Broadly neutralizing antibodies for HIV treatment and cure approaches.

PURPOSE OF REVIEW: In recent years, clinical trials have explored broadly neutralizing antibodies (bNAbs) as treatment and cure of HIV. Here, we summarize the current knowledge, review the latest clinical studies, and reflect on the potential role of bNAbs in future applications in HIV treatment and cure strategies. RECENT FINDINGS: In most individuals who switch from standard antiretroviral therapy to bNAb treatment, combinations of at least two bNAbs effectively suppress viremia. However, sensitivity of archived proviruses to bNAb neutralization and maintaining adequate bNAb plasma levels are key determinants of the therapeutic effect. Combinations of bNAbs with injectable small-molecule antiretrovirals are being developed as long-acting treatment regimens that may require as little as two annual administrations to maintain virological suppression. Further, interventions that combine bNAbs with immune modulators or therapeutic vaccines are under investigation as HIV curative strategies. Interestingly, administration of bNAbs during the early or viremic stage of infection appears to enhance host immune responses against HIV. SUMMARY: While accurately predicting archived resistant mutations has been a significant challenge for bNAb-based treatments, combinations of potent bNAbs against nonoverlapping epitopes may help overcome this issue. As a result, multiple long-acting HIV treatment and cure strategies involving bNAbs are now being investigated.

The Impact of IFNλ4 on the Adaptive Immune Response to SARS-CoV-2 Infection.

Genetic polymorphisms at the IFNL4 loci are known to influence the clinical outcome of several different infectious diseases. Best described is the association between the IFNL4 genotype and hepatitis C virus clearance. However, an influence of the IFNL4 genotype on the adaptive immune system was suggested by several studies but never investigated in humans. In this cross-sectional study, we have genotyped 201 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive participants for 3 IFNL4 polymorphisms (rs368234815, rs12979860, and rs117648444) and stratified them according to the IFNλ4 activity. Based on this stratification, we investigated the association between the IFNL4 genotype and the antibody as well as the CD8+ T cell response in the acute phase of the SARS-CoV-2 infection. We observed no differences in the genotype distribution compared with a Danish reference cohort or the 1,000 Genome Project, and we were not able to link the IFNL4 genotype to changes in either the antibody or CD8+ T cell responses of these patients.