François Bricaire

To evaluate the potential benefits of a tailored antiretroviral treatment interruption with duration based on the observed reversion of resistance mutations. In this open single-arm pilot study, 23 patients with multiple treatment failure interrupted therapy and underwent longitudinal genotypic resistance testing. Salvage gigatherapy was started when resistance mutations to at least two antiretroviral drug classes reverted. The primary endpoint was a fall in viral load by > 1 log10 copies/ml after 12 weeks of salvage therapy. Baseline median viral load was 5.14 log copies/ml and CD4 cell count 43 x 10 cells/l. Genotypic resistance testing showed a median of six, two and nine resistance mutations to nucleoside analogue reverse transcriptase inhibitors, non-nucleoside analogue reverse transcriptase inhibitors and protease inhibitors, respectively; viral strains were susceptible to no more than one drug in 17/23 patients. The median duration of treatment interruption was 24 weeks (range, 12-37), leading to median changes from baseline of + 0.54 log10 copies/ml and -30 x 10(6) cells/l. At the end of treatment interruption, plasma HIV was susceptible to at least three drugs in 16/23 patients. After 12 weeks of salvage multitherapy, only one patient had a decrease in viral load > 1 log copies/ml. All baseline resistance mutations recurred after treatment resumption. AIDS-defining events occurred in two-thirds of patients during the study period. In HIV-infected patients with multiple failures and no therapeutic options at baseline, significant reversion of resistance mutations after prolonged treatment interruption failed to restore antiviral efficacy of a salvage regimen and was clinically deleterious.

Disseminated toxoplasmosis during acute infections has rarely been observed in immunocompetent patients. We report a case of severe acute disseminated toxoplasmosis acquired by an immunocompetent patient in French Guiana and review the literature.

The natural history of hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected patients has never been studied according to the concept of liver fibrosis progression. The aim of this work was to assess the fibrosis progression rate in HIV-HCV coinfected patients and in patients infected by HCV only. A cohort of 122 HIV-HCV coinfected patients was compared with a control group of 122 HIV-negative HCV-infected patients. Groups were matched according to age, sex, daily alcohol consumption, age at HCV infection, and duration and route of HCV infection. The fibrosis progression rate was defined as the ratio between fibrosis stage (METAVIR scoring system) and the HCV duration. The prevalence of extensive liver fibrosis (METAVIR fibrosis scores 2, 3, and 4) and moderate or severe activity were higher in HIV-infected patients (60% and 54%, respectively) than in control patients (47% and 30%, respectively; P <.05 and P <.001, respectively). The median fibrosis progression rate in coinfected patients and in control patients was 0.153 (95% confidence interval [CI], 0.117-0.181) and 0.106 (95% CI, 0.084-0.125) fibrosis units per year, respectively (P <.0001). HIV seropositivity (P <.0001), alcohol consumption (>50 g/d, P =.0002), age at HCV infection (<25 years old, P <.0001), and severe immunosuppression (CD4 count </=200 cells/microL, P <.0001) were associated with an increase in the fibrosis progression rate. In coinfected patients, alcohol consumption (>50 g/d), CD4 count (</=200 cells/microL), and age at HCV infection (<25 years old) (P <. 0001, respectively) were associated with a higher fibrosis progression rate. HIV seropositivity accelerates HCV-related liver fibrosis progression. In coinfected patients, a low CD4 count, alcohol consumption rate, and age at HCV infection are associated with a higher liver fibrosis progression rate.

The effects of a 10-year control of HIV replication without viral blips with antiretroviral therapy were examined in progressors. CD4 cell counts did not plateau but showed a continuous increase until the 10th year. Ultrasensitive techniques showed very low plasma HIV RNA and cell-associated DNA levels. Robust memory T cell responses to HIV-p24 were higher than in 3-year treated patients and comparable to those of Elite controllers, whereas interferon-gamma-producing HIV-specific T cells were infrequent. Long-term and efficient antiretroviral therapy provides continuous benefits both on the immune system and on the HIV reservoirs.

In France, young adults are legally freed from parental authority at the age of 18 years and are, thus, responsible for their own vaccine record. This young adult population is more frequently exposed to vaccine-preventable infectious diseases. To determine the factors associated with students' knowledge of the interval between two antitetanus boosters and their report of having up-to-date vaccinations. In April 2009, a survey was conducted involving a random sample of students between 18 and 25 years of age eating lunch at university dining facilities in Paris and its suburbs (Ile de France). Among the 677 students approached, 583 agreed to participate. Only 207 (36%) of respondents knew the recommended dosing interval between two doses of tetanus vaccine booster (10 years). The majority of students (69%) reported having up-to-date vaccinations. Declaring having up-to-date vaccinations was significantly associated with having a general practitioner (OR 3.03 [95% CI 1.69 to 5.55...

