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Background: The fourth-generation (4th-gen) human immunodeficiency virus (HIV)-1/2 antibody/antigen (Ab/Ag) combination immunoassay currently used for HIV screening offers greater sensitivity than previous assays, but false-reactive results occur in up to 20% of patients. Large-scale observations in cancer patients are lacking., Methods: We conducted a retrospective study of cancer patients seen at the University of Texas MD Anderson Cancer Center (March 2016-January 2023) who had reactive 4th-gen ARCHITECT HIV-1/2 Ab/Ag combination immunoassay results. We analyzed characteristics of patients with true-reactive and false-reactive results, defined based on Centers for Disease Control and Prevention criteria., Results: A total of 43 637 patients underwent 4th-gen HIV screening, and 293 had reactive 4th-gen HIV test results. Twenty-one patients were excluded because they did not have cancer. Among the remaining 272 patients, 78 (29%) had false-reactive results. None of these patients experienced delays in their cancer treatment, but 26% experienced mental distress. Multivariate logistic regression analysis identified 5 predictors of having false-reactive results: age >60 years (adjusted odds ratio [aOR], 6.983; P < .0001), female sex (aOR, 6.060; P < .0001), race/ethnicity (Black: aOR, 0.274; Hispanic: aOR, 0.236; P = .002), syphilis coinfection (aOR, 0.046; P = .038), and plant alkaloids therapy (aOR, 2.870; P = .013)., Conclusions: False-reactive 4th-gen HIV test results occur in almost one-third of cancer patients. Physicians should be aware of the high rates of false-reactive HIV screening results in this patient population. These findings may have implications for counseling regarding testing, especially among those at low risk for HIV infection., Competing Interests: Potential conflicts of interest. H. A. T. is or has been the principal investigator for research grants from the National Cancer Institute, Gilead Sciences, and Merck & Co, Inc, with all funds paid to the University of Texas MD Anderson Cancer Center; is or has been a paid scientific advisor for AbbVie, Inc, Gilead Sciences, Janssen Pharmaceuticals, Inc, Merck & Co, Inc, and Dynavax Technologies; and reports consulting fees from AbbVie, Inc, Gilead Sciences, Janssen Pharmaceuticals, Inc, Merck & Co, Inc, and Dynavax Technologies. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Data are scarce regarding the virologic impact and safety of immune checkpoint inhibitors (ICI) in patients with chronic hepatitis C virus (HCV) infection. We examined the virologic impact of ICI in HCV-infected patients with solid tumors and their safety., Methods: HCV-infected patients with solid tumor treated with ICI at our institution between April 26, 2016, and January 5, 2022, were enrolled in a prospective observational study. The primary outcomes were ICI-induced changes in HCV viremia (HCV inhibition and HCV reactivation) and safety of ICI., Results: We enrolled 52 consecutive patients with solid tumors treated with ICI. Most were men (41; 79%), White (31; 59%), without cirrhosis (34; 65%), and with HCV genotype 1 (40; 77%). Four patients (7.7%) experienced HCV inhibition while receiving ICI including 1 patient who developed undetectable viremia for 6 months in the absence of direct-acting antivirals (DAA). Two patients (4%) developed HCV reactivation, both while receiving immunosuppressive therapy for ICI-related toxic effects. Adverse events occurred in 36 patients (69%), and 39 of the 47 adverse events (83%) were grade 1-2. Grade 3-4 adverse events occurred in 8 patients (15%), and in all cases, they were related to ICI, not to HCV. No HCV-associated liver failure or death occurred., Discussion: Inhibition of HCV replication with virologic cure can develop in patients receiving ICI without DAA. HCV reactivation occurs primarily in patients receiving immunosuppressants for ICI-related toxic effects. ICI are safe in HCV-infected patients with solid tumors. Chronic HCV infection should not be considered a contraindication for ICI therapy., (Copyright © 2023 by The American College of Gastroenterology.)

Background: Despite the clinical benefit of immune checkpoint inhibitors (ICIs), patients with a viral hepatitis have been excluded from clinical trials because of safety concerns. The purpose of this study was to determine the incidence rate of adverse events (AEs) in patients with viral hepatitis who received ICIs for cancer treatment., Materials and Methods: We conducted a retrospective study in patients with cancer and concurrent hepatitis B or C, who had undergone treatment with ICI at MD Anderson Cancer Center from January 1, 2010 to December 31, 2019., Results: Of the 1076 patients screened, we identified 33 with concurrent hepatitis. All 10 patients with HBV underwent concomitant antiviral therapy during ICI treatment. Sixteen of the 23 patients with HCV received it before the initiation of ICI. The median follow-up time was 33 months (95% CI, 23-45) and the median duration of ICI therapy was 3 months (IQR, 1.9-6.6). Of the 33 patients, 12 (39%) experienced irAEs (immune-related adverse events) of any grade, with 2 (6%) having grade 3 or higher. None of the patients developed hepatitis toxicities., Conclusion: ICIs may be a therapeutic option with an acceptable safety profile in patients with cancer and advanced liver disease., (© The Author(s) 2023. Published by Oxford University Press.)

