Person:

Rowley, Christopher

Background: Abacavir (ABC) may be associated with a small, increased risk of myocardial infarction in HIV-infected adults, possibly related to cytokine-mediated inflammation. Methods: To evaluate the induction of inflammatory cytokine transcription by ABC, we used samples from women randomized to receive zidovudine/lamivudine/ABC (Trizivir) or lopinavir/ritonavir and zidovudine/lamividine (Kaletra/Combivir) from the third trimester through six-months postpartum for the prevention of mother-to-child transmission (PMTCT). Women were matched by CD4 count and baseline HIV RNA. All women attained viral suppression (<50 copies/ml) by the time of sampling. Results: Four cytokines showed a difference in expression between the treatment arms, all in a proinflammatory direction for the ABC arm: CD40LG 1.82-fold, (p=.027); IL-8 3.16-fold (p=.020); LTA 2.82-fold, (p=.008); and CCL5 −1.67-fold, (p=.035). At 12-months postpartum, 6-months after antiretroviral discontinuation, cytokine expression was similar by treatment arm. Conclusions: We conclude that ABC may upregulate proinflammatory cytokines at the transcriptional level in this population.

Cytotoxic-T-lymphocyte (CTL) escape mutations in human immunodeficiency viruses encode amino acid substitutions in positions that disrupt CTL targeting, thereby increasing virus survival and conferring a relative fitness benefit. However, it is now clear that CTL escape mutations can also confer a fitness cost, and there is increasing evidence to suggest that in some cases, e.g., escape from HLA-B57/B5801-restricted responses, the costs to the escape virus may affect the clinical course of infection. To quantify the magnitude of the costs of HLA-B57/B5801 escape, a highly sensitive dual-infection assay that uses synonymous nucleotide sequence tags to quantify viral relative replication capacity (RRC) was developed. We then asked whether such CTL escape mutations had an impact equivalent to that seen for a benchmark mutation, the M184V antiretroviral drug resistance mutation of reverse transcriptase (RRC(V184) = 0.86). To answer the question, the RRCs were quantified for escape mutations in three immunodominant HLA-B57/B5801 epitopes in capsid: A146P in IW9 (RRC(P146) = 0.91), A163G in KF11 (RRC(G163) = 0.89), and T242N in TW10 (RRC(N242) = 0.86). Individually, the impact of the escape mutations on RRC was comparable to that of M184V, while coexpression of the mutations resulted in substantial further reductions, with the maximum impact observed for the triple mutant (RRC(P146-G163-N242) = 0.62). By comparison to M184V, the magnitude of the reductions in RRC caused by the escape mutations, particularly when coexpressed, suggests that the costs of escape are sufficient to affect in vivo viral dynamics and may thus play a role in the protective effect associated with HLA-B57/B5801.

Background In the context of the opioid epidemic, injection drug use (IDU)–related infections are an escalating health issue for infectious diseases (ID) physicians in the United States.

Methods We conducted a mixed methods survey of the Infectious Diseases Society of America’s Emerging Infections Network between February and April 2017 to evaluate perspectives relating to care of persons who inject drugs (PWID). Topics included the frequency of and management strategies for IDU-related infection, the availability of addiction services, and the evolving role of ID physicians in substance use disorder (SUD) management.

Results More than half (53%, n = 672) of 1273 network members participated. Of these, 78% (n = 526) reported treating PWID. Infections frequently encountered included skin and soft tissue (62%, n = 324), bacteremia/fungemia (54%, n = 281), and endocarditis (50%, n = 263). In the past year, 79% (n = 416) reported that most IDU-related infections required ≥2 weeks of parenteral antibiotics; strategies frequently employed for prolonged treatment included completion of the entire course in the inpatient unit (41%, n = 218) or at another supervised facility (35%, n = 182). Only 35% (n = 184) of respondents agreed/strongly agreed that their health system offered comprehensive SUD management; 46% (n = 242) felt that ID providers should actively manage SUD.

Conclusions The majority of physicians surveyed treated PWID and reported myriad obstacles to providing care. Public health and health care systems should consider ways to support ID physicians caring for PWID, including (1) guidelines for providing complex care, including safe provision of multiweek parenteral antibiotics; (2) improved access to SUD management; and (3) strategies to assist those interested in roles in SUD management.

Abstract Background: The opioid epidemic has swept across the U.S. at a staggering rate, with an estimated half million to one million persons injecting drugs annually. Rates of hospitalization for injection drug use (IDU)-related infection have risen precipitously, comprising an escalating proportion of infectious diseases provider volume in highly impacted regions. Methods: In March 2017, the Emerging Infections Network surveyed their national network of infectious diseases (ID) physicians to evaluate perspectives relating to the care of persons who inject drugs (PWID), including the frequency of, and management strategies for, IDU-related infection, the availability of addiction services, and the evolving role of ID physicians in the management of addiction. Results: Over half (53%; N = 672) of 1,276 members with an adult ID practice participated; 78% (n = 526) reported treating PWID. Of 526 respondents, 464 (88%) reported seeing ≥1 patient per month with an IDU-related infection; 228 (43%) reported ≥6 per month. In the past year, 79% of respondents reported the majority of IDU-related infections seen required ≥2 weeks of parenteral therapy and reported frequently encountering skin and soft-tissue infections (61%), bacteremia/fungemia (53%), and endocarditis (50%). Strategies most commonly employed for management of prolonged parenteral antibiotic therapy included: completion of entire course on inpatient unit (by 41%) and transfer to supervised facility for completion (35%). Only 35% of respondents agree/strongly agree their health system offers comprehensive treatment of substance use disorders (N = 181). Though nearly half of respondents felt that ID providers should actively manage substance use disorders (46%; N = 241), only 3% reported being waivered to prescribe buprenorphine for treatment of opioid use disorder. Conclusion: The majority of infectious diseases physicians frequently care for PWID with serious infections. There is significant diversity amongst providers with regards to the availability of comprehensive addiction services as well as perceptions regarding the role providers should play in the management of addiction. Guidelines for the management of serious infections and concurrent addiction in the midst of the escalating national opioid crisis should be considered. Disclosures All authors: No reported disclosures.