non-AIDS Cancers Research Articles

Immunodeficiency and the risk of serious clinical endpoints in a well studied cohort of treated HIV-infected patients.

To investigate the relative predictive value of CD4(+) metrics for serious clinical endpoints. Observational. Patients (3012; 20 317 person-years) from control arms of ESPRIT and SILCAAT were followed prospectively. We used Cox regression to identify CD4(+) metrics (latest, baseline and nadir CD4(+) cell count, latest CD4(+)%, time spent with CD4(+) count below certain thresholds and CD4(+) slopes) independently predictive of all-cause mortality, non-AIDS deaths, non-AIDS (cardiovascular, hepatic, renal and non-AIDS malignancy) and AIDS events. Akaike information criteria (AIC) were calculated for each model. Significant metrics (P < 0.05) were then additionally adjusted for latest CD4(+) cell count. Non-AIDS deaths occurred at a higher rate than AIDS deaths [rate ratio: 6.48, 95% confidence interval (CI) 5.1-8.1], and non-AIDS events likewise (rate ratio: 1.72, 95% CI 1.65-1.79). Latest CD4(+) cell count was strongly predictive of lower risk of death (hazard ratio per log2 rise: 0.48, 95% CI 0.43-0.54), with lowest AIC of all metrics. CD4(+) slope over seven visits, after additional adjustment for latest CD4(+) cell count, was the only metric to be an independent predictor for all-cause (hazard ratio for slope <-10 cells/microl per month vs. 0 +/- 10: 3.04, 95% CI 1.98-4.67) and non-AIDS deaths (hazard ratio for slope <-10 cells/microl per month vs. 0 +/- 10: 2.62, 95% CI 1.62-4.22). Latest CD4(+) cell count (per log(2) rise) was the best predictor across all four endpoints and predicted hepatic (hazard ratio 0.46, 95% CI 0.33-0.63) and renal events (hazard ratio 0.39, 95% CI 0.21-0.70), but not cardiovascular events (hazard ratio 1.05, 95% CI 0.77-1.43) or non-AIDS cancers (hazard ratio 0.78, 95% CI 0.59-1.03). Latest CD4(+) cell count is the best predictor of serious endpoints. CD4(+) slope independently predicts all-cause and non-AIDS deaths.

Factors associated with specific causes of death amongst HIV-positive individuals in the D:A:D study

To investigate any emerging trends in causes of death amongst HIV-positive individuals in the current cART era, and to investigate the factors associated with each specific cause of death. An observational multicentre cohort study. All HIV-positive individuals included in one of the cohorts in the Data Collection on Adverse Events of Anti-HIV drugs (D:A:D) Study were included. The association between HIV-specific and non HIV-specific risk factors and death were studied using multivariable Poisson regression. We observed 2482 deaths in 180,176 person-years (PY) on 33,308 individuals [rate/1000 PY = 13.8 (95% CI 13.2-14.3)]. Primary causes of death were: AIDS (n = 743; rate/1000 PY = 4.12), liver-related (341; 1.89), CVD-related (289; 1.60), non-AIDS malignancy (286; 1.59). The overall rate of death fell from 16.9 in 1999/2000 to 9.6/ 1000 PY in 2007/2008. Smoking was associated with CVD and non-AIDS cancers, HBV and HCV co-infection with liver-related deaths, and hypertension with liver-related and CVD deaths. Diabetes was a risk factor for all specific causes of death except non-AIDS cancers, and higher current HIV RNA for AIDS-related deaths. Lower CD4 cell counts were associated with a higher risk of death from all specific causes of death. Multiple potentially modifiable traditional and HIV-specific risk factors for death of HIV-infected persons were identified. The maximum reduction in mortality in HIV-infected populations will require that each of these factors be appropriately addressed. No trends in terms of emerging causes of unexpected deaths were observed, although monitoring will continue.