Background: In this international multicenter study, we aimed to determine the independent risk factors associated with increased 30 day mortality and the impact of cancer and novel treatment modalities in a large group of patients with and without cancer with COVID-19 from multiple countries., Methods: We retrospectively collected de-identified data on a cohort of patients with and without cancer diagnosed with COVID-19 between January and November 2020 from 16 international centers., Results: We analyzed 3966 COVID-19 confirmed patients, 1115 with cancer and 2851 without cancer patients. Patients with cancer were more likely to be pancytopenic and have a smoking history, pulmonary disorders, hypertension, diabetes mellitus, and corticosteroid use in the preceding 2 wk (p≤0.01). In addition, they were more likely to present with higher inflammatory biomarkers (D-dimer, ferritin, and procalcitonin) but were less likely to present with clinical symptoms (p≤0.01). By country-adjusted multivariable logistic regression analyses, cancer was not found to be an independent risk factor for 30 day mortality (p=0.18), whereas lymphopenia was independently associated with increased mortality in all patients and in patients with cancer. Older age (≥65y) was the strongest predictor of 30 day mortality in all patients (OR = 4.47, p<0.0001). Remdesivir was the only therapeutic agent independently associated with decreased 30 day mortality (OR = 0.64, p=0.036). Among patients on low-flow oxygen at admission, patients who received remdesivir had a lower 30 day mortality rate than those who did not (5.9 vs 17.6%; p=0.03)., Conclusions: Increased 30 day all-cause mortality from COVID-19 was not independently associated with cancer but was independently associated with lymphopenia often observed in hematolgic malignancy. Remdesivir, particularly in patients with cancer receiving low-flow oxygen, can reduce 30 day all-cause mortality., Funding: National Cancer Institute and National Institutes of Health., Competing Interests: IR, RH, NM, TD, HD, YJ, VS, BS, AB, RS, AF, EG, AB, NM, NH, SS, TD, YV, SF, AP, RC, VM, JA, JB, FK, BG, TJ, EY, HT, NA, MY, CR, MP, NA, RR, SA, RD, PC, TM, KI, RH, RA, AG, CP, DL, MS, BT, CA, DK, AM, AC No competing interests declared, (© 2023, Raad, Hachem et al.)

Hepatitis E virus (HEV) infection in immunocompetent patients can lead to chronic hepatitis and liver failure. However, the burden of HEV infection in cancer patients is largely unknown. We studied the characteristics of HEV infection in patients at a tertiary care cancer center in the United States. This retrospective study included adult cancer patients with HEV infection diagnosed between September 2011 to September 2021. A total of 405 patients were tested for HEV, and 63 (16%) had detectable HEV IgG. Thirty-three patients (52%) were male, 43 were born in America (68%), 46 (73%) were screened for HEV because of pre-existing liver conditions, and 22 (35%) had hematological malignancies. Only 2 patients had detectable HEV RNA. The first patient had myelodysplastic syndrome and underwent allogeneic stem cell transplantation (HSCT). He developed elevated liver enzymes with HEV RNA 14,000 IU/mL (4.2 log IU/mL) 13 months after HSCT. After reducing immunosuppression, his HEV viremia resolved. The second patient had diffuse large B-cell lymphoma and underwent anti-CD19 chimeric antigen receptor (CAR) T-cell therapy. She had elevated liver enzymes with HEV RNA 4,560,000 IU/mL (6.7 log IU/mL) 12 months after CAR T-cell therapy. She developed chronic HEV infection, and ribavirin treatment failed. Now she is being considered for salvage treatment with peginterferon alfa-2a and ribavirin. This study is the first report of chronic HEV infection in patients who received CAR T-cell therapy. HEV infection in cancer patients appears to be at least as common as in the general population. Cancer patients with hematologic malignancies may be at risk for HEV viremia and chronic infection refractory to antiviral treatment., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Limited data are available on the use of CD4+ T-cell count and percentage to predict response to direct-acting antiviral (DAA) treatment outside the hepatitis C virus (HCV)-HIV coinfected population. We sought to determine the impact of CD4+ T-cell count and percentage on response to DAAs in cancer patients with HCV monoinfection. Patients treated with DAAs were enrolled in a prospective observational study. CD4+ T-cell count and percentage was measured at baseline, end of treatment (EOT), and 12 weeks after the EOT (SVR12). A total of 174 patients were enrolled. Most patients (155/174, 89%) achieved an SVR12. A multivariate logistic regression model found that patients with hepatocellular carcinoma, HCV-3 and previous DAA treatment were more likely to develop treatment failure. Neither univariate analysis nor multivariate logistic regression analysis did show any association between CD4+ T-cell count or percentage and SVR12. CD4 T-cell count or percentage does not appear to impact SVR rates in cancer patients with HCV monoinfection receiving DAAs., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Data are sparse on treatment of chronic hepatitis C virus (HCV) in cancer patients. We evaluated the efficacy and safety of sofosbuvir-based therapy (SOFBT) in cancer patients., Methods: Patients treated with SOFBT at our center during 2014-2017 were included in a prospective observational study. Efficacy [sustained virologic response at 12 weeks after the end of treatment (SVR12)], cancer-related outcomes and adverse events (AEs) were assessed., Results: We included 153 patients. Most were men (109; 71%), white (92; 60%), non-cirrhotic (105; 69%), and with HCV genotype 1 (110; 72%). The most common cancers were hepatocellular carcinoma (HCC) (27; 18%) and multiple myeloma (14; 9%). The overall SVR12 rate was 91% (128/141). SVR12 was 100% in patients treated with ledipasvir/sofosbuvir for 8 weeks. Of the 32 patients initially excluded from cancer clinical trials because of HCV, 27 (84%) were granted cancer therapy access after starting SOFBT. Six patients with indolent non-Hodgkin's lymphoma (NHL) received SOFBT without cancer treatment. Two achieved complete remission, one had partial remission, and two had stable cancer. Within 6 months after SOFBT, 5% (6/121) of patients in remission or with stable cancer, had progression or recurrence (two with HCC and one each with esophageal cancer, cholangiocarcinoma, NHL, and tonsillar cancer). No de novo HCCs occurred. AEs were most commonly grade 1-2 (90%)., Conclusions: SOFBT in HCV-infected cancer patients is effective and safe, may permit access to investigational cancer therapy expanding treatment options, may induce remission of NHL, and may be used for 8 weeks.

Purpose of Review: To provide an update on recent studies of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in cancer patients with an emphasis on viral reactivation after cancer treatment, new antiviral therapies, and safety concerns., Recent Findings: The diagnostic criteria for HBV reactivation in patients receiving cancer therapy were revised in 2018. HBV reactivation in these patients is preventable, even with the use of new cancer therapies. HCV reactivation also has been reported in cancer patients, particularly those with hematologic malignancies, and is not a virologic condition usually associated with poor outcome. Prophylaxis to prevent HCV reactivation is not recommended because therapy with direct-acting antivirals eradicates the infection in the majority of cancer patients., Summary: Cancer patients with HBV or HCV infection are at risk for viral reactivation, with many similarities between these two infections. Patients at high risk for reactivation will benefit significantly from taking oral antivirals, which will reduce the risk of HBV reactivation or prevent development of HCV reactivation following its virologic cure.

