Treatment options after virological failure of first-line tenofovir-based regimens in South Africa

AbstractColorectal cancer is the second leading cause of cancer-related death worldwide. For metastatic colorectal cancer (mCRC) patients, it is recommended, as first-line treatment, chemotherapy (CT) based on doublet cytotoxic combinations of fluorouracil, leucovorin, and irinotecan (FOLFIRI) and fluorouracil, leucovorin, and oxaliplatin (FOLFOX). In addition to CT, biological (targeted agents) are indicated in the first-line treatment, unless contraindicated. In this context, most of mCRC patients are likely to progress and to change from first line to second line treatment when they develop resistance to first-line treatment options. It is in this second line setting where Aflibercept offers an alternative and effective therapeutic option, thought its specific mechanism of action for different patient’s profile: RAS mutant, RAS wild-type (wt), BRAF mutant, potentially resectable and elderly patients. In this paper, a panel of experienced oncologists specialized in the management of mCRC experts have reviewed and selected scientific evidence focused on Aflibercept as an alternative treatment.

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Immunotherapy in hepatocellular carcinoma: evaluation and management of adverse events associated with atezolizumab plus bevacizumab

Therapeutic Advances in Medical Oncology ◽

10.1177/17588359211031141 ◽

2021 ◽

Vol 13 ◽

pp. 175883592110311

Author(s):

Chiun Hsu ◽

Lorenza Rimassa ◽

Hui-Chuan Sun ◽

Arndt Vogel ◽

Ahmed O. Kaseb

Keyword(s):

Hepatocellular Carcinoma ◽

Adverse Events ◽

Kinase Inhibitor ◽

Treatment Options ◽

Healthcare Providers ◽

Safety Data ◽

Standard Of Care ◽

Antiangiogenic Agents ◽

Efficacy And Safety ◽

First Line

In light of positive efficacy and safety findings from the IMbrave150 trial of atezolizumab plus bevacizumab, this novel combination has become the preferred first-line standard of care for patients with unresectable hepatocellular carcinoma (HCC). Several additional trials are ongoing that combine an immune checkpoint inhibitor with another agent such as a multiple kinase inhibitor or antiangiogenic agent. Therefore, the range of first-line treatment options for unresectable HCC is likely to increase, and healthcare providers need succinct information about the use of such combinations, including their efficacy and key aspects of their safety profiles. Here, we review efficacy and safety data on combination immunotherapies and offer guidance on monitoring and managing adverse events, especially those associated with atezolizumab plus bevacizumab. Because of their underlying liver disease and high likelihood of portal hypertension, patients with unresectable HCC are at particular risk of gastrointestinal bleeding, and this risk may be exacerbated by treatments that include antiangiogenic agents. Healthcare providers also need to be alert to the risks of proteinuria and hypertension, colitis, hepatitis, and reactivation of hepatitis B or C virus infection. They should also be aware of the possibility of rarer but potentially life-threatening adverse events such as pneumonitis and cardiovascular events. Awareness of the risks associated with these therapies and knowledge of adverse event monitoring and management will become increasingly important as the therapeutic range broadens in unresectable HCC.

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Predictors of virological failure among people living with HIV receiving first line antiretroviral treatment in Myanmar: retrospective cohort analysis

AIDS Research and Therapy ◽

10.1186/s12981-021-00336-0 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Anita Mesic ◽

Alexander Spina ◽

Htay Thet Mar ◽

Phone Thit ◽

Tom Decroo ◽

...

Keyword(s):

Viral Load ◽

Virological Failure ◽

Antiretroviral Treatment ◽

People Living With Hiv ◽

First Line ◽

Hiv Viral Load ◽

Loss To Follow Up ◽

History Of ◽

Living With Hiv

Abstract Background Progress toward the global target for 95% virological suppression among those on antiretroviral treatment (ART) is still suboptimal. We describe the viral load (VL) cascade, the incidence of virological failure and associated risk factors among people living with HIV receiving first-line ART in an HIV cohort in Myanmar treated by the Médecins Sans Frontières in collaboration with the Ministry of Health and Sports Myanmar. Methods We conducted a retrospective cohort study, including adult patients with at least one HIV viral load test result and having received of at least 6 months’ standard first-line ART. The incidence rate of virological failure (HIV viral load ≥ 1000 copies/mL) was calculated. Multivariable Cox’s regression was performed to identify risk factors for virological failure. Results We included 25,260 patients with a median age of 33.1 years (interquartile range, IQR 28.0–39.1) and a median observation time of 5.4 years (IQR 3.7–7.9). Virological failure was documented in 3,579 (14.2%) participants, resulting in an overall incidence rate for failure of 2.5 per 100 person-years of follow-up. Among those who had a follow-up viral load result, 1,258 (57.1%) had confirmed virological failure, of which 836 (66.5%) were switched to second-line treatment. An increased hazard for failure was associated with age ≤ 19 years (adjusted hazard ratio, aHR 1.51; 95% confidence intervals, CI 1.20–1.89; p < 0.001), baseline tuberculosis (aHR 1.39; 95% CI 1.14–1.49; p < 0.001), a history of low-level viremia (aHR 1.60; 95% CI 1.42–1.81; p < 0.001), or a history of loss-to-follow-up (aHR 1.24; 95% CI 1.41–1.52; p = 0.041) and being on the same regimen (aHR 1.37; 95% CI 1.07–1.76; p < 0.001). Cumulative appointment delay was not significantly associated with failure after controlling for covariates. Conclusions VL monitoring is an important tool to improve programme outcomes, however limited coverage of VL testing and acting on test results hampers its full potential. In our cohort children and adolescents, PLHIV with history of loss-to-follow-up or those with low-viremia are at the highest risk of virological failure and might require more frequent virological monitoring than is currently recommended.