A Meta-Analysis of the Incidence of Non-AIDS Cancers in HIV-Infected Individuals

To estimate summary standardized incidence ratios (SIRs) of non-AIDS cancers among HIV-infected individuals compared with general population rates overall and stratified by gender, AIDS, and highly active antiretroviral therapy (HAART) era. A meta-analysis using SIRs from 18 studies of non-AIDS cancer in HIV-infected individuals. SIRs for non-AIDS cancers in HIV-infected individuals and 95% confidence limits (CLs) were abstracted from each study. Random effects meta-analyses were used to estimate summary SIRs. Modifications by gender, AIDS, and HAART era were estimated with meta-regression. Four thousand seven hundred ninety-seven non-AIDS cancers occurred among 625,716 HIV-infected individuals. SIRs for several cancers were elevated. In particular, cancers associated with infections, such as anal (SIR = 28; 95% CL 21 to 35), liver (SIR = 5.6; 95% CL 4.0 to 7.7), and Hodgkin lymphoma (SIR = 11; 95% CL 8.8 to 15) and smoking, such as lung (SIR = 2.6; 95% CL 2.1 to 3.1), kidney (SIR = 1.7; 95% CL 1.3 to 2.2), and laryngeal (SIR = 1.5; 95% CL 1.1 to 2.0). AIDS was associated with greater SIRs for Hodgkin lymphoma, leukemia, lung, brain, and all non-AIDS cancers combined. HIV-infected individuals may be at an increased risk of developing non-AIDS cancers, particularly those associated with infections and smoking. An association with advanced immune suppression was suggested for certain cancers.

Distribution, characteristics, and prognostic of AIDS and non-AIDS cancers in HIV-infected patients, the ONCOVIH study

Address: 1INSERM, U720; UPMC Univ Paris 06, Paris, France, 2UPMC Univ Paris 06; AP-HP, Groupe hospitalier Pitie-Salpetriere, Service de Cancerologie Medicale, Paris, France, 3CHU de Bordeaux, Hopital Saint-Andre, Service de Medecine Interne et Maladies Infectieuses, Bordeaux, France, 4INSERM, U897; Universite Victor Segalen Bordeaux 2, Bordeaux, France, 5Universite Paris Sud; AP-HP, Hopital Antoine Beclere, Service de medecine interne, Clamart, France and 6AP-HP, Groupe hospitalier Pitie-Salpetriere, Service de Maladies Infectieuses et Tropicales, Paris, France * Corresponding author

A Meta-Analysis of the Incidence of Non-AIDS Cancers in HIV-Infected Individuals

A Meta-Analysis of the Incidence of Non-AIDS Cancers in HIV-Infected Individuals

Abstract A117: A meta-analysis of the incidence of non-AIDS cancers in HIV-infected individuals

Abstract A117 Objective To compare the incidence rate of all non-AIDS cancers combined among HIV-infected individuals with the general population rate and to estimate modification of the association by gender and AIDS diagnosis. Design A meta-analysis was carried out using data from 11 studies of non-AIDS cancer incidence in HIV-infected individuals. Methods Standardized incidence rate ratios (SIR) for non-AIDS cancers in HIV-infected individuals compared to the general population and 95% confidence limits (CL) were abstracted from each study. The results were assessed for between-study heterogeneity and funnel plot asymmetry. Meta-regression was used to estimate modification of the general-population SIR by gender and AIDS. Results There was pronounced heterogeneity between studies, thus, an overall pooled estimate was not calculated. The SIR of non-AIDS cancers in HIV-infected individuals, adjusted for AIDS and study design was greater among men (2.3; 95% CL: 1.7, 3.1) than women (1.5; 95% CL: 0.9; 2.3; ratio of SIRs = 1.6; 95% CL: 0.7, 3.2). The SIR also appeared slightly greater among those with an AIDS diagnosis; however, when the analysis was adjusted for gender and study design, the SIRs for those with (1.88; 95% CL: 1.34, 2.66) and without AIDS (1.98; 95% CL: 1.35, 2.88) were similar (ratio of SIRs: 0.95; 95% CL: 0.46, 1.96). Conclusions The incidence rate of non-AIDS cancers was elevated among HIV-infected individuals. Additionally, HIV-infected men appeared to have a greater SIR for non-AIDS cancers than HIV-infected women. However, no difference was seen between the SIRs for non-AIDS cancers among those with and without AIDS. Citation Information: Cancer Prev Res 2008;1(7 Suppl):A117.

Mortality and causes of death in HIV-positive patients receiving antiretroviral therapy at Tshepang Clinic in Doctor George Mukhari Hospital

Since the initiation of regular antiretroviral therapy and highly active antiretroviral therapy (HAART) in South Africa in 2004, data on effects of HAART on mortality are not available in our hospital. We sought to describe mortality trends and causes of deaths among HIV-infected patients in the HAART era. Consecutive HIV-infected adults who were prescribed HAART in our hospital were prospectively followed-up from July 2004 to December 2006 or until death, loss to follow-up, discontinuation of HAART or referral to another center. Out of 2605 HIV-infected patients analyzed at the end of 2006, 7.8% (n = 205) died. The causes of these 205 deaths were dominated by AIDS related disorders such as opportunistic infection (47.6%) and advanced AIDS status (37.3%). Non-AIDS infectious diseases, liver diseases, cardiovascular diseases, and cancers were rare. Mortality rate was higher in males (28%, p < 0.0001) than females (8%) as well as in subgroup with CD4 cell counts < 200/microl (8%, p < 0.0001) than in subgroup with CD4 cell counts > 200/microl (4.9%). There was a negative significant dose - response relationship (p for linear trend < 0.0001) between mortality and baseline CD4 cell counts among patients with CD4 cell counts < 200/microl, 13% in the CD4 < 50/microl group, 6% in the CD4 51-100/microl group, 5.5% in the CD4101-150/microl group, and 3% in the CD4 > 151/microl group. Mortality was not associated with age and HAART regimens. Prevention of AIDS-defining conditions and expansion of earlier access to HAART could substantially reduce mortality in resource-poor settings.

