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Although decreasing in prevalence, heavily treatment-experienced (HTE) persons with limited options for HIV treatment present unique complexities, even amongst experienced providers, as there is no single approach to successful management. HTE patients are described as those having two or less antiretroviral (ARV) classes available for use with limited fully active ARV agents within each class. A detailed understanding of the underlying processes that caused previous treatment failures, diagnostics to define resistance, resistance mechanisms and ARV pharmacology should all function in tandem to determine the next steps of clinical care. This narrative review provides an overview of the clinician approach to care, including diagnostics, approaches to regimen creation, relevant resources, and a broad array of both currently available and upcoming ARVs that may be used in regimens for HTE patients.

Background Invasive infection from Group A streptococcus (iGAS) is rising nationally, and we report a significant increase in incidence at an urban, quaternary care health center, which serves the Kensington neighborhood, the epicenter of the opioid crisis in Philadelphia, PA. We examined iGAS infection in the Temple University Health System catchment area Methods iGAS was defined as an of streptococcus pyogenes cultured from a previously sterile site. Injection drug use (IDU) is a known risk factor for bacterial infection, including iGAS infection. All blood, sterile fluid, and/or tissue cultures that yielded S. pyogenes were identified using the laboratory information system at Temple University Hospital – Main Campus. Two cohorts were compared: January 1, 2021, to December 31, 2021, and January 1, 2019, to December 31, 2019. Electronic health records were reviewed and data pertaining to age, gender, and injection drug use were abstracted. Descriptive statistics were used to summarize findings. Results 155 cases of iGAS were identified in 2021 (105 of which involved bacteremia) compared to 69 in 2019 (42 of which involved bacteremia), representing a 224% increase overall. Of the cases in 2021, 130 (84%) were Persons Who Inject Drugs (PWID) compared to only 39 (57%) in 2019. PWID with iGAS were younger (median age 35 vs 54 in 2019, 39 vs 53 in 2021) and more likely to be male (57% vs 43% in 2019, 68% vs 32% in 2021). Male patients also had a higher incidence of PWID than female patients (56% vs 44% in 2019 and 64% vs 36% in 2021). Conclusion During this same time period, the COVID-19 pandemic added to the ongoing opioid crisis in Philadelphia. The city of Philadelphia publicly reports opioid data, which shows that hospitalizations related to non-fatal opioid overdose have exponentially risen in the past two decades. This also coincides with an increase in the presence of xylazine, an adulterant in the Philadelphia fentanyl supply. Xylazine has been implicated in worsening wounds. Our data supports a concerning association between iGAS and PWID. Disclosures All Authors: No reported disclosures.

Background People who inject drugs (PWID) are at risk for infectious complications of their injection practices, including Staphylococcus aureus (SA) bacteremia. Prolonged hospitalization is sometimes required; however, rates of discharges against medical advice (AMA) are elevated in this patient population. Inadequate control of pain and opioid withdrawal are commonly cited. Our aim was to assess the effectiveness of addiction medicine consultation for preventing AMA discharges. Methods We performed a retrospective chart review of adult PWID admitted to an urban hospital with SA bacteremia between August 2016 and May 2018. Demographics, HIV and HCV status, and presence or absence of addiction medicine consultation were recorded. We assessed whether discharges were planned or AMA; the number of hospitalizations at 30 days, 90 days, and 1 year from index admission; and death within one year. EpiInfo6 was used for data analysis. Results A total of 360 patients with SA bacteremia were reviewed. Of these, 101 reported intravenous opioid use at admission. Average age was 37 years, and 64% were male. HIV and HCV were present in 13% and 82% of patients, respectively. Addiction medicine was consulted on 29 patients. Of these, 4/29 (13.8%) left AMA, compared to 27/72 (37.5%) of patients without an addiction consult (RR = 0.3678 [95% CI = 0.1412 - 0.9583], p = 0.02). Patients receiving addiction medicine consultation averaged 0.17 readmissions within 30 days of their index admission, compared to 0.39 readmissions in the group without addiction medicine consult (p = 0.27). Readmissions at 90 days and 1 year were also lower but not statistically significant. At 1 year, 6 deaths were observed; 2 who had addiction medicine consultation and 4 who did not. Conclusion Consultation with an addiction medicine specialist significantly reduced the number of patients discharged AMA in a high-risk cohort of PWID presenting with SA bacteremia. Numerically fewer readmissions occurred after consultation, though this difference was not statistically significant. Mortality in both groups was low. There were high rates of HIV and HCV in this patient population, suggesting a particularly vulnerable patient population, which warrants further study. Disclosures All Authors: No reported disclosures

Studies on the innate immune response against microbial infections in Drosophila melanogaster involve mutant strains and their reference strains that act as experimental controls. We used five standard D. melanogaster laboratory reference strains (Oregon R, w1118, Canton-S, Cinnabar Brown, and Yellow White [YW]) and investigated their response against two pathogenic bacteria ( Photorhabdus luminescens and Enterococcus faecalis ) and two nonpathogenic bacteria ( Escherichia coli and Micrococcus luteus ). We detected high sensitivity among YW flies to bacterial infections and increased bacterial growth compared to the other strains. We also found variation in the transcription of certain antimicrobial peptide genes among strains, with Oregon and YW infected flies showing the highest and lowest gene transcription levels in most cases. We show that Oregon and w1118 flies possess more circulating hemocytes and higher levels of phenoloxidase activity than the other strains upon infection with the nonpathogenic bacteria. We further observed reduced fat accumulation in YW flies infected with the pathogenic bacteria, which suggests a possible decline in physiological condition. Finally, we found that nitrite levels are significantly lower in infected and uninfected YW flies compared to w1118 flies and that nitric oxide synthase mutant flies in YW background are more susceptible to bacterial infection compared to mutants in w1118 background. Therefore, increased sensitivity of YW flies to bacterial infections can be partly attributed to lower levels of nitric oxide. Such studies will significantly contribute toward a better understanding of the genetic variation between D. melanogaste r reference strains.