Implementation of Bedaquiline, Pretomanid, and Linezolid in the United States: Experience Using a Novel All-Oral Treatment Regimen for Treatment of Rifampin-Resistant or Rifampin-Intolerant Tuberculosis Disease.

BACKGROUND: Rifampin-resistant tuberculosis is a leading cause of morbidity worldwide; only one-third of persons start treatment, and outcomes are often inadequate. Several trials demonstrate 90% efficacy using an all-oral, 6-month regimen of bedaquiline, pretomanid, and linezolid (BPaL), but significant toxicity occurred using 1200-mg linezolid. After US Food and Drug Administration approval in 2019, some US clinicians rapidly implemented BPaL using an initial 600-mg linezolid dose adjusted by serum drug concentrations and clinical monitoring. METHODS: Data from US patients treated with BPaL between 14 October 2019 and 30 April 2022 were compiled and analyzed by the BPaL Implementation Group (BIG), including baseline examination and laboratory, electrocardiographic, and clinical monitoring throughout treatment and follow-up. Linezolid dosing and clinical management was provider driven, and most patients had linezolid adjusted by therapeutic drug monitoring. RESULTS: Of 70 patients starting BPaL, 2 changed to rifampin-based therapy, 68 (97.1%) completed BPaL, and 2 of the 68 (2.9%) experienced relapse after completion. Using an initial 600-mg linezolid dose daily adjusted by therapeutic drug monitoring and careful clinical and laboratory monitoring for adverse effects, supportive care, and expert consultation throughout BPaL treatment, 3 patients (4.4%) with hematologic toxicity and 4 (5.9%) with neurotoxicity required a change in linezolid dose or frequency. The median BPaL duration was 6 months. CONCLUSIONS: BPaL has transformed treatment for rifampin-resistant or intolerant tuberculosis. In this cohort, effective treatment required less than half the duration recommended in 2019 US guidelines for drug-resistant tuberculosis. Use of individualized linezolid dosing and monitoring likely enhanced safety and treatment completion. The BIG cohort demonstrates that early implementation of new tuberculosis treatments in the United States is feasible.

Construct validity and responsiveness of a health-related symptom index for persons either treated or monitored for anal high-grade squamous intraepithelial lesions (HSIL): AMC-A01/-A03.

PURPOSE: To determine whether treatment of anal high-grade squamous intraepithelial lesions (HSIL), vs active monitoring, is effective in reducing incidence of anal cancer in persons living with HIV, the US National Cancer Institute funded the Phase III ANal Cancer/HSIL Outcomes Research (ANCHOR) clinical trial. As no established patient-reported outcomes (PRO) tool exists for persons with anal HSIL, we sought to estimate the construct validity and responsiveness of the ANCHOR Health-Related Symptom Index (A-HRSI). METHODS: The construct validity phase enrolled ANCHOR participants who were within two weeks of randomization to complete A-HRSI and legacy PRO questionnaires at a single time point. The responsiveness phase enrolled a separate cohort of ANCHOR participants who were not yet randomized to complete A-HRSI at three time points: prior to randomization (T1), 14-70 (T2), and 71-112 (T3) days following randomization. RESULTS: Confirmatory factor analysis techniques established a three-factor model (i.e., physical symptoms, impact on physical functioning, impact on psychological functioning), with moderate evidence of convergent validity and strong evidence of discriminant validity in the construct validity phase (n = 303). We observed a significant moderate effect for changes in A-HRSI impact on physical functioning (standardized response mean = 0.52) and psychological symptoms (standardized response mean = 0.60) from T2 (n = 86) to T3 (n = 92), providing evidence of responsiveness. CONCLUSION: A-HRSI is a brief PRO index that captures health-related symptoms and impacts related to anal HSIL. This instrument may have broad applicability in other contexts assessing individuals with anal HSIL, which may ultimately help improve clinical care and assist providers and patients with medical decision-making.

Characterization of Patients Seeking Care at a Sexual Health Clinic Who Report Engaging in Exchange Sex.

