Integrative analysis of blood transcriptome profiles in small-cell lung cancer patients for identification of novel chemotherapy resistance-related biomarkers.

Introduction: Chemoresistance constitutes a prevalent factor that significantly impacts thesurvival of patients undergoing treatment for smal-cell lung cancer (SCLC). Chemotherapy resistance in SCLC patients is generally classified as primary or acquired resistance, each governedby distinct mechanisms that remain inadequately researched. Methods: In this study, we performed transcriptome screening of peripheral blood plasma obtainedfrom 17 patients before and after receiving combined etoposide and platinum treatment. We firs testimated pseudo-single-cell analysis using xCell and ESTIMATE and identified differentially expressed genes (DEGs), then performed network analysis to discover key hub genes involved in chemotherapy resistance. Results: Our analysis showed a significant increase in class-switched memory B cell scores acrossboth chemotherapy resistance patterns, indicating their potential crucial role in mediatingresistance. Moreover, network analysis identifed PRICKLE3, TNFSFI0, ACSLl and EP300 as potential contributors to primary resistance, with SNWl, SENP2 and SMNDCl emerging assignificant factors in acquired resistance, providing valuable insights into chemotherapy resistancein SCLC. Discussion: These findings offer valuable insights for understanding chemotherapy resistance and related gene signatures in SCLC, which could help further biological validation studies.

New insights into azelaic acid-induced resistance against Alternaria Solani in tomato plants.

BACKGROUND: The effect of azelaic acid (Aza) on the response of tomato plants to Alternaria solani was investigated in this study. After being treated with Aza, tomato plants were infected with A. solani, and their antioxidant, biochemical, and molecular responses were analyzed. RESULTS: The results demonstrated that H2O2 and MDA accumulation increased in control plants after pathogen infection. Aza-treated plants exhibited a remarkable rise in peroxidase (POD) and catalase (CAT) activities during the initial stages of A. solani infection. Gene expression analysis revealed that both Aza treatment and pathogen infection altered the expression patterns of the SlNPR1, SlERF2, SlPR1, and SlPDF1.2 genes. The expression of SlPDF1.2, a marker gene for the jasmonic acid/ethylene (JA/ET) signaling pathway, showed a remarkable increase of 4.2-fold upon pathogen infection. In contrast, for the SlNPR1, a key gene in salicylic acid (SA) pathway, this increased expression was recorded with a delay at 96 hpi. Also, the phytohormone analysis showed significantly increased SA accumulation in plant tissues with disease development. It was also revealed that tissue accumulation of JA in Aza-treated plants was increased following pathogen infection, while it was not increased in plants without pathogen inoculation. CONCLUSION: The results suggest that the resistance induced by Aza is mainly a result of modulations in both SA and JA pathways following complex antioxidant and molecular defense responses in tomato plants during A. solani infection. These findings provide novel information regarding inducing mechanisms of azelaic acid which would add to the current body of knowledge of SAR induction in plants as result of Aza application.

Transformation of epidermal growth factor receptor mutated lung adenocarcinoma to small-cell carcinoma long after the cessation of tyrosine kinase inhibitor treatment: A case series and literature review.

Histological transformation to small-cell lung cancer (SCLC) is a well-known mechanism of acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), and almost all patients receive EGFR-TKIs at the time of transformation. We herein report three cases of EGFR-mutated lung adenocarcinoma that transformed into SCLC long after the cessation of EGFR-TKIs. Rapid tumor progression and elevated SCLC marker levels were observed at the time of transformation. Our case highlights the importance of considering SCLC transformation throughout the clinical course. Careful observation of the tumor behavior and SCLC markers should be performed to avoid diagnostic delays.

Drug resistance in human cancers - Mechanisms and implications.

Cancers have complex etiology and pose a significant impact from the health care perspective apart from the socio-economic implications. The enormity of challenge posed by cancers can be understood from the fact that clinical trials for cancer therapy has yielded minimum potential promises compared to those obtained for other diseases. Surgery, chemotherapy and radiotherapy continue to be the mainstay therapeutic options for cancers. Among the challenges posed by these options, induced resistance to chemotherapeutic drugs is probably the most significant contributor for poor prognosis and ineffectiveness of the therapy. Drug resistance is a property exhibited by almost all cancer types including carcinomas, leukemias, myelomas, sarcomas and lymphomas. The mechanisms by which drug resistance is induced include the factors within the tumor microenvironment, mutations in the genes responsible for drug metabolism, changes in the surface drug receptors and increased drug efflux. We present here comprehensively the drug resistance in cancers along with their mechanisms. Also, apart from resistance to regularly used chemotherapeutic drugs, we present resistance induction to new generation therapeutic agents such as monoclonal antibodies. Finally, we have discussed the experimental approaches to understand the mechanisms underlying induction of drug resistance and potential ways to mitigate induced drug resistance.

