non-AIDS-defining Cancers Research Articles

Epidemiologic contributions to recent cancer trends among HIV-infected people in the United States.

HIV-infected people have elevated risk for some cancers. Changing incidence of these cancers over time may reflect changes in three factors: HIV population demographic structure (e.g. age distribution), general population (background) cancer rates, and HIV-associated relative risks. We assessed the contributions of these factors to time trends for 10 cancers during 1996-2010. Population-based registry linkage study. We applied Poisson models to data from the U.S. HIV/AIDS Cancer Match Study to estimate annual percentage changes (APCs) in incidence rates of AIDS-defining cancers [ADCs: Kaposi sarcoma, non-Hodgkin lymphoma (NHL), and cervical cancer] and seven non-AIDS-defining cancers (NADCs). We evaluated HIV-infected cancer trends with and without adjustment for demographics, trends in background rates, and trends in standardized incidence ratios (SIRs, to capture relative risk). Cancer rates among HIV-infected people rose over time for anal (APC 3.8%), liver (8.5%), and prostate (9.8%) cancers, but declined for Kaposi sarcoma (1996-2000: -29.3%; 2000-2010: -7.8%), NHL (1996-2003: -15.7%; 2003-2010: -5.5%), cervical cancer (-11.1%), Hodgkin lymphoma (-4.0%), and lung cancer (-2.8%). Breast and colorectal cancer incidence did not change over time. Based on comparison to adjusted models, changing demographics contributed to trends for Kaposi sarcoma and breast, colorectal, liver, lung, and prostate cancers (all P < 0.01). Trends in background rates were notable for liver (APC 5.6%) and lung (-3.2%) cancers. SIRs declined for ADCs, Hodgkin lymphoma (APC -3.2%), and lung cancer (-4.4%). Demographic shifts influenced several cancer trends among HIV-infected individuals. Falling relative risks largely explained ADC declines, while background incidence contributed to some NADC trends.

Malignancies in HIV/AIDS

The incidence of AIDS-defining cancers (ADCs) - Kaposi sarcoma, primary central nervous system lymphoma, non-Hodgkin lymphoma, and cervical cancer - although on the decline since shortly after the introduction of HAART, has continued to be greater even in treated HIV-infected persons than in the general population. Although the survival of newly infected people living with HIV/AIDS now rivals that of the general population, morbidity and mortality associated with non-AIDS-defining cancers (NADCs) such as lung, liver, anal, and melanoma are significant and also continue to rise. Increasing age (i.e. longevity) is the greatest risk factor for NADCs, but longevity alone is not sufficient to fully explain these trends in cancer epidemiology. In this review, we briefly review the epidemiology and etiology of cancers seen in HIV/AIDS, and in this context, discuss preclinical research and broad treatment considerations. Investigation of these considerations provides insight into why malignancies continue to be a major problem in the current era of HIV/AIDS care.

Combination antiretroviral therapy (cART) component ritonavir significantly alters docetaxel exposure.

Non-AIDS-defining cancers (NADCs) now exceed rates of AIDS-defining cancers in HIV-positive patients. Treatment of NADCs may be complicated by drug-drug interactions between antiretrovirals and chemotherapy. Docetaxel is a widely used anticancer agent that is primarily metabolized by CYP3A4 enzymes and used to treat NADCs. A preclinical in vivo assessment was performed to gain a better understanding of CYP3-mediated drug-drug interactions between antiretrovirals and docetaxel, as well as to assess any alterations in gene expression with these combinations. Docetaxel (20 mg/kg i.v.) was administered to male FVB mice in the presence and absence of dexamethasone (10 mg/kg p.o. ×4d), efavirenz (25 mg/kg p.o. ×4d), ketoconazole (50 mg/kg p.o.), or ritonavir (12.5 mg/kg p.o.). At various time points, plasma and liver tissue were harvested. Docetaxel concentrations were determined by LC/MS/MS. Pharmacokinetic parameters were calculated. Liver tissue RNA was used to evaluate alterations in Cyp3a11 and Abcb1a gene expression. Docetaxel exposure was altered by CYP3A4 inhibitors but not by inducers. The CYP3A4 inducers efavirenz and dexamethasone did not have a significant effect on docetaxel exposure (AUC). However, the CYP3A4 inhibitors ritonavir and ketoconazole resulted in a 6.9- and 3.1-fold increase in AUC, respectively. Alterations in gene expression did not account for the altered docetaxel exposure. Docetaxel exposure was significantly altered by CYP3A4 inhibitors. Until a definitive clinical trial is performed, docetaxel should be used with caution in patients on a ritonavir-containing antiretroviral regimen or an alternative antineoplastic therapy or antiretroviral regimen should be considered.