BACKGROUND: People who exchange sex (PWES) for money or drugs are at increased risk for poor health outcomes and may be reluctant to engage in health services. METHODS: We conducted a cross-sectional analysis of patients seen for new problem visits at the Public Health-Seattle and King County Sexual Health Clinic between October 2010 and March 2020 who reported exchanging sex for drugs or money in a computer assisted self-interview. We analyzed demographics; sexually transmitted infections (STIs), human immunodeficiency virus (HIV), and hepatitis C virus (HCV) history; and HIV preexposure prophylaxis (PrEP) use, stratified by gender. We compared characteristics of people who ever versus never exchanged sex using χ 2 tests and analyzed the visit reason and outcomes among PWES. RESULTS: Among 30,327 patients, 1611 (5%) reported ever exchanging sex: 981 (61%) cisgender men, 545 (34%) cisgender women, and 85 (5%) transgender and gender diverse persons. Compared with people who never exchanged sex, PWES were more likely to report homelessness (29% vs 7%, P < 0.001), injection drug use (39% vs 4%, P < 0.001), prior STIs (36% vs 19%, P < 0.001), prior HIV diagnosis (13% vs 5%, P < 0.001), and prior HCV diagnosis (13% vs 2%, P < 0.001). People who exchange sex came to the clinic seeking STI tests (60%), HIV tests (45%), and care for STI symptoms (38%). Overall, 320 (20%) PWES were diagnosed with STIs, 15 (1%) were newly diagnosed with HIV, and 12 (1%) initiated PrEP at the visit. CONCLUSION: People who exchange sex have complex barriers to care, and sexual health clinic visits present an opportunity to improve health services for this population.

Human Immunodeficiency Virus Training Pathways in Residency: A National Survey of Curricula and Outcomes.

BACKGROUND: The Ending the HIV Epidemic initiative, which aims to decrease the annual incidence of HIV infections in the United States (US) by 90% over the next decade, will require growth of a limited HIV provider workforce. Existing HIV training pathways within Family Medicine (FM) and Internal Medicine (IM) residency programs may address the shortage of HIV medical providers, but their curricula and outcomes have not previously been assessed. METHODS: We identified HIV residency pathways via literature review, Internet search, and snowball sampling and designed a cross-sectional study of existing HIV pathways in the US. This survey of pathway directors included 33 quantitative items regarding pathway organization, curricular content, graduate outcomes, and challenges. We used descriptive statistics to summarize responses. RESULTS: Twenty-five residency programs with dedicated HIV pathways in the US were identified (14 FM and 11 IM), with most located in the West and Northeast. All 25 (100%) pathway directors completed the survey. Since 2006, a total of 228 residents (77 FM and 151 IM) have graduated from these HIV pathways. Ninety (39%) of 228 pathway graduates provide primary care to persons with HIV (PWH). CONCLUSIONS: HIV pathways are effective in graduating providers who can care for PWH, but generally are not located in nor do graduates practice in the geographic areas of highest need. Our findings can inform quality improvement for existing programs, development of new pathways, and workforce development strategies. Specifically, expanding pathways in regions of greatest need and incentivizing pathway graduates to work in these regions could augment the HIV workforce.

Advancing Digital Health Equity: A Policy Paper of the Infectious Diseases Society of America and the HIV Medicine Association.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has revolutionized the practice of ambulatory medicine, triggering rapid dissemination of digital healthcare modalities, including synchronous video visits. However, social determinants of health, such as age, race, income, and others, predict readiness for telemedicine and individuals who are not able to connect virtually may become lost to care. This is particularly relevant to the practice of infectious diseases (ID) and human immunodeficiency virus (HIV) medicine, as we care for high proportions of individuals whose health outcomes are affected by such factors. Furthermore, delivering high-quality clinical care in ID and HIV practice necessitates discussion of sensitive topics, which is challenging over video without proper preparation. We describe the "digital divide," emphasize the relevance to ID and HIV practice, underscore the need to study the issue and develop interventions to mitigate its impact, and provide suggestions for optimizing telemedicine in ID and HIV clinics.

Tocilizumab in hospitalized patients with COVID-19: Clinical outcomes, inflammatory marker kinetics, and safety.

Coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus 2 causes substantial morbidity. Tocilizumab, an interleukin-6 receptor antagonist, might improve outcomes by mitigating inflammation. We conducted a retrospective study of patients admitted to the University of Washington Hospital system with COVID-19 and requiring supplemental oxygen. Outcomes included clinical improvement, defined as a two-point reduction in severity on a six-point ordinal scale or discharge, and mortality within 28 days. We used Cox proportional-hazards models with propensity score inverse probability weighting to compare outcomes in patients who did and did not receive tocilizumab. We evaluated 43 patients who received tocilizumab and 45 who did not. Patients receiving tocilizumab were younger with fewer comorbidities but higher baseline oxygen requirements. Tocilizumab treatment was associated with reduced C-reactive protein, fibrinogen, and temperature, but there were no meaningful differences in time to clinical improvement (adjusted hazard ratio [aHR], 0.92; 95% confidence interval [CI], 0.38-2.22) or mortality (aHR, 0.57; 95% CI, 0.21-1.52). A numerically higher proportion of tocilizumab-treated patients had subsequent infections, transaminitis, and cytopenias. Tocilizumab did not improve outcomes in hospitalized patients with COVID-19. However, this study was not powered to detect small differences, and there remains the possibility for a survival benefit.

The Impact of COVID-19 on HIV Care Provided via Telemedicine-Past, Present, and Future.

PURPOSE OF REVIEW: This review summarizes HIV care delivered via telemedicine before and during the COVID-19 pandemic and highlights areas of study to inform optimal usage of telemedicine in HIV clinical practice in the future. RECENT FINDINGS: To address barriers to care created by the COVID-19 pandemic, regulatory agencies and payors waived longstanding restrictions, which enabled rapid expansion of telemedicine across the country. Preliminary data show that providers and persons with HIV (PWH) view telemedicine favorably. Some data suggest telemedicine has facilitated retention in care, but other studies have found increasing numbers of PWH lost to follow-up and worsened virologic suppression rates despite offering video and/or telephone visits. The COVID-19 pandemic has exacerbated gaps in the HIV care continuum. To help mitigate the impact, most clinics have adopted new virtual care options and are now evaluating usage, impact, and concerns. Further research into the effects of telemedicine on HIV care and continued work towards universal access are needed.

Are Oral Antibiotics an Effective Alternative to Intravenous Antibiotics in Treatment of Osteomyelitis of the Jaw?

PURPOSE: To review treatment of osteomyelitis of the jaw (OMJ) and determine whether antibiotic route and/or length of administration impacts resolution of infection postsurgically. METHODS: The investigators designed a retrospective cohort study enrolling a sample of patients treated at Harborview Medical Center from January 1, 2009 to December 31, 2019. The primary predictor variable was antibiotic administration route: oral (PO) only, intravenous (IV) only, IV transitioned to PO (IV + PO), or none. The secondary predictor was duration of antibiotic therapy (≤6 weeks or >6 weeks). The primary outcome variable was resolution of infection at 2 months follow-up posttreatment completion. The secondary outcome variable was number of surgeries to resolution of infection. Descriptive, bivariate, and multiple linear regression statistics were computed, with statistical significance set at P < .05. RESULTS: Sixty-seven individuals met inclusion criteria (38 male), mean age 51 years (18 to 88). Forty-nine (73%) received PO antibiotics, 12 (18%) IV + PO, 3 (4%) IV, and 3 (4%) none. Both PO and IV antibiotics were associated with clinical resolution (P = .022, .005, respectively) compared with debridement alone. Antibiotic duration of ≤6 weeks compared with >6 weeks was not significant. Seventy-six percent (51 of 67) required only 1 surgery. In the multivariate logistic regression, PO was associated with clinical resolution (P = .025, OR = 5.05). Penicillin allergy (P = 0.049, OR = 0.223) and diabetes (P = .008, OR = 0.104) were adversely associated with outcome. CONCLUSIONS: OMJ was successfully treated with oral antibiotics and surgery. Prescribing 6 weeks of IV antibiotics may be antiquated. Clinicians should consider oral penicillins as first line whenever possible. Further studies are recommended.

A Co-Located Continuity Clinic Model to Address Healthcare Needs of Women Living Unhoused With Opioid Use Disorder, Who Engage in Transactional Sex in North Seattle.

