John D. Szumowski

Although paradoxical tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS) in HIV-TB coinfection is typically thought of as occurring within several months of starting antiretroviral therapy, more prolonged manifestations have been reported. We describe 2 cases in which manifestations of TB-IRIS continued for longer than 1 year after the end of TB treatment and review the literature on prolonged TB-IRIS. These cases are often characterized by a history of extrapulmonary TB and initially low CD4 counts and commonly demonstrate lymphadenitis or abscesses. In the absence of clear consensus around its appropriate management, prolonged TB-IRIS presents a significant diagnostic and therapeutic dilemma.

Linezolid is recommended for the treatment of rifampin-resistant tuberculosis (TB), but its role in rifampin-susceptible TB (RS-TB) is less understood. In 45 RS-TB patients treated with linezolid, 8 stopped due to adverse events, most commonly cytopenias. Further research is needed on linezolid efficacy, dosing, and adverse event management in RS-TB.

Background: Targeted immunotherapies have transformed the treatment of many diseases. However, some increase the risk of tuberculosis (TB) disease. We sought to develop a comprehensive list of targeted immunotherapies with TB infection screening recommendations in US Food and Drug Administration (FDA)-approved prescribing information and compare these recommendations to clinical resources and quality measures. Methods: Through a gray literature review, we identified TB clinical resources and US quality measures. We created a list of targeted immunotherapies and TB infection screening recommendations by analyzing 4 FDA databases. We then evaluated the consistency of screening recommendations in prescribing information, TB clinical resources, and quality measures. Results: We identified 6 TB clinical resources and 1 quality measure for TB infection. While TB infection screening recommendations for tumor necrosis factor (TNF) inhibitors were consistently included, recommendations for other therapies were less consistent. Through FDA database analyses, we identified 269 targeted immunotherapies, 35 (13%) of which had TB infection screening recommendations in prescribing information, including all therapies targeting TNF and several interleukins (IL); however, therapies targeting IL-6, Janus-associated kinase, and others had variable recommendations. Significant discordance in screening recommendations for immunotherapies was further identified when comparing prescribing information, clinical resources, and quality measures. Conclusions: The number and targets of immunotherapies are rapidly evolving resulting in challenges with creating up-to-date and consistent TB infection screening recommendations. Inconsistent recommendations in clinical resources may contribute to gaps in TB preventive care. Harmonized recommendations and additional epidemiologic studies of TB disease risk with the use of these agents are needed.

Background Targeted immunotherapies have transformed the treatment of many diseases. However, some increase the risk of tuberculosis (TB) disease. We sought to develop a comprehensive list of targeted immunotherapies with TB infection screening recommendations in U.S. Food and Drug Administration (FDA)-approved prescribing information and compare these recommendations to clinical resources and quality measures. Methods Through a grey literature review, we identified TB clinical resources and U.S. quality measures. We created a list of targeted immunotherapies and TB infection screening recommendations by analyzing four FDA databases. We then evaluated the consistency of screening recommendations in prescribing information, TB clinical resources and quality measures. Results We identified six TB clinical resources and one quality measure for TB infection. While TB infection screening recommendations for tumor necrosis factor (TNF) inhibitors were consistently included, recommendations for other therapies were less consistent. Through FDA database analyses, we identified 269 targeted immunotherapies, 35 (13%) of which had TB infection screening recommendations in prescribing information, including all therapies targeting TNF and several interleukins (IL); however, therapies targeting IL-6, Janus-associated kinase and others had variable recommendations. Significant discordance in screening recommendations for immunotherapies were further identified when comparing prescribing information, clinical resources and quality measures. Conclusions The number and targets of immunotherapies are rapidly evolving resulting in challenges with creating, up-to-date and consistent TB infection screening recommendations. Inconsistent recommendations in clinical resources may contribute to gaps in TB preventive care. Harmonized recommendations and additional epidemiologic studies of TB disease risk with the use of these agents are needed. Article summary Targeted immunotherapies are increasing in number and complexity but may increase tuberculosis risk, highlighting the challenge of creating tuberculosis infection screening recommendations. We systematically identified these therapies and compared screening recommendations in prescribing information, clinical resources and quality measures.

Background: We previously demonstrated at the Ward 86 human immunodeficiency virus (HIV) clinic in San Francisco that long-acting (LA) cabotegravir (CAB)/rilpivirine (RPV) (LA-CAB/RPV) can rapidly lead to viral suppression in people with HIV (PWH) with viremia due to adherence challenges. We now evaluate the durability of viral suppression in this population. Methods: We conducted a retrospective cohort study of PWH who started LA-CAB/RPV with viremia (HIV RNA viral load ≥50 copies/mL) before December 2022. Our primary outcome was viral suppression (viral load 14 days) at 48 weeks, using the viral load closest to 48 ± 8 weeks. We also describe viral failure, defined as a <2-log decline in viral load at 4 weeks or a viral load ≥200 copies/mL after initial viral suppression with emergent CAB- or RPV-associated resistance mutations; overall 48-week viral suppression including those switched to alternative antiretroviral therapy (ART). Results: Fifty-nine PWH initiated LA-CAB/RPV with viremia and were included in the analysis; 49% had a CD4 cell count <200/µL, and the median baseline viral load was 42 900 copies/mL (quarter 1–quarter 3, 5272–139 038). At 48 weeks, 47 PWH met the primary outcome of viral suppression with LA-CAB/RPV persistence (80% [95% confidence interval, 67%–89%]). Five had viral failure with resistance (3 with RPV-associated and 2 with CAB- and RPV-associated mutations), and 1 was lost to follow-up. At week 48, 2 of those with viral failure were suppressed on alternative regimens (lenacapavir + bictegravir/tenofovir alafenamide/emtricitabine and CAB + lenacapavir). The overall viral suppression at week 48 with either LA-CAB/RPV or alternative ART was 92% (54 of 59). Conclusions: In PWH initiating LA-CAB/RPV with initial viremia, 48-week viral suppression (<50 copies/mL) was seen in 92%. LA ART can be an important tool for improving viral suppression among patients who face adherence challenges to oral ART.

