However, the use of cART appeared to be beneficial in protecting against the development of these malignancies.

Time trends in cancer incidence in persons living with HIV/AIDS in the antiretroviral therapy era

“…The significant decreasing trend we observed in the HIV+ non-virus-NADC IR was consistent with findings from the HIV Outpatient Study [24], but inconsistent with results from northern Italy, where a borderline significant increasing trend was observed [25] and from Kaiser, where no trend was observed, either in the HIV+ IR or in the IRR [23]. The decreasing non-virus-NADC IRR trend that we observed, which took the decreasing uninfected non-virus-NADC IR trend into account, was only marginally significant.…”

“…Studies of adjusted IR time trends that classified NADC into broad groupings have produced inconsistent results [20, 23–25]. Evidence supports decreasing trends for lung cancer and Hodgkin lymphoma and an increasing trend for liver cancer, but results for anal cancer have been inconsistent; many nonsignificant trends for specific NADC have been observed, perhaps due to insufficient statistical power [11, 16–19, 21–23, 26].…”

Micronucleated Erythrocytes in Newborn Rats Exposed to Raltegravir Placental Transfer

“…The genotoxic evaluation of antiretroviral drugs, including raltegravir, might be considered due to the high frequency of cancer in patients with AIDS [33]. …”

Cancer prevention in HIV-infected populations

“…The effect of cART on cancer incidence is likely to be heterogeneous across cancer types. While some studies show no decreased risk of NADM as a whole for patients on cART 139,141,143 , a few large studies have identified HIV viremia as an independent risk factor for cervical cancer and anal cancer 149,151,152 , while others have found time on cART (or controlled HIV viremia) associated with decreased risk of certain non-virally associated NADM (largely lung cancer) 153 , as well as classical Hodgkin lymphoma 147 and anal cancer 152 . Differences between studies may depend in part on the definition of HIV viremia, with percent time with undetectable HIV a more sensitive measure of cART effect than single measurements of HIV viremia.…”