No abstract

One likely mechanism of virological failure is poor antiretroviral drug diffusion in sites of viral replication such as the genital tract. We measured antiretroviral drug concentrations in blood and semen in 13 HIV-infected men failing treatment. Enfuvirtide did not cross the blood-testis barrier, whereas tenofovir accumulated in semen. Unlike indinavir, semen concentrations of lopinavir, amprenavir, saquinavir and efavirenz were ineffective. These are worrying findings, because suboptimal semen drug concentrations may enhance the risk of sexually transmitted drug-resistant HIV variants.

A human trial was carried out to assess the ileal and fecal survival of Lactobacillus casei DN-114 001 ingested in fermented milk. Survival rates were up to 51.2% in the ileum and 28.4% in the feces. The probiotic bacterium has the capacity to survive during its transit through the human gut.

The aim of this study was to evaluate the survival of Lactobacillus rhamnosus R11 and Lactobacillus acidophilus R52 in the human digestive tract and their effects on the microbiota homeostasis. We designed an open human trial including 14 healthy volunteers. A 3-week exclusion period of fermented products was followed by a 12-day consumption period of 4 capsules daily containing 2 × 10⁹L. rhamnosus R11 and 1 × 10⁸L. acidophilus R52, and a 12-day wash-out period. The 2 strains and dominant bacterial groups of the microbiota were quantified by real-time polymerase chain reaction. At the end of the capsule consumption period, high levels of L. rhamnosus R11 were detected in faecal samples from all volunteers, reaching a mean value of 7.1 log₁₀ colony-forming unit (CFU) equivalents/g of stool. L. acidophilus R52 was detected in the stools of only 1 volunteer, reaching a maximum level of 6.1 log₁₀ CFU equivalents/g of stool. Dilution plating enumerations performed in parallel provided less consistent and generally lower levels. No significant effect of capsule consumption was observed on microbiota homeostasis for the dominant faecal populations. Mean values of 8.8, 9.2, 9.9 and 10.6 log₁₀ CFU equivalents/g of stool were obtained for the Clostridium coccoides, Bifidobacterium sp., Bacteroides sp. and Clostridium leptum groups, respectively.

Lactobacillus casei DN-114 001 is a probiotic strain able to interact with the immune system and to interfere with gastrointestinal pathogens. The derived strain DN-114 001Rif was studied during its transit through the upper and distal intestine of human volunteers. Seven volunteers participated in the study, which involved intestinal intubation to sample ileal contents and collection of fecal samples, with a wash-out period of 8 days between the 2 steps. The retrieval of the probiotic was analyzed in the ileum every 2 h for 8 h following the ingestion of one dose of the test product and in the feces prior to, during, and after daily consumption of the test product for 8 days. Persistence of the probiotic amplifiable DNA was assessed using temporal temperature gradient gel electrophoresis and real-time PCR. Fluorescent in situ hybridization allowed analysis of the composition of the dominant digestive microbiota. The ingestion of L. casei DN-114 001Rif led to a significant and transient increase of its amplifiable DNA in ileal and fecal samples. This is related to a high stability in the composition of dominant groups of the gut microbiota. Data from ileal samples are scarce and our study confirms the potentiality for interaction between probiotics and the human immune system.

A retrospective study was conducted to assess changes in cerebrovascular lesions, as assessed by magnetic resonance (MR) imaging and angiography in 18 children with sickle cell disease (SCD) receiving optimised chronic transfusions for primary stroke prevention (abnormal transcranial Doppler flow, nine patients, median follow-up 14.3 months (range, 7.9-48.9)) or secondary stroke prevention (nine patients, median follow-up 59.6 months (range, 11.0-127.9)). An experienced neuroradiologist blinded to patient data reviewed the 41 MR scans (median/patient, three (2-4)). Standard scores were used to evaluate parenchymal and vascular abnormalities at baseline and last follow-up. Within-patient score changes evaluated using Wilcoxon's paired rank test indicated lesion progression in the secondary-prevention group (p = 0.027). Optimised transfusion therapy does not prevent progression of cerebral vasculopathy in SCD children with a history of stroke.

The survival of Bifidobacterium animalis strain DN-173 010 was assessed after its ingestion in a fermented product or in a lyophilised form. Twelve healthy subjects were included in a randomised, open study with 2 parallel groups. The composition and activities of the faecal microbiota were monitored before (10-day baseline step), during (1-week product administration step) and after (10-day follow-up step) the ingestion of 1 of the 2 products. A colony immunoblotting method, fluorescent in situ hybridisation with group-specific DNA probes, and temporal temperature gradient gel electrophoresis using group-specific primers were carried out to compare survival of B. animalis strain DN-173 010 after ingestion of the 2 products, together with analyses of enzyme activities and faecal metabolites. At the end of the supplementation step, the mean number of B. animalis DN-173 010 quantified by immunodetection in the faeces of 5 of 6 subjects in each treatment group was ≧10⁸ colony-forming units/g faeces. These numbers corresponded to an average survival of 22% for the lyophilised form and 20% for the fermented product. At the same step, the PCR temporal temperature gradient gel electrophoresis profiles showed a double band corresponding to the B. animalis DN-173 010 pattern for 11 subjects. No major modification was observed during the trial in either the dominant members of the faecal microbiota assessed by fluorescent in situ hybridisation or their activities. In conclusion, we show that the lyophilised form of B. animalis DN-173 010 survives transit and could represent a more convenient form to administer for long-term clinical trials.

No local viral production was evident in semen, despite the local absence of therapeutic antiretroviral drug concentrations in the five patients receiving lopinavir/ritonavir alone.