Background: Patients previously infected with hepatitis B virus (HBV; indicated by positivity for anti-HBc) can experience HBV reactivation during cancer chemotherapy. Intravenous immunoglobulin infusion, which is frequently used in supportive care, might facilitate passive transfer of anti-HBc. We aimed to estimate the probability of passive transfer of anti-HBc after intravenous immunoglobulin infusion in patients with cancer., Methods: We reviewed institutional databases to identify adult patients who received outpatient chemotherapy between Jan 1, 2004, and Dec 31, 2011, at the University of Texas MD Anderson Cancer Center, Houston, TX, USA. Eligible patients had received intravenous immunoglobulin therapy, had tested negative for both anti-HBc and HBsAg before infusion, and had been tested for anti-HBc after infusion. The primary endpoint was the proportion of patients who became positive for anti-HBc after intravenous immunoglobulin infusion., Findings: 950 of 18 874 patients who underwent chemotherapy within the study time frame received intravenous immunoglobulin, of whom 870 had been tested for anti-HBc before infusion. 199 patients who were negative for anti-HBc before receiving intravenous immunoglobulin were retested after infusion, of whom 29 (15% [95% CI 10-20]) became positive for anti-HBc. The probability of anti-HBc conversion at 1 week after intravenous immunoglobulin infusion was 34% (95% CI 22-48) and at 12 weeks was 4% (2-7)., Interpretation: Conversion of patients from anti-HBc negativity to anti-HBc positivity was common after intravenous immunoglobulin administration. However, the probability of a positive test decreased with time since infusion. Positive anti-HBc tests done shortly after intravenous immunoglobulin infusion should be interpreted with caution because they might indicate passive transfer instead of true infection., Funding: None., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Hepatitis C virus (HCV) reactivation in patients receiving cancer treatment has been reported in retrospective studies. We sought to determine prospectively the incidence, predictors, and clinical significance of HCV reactivation during cancer treatment. HCV-infected patients receiving cancer treatment at our institution between November 2012 and July 2016 were studied. Reactivation was defined as an increase in HCV-RNA ≥1 log 10 IU/mL over baseline and hepatitis flare as an increase in alanine aminotransferase to ≥3 times the upper limit of normal. One hundred patients were studied, 50 with hematologic malignancies and 50 with solid tumors. Reactivation occurred in 23 (23%) patients, including 18 (36%) patients with hematologic malignancies and 5 (10%) patients with solid tumors. In univariate analysis, patients with reactivation were more likely than those without reactivation to have prolonged lymphopenia (median, 95 versus 22 days; P = 0.01) and to have received rituximab (44% versus 9%; P < 0.0001), bendamustine (22% versus 0%; P < 0.001), high-dose steroids (57% versus 21%; P = 0.001), or purine analogs (22% versus 5%; P = 0.02). Rituximab (odds ratio = 9.52; P = 0.001), and high-dose steroids (odds ratio = 5.05; P = 0.01) retained significance in multivariable analysis. Of the 23 patients with reactivation, 10 (43%) had hepatitis flare. No patient with reactivation experienced liver failure or liver-related death within 36 weeks after initiation of cancer treatment. Fourteen patients with hepatitis flare, six of whom had reactivation, required discontinuation or dose reduction of cancer treatment., Conclusion: HCV reactivation occurred in 23% of HCV-infected patients receiving cancer treatment, and most had an unremarkable clinical course. However, reactivation can affect the cancer treatment plan. Our findings suggest that HCV infection should not contraindicate cancer therapy and infected patients should have access to multiple cancer treatments with close monitoring while receiving regimens associated with HCV reactivation. (Hepatology 2018;67:36-47)., (© 2017 by the American Association for the Study of Liver Diseases.)

Background: Hepatitis C virus (HCV) infection causes hepatocellular carcinoma (HCC) and subtypes of non-Hodgkin lymphoma (NHL). Associations with other cancers are not established. The authors systematically assessed associations between HCV infection and cancers in the US elderly population., Methods: This was a registry-based case-control study using Surveillance, Epidemiology, and End Results (SEER)-Medicare data in US adults aged ≥66 years. Cases (n = 1,623,538) were patients who had first cancers identified in SEER registries (1993-2011). Controls (n = 200,000) were randomly selected, cancer-free individuals who were frequency-matched to cases on age, sex, race, and calendar year. Associations with HCV (documented by Medicare claims) were determined using logistic regression., Results: HCV prevalence was higher in cases than in controls (0.7% vs 0.5%). HCV was positively associated with cancers of the liver (adjusted odds ratio [aOR] = 31.5; 95% confidence interval [CI], 29.0-34.3), intrahepatic bile duct (aOR, 3.40; 95% CI, 2.52-4.58), extrahepatic bile duct (aOR, 1.90; 95% CI, 1.41-2.57), pancreas (aOR, 1.23; 95% CI, 1.09-1.40), and anus (aOR, 1.97; 95% CI, 1.42-2.73); nonmelanoma nonepithelial skin cancer (aOR, 1.53; 95% CI, 1.15-2.04); myelodysplastic syndrome (aOR, 1.56; 95% CI, 1.33-1.83); and diffuse large B-cell lymphoma (aOR, 1.57; 95% CI, 1.34-1.84). Specific skin cancers associated with HCV were Merkel cell carcinoma (aOR, 1.92; 95% CI, 1.30-2.85) and appendageal skin cancers (aOR, 2.02; 95% CI, 1.29-3.16). Inverse associations were observed with uterine cancer (aOR, 0.64; 95% CI, 0.51-0.80) and prostate cancer (aOR, 0.73; 95% CI, 0.66-0.82). Associations were maintained in sensitivity analyses conducted among individuals without documented alcohol abuse, cirrhosis, or hepatitis B or human immunodeficiency virus infections and after adjustment for socioeconomic status. Associations of HCV with other cancers were not observed., Conclusions: HCV is associated with increased risk of cancers other than HCC in the US elderly population, notably bile duct cancers and diffuse large B-cell lymphoma. These results support a possible etiologic role for HCV in an expanded group of cancers. Cancer 2017;123:1202-1211. © 2016 American Cancer Society., (© 2017 American Cancer Society.)