This is a review of the first 50 patients attending a colocated continuity clinic with harm reduction services to women experiencing homelessness in north Seattle. Among those tested, patients had high rates of curable sexually transmitted infections (44%), injection opioid use (36%), transactional sex (69%), unintended pregnancy (10%), and human immunodeficiency virus infections (10%).

Outbreak of Human Immunodeficiency Virus Infection Among Heterosexual Persons Who Are Living Homeless and Inject Drugs - Seattle, Washington, 2018.

Although diagnoses of human immunodeficiency virus (HIV) infection among persons who inject drugs in the United States are declining, an HIV outbreak among such persons in rural Indiana demonstrated that population's vulnerability to HIV infection (1). In August 2018, Public Health-Seattle and King County (PHSKC) identified a cluster of cases of HIV infection among persons living homeless, most of whom injected drugs. Investigation identified 14 related cases diagnosed from February to mid-November 2018 among women who inject drugs and men who have sex with women (MSW) who inject drugs and their sex partners. All 14 persons were living homeless in an approximately 3-square-mile area and were part of a cluster of 23 cases diagnosed since 2008. Twenty-seven cases of HIV infection were diagnosed among women and MSW who inject drugs in King County during January 1-November 15, 2018, a 286% increase over the seven cases diagnosed in 2017. PHSKC has alerted medical and social service providers and the public about the outbreak, expanded HIV testing among persons who inject drugs or who are living homeless, and is working to increase the availability of clinical and prevention services in the geographic area of the outbreak. This outbreak highlights the vulnerability of persons who inject drugs, particularly those who also are living homeless, to outbreaks of HIV infection, even in areas with high levels of viral suppression and large syringe services programs (SSPs).

Characterising HIV transmission risk among US patients with HIV in care: a cross-sectional study of sexual risk behaviour among individuals with viral load above 1500 copies/mL.

OBJECTIVES: Viral load and sexual risk behaviour contribute to HIV transmission risk. High HIV viral loads present greater transmission risk than transient viral 'blips' above an undetectable level. This paper therefore characterises sexual risk behaviour among patients with HIV in care with viral loads>1500 copies/mL and associated demographic characteristics. METHODS: This cross-sectional study was conducted at six HIV outpatient clinics in USA. The study sample comprises 1315 patients with HIV with a recent viral load >1500 copies/mL. This study sample was drawn from a larger sample of individuals with a recent viral load >1000 copies/mL who completed a computer-assisted self-interview (CASI) regarding sexual risk practices in the last 2 months. The study sample was 32% heterosexual men, 38% men who have sex with men (MSM) and 30% women. RESULTS: Ninety per cent of the sample had their viral load assay within 60 days of the CASI. Thirty-seven per cent reported being sexually active (vaginal or anal intercourse) in the last 2 months. Most of the sexually active participants reported always using condoms (56.9%) or limiting condomless sex to seroconcordant partners (serosorting; 29.2% overall and 42.9% among MSM). Among sexually active participants who reported condomless anal or vaginal sex with an at-risk partner (14%), most had viral loads>10 000 copies/mL (62%). CONCLUSIONS: A relatively small number of patients with HIV in care with viral loads above 1500 copies/mL reported concurrent sexual transmission risk behaviours. Most of the individuals in this small group had markedly elevated viral loads, increasing the probability of transmission. Directing interventions to patients in care with high viral loads and concurrent risk behaviour could strengthen HIV prevention and reduce HIV infections. TRIAL REGISTRATION NUMBER: NCT02044484, completed.

Health Care Provider Perceptions of a Sexually Transmitted Infection Self-testing Program in an HIV Care Clinic.