Induction of mycobacterial efflux pumps is a cause of Mycobacterium tuberculosis (Mtb) drug tolerance, a barrier to shortening antitubercular treatment. Verapamil inhibits Mtb efflux pumps that mediate tolerance to rifampin, a cornerstone of tuberculosis (TB) treatment. Verapamil's mycobacterial efflux pump inhibition also limits Mtb growth in macrophages in the absence of antibiotic treatment. These findings suggest that verapamil could be used as an adjunctive therapy for TB treatment shortening. However, verapamil is rapidly and substantially metabolized when co‐administered with rifampin. We determined in a dose‐escalation clinical trial of persons with pulmonary TB that rifampin‐induced clearance of verapamil can be countered without toxicity by the administration of larger than usual doses of verapamil. An oral dosage of 360 mg sustained‐release (SR) verapamil given every 12 hours concomitantly with rifampin achieved median verapamil exposures of 903.1 ng.h/mL (area under the curve (AUC)_0‐12 h) in the 18 participants receiving this highest studied verapamil dose; these AUC findings are similar to those in persons receiving daily doses of 240 mg verapamil SR but not rifampin. Moreover, norverapamil:verapamil, R:S verapamil, and R:S norverapamil AUC ratios were all significantly greater than those of historical controls receiving SR verapamil in the absence of rifampin. Thus, rifampin administration favors the less‐cardioactive verapamil metabolites and enantiomers that retain similar Mtb efflux inhibitory activity to verapamil, increasing overall benefit. Finally, rifampin exposures were 50% greater after verapamil administration, which may also be advantageous. Our findings suggest that a higher dosage of verapamil can be safely used as adjunctive treatment in rifampin‐containing treatment regimens.

Intramuscular cabotegravir (CAB) and rilpivirine (RPV) is the only long-acting antiretroviral therapy (LA-ART) regimen approved for people with HIV (PWH). Long-acting ART holds promise for improving outcomes among populations with barriers to adherence but is only approved for PWH who have virologic suppression with use of oral ART before initiating injectables. To examine LA-ART in a population of PWH that includes those with viremia. Observational cohort study. Urban academic safety-net HIV clinic. Publicly insured adults living with HIV with and without viral suppression, high rates of unstable housing, mental illness, and substance use. Demonstration project of long-acting injectable CAB-RPV. Descriptive statistics summarizing cohort outcomes to date, based on pharmacy team logs and electronic medical record data. Between June 2021 and November 2022, 133 PWH at the Ward 86 HIV Clinic were started on LA-ART, 76 of whom had virologic suppression while using oral ART and 57 of whom had viremia. The median age was 46 years (IQR, 25 to 68 years); 117 (88%) were cisgender men, 83 (62%) had non-White race, 56 (42%) were experiencing unstable housing or homelessness, and 45 (34%) had substance use. Among those with virologic suppression, 100% (95% CI, 94% to 100%) maintained suppression. Among PWH with viremia, at a median of 33 days, 54 of 57 had viral suppression, 1 showed the expected 2-log₁₀ reduction in HIV RNA level, and 2 experienced early virologic failure. Overall, 97.5% (CI, 89.1% to 99.8%) were projected to achieve virologic suppression by a median of 33 weeks. The current virologic failure rate of 1.5% in the cohort is similar to that across registrational clinical trials at 48 weeks. Single-site study. This project demonstrates the ability of LA-ART to achieve virologic suppression among PWH, including those with viremia and challenges to adherence. Further data on the ability of LA-ART to achieve viral suppression in people with barriers to adherence are needed. National Institutes of Health, City and County of San Francisco, and Health Resources and Services Administration.

Lymphogranuloma venereum (LGV) has been increasingly reported, and many clinicians are familiar with it as a cause of proctocolitis or inguinal adenopathy. On the other hand, LGV is less commonly considered as a cause of isolated genital ulcerative disease in comparison to other etiologies such as syphilis or herpes simplex. We report a case of persistent perianal ulcerations due to LGV in an HIV-positive patient, confirmed by nucleic acid amplification testing.

We describe a case of a 19-year-old female presenting with Mycobacterium bovis meningitis, a rarely encountered infection. We discuss the use of pyrosequencing to aid in prompt diagnosis of M. bovis infection, as well as treatment strategies and challenges given the organism’s intrinsic resistance to pyrazinamide.