Psychological consequences of cancer screening in HIV

There is a growing awareness of the increase in non-AIDS-defining cancers (NADC) in the HIV-infected population. Cancer screening is one means of reducing morbidity and mortality, but such screening may have psychological consequences across those with high and low-risk results, such as increased anxiety, worry and potential behavior change like increased self-examination or medical follow-up. This review examines the literature on psychological consequences of screening for NADC in HIV-infected populations. Anal cancer is the only cancer type in which the psychological consequence of screening has been investigated in HIV-infected populations. Screening increases worry about anal cancer, particularly in those who are younger, have higher baseline anxiety or more symptoms. Participants with low-risk results show unrealistic optimism; this is a potential concern as it may lead to unrealistic beliefs about future risk, the need for healthy behaviors or follow-up screening. The lack of standardized screening protocols and programs makes assessing psychological consequences difficult. More research is needed to determine if HIV populations differ from general population studies. Increased health promotion or symptom awareness is important for NADC with no standardized screening. Screening programs need to be aware of the potential for increased anxiety and worry and provide support as needed.

Non-AIDS-defining Cancers Among HIV-Infected Patients

In the highly active antiretroviral therapy (HAART) era, the incidence of non-AIDS-defining cancers (NADC) has increased and contributes to a growing proportion of mortality in the aging HIV-infected population. The underlying pathogenic mechanisms of increased cancer risk are incompletely understood. Potential contributors include oncogenic effects of the HIV virus, immunosuppression, chronic inflammation and immune activation, exposure to HAART, higher rates of oncogenic viral coinfections and traditional cancer risk factors. HIV-infected patients often present with NADC at younger ages with more aggressive or advanced stage disease. However, when standard cancer therapy is given, treatment outcomes appear similar to the non-HIV population. These facts highlight the importance of clinicians' maintaining a high index of suspicion, performing age-appropriate screening, and optimizing cancer therapy. Development of novel strategies for screening, prevention, and treatment of NADC will be required to reverse these epidemiologic trends and improve the survival of HIV-infected patients.

Adverse events in non-AIDS-defining cancer patients receiving chemotherapy and combined antiretroviral therapy.

e12523 Background: From 1991 to 2005, the number of cases of non-AIDS defining cancers (NADC) rose from 3,192 to 10,059 in the USA. Studies have shown an improvement in survival for many HIV-associated malignancies in the post HAART era. Drug-drug interactions between HIV therapy and chemotherapy (CTX) are not well understood. HIV medications can inhibit or induce the cytochrome p450 system, modulating CTX clearance. To understand CTX-HIV medication interactions, we performed a retrospective analysis of all patients (pts) diagnosed with a solid NADC who took CTX with combined antiretroviral therapy (cART). Methods: 157 pts with solid NADC were identified via a computer search at County Hospital. Adverse events (AE) during CTX in pts taking cART were assessed by chart review and graded per the NCI Common Terminology Criteria. Statistics: A Fisher's exact test was used to examine the differences in AE incidence. Results: Patients who did not take cART in conjunction with, or did not require CTX, were excluded. The number of pts analyzed for anal cancer (n=25), lung carcinoma (n=9), breast (n=7), and head and neck carcinoma (HNSCC) (n=4) represents 94% of pts taking cART with CTX in our cohort. Interestingly, Forty-two pts (50%) never received cART during therapy. All pts with anal carcinoma were treated with mitomycin/5FU/radiotherapy. 46 % of the patients taking ritonavir-based cART (6 pts of 13) developed a G4 neutropenia versus 8% (1 pt of 12) taking non-ritonavir cART (p&lt;0.07). Anemia all grades with ritonavir, 54%, versus non-ritonavir cART 16% (p&lt;0.09). All grades neutropenia for lung carcinoma while taking ritonavir was 83% versus 33% while taking non-ritonavir cART. No other correlations were identified. In this cohort, 17 pts received platinum (37%), taxanes (n=5) (11%), anthracyclines (n=5) 11%, gemcitabine (n=2) (4%), and pemetrexed (n=1). No difference in AE was noted between any CTX class, AE, and cART. Conclusions: Ritonavirinduced a 38% increase in G4 neutropenia and anemia during treatment of anal carcinoma with mitomycin/5FU. More trials including HIV-associated cancer pts are needed to assess the role of cART when given in conjunction with CTX.