BACKGROUND: Sexually transmitted infections (STIs) disproportionately affect men who have sex with men. Although clinical practice guidelines recommend routine STI screening of men who have sex with men who have high-risk behaviors, extragenital STI testing rates have been low in HIV clinics across the nation. The University of Washington STD Prevention Training Center implemented an STI self-testing program at a large HIV primary care clinic in Seattle, WA, to facilitate extragenital STI testing. METHODS: We performed a mixed-methods program evaluation to assess health care provider acceptability of the program at 9 months after implementation. Twenty-eight clinicians were invited to complete an online survey. We conducted one-on-one, semistructured interviews with 6 clinicians and a focus group with 7 members of the clinic nursing staff. Survey responses were tallied. Conventional content analysis was performed on survey comments and transcripts from the interviews and focus group. RESULTS: Ninety-one percent of clinicians were either satisfied or very satisfied with the program. Perceived advantages of the program included saving time for clinicians, overcoming patient discomfort, and increasing patient access to testing. Perceived program disadvantages included unclear responsibility of directing patients through the self-testing process and incorrect sample collection and labeling. CONCLUSIONS: Despite perceived disadvantages, the self-testing program was acceptable to clinicians and nursing staff, key population for successful program adoption. Implementation of STI self-testing programs in clinic settings could help to increase extragenital STI testing rates by removing provider and patient barriers to testing.

Fertility desires and preferences for safer conception strategies among people receiving care for HIV at a publicly-funded clinic in Seattle, WA.

Understanding fertility desires and preferences for HIV prevention among individuals living with HIV, including the potential use of pre-exposure prophylaxis (PrEP) by HIV uninfected partners, can inform the delivery of safer conception counseling to reduce the risk of HIV transmission during pregnancy attempts. Men and women, predominantly heterosexual, engaged in HIV care in Seattle, WA, self-administered a questionnaire and we abstracted antiretroviral therapy (ART) status and HIV viral levels from medical records. We summarized participants' sexual behavior, fertility desires, and preferences for safer conception strategies and used log-binomial regression to identify demographic, sexual, and behavioral factors associated with perceived acceptability of PrEP for HIV uninfected partners during pregnancy attempts. 52% of the 150 participants were female and the mean age was 48 years (range 23-74). 94.7% of participants were using ART and 79.3% had HIV viral load < 40 copies/mL. 22.2% of men and 34.6% of women reported that a healthcare provider had initiated discussion about fertility desires. 28.7% of participants were reproductive-age and desired children. Among sexually active reproductive-age participants with fertility desires, 56.3% reported inconsistent condom use and 62.5% did not report using effective birth control. 74.4% of reproductive age participants with fertility desires perceived that PrEP would be acceptable to an HIV uninfected partner and there were no significant predictors of PrEP acceptability. Nearly one third of reproductive-aged individuals living with HIV expressed fertility desires, highlighting a need for safer conception counseling in this setting. PrEP and ART were favored safer conception strategies.

Evaluation of a computer-based and counseling support intervention to improve HIV patients' viral loads.

We sought to integrate a brief computer and counseling support intervention into the routine practices of HIV clinics and evaluate effects on patients' viral loads. The project targeted HIV patients in care whose viral loads exceeded 1000 copies/ml at the time of recruitment. Three HIV clinics initiated the intervention immediately, and three other HIV clinics delayed onset for 16 months and served as concurrent controls for evaluating outcomes. The intervention components included a brief computer-based intervention (CBI) focused on antiretroviral therapy adherence; health coaching from project counselors for participants whose viral loads did not improve after doing the CBI; and behavioral screening and palm cards with empowering messages available to all patients at intervention clinics regardless of viral load level. The analytic cohort included 982 patients at intervention clinics and 946 patients at control clinics. Viral loads were assessed at 270 days before recruitment, at time of recruitment, and +270 days later. Results indicated that both the control and intervention groups had significant reductions in viral load, ending with approximately the same viral level at +270 days. There was no evidence that the CBI or the targeted health coaching was responsible for the viral reduction in the intervention group. Results may stem partially from statistical regression to the mean in both groups. Also, clinical providers at control and intervention clinics may have taken action (e.g., conversations with patients, referrals to case managers, adherence counselors, mental health, substance use specialists) to help their patients reduce their viral loads. In conclusion, neither a brief computer-based nor targeted health coaching intervention reduced patients' viral loads beyond levels achieved with standard of care services available to patients at well-resourced HIV clinics.

Prevention of Sexually Transmitted Diseases in HIV-Infected Individuals.

