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Drugs May 1998Abacavir is a nucleoside analogue reverse transcriptase inhibitor that inhibits clinical isolates of HIV in vitro with a potency similar to that of zidovudine.... (Review)
Review
Abacavir is a nucleoside analogue reverse transcriptase inhibitor that inhibits clinical isolates of HIV in vitro with a potency similar to that of zidovudine. Resistance to abacavir develops relatively slowly. Cross-resistance between abacavir and didanosine, zalcitabine or lamivudine, but not zidovudine or stavudine, has been reported in vitro. Abacavir has good oral bioavailability, as demonstrated in animals, and penetrates the CNS. Treatment with abacavir, alone or in combination with other anti-HIV agents (zidovudine, lamivudine, nevirapine, amprenavir and/or other protease inhibitors), decreased viral load and increased CD4+ cell count in patients with HIV infection. Effectiveness was maintained for at least 48 weeks. In early phase I/II trials, headache, gastrointestinal disturbances, rash, malaise, fatigue and/or asthenia were the most common adverse events reported with abacavir alone or in combination with other anti-HIV agents. Hypersensitivity reactions lead to discontinuation of therapy in 2 to 3% of patients.
Topics: Anti-HIV Agents; Clinical Trials as Topic; Dideoxynucleosides; Humans; Reverse Transcriptase Inhibitors
PubMed: 9585869
DOI: 10.2165/00003495-199855050-00018 -
The Brazilian Journal of Infectious... 2016Abacavir-induced liver toxicity is a rare event almost exclusively occurring in HLA B*5701-positive patients. Herein, we report one case of abnormal liver function tests... (Review)
Review
Abacavir-induced liver toxicity is a rare event almost exclusively occurring in HLA B*5701-positive patients. Herein, we report one case of abnormal liver function tests occurring in a young HLA B*5701-negative woman on a stable nevirapine-based regimen with no history of liver problems or alcohol abuse after switching to abacavir from tenofovir. We also investigated the reasons for abacavir discontinuation in a cohort of patients treated with abacavir-lamivudine-nevirapine.
Topics: Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Chemical and Drug Induced Liver Injury; Dideoxynucleosides; Female; HIV Infections; HLA-B Antigens; Humans; Retrospective Studies; Risk Factors; Treatment Outcome
PubMed: 27054757
DOI: 10.1016/j.bjid.2016.03.002 -
Antiviral Research Aug 2016Most HIV-infected subjects will receive a treatment regimen including abacavir or tenofovir. Therefore, clarifying if there is an increased risk of acute myocardial... (Review)
Review
Most HIV-infected subjects will receive a treatment regimen including abacavir or tenofovir. Therefore, clarifying if there is an increased risk of acute myocardial infarction (AMI) among those exposed to abacavir is of the utmost importance. Due to the low frequency of AMI in this young population (2-5 per 1000 patients/year), efforts to clarify this have been quite controversial. While some observational cohorts have found a statistically significant association, others have not. Meta-analysis of randomized clinical trials offering the highest scientific evidence found no association at all, but with a limited statistical power to definitely rule out a small effect. A channelling or selection bias has been demonstrated in cohort studies, favouring the prescription of abacavir to subjects with or at risk for chronic kidney disease, and therefore, with an intrinsic increased cardiovascular risk. The recent NA-ACCORD cohort study does not identify an increased risk for AMI associated with recent abacavir use in a fully adjusted model (HR 1.33; 95%CI:0.96, 1.88). However, it does find an association in a second analysis restricted to treatment-naïve persons, with higher differences in baseline characteristics among compared arms. A critical review of the compiled available evidence is therefore mandatory, particularly in light of the first single-tablet regimen to receive approval that does contain abacavir.
Topics: Anti-HIV Agents; Cardiovascular Diseases; Clinical Trials as Topic; Dideoxynucleosides; HIV Infections; Humans; Meta-Analysis as Topic; Myocardial Infarction; Risk
PubMed: 27260856
DOI: 10.1016/j.antiviral.2016.05.015 -
Expert Opinion on Pharmacotherapy Mar 2022There are more than 30 agents available for the treatment of HIV with guidelines shifting toward integrase strand transfer inhibitors (INSTIs) as part of first line... (Review)
Review
INTRODUCTION
There are more than 30 agents available for the treatment of HIV with guidelines shifting toward integrase strand transfer inhibitors (INSTIs) as part of first line therapy. The fixed dose combination of dolutegravir (DTG), abacavir (ABC), and lamivudine (3TC) is a convenient, well tolerated, and highly effective option for treating HIV infection and remains a first line therapy across several prominent guidelines.