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

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.

Neoplasms and infections as the main causes of death in patients in complete response to HIV‐related non‐Hodgkin lymphoma in the combination antiretroviral therapy era: a study out of a series of 146 patients

Neoplasms and infections as the main causes of death in patients in complete response to HIV‐related non‐Hodgkin lymphoma in the combination antiretroviral therapy era: a study out of a series of 146 patients

Trends and Predictors of Non–AIDS-Defining Cancers in Men and Women With HIV Infection

The incidence of non-AIDS-defining cancers (NADCs) in HIV-positive patients has increased over recent years. Most studies of the risk and spectrum of NADCs are primarily based on male populations, and only a few have provided specific information regarding females. We retrospectively analyzed all incident NADCs occurring in a cohort of HIV-positive patients followed up between 1985 and 2011. Incidence rates before and after the introduction of highly active antiretroviral therapy (HAART) were examined using Poisson regression models. Standardized incidence ratios (SIRs) were used to compare the cancer risk of HIV-infected subjects with that of the age- and gender-matched general population as estimated by the Milan Cancer Registry. Five thousand nine hundred twenty-four patients (4382 men and 1542 women) contributed 50,990 person-years to the follow-up. Among them, 144 had new NADC diagnosis. The overall incidence increased from 1.0 case/1000 person-years in the pre-HAART period to 4.5 cases/1000 person-years in the HAART period (P < 0.01). In women, the risks were higher than expected in the case of cancer of the vulva (SIR = 69.2), Hodgkin lymphoma (SIR = 7.5), anal cancer (SIR = 41.2), and lung cancer (SIR = 4.8). In men, the risks were higher than expected in the case of anal cancer (SIR = 91.5), Hodgkin lymphoma (SIR = 13.0), tonsil cancer (SIR = 10.9), lung cancer (SIR = 2.1), and liver cancer (SIR = 7.1). The spectrum and incidence of NADCs in our cohort increased over time. The incidence of NADCs, especially virus- and smoking-associated cancers, was significantly higher than expected in HIV-positive men and women.

Short Communication: Lack of Occult HIV Infection Among Non-AIDS-Defining Cancer Patients in Three Academic Oncology Clinics in the United States

The Centers for Disease Control (CDC) testing recommendations suggest universal opt-out testing in all health care settings, including cancer clinics. The incidence of non-AIDS-defining cancers (NADCs) is on the rise among HIV patients. However, to date, no data exist on the prevalence of HIV infection among NADC patients in the United States. Knowledge of HIV infection may affect clinical management, prognosis, and overall patient survival and decrease new infections in the population. The purpose of this study was to determine the point seroprevalence of HIV infection in cancer patients being seen in medical oncology clinics. A total of 634 individuals (mean age=53.2 years) participated and were tested for HIV. None of the participants tested positive for HIV in any of the three clinics. Using a futility analysis, the upper end of the 95% confidence interval for prevalence of undiagnosed HIV in cancer patients was less than 0.3%. Most participants were female (59.2%) and non-Hispanic (96.6%). The majority of study participants were white (76.5%) or African-American (17.7%). Breast cancer (19.7%), colon cancer (10.3%), and melanoma (9.7%) were the most commonly reported non-AIDS-defining cancers. While our study suggested that there was no occurrence of undiagnosed HIV among NADC patients, it is important to note that our population was largely white, females with insurance and with a different distribution of cancer than the most prevalent NADC among HIV patients. Furthermore, one-third of the patients did not consent to participate and further studies are needed to assess reasons for their unwillingness along with other populations, specifically minorities and individuals with low socioeconomic status (SES).

