We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log 10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV—CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences—is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence.

Combined antiretroviral treatment in some human immunodeficiency virus-infected persons does not lead to a rapid increase in CD4 cell counts, and these patients may remain susceptible to opportunistic infections. A group of 13 patients with CD4 cell counts <200 cells/mm3 after > or =9 months of combined antiretroviral treatment received interleukin (IL)-2 immunotherapy (4.5x106 IU twice daily for 5 days every 6 weeks). After only 3 cycles, their CD4 cell counts increased from 123 cells/mm3 (range, 104-134 cells/mm3) to 229 cells/mm3 (range, 176-244 cells/mm3). A marked increase was noted in the naive CD45RA subpopulation of CD4 T lymphocytes. Furthermore, the magnitude of the CD4 cell count response correlated with the baseline expression levels of the antiapoptotic molecule Bcl-2. This study demonstrates that IL-2 immunotherapy can accelerate the recovery of CD4 lymphocytes in persons whose CD4 cell counts fail to increase rapidly in response to combined antiretroviral treatment.

Our study characterizes the defective maintenance of peripheral CD4 T lymphocytes in CD4-LR patients, probably resulting from Bcl-2 underexpression and dysregulation of the IL-2R system.

Patient QoL improved significantly over a 24-month period of treatment with a raltegravir-containing regimen. FIS and HSI are sensitive tools to measure the impact of new antiretroviral combinations on a patient's perception of QoL.

The French RACING cohort study is a 24-month, observational, longitudinal, prospective, multicenter study on HIV-1 infected patients being treated with an antiretroviral combination therapy containing raltegravir. The objectives of this study are to describe the viro-immunological course, characterize and document adverse events (AEs), describe patient adherence at M6 (month 6) and examine clinical-biological data for patients undergoing ARV therapy including raltegravir at M12 (month 12). Demographic, viro-immunological, safety and clinical-biological data were collected at M6 and M12 and self-reported patient adherence to treatment regimen at M6. Data from 478 of 482 patients were available at M12. The median age was 45.9 years (IQR: 40.0–52.2), 64.1% were male and the median duration of infection was 13.2 years (IQR: 5.5–21). At the baseline, 64.1% of patients had a cardiovascular risk factor or a history of cardiovascular events and 65.2% had received concomitant treatment (psychotropic drugs: 33.5%, lipid-lowering drugs: 30% and antihypertensive agents: 24.8%). The virological response, viral load and CD4 cell count are shown in Table 1 (based on data available at M6 and M12). Of the 134 reported and treatment-related AEs, the symptoms most frequently described (>5%) were myalgia (6.7%) and nausea (5.2%). A total of 34 serious adverse events were reported, of which 5 were possibly or probably related to raltegravir. Self-reported patient adherence at M6 is described as follows: ‘high’ for 56% of patients, ‘average’ for 36% of patients and ‘low’ for 8% of patients (205 questionnaires). To conclude, in a real-life setting concerning patients with a strong proportion of co-morbidity and variation in adherence, the efficacy and safety data observed after 12 months are comparable to the data observed (not shown) in clinical studies