scholarly journals Hepatotoxicity of Contemporary Antiretroviral Drugs: A Review and Evaluation of Published Clinical Data

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1263
Author(s):  
Ashley O. Otto ◽  
Christina G. Rivera ◽  
John D. Zeuli ◽  
Zelalem Temesgen
Keyword(s):  
Reverse Transcriptase ◽  
Adverse Reactions ◽  
Antiretroviral Drugs ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Antiretroviral Agents ◽  
Entry Inhibitors ◽  
Clinical Literature ◽  
Contemporary Practice ◽  
Living With Hiv

Contemporary antiretroviral agents afford enhanced potency and safety for patients living with HIV. Newer antiretroviral drugs are often better tolerated than those initially approved in the early stages of the HIV epidemic. While the safety profile has improved, adverse drug reactions still occur. We have segregated the antiretroviral agents used in contemporary practice into class groupings based on their mechanism of antiviral activity (non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, integrase inhibitors, protease inhibitors, and entry inhibitors) while providing a review and discussion of the hepatoxicity seen in the most relevant clinical literature published to date. Clinical literature for individual agents is discussed and agent comparisons afforded within each group in tabular format. Our review will provide a summative overview of the incidence and medications associated with hepatic adverse reactions linked to the use of contemporary antiretroviral drugs.

scholarly journals Twenty-six years of HIV science: an overview of anti-HIV drugs metabolism

2011 ◽  
Vol 47 (2) ◽  
pp. 209-230 ◽  
Author(s):  
Carolina Horta Andrade ◽  
Lenis Medeiros de Freitas ◽  
Valéria de Oliveira
Keyword(s):  
Reverse Transcriptase ◽  
Pharmacokinetic Profile ◽  
Antiretroviral Drugs ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Entry Inhibitors ◽  
Fusion Inhibitors ◽  
Hiv Research ◽  
Hiv Drugs ◽  
Anti Hiv

From the identification of HIV as the agent causing AIDS, to the development of effective antiretroviral drugs, the scientific achievements in HIV research over the past twenty-six years have been formidable. Currently, there are twenty-five anti-HIV compounds which have been formally approved for clinical use in the treatment of AIDS. These compounds fall into six categories: nucleoside reverse transcriptase inhibitors (NRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), cell entry inhibitors or fusion inhibitors (FIs), co-receptor inhibitors (CRIs), and integrase inhibitors (INIs). Metabolism by the host organism is one of the most important determinants of the pharmacokinetic profile of a drug. Formation of active or toxic metabolites will also have an impact on the pharmacological and toxicological outcomes. Therefore, it is widely recognized that metabolism studies of a new chemical entity need to be addressed early in the drug discovery process. This paper describes an overview of the metabolism of currently available anti-HIV drugs.

An Overview of Antiretroviral Agents for Treating HIV Infection in Paediatric Population

2020 ◽  
Vol 27 (5) ◽  
pp. 760-794 ◽  
Author(s):  
Rita Melo ◽  
Agostinho Lemos ◽  
António J. Preto ◽  
Beatriz Bueschbell ◽  
Pedro Matos-Filipe ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Reverse Transcriptase ◽  
Targeted Delivery ◽  
Highly Active Antiretroviral Therapy ◽  
Antiretroviral Drugs ◽  
Viral Reservoir ◽  
Reverse Transcriptase Inhibitors ◽  
Replication Process ◽  
Antiretroviral Agents ◽  
Multiple Drugs

Paediatric Acquired ImmunoDeficiency Syndrome (AIDS) is a life-threatening and infectious disease in which the Human Immunodeficiency Virus (HIV) is mainly transmitted through Mother-To- Child Transmission (MTCT) during pregnancy, labour and delivery, or breastfeeding. This review provides an overview of the distinct therapeutic alternatives to abolish the systemic viral replication in paediatric HIV-1 infection. Numerous classes of antiretroviral agents have emerged as therapeutic tools for downregulation of different steps in the HIV replication process. These classes encompass Non- Nucleoside Analogue Reverse Transcriptase Inhibitors (NNRTIs), Nucleoside/Nucleotide Analogue Reverse Transcriptase Inhibitors (NRTIs/NtRTIs), INtegrase Inhibitors (INIs), Protease Inhibitors (PIs), and Entry Inhibitors (EIs). Co-administration of certain antiretroviral drugs with Pharmacokinetic Enhancers (PEs) may boost the effectiveness of the primary therapeutic agent. The combination of multiple antiretroviral drug regimens (Highly Active AntiRetroviral Therapy - HAART) is currently the standard therapeutic approach for HIV infection. So far, the use of HAART offers the best opportunity for prolonged and maximal viral suppression, and preservation of the immune system upon HIV infection. Still, the frequent administration of high doses of multiple drugs, their inefficient ability to reach the viral reservoirs in adequate doses, the development of drug resistance, and the lack of patient compliance compromise the complete HIV elimination. The development of nanotechnology-based drug delivery systems may enable targeted delivery of antiretroviral agents to inaccessible viral reservoir sites at therapeutic concentrations. In addition, the application of Computer-Aided Drug Design (CADD) approaches has provided valuable tools for the development of anti-HIV drug candidates with favourable pharmacodynamics and pharmacokinetic properties.