Epidemic of Lung Cancer in Patients With HIV Infection

The survival of patients with HIV infection has improved dramatically over the past 20 years, largely owing to a significant reduction in opportunistic infections and AIDs-defining malignancies, such as lymphoma and Kaposi sarcoma. However, with improved survival, patients with HIV are experiencing morbidity and mortality from other (non-AIDs-defining) complications, such as solid organ malignancies. Of these, the leading cause of mortality in the HIV-infected population is lung cancer, accounting for nearly 30% of all cancer deaths and 10% of all non-HIV-related deaths. Importantly, the average age of onset of lung cancer in the HIV-infected population is 25 to 30 years earlier than that in the general population and at lower exposure to cigarette smoke. This article provides an overview of the epidemiology of lung cancer in the HIV-infected population and discusses some of the important risk factors and pathways that may enhance the risk of lung cancer in this population.

Exposure to antiretroviral therapy and risk of cancer in HIV-infected persons

The incidence of certain non-AIDS-defining cancers (NADCs) in HIV patients has been reported to have increased in the combination antiretroviral therapy (ART) era. Studies are needed to directly evaluate the effect of ART use on cancer risk. We followed 12 872 HIV-infected Kaiser Permanente members whose complete ART history was known for incident cancers between 1996 and 2008. Cancers, identified from Surveillance, Epidemiology, and End Results (SEER)-based cancer registries, were grouped as ADCs, infection-related NADCs, or infection-unrelated NADCs. We also evaluated the most common individual cancer types. Rate ratios for ART use (yes/no) and cumulative duration of any ART, protease inhibitor, and nonnucleotide reverse transcriptase inhibitor (NNRTI) therapy were obtained from Poisson models adjusting for demographics, pretreatment or recent CD4 cell count and HIV RNA levels, years known HIV-infected, prior antiretroviral use, HIV risk, smoking, alcohol/drug abuse, overweight/obesity, and calendar year. The cohort experienced 32 368 person-years of ART, 21 249 person-years of protease inhibitor therapy, and 15 643 person-years of NNRTI therapy. The mean follow-up duration was 4.5 years. ADC rates decrease with increased duration of ART use [rate ratio per year = 0.61 (95% confidence interval 0.56-0.66)]; the effect was similar by therapy class. ART, protease inhibitor, or NNRTI therapy duration was not associated with infection-related or infection-unrelated NADC [rate ratio per year ART = 1.00 (0.91-1.11) and 0.96 (0.90-1.01), respectively], except a higher anal cancer risk with longer protease inhibitor therapy [rate ratio per year = 1.16 (1.02-1.31)]. No therapy class-specific effect was found for ADC. ART exposure was generally not associated with NADC risk, except for long-term use of protease inhibitor, which might be associated with increased anal cancer risk.

The Rising Challenge of Non-AIDS-Defining Cancers in HIV-Infected Patients

Since the advent of HAART, patients with HIV infection have seen a significant improvement in their morbidity, mortality, and life expectancy. The incidence of AIDS-defining illnesses, including AIDS-defining malignancies, has been on the decline. However, deaths due to non-AIDS-defining illnesses have been on the rise. These so-called non-AIDS-defining cancers (NADCs) include cancers of the lung, liver, kidney, anus, head and neck, and skin, as well as Hodgkin's lymphoma. It is poorly understood why this higher rate of NADCs is occurring. The key challenge facing oncologists is how to administer chemotherapy effectively and safely to patients on antiretroviral therapy. The challenge to clinicians caring for HIV-infected patients is to develop and implement effective means to screen, treat, and prevent NADCs in the future. This review presents data on the epidemiology and etiology of NADCs, as well as ongoing research into this evolving aspect of the HIV epidemic.

Mortality due to cancer among people with AIDS: a novel approach using registry-linkage data and population attributable risk methods.