Molecular, biological characterization and drug sensitivity of chidamide-resistant MCF7 cells.

Background: Chidamide (CHI) is a subtype-selective histone deacetylase inhibitor (HDACI) developed in China and approved as a second-line treatment combined with the aromatase inhibitor for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. However, drug resistance is commonly occurred after a long period of medication. This study aimed to investigate the characterization of induced resistance to CHI and explore the potential cross-resistance to chemotherapeutic agents. Methods: CHI with gradually increasing concentrations was added to breast cancer MCF7 cells to establish a CHI-resistant MCF7 (MCF7-CHI-R) cell line. Cell counting kit-8 (CCK-8) assays were performed to detect half-maximal inhibitory concentration (IC50) of CHI. Colony formation was used to determine the proliferation inhibition rate. Western blot analysis was conducted to detect expressions of protein related with cell cycle, apoptosis, ferroptosis, and histone deacetylase (HDAC). Flow cytometry was used to analyze apoptosis and cell cycle. Results: The IC50 value of CHI of MCF7-CHI-R cells was increased in comparison with MCF7 cells. And CHI led to cell cycle arrest and ferroptosis, which were not exhibited in MCF7-CHI-R cells. Moreover, HDAC activity decreased in MCF7-CHI-R cells in comparison with MCF7 cells, and HDAC1 and HDAC10 might be involved in the resistance to CHI. In addition, MCF7-CHI-R cells were resistant to gemcitabine (GEM), doxorubicin (ADM), docetaxel (DXT), albumin-bound paclitaxel (nab-PTX) and paclitaxel (PTX). Conclusions: The MCF7-CHI-R was established and the anti-ferroptosis pathway activation was involved in the resistance of MCF-CHI-R cells. Also, MCF7-CHI-R cells were resistant to GEM, ADM, DXT, nab-PTX and PTX.

Pathways and targeting avenues of BRAF in non-small cell lung cancer.

INTRODUCTION: BRAF is a serine-threonine kinase implicated in the regulation of MAPK signaling cascade. BRAF mutation-driven activation occurs in approximately 2-4% of treatment-naive non-small cell carcinomas (NSCLCs). BRAF upregulation is also often observed in tumors with acquired resistance to receptor tyrosine kinase inhibitors (TKIs). AREAS COVERED: This review describes the spectrum of BRAF mutations and their functional roles, discusses treatment options available for BRAF p.V600 and non-V600 mutated NSCLCs, and identifies some gaps in the current knowledge. EXPERT OPINION: Administration of combined BRAF/MEK inhibitors usually produces significant, although often a short-term, benefit to NSCLC patients with BRAF V600 (class 1) mutations. There are no established treatments for BRAF class 2 (L597, K601, G464, G469A/V/R/S, fusions, etc.) and class 3 (D594, G596, G466, etc.) mutants, which account for up to two-thirds of BRAF-driven NSCLCs. Many important issues related to the use of immune therapy for the management of BRAF-mutated NSCLC deserve further investigation. The rare occurrence of BRAF mutations in NSCLC is compensated by high overall incidence of lung cancer disease; therefore, clinical studies on BRAF-associated NSCLC are feasible.

Molecular insights into PGPR fluorescent Pseudomonads complex mediated intercellular and interkingdom signal transduction mechanisms in promoting plant's immunity.

The growth-promoting and immune modulatory properties of different strains of plant growth promoting rhizobacteria (PGPR) fluorescent Pseudomonads complex (PFPC) can be explored to combat food security challenges. These PFPC prime plants through induced systemic resistance, fortify plants to overcome future pathogen-mediated vulnerability by eliciting robust systemic acquired resistance through regulation by nonexpressor of pathogenesis-related genes 1. Moreover, outer membrane vesicles released from Pseudomonas fluorescens also elicit a broad spectrum of immune responses, presenting a rapid viable alternative to whole cells. Thus, PFPC can help the host to maintain an equilibrium between growth and immunity, ultimately leads to increased crop yield.

Salinity stress alters plant-mediated interactions between above- and below-ground herbivores.

