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.

Epidemiologic and Clinical Features of Mpox-Associated Deaths - United States, May 10, 2022-March 7, 2023.

As of March 7, 2023, a total of 30,235 confirmed and probable monkeypox (mpox) cases were reported in the United States,† predominantly among cisgender men§ who reported recent sexual contact with another man (1). Although most mpox cases during the current outbreak have been self-limited, cases of severe illness and death have been reported (2-4). During May 10, 2022-March 7, 2023, 38 deaths among persons with probable or confirmed mpox¶ (1.3 per 1,000 mpox cases) were reported to CDC and classified as mpox-associated (i.e., mpox was listed as a contributing or causal factor). Among the 38 mpox-associated deaths, 94.7% occurred in cisgender men (median age = 34 years); 86.8% occurred in non-Hispanic Black or African American (Black) persons. The median interval from symptom onset to death was 68 days (IQR = 50-86 days). Among 33 decedents with available information, 93.9% were immunocompromised because of HIV. Public health actions to prevent mpox deaths include integrated testing, diagnosis, and early treatment for mpox and HIV, and ensuring equitable access to both mpox and HIV prevention and treatment, such as antiretroviral therapy (ART) (5).

Routine, rapid HIV testing of medicine service admissions in the emergency department.

OBJECTIVE: We identify undiagnosed HIV among adult emergency department (ED) patients awaiting medicine admission through rapid testing, expedite their redirection to the inpatient HIV service, and improve linkage to ambulatory HIV care. METHODS: Two ED health educators offered rapid testing to patients aged 18 to 64 years from the high-acuity ED area from which most medicine admissions originate. Heath educators obtained consent, obtained fingerstick blood, and performed point-of-care testing. Patients with reactive results received counseling, confirmatory testing, and appointments at the affiliated HIV clinic. RESULTS: Between March 1, 2008, and February 28, 2009, 4,755 patients received testing. Thirty patients (0.6%) had received a new diagnosis of HIV; 26 were admitted and redirected to the HIV service. Characteristics of HIV positive patients were mean age 38 years, 87% men, 64% black, and 33% Hispanic; 76% had CD4 counts less than 200 cells/mm(3); 67% had HIV-related diagnoses; and 93% reported for ambulatory HIV care in a median of 10 days. During 2 preceding years, these patients had a mean of 3 previous health system visits without testing. During a 6-month quality assurance interval of the 5,340 ED medicine admissions, 31% of patients were eligible for testing, of whom 88% received testing (1% positive) and 12% declined; 29% of the 5,340 were not approached for testing; and 40% were deemed ineligible. Common reasons for ineligibility included older age, recent previous test, and known HIV-positive status. CONCLUSION: Patients who receive a diagnosis of HIV in our ED before admission are extremely ill, most having AIDS. Targeted HIV screening of ED patients awaiting hospital admission facilitated timely diagnosis and reliable linkage to inpatient and outpatient HIV care.

Care Facilitation Advances Movement Along the Hepatitis C Care Continuum for Persons With Human Immunodeficiency Virus, Hepatitis C, and Substance Use: A Randomized Clinical Trial (CTN-0064).

BACKGROUND: Direct-acting antivirals can cure hepatitis C virus (HCV). Persons with HCV/HIV and living with substance use are disadvantaged in benefiting from advances in HCV treatment. METHODS: In this randomized controlled trial, participants with HCV/HIV were randomized between February 2016 and January 2017 to either care facilitation or control. Twelve-month follow-up assessments were completed in January 2018.Care facilitation group participants received motivation and strengths-based case management addressing retrieval of HCV viral load results, engagement in HCV/HIV care, and medication adherence. Control group participants received referral to HCV evaluation and an offer of assistance in making care appointments. Primary outcome was number of steps achieved along a series of 8 clinical steps (eg, receiving HCV results, initiating treatment, sustained virologic response [SVR]) of the HCV/HIV care continuum over 12 months postrandomization. RESULTS: Three hundred eighty-one individuals were screened and 113 randomized. Median age was 51 years; 58.4% of participants were male and 72.6% were Black/African American. Median HIV-1 viral load was 27 209 copies/mL, with 69% having a detectable viral load. Mean number of steps completed was statistically significantly higher in the intervention group vs controls (2.44 vs 1.68 steps; χ 2 [1] = 7.36, P = .0067). Men in the intervention group completed a statistically significantly higher number of steps than controls. Eleven participants achieved SVR with no difference by treatment group. CONCLUSIONS: The care facilitation intervention increased progress along the HCV/HIV care continuum, as observed for men and not women. Study findings also highlight continued challenges to achieve individual-patient SVR and population-level HCV elimination. CLINICAL TRIALS REGISTRATION: NCT02641158.

Early development of non-hodgkin lymphoma following initiation of newer class antiretroviral therapy among HIV-infected patients - implications for immune reconstitution.