Deaths related to HIV/AIDS have declined due to improved HIV therapies. However, people with AIDS remain at elevated risk for cancer and cancer deaths. Prior studies evaluated cancer deaths using death certificates, which may be inaccurate. We utilized population attributable risk methods (which do not rely on death certificates) to assess cancer mortality. Data from a US population-based record linkage study were used to identify incident cancers and deaths in 372 364 people with AIDS (1980-2006) followed for up to 5 years after AIDS onset. We utilized Cox regression to compare mortality in individuals with and without cancer and to calculate cancer-attributable mortality across calendar periods (AIDS onset in 1980-1989, 1990-1995, and 1996-2006). Mortality declined across calendar periods for all people with AIDS but remained higher among those with cancer relative to those without. During 1996-2006, among individuals with an AIDS-defining cancer (ADC) who died, 88.3% of deaths were attributable to their ADC; likewise, among individuals with a non-AIDS-defining cancer (NADC), 87.1% of deaths were attributable to their NADC. The fraction of all deaths in people with AIDS attributable to ADC (i.e. population-attributable risk) decreased significantly from 6.3% (1980-1990) to 3.9% (1996-2006), but NADC population attributable mortality increased significantly over time from 0.5% (1980-1989) to 2.3% (1996-2006). Among individuals with AIDS and cancer who subsequently die, most deaths are attributable to cancer. With a decline in overall mortality, the proportion of all deaths attributable to NADCs has increased. These results highlight the need for improved cancer prevention and treatment.

A retrospective analysis of all non-AIDS defining cancers (NADC): A subset analysis of the County Hospital AIDS Malignancy Project (CHAMP).

1611 Background: County Hospital (CCH) with its HIV clinic, the CORE Center (CC) is the largest provider for HIV patients (pts) in Chicago, treating over 5,500 HIV pts yearly. There is paucity of data on characteristics of HIV+ cancers (ca) in the inner city. The CHAMP cohort is a retrospective study of all HIV associated cancers at CC and CCH over past 14 years (yrs). We analyzed all of the NADC from this cohort. Methods: All HIV pts with NADC were identified from the CHAMP cohort and retrospectively reviewed for HIV and cancer characteristics, overall survival (OS), and pt demographics. Statistics: Survival data was analyzed using Kaplan-Meier analysis and Cox Proportional Hazards model. Results: Of 438 pts identified, 157 were NADC representing 21 ca. The average (ave) age was 48 yrs (range 44-57), with prostate ca having highest age presentation. Over the past 10 yrs, the number of NADC has risen from 10 to over 20 each yr. Unlike historical controls (HC) where lung ca is most common, anal ca (21%) was most frequent followed by lung ca (17%). Prostate, head and neck (HNSCC), liver, and colorectal ca were seen in 9, 9, 8, and 7% respectively. 65% of pts were African Americans (AA) and 18% Caucasians. 78% of all NADC were men. 45% of anal ca present with stage IIIa/b disease, moderately to poorly differentiated ca in 48%, with a median OS of 34 mo. CD4 count did not alter OS but stage predicted better outcomes. 86% lung ca presented as stage III/IV disease with ave CD4 count 204. Histologically, 36% were SCC, 28% adenosquamous and 20% adenocarcinoma. OS was 5.5 mo and did not change by histology, CD4, or age. 68% HNSCC present with stage IVa/b but no IVc. Ave age was 48 yrs with an OS of 18mo. 50% were oropharyngeal compared to 22% in HC. Conclusions: Based on data by Sheilds et. al, CCH treats just over 1% of the country’s NADC population. We demonstrate a higher incidence of NADC over time, dominated by a younger, AA and male population. Each ca presents with advanced stage 45-86% and poorly differentiated tumors ranging from 15-30%. The OS of each cancer is consistent with HC with exception of HNSCC. As HIV pts age becoming prone to cancers of elderly, education and screening of inner city HIV pts will help improve cancer rates.

A phase 1/PK study of Sunitinib with highly active antiretroviral therapy (HAART) in HIV+ patients with solid tumors: AIDS malignancy consortium study 061

Background In developed counties the rates of non-AIDS defining cancers (NADCs) now exceed those of AIDS-defining cancers in HIV-positive patients. Drug-drug interactions between HAART and chemotherapy may complicate the treatment of patients with NADCs. In order to determine the proper dosing of new targeted chemotherapies in patients with NADCs who are also on HAART, the AMC is performing a series of phase I/pharmacokinetic (PK) studies to determine the proper dosing of these agents in HIV+ cancer patients. We present the results of the first such study which investigated sunitinib, an oral multiple tyrosine kinase inhibitor.