Prevention of sexually transmitted infections (STIs) is an important part of the care of the HIV-infected individual. STIs have been associated with increased risk of transmission and acquisition of HIV. Among HIV-infected persons, treatment failures and high recurrence rates of some STIs are more common. Despite the recognized importance of prevention and discussion of sexual health, rates of screening for STIs are suboptimal. Moreover, rates of STIs such as syphilis continue to increase particularly in men who have sex with men (MSM). This review focuses on the most common STIs seen among HIV-infected individuals and recommendations for screening and prevention.

HIV Provider Documentation and Actions Following Patient Reports of At-risk Behaviors and Conditions When Identified by a Web-Based Point-of-Care Assessment.

We compared same-day provider medical record documentation and interventions addressing depression and risk behaviors before and after delivering point-of-care patient-reported outcomes (PROs) feedback for patients who self-reported clinically relevant levels of depression or risk behaviors. During the study period (1 January 2006-15 October 2010), 2289 PRO assessments were completed by HIV-infected patients. Comparing the 8 months before versus after feedback implementation, providers were more likely to document depression (74% before vs. 87% after feedback, p = 0.02) in patients with moderate-to-severe depression (n = 317 assessments), at-risk alcohol use (41 vs. 64%, p = 0.04, n = 155) and substance use (60 vs. 80%, p = 0.004, n = 212). Providers were less likely to incorrectly document good adherence among patients with inadequate adherence after feedback (42 vs. 24%, p = 0.02, n = 205). While PRO feedback of depression and adherence were followed by increased provider intervention, other domains were not. Further investigation of factors associated with the gap between awareness and intervention are needed in order to bridge this divide.

Treatment completion for latent tuberculosis infection: a retrospective cohort study comparing 9 months of isoniazid, 4 months of rifampin and 3 months of isoniazid and rifapentine.

BACKGROUND: The U.S. Centers for Disease Control and Prevention (CDC) recommended a new regimen for treatment of latent tuberculosis (three months of weekly isoniazid and rifapentine) in late 2011. While completion rates of this regimen were reported to be higher than nine months of isoniazid, little is known about the completion rates of three months of isoniazid and rifapentine compared to nine months of isoniazid or four months of rifampin in actual use scenarios. METHODS: We conducted a retrospective cohort study comparing treatment completion for latent tuberculosis (TB) infection in patients treated with nine months of isoniazid, three months of isoniazid and rifapentine or four months of rifampin in outpatient clinics and a public health TB clinic in Seattle, Washington. The primary outcome of treatment completion was defined as 270 doses of isoniazid within 12 months, 120 doses of rifampin within six months and 12 doses of isoniazid and rifapentine within four months. RESULTS: Three hundred ninety-three patients were included in the study. Patients were equally likely to complete three months of weekly isoniazid and rifapentine or four months of rifampin (85% completion rate of both regimens), as compared to 52% in the nine months of isoniazid group (p < 0.001). These associations remained statistically significant even after adjusting for clinic location and type of monitoring. Monitoring type (weekly versus monthly versus less often than monthly) had less impact on treatment completion than the type of treatment offered. CONCLUSIONS: Patients were equally as likely to complete the three months of isoniazid and rifapentine as four months of rifampin. Four months of rifampin is similar in efficacy compared to placebo as isoniazid and rifapentine but does not require directly observed therapy (DOT), and is less expensive compared to combination therapy with isoniazid and rifapentine, and thus can be the optimal treatment regimen to achieve the maximal efficacy in a community setting.

Variations in Clinical Presentation of Ocular Syphilis: Case Series Reported From a Growing Epidemic in the United States.

Ocular syphilis, a form of neurosyphilis, has been increasingly diagnosed in the United States. This case series summarizes the course of 6 patients recently diagnosed with ocular syphilis, emphasizing the varied sociodemographic factors and the wide range of symptoms and outcomes that are seen in patients with this disease.

Human Diphyllobothrium nihonkaiense infection in Washington State.

A patient in Washington State harbored a fish tapeworm most likely acquired from eating raw salmon. Diphyllobothrium nihonkaiense was identified by cox1 sequence analysis. Although this is the first documented human D. nihonkaiense infection in the United States, the parasite may have been present earlier but misidentified as Diphyllobothrium latum.