Below-ground herbivory impacts plant development and often induces systemic responses in plants that affect the performance and feeding behavior of above-ground herbivores. Meanwhile, pest-damaged root tissue can enhance a plant's susceptibility to abiotic stress such as salinity. Yet, the extent to which herbivore-induced plant defenses are modulated by such abiotic stress has rarely been studied. In this study, we examine whether root feeding by larvae of the turnip moth, Agrotis segetum (Lepidoptera: Noctuidae) affects the performance of the above-ground, sap-feeding aphid Aphis gossypii (Hemiptera: Aphididae) on cotton, and assess whether those interactions are modulated by salinity stress. In the absence of salinity stress, A. segetum root feeding does not affect A. gossypii development. On the other hand, under intense salinity stress (i.e., 600 mM NaCl), A. segetum root feeding decreases aphid development time by 16.1 % and enhances fecundity by 72.0 %. Transcriptome, metabolome and bioassay trials showed that root feeding and salinity stress jointly trigger the biosynthesis of amino acids in cotton leaves. Specifically, increased titers of valine in leaf tissue relate to an enhanced performance of A. gossypii. Taken together, salinity stress alters the interaction between above- and below-ground feeders by changing amino acid accumulation. Our findings advance our understanding of how plants cope with concurrent biotic and abiotic stressors, and may help tailor plant protection strategies to varying production contexts.

Adaptive resistance of tumor cells to anti-vascular endothelial growth factor therapy: A reversible phenomenon.

Vascular endothelial growth factor (VEGF) inhibition is an essential targeted strategy for malignant tumors, but its efficacy is severely constrained by drug resistance. The traditional view holds that the target of VEGF inhibition is endothelial cells, and thus compensatory angiogenesis is considered the main mechanism of drug resistance. In this study, we found that tumor cells themselves could develop acquired resistance to VEGF therapy, indicating an independent resistance mechanism apart from angiogenesis. Notably, this acquired resistance was temporary, disappearing completely four days after discontinuing exposure to the drug in vitro. Our findings suggest that tumor cells may also be targets of VEGF inhibition, and their response to treatment should not be overlooked in contributing to drug resistance.

Nano- and Microplastics Increase the Occurrence of Bacterial Wilt in Tomato (Solanum lycopersicum L.).

Concern over nano- and microplastic contamination of terrestrial ecosystems has been increasing. However, little is known about the effect of nano- and microplastics on the response of terrestrial ecosystems already under biotic stress. Here, nano- and microplastics at 150-500 mg·kg-1 were exposed to tomatoes (Solanum lycopersicum L.), and the results demonstrate that the presence of nano- and microplastics increased the occurrence of bacterial wilt caused by Ralstonia solanacearum in tomatoes as a function of contaminant concentration, surface modification, and size. Our work shows that nanoplastics (30 nm, 250 mg·kg-1) increased the disease incidence by 2.19-fold. The disease severities in amino- and carboxyl-modified nanoplastic treatments were 30.4 and 21.7% higher than that in unmodified nanoplastic treatment, respectively. The severity of disease under the influence of different-sized nano- and microplastic treatments followed the order 30 > 100 nm > 1 > 50 µm. Mechanistically, nanoplastics disrupted the structure of the tomato rhizosphere soil bacterial community and suppressed the induced systemic resistance in tomato; nanoplastics in planta decreased the salicylic acid and jasmonic acid content in tomatoes, thus inhibiting systemic acquired resistance; and microplastics increased the soil water retention, leading to increased pathogen abundance in the rhizosphere. Additionally, the leachates from nano- and microplastics had no effect on disease occurrence or the growth of tomatoes. Our findings highlight a potential risk of nano- and microplastic contamination to agriculture sustainability and food security.

Structural perspectives on recent breakthrough efforts toward direct drugging of RAS and acquired resistance.