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Pharmacological Treatment of Schizophrenia: Japanese Expert Consensus

Pharmacopsychiatry ◽

10.1055/a-1324-3517 ◽

2021 ◽

Author(s):

Hitoshi Sakurai ◽

Norio Yasui-Furukori ◽

Takefumi Suzuki ◽

Hiroyuki Uchida ◽

Hajime Baba ◽

...

Keyword(s):

Relapse Prevention ◽

Negative Symptoms ◽

Japanese Society ◽

Treatment Guidelines ◽

Treatment Options ◽

Standard Deviation Score ◽

Expert Consensus ◽

Depression And Anxiety ◽

First Line ◽

A Current

Abstract Introduction Conventional treatment guidelines of schizophrenia do not necessarily provide solutions on clinically important issues. Methods A total of 141 certified psychiatrists of the Japanese Society of Clinical Neuropsychopharmacology evaluated treatment options regarding 19 clinically relevant situations in the treatment of schizophrenia with a 9-point scale (1=“disagree” and 9=“agree”). Results First-line antipsychotics varied depending on predominant symptoms: risperidone (mean±standard deviation score, 7.9±1.4), olanzapine (7.5±1.6), and aripiprazole (6.9±1.9) were more likely selected for positive symptoms; aripiprazole (7.6±1.6) for negative symptoms; aripiprazole (7.3±1.9), olanzapine (7.2±1.9), and quetiapine (6.9±1.9) for depression and anxiety; and olanzapine (7.9±1.5) and risperidone (7.5±1.5) for excitement and aggression. While only aripiprazole was categorized as a first-line treatment for relapse prevention (7.6±1.0) in patients without noticeable symptoms, aripiprazole (8.0±1.6) and brexpiprazole (6.9±2.3) were categorized as such for social integration. First-line treatments in patients who are vulnerable to extrapyramidal symptoms include quetiapine (7.5±2.0) and aripiprazole (6.9±2.1). Discussion These clinical recommendations represent the expert consensus on the use of a particular antipsychotic medication for a particular situation, filling a current gap in the literature.

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High prevalence of virological failure and HIV drug mutations in a first-line cohort of Malawian children

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dky348 ◽

2018 ◽

Vol 73 (12) ◽

pp. 3471-3475 ◽

Cited By ~ 3

Author(s):

M H W Huibers ◽

P Moons ◽

M Cornelissen ◽

F Zorgdrager ◽

N Maseko ◽

...

Keyword(s):

Virological Failure ◽

First Line ◽

High Prevalence

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Comparing effectiveness of first‐line antiretroviral therapy between peri‐urban and rural clinics in KwaZulu‐Natal, South Africa

HIV Medicine ◽

10.1111/hiv.13231 ◽

2022 ◽

Author(s):

Jaysingh Brijkumar ◽

Johnathan A. Edwards ◽

Brent A. Johnson ◽

Claudia Ordonez ◽

Henry Sunpath ◽

...

Keyword(s):

South Africa ◽

Antiretroviral Therapy ◽

First Line ◽

Kwazulu Natal ◽

Rural Clinics

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Clostridium difficile—Associated Diarrhea, an Emerging Epidemic: Therapeutic Options

Journal of Pharmacy Practice ◽

10.1177/0897190007302892 ◽

2007 ◽

Vol 20 (4) ◽

pp. 347-353

Author(s):

Christopher R. Emerson

Keyword(s):

Clostridium Difficile ◽

Hospital Admissions ◽

Treatment Options ◽

Infectious Diarrhea ◽

First Line ◽

Oral Vancomycin ◽

Considerable Morbidity ◽

Clostridium Difficile Associated Diarrhea ◽

Pharmacologic Agents ◽

Oral Metronidazole

Clostridum difficile—associated disease (CDAD) is the leading cause of infectious diarrhea and is associated with considerable morbidity and mortality. The incidence is estimated to range from 3.4 to 8.4 cases per 1000 hospital admissions, and it has become a growing problem at many institutions. Treatment options for CDAD are limited due to a paucity of new pharmacologic agents and studies examining other potential treatments. Historically oral metronidazole and oral vancomycin have been used as first-line agents in the treating CDAD, however recent reports of treatment failure and recurrence with these agents have surfaced. These reports illustrate a need for novel pharmacologic agents and a thorough review of currently available agents that may have activity against C difficile. Available data on the treatment of CDAD were extracted and reviewed to outline the appropriate management of CDAD.

