scholarly journals Maternal Lopinavir/Ritonavir Is Associated with Fewer Adverse Events in Infants than Nelfinavir or Atazanavir

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Christiana Smith ◽  
Adriana Weinberg ◽  
Jeri E. Forster ◽  
Myron J. Levin ◽  
Jill Davies ◽  
...  
Keyword(s):  
Adverse Events ◽  
Hiv Transmission ◽  
Illicit Drug ◽  
Combination Antiretroviral Therapy ◽  
Liver Enzyme Elevation ◽  
Perinatal Hiv ◽  
Confounding Variables ◽  
Race Ethnicity ◽  
Grade 3 ◽  
Enzyme Elevation

Combination antiretroviral therapy (cART) is successfully used for prevention of perinatal HIV transmission. To investigate safety, we compared adverse events (AE) among infants exposed to different maternal cART regimens. We reviewed 158 HIV-uninfected infants born between 1997 and 2009, using logistic regression to model grade ≥1 AE and grade ≥3 AE as a function of maternal cART and confounding variables (preterm, C-section, illicit drug use, race, ethnicity, infant antiretrovirals, and maternal viremia). Frequently used cART regimens included zidovudine (63%), lamivudine (80%), ritonavir-boosted lopinavir (37%), nelfinavir (26%), and atazanavir (10%). At birth, anemia occurred in 13/140 infants (9%), neutropenia in 27/107 (25%), thrombocytopenia in 5/133 (4%), and liver enzyme elevation in 21/130 (16%). Corresponding rates of AE at 4 weeks were 59/141 (42%), 54/130 (42%), 3/137 (2%), and 3/104 (3%), respectively. Serious AE (grade ≥ 3) exceeded 2% only for neutropenia (13% at birth; 9% at 4 weeks). Compared with infants exposed to maternal lopinavir/ritonavir, infants exposed to nelfinavir and atazanavir had a 5-fold and 4-fold higher incidence of AE at birth, respectively. In conclusion, hematologic and hepatic AE were frequent, but rarely serious. In this predominantly protease inhibitor-treated population, lopinavir/ritonavir was associated with the lowest rate of infant AE.

Randomization of dose-reduced subcutaneous interleukin-2 (scIL2) in maintenance immunotherapy (IT) with anti-GD2 antibody dinutuximab beta (DB) long-term infusion (LTI) in front–line high-risk neuroblastoma patients: Early results from the HR-NBL1/SIOPEN trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 10013-10013 ◽  
Author(s):  
Ruth Lydia Ladenstein ◽  
Ulrike Poetschger ◽  
Dominique Valteau-Couanet ◽  
Juliet Gray ◽  
Roberto Luksch ◽  
...  
Keyword(s):  
High Risk ◽  
Liver Enzyme ◽  
General Condition ◽  
Response Rate ◽  
Capillary Leak ◽  
Liver Enzyme Elevation ◽  
Stage 4 ◽  
Oral Isotretinoin ◽  
Grade 3 ◽  
Enzyme Elevation