The Kirsten rat sarcoma viral oncoprotein homolog (KRAS) is currently a primary focus of oncologists and translational scientists, driven by exciting results with KRAS-targeted therapies for non-small cell lung cancer (NSCLC) patients. While KRAS mutations continue to drive high cancer diagnosis and death, researchers have developed unique strategies to target KRAS variations. Having been investigated over the past 40 years and considered "undruggable" due to the lack of pharmacological binding pockets, recent breakthroughs and accelerated FDA approval of the first covalent inhibitors targeting KRASG12C, have largely sparked further drug development. Small molecule development has targeted the previously identified primary location alterations such as G12, G13, Q61, and expanded to address the emerging secondary mutations and acquired resistance. Of interest, the non-covalent KRASG12D targeting inhibitor MRTX-1133 has shown promising results in humanized pancreatic cancer mouse models and is seemingly making its way from bench to bedside. While this manuscript was under review a novel class of first covalent inhibitors specific for G12D was published, These so-called malolactones can crosslink both GDP and GTP bound forms of G12D. Inhibition of the latter state suppressed downstream signaling and cancer cell proliferation in vitro and in mouse xenografts. Moreover, a non-covalent pan-KRAS inhibitor, BI-2865, reduced tumor proliferation in cell lines and mouse models. Finally, the next generation of KRAS mutant-specific and pan-RAS tri-complex inhibitors have revolutionized RAS drug discovery. This review will give a structural biology perspective on the current generation of KRAS inhibitors through the lens of emerging secondary mutations and acquired resistance.

ALK inhibitors in cancer: mechanisms of resistance and therapeutic management strategies.

Anaplastic lymphoma kinase (ALK) gene rearrangements have been identified as potent oncogenic drivers in several malignancies, including non-small cell lung cancer (NSCLC). The discovery of ALK inhibition using a tyrosine kinase inhibitor (TKI) has dramatically improved the outcomes of patients with ALK-mutated NSCLC. However, the emergence of intrinsic and acquired resistance inevitably occurs with ALK TKI use. This review describes the molecular mechanisms of ALK TKI resistance and discusses management strategies to overcome therapeutic resistance.

Genetic Mutations in FKS1 Gene Associated with Acquired Echinocandin Resistance in Candida parapsilosis Complex.

Candida parapsilosis complex has recently received special attention due to naturally occurring FKS1 polymorphism associated with high minimal inhibitory concentrations for echinocandin and the increase of clonal outbreaks of strains resistant to commonly used antifungals such as fluconazole. Despite the previous fact, little is known about the genetic mechanism associated with echinocandin resistance. Therefore, the present study was designed to investigate the mechanism of acquired echinocandin resistance in C. parapsilosis complex strains. A total of 15 clinical C. parapsilosis complex isolates were sub-cultured for 30 days at a low concentration of micafungin at ½ the lowest MIC value of the tested isolates (0.12 µg/ml). After culturing, all the isolates were checked phenotypically for antifungal resistance and genotypically for echinocandin resistance by checking FKS1 gene hot spot one (HS1) and HS2 mutations. In vitro induction of echinocandin resistance confirmed the rapid development of resistance at low concentration micafungin, with no difference among C. parapsilosis, C. metapsilosis, and C. orthopsilosis in the resistance development. For the first time we identified different FKS1 HS1 and or HS2 mutations responsible for echinocandin resistance such as R658S and L1376F in C. parapsilosis, S656X, R658X, R658T, W1370X, X1371I, V1371X, and R1373X (corresponding to their location in C. parapsilosis) in C. metapsilosis, and L648F and R1366H in C. orthopsilosis. Our results are of significant concern, since the rapid development of resistance may occur clinically after short-term exposure to antifungals as recently described in other fungal species with the potential of untreatable infections.

Acquired bedaquiline and fluoroquinolones resistance during treatment follow-up in Oromia Region, North Shewa, Ethiopia.

Background: Bedaquiline (BDQ) is an effective drug currently used for multidrug-resistant or rifampicin-resistant TB (MDR/RR-TB) and pre-extensively drug-resistant TB (pre-XDR-TB) treatment. However, resistance to this new drug is emerging. We discussed the characteristics of the first patient in Ethiopia who acquired BDQ and fluoroquinolones (FQs) resistance during treatment follow-up. Case report: In this case report, we present the case of a 28-year-old male pulmonary TB patient diagnosed with MDR-TB who is a resident of the Oromia Region of North Shewa, Mulona Sululta Woreda, Ethiopia. Sputum specimen was collected initially and for treatment monitoring using culture and for phenotypic drug susceptibility testing (DST) to first-line and second-line TB drugs. Initially, the patient was infected with a mycobacterial strain resistant to the first-line anti-TB drugs Rifampicin (RIF), Isoniazid (INH), and Pyrazinamide (PZA). Later, during treatment, he acquired additional drug resistance to ethambutol (EMB), ofloxacin (OFX), levofloxacin (LFX), moxifloxacin (MFX), and BDQ. The patient was tested with MTBDRplus and MTBDRsl to confirm the presence of resistance-conferring mutation and mutation was detected in rpoB, katG, and gyrA genes. Finally, the patient was registered as having extensively drug-resistant tuberculosis (XDR-TB) and immediately started an individualized treatment regimen. Conclusion: This case report data has revealed the evolution of BDQ resistance during treatment with a BDQ-containing regimen in Ethiopia. Therefore, there is a need for DST to new second-line drugs to monitor and prevent the spread of DR-TB.