AREAS COVERED
In this drug evaluation, the authors provide a comprehensive overview of DTG/ABC/3TC for the treatment of HIV including the pharmacokinetics, pharmacodynamics, efficacy, safety, and tolerability. The authors also provide the reader with their expert perspectives on this particular treatment strategy.
EXPERT OPINION
While DTG/ABC/3TC remains a valuable HIV treatment option, newer combination regimens have entered the market. Bictegravir with tenofovir alafenamide and emtricitabine offers the benefit of same day initiation and efficacy in hepatitis B co-infection, while new two-drug regimens enhance the simplicity of HIV treatment. Continued study is required into the mechanisms and optimal management strategies for weight gain for many regimens, including DTG/ABC/3TC.
Topics: Anti-HIV Agents; Dideoxynucleosides; Drug Combinations; HIV Infections; Heterocyclic Compounds, 3-Ring; Humans; Lamivudine; Oxazines; Piperazines; Pyridones
PubMed: 35073817
DOI: 10.1080/14656566.2022.2029409 -
Pharmacotherapy Jul 2013Abacavir is a nucleoside analogue reverse transcriptase inhibitor indicated for the treatment of human immunodeficiency virus infection as part of a multidrug, highly... (Review)
Review
Abacavir is a nucleoside analogue reverse transcriptase inhibitor indicated for the treatment of human immunodeficiency virus infection as part of a multidrug, highly active antiretroviral therapy regimen. Despite its efficacy, approximately 5% of individuals who receive abacavir develop an immune-mediated hypersensitivity reaction (HSR) that warrants immediate discontinuation of abacavir and switching to an alternative antiretroviral regimen. Abacavir HSR is associated with individuals who carry the *57:01 variant in the human leukocyte antigen B (HLA-B) gene. There is a large volume of evidence to show that those who carry HLA-B*57:01 are at significantly increased risk of developing HSR and should not receive abacavir. Pharmacogenetic screening to ensure individuals who carry HLA-B*57:01 do not receive abacavir can reduce the incidence of HSR and is now considered the standard of care before prescribing abacavir. Genetic testing to prevent abacavir HSR is currently one of the best examples of integrating pharmacogenetic testing into clinical practice.
Topics: Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Dideoxynucleosides; Drug Hypersensitivity; HIV Infections; HLA-B Antigens; Humans; Pharmacogenetics; Reverse Transcriptase Inhibitors; Standard of Care
PubMed: 23649914
DOI: 10.1002/phar.1278 -
Drugs Apr 2015A fixed-dose, single-tablet regimen comprising the integrase strand transfer inhibitor (INSTI) dolutegravir and the nucleos(t)ide reverse transcriptase inhibitors... (Review)
Review
A fixed-dose, single-tablet regimen comprising the integrase strand transfer inhibitor (INSTI) dolutegravir and the nucleos(t)ide reverse transcriptase inhibitors (NRTIs) abacavir and lamivudine (abacavir/dolutegravir/lamivudine; Triumeq®) is now available for the treatment of HIV-1 infection. In a randomized, double-blind, phase III trial in antiretroviral therapy (ART)-naive adults (SINGLE), once-daily dolutegravir plus abacavir/lamivudine had noninferior efficacy to once-daily efavirenz/tenofovir disoproxil fumarate (tenofovir DF)/emtricitabine with regard to establishing and sustaining virological suppression over 144 weeks, and subsequent superiority testing significantly favoured dolutegravir plus abacavir/lamivudine. This outcome was predominantly driven by more favourable rates of discontinuation due to adverse events versus the efavirenz/tenofovir DF/emtricitabine group. These data were generally supported by findings from other phase III trials in ART-naive adults receiving dolutegravir plus either abacavir/lamivudine or tenofovir DF/emtricitabine (SPRING-2 and FLAMINGO). Dolutegravir plus abacavir/lamivudine is generally well tolerated, with a tolerability profile that appears to be more favourable than efavirenz/tenofovir DF/emtricitabine. In the SINGLE trial, there were no major treatment-emergent INSTI or NRTI resistance-associated mutations in dolutegravir plus abacavir/lamivudine recipients with protocol-defined virological failure, indicating a high genetic barrier to resistance. Thus, triple combination therapy with abacavir, dolutegravir and lamivudine is an effective, generally well tolerated option for the management of HIV-1 infection, with the convenient once-daily fixed-dose tablet providing the first single-tablet regimen option without tenofovir DF.