Demographics and survival of AIDS cases with cancer, Washington, DC, 1996-2006

Background Washington, DC (DC) has one of the highest HIV/AIDS rates in the U.S and cancer is the second leading cause of death among DC residents. This study sought to examine the demographic characteristics and survival of persons with AIDS defining cancers (ADCs) compared to those with non-AIDS defining cancers (NADCs) between the early HAART era (1996-2001) and the late HAART era (2002-2006) in DC.

HIV and cancer in Africa: mutual collaboration between HIV and cancer programs may provide timely research and public health data

The eruption of Kaposi sarcoma (KS) and aggressive non-Hodgkin lymphoma (NHL) in young homosexual men in 1981 in the West heralded the onset of the human immunodeficiency virus (HIV) infection epidemic, which remains one of the biggest challenges to global public health and science ever. Because KS and NHL were increased >10,000 and 50-600 times, respectively, with HIV, they were designated AIDS defining cancers (ADC). Cervical cancer (CC), increased 5-10 times was also designated as an ADC. A few other cancers are elevated with HIV, including Hodgkin lymphoma (10 times), anal cancer (15-30 times), and lung cancer (4 times) are designated as non-AIDS defining cancers (NADCs). Since 1996 when combination antiretroviral therapy (cART) became widely available in the West, dramatic decreases in HIV mortality have been observed and substantial decrease in the incidence of ADCs. Coincidentally, the burden of NADCs has increased as people with HIV age with chronic HIV infection. The impact of HIV infection on cancer in sub-Saharan Africa, where two thirds of the epidemic is concentrated, remains poorly understood. The few studies conducted indicate that risks for ADCs are also increased, but quantitatively less so than in the West. The risks for many cancers with established viral associations, including liver and nasopharynx, which are found in Africa, do not appear to be increased. These data are limited because of competing mortality, and cancer is under diagnosed, pathological confirmation is rare, and cancer registration not widely practiced. The expansion of access to life-extending cART in sub-Saharan Africa, through programs such as the Global Fund for AIDS, Malaria, and Tuberculosis and the US President's Emergency Program for AIDS Relief (PEPFAR), is leading to dramatic lengthening of life of HIV patients, which will likely influence the spectrum and burden of cancer in patients with HIV. In this paper, we review current literature and explore merits for integrating cancer research in established HIV programs to obtain timely data about the incidence and burden of cancer in HIV-infected persons in Africa.

AIDS-Related Pathology

AIDS-Related Pathology

Incidence of Non-AIDS-Defining Cancer in Antiretroviral Treatment-Naïve Subjects after Antiretroviral Treatment Initiation: An ACTG Longitudinal Linked Randomized Trials Analysis

Background: Prospective data on factors associated with the non-AIDS-defining cancer (NADC) incidence in HIV-infected individuals are limited. Methods: We examined the NADC incidence in 3,158 antiretroviral treatment (ART)-naïve subjects after ART initiation in AIDS Clinical Trials Group trials; extended follow-up was available for 2,122 subjects. Poisson regression was used to examine the associations between covariates and incident NADC. Results: At ART initiation, subjects (median age 37 years) were 40% non-Hispanic whites, and 82% were male; 23% had CD4+ T cell count ≤50 cells/mm³ and 25% had CD4 >350 cells/mm³. Median follow-up was 3.8 years. Among 64 incident NADCs, the most common were 8 anal cancers, 8 basal cell carcinomas, 8 Hodgkin’s disease, and 6 lung cancers. In univariate models, age, smoking and recent (time-updated) CD4 were associated with incident NADC. There was no association between initial ART drug class (protease inhibitor, nucleoside reverse transcriptase inhibitor and nonnucleoside reverse transcriptase inhibitor) and NADC. After adjusting for age, race and sex: smoking [relative risk = 2.12 (95% CI = 1.1–4.08)] and recent CD4 (≤50 cells/mm³: 3.58, 1.22–10.45; 51–200 cells/mm³: 2.54, 1.30–5.0; 201–350 cells/mm³: 2.37, 1.32–4.26 vs. >350 cells/mm³) were associated with NADC. Conclusion: Smoking and lower recent CD4 levels, but not initial ART drug class, were associated with NADC. Strategies for maintaining higher CD4 cell counts and successful smoking cessation may reduce the NADC incidence in the HIV-infected population.