Interleukine-2 therapy does not increase the risk of Hodgkin or non-Hodgkin lymphoma in HIV-infected patients: results from FHDH ANRS CO4.

BACKGROUND: Concerns have been raised about a possible excess risk of lymphomas in HIV-infected patients exposed to interleukin 2 (IL-2) therapy. Here we compared the risks of non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) in IL-2-treated and IL-2-untreated HIV-infected patients. METHODS: Patients monitored through the French Hospital Database on HIV between May 1, 1995, and December 31, 2005, were enrolled in this study. Lymphomas that occurred between the day after study entry and the end of follow-up were eligible for analysis. Poisson regression models were used in 2 separate analyses to quantify the possible relationship between IL-2 therapy and the incidence of NHL and HL. RESULTS: The IL-2-treated group consisted of 861 patients and the IL-2-untreated group of 77,605 patients. Follow-up lasted a total of 3643 and 382,720 person-years, respectively. After adjustment for sex and time-updated age, period, the CD4 cell counts, the plasma HIV RNA levels, and AIDS status, the relative rates of NHL and HL associated with IL-2 therapy were 0.64 (95% confidence interval, 0.25 to 1.65) and 0.33 (95% confidence interval, 0.04 to 2.86), respectively. CONCLUSIONS: In this large observational study, IL-2 therapy did not increase the risk of lymphoma, either NHL or HL, in HIV-infected patients.

Evolution of genetic diversity and drug resistance mutations in HIV-1 among untreated patients from Mali between 2005 and 2006.

OBJECTIVES: To describe HIV-1 variants circulating in Mali and to estimate the rate of transmission of HIV-1 drug resistance in 2006. PATIENTS AND METHODS: Viral reverse transcriptase (RT) and protease (PR) genes from 198 antiretroviral (ARV)-naive patients diagnosed HIV-1 positive in May 2006 in Bamako and Segou were sequenced. RESULTS: Although CRF02_AG was always the predominant HIV-1 subtype observed (72%), a higher genetic diversity than that in 2005 was observed. The overall prevalence of primary resistance is 11.5% in Mali in 2006, according to the 2007 IAS-USA list of mutations [nucleoside RT inhibitor (NRTI): 1.5%, non-NRTI (NNRTI): 9% and PI: 1%], and 2.5% (NRTI: 1%, NNRTI: 1.5% and PI: 0%), according to the Stanford list of mutations. There was no significant difference between 2005 and 2006 in the overall primary resistance prevalence or in the prevalence of mutations in the different ARV classes. Resistance mutations found in RT and PR genes are in agreement with the highly active antiretroviral therapy regimen available in Mali, except for V90I, V106I and A98G mutations which are associated with etravirine resistance, but polymorphic in non-B subtypes. CONCLUSIONS: HIV-1 genetic diversity seems increased in Mali, but the overall HIV-1 primary resistance prevalence remains low. This is consistent with the findings from other West African countries where prevalence rates are lower than 5%. However, considering the large scaling up of ARV use in this country, it is necessary to regularly monitor the development of primary resistance in Mali.

HIV drug resistance after the use of generic fixed-dose combination stavudine/lamivudine/nevirapine as standard first-line regimen.

Early failures to stavudine/lamivudine/nevirapine used as a generic fixed-dose combination in Mali showed resistance mutations in 50% of cases (mostly M184V and Y181C). No thymidine analogue mutations were seen, suggesting that most nucleoside reverse transcriptase inhibitors could be used in a second-line regimen. This highlights the importance of the accessibility of HIV-RNA assays for monitoring treated patients in resource-poor countries to detect early virological failure in order to preserve future therapeutic options.

Role of long-term nucleoside-analogue therapy in lipodystrophy and metabolic disorders in human immunodeficiency virus-infected patients.

The role of nucleoside analogues (NAs) in lipodystrophy (LD) syndrome in human immunodeficiency virus (HIV)-infected patients remains controversial. We studied the prevalence of LD in previously untreated patients randomized to receive different NA combinations (in the ALBI-ANRS 070 trial) for 6 months. At month 30 of follow-up, 37 (31%) of 120 patients had >/=1 morphologic change, and 21 (57%) of 37 had isolated peripheral lipoatrophy; corresponding values for the patients who received only NAs throughout follow-up were 20 (30%) of 66 and 14 (67%) of 21, respectively. In multivariate analysis, factors associated with presence of LD at month 30 were initial assignment to the group receiving stavudine and didanosine (odds ratio [OR], 6.7; P=.02), age (OR for being 10 years older, 3.6; P=.002), and HIV RNA level at month 30 (OR, 0.4; P=.007). No difference was observed in cholesterol and glucose levels as a function of any pattern of antiretroviral exposure. Exposure to stavudine and didanosine was associated with LD syndrome (predominantly lipoatrophy).

Phylogenetic analyses confirm the high prevalence of hepatitis C virus (HCV) type 4 in the Seine-Saint-Denis district (France) and indicate seven different HCV-4 subtypes linked to two different epidemiological patterns.

Hepatitis C virus (HCV) has been classified into six clades as a result of high genetic variability. In the Seine-Saint-Denis district of north-east Paris, the prevalence of HCV-4, which usually infects populations from Africa or the Middle East, is twice as high as that recorded for the whole of continental France (10.2 versus 4.5%). Although the pathogenicity of HCV-4 remains unknown, resistance of HCV-4 to therapy appears to be similar to that observed for HCV-1. In order to characterize the epidemiology of HCV-4 in Paris, sequences of the non-structural 5B gene (332 bp) were obtained from 38 HCV-4-infected patients. Extensive phylogenetic analyses indicated seven different HCV-4 subtypes. Moreover, phylogenetic tree topologies clearly distinguished two epidemiological profiles. The first profile (52.6% of patients) reflects the intra-suburban emergence of two distinct HCV-4 subclades occurring mainly among intravenous drug users (65% of patients). The second profile shows six subclades [HCV-4a, -4f, -4h, -4k, -4a(B) and a new sequence] and accounts for patients from Africa (Egypt and sub-Saharan countries) who have unknown risk factors (77.8% of patients) and in whom no recent diffusion of HCV-4 is evident. This study indicates the high diversity of HCV-4 and the extension of HCV-4a and -4d subclades among drug users in FRANCE: