Effect of immunodeficiency, HIV viral load, and antiretroviral therapy on the risk of individual malignancies (FHDH-ANRS CO4): a prospective cohort study

Summary

Background

The relative roles of immunodeficiency, HIV viral load, and combination antiretroviral therapy (cART) in the onset of individual cancers have rarely been examined. We examined the effect of these factors on the risk of specific cancers in patients infected with HIV-1.

Methods

We investigated the incidence of both AIDS-defining cancers (Kaposi's sarcoma, non-Hodgkin lymphoma, and cervical cancer) and non-AIDS-defining cancers (Hodgkin's lymphoma, lung cancer, liver cancer, and anal cancer) in 52 278 patients followed up in the French Hospital Database on HIV cohort during 1998–2006 (median follow-up 4·9 years, IQR 2·1–7·9; 255 353 person-years). We tested 78 models with different classifications of immunodeficiency, viral load, and cART with Poisson regression.

Findings

Current CD4 cell count was the most predictive risk factor for all malignancies apart from anal cancer. Compared with patients with CD4 count greater than 500 cells per μL, rate ratios (RR) ranged from 1·9 (95% CI 1·3–2·7) for CD4 counts 350–499 cells per μL to 25·2 (17·1–37·0) for counts less than 50 cells per μL for Kaposi's sarcoma (p<0·0001), from 1·3 (0·9–2·0) to 14·8 (9·7–22·6) for non-Hodgkin lymphoma (p<0·0001), from 1·2 (0·7–2·2) to 5·4 (2·4–12·1) for Hodgkin's lymphoma (p<0·0001), from 2·2 (1·3–3·6) to 8·5 (4·3–16·7) for lung cancer (p<0·0001), and from 2·0 (0·9–4·5) to 7·6 (2·7–20·8) for liver cancer (p<0·0001). For cervical cancer, we noted a strong effect of current CD4 (RR 0·7 per log₂, 95% CI 0·6–0·8; p=0·0002). The risk of Kaposi's sarcoma and non-Hodgkin lymphoma increased for current plasma HIV RNA greater than 100 000 copies per mL compared with patients with controlled viral load (RR 3·1, 95% CI 2·3–4·2, p<0·0001; and 2·9, 2·1–3·9, p<0·0001, respectively), whereas cART was independently associated with a decreased incidence (0·3, 0·2–0·4, p<0·0001; and 0·8, 0·6–1·0, p=0·07, respectively). The RR of cervical cancer for those receiving cART was 0·5 (0·3–0·9; p=0·03). The risk of anal cancer increased with the time during which the CD4 count was less than 200 cells per μL (1·3 per year, 1·2–1·5; p=0·0001), and viral load was greater than 100 000 copies per mL (1·2 per year, 1·1–1·4, p=0·005).

Interpretation

cART would be most beneficial if it restores or maintains CD4 count above 500 cells per μL, thereby indicating an earlier diagnosis of HIV infection and an earlier treatment initiation. Cancer-specific screening programmes need to be assessed in patients with HIV.

Funding

Agence Nationale de Recherches sur le SIDA et les hépatites (ANRS), INSERM, and the French Ministry of Health.

Introduction

HIV infection is associated with an increased risk of several cancers.1, 2, 3 Since the introduction of combination antiretroviral therapy (cART) in 1996, the incidence of AIDS-defining cancers has decreased, whereas the relative frequency of non-AIDS-defining cancers has risen.4, 5, 6 Patients with HIV have a higher risk of both AIDS-defining and non-AIDS-defining cancers than does the general population.4, 5, 7, 8 HIV-infected patients and immunosuppressed organ-transplant recipients have an increased risk of developing malignancies associated with Epstein–Barr virus, human herpesvirus 8, hepatitis B and C viruses (HBV and HCV), and human papillomavirus (HPV), and both populations have a heightened risk of lung cancer.⁹ Although immune deficiency is an obvious feature shared by these two populations, the effect of HIV infection itself and antiretroviral therapy on the risk of specific cancers is controversial.2, 3 We examined the incidence rates of seven specific cancers in HIV-infected patients according to the extent of immunodeficiency, viral load, and antiretroviral treatment.