BACKGROUND: In the HAART era, the incidence of HIV-associated non-Hodgkin lymphoma (NHL) is decreasing. We describe cases of NHL among patients with multi-class antiretroviral resistance diagnosed rapidly after initiating newer-class antiretrovirals, and examine the immunologic and virologic factors associated with potential IRIS-mediated NHL. METHODS: During December 2006 to January 2008, eligible HIV-infected patients from two affiliated clinics accessed Expanded Access Program antiretrovirals of raltegravir, etravirine, and/or maraviroc with optimized background. A NHL case was defined as a pathologically-confirmed tissue diagnosis in a patient without prior NHL developing symptoms after starting newer-class antiretrovirals. Mean change in CD4 and log10 VL in NHL cases compared to controls was analyzed at week 12, a time point at which values were collected among all cases. RESULTS: Five cases occurred among 78 patients (mean incidence = 64.1/1000 patient-years). All cases received raltegravir and one received etravirine. Median symptom onset from newer-class antiretroviral initiation was 5 weeks. At baseline, the median CD4 and VL for NHL cases (n = 5) versus controls (n = 73) were 44 vs.117 cells/mm3 (p = 0.09) and 5.2 vs. 4.2 log10 (p = 0.06), respectively. The mean increase in CD4 at week 12 in NHL cases compared to controls was 13 (n = 5) vs. 74 (n = 50)(p = 0.284). Mean VL log10 reduction in NHL cases versus controls at week 12 was 2.79 (n = 5) vs. 1.94 (n = 50)(p = 0.045). CONCLUSIONS: An unexpectedly high rate of NHL was detected among treatment-experienced patients achieving a high level of virologic response with newer-class antiretrovirals. We observed trends toward lower baseline CD4 and higher baseline VL in NHL cases, with a significantly greater decline in VL among cases by 12 weeks. HIV-related NHL can occur in the setting of immune reconstitution. Potential immunologic, virologic, and newer-class antiretroviral-specific factors associated with rapid development of NHL warrants further investigation.

The role of rapid vs conventional human immunodeficiency virus testing for inpatients: effects on quality of care.

BACKGROUND: Rapid testing for human immunodeficiency virus (HIV) has improved HIV screening in the outpatient and perinatal settings, but few data report how it may be used to improve the quality of inpatient care. We compared quality of care for inpatients diagnosed in the emergency department via rapid testing vs patients whose conditions were diagnosed via conventional testing during their hospital admission. METHODS: We reviewed medical records to identify patients with first-time positive HIV tests and concurrent hospital admission who were tested via either rapid testing in the emergency department or conventional testing during their hospital admission. We compared quality-of-care end points for these patients. RESULTS: We identified 103 HIV-infected inpatients with no previous HIV diagnosis; the conditions of 48 patients (47%) were diagnosed by rapid testing and 55 (53%) by conventional testing. Mean length of stay was 6 days for the rapid test group vs 13 days for the conventional test group (P<.001); multivariate regression analysis showed that testing modality had an independent, statistically significant effect on length of stay. Nine (16%) of the patients in the conventional test group vs none in the rapid test group were discharged without receiving their HIV test results (P = .002). Patients in the rapid test group attended the outpatient HIV clinic in a mean of 22 days vs 50 days for the conventional test group patients (P = .05). CONCLUSIONS: Rapid HIV testing in the emergency department preceding admission may shorten hospital stay, increase the number of newly diagnosed patients with HIV who are discharged from the hospital aware of their HIV status, and improve entry into outpatient care for patients admitted at the time of their initial HIV diagnosis.

Assessing the use of HIV surveillance data to help gauge patient retention-in-care.

BACKGROUND: Improved retention-in-care may enhance health outcomes for people living with HIV/AIDS (PLWHA). Although laboratory surveillance data may be used to gauge retention, no previous reports have compared laboratory surveillance vs. clinic visit-based measures of retention-in-care. We compared laboratory surveillance vs. clinic visit-based approaches for identifying retention status for PLWHA. METHODS: We examined 2011 patient visit data from the Ruth M. Rothstein CORE Center, Cook County's HIV clinic. We defined retained patients as those with visits every 6 months over 2 years and matched patients classified through visit data against HIV surveillance laboratories reported to the Chicago Department of Health. We determined the sensitivity, specificity, and receiver operator characteristics of varying laboratory surveillance vs. clinic visit measures of retention. RESULTS: Of patients classified through clinic visit data, 91% of 1714 in-care vs. 22% of 200 out-of-care patients met our most stringent surveillance-based retention definition-having ≥2 viral load/CD4s performed 90 days apart reported by the same laboratory in 2011. Of surveillance laboratory-based definitions for retention, having ≥2 HIV viral load and/or CD4 values at least 3 months apart reported from the same facility possessed the best receiver operator parameters and the receiver operator characteristics' curve comparing several laboratory surveillance vs. clinic visit-based retention measures that had an area under the curve of 0.95. CONCLUSIONS: Our findings demonstrate that surveillance laboratory data can be used to assess retention-in-care for PLWHA. These data suggest that bi-directional data sharing between public health entities and care providers could advance re-engagement efforts.

