Characteristics of non-Hodgkin Lymphoma Arising in HIV-infected Patients with Suppressed HIV Replication

Laurence Gérard; Véronique Meignin; Lionel Galicier; Claire Fieschi; Nicolas Leturque; Christophe Piketty; Laurent Fonquernie; Felix Agbalika; Eric Oksenhendler

Disclosures

AIDS. 2009;23(17):2301-2308. 

In This Article

Abstract and Introduction

Abstract

Objective: Despite effective treatment of HIV infection, some patients still develop non-Hodgkin lymphoma (NHL). We analysed patients with HIV-associated NHL and undetectable plasma HIV-RNA, according to the duration of HIV suppression.
Methods: Out of 388 patients included in a prospective cohort of HIV-associated NHL from 1996 to 2008, 128 (33%) had a plasma HIV-RNA below 500 copies/ml and were included in the study. Patients with long-term HIV suppression (>18 months) were compared with patients with recent HIV suppression (≤18 months).
Results: All patients but three were treated with combination antiretroviral therapy, with a median duration of 2.2 years. The median duration of HIV suppression was 10.1 months. Most cases (65%) occurred within 18 months following HIV suppression. In the more than 18 months group, patients developed NHL at a higher CD4 cell count than patients with 18 months or less of HIV suppression (359 versus 270 cells/μl, P = 0.02). None of the NHL characteristics were different between the two groups. Outcome was similar in the two groups (complete remission, 64 versus 72.5%; P = 0.35 and 3-year survival, 46 versus 56%; P = 0.08). In addition, 52% of the tumours were Epstein-Barr virus or human herpesvirus 8 associated, without any difference in the proportion of virus-associated tumours according to the duration of HIV suppression.
Conclusion: In patients with undetectable HIV-RNA, NHL occurred mainly within the first 18 months following HIV suppression. In patients developing NHL after long-term HIV suppression, the level of CD4 cell count was higher, but the association with Epstein-Barr virus or human herpesvirus 8 and the prognosis were similar to that observed in patients with recent HIV suppression.

Introduction

Since the introduction of effective combination antiretroviral therapy (cART), HIV-associated morbidity and mortality rates have dramatically fallen.[1–3] The incidence of HIV-associated non-Hodgkin lymphoma (HIV-NHL) has also decreased significantly, with the most dramatic decline observed in primary central nervous system lymphoma (PCNSL).[4–6] However, this decline is less marked than in other HIV-associated complications after initiation of cART.[4,7,8] In HIV-infected patients, the relative risk for developing NHL remains around 13–20 in population-based studies, even in the late cART era.[6,8,9] In Western Europe, the proportion of AIDS-defining illness attributable to NHL has increased since the widespread use of cART from less than 4% in 1994 to almost 16% in 1998.[10] Although cART had a marked favourable impact on outcome,[5,11–14] with complete remission rates close to that observed in patients with aggressive NHL in the general population, NHL remains a major cause of death in HIV-infected patients.[15,16]

Characteristics of HIV-NHL have been extensively described in the pre-cART era. The clinical presentation is more aggressive, with a different spectrum of lymphoma pathological subtypes than in the general population. Up to 30% of HIV-NHL are considered to be Burkitt lymphoma, which is a rare B-cell proliferation in HIV-negative adults outside of endemic areas.[13,14,17–19] The association with some herpes viruses such as Epstein–Barr virus (EBV), detected in 25% of the Burkitt subtype and in 60–80% of the immunoblastic subtype of diffuse large B-cell lymphoma (IBL-DLBCL), and human herpesvirus 8 (HHV-8), detected in rare lymphoproliferative diseases, is mainly observed in the HIV setting.[13,18,20–24] Controversial data have been published on a possible change of HIV-NHL spectrum in the cART era.[4,5,12,14,25]

Apart from CD4 cell count deficiency, recent studies[4,26,27] have demonstrated that incomplete viral suppression during cART was a strong, independent risk factor for the development of HIV-NHL. In France, about 80% of patients receiving cART have an undetectable plasma HIV-RNA (French Hospital Database on HIV, http://www.ccde.fr). However, despite effective ART and subsequent complete suppression of HIV replication, some patients still develop NHL. One could expect that, in patients successfully treated for HIV infection, the duration of the virological control could influence the clinical features and the pathological distribution of lymphomas arising in these patients, with a trend to move closer to those observed in the general population. The objective of this study was to determine, in a population of patients diagnosed with NHL while plasma HIV-RNA is undetectable, whether the characteristics of lymphoma vary with the duration of HIV suppression, and particularly, whether the association with EBV or HHV-8 decreases over time.

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