Background: Antiviral therapy improves hepatic outcomes in hepatitis C virus (HCV)-infected cancer patients. However, such patients are not treated simultaneously with antivirals and chemotherapy, owing to overlapping toxicities with previous standard of care treatment of pegylated interferon and ribavirin., Aim: To examine the safety and clinically-significant drug-drug interactions observed in patients who received simultaneous treatment with direct-acting antivirals (DAAs) and chemotherapy., Methods: Safety was determined by the presence of adverse events which were graded according to the division of AIDS Table (version 2.0). Adverse events were monitored throughout antiviral treatment and up to 3 months after its completion. Drug-drug interactions were assessed using current online databases. Sustained virological response (SVR) was defined as absence of serum HCV RNA 12 weeks after end of DAA treatment. Cirrhosis was diagnosed via imaging, biopsy or with the use of non-invasive fibrosis markers., Results: Twenty-one patients received concomitant treatment with DAAs and chemotherapy between January 2013 and September 2016. Concomitant treatment was started either for virological (14; 67%) or oncologic (7; 33%) reasons. DAAs used were sofosbuvir, ledipasvir, simeprevir, daclatasvir ± ribavirin. The adverse events observed were mainly constitutional (12; 57%), hematological and gastrointestinal (7; 33% each). Physicians changed the DAA regimens in two patients (10%) in anticipation of drug-drug interactions with daclatasvir and dexamethasone. The overall SVR rate was 95% (20/21)., Conclusions: Hepatitis C virus-targeted antiviral therapy can be used concomitantly with selected anti-neoplastic agents under close monitoring for drug-drug interactions. This therapeutic intervention may prevent delay in the administration of chemotherapy in HCV-infected cancer patients., Competing Interests: Statement of interests Disclosures: Dr. Torres is or has been the principal investigator for research grants from Gilead Sciences, Merck & Co., Inc., and Vertex Pharmaceuticals, with all funds paid to MD Anderson. He also is or has been a paid scientific advisor for Gilead Sciences, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Vertex Pharmaceuticals, Genentech, Novartis, Astellas Pharma, Pfizer Inc., and Theravance Biopharma, Inc.; the terms of these arrangements are being managed by MD Anderson in accordance with its conflict of interest policies. The other authors have no conflicts to disclose., (© 2016 John Wiley & Sons Ltd.)

Purpose: To determine the rates of HIV testing and infection among patients with cancer at initiation of systemic cancer therapy., Methods: We conducted a retrospective cohort study of adults with cancer who registered at a comprehensive cancer center from January 2004 through April 2011 and received systemic cancer therapy. We determined rates of HIV-1/2 and/or Western blot testing and HIV positivity at initiation of systemic cancer therapy. Multivariable logistic regression was used to determine predictors of HIV testing., Results: Of 18,874 patients with cancer who received systemic cancer therapy during the study period, 3,514 (18.6%) were tested for HIV at initiation of cancer therapy. The prevalence of positive HIV test results was 1.2% (41 of 3,514), and the prevalence of newly diagnosed HIV was 0.3% (12 of 3,514). The HIV testing rate was lower in black than in white patients (13.7% v 19.2%), but the prevalence of positive test results was higher in black patients (4.5%) than in any other racial/ethnic group. Among patients with AIDS-defining cancers (eg, non-Hodgkin lymphoma and cervical cancer), predictors of HIV testing were history of non-Hodgkin lymphoma, younger age, and registration after 2006. Among patients with non-AIDS-defining cancers, predictors of HIV testing were younger age, registration after 2006, male sex, history of illicit drug use or sexually transmitted disease, having a hematologic malignancy, and black race., Conclusion: The prevalence of HIV infection among patients with cancer was 1.2%, higher than the 0.1% prevalence threshold above which national guidelines recommend routine opt-out testing; however, the overall HIV testing rate was low., (Copyright © 2015 by American Society of Clinical Oncology.)

Background: Hepatitis C virus (HCV) infection is a neglected disease in patients with cancer. Therefore, this study examined the impact of HCV infections in these patients., Methods: The records of HCV-infected patients with cancer seen at The University of Texas MD Anderson Cancer Center (2008-2011) were reviewed. The outcomes of those who underwent HCV treatment were analyzed., Results: Of 1291 patients who had positive test results for an antibody to HCV (anti-HCV), 744 (58%) were tested for HCV-RNA; 642 (86%) of which had chronic HCV infections. Most had solid tumors (72%) and genotype-1 (G-1) infections (66%). HCV therapy was administered in 348 patients (98 of them after cancer diagnosis). Sustained virologic response (SVR) occurred in 27 (35%) of the 78 patients treated for whom outcome data were available. Compared with patients who experienced an SVR, more patients who did not were black (29% vs 4%; P=.007), had G-1 infections (72% vs 6%; P<.0001), and had higher baseline aspartate aminotransferase (78 vs 47 IU/L; P=.006) and alanine aminotransferase levels (71.1 vs 43.3 IU/L; P=.009). Overall, progression to cirrhosis (hazard ratio [HR], 0.38; P=.03) and portal hypertension (HR, 0.19; P=.009) was less common in those treated, irrespective of the treatment outcome (SVR or non-SVR). Hepatocellular carcinoma (HCC) developed as a second primary malignancy in 7% of patients with non-HCC cancer., Conclusions: This is the largest series to analyze HCV infections in patients with cancer. HCV therapy is feasible and prevents liver disease progression in this forgotten population. A treatment algorithm is provided., (Copyright © 2015 by the National Comprehensive Cancer Network.)

