Interest of proviral HIV-1 DNA genotypic resistance testing in virologically suppressed patients candidate for maintenance therapy.

Switch of antiretroviral therapy in virologically suppressed HIV-infected patients is frequent, to prevent toxicities, for simplification or convenience reasons. Pretherapeutic genotypic resistance testing on RNA can be lacking in some patients, which could enhance the risk of virologic failure, if resistance-associated mutations of the new regimen are not taken into account. Proviral DNA resistance testing in 69 virologically suppressed patients on antiretroviral treatment with no history of virological failure were pair-wised compared with pre-ART plasma RNA resistance testing. The median time between plasma (RNA testing) and whole blood (proviral DNA testing) was 47 months (IQR 29-63). A stop codon was evidenced in 23% (16/69) of proviral DNA sequences; these strains were considered as defective, non-replicative, and not taken into consideration. Within the non defective strains, concordance rate between plasma RNA and non-defective proviral DNA was high both on protease (194/220 concordant resistance-associated mutations=88%) and reverse transcriptase (28/37 concordant resistance-associated mutations=76%) genes. This study supports that proviral DNA testing might be an informative tool before switching antiretrovirals in virologically suppressed patients with no history of virological failure, but the interpretation should be restricted to non-defective viruses.

Experimental human exposure to n-Hexane. Study of the respiratory uptake and elimination, and of n-Hexane concentrations in peripheral venous blood.

The respiratory uptake rate of n-hexane showed considerable differences in six healthy male persons, exposed at rest to 360 mg/m3 and 720 mg/m3 of n-hexane in inspired air and to 360 mg/m3 under different levels of physical exercise. These differences could partly be explained by a positive correlation with the amount of body fat. At rest also a strong influence of the respiratory minute volume and respiratory frequency on the uptake rate could be proven. The average uptake rate remained virtually constant over a range of 20 to 60 W of continuous external physical load, indicating that under these circumstances the inspired n-hexane concentration alone predominantly determines the uptake rate. The respiratory elimination during the first hours after an exposure was also subject to important inter- and intraindividual fluctuations. The pulmonary ventilation rate at the moment of breath sampling had a pronounced influence on the measured exhaled concentration. On the other hand, there was no apparent effect of the amount of body fat. Generally, the correlation between the amount of n-hexane taken up and breath concentrations at different time intervals was rather poor. n-Hexane concentrations in peripheral venous blood reacted rapidly to changes in exposure conditions, but not in the same proportion as the uptake rate. The blood concentration proved more closely related to respiratory n-hexane retention than to the uptake rate, reflecting the state of saturation of different body tissues. At rest this parameter was clearly influenced by the amount of body fat. A decrease in relative blood perfusion of fatty tissue could explain why such relation was not found during exposure combined with physical effort.