10013 Background: We tested dose-reduced scIL2 in combination with DB-LTI and oral isotretinoin and evaluated toxicity and efficacy in high-risk neuroblastoma patients (EudraCT:2006-001489-17). Methods: High-risk patients (stage 4 ≥1y; stage 4 < 1y with MYCN amplification (MNA); stage 2, 3, 0-21y with MNA) received high intensity induction (rapid COJEC or N5-MSKC and TVD for insufficient response), surgery, high dose therapy with busulfan/melphalan and local radiotherapy. Patients ≤9 months between diagnosis and HDT/SCT who achieved at least a partial response prior to HDT/SCT and without progression thereafter were randomized to receive up to 5 cycles of 100mg/m2 DB-LTI (d8-17) ± 3x106 IU/m2 scIL2 (d1-5; d8, d10, d12, d14, d16) and 160mg/m2 oral isotretinoin (d19-32). Results: Between 04/2014 and 06/2018, 408 patients from 18 countries were randomized. Median follow-up is 1.8 years. Stage, age, MNA, induction treatments and remission status were well balanced between randomization arms. The 2yrs-EFS and -OS for DB-LTI (205 pts) vs. DB-LTI&scIL2 (203 pts) was 64%±4%vs63%±5% (p = 0.844) and 83%±3%vs74%±4% (p = 0.337). For patients in CR the 2yrs-EFS was 69%±5% for DB and 66%±6% for DB&scIL2. Patients with evaluable disease prior DB or DB&scIL2, the end of treatment response rate was 57% (26% CR, 31% PR) vs 52% (27% CR, 25% PR) with 2yrs-EFS rates of 58%±7% and 64% ±8%, respectively. Grade 3&4 toxicity was lower in the group with DB vs DB&scIL2 for fever (14%vs31%, p < 0.001) and pain (7%vs18%, p = 0.005), and no significant difference was seen for general condition (17%vs22%,ns), allergy (3%vs3%,ns), capillary leak (4%vs8%,ns), liver enzyme elevation (20%vs27%, ns) and neurological toxicities (2%vs2%,ns). Conclusions: We previously reported grade 3&4 toxicity to DB short-term infusion (STI) ± 10x6x106IU/m2 scIL2 for general condition (16%vs41%, p = 0.000), fever (14%vs40%, p = 0.000), allergic reaction (10%vs20%, p = p = 0.006), capillary leak (4%vs15%, p = 0.004), liver enzyme elevation (17%vs23%, ns), central neurotoxicity (3%vs8%, p = 0.034) and pain (16%vs26%, p = 0.048). Our results indicate that DB-LTI and dose-reduced scIL2 clearly reduced the toxicity profile, but showed absence of benefits of scIL2. DB-LTI achieved 2yrs-EFS in line with DB-STI (Ladenstein, Lancet Oncology 2018; Yu, NEJM, 2010) and a response rate > 50% supporting its use as standard of care IT. Clinical trial information: EudraCT:2006-001489-17.

Missed Opportunities for Perinatal HIV Prevention Among HIV-Exposed Infants Born 1996–2000, Pediatric Spectrum of HIV Disease Cohort

PEDIATRICS ◽  
2003 ◽  
Vol 111 (Supplement_1) ◽  
pp. 1186-1191 ◽  
Author(s):  
Vicki Peters ◽  
Kai-Lih Liu ◽  
Kenneth Dominguez ◽  
Toni Frederick ◽  
Sharon Melville ◽  
...  
Keyword(s):  
Drug Use ◽  
Hiv Prevention ◽  
Prenatal Care ◽  
Hiv Testing ◽  
Hiv Transmission ◽  
Illicit Drug ◽  
Missed Opportunities ◽  
Perinatal Hiv ◽  
Hiv Exposed ◽  
Perinatal Hiv Prevention

Objective. Despite dramatic reductions in perinatal human immunodeficiency virus (HIV) transmission in the United States, obstacles to perinatal HIV prevention that include lack of prenatal care; failure to test pregnant women for HIV before delivery; and lack of prenatal, intrapartum, or neonatal antiretroviral (ARV) use remain. The objective of this study was to describe trends in perinatal HIV prevention methods, perinatal transmission rates, and the contribution of missed opportunities for perinatal HIV prevention to perinatal HIV infection. Methods. We analyzed data obtained from infant medical records on 4755 HIV-exposed singleton deliveries in 1996–2000, from 6 US sites that participate in the Centers for Disease Control and Prevention’s Pediatric Spectrum of HIV Disease Project. HIV-exposed deliveries refer to deliveries in which the mother was known to have HIV infection during the pregnancy. Results. Of the 4287 women with data on prenatal care, 92% had prenatal care. From 1996 to 2000, among the 3925 women with prenatal care, 92% had an HIV test before delivery; the use of prenatal zidovudine (ZDV) alone decreased from 71% to 9%, and the use of prenatal ZDV with other ARVs increased from 6% to 70%. Complete data on maternal and neonatal ARVs were available for 3284 deliveries. Perinatal HIV transmission was 3% in 1651 deliveries with prenatal ZDV in combination with other ARVs, intrapartum ZDV, and neonatal ZDV; 6% in 1111 deliveries with prenatal, intrapartum, and neonatal ZDV alone; 8% in 152 deliveries with intrapartum and neonatal ZDV alone; 14% of 73 deliveries with neonatal ZDV only started within 24 hours of birth; and 20% in 297 deliveries with no prenatal, intrapartum, and neonatal ARVs. Complete data on prenatal events were available in 328 HIV-infected and 3258 HIV-uninfected infants. A total of 56% of mothers of HIV-infected infants had missed opportunities for perinatal HIV prevention versus 16% of mothers of HIV-uninfected infants. Forty-four percent of the infected infants were born to mothers who had prenatal care, a prenatal HIV diagnosis, and documented prenatal ARV therapy. Seventeen percent of women with reported illicit drug use had no prenatal care versus 3% of women with no reported drug use. In a multivariate analysis, maternal illicit drug use was significantly associated with lack of prenatal care. In a multivariate analysis, year of infant birth and the combination of lack of maternal HIV testing before delivery and lack of prenatal antiretroviral therapies were significantly associated with perinatal HIV transmission. Conclusions. Missed opportunities for perinatal HIV prevention contributed to more than half of the cases of HIV-infected infants. Prenatal care and HIV testing before delivery are major opportunities for perinatal HIV prevention. Illicit drug use was highly associated with lack of prenatal care, and lack of HIV testing before delivery was highly associated with perinatal HIV transmission.

