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

Results

Description of the Population

Out of the 638 patients with HIV-NHL included in the HIV lymphoproliferative cohort, 388 were enrolled in the cART era (July 1996–September 2008) and 128 (33%) had plasma HIV-RNA below 500 copies/ml at diagnosis of NHL. The patients were followed for a mean period of 32.3 months, with a lost of follow-up rate of 4.7%. The number of cases diagnosed dramatically decreased over time of HIV suppression. For 83 patients (65%), NHL developed within the first 18 months after HIV suppression (Fig. 1).

Figure 1.

Distribution of the numbers of non-Hodgkin lymphoma diagnoses according to the duration of HIV suppression (a) and the duration of combination antiretroviral therapy (b). cART, combination antiretroviral therapy.

The baseline characteristics of the 128 study patients are provided in Table 1. The majority of patients were men (87.5%), with a median age of 43 years. At NHL diagnosis, the median CD4 cell count was 297 cells/μl, and the nadir CD4 cell count 112 cells/μl. All but three patients were treated with cART before NHL diagnosis for a median duration of 26.2 months. Regimens included a protease inhibitor in 89 patients, a nonnucleosidic reverse transcriptase inhibitor in 24 patients, and both types of drugs in eight patients. Furthermore, four patients received enfuvirtide or raltegravir. Of the three individuals who developed NHL while not on cART, two received dual ART and one had spontaneous control of HIV replication. The median duration of effective HIV suppression was 10.1 months (IQR 4–27.5 months).

Lymphoma was of the non-IBL-DLBCL type in 46 cases (36%) and Burkitt lymphoma type in 31 cases (24%). More than half of the patients (55%) presented with unfavourable prognostic factor, defined by IPI 3 or 4. Complete remission was achieved in 69% of patients. At follow-up visit, after the end of chemotherapy, the CD4 cell count was 185 cells/μl, and 67% of patients had persistent undetectable plasma HIV-RNA. There were 65 deaths during the follow-up period: 42 (65%) were NHL related, 15 (23%) were treatment related, one was AIDS related, and seven (11%) were from other causes. The median overall survival (OS) was 41.7 months, with a 3-year OS of 52.4% [95% confidence interval (CI) 42.8–61.2].

Analysis was extended to compare these features with those of the 260 patients with NHL and incomplete HIV suppression (plasma HIV-RNA >500 copies/ml) enrolled in the HIV lymphoproliferative cohort during the same period. Patients with suppression of HIV replication were slightly older, had a higher CD4 cell count (297 versus 155 cells/μl, P < 10−4), and were more often treated with cART than patients without suppression of HIV replication. All the NHL characteristics were similar between the two groups.

Comparisons of Patients According to the Duration of HIV Suppression

Characteristics of the patients with long-term HIV suppression, defined as duration of HIV suppression above 18 months were compared with those of patients with recent HIV suppression, defined as a duration of HIV suppression lower than 18 months (Table 1). Date of first undetectable HIV viral load was unknown for three patients, and they could not be included in the following analysis. In the above 18-month group, patients were more frequently women and were older than in the lower than 18-month group. The differences in HIV characteristics were a longer duration of HIV infection, a longer duration of cART, and a higher CD4 cell count at diagnosis of NHL in the above 18-month group. The distribution of the CD4 cell count by year of HIV suppression is presented in Fig. 2, showing that the most striking feature was a rapid decrease in numbers and proportions of patients with a CD4 cell count below 200 cells/μl. Proportion of patients with a CD4 cell count above 350 cells/μl was not different between the lower than 18-month and the above 18-month groups (38.5 versus 50%, P = 0.22). The other HIV characteristics, including the nadir CD4 cell count (P = 0.71), and classes of antiretroviral regimens received at NHL diagnosis (data not shown) were not significantly different between the two groups.

Figure 2.

Numbers of non-Hodgkin lymphoma diagnoses by strata of CD4 cell count and by year of HIV suppression in 128 patients with non-Hodgkin lymphoma and HIV suppression. CD4 cell count was stratified in three groups: ≤200, 201–350, and >350 cells/μl.

None of the NHL characteristics, including clinical and pathological features, staging, performance status, lacticodehydrogenase (LDH) level, 'B' symptoms, IPI, and therapy regimens used, differed significantly between the two groups (Table 1). A higher CD4 cell count was observed in the above 18-month group for the two main histological groups (377 versus 131 cells/μl for non-IBL-DLBCL and 357 versus 281 cells/μl for Burkitt lymphoma). Response to chemotherapy and relapse rate was not different between the two groups (64% in the over 18-month group versus 72.5% in the less than 18-month group, P = 0.35; and 36% in the over 18-month group versus 21% in the less than 18-month group, P = 0.14). The 3-year OS for the over 18-month group was 46% (95% CI 28.4–61.3%) compared with 56% (95% CI 44.4–66.7%) for the less than 18-month group (log-rank, P = 0.08).

Virus-associated Lymphomas

Virus association could be assessed for EBV in 115 tumours (90%) and for HHV-8 in 105 tumours (82%). Fifty-seven patients (52%) presented with a virus-associated tumour. Of these cases, 33 expressed EBV alone, 15 expressed HHV-8 alone, and nine expressed both EBV and HHV-8 (Table 2). Among virus-associated tumours, 22 were DLBCL (39%) and 19 were PEL (33%). Of the 24 HHV-8-associated tumours, 19 were PEL and five large B-cell lymphomas arising in HHV-8-associated multicentric Castleman disease (MCD) (LBCL arising in HHV-8 MCD). All other HIV-related and NHL-related characteristics were not different between the two groups, even though there was a slight trend for a lower nadir CD4 cell count in the virus-associated group (Table 3). The proportion of virus (either EBV or HHV-8)-associated tumour was not associated with the duration of HIV suppression (Table 2). Kaposi sarcoma was more frequent in patients with virus-associated tumour than in patients with nonvirus-associated tumour (22 versus 7.5%, P = 0.02).

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