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.

The interindividual variability of tenofovir pharmacokinetics in HIV+ patients is quite large, but the sources of variability are incompletely understood. Intraindividual variability has not been characterized, although it may have an impact on efficacy and therapeutic drug monitoring. The aims of the study were to estimate intraindividual variability of tenofovir clearance and to assess interactions with associated antiviral drugs. Tenofovir concentrations (median 2; range, 1-5) were measured in 175 patients during several dosing intervals. Covariates and dosing regimen of associated antiretroviral drugs were recorded prospectively. The data were analyzed by a population approach. The final model was a 2-compartment model with first-order absorption rate. The elimination clearance was found to be related to the ratio of body weight to serum creatinine. Among the 15 drugs coadministered, no interaction on tenofovir kinetics was significant. The global variability of CL/F, after accounting for variability to variation of body weight and serum creatinine, was about 50%, with 20% due to interindividual variability and 30% due to interoccasion variability. In a few patients, clearance (and AUC) could vary by a factor of 2 between occasions. The interoccasion variability was not related to the delay between occasions. In the context of drug monitoring, for a given patient, the dose should not be adapted unless the variation of concentration between 2 occasions is large, or the 24-hour trough concentration at steady state is lower than 12 microg/L.

Since 2016, an increase in the number of hepatitis A cases affecting mainly men who have sex with men (MSM) has been reported in low endemic countries in Europe. We calculated the attack rate in Lyon, France, in populations considered at high-risk: HIV-infected MSM and HIV-negative MSM receiving HIV pre-exposure prophylaxis (PrEP). In these populations, high level of immunity did not prevent the outbreak, indicating that vaccination should be reinforced, particularly in younger individuals.