At 30 years into the HIV infection epidemic, the optimal antiretroviral (ARV) regimen for infected patients with cancer remains unknown. We therefore sought to retrospectively study different ARV regimens used in this population. Data from HIV-infected patients seen at The University of Texas MD Anderson Cancer Center in Houston, Texas, USA, from 2001 to 2012 were reviewed. Patients received nucleoside reverse transcriptase inhibitors (NRTIs) plus protease inhibitors (PIs), non-NRTIs (NNRTIs), integrase strand-transfer inhibitors (INSTIs), or combinations of these. A total of 154 patients were studied. Most patients were male (80%), white (51%) and had haematological malignancies (HMs) (58%). NRTIs were combined with PIs (37%), NNRTIs (32%), INSTIs (19%) or combinations of these (11%). INSTIs were the most commonly used in patients with HM and in those receiving high-dose steroids or topoisomerase inhibitors (p <0.05). Side-effects occurred in 35%, 14%, 3% and 6% of patients receiving PIs, NNRTIs, INSTIs and combinations, respectively (p 0.001). Grade 3-4 adverse events were uncommon. Multivariate logistic regression analysis demonstrated that INSTIs and NNRTIs were nine times (95% confidence interval (CI), 1.4-50.8) and 11 times (95% CI, 1.9-64.7) more likely to be effective at 6 months, respectively, than PIs. This is the largest reported analysis studying different ARV regimens in HIV-infected cancer patients. Combinations that included PIs were the least favourable. NNRTIs and INSTIs had comparable efficacy, but INSTIs appeared to be the better tolerated ARVs in patients with HM or those receiving various chemotherapeutic agents., (© 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.)

The optimal antiretroviral therapy (ART) regimen for human immunodeficiency virus (HIV)-infected patients with cancer remains unknown, as clinical trials are lacking and published data are insufficient to guide recommendations. When concomitant use of chemotherapy and ART is anticipated, overlap of toxic effects and drug-drug interactions between chemotherapy and ART may alter the optimal choice of ART. Prospective studies are urgently needed to further define the toxic effects of combined chemotherapy and ART in HIV-positive cancer patients. Such studies should aid the development of guidelines for treatment of this population. For now, clinicians should individualize decisions regarding treatment of HIV according to clinical and laboratory findings, cancer treatment plan (chemotherapy, radiotherapy, or surgery), liver or renal disease, potential adverse drug effects (eg, rash, gastrointestinal intolerance, bone marrow suppression), and patient preference. This review focuses on what infectious disease specialists need to know to select the most appropriate ART regimens for patients receiving chemotherapy., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Cancer patients have unique problems associated with hepatitis C virus (HCV) infection and treatment not seen in the general population. HCV infection poses additional challenges and considerations for the management of cancer, and vice versa. HCV infection also can lead to the development of cancer, particularly hepatocellular carcinoma and non-Hodgkin lymphoma. In severely immunocompromised cancer patients, diagnosis of HCV infection requires increased reliance on RNA detection techniques. HCV infection can affect chemotherapy, and delay of HCV infection treatment until completion of chemotherapy and achievement of cancer remission may be required to decrease the potential for drug-drug interactions between antineoplastic agents and HCV therapeutics and potentiation of side effects of these agents. In addition, hematopoietic stem cell transplant (HSCT) recipients have an increased risk of early development of cirrhosis and fibrosis. Whether this increased risk applies to all patients regardless of cancer treatment is unknown. Furthermore, patients with cancer may have poorer sustained virological responses to HCV infection treatment than do those without cancer. Unfortunately, not all cancer patients are candidates for HCV infection therapy. In this article, we review the challenges in managing HCV infection in cancer patients and HSCT recipients.

Background & Aims: Data on acute exacerbation and reactivation of chronic hepatitis C virus (HCV) infection following chemotherapy are very limited. We sought to characterize the episodes of acute exacerbation and viral reactivation of HCV infection in cancer patients., Methods: The medical records of HCV-infected patients seen at our institution (2008-2009) were analyzed retrospectively. Acute exacerbation was defined as greater than 3-fold increase in serum level of alanine aminotransferase, and viral reactivation as ≥ 1 log(10) IU/ml increase of HCV viral load following chemotherapy., Results: Acute exacerbation occurred in 33 (11%) of 308 patients with proven HCV infection. Patients with acute exacerbation more often had underlying hematological malignancies (73% vs. 29%; p<0.001) and lymphopenia (6% vs. 0%; p=0.01) than patients without it. In multivariate analysis, underlying hematological malignancies (p=0.02; odds ratio, 3.2; 95% confidence interval, 1.2-8.7) and use of rituximab (p=0.004; odds ratio, 4.2; 95% confidence interval, 1.6-10.9) were associated with acute exacerbation. Patients with acute exacerbation received higher median cumulative dose of rituximab than those without exacerbation. Discontinuation of chemotherapy due to liver dysfunction was more common in patients with acute exacerbation than in patients without it (45% vs. 11%; p<0.001). Eight (36%) of 22 patients with known pre- and post-chemotherapy viral load had viral reactivation., Conclusions: Acute exacerbation and reactivation of chronic HCV infection occur often after chemotherapy. Liver dysfunction can lead to discontinuation of potentially life-saving chemotherapy in nearly one-half of the patients with exacerbation of HCV infection., (Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

A continuous dosing schedule of aerosolized ribavirin has been used for respiratory syncytial virus (RSV) upper respiratory tract infection and lower respiratory tract infection (LRTI) but is associated with high cost and inconvenient administration. We conducted an adaptive randomized trial to evaluate the effectiveness of an intermittent dosing schedule of ribavirin versus that of a continuous dosing schedule of ribavirin in preventing RSV LRTIs in 50 hematopoietic stem cell transplant recipients or patients with hematologic malignancies. LRTI occurred in 3 patients (9%) receiving the intermittent schedule and in 4 (22%) receiving the continuous schedule, with a 0.889 posterior probability. Because the intermittent schedule is easy to administer and has a higher efficacy than the continuous schedule, we recommend the intermittent schedule for patients who are at risk for RSV LRTI. Clinical Trials Registration. NCT00500578.