Topics: Anti-HIV Agents; Dideoxynucleosides; Drug Administration Schedule; Drug Combinations; Drug Resistance, Viral; HIV Infections; HIV Integrase Inhibitors; HIV-1; Heterocyclic Compounds, 3-Ring; Humans; Lamivudine; Medication Adherence; Mutation; Oxazines; Piperazines; Practice Guidelines as Topic; Pyridones; Reverse Transcriptase Inhibitors; Tablets
PubMed: 25698454
DOI: 10.1007/s40265-015-0361-6 -
The Annals of Pharmacotherapy Mar 2008To review the clinical features, risk factors, diagnosis, and management of abacavir hypersensitivity reaction (HSR). (Review)
Review
OBJECTIVE
To review the clinical features, risk factors, diagnosis, and management of abacavir hypersensitivity reaction (HSR).
DATA SOURCES
A MEDLINE (1950-October 2007) and EMBASE (1980-October 2007) search using key words abacavir, HIV, human immunodeficiency virus, hypersensitivity reaction, HLA-B(*)5701, and patch tests was conducted. Conference abstracts and article bibliographies were reviewed to identify relevant studies.
STUDY SELECTION AND DATA EXTRACTION
Studies that investigated the clinical and immunogenetic risk factors for abacavir hypersensitivity and the benefit of genetic screening, as well as articles that focused on the clinical presentation, assessment, and management of abacavir HSR, were considered for this review.
DATA SYNTHESIS
Abacavir hypersensitivity is an immune-mediated reaction that typically occurs within the first 6 weeks of therapy. Signs and symptoms of abacavir HSR are nonspecific, which makes the diagnosis challenging, particularly in medically complex patients. Patch testing may improve the diagnosis and confirmation of abacavir HSR, but it remains experimental. Clinical management is aimed at supportive therapy and discontinuation of abacavir. Rechallenge with abacavir is contraindicated due to the risk of precipitating a life-threatening reaction. Appropriate patient education and a clear communication plan are essential for the safe use of this medication. Identification of patients at risk of developing abacavir hypersensitivity through routine genetic screening for human leukocyte antigen (HLA) HLA-B(*)5701 represents a significant advance in the field of pharmacogenomics, with an apparent 100% negative predictive value when used to screen for abacavir HSR. Preliminary data suggest that pharmacogenetic testing for HLA-B(*)5701 is cost effective. However, until routine testing is available, pharmacovigilance is necessary for the safe and effective use of abacavir.
CONCLUSIONS
Serious adverse events associated with the use of abacavir can be avoided by appropriate recognition and management of the HSR. Screening patients for HLA-B(*)5701 prior to initiation of abacavir represents a tool to further decrease the risk of HSRs as well as unnecessary discontinuation of this drug.
Topics: Anti-HIV Agents; Dideoxynucleosides; Drug Hypersensitivity; HIV Infections; HLA-B Antigens; Humans
PubMed: 18303141
DOI: 10.1345/aph.1K522 -
Expert Opinion on Drug Metabolism &... Dec 2009Fixed dose antiretroviral combinations (FDC) may improve therapy adherence with reduced pill burden. Abacavir and lamivudine are well-established nucleoside... (Review)
Review
BACKGROUND
Fixed dose antiretroviral combinations (FDC) may improve therapy adherence with reduced pill burden. Abacavir and lamivudine are well-established nucleoside reverse-transcriptase inhibitors available as a once-daily FDC. Abacavir is currently considered an alternative treatment option in most established treatment guidelines based on associations with cardiovascular events and lesser efficacy in patients with higher baseline viremia.
OBJECTIVE
To summarize rigorous clinical trial data and cohort studies that examine efficacy, safety and tolerability of the individual components and the FDC of abacavir-lamivudine.
METHODS
Clinical trial data, post-marketing research findings and clinical cohort data were reviewed to assess the efficacy, safety and tolerability of the individual components and the FDC of abacavir-lamivudine along with recommendations from published clinical treatment guidelines.
RESULTS/CONCLUSION
The efficacy of abacavir-lamivudine is well documented in numerous clinical studies and treatment guidelines. The introduction of laboratory testing to identify patients at risk for hypersensitivity has decreased the incidence of these reactions. Recent findings suggest that abacavir is an alternative treatment agent with baseline HIV RNA > 100,000 copies/ml. Data related to cardiovascular events associated with abacavir are conflicting. Hepatic function should be monitored closely in HIV/HBV co-infected patients who discontinue lamivudine-containing products as severe acute exacerbations of HBV have been reported.
Topics: Anti-HIV Agents; Clinical Trials as Topic; Dideoxynucleosides; Drug Combinations; Drug Monitoring; HIV Infections; Humans; Lamivudine; Reverse Transcriptase Inhibitors
PubMed: 19929448
DOI: 10.1517/17425250903439720 -
Expert Opinion on Pharmacotherapy Oct 2016Since the last revision of both European and American guidelines (EACS and DHHS), new data from clinical trials and cohort studies, as well as experience in clinical... (Review)
Review
INTRODUCTION
Since the last revision of both European and American guidelines (EACS and DHHS), new data from clinical trials and cohort studies, as well as experience in clinical practice, have prompted significant changes to the list of recommended/preferred options for the treatment of HIV infected patients, highlighted the role of INSTI-based regimens. Dolutegravir (DTG) in combination with abacavir/lamivudine (ABC/3TC) is one of these preferred regimens in multiple clinical scenarios, including treatment-naive and treatment-experienced patients.
