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HLA-DM removes CLIP and other loosely bound peptides from MHC class II molecules. The crystal structures of class II molecules and of HLA-DM have not permitted identification of their interaction sites. Here, we describe mutations in class II that impair interactions with DM. Libraries of randomly mutagenized DR3 alpha and beta chains were screened for their ability to cause cell surface accumulation of CLIP/DR3 complexes in EBV-B cells. Seven mutations were associated with impaired peptide loading in vivo, as detected by SDS stability assays. In vitro, these mutant DR3 molecules were resistant to DM-catalyzed CLIP release and showed reduced binding to DM. All mutations localize to a single lateral face of HLA-DR, which we propose interacts with DM during peptide exchange.

Findings suggest that a network-based strategy for self-test distribution is a promising intervention to increase testing uptake and reduce undiagnosed infections among AAMSM and LMSM.

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Objective Young men who have sex with men (MSM) and MSM of color have the highest HIV incidence in the US. To explore possible explanations for these disparities and known individual risk factors we analyzed the per-contact risk (PCR) of HIV seroconversion in the early highly active antiretroviral therapy era. Methods Data from three longitudinal studies of MSM, HIVNET Vaccine Preparedness Study, EXPLORE behavioral efficacy trial, and VAX004 vaccine efficacy trial were pooled. The analysis included visits where participants reported unprotected receptive anal intercourse (URA), protected receptive anal intercourse (PRA), or unprotective insertive anal intercourse (UIA) with an HIV seropositive, unknown HIV serostatus, or an HIV seronegative partner. We used regression standardization to estimate average PCRs for each type of contact, with bootstrap confidence intervals. Results The estimated PCR was highest for URA with an HIV seropositive partner (0.73%; 95%BCI 0.45%-0.98%) followed by URA with a partner of unknown HIV serostatus (0.49%; 95%BCI 0.32%-0.62%). The estimated PCR for PRA and UIA with an HIV seropositive partner was 0.08% (95%BCI 0.0%-0.19%) and 0.22% (95%BCI 0.05%-0.39%) respectively. Average PCRs for URA and UIA with HIV seropositive partners were higher by 0.14-0.34% among younger participants and higher by 0.08% for UIA among Latino participants compared to White participants. Estimated PCRs increased with increasing number of sexual partners, use of methamphetamines or poppers, and history of sexually transmitted infection. Conclusions Susceptibility or partner factors may explain the higher HIV conversion risk for younger MSM, some MSM of color, and those reporting individual risk factors.

COVID-19 can cause significant mortality in the elderly in Long Term Care Facilities (LTCF). We describe four LTCF outbreaks where mass testing identified a high proportion of asymptomatic infections (4-41% in health care workers and 20-75% in residents), indicating that symptom-based screening alone is insufficient for monitoring for COVID-19 transmission.

Pre-Exposure Prophylaxis (PrEP) has shown high efficacy in preventing human immunodeficiency virus (HIV) infection among men who have sex with men (MSM) in several large clinical trials, and more recently in “real world” reports of clinical implementation and a PrEP demonstration project. Those studies also demonstrated high bacterial sexually transmitted infection (STI) incidence and raised the discussion of how PrEP may impact STI control efforts, especially in the setting of increasing Neisseria gonorrhoeae antimicrobial resistance and the increase in syphilis cases among MSM. Here, we discuss STIs as a driver of HIV transmission risk among MSM, and the potential opportunities and challenges for STI control afforded by expanded PrEP implementation among high-risk MSM.