Abacavir is an anti-HIV drug that reduces the amount of virus in the body. Anti-HIV drugs such as abacavir slow down or prevent damage to the immune system and reduce the risk of developing AIDS-related illnesses.
Abacavir belongs to a class of drugs known as nucleoside reverse transcriptase inhibitors (NRTIs). This class of antiretroviral disrupts the activity of the HIV enzyme reverse transcriptase, which is needed to copy the genetic code of HIV into a form that can be inserted into human cells.
In July 1999, abacavir was approved in the European Union for use in combination with other anti-HIV drugs. The drug was licensed in the United States in December 1998.
Abacavir was previously known by the codename 1592U89 and the trade name Ziagen. Generic versions are available.
Abacavir is also available as part of the following combinations:
- Abacavir/lamivudine (600mg abacavir combined with 300mg lamivudine). Further details of this tablet are provided on another page. It may be marketed as Kivexa in Europe or Epzicom in the United States. Generic versions of this product are available.
- Triumeq (600mg abacavir combined with 300mg lamivudine and 50mg dolutegravir). See Triumeq for further details.
Trizivir, a pill that combines 300mg abacavir, 150mg lamivudine and 300mg zidovudine is also available from ViiV Healthcare. It was approved in the United States in November 2000 and in the European Union in March 2001. Trizivir is no longer recommended for use as first-line treatment.
Clinical studies have shown that abacavir can reduce HIV viral load and improve immune function in the majority of people when taken in combination with at least two other anti-HIV drugs. Abacavir is active against HIV-1 and HIV-2.
Abacavir was licensed after the results of the CNA 3003 study showed that adding the drug to a combination of zidovudine (AZT) and lamivudine (3TC) led to more patients having suppressed viral loads when taking antiretroviral therapy for the first time. (Fischl) The CNAB 3005 study extended this by comparing abacavir to the protease inhibitor indinavir (Crixivan), in combination with zidovudine and lamivudine, with both groups having similar viral load reductions. (Staszewski)
Since its approval, studies have shown that abacavir is effective when used as a part of a dual NRTI ‘backbone’. The CNA 30024 study showed that abacavir is just as effective in reducing viral load as zidovudine when combined with lamivudine and efavirenz (Sustiva). However, people who received abacavir had a significantly better CD4 cell count increase after 48 weeks. (de Jesus)
The ZODIAC study showed that once-daily dosing of abacavir was just as safe and effective as the twice-daily separate doses in people starting antiretroviral therapy for the first time. The two dosing schedules produced similar rates of side effects. (Moyle, 2005)
The ACTG-5202 study found that abacavir/lamivudine was inferior to tenofovir disoproxil fumarate/emtricitabine in people with baseline viral load above 100,000 copies/ml. (Sax)
Abacavir/lamivudine is recommended as an alternative to tenofovir disoproxil fumarate/emtricitabine in United Kingdom guidelines as a backbone for first-line antiretroviral therapy, for people with viral load below 100,000 copies/ml. United States guidelines recommend the use of abacavir in first-line treatment in combination with lamivudine and dolutegravir (Triumeq) as one of the preferred options for first-line treatment, or as part of an alternative to the preferred regimens, if combined with lamivudine and darunavir/ritonavir. In all cases, abacavir should be used only in people who test HLA-B*5701 negative (see Hypersensitivity reaction below).
Like zidovudine and stavudine (d4T), abacavir is able to cross the blood-brain barrier and combat HIV in the central nervous system. One study of treatment-experienced people with dementia found that abacavir reduces the viral load in the cerebrospinal fluid that surrounds the brain and spinal cord. (Lanier, AIDS 2001)
Abacavir is recommended for use only as part of a fixed-dose combination tablet with lamivudine (taken once daily) or as part of a combination tablet with dolutegravir and lamivudine (taken once a day). Each tablet contains 600mg of abacavir. Each tablet can be taken with or without food.
A strawberry- and banana-flavoured abacavir solution at a concentration of 20mg/ml is also available for use in children and adults who cannot take tablets. The oral solution of abacavir contains 340mg/l sorbitol. This means that the product is unsuitable for people with hereditary fructose intolerance. Sorbitol can also cause stomach upset and diarrhoea.
Abacavir is not recommended for people with cirrhosis or mild liver impairment because they are not able to process the drug properly and high drug levels occur.
Abacavir should not be taken by people with end-stage kidney disease.
As with all anti-HIV drugs, it is important to take the drug as prescribed to maintain the right level of the drug in the blood. If blood levels of the drug fall too low, this will help the development of resistance to abacavir and may affect future treatment options.
The most common side effects of abacavir are nausea, vomiting, lethargy, and fatigue. Other commonly reported side effects are fever, headache, diarrhoea, and loss of appetite. In general, symptoms appear in the first few weeks of treatment, are mild to moderate in severity, and tend to resolve on their own.
Lactic acidosis and severe skin rash (Stevens-Johnson syndrome) are rare but potentially severe side effects of abacavir, affecting less than one in a thousand people. Pancreatitis is an uncommon side effect, occurring in less than one in a hundred people. Abacavir causes less damage to fat cells than other nucleoside reverse transcriptase inhibitors (NRTIs) and is less likely to cause fat loss from under the skin. (Hoy) (Podzamczer) A number of studies have examined the effects of switching from these drugs to abacavir, with most showing modest improvements in fat levels. (Martin) (Katlama, 2003) (Moyle, 2003)
There is conflicting evidence as to whether abacavir increases the risk of heart