AREAS COVERED
In this article we describe the coformulation of ABC/3TC/DTG in a fixed-dose combination (FDC) approved in September 2014 for the treatment of HIV infection. We focused our research on the efficacy and safety data resulting from phase 2 and 3 clinical study, particularly on the results of both SPRING (1 and 2) and SINGLE studies.
EXPERT OPINION
Triple combination therapy with ABC/3TC/DTG should be considered among the initial options for treatment-naive patients, being effective, well tolerated, with a high genetic barrier to resistance along with a convenient once-daily administration. In treatment-experienced patients the single-tablet regimen (STR) based on ABC/3TC/DTG could be used as simplification strategy in subjects with sustained viral suppression, as the high genetic barrier of DTG should ensure a safe switch from both NNRTI or PI based regimens.
Topics: Anti-HIV Agents; Dideoxynucleosides; Drug Combinations; HIV Infections; Heterocyclic Compounds, 3-Ring; Humans; Lamivudine; Oxazines; Piperazines; Pyridones; Tablets
PubMed: 27616133
DOI: 10.1080/14656566.2016.1232387 -
Drugs Aug 2000Abacavir is a carbocyclic 2'-deoxyguanosine nucleoside analogue. It is metabolised intracellularly to a 2'-deoxyguanosine nucleoside analogue which competitively... (Review)
Review
UNLABELLED
Abacavir is a carbocyclic 2'-deoxyguanosine nucleoside analogue. It is metabolised intracellularly to a 2'-deoxyguanosine nucleoside analogue which competitively inhibits HIV reverse transcriptase and terminates proviral DNA chain extension. In double-blind trials in antiretroviral therapy-experienced or -naive patients, reductions in HIV RNA levels were greater and more prolonged in patients receiving abacavir in combination with other antiretroviral drugs than in those receiving placebo in combination with the same agents. Furthermore, abacavir in combination with lamivudine and zidovudine reduced viral load to below detectable levels in a proportion of patients, and to a similar extent to the protease inhibitor indinavir in combination with lamivudine and zidovudine. Greatest viral load reductions were seen in antiretroviral therapy-naive patients. Preliminary results suggest that the viral suppression achieved with a protease inhibitor plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) can be maintained as effectively with abacavir in combination with 2 NRTIs as it can be by continuing the protease inhibitor-containing treatment regimen. Initial virological data from studies of combination regimens including abacavir and protease inhibitors appear promising but larger controlled trials are required to confirm these observations. Nausea is the most frequently reported adverse event in patients receiving abacavir-containing combination therapy. Adverse events tend to be reported most frequently soon after starting treatment; the majority of events are mild or moderate in intensity and transient. Other adverse events reported in >5% of patients include vomiting, malaise and fatigue, headache, diarrhoea, sleep disorders, cough, anorexia and rash. A major cause of abacavir treatment discontinuation is the development of a hypersensitivity reaction which has been reported in 3 to 5% of patients. The reaction usually occurs within 6 weeks of commencing treatment, shows evidence of multiorgan system involvement and typically includes fever and/or rash. Symptoms resolve rapidly after discontinuation of treatment. Continuing treatment or rechallenge can result in more severe symptoms, life-threatening hypotension and even death.
CONCLUSION
Abacavir used in combination with other antiretroviral drugs effectively reduces viral load in both adults and children with HIV infection. Although these responses are greatest in individuals with little or no previous antiretroviral treatment, useful responses are still sometimes achieved in heavily pretreated individuals. Abacavir in combination with lamivudine and zidovudine provides a simple and convenient dosage regimen which is generally well tolerated, able to produce sustained suppression of viral replication and has the advantage of sparing other classes of antiretroviral drugs for subsequent use. This triple combination represents an alternative antiretroviral regimen for patients intolerant to protease inhibitors or those wishing to retain the option of protease inhibitors for later use. Further clinical studies are needed to define the activity of abacavir in combination with protease inhibitors and non-nucleoside reverse transcriptase inhibitors.
Topics: Animals; Anti-HIV Agents; Clinical Trials as Topic; Dideoxynucleosides; Drug Resistance; Drug Therapy, Combination; HIV Infections; Humans; Reverse Transcriptase Inhibitors
PubMed: 10983741
DOI: 10.2165/00003495-200060020-00015