Neuropsychiatric adverse effects of HIV antiviral medication

2017 ◽  
Vol 41 (S1) ◽  
pp. S697-S698
Author(s):  
S. Nascimento ◽  
M. Mendes ◽  
C. Solana ◽  
M. Croca ◽  
J. Reis
Keyword(s):  
Antiretroviral Therapy ◽  
Adverse Effects ◽  
Reverse Transcriptase ◽  
Opportunistic Infections ◽  
Antiretroviral Drugs ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Neuropsychiatric Complications ◽  
Competing Interest ◽  
Neuropsychiatric Adverse Effects

IntroductionHIV (human immunodeficiency virus) infection is related to several neuropsychiatric complications, such as dementia, encephalopathy, psychosis, as well as, opportunistic infections of the central nervous system (CNS). The discovery of antiretroviral therapy (ART) has limited these conditions and extended the life span of infected patients into a chronic illness, but it is also associated with neuropsychiatric adverse effects.ObjectivesTo review the literature on the most common neuropsychiatric complications of the ART, since it can be difficult to distinguish drugs toxicity, the effects of the virus, immune system and psycho-social events.MethodsThe authors have conducted an online search in PubMed with the terms: “Psychiatry”, “HIV”, “adverse effects” and “antiretroviral drugs” from 2011 until 2016. From the outcome were collected, analyzed and summarized the articles considered to be relevant.ResultsThe antiretroviral therapy (ART) are associated with a numerous adverse effects on the central and peripheral nervous systems, as well as, metabolic, gastrointestinal, cardiac, and other toxicities. The neuropsychiatric effects are common and highly variable, including depression, cognitive impairment and sleep disturbance. The nucleoside reverse transcriptase inhibitors and the non-nucleoside reverse transcriptase inhibitors are one of the two classes of antiviral drugs most frequently associated with neuropsychiatric complications.ConclusionsThe occurrence of new-onset conditions related to ART makes it difficult to determine the association between psychiatric disorders and ART adverse effects, and given the fact that patients commit to lifelong therapy, as well as, they can diminish quality of life; it makes these assessment important in treating these conditions.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Patent Pooling for Promoting Access to Antiretroviral Drugs (ARVs) – A Strategic Option for India

2010 ◽  
Vol 4 (1) ◽  
pp. 41-53
Author(s):  
Kanikaram Satyanarayana ◽  
Sadhana Srivastava
Keyword(s):  
Developing Countries ◽  
Intellectual Property ◽  
Reverse Transcriptase ◽  
Andhra Pradesh ◽  
Antiretroviral Drugs ◽  
People Living With Hiv ◽  
Second Line ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Hiv Aids

The current HIV/AIDS scenario in India is quite grim with an estimated 2.4 million people living with HIV/AIDS (PLHA) in 2008, just behind South Africa and Nigeria. The anti-retroviral drugs (ARVs) remain the main stay of global HIV/AIDS treatment. Over 30 ARVs (single and FDCs) available under six categories viz., NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), Protease inhibitors, the new Fusion inhibitors, Entry inhibitors-CCR5 co-receptor antagonists and HIV integrase strand transfer inhibitors. The major originator companies for these ARVs are: Abbott, Boehringer Ingelheim (BI), Bristol-Myers Squibb (BMS), Gilead, GlaxoSmithKline (GSK), Merck, Pfizer, Roche, and Tibotec. Beginning with zidovidine in 1987, all the drugs are available in the developed countries. In India, about 30 ARVs are available as generics manufactured by Aurobindo, Hyderabad, Andhra Pradesh; Cipla Limited, Goa; Emcure Pharmaceuticals, Pune, Maharashtra; Hetero Drugs, Hyderabad, Andhra Pradesh; Macleods Pharmaceuticals, Daman; Matrix Laboratories, Nashik, Maharashtra; Ranbaxy, Sirmour, Himachal Pradesh; and Strides Arcolab, Bangalore, Karnataka. The National AIDS Control Organization (NACO) set up in 1992 by the Govt. of India provides free ARVs to HIV positive patients in India since 2004. The drugs available in India include both single drugs and FDCs covering both first line and second line ARVs. Even while there are claims of stabilization of the disease load, there is still huge gap of those who require ARVs as only about 150,000 PLHA receive the ARVs from the Govt. and other sources. Access to ARVs therefore is still a cause of serious concern ever since India became fully Trade Related Aspects of Intellectual Property Rights (TRIPS)-complaint in 2005. Therefore, the Indian pharmaceutical companies cannot make generics for those for drugs introduced post-2005 due to product patent regime. Other concerns include heat stable, other better formulations and second line ARVs for adults and more drugs and formulations for paediatric groups, that are still to be widely available in India and other developing countries. To examine whether strong intellectual property (IP) protection systems are to be considered important barriers for the limited or lack of access to ARVs, we studied the patent profile of the ARVs of the originator companies within and outside India. We could record 93 patents in the United States Patent & Trademark Office (USPTO). The originator companies have been also aggressively filing and enforcing patents in India. There have been a few efforts by companies like Gilead and GSK to grant licenses to generic manufacturers in developing countries, ostensibly to promote access to ARVs through lower (two-tier) pricing. These steps are considered as too little and too late. There is an urgent need to look for alternative strategies to promote access to ARVs both linked to and independent of IPRs. Patent pooling as a viable strategy mooted by the UNITAID should be seriously explored to promote access to ARVs. India is ideally suited for trying out the patent pool strategy as most of the global requirement of affordable ARV drugs for HIV/AIDS treatment is sourced from Indian generic companies.