Background: Hepatitis C virus (HCV) is a known carcinogen with considerable genetic heterogeneity: six different genotypes have been identified. HCV genotype distribution varies from country to country. In the United States, the most prevalent genotypes are 1a, and 1b followed by genotypes 2, and 3., Objectives: To examine whether the distribution of HCV genotypes differed by cancer status among patients in the same area., Study Design: We reviewed epidemiologic and virological data of 636 patients with HCV infection evaluated at 3 institutions in Houston, Texas, in 2008 and 2009., Results: We included 129 cancer patients (53 with hematologic malignancies and 76 with solid tumors), 333 immunocompetent patients, and 102 HIV-co-infected patients. The prevalence of genotype 1 (G-1) was 66% among cancer patients, 84% among immunocompetents (P=0.00004), and 99% among HIV-co-infected patients (P<0.00001). G-2 and G-3 were more common in cancer patients than other patients. Demographics, risk factors, and duration of HCV infection were similar between cancer and immunocompetent patients. G-1 was more prevalent in immunocompetents (84%) than in patients with hepatocellular carcinoma (74%, P=0.08) or lymphoma (59%, P=0.001). G-2 was more prevalent in lymphoma patients (24%) than in immunocompetents (8%, P=0.003); cancer risk was 3 times as great with G-2 as with other genotypes (OR 3.72, 95% CI 1.38-9.76)., Conclusions: This multicenter retrospective study provides evidence of differences in HCV genotype distribution by underlying disease among geographically related patients and suggests a possible greater carcinogenic potential of some variants. Large-scale prospective studies are warranted to investigate HCV genotype distribution in other regions., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Infections with hepatitis B virus (HBV) or hepatitis C virus (HCV) are associated with significant morbidity and mortality among patients with cancer, especially in patients with hematologic malignancies and those who undergo hematopoietic stem-cell transplantation. Reported rates of HBV reactivation in HBV carriers who undergo chemotherapy range from 14-72%. In these patients, mortality rates range from 5-52%. HCV reactivation seems to be less common than HBV reactivation and is usually associated with a good outcome and low mortality. However, once severe hepatitis develops, as a result of viral reactivation, mortality rates seem to be similar among patients infected with HBV or HCV. Liver damage owing to viral reactivation frequently leads to modifications or interruptions of chemotherapy, which can negatively affect patients' clinical outcome. Risk factors for the development of severe HBV or HCV reactivation need to be better defined to permit identification of patients who may benefit from preventive measures, early diagnosis, and therapy. In this article, we review the epidemiology, pathogenesis, risk factors, and clinical and laboratory manifestations associated with reactivation of HBV and HCV during immunosuppressive therapy. We also discuss strategies for the prevention and treatment of viral reactivation, including the management of reactivation with new antiviral agents.

Background: The clinical significance of herpes simplex virus (HSV) isolated in lower respiratory tract specimens (LRTS) of patients with solid tumors (ST) is unknown. In the current study, the authors attempted to determine the clinical relevance of this finding among ST patients., Methods: The authors reviewed records of ST patients admitted to the study institution between April 2000 and April 2004 with clinical and radiologic evidence of pneumonia, and HSV identified in LRTS by culture alone or culture and cytology. Patients were categorized as having proven (HSV identified by culture and cytology from the LRTS), probable (HSV as the sole pathogen by culture alone), and possible (HSV along with copathogens identified by culture) HSV pneumonia., Results: Forty-five ST patients with either proven (6 patients), probable (25 patients), or possible (14 patients) HSV pneumonia were identified. When compared with patients with probable or possible HSV pneumonia, more patients with proven infection were on mechanical ventilation (40% vs 50% vs 100%, respectively; P=.03), and had longer length of stay in the intensive care unit (12 days vs 13 days vs 26 days, respectively; P=.05). The overall mortality rate was 22% (10 patients). Four of 25 (16%) patients who received HSV-directed antiviral therapy died during their hospital stay versus 6 of 20 (30%) who were not treated (P=.3). None of the 6 patients with proven HSV pneumonia who were treated with acyclovir died. On univariate analysis, risk factors for mortality included underlying breast cancer, an Acute Physiology and Chronic Health Evaluation (APACHE) II score>15, admission to the intensive care unit, and use of mechanical ventilation and vasopressors (all P15 being found to be independent predictors of death by multiple logistic regression analysis (all P

Pneumocystis jiroveci pneumonia is a common infection in patients with AIDS but an infrequent cause of pneumonia in cancer patients. Little is known about the impact of cancer type and hematopoietic stem cell transplantation on the presentation and outcome of P. jiroveci pneumonia in cancer patients. A retrospective cohort study of all patients with cancer and P. jiroveci pneumonia cared for at The M.D. Anderson Cancer Center during 1990-2003 was conducted. Eighty episodes of P. jiroveci pneumonia in 79 patients were identified. In most (67%) episodes, patients had a hematologic malignancy. In 23 (29%) episodes, patients had undergone hematopoietic stem cell transplantation. Twenty-seven percent of patients with histopathologically confirmed P. jiroveci pneumonia had nodular infiltrates on the radiographic study. Pleural effusion and pneumothorax were more common in patients with hematopoietic stem cell transplantation than in those with solid tumors. Clinical suspicion of P. jiroveci pneumonia was less common in patients with nodular infiltrates than in those without such a radiographic finding (7 vs. 39%; p=0.002). Twenty-six of 76 (34%) patients with data available died of P. jiroveci pneumonia. Predictors of death by univariate analysis included older age, tachypnea, high APACHE II score, use of mechanical ventilation or vasopressors, lower arterial pH level, absence of interstitial component, pneumothorax, and comorbid conditions (all p<0.05). Multivariate analysis identified the use of mechanical ventilation as an independent predictor of death. Death attributable to P. jiroveci pneumonia appeared to be higher in patients with hematopoietic stem cell transplantation. The clinical presentation of P. jiroveci pneumonia in cancer patients may be affected by the category of cancer and the history of hematopoietic stem cell transplantation. P. jiroveci pneumonia remains a rare yet severe infection in cancer patients.