Poor Initial CD4+ Recovery With Antiretroviral Therapy Prolongs Immune Depletion and Increases Risk for AIDS and Non-AIDS Diseases

Low CD4+ increases risk for both AIDS- and non-AIDS-related morbidity and mortality. The magnitude of CD4+ recovery early after initial antiretroviral therapy (ART) is important in the ultimate duration of immune depletion. We examined CD4+ recovery among 850 participants in the Community Program for Clinical Research on AIDS Flexible Initial Retrovirus Suppressive Therapies study with virologic suppression (ie, achieved an HIV RNA level <400 copies/mL) with 8 months of initial ART and determined subsequent risk for AIDS, non-AIDS diseases (non-AIDS cancers and cardiovascular, end-stage renal, and liver diseases), or death using Cox regression during a median 5-year follow-up. Mean pretreatment CD4+ was 221 cells/microL; 18% (n = 149) had a poor CD4+ recovery (<50 cells/microL) after 8 months of effective ART, resulting in lower CD4+ over 5 years. Older age (hazard ratio 1.34/10 yrs, P = 0.003) and lower screening HIV RNA (hazard ratio 0.65 per log10 copies/mL higher, P = 0.001), but not screening CD4+, were associated with a poor CD4+ recovery. After 8 months of effective ART, 30 patients experienced the composite outcome of AIDS, non-AIDS, or death among participants with a poor CD4+ recovery (rate = 5.8/100 person-years) and 74 patients among those with an adequate recovery (>or=50 cells/muL; rate = 2.7/100 person-years) (adjusted hazard ratio = 2.24, P < 0.001). The risk of this composite outcome associated with a poor CD4+ recovery declined when ART was initiated at higher CD4+ counts (P < 0.01). Impaired immune recovery, despite effective ART, results in longer time spent at low CD4+, thereby increasing risk for a broad category of HIV-related morbidity and mortality conditions.

Trends and determinants of severe morbidity in HIV‐infected patients: the ANRS CO3 Aquitaine Cohort, 2000–2004*

The aim of the study was to characterize the causes, trends and determinants of severe morbidity in a large cohort of HIV-infected patients between 2000 and 2004. Severe morbid events were defined as medical events associated with hospitalization or death. Epidemiological and biological data were recorded at the time of the morbid event. Trends were estimated using Poisson regression. Among 3863 individuals followed between 2000 and 2004, 1186 experienced one or more severe events, resulting in 1854 hospitalizations or deaths. The severe events recorded included bacterial infections (21%), AIDS events (20%), psychiatric events (10%), cardiovascular events (9%), digestive events including cirrhosis (7%), viral infections (6%) and non-AIDS cancers (5%). Between 2000 and 2004, the incidence rate of AIDS events decreased from 60 to 20 per 1000 person-years, that of bacterial infections decreased from 45 to 24 per 1000 person-years, and that of psychiatric events decreased from 26 to 14 per 1000 person-years (all P<0.01), whereas the incidences of cardiovascular events and of non-AIDS cancers remained stable at 14 and 10 per 1000 person-years, on average, respectively. Severe morbidity has shifted from AIDS-related to non-AIDS-related events during the course of HIV infection in developed countries. Limiting endpoints to AIDS events and death is insufficient to describe HIV disease progression in the era of combination antiretroviral therapy.

Non-AIDS Cancers More Common Than AIDS Cancers in HIV Patients

Non-AIDS Cancers More Common Than AIDS Cancers in HIV Patients

Cancers et infection par le VIH : quelles associations ?

