BK polyomavirus (BKPyV)-associated nephropathy (BKPyVAN) is one of the major causes of kidney graft dysfunction, and there are no BKPyV-specific antiviral therapies available. BKPyV neutralizing antibodies (NAbs) play key roles in protecting against BKPyV replication and represent a potential therapeutic or preventive strategy. In this study, we evaluated NAb titers in intravenous immunoglobulin (i.v. Ig) preparations and in kidney transplant recipients (KTR) before and after i.v. Ig administration. NAb titers directed against major BKPyV genotypes were measured using a BKPyV pseudovirion system. Thirty-three KTR receiving high (1 g/kg of body weight/day; n = 17) or low (0.4 g/kg/day; n = 16) i.v. Ig doses were included. Median NAb titers in i.v. Ig preparations ranged from 5.9 log₁₀ 50% inhibitory concentration (IC₅₀) for genotype I to 4.1 log₁₀ IC₅₀ for genotype IV. A mean of 90% of patients (range, 88% to 100%) displaying low or negative BKPyV NAb titers against genotype I reached 4 log₁₀ IC₅₀ after the first i.v. Ig administration. This value was reached by a mean of 44% (range, 13% to 83%) and 19% (range, 0% to 38%) of patients against genotype II and genotype IV, respectively. The benefit of i.v. Ig administration persisted until the following course of treatment (day 22 ± 7 days) for genotypes I and II, and no cumulative effect was observed through the three doses. Our findings demonstrate that i.v. Ig administration results in a significant increase in BKPyV NAb titers in KTR. These in vitro and in vivo pharmacokinetic data provide the rationale for a proof-of-concept study investigating the efficacy of i.v. Ig for the prevention of BKPyV infection in KTR.

The objective of this study was to address the dynamics of archived resistant quasispecies in cell-associated HIV-1 DNA over time in heavily ART-experienced patients with currently suppressed plasma HIV-1 RNA. Longitudinal ultra-deep sequencing (UDS) analysis of reverse transcriptase, protease and V3 Env regions was performed on blood-cell-associated HIV-1 DNA samples. Drug-resistance-associated mutations (DRAMs) and tropism were interpreted using the ANRS and Geno2Pheno algorithms. We analysed frozen blood cells from patients enrolled in the INNOVE and ANRS 123 ETOILE studies who achieved sustained viral suppression after salvage optimized ART (SOT). Samples were available at baseline and 6 and ≥12 months after SOT initiation in 10 patients. V3 loop sequences displayed wide intra-individual dynamics over time. Viral variants harbouring DRAMs exhibited three non-exclusive scenarios. First, when SOT exerted the same selective pressure as previous failing regimens, some viral quasispecies still harboured the same DRAMs at the same level as at the time of virological failure. Thus, as DRAMs were mostly associated with the same viral variant, variants with a complete resistance pattern remained archived. Second, some viral variants harbouring DRAMs were no longer detected over time when SOT consisted of new antiretroviral classes or had resistance profiles distinct from those of previous failing regimens. Third, variants with new DRAMs associated with SOT emerged in blood cells during follow-up despite sustained virological control. Using longitudinal UDS analysis and focusing on DRAMs and tropism as markers, we demonstrated that, despite sustained virological control, archived HIV-1 DNA quasispecies continued to evolve.

Objectives Emtricitabine/tenofovir/rilpivirine as a single‐tablet regimen (STR) is widely used without licence in treatment‐experienced patients. The purpose of this retrospective observational study was to assess viral suppression of ART‐experienced patients switching to STR. Methods We assessed 131 pretreated patients switching to STR with HIV RNA < 400 HIV‐1 RNA copies/mL. The primary outcome measure was the proportion of patients at week 24 with HIV RNA < 40 copies/mL. Results By week 24, eight patients had stopped STR: four because of adverse events and four for other reasons. Three virological failures were observed; among these, at least one patient developed cross‐resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs), in particular with the E138K pattern. In intent‐to‐treat analysis, 92% of participants (120 of 131) achieved HIV RNA < 40 copies/mL. Only grade 1 to 2 adverse events were observed, mainly consisting of increased liver enzymes (n = 33). Systemic exposure to rilpivirine was above the usually observed steady‐state levels for the 18 measurements assessed. Conclusions Efficacy and tolerability are similar to those in treatment‐naïve patients.