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.

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.

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.

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.