Although gastrointestinal cytomegalovirus disease (GI-CMVd) is not common in cancer patients, it is associated with high morbidity and mortality. Herein, we review our 2-decade experience with GI-CMVd in such patient population at The University of Texas M.D. Anderson Cancer Center. Forty-seven patients were identified. Thirty-four patients (72%) had an underlying haematological malignancy, and 18 patients (38%) developed GI-CMVd following hematopoietic stem cell transplantation (HSCT). Nine (25%) of the 36 cancer patients with data available had AIDS. Upper-GI tract involvement was more common in patients with haematological malignancies than in those with solid tumours (P=0.02). Patients with AIDS were more likely to have colonic involvement than were those without AIDS (67% vs. 15%, P=0.006), and patients without AIDS were more likely to have gastric involvement (59% vs. 11%, P=0.01). The CMV-attributable mortality rate was 42%. Independent predictors of death by multivariate analysis included disseminated CMV and AIDS (P<0.01). The presentation of GI-CMVd varies according to the type of cancer, and AIDS. GI-CMVd is associated with a high mortality among cancer patients, particularly those with disseminated CMV disease or AIDS.

Invasive aspergillosis (IA) can occur despite prior prophylactic or empiric use of triazoles or amphotericin B (AMB). Although profound immunosuppression may account for breakthrough IA, resistance of Aspergillus to antifungals may also play a role. To examine this question, we measured the minimal inhibitory concentration of 105 Aspergillus isolates recovered from 105 cancer patients (64 with IA, 41 with Aspergillus colonization) to AMB, itraconazole (ITC), and voriconazole (VRC) using the National Committee for Clinical Laboratory Standards (NCCLS) M38-A microdilution and E-test methods. We also determined the minimal fungicidal concentration (MFC) of these agents and the minimal effective concentration (MEC) of caspofungin (CAS) using standardized methods. We then collected information regarding pre-exposure to AMB or triazoles (fluconazole, ITC, VRC) within 3 months before Aspergillus isolation. Pre-exposure of cancer patients to AMB or triazoles was associated with increased frequency of non-fumigatus Aspergillus species. Aspergillus isolates recovered from patients who previously received AMB exhibited higher E-test AMB MICs compared with isolates from patients without prior AMB exposure (P = 0.01). In addition, the AMB MICs by E-test were higher in triazole-pre-exposed patients compared with those not exposed to triazoles (P = 0.001). The ITC and VRC MICs by E-test were not affected by prior AMB or triazole exposure. Finally, neither the AMB, ITC, and VRC MICs and MFCs by NCCLS method nor CAS MECs showed such changes. In conclusion, cancer patients with positive Aspergillus cultures who are pre-exposed to AMB or triazoles have high frequency of non-fumigatus Aspergillus species. These Aspergillus isolates were found to be AMB-resistant by the more sensitive E-test method.

Background: Response rates for candidemia treated with standard-dose fluconazole (400 mg/day) are approximately 70%. Higher doses of fluconazole have been recommended for susceptible dose-dependent Candida isolates. Herein, we describe the outcome of 20 patients with solid tumors and candidemia treated with high-dose fluconazole (HDF) at The University of Texas M.D. Anderson Cancer Center (1998-2002)., Patients and Methods: Patients were identified either by searching the microbiology laboratory database or through direct referral from primary oncology services to the Infectious Diseases Consultative Services. A retrospective review of cases was performed. HDF was defined as > or =600 mg/day., Results: Five patients were treated with 600 mg/day, whereas 15 patients received 800 mg/day. Only one patient was neutropenic. The median APACHE II score at the onset of candidemia was 12 (range 6-24). The most common species identified were Candida albicans (eight patients, 40%) and Candida parapsilosis (seven patients, 35%). Of 19 patients whose quantitative data were available, eight (42%) had high-grade candidemia [> or =200 colony forming units (CFU)/ml]. Fifteen (83%) of 18 isolates were fluconazole susceptible, and two (both Candida glabrata) were fluconazole resistant (MIC 64 each) in vitro. Nineteen patients (95%) responded to HDF therapy. The only HDF failure occurred in a patient with C. glabrata (MIC 64.0) infection. The other patient with C. glabrata (MIC 64.0) infection responded to HDF. Central venous catheters were removed from all patients with > or =10 CFU/ml candidemias. All patients with high-grade candidemias responded to HDF. The median duration of HDF therapy was 16 (range 6-42) days. No significant toxicity occurred., Conclusions: Although our data are limited, HDF appears to be well tolerated and may be associated with higher response rates than standard-dose fluconazole in a selected group of patients with solid tumors and candidemia caused by species that are susceptible to this triazole.

To assess the spectrum and outcome of trichosporonosis (TS) in cancer patients, we reviewed the medical records of 17 such patients with TS. TS presented most commonly as fungemia (n = 10, including 7 with central-venous-catheter-related infection) and either pulmonary or soft tissue infection (n = 3, each). Most patients (65%) had acute leukemia, 11 (65%) had neutropenia, and 9 (53%) had received high doses of corticosteroids. 10 patients had breakthrough TS during therapy with at least 1 of the following: amphotericin B, fluconazole, itraconazole, and voriconazole. The 30-d crude mortality rate was 53%. Predictors of mortality by using univariate analysis included: high median APACHE II score (p < 0.01), use of high dose of corticosteroids (p = 0.01), and admission to the intensive care unit (p < 0.01). TS is associated with a high mortality rate in cancer patients. The spectrum of infection at our institution has shifted from a predominance of disseminated infection to CVC-related fungemias without evidence of tissue invasion.

Listeriosis (LT) is an important infection in immunocompromised patients, but no large series of LT in cancer patients have been recently described. We reviewed the records of 34 cancer patients with LT at our institution (1990-2001). Twenty patients (59%) had an underlying hematologic malignancy. In 11 patients, LT complicated bone marrow transplantation. Lymphocytopenia was observed in 62% of the patients. Twenty-six patients (76%) received prior corticosteroids. Bacteremia was the most common presentation of LT (74%) followed by meningoencephalitis (21%). The most common treatment of LT was ampicillin with or without gentamicin (68%). The median duration of treatment was 26 days (range, 8-74 days). The rate of response to antimicrobial therapy was 79%. No relapses were identified. LT contributed to death in 9 (75%) of the 12 patients who died. Meningoencephalitis had the worst prognosis (3 of 6 cases were fatal). Treatment of central nervous system LT continues to have a high failure rate.