Purpose. – Morbidity and mortality related to neoplasia are increasing in HIV-infected patients. Current knowledge and key-points. – The incidence of AIDS opportunistic infections dramatically decreased since the introduction of highly active antiretroviral therapy (HAART). Among AIDS-cancers, the incidences of Kaposi sarcoma and of cerebral lymphoma decreased in a same way than AIDS infections but the incidences of systemic non-Hodgkin lymphoma and of cervical cancer decreased less than the others and remain higher than in the general population. This suggests that other factors than the quantitative immune reconstitution could be implicated. The most recent and large studies have also shown a 1.7 to 3 fold increased risk of developing non-AIDS cancers in HIV-infected patients when compared to the general population without significant impact of HAART on incidence curves. These malignancies include Hodgkin disease, lung, anal, head and neck cancers, hemopathies, and conjunctival cancers. Perspectives. – Epidemiologic survey will help to define priorities in terms of prevention and screening in this specific population and to evaluate interventions which should be systematically proposed (alcohol and tobacco cessation programs, viral coinfection). The own roles of HIV itself and of antiretrovirals as prooncogenic factors need to be assessed.

Progression of HIV infection in the post‐HAART era among a cohort of HIV+ Greek haemophilia patients

The study aims to describe the course of HIV-1 infection in the pre- and post-HAART period in a cohort of HIV+ haemophilia patients followed up for up to 21 years. The cohort includes 158 haemophilic men with known seroconversion dates followed up prospectively for a median time of 12 and 5.7 years in the pre- (1980-96) and post-HAART period (1997-2003), respectively. The risk of developing AIDS was lowered by 56% in the post- as compared to the pre-HAART period. Of the 158 patients 69 developed AIDS in the pre-HAART period while of the 59 subjects still alive and AIDS free on 1/1/1997 six developed AIDS. The rate of PCP (12.0 cases per 1000 person-years) and NHL (5.4 cases per 1000 person-years), the most common causes of AIDS diagnosis in the pre-HAART era, were remarkably reduced in the post-HAART era (both rates: 2.8 cases per 1000 person-years). On the contrary, the corresponding risk for non-AIDS deaths was fourfold increased in the post-HAART period. Of the 38 non-AIDS related deaths in both periods, 13 occurred post-HAART. The predominant cause of non-AIDS mortality in both periods was end-stage liver disease (ESLD) (7 pre- and 4 post-HAART). The rate of non-AIDS related cancers was also increased during the post-HAART period. In this haemophilia cohort the risk of AIDS has substantially reduced in the post-HAART period, but the rate of non-AIDS mortality tended to increase. Among haemophilia subjects, due to the high rates of HCV/HIV coinfection, ESLD, the predominant cause of non-AIDS mortality, will become an increasingly important clinical problem.

Opportunistic infections as causes of death in HIV-infected patients in the HAART era in France

The objective of the study was to describe the underlying causes of death of HIV-infected patients in the HAART era and to focus on those related to opportunistic infection (OI), in a national multicentre study ('Mortalité 2000'). A total of 964 deaths were recorded and 924 cases were available for analysis. Underlying cause of death were AIDS-related (47%), viral hepatitis (11%), non-AIDS cancers (11%), cardiovascular diseases (7%) and others (11%). Among patients who died of AIDS events, 262 (27%) died of at least one OI. OIs reported at the time of death were Cytomegalovirus infection 67 times, Pneumocystis jiroveci pneumonia 56, disseminated Mycobacterium avium intracellulare infection 53 and cerebral toxoplasmosis 48. Compared to patients who died of other causes, patients who died of OIs were younger and more likely to be infected through heterosexual contact, in poor socioeconomic conditions, migrants, more recently diagnosed for HIV infection, and naive of antiretroviral therapy and OI prophylaxis. OIs are still a major cause of death in HIV-infected patient in the HAART era, especially among patients recently diagnosed for HIV infection and who do not have access to care, as well as in long term infected patients where prophylaxis should be revisited.

Causes of death among human immunodeficiency virus (HIV)-infected adults in the era of potent antiretroviral therapy: emerging role of hepatitis and cancers, persistent role of AIDS

In the era of highly active antiretroviral therapy (HAART) mortality has decreased substantially among human immunodeficiency virus (HIV)-infected people with access to HAART, but there are concerns regarding co-morbidities and adverse effects of HAART, which may impair vital prognosis. The Mortality 2000 study examined the causes of death in HIV-infected adults at a national level in France in the year 2000. All French hospital wards known to be involved in the management of HIV infection were asked to notify prospectively the deaths that occurred in 2000 among HIV-infected adults. The causes of death were documented using a standardized questionnaire. The 185 participating wards notified 964 deaths. The main underlying causes of death were AIDS-related (47%, non-Hodgkin's lymphoma: 23%), viral hepatitis (11%, hepatitis C: 9%, hepatitis B: 2%), cancer not related to AIDS or hepatitis (11%), cardiovascular disease (7%), bacterial infections (6%), suicide (4%), and adverse effect of antiretroviral treatments (1%). Among AIDS-related deaths, HIV infection had been diagnosed recently in 20%. Smoking was recorded in 72% of cancer-related deaths and alcohol consumption in 54% of hepatitis-related deaths. Among non-HIV related deaths between 25 and 64 years, the proportion of infectious diseases (including HCV and HBV-related deaths) was higher in HIV-infected adults than in the general population. Improved strategies for detecting HIV infection before AIDS-defining complications occur are needed in the era of HAART. The prevention of non-AIDS related cancers, especially lung cancer, the management of non-Hodgkin's lymphoma, and of viral hepatitis are also important priorities.