Randomized comparison of neoadjuvant docetaxel (D), epirubicin (E) and pegfilgrastim (P) (+ trastuzumab [T] in HER2+ patients [pts]) with and without capecitabine (C) for operable breast cancer (BC): Results of a planned safety analysis of ABCSG 24

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 11034-11034
Author(s):  
G. G. Steger ◽  
R. Greil ◽  
H. Samonigg ◽  
R. Jakesz ◽  
R. Bartsch ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Peripheral Neuropathy ◽  
Symptom Management ◽  
Cardiac Toxicity ◽  
Operable Breast Cancer ◽  
Close Monitoring ◽  
Liver Enzyme Elevation ◽  
Grade 3 ◽  
Enzyme Elevation ◽  
Weekly Cycles

11034 Background: ABCSG-24 is assessing the effect of adding C to DE and adding T to DE or DEC on pCR rate. Methods: Pts with operable BC (any T stage except T4d, N±, M0) scheduled for pre-operative chemotherapy were randomized to six 3- weekly cycles of D 75 mg/m2, d1 + E 75 mg/m2 d1 + P 6 mg d2, ± C 1,000 mg/m2 bid d1–14. Primary endpoint was pCR rate. After protocol amendment, HER2+ pts were also randomized to adjuvant ± neoadjuvant T. Results: From Nov 04 to Nov 06, 262 pts were enrolled, including 29 HER2+ pts. 145 are evaluable (DE: 74 pts, 400 cycles; DEC: 74 pts, 344 cycles). The table shows grade 3/4 adverse events (AEs) in >2% of pts in either arm. Febrile neutropenia was absent. Serious AEs occurred in 22% vs 20% of pts in DE vs DEC, respectively. Fewer pts in the DE than the DEC arm required dose reduction (0.5% vs 6.6% of cycles), withdrew consent (4% vs 13%) or were withdrawn by the investigator (1% vs 17%). Reasons for withdrawal by investigator were: HFS, stomatitis, mucositis, diarrhea, vomiting, peripheral neuropathy, fatigue, asthenia, docetaxel hypersensitivity, and asymptomatic liver enzyme elevation. No serious or grade 3/4 cardiac toxicity has occurred with T. Conclusions: Despite infrequent grade 3/4 AEs in both arms, more pts discontinued DEC than DE, by either patient’s or investigator’s choice. Since May 06, no DEC pts have withdrawn consent, perhaps because of improved pt education and symptom management. This finding reinforces the need for close monitoring and prompt management of AEs. The addition of C to DE presents no safety concerns. Efficacy results are due in 2008. [Table: see text] [Table: see text]

scholarly journals Comparison of Clinical Features between Immune-Related Sclerosing Cholangitis and Hepatitis

2021 ◽  
Author(s):  
Masaki Takinami ◽  
Akira Ono ◽  
Takanori Kawabata ◽  
Nobuaki Mamesaya ◽  
Haruki Kobayashi ◽  
...  
Keyword(s):  
Sclerosing Cholangitis ◽  
Immune Checkpoint Inhibitor ◽  
Liver Enzymes ◽  
Checkpoint Inhibitor ◽  
Single Center ◽  
Liver Enzyme Elevation ◽  
Registration Number ◽  
Grade 3 ◽  
Enzyme Elevation ◽  
Different Characteristics