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Updates in insomnia diagnosis and treatment

The International Journal of Psychiatry in Medicine ◽

10.1177/0091217419860716 ◽

2019 ◽

Vol 54 (4-5) ◽

pp. 275-289 ◽

Cited By ~ 1

Author(s):

Scott Bragg ◽

JJ Benich ◽

Natalie Christian ◽

Josh Visserman ◽

John Freedy

Keyword(s):

Drug Therapy ◽

Behavioral Therapy ◽

Treatment Plan ◽

Treatment Options ◽

First Line ◽

Safety Concerns ◽

Diagnostic And Statistical Manual ◽

First Line Therapy ◽

Appropriate Treatment ◽

Central Nervous System Depression

Introduction Insomnia is the most commonly reported sleep disorder and remains undertreated in many patients. New changes to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, have changed the way insomnia is diagnosed. In patients who suffer from insomnia, a number of available treatment options exist including both behavioral therapy and medications. Literature Review: First line therapy for insomnia should always include behavioral modifications such as sleep hygiene and insomnia-oriented cognitive behavioral therapy. In patients deemed to need pharmacotherapy, first line medications include nonbenzodiazepine hypnotics (i.e., z-drugs) and antidepressants depending on the patients’ needs and comorbidities. The risk of next day impairment, parasomnias, and central nervous system depression are some of the most feared side effects with z-drugs. Second line drug therapy includes melatonin and suvorexant. Several concerns exist for suvorexant similar to other insomnia medications, but melatonin remains one of the safest medication alternatives. Other medication options such as benzodiazepines, antihistamines, and antipsychotics should rarely be used because of weak effectiveness data or serious safety concerns. Discussion The most appropriate treatment plan needs to be tailored to meet the needs of individual patients. Many patient factors (e.g., age, other comorbidities, specific problems with sleep) need to be considered before prescribing drug therapy for patients suffering from insomnia. Medications with the best evidence and fewest safety concerns should be prioritized when clinicians work with patients to determine the most appropriate treatment plan. Conclusions Nondrug treatment should be the emphasis for managing insomnia, but several options exist for patients needing multimodal therapy to improve their symptoms and maximize their quality of life. Z-drugs and antidepressants are first line medications options, but other options may be considered when tailored to individual patients. Medications should only be used intermittently and short term until nondrug treatments help to change a patient’s sleep routine.

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Comparative efficacy and safety of first-line treatments for advanced non-small cell lung cancer with ALK-rearranged: a meta-analysis of clinical trials

BMC Cancer ◽

10.1186/s12885-021-08977-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Hao-chuan Ma ◽

Yi-hong Liu ◽

Kai-lin Ding ◽

Yu-feng Liu ◽

Wen-jie Zhao ◽

...

Keyword(s):

Lung Cancer ◽

Adverse Events ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Treatment Options ◽

Small Cell ◽

Efficacy And Safety ◽

Small Cell Lung ◽

First Line ◽

Grade 3

Abstract Background Whereas there are many pharmacological interventions prescribed for patients with advanced anaplastic lymphoma kinase (ALK)- rearranged non-small cell lung cancer (NSCLC), comparative data between novel generation ALK-tyrosine kinase inhibitors (TKIs) remain scant. Here, we indirectly compared the efficacy and safety of first-line systemic therapeutic options used for the treatment of ALK-rearranged NSCLC. Methods We included all phase 2 and 3 randomised controlled trials (RCTs) comparing any two or three treatment options. Eligible studies reported at least one of the following outcomes: progression free survival (PFS), overall survival (OS), objective response rate (ORR), or adverse events of grade 3 or higher (Grade ≥ 3 AEs). Subgroup analysis was conducted according to central nervous system (CNS) metastases. Results A total of 9 RCTs consisting of 2484 patients with 8 treatment options were included in the systematic review. Our analysis showed that alectinib (300 mg and 600 mg), brigatinib, lorlatinib and ensartinib yielded the most favorable PFS. Whereas there was no significant OS or ORR difference among the ALK-TKIs. According to Bayesian ranking profiles, lorlatinib, alectinib 600 mg and alectinib 300 mg had the best PFS (63.7%), OS (35.9%) and ORR (37%), respectively. On the other hand, ceritinib showed the highest rate of severe adverse events (60%). Conclusion Our analysis indicated that alectinib and lorlatinib might be associated with the best therapeutic efficacy in first-line treatment for major population of advanced NSCLC patients with ALK-rearrangement. However, since there is little comparative evidence on the treatment options, there is need for relative trials to fully determine the best treatment options as well as the rapidly evolving treatment landscape.

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