Since the 1990s, changing trends have been documented in species distribution and susceptibility to bloodstream infections caused by Candida species in cancer patients. However, few data are available regarding the association between in vitro antifungal susceptibility and outcome of candidemia in this patient population. We therefore evaluated the association of in vitro antifungal susceptibility and other risk factors with failure of initial antifungal therapy in cancer patients with candidemia. Candidemia cases in cancer patients from 1998 to 2001 (n = 144) were analyzed retrospectively along with their in vitro susceptibility to amphotericin B, fluconazole, and itraconazole (National Committee for Clinical and Laboratory Standards M27-A method). Patients were evaluable for outcome analysis if they received continuous unchanged therapy with either fluconazole or amphotericin B for >/=5 days. We excluded cases of mixed candidemia. In vitro susceptibility testing data of the first Candida bloodstream isolate were analyzed. Appropriate therapy was defined as that using an active in vitro antifungal for >/=5 days. For fluconazole susceptible-dose dependent Candida species, we defined appropriate therapy as a fluconazole dose of >/=600 mg/day. The Candida species distribution was 30% Candida albicans, 24% Candida glabrata, 23% Candida parapsilosis, 10% Candida krusei, 9% Candida tropicalis, and 3% other. Overall, amphotericin B was the most active agent in vitro, with only 3% of the isolates exhibiting resistance to it (>1 mg/L). Dose-dependent susceptibility to fluconazole and itraconazole was seen in 13% and 21% of the isolates, respectively, while resistance to fluconazole and itraconazole was seen in 13% and 26%, respectively.Eighty patients were evaluable for outcome analysis. In multivariate analysis, the following factors emerged as independent predictors of failure of initial antifungal therapy: leukemia (p = 0.01), bone marrow transplantation (p = 0.006), and intensive care unit stay at onset of infection (p = 0.02). Inappropriate antifungal therapy, as defined by daily dose and in vitro susceptibility, was not shown consistently to be a significant factor (it was significant in multivariate analysis, p = 0.04, but not in univariate analysis), indicating the complexity of the variables that influence the response to antifungal treatment in cancer patients with candidemia.

Objective: To review our recent experience with protothecosis in patients with cancer at The University of Texas MD Anderson Cancer Center, and compare these cases with others reported in the literature., Methods: We report on three patients with protothecosis and cancer who were seen at The University of Texas MD Anderson Cancer Center from January 1979 to May 2002, and reviewed all cases of protothecosis in patients with cancer reported in the literature since 1966., Results: Overall, 13 cases of protothecosis complicating cancer were evaluated. The median age of the patients was 41 years (range, 7-73 years). Seven patients (54%) had an underlying hematologic malignancy, and one infection occurred after bone marrow transplantation. Neutropenia was uncommon in these patients (14%). Prototheca wickerhamii was the most common Prototheca species identified as the causative agent of infection. Skin infection was the most common presentation of protothecosis, occurring in five patients (38%), followed by disseminated disease in three patients (23%), algaemia in three patients (23%), pulmonary infection in one patient (8%), and olecranon bursitis in one patient (8%). Information on the use of antifungal therapy was available for ten patients. Seven of the ten patients received amphotericin B, while three received triazoles (fluconazole in two, itraconazole in one). Breakthrough protothecosis occurred during the administration of systemic antifungal therapy with itraconazole in one patient. All seven patients who received amphotericin B showed a response, as did one of the three patients given triazoles. Seven (58%) of the patients died during the study period, only one (17%) of protothecosis., Conclusions: Protothecosis is an uncommon infection in cancer patients, implying that Prototheca spp. have a low pathogenic potential in this population. Pulmonary involvement in particular is uncommon in these patients. Amphotericin B appears to be the most effective antifungal agent; the role of triazoles in treating protothecosis is uncertain, but they may be less effective.

Nocardiosis (NOC) is an important cause of infection in immunocompromised patients. However, large series in patients with cancer have not been described. We review the records of patients with cancer and NOC who were evaluated at The University of Texas M. D. Anderson Cancer Center, Houston, Texas, between 1988 and 2001, and we describe the incidence, microbiologic and clinical characteristics, treatment, and outcome of NOC in this population. Forty-two patients with a total of 43 episodes of NOC were identified (incidence of 60 cases of NOC per 100,000 admissions). Twenty-seven patients (64%) had hematologic malignancies. In 13 patients, NOC complicated bone marrow transplantation. Neutropenia was observed in 4 (10%) of 40 episodes with information available, and lymphopenia in 20 (50%) of 40 episodes. Patients had received steroids for 25 episodes (58%) and had received chemotherapy for 10 episodes (23%) within 30 days before the onset of NOC. Nine episodes of breakthrough NOC were identified in 7 (23%) of the 40 patients with information available. Pulmonary NOC was seen in 30 (70%) of 43 cases; soft-tissue NOC in 7 (16%); central venous catheter-related nocardemia in 3 (7%); and disseminated NOC, central nervous system NOC, and a perinephric abscess each in 1 (2%). Twenty-three percent of patients with pulmonary NOC had an acute presentation. complex was the most common causative species (77%). Therapy for NOC was mainly concurrent trimethoprim/ sulfamethoxazole and either a tetracycline or a beta-lactam. The median duration of treatment was 113 days (range, 10-600 d). Nine (60%) of 15 patients with outcome data died from NOC. NOC, although infrequent, is an important cause of morbidity and mortality in patients with cancer. It has pleomorphic manifestations, and it can be seen as a breakthrough infection. The present study confirms that timely diagnosis, the site of NOC, the type of, the presence of comorbidities, and cytomegalovirus coinfection influence the outcome of patients with cancer and NOC.

For patients who had cancer and autopsy-proven pneumonia, we evaluated whether cultures of respiratory secretions (sputum and/or bronchoalveolar lavage) performed < or =4 weeks before autopsy were a reliable basis for the diagnosis of pulmonary candidiasis. Pulmonary candidiasis was identified at autopsy in 36 patients, but common clinical predictors were insensitive for this diagnosis. For sputum culture, the sensitivity, specificity, and the positive and negative predictive values were 85%, 60%, 42%, and 93%, respectively; for bronchoalveolar lavage culture, these values were 71%, 57%, 29%, and 89%, respectively.