Abstract Background Immune-related hepatotoxicity is often regarded as immune-related hepatitis (irHepatitis) despite including immune-related sclerosing cholangitis (irSC). This study examined the clinical differences between irSC and irHepatitis.Methods A single-center retrospective study of 530 consecutive patients who received immunotherapy between August 2014 and April 2020 was performed. IrSC and irHepatitis were respectively defined as the radiological presence and absence of bile duct dilation and wall thickness.Results Forty-one patients (7.7%) developed immune-related hepatotoxicity. A CT scan was performed on 12 patients, including 11 of 12 with ≥grade 3 aminotransferase elevations. IrSC and irHepatitis were diagnosed in 4 (0.8%) and 8 (1.5%) patients, respectively. All the irSC patients had been treated with anti-PD-1. IrHepatitis was more common among patients receiving anti-CTLA-4 than among those receiving anti-PD-1/PD-L1 inhibitors (14%, 7/50 vs. 0.2%, 1/480, P <0.001). A ≥grade 2 alkaline phosphatase (ALP) elevation resulting in a cholestatic pattern was seen in all 4 irSC patients. Among the irSC patients, 3 (3/4, 75%) developed ≥grade 3 aminotransferases elevation. The median duration from the start of immunotherapy until ≥grade 2 liver enzymes elevation was 257 and 55.5 days in irSC and irHepatitis patients. The median times for progression from grade 2 to 3 liver enzyme elevation were 17.5 and 0 days, respectively.Conclusions IrSC and irHepatitis have different characteristics in the class of immune checkpoint inhibitor and onset pattern. Radiological examination for the diagnosis of irSC should be considered for patients with ≥grade 2 ALP elevation resulting in a cholestatic pattern. (Registration number J2020-36, Date of registration June 3, 2020)

scholarly journals Risk Factors Associated with Chronic Liver Enzyme Elevation (cLEE) in Persons Living with HIV without Hepatitis B or C co-infection in the Combination Antiretroviral Therapy Era

2021 ◽  
Author(s):  
Shannon Wood ◽  
Seung Hyun Won ◽  
Hsing-Chuan Hsieh ◽  
Tahaniyat Lalani ◽  
Karl Kronmann ◽  
...  
Keyword(s):  
Risk Factors ◽  
Antiretroviral Therapy ◽  
Liver Enzyme ◽  
Cox Proportional Hazards ◽  
Chronic Liver ◽  
Combination Antiretroviral Therapy ◽  
Liver Enzyme Elevation ◽  
Factors Associated ◽  
Persons Living With Hiv ◽  
Enzyme Elevation

Abstract Background As morbidity due to viral co-infections declines among HIV-infected persons, changes in liver related morbidity are anticipated. We examined data from the US Military HIV Natural History Study (NHS), a cohort of military beneficiaries, to evaluate incidence and risk factors associated with chronic liver enzyme elevation (cLEE) in HIV mono-infected patients in the combination antiretroviral therapy (cART) era. Methods Participants who were HBV and HCV seronegative with follow-up after 1996 were included. We defined chronic liver enzyme elevation (cLEE) as alanine aminotransferase (ALT) elevations ≥ 1.25 times the upper limit of normal on at least two visits, for a duration of six months or more within 2 years. We used multivariate Cox proportional hazards models to examine risk factors for cLEE. Results Of 2,779 participants, 309 (11%) met criteria for cLEE for an incidence of 1.28/100 PYFU (1.28 – 1.29). In an adjusted model, cLEE was associated with Hispanic/other ethnicity [Reference Caucasian: HR 1.744 (1.270 – 2.395)], non–nucleoside reverse transcriptase (NNRTI) based cART [Reference boosted protease inhibitors: HR 2.232 (1.378 – 3.616)], being cART naïve [HR 6.046 (3.686 – 9.915)] or having cART interruptions [HR 8.671 (4.651 – 16.164)]. African American race [HR 0.669 (0.510 – 0.877)] and integrase strand transfer inhibitor (INSTI) based cART [HR 0.222 (0.104 – 0.474)] were protective. Conclusions Our findings demonstrate initiation and continued use of cART is protective against cLEE and supports the hypothesis HIV infection directly impacts the liver. INSTI based regimens were protective and could be considered in persons with cLEE.

