Non-AIDS defining cancers in the D:A:D Study--time trends and predictors of survival: a cohort study

Signe W Worm, Mark Bower, Peter Reiss, Fabrice Bonnet, Matthew Law, Gerd Fätkenheuer, Antonella d'Arminio Monforte, Donald I Abrams, Andrew Grulich, Eric Fontas, Ole Kirk, Hansjakob Furrer, Stephane De Wit, Andrew Phillips, Jens D Lundgren, Caroline A Sabin, D:A:D Study Group

Abstract

Background: Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004-2010, and described subsequent mortality and predictors of these.

Methods: Individuals were followed from 1st January 2004/enrolment in study, until the earliest of a new NADC, 1st February 2010, death or six months after the patient's last visit. Incidence rates were estimated for each year of follow-up, overall and stratified by gender, age and mode of HIV acquisition. Cumulative risk of mortality following NADC diagnosis was summarised using Kaplan-Meier methods, with follow-up for these analyses from the date of NADC diagnosis until the patient's death, 1st February 2010 or 6 months after the patient's last visit. Factors associated with mortality following NADC diagnosis were identified using multivariable Cox proportional hazards regression.

Results: Over 176,775 person-years (PY), 880 (2.1%) patients developed a new NADC (incidence: 4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal cancer and Hodgkin's lymphoma were broadly consistent. Kaplan-Meier cumulative mortality estimates at 1, 3 and 5 years after NADC diagnosis were 28.2% [95% CI 25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant predictors of poorer survival after diagnosis of NADC were lung cancer (compared to other cancer types), male gender, non-white ethnicity, and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis were associated with improved survival. The incidence of NADC remained stable over the period 2004-2010 in this large observational cohort.

Conclusions: The prognosis after diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but has improved somewhat over time. Modifiable risk factors, such as smoking and low CD4 counts, were associated with mortality following a diagnosis of NADC.

Figures

Figure 1
Figure 1
Crude incidence rate (/1000 PY) of NADC, with 95% confidence intervals, stratified by calendar year. a) any NADC (880 events), b) lung cancer (140 events), c) anal cancer (79 events), d) Hodgkin’s lymphoma (112).
Figure 2
Figure 2
Cumulative mortality following diagnosis of NADC, stratified by type of NADC.

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