Clinical approach and utilizing liquid biopsies to interrogate suspected acquired resistance to PD-1 blockade.

PD-1 blockade is now routine for nearly all patients with non-small lung cancer. Acquired resistance to PD-1 blockade - defined generally as an initial response followed later by progression [1-3] is a common yet poorly understood concept. A key clinical challenge to insight has been a lack of standard guidance for clinical management of a case of suspected acquired resistance. The infrequency of performing tumor biopsies and the uncertainty of actionability from tissue sampling likely also contribute to limited insight into the biology of acquired resistance [4]. To address this knowledge gap and to highlight the value of tumor and liquid biopsy, we present a representative case of suspected acquired resistance to PD-1 blockade and propose a multi-modal guide for approaching this clinical scenario.

T790M mutation sensitizes non-small cell lung cancer cells to radiation via suppressing SPOCK1.

Background: Approximately 50% of patients harbor the T790M mutation after developing first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance. Evidence has showed the major treatment failure is local relapses and limited metastases. Several studies have demonstrated the value of radiotherapy in metastatic non-small cell lung cancer (NSCLC) with the EGFR T790M mutation after the development of TKI resistance. The aim of this study was to explore the role of radiation in T790M-mutant NSCLC and the value of early radiotherapy for NSCLC with T790M-mediated EGFR-TKI resistance. Methods: Gefitinib-resistant NSCLC cell lines were established via stepwise exposure to increasing concentrations of gefitinib (PC-9-GR). Droplet digital PCR was used to determine the relative T790M subclone abundance. In vitro and in vivo models were established using different mixtures of PC-9-GR and PC-9 cells. Differentially expressed genes were identified using RNA sequencing. Two research models were constructed (salvage and prophylactic radiotherapy) to determine the effects of early radiotherapy on gefitinib-resistant cells. Results: PC-9-GR cells exhibited higher radiosensitivity than PC-9 cells (sensitivity enhancement ratio = 1.5). Salvage radiation reduced the number of T790M-mutant subclones, and the relative T790M abundance was significantly lower than that without radiation at 90 days (10.94% vs. 21.54%). Prophylactic radiation prevented the development of T790M subclones. These results were also confirmed in vivo. qRT-PCR revealed threefold elevation of miR-1243 in PC-9-GR cells, and the increased radiosensitivity of PC-9-GR cells was inhibited when miR-1243 was knocked down. RNA sequencing revealed that SPOCK1 was downregulated in PC-9-GR cells. Interestingly, bioinformatic analysis showed that SPOCK1 was a target gene of miR-1243. SPOCK1 knockdown markedly increased the radiosensitivity of PC-9 cells. Conclusion: Gefitinib-resistant NSCLC with the T790M mutation had higher radiosensitivity than that without the mutation, possibly mediated by SPOCK1. Early radiotherapy can eliminate T790M subclones, providing evidence for the benefit of early local treatment in patients with TKI-resistant NSCLC.

Unveiling acquired resistance to anti-EGFR therapies in colorectal cancer: a long and winding road.

Emergence of acquired resistance limits the efficacy of the anti-EGFR therapies cetuximab and panitumumab in metastatic colorectal cancer. In the last decade, preclinical and clinical cohort studies have uncovered genomic alterations that confer a selective advantage to tumor cells under EGFR blockade, mainly downstream re-activation of RAS-MEK signaling and mutations in the extracellular domain of EGFR (EGFR-ECD). Liquid biopsies (genotyping of ctDNA) have been established as an excellent tool to easily monitor the dynamics of genomic alterations resistance in the blood of patients and to select patients for rechallenge with anti-EGFR therapies. Accordingly, several clinical trials have shown clinical benefit of rechallenge with anti-EGFR therapy in genomically-selected patients using ctDNA. However, alternative mechanisms underpinning resistance beyond genomics -mainly related to the tumor microenvironment-have been unveiled, specifically relevant in patients receiving chemotherapy-based multi-drug treatment in first line. This review explores the complexity of the multifaceted mechanisms that mediate secondary resistance to anti-EGFR therapies and potential therapeutic strategies to circumvent acquired resistance.