Causes de décès des adultes infectés par le VIH dans les départements français d'Amérique à l'ère des traitements antirétroviraux hautement actifs

Objective. – The survey “Mortality 2000” had for aim to describe the distribution of causes of death in HIV-infected adults in France. Method. – Hospital wards involved in the management of HIV infection prospectively reported deaths occurring in 2000. The causes of death were documented using a standardized questionnaire. Results. – In French Guyana and the French West Indies the five referent wards reported 81 deaths. The main underlying causes of death were AIDS-related (67%), non-AIDS and non-hepatitis related cancer (9%), cardiovascular disease (7%), bacterial infections (5%), and end stage liver disease (4%). Among AIDS-related deaths, the more frequent diseases were histoplasmosis and toxoplasmosis in Guyana and atypical mycobacterial infection, tuberculosis, and cytomegalovirus disease in the West Indies. Median age was 43 years, transmission of HIV infection was heterosexual in 79%; 56% lived in poor socio-economic conditions, and 30% were born abroad. One out of five had been recently diagnosed with HIV infection and one out of three had never received antiretroviral treatment. Conclusion. – In 2000, two in three death cases in HIV-infected adults were AIDS-related in French Guyana and the French West Indies. Improved strategies for screening HIV infection before the occurrence of AIDS are still needed taking into consideration poor socio-economic and migrant conditions.

Immune deficiency and risk for malignancy among persons with AIDS.

People with AIDS have an elevated risk for cancer. We studied the relationship between cancer risk and AIDS-related immunosuppression as measured by CD4 count at AIDS onset. We linked records from AIDS and cancer registries in 11 US regions (1990-1996). We studied 82,217 (86.6%) adults who had a CD4 count measured at AIDS onset and survived into the follow-up period. We calculated standardized incidence ratios (SIRs) for AIDS-defining (Kaposi sarcoma [KS], non-Hodgkin lymphoma [NHL] and cervical cancer) as well as non-AIDS-defining cancers in the 2 years after AIDS onset. For each cancer, the change in SIRs across CD4 counts (0-49 cells/mm3, 50-99 cells/mm3, 100-199 cells/mm3, and > or =200 cells/mm3) was modeled using Poisson regression. The SIRs for KS, NHL, and cervical cancer were 258, 78, and 8.8, respectively. For each fall of 100 CD4 cells/mm3, RRs were 1.36 (95% CI: 1.29-1.43) for KS and 1.48 (95% CI: 1.37-1.59) for NHL. Among NHL subtypes, the association with lower CD4 counts was strongest for immunoblastic lymphoma (RR =1.64, 95% CI: 1.37-1.96, per decline of 100 CD4 cells/mm3) and central nervous system lymphoma (RR = 2.29, 95% CI: 1.95-2.69). The SIR for cervical cancer did not vary with CD4 count (p =.74). For non-AIDS-defining cancers (overall SIR = 2.1), neither the combined risk nor the risk of specific types was associated with declining CD4 counts. SKS and NHL risk increased with level of immunosuppression at AIDS onset. Risks for other cancers, including cervical cancer, were unrelated to CD4 counts. Elevated risks for non-AIDS cancers may be a result of lifestyle factors.

NON–AIDS-DEFINING CANCERS

As the AIDS epidemic advances, the spectrum of malignancies encountered is expanding. Several non-AIDS-defining cancers are seen in increased incidence in HIV-infected patients. These include basal cell carcinoma of the skin, squamous cell carcinoma of the anus, Hodgkin's disease, seminoma, and pediatric leiomyosarcoma. There appears to be an emerging role for various concurrent viral infections in the HIV-infected host that are likely implicated in the pathogenesis of AIDS-related neoplasms. It will be important to track the epidemiologic and biologic features of non-AIDS cancers in HIV-infected patients. It is likely that further clues about malignant transformation and oncogenesis unraveled in this setting will have broader clinical implications.