scholarly journals Terapi ARV pada Penderita Ko-Infeksi TB-HIV

2019 ◽  
Vol 1 (1) ◽  
pp. 22
Author(s):  
Indana Eva Ajmala ◽  
Laksmi Wulandari
Keyword(s):  
T Lymphocytes ◽  
Reverse Transcriptase ◽  
Clinical Symptoms ◽  
Treatment Recommendation ◽  
People Living With Hiv ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Ifn Gamma ◽  
Increased Risk ◽  
Living With Hiv

TB and HIV have a very close relationship since the development of AIDS. Through a significant reduction in cellular immunity, HIV affects the pathogenesis of tuberculosis, thereby increasing the risk of TB in HIV co-infected individuals. In 2006, there were an estimated 9.2 million new TB cases worldwide, there were 710.00 in patients with HIV and 500,000 cases with MDR-TB. Sensitivity to TB associated with cytokine production by T lymphocytes (IFN gamma and TNF are like alpha). During HIV infection, IFN gamma production declined dramatically in line with the decrease in CD4 T lymphocytes This leads to an increased risk of developing reactivation or reinfection Mycobacterium tuberculosis. Clinical symptoms of pulmonary TB in people living with HIV are often non-specific. Clinical symptoms often found are fever and significant weight loss. The other symptoms usually associated with extrapulmonary TB. Antiretrovirals are drugs that inhibit HIV replication. The main priority in patients co-infected with TB-HIV is a start of TB therapy, followed by cotrimoxazole and ARV. ARV treatment recommendation on co-infection tuberculosis is starting ARV therapy to all people living with HIV with active TB, regardless of CD4 cell count. Antiretroviral therapy start as soon as possible after TB treatment can be tolerated, as soon as 2 weeks and no more than 8 weeks. Regimen set by WHO for first-line regimen containing two nucleoside reverse transcriptase inhibitors (NRTIs) plus one non-nucleoside reverse transcriptase inhibitors (NNRTIs). In the co-infection of TB-HIV nucleoside was elected WHO recommended Zidovudine (AZT) or tenofovir disoproxil fumarate (TDF), in combination with lamivudine (3TC) or emricitabine (FTC). For NNRTI, WHO recommends efavirenz (EFV) or nevirapine (NVP).

Complexity of Interactions Between Voriconazole and Antiretroviral Agents

2008 ◽  
Vol 42 (5) ◽  
pp. 698-703 ◽  
Author(s):  
Erin M Yakiwchuk ◽  
Michelle M Foisy ◽  
Christine A Hughes
Keyword(s):  
Reverse Transcriptase ◽  
Protease Inhibitors ◽  
Product Information ◽  
Chronic Administration ◽  
Antiretroviral Drugs ◽  
Data Sources ◽  
Limited Information ◽  
Reverse Transcriptase Inhibitors ◽  
Antiretroviral Agents ◽  
Nonnucleoside Reverse Transcriptase Inhibitors