Patients with severe malaria treated with artesunate sometimes experience a delayed hemolytic episode. Artesunate (AS) induces pitting, a splenic process whereby dead parasites are expelled from their host erythrocytes. These once-infected erythrocytes then return to the circulation. We analyzed hematologic parameters in 123 travelers treated with AS for severe malaria. Among 60 nontransfused patients observed for more than 8 days, 13 (22%) had delayed hemolysis. The peak concentration of circulating once-infected erythrocytes was measured during the first week in 21 patients and was significantly higher in 9 patients with delayed hemolysis than in 12 with other patterns of anemia (0.30 vs 0.07; P = .0001). The threshold of 180 million once-infected erythrocytes per liter discriminated patients with delayed hemolysis with 89% sensitivity and 83% specificity. Once-infected erythrocyte morphology analyzed by using ImageStream in 4 patients showed an 8.9% reduction in their projected a...

Although the risk of smallpox virus being used as a terrorist weapon is very low, it is mandatory to examine potential vaccination strategies, and also the residual immunization rate in the general population. During revaccination of a national intervention team, the residual immunity of 184 volunteers was determined by assaying T memory cells in the gamma interferon ELISpot test, and central T memory cell responses in a proliferation assay. Three-quarters of the subjects had a proliferative response. This response was lower after the age of 55 years but could be reactivated by revaccination.

Emerging and re-emerging infectious diseases have again entered the public arena in recent years. This is due to factors such as evolving lifestyles, ecological and socio-political upheavals, and recent diagnostic advances. Numerous pathogens, including viruses like West Nile, Chikungunya and Japanese encephalitis on the one hand, and hemorrhagic fever viruses like Ebola and Maburg, are particular concerns. Recently, the Corona virus responsible for SARS, which caused an epidemic sufficiently worrisome to challenge crisis management concepts, was successfully isolated. It is in this context that so-called "bird flu'", may be on the verge of causing a human pandemic. Pox and Monkeypox are "virtually emerging" viruses that have potential for use in bioterrorism. The management and treatment of these emerging infectious diseases calls for new approaches, organizations and infrastructures.

The relationship between dementia and human immunodeficiency virus type 1 (HIV-1) cerebral load is not clearly understood. We used immunohistochemistry and competitive polymerase chain reaction to evaluate the density ofgp 41 immunostained cells and the amount of HIV-1 DNA and RNA in the midfrontal gyrus of 21 HIV-1 infected patients, nine of whom were demented. The amounts of HIV-1 DNA and RNA, and the density of gp 41-positive cells were significantly linked. In this small series of cases, (1) although as a mean, there was a larger viral load in demented patients than in nondemented, this did not reach the significance level (2) discrepancies appeared in the population under study, some demented patients having low viral loads.

The pathogenesis of HIV-associated cognitive changes is poorly understood. Cytokines such as tumor necrosis factor-α (TNF-α) have been postulated to contribute to the mechanism of the neurological complications of HIV infection. One of the effects of TNF-α is to induce astrocyte proliferation in vitro. The purpose of this study was to look for a correlation between the expression of TNF-α,

We prospectively evaluated the level of human immunodeficiency virus (HIV) type 1 RNA in cerebrospinal fluid (CSF) as a marker of HIV encephalitis. Fifty-two HIV-1-infected patients (41 males and 11 females; mean age, 39 years) were tested for the presence of HIV-1 RNA in plasma and CSF. Samples of CSF were obtained by lumbar puncture to evaluate cognitive deficits, seizures, or fever among these patients. HIV encephalitis was diagnosed in 11 patients (21%), other CNS diseases were diagnosed in 12 (23%), and fever without CNS disease was diagnosed in 29 (56%). HIV-1 RNA was detectable in 92% of the plasma specimens and 75% of the CSF specimens. No significant difference was observed in CSF levels of HIV-1 RNA between patients with or without HIV encephalitis. CSF levels of HIV-1 RNA correlated with plasma levels of HIV-1 RNA (Spearman's rank correlation, +0.31; P = .02) and CSF white blood cell counts (Spearman's rank correlation, +0.4; P < .01). The absence of any significant difference between patients with or without HIV encephalitis suggests that the CSF HIV-1 RNA level is not a good marker for the diagnosis of HIV encephalitis.