Transmission clustering among newly diagnosed HIV patients in Chicago, 2008 to 2011: using phylogenetics to expand knowledge of regional HIV transmission patterns.

INTRODUCTION: HIV transmission cluster analyses can inform HIV prevention efforts. We describe the first such assessment for transmission clustering among HIV patients in Chicago. METHODS: We performed transmission cluster analyses using HIV pol sequences from newly diagnosed patients presenting to Chicago's largest HIV clinic between 2008 and 2011. We compared sequences through progressive pairwise alignment, using neighbor joining to construct an unrooted phylogenetic tree. We defined clusters as >2 sequences among which each sequence had at least 1 partner within a genetic distance of ≤1.5%. We used multivariable regression to examine factors associated with clustering and used geospatial analysis to assess geographic proximity of phylogenetically clustered patients. RESULTS: We compared sequences from 920 patients, median age of 35 years, 75% male, 67% black, 23% Hispanic, and 8% had a rapid plasma reagin titer ≥1:16 concurrent with their HIV diagnosis. We had HIV transmission risk data for 54%; 43% identified as men who have sex with men (MSM). Phylogenetic analysis demonstrated 123 patients (13%) grouped into 26 clusters, the largest having 20 members. In multivariable regression, age <25, black race, MSM status, male gender, higher HIV viral load, and rapid plasma reagin ≥1:16 associated with clustering. We did not observe geographic grouping of genetically clustered patients. DISCUSSION: Our results demonstrate high rates of HIV transmission clustering, without local geographic foci, among young black MSM in Chicago. Applied prospectively, phylogenetic analyses could guide prevention efforts and help break the cycle of transmission.

Scaling up routine HIV testing at specialty clinics: assessing the effectiveness of an academic detailing approach.

INTRODUCTION: Scaling up routine HIV testing represents a key component of the National HIV/AIDS Strategy. Barriers to routine HIV testing have limited widespread adoption. Although many patients visit specialty care providers, few efforts to increase routine HIV testing in specialty care settings have been made. We report on use of a survey of barriers to routine testing coupled with academic detailing-type educational sessions to increase routine testing at specialty clinics in Chicago's main safety-net health system. METHODS: We devised a survey to assess specialty provider knowledge, attitudes, and barriers to routine HIV testing. We administered this at 3 specialty clinics. Each clinic's survey responses informed content for academic detailing-type presentations to each clinic's medical providers. We provide descriptive statistics summarizing survey responses. We report changes in the HIV testing rates and use logistic regression to examine associations between time period and odds of testing at each clinic. RESULTS: Specialty clinic providers demonstrated varying knowledge regarding routine HIV testing guidelines-with trauma providers having the least knowledge. Concerns regarding arranging follow-up for patients with positive results was the most cited barrier to testing. Two of the 3 specialty clinics experienced significant increases in routine HIV testing, whereas the third specialty service, which uses more rotating residents, had downtrending routine testing rates. DISCUSSION: The increase in routine HIV testing in 2 of 3 specialty services suggests that academic detailing-type interventions can improve routine testing uptake in public safety-net specialty care settings and may represent a useful component to incorporate into system-wide scale-up efforts.

Reliability at the lower limits of HIV-1 RNA quantification in clinical samples: a comparison of RT-PCR versus bDNA assays.

INTRODUCTION: To explore whether an assay change was responsible for an increasing proportion of patients with undetectable HIV viral loads at our urban HIV clinic, we selected highly stable patients, examining their viral loads before and after changing assays. We compared the proportion with detectable viremia during RT-PCR vs. bDNA periods. METHODOLOGY/PRINCIPAL FINDINGS: We selected patients with > or =1 viral loads assessed during both RT-PCR and bDNA periods. We included patients with stable CD4 counts, excluding patients with viral loads > or =1,000 copies/ml or any significant changes in therapy. Out of 4500 clinic patients, 419 patients (1588 viral loads) were included. 39% of viral loads were reported as detectable by RT-PCR vs. 5% reported as detectable by bDNA. The mean coefficient of variation was higher before vs. after assay change. We found an odds' ratio of 16.7 for having a viral load >75 copies/ml during the RT-PCR vs. bDNA periods. DISCUSSION: These data support previous reports, suggesting that bDNA may more reliably discriminate between viral suppression and low level viremia in stable patients on therapy. Low-level viremia, noted more with RT-PCR, may promote unneeded testing, while differences in viral load reliability may impact antiretroviral trial and quality assurance endpoints. Commonly used plasma separator tubes may differentially affect RT-PCR and bDNA results.