Background Due to increasing multidrug-resistant (MDR) infections, there is an interest in assessing the use of bacteriophage therapy (BT) as an antibiotic alternative. After the first successful case of intravenous BT to treat a systemic MDR infection at our institution in 2017, the Center for Innovative Phage Applications and Therapeutics (IPATH) was created at the University of California, San Diego, in June 2018. Methods We reviewed IPATH consult requests from June 1, 2018, to April 30, 2020, and reviewed the regulatory process of initiating BT on a compassionate basis in the United States. We also reviewed outcomes of the first 10 cases at our center treated with intravenous BT (from April 1, 2017, onwards). Results Among 785 BT requests to IPATH, BT was administered to 17 of 119 patients in whom it was recommended. One-third of requests were for Pseudomonas aeruginosa, Staphylococcus aureus, and Mycobacterium abscessus. Intravenous BT was safe with a successful outcome in 7/10 antibiotic-recalcitrant infections at our center (6 were before IPATH). BT may be safely self-administered by outpatients, used for infection suppression/prophylaxis, and combined successfully with antibiotics despite antibiotic resistance, and phage resistance may be overcome with new phage(s). Failure occurred in 2 cases despite in vitro phage susceptibility. Conclusions We demonstrate the safety and feasibility of intravenous BT for a variety of infections and discuss practical considerations that will be critical for informing future clinical trials.

The majority of adult infectious disease physicians across the United States and Canada support PrEP but have vast differences of opinion and practice, despite the existence of CDC guidance documents. The success of real-world PrEP will likely require multifaceted programs addressing barriers to its provision and will be assisted with the development of comprehensive guidelines for real-world PrEP.

Objective Early HIV infection is characterized by a dramatic depletion of CD4 T cells in the gastrointestinal tract and translocation of bacterial products from the gut into the blood. In this study, we evaluated if gut bacterial profiles were associated with immune status before and after starting antiretroviral therapy (ART). Design We evaluated the gut microbiota of men recently infected with HIV (n = 13) who were participating in a randomized, double-blind controlled trial of combination ART and maraviroc versus placebo and who were followed for 48 weeks. Methods To evaluate the gut microbiota of participants, we pyrosequenced the bacterial populations from anal swabs collected before and longitudinally after the initiation of ART. Associations of the gut flora with clinical variables (lymphocyte profiles and viral loads), activation and proliferation markers in peripheral blood mononuclear cells and gut biopsies (measured by flow cytometry) and markers of microbial translocation (lipopolysaccharide and soluble CD14) were performed by regression analyses using R statistical software. Results Using pyrosequencing, we identified that higher proportions of Lactobacillales in the distal gut of recently HIV-infected individuals were associated with lower markers of microbial translocation, higher CD4% and lower viral loads before ART was started. Similarly, during ART, higher proportions of gut Lactobacillales were associated with higher CD4%, less microbial translocation, less systemic immune activation, less gut T lymphocyte proliferation, and higher CD4% in the gut. Conclusion Shaping the gut microbiome, especially proportions of Lactobacillales, could help to preserve immune function during HIV infection.

Objective Sexual partner concurrency is common among men who have sex with men (MSM) and may increase the probability of HIV transmission during recent (acute or early) infection. We examined the relationship between concurrency and HIV transmission network characteristics (proxies for HIV transmission) among MSM with recent HIV infection. Design Observational study integrating behavioral, clinical, and molecular epidemiology. Methods We inferred a partial HIV transmission network using 986 HIV-1 pol sequences obtained from HIV-infected individuals in San Diego, California (1996-2015). We further analyzed data from 285 recently HIV-infected MSM in the network who provided information on up to three sexual partners in the past three months, including the timing of intercourse with each partner. Concurrency was defined as sexual partners overlapping in time. Logistic and negative binomial regression were used to investigate the link between concurrency and HIV transmission network characteristics (i.e., clustering and degree or number of connections to others in the network) among these MSM. Results Of recently HIV-infected MSM (N=285), 54% reported concurrent partnerships and 54% were connected by ≥1 putative transmission link to others (i.e., clustered) in the network (median degree=1.0; interquartile range: 0.0-3.0). Concurrency was positively associated with HIV transmission network clustering (adjusted odds ratio=1.83, 95% confidence interval [CI]: 1.08-3.10) and degree (adjusted incidence rate ratio=1.48, 95% CI: 1.02-2.15) Conclusions Our findings provide empirical evidence consistent with the hypothesis that concurrency facilitates HIV transmission during recent infection. Interventions to mitigate the impact of concurrency on HIV transmission may help curb the HIV epidemic among MSM.

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Purpose of reviewPartnerships between academia and the community led to historic advances in HIV and paved the way for ongoing community engagement in research. Three decades later, we review the state of community engagement in HIV research, discuss best practices as supported by literature, explore innovations, and identify ongoing gaps in knowledge. Recent findingsThe community of people living with and at risk for HIV remains actively involved in the performance of HIV research. However, the extent of participation is highly variable despite long standing and established principles and guidelines of good participatory practices (GPP) and community-based participatory research (CBPR). Current literature reveals that known barriers to successful community engagement continue to exist such as power differences, and poor scientific or cultural competency literacy. Several high-quality studies share their experiences overcoming these barriers and demonstrate the potential of CBPR through reporting of qualitative and quantitative outcomes. SummaryGreater time and attention should be placed on the development of community engagement in HIV research. A large body of literature, including innovative cross-cutting approaches, exists to guide and inform best practices and mitigate common barriers. However, we recognize that true growth and expansion of CBPR within HIV and in other fields will require a greater breadth of research reporting qualitative and quantitative outcomes. Keywords community-based participatory research, community engagement, good participatory practices, HIV research family, activists refusing to be passive 'victims' of AIDS embraced self-empowerment and effectively organized. The Denver Principles formed in 1983, served as the foundation of the activist movement and detailed how people living with HIV expect to be treated, how PLWH should respond to the AIDS crisis and the human rights they demand (Table 1) [1,5,6].To address the ongoing outcry of activists, the National Institutes of Allergy and Infectious Diseases recommended including community members at AIDS Clinical Trials Group (ACTG) meetings [7].

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