scholarly journals Safety and Tolerability of Antiretrovirals during Pregnancy

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Adriana Weinberg ◽  
Jeri Forster-Harwood ◽  
Jill Davies ◽  
Elizabeth J. McFarland ◽  
Jennifer Pappas ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Adverse Events ◽  
Pregnant Women ◽  
Combination Antiretroviral Therapy ◽  
Fetal Demise ◽  
Maternal Deaths ◽  
Grade 3 ◽  
Mother To Child ◽  
Hiv 1 ◽  
In Pregnancy

Combination antiretroviral therapy (CART) dramatically decreases mother-to-child HIV-1 transmission (MTCT), but maternal adverse events are not infrequent. A review of 117 locally followed pregnancies revealed 7 grade ≥3 AEs possibly related to antiretrovirals, including 2 hematologic, 3 hepatic, and 2 obstetric cholestasis cases. A fetal demise was attributed to obstetric cholestasis, but no maternal deaths occurred. The drugs possibly associated with these AE were zidovudine, nelfinavir, lopinavir/ritonavir, and indinavir. AE or intolerability required discontinuation/substitution of nevirapine in 16% of the users, zidovudine in 10%, nelfinavir in 9%, lopinavir/ritonavir in 1%, but epivir and stavudine in none. In conclusion, nevirapine, zidovudine, and nelfinavir had the highest frequency of AE and/or the lowest tolerability during pregnancy. Although nevirapine and nelfinavir are infrequently used in pregnancy at present, zidovudine is included in most MTCT preventative regimens. Our data emphasize the need to revise the treatment recommendations for pregnant women to include safer and better-tolerated drugs.

scholarly journals Comparison of clinical features between immune-related sclerosing cholangitis and hepatitis

2021 ◽  
Author(s):  
Masaki Takinami ◽  
Akira Ono ◽  
Takanori Kawabata ◽  
Nobuaki Mamesaya ◽  
Haruki Kobayashi ◽  
...  
Keyword(s):  
Sclerosing Cholangitis ◽  
Immune Checkpoint Inhibitor ◽  
Liver Enzymes ◽  
Checkpoint Inhibitor ◽  
Single Center ◽  
Liver Enzyme Elevation ◽  
Registration Number ◽  
Grade 3 ◽  
Enzyme Elevation ◽  
Different Characteristics

SummaryBackground Immune-related hepatotoxicity is often regarded as immune-related hepatitis (irHepatitis) despite including immune-related sclerosing cholangitis (irSC). This study examined the clinical differences between irSC and irHepatitis. Methods A single-center retrospective study of 530 consecutive patients who received immunotherapy between August 2014 and April 2020 was performed. IrSC and irHepatitis were respectively defined as the radiological presence and absence of bile duct dilation and wall thickness. Results Forty-one patients (7.7%) developed immune-related hepatotoxicity. A CT scan was performed on 12 patients, including 11 of 12 with ≥ grade 3 aminotransferase elevations. IrSC and irHepatitis were diagnosed in 4 (0.8%) and 8 (1.5%) patients, respectively. All the irSC patients had been treated with anti-PD-1. IrHepatitis was more common among patients receiving anti-CTLA-4 than among those receiving anti-PD-1/PD-L1 inhibitors (14%, 7/50 vs. 0.2%, 1/480, P < 0.001). A ≥ grade 2 alkaline phosphatase (ALP) elevation resulting in a cholestatic pattern was seen in all 4 irSC patients. Among the irSC patients, 3 (3/4, 75%) developed ≥ grade 3 aminotransferases elevation. The median duration from the start of immunotherapy until ≥ grade 2 liver enzymes elevation was 257 and 55.5 days in irSC and irHepatitis patients. The median times for progression from grade 2 to 3 liver enzyme elevation were 17.5 and 0 days, respectively. Conclusions IrSC and irHepatitis have different characteristics in the class of immune checkpoint inhibitor and onset pattern. Radiological examination for the diagnosis of irSC should be considered for patients with ≥ grade 2 ALP elevation resulting in a cholestatic pattern. (Registration number J2020-36, Date of registration June 3, 2020)

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