Objective: To evaluate and summarize pertinent aspects of the literature on interactions between voriconazole and antiretroviral agents. Data Sources: Primary literature was identified through MEDLINE (1950-February 2008), EMBASE (1988-February 2008), and International Pharmaceutical Abstracts (1970-February 2008) using the search terms voriconazole, ritonavir, protease inhibitors, nonnucleoside reverse transcriptase inhibitors, raltegravir, maraviroc, and drug interactions. Additionally, relevant abstracts from infectious diseases and HIV conferences (2004-February 2008), reference citations from relevant publications, and product information monographs were reviewed. Study Selection And Data Abstraction: All articles identified from the data sources and published in English were reviewed. Of these, studies and reports addressing voriconazole pharmacokinetics or interactions with antiretroviral agents were evaluated. Data Synthesis: The interactions between voriconazole and antiretroviral drugs are complex. Voriconazole and ritonavir exhibit a time- and dose-dependent interaction. Ritonavir initially inhibits voriconazole metabolism, but, with chronic administration, subsequently induces voriconazole metabolism. This interaction is more pronounced with high doses of ritonavir. Coadministration of voriconazole and efavirenz at usual doses is contraindicated because of a 2-way interaction resulting in efavirenz toxicity and decreased therapeutic effect of voriconazole. Dosage adjustments of both drugs are required. Based on pharmacokinetic characteristics, interactions between voriconazole and other protease inhibitors, nonnucleoside reverse transcriptase inhibitors (including etravirine), and maraviroc are likely but have not been well characterized in the literature. Interactions between voriconazole and nucleoside reverse transcriptase inhibitors or raltegravir are not anticipated. Conclusions: Interactions between voriconazole and antiretrovirals have the potential for serious consequences. However, because there is limited information available, further studies are warranted to establish these interactions and clarify their appropriate management. Until then, clinicians should be aware of the potential for interactions between voriconazole and antiretroviral agents and how to monitor for these interactions in clinical practice.

scholarly journals Comparison of the Dynamics of Resistance-Associated Mutations to Nucleoside Reverse Transcriptase Inhibitors, Nonnucleoside Reverse Transcriptase Inhibitors, and Protease Inhibitors after Cessation of Antiretroviral Combination Therapy

2004 ◽  
Vol 48 (2) ◽  
pp. 644-647 ◽  
Author(s):  
Marc Wirden ◽  
Constance Delaugerre ◽  
Anne Genevieve Marcelin ◽  
Nadine Ktorza ◽  
Hocine Ait Mohand ◽  
...  
Keyword(s):  
Amino Acid ◽  
Reverse Transcriptase ◽  
Protease Inhibitors ◽  
Antiretroviral Drugs ◽  
Amino Acid Residues ◽  
Wild Type ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Nonnucleoside Reverse Transcriptase Inhibitors ◽  
Kinetics Of

ABSTRACT The dynamics of mutations associated with resistance to antiretroviral drugs were analyzed after cessation of therapy. The results showed that the kinetics of the shift to wild-type amino acid residues were significantly faster for protease inhibitors, intermediate for nonnucleoside reverse transcriptase inhibitors, and slower for nucleoside reverse transcriptase inhibitors.

Voltammetric Methods Used in the Determination of Nucleoside Reverse Transcriptase Inhibitors

2020 ◽  
Vol 16 ◽  
Author(s):  
Fatma Agin ◽  
İnci Selin Dogan
Keyword(s):  
Reverse Transcriptase ◽  
Biological Samples ◽  
Antiretroviral Drugs ◽  
Clinical Samples ◽  
Pharmacokinetic Studies ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Pharmaceutical Dosage Forms ◽  
Voltammetric Methods

Background: The human immunodeficiency virus (HIV) has now been established as the causative agent of the acquired immunodeficiency syndrome (AIDS) and exactly 25 antiretroviral drugs have been formally approved for clinical use in the treatment of AIDS. The life quality and duration of HIVpositive patients have increased with the using antiretroviral drugs in the treatment of AIDS. Nucleoside reverse transcriptase inhibitors (NRTIs) are one of the subgroup of antiretroviral. Objective: The quantification of drugs is important, as they make positive contributions to dose adjustment in practice. Voltammetric methods are very powerful analytical methods used in the pharmaceutical industry because of the determination of therapeutic agents and/or their metabolites in clinical samples at extremely low concentrations (10-50 ng/ml). Method: This review mainly includes the pharmacological properties and recent determination studies by voltammetric methods from pharmaceutical dosage forms and biological samples of eight NRTIs group antiretroviral drugs (zidovudine, abacavir, adefovir, entecavir, zalcitabine, didanosine, emtricitabine, lamivudine) that are used in the clinic and show electroactive properties were performed. Conclusion: Due to the variety of working electrodes in voltammetric methods, it is possible to choose the electrode that best responds. In this way, the analyze of NRTIs were possible at lower concentrations in pharmaceuticals and biological samples with voltammetric methods in these studies without the necessity for the sample pre-treatment or time consuming extraction steps. The voltammetric methods provide good stability, repeatability, reproducibility and high recovery for the analysis of the analyte. They could be used for the pharmacokinetic studies as well as for quality control laboratory studies.

Sign in / Sign up

Export Citation Format

Share Document