Redox signaling and oxidative stress in systemic acquired resistance.

Plants fully depend on their immune systems to defend against pathogens. Upon pathogen attack, plants not only activate immune responses at the infection site but also trigger a defense mechanism known as systemic acquired resistance (SAR) in distal systemic tissues to prevent subsequent infections by a broad-spectrum of pathogens. SAR is induced by mobile signals produced at the infection site. Accumulating evidence suggests that reactive oxygen species (ROS) play a central role in SAR signaling. ROS burst at the infection site is one of the earliest cellular responses following pathogen infection and can spread to systemic tissues through membrane-associated NADPH oxidase-dependent relay-production of ROS. It is well known that ROS ignite redox signaling and when in excess, cause oxidative stress damaging cellular components. In this review, we summarize current knowledge on redox regulation of several SAR signaling components. We discuss the ROS amplification loop in systemic tissues involving multiple SAR mobile signals. Moreover, we highlight the essential role of oxidative stress in generating SAR signals including azelaic acid and extracellular NAD(P) [eNAD(P)]. Finally, we propose that eNAD(P) is a damage-associated molecular pattern serving as a converging point of SAR mobile signals in systemic tissues.

Case report: Acquired resistance to crizotinib from a MET Y1230H mutation in a patient with non-small cell lung cancer and KIF5B-MET fusion.

Background: The c-met proto-oncogene (MET) serves as a significant primary oncogenic driver in non-small cell lung cancer (NSCLC) and has the potential to fuse with other genes, such as KIF5B, although it occurs infrequently. Only a limited number of reported cases have examined the clinical efficacy of crizotinib in patients with KIF5B-MET gene fusion, with no known data regarding acquired resistance to crizotinib and its potential mechanisms. In this report, we present the clinical progression of a female patient diagnosed with NSCLC and harboring a KIF5B-MET gene fusion. Case description: The patient initially exhibited partial response to first-line crizotinib treatment, albeit for a short duration and with limited efficacy. Subsequent disease progression revealed the emergence of a secondary MET mutation, specifically MET Y1230H, leading to acquired resistance to crizotinib. Conclusion: The reporting of this case is imperative for informing clinical practice, given the uncommon occurrence of NSCLC with MET fusion, displaying responsiveness to MET tyrosine kinase inhibitor therapy, as well as the emergence of the secondary Y1230H alteration as a potential resistance mechanism.

Acquired rifamycin resistance among patients with tuberculosis and HIV in new York City, 2001-2023.

Introduction: Acquired rifamycin resistance (ARR) in tuberculosis (TB) has been associated with HIV infection and can necessitate complicated TB treatment regimens, particularly in people living with HIV (PLWH). This work examines clinical characteristics and treatment outcomes of PLWH who developed ARR from 2001 to 2023 in New York City (NYC) to inform best practices for treating these patients. Methods: PLWH who developed ARR 2001-2023 were identified from the NYC TB registry. Results: Sixteen PLWH developed ARR; 15 were diagnosed 2001-2009 and the 16th was diagnosed in 2017. Median CD4 count was 48/mm3. On initial presentation, 14 had positive sputum cultures; of these, 12 culture-converted prior to developing ARR. Ten patients completed a course of TB treatment but subsequently relapsed; in six of these cases, ARR was discovered upon relapse, triggering treatment with a non-rifamycin-containing regimen, while in the other four, ARR was discovered during a second round of rifamycin-containing treatment. Three patients were lost to follow-up during their initial course of TB treatment and later returned to care; after being restarted on a rifamycin-containing regimen, ARR was discovered. Finally, three patients culture-converted during their first course of treatment but subsequently had cultures that grew rifamycin-resistant Mycobacterium tuberculosis prior to treatment completion, leading to changes in their treatment regimens. Among the 16 patients, eight died before being cured of TB, seven successfully completed treatment, and one was lost to follow-up. Conclusions: PLWH should be monitored closely for the development of ARR during treatment for TB, and sputum culture conversion should be interpreted cautiously in this group. Collecting a final sputum sample may be especially important for PLWH, as treatment failure and relapse were common in this population. The decrease in the number of cases of ARR among PLWH during the study period may reflect the decrease in the total number of PLWH diagnosed with TB in NYC in recent years, improved immune status of PLWH due to increased uptake of antiretroviral drugs, and improvements in the way anti-TB regimens are designed for PLWH (such as recommending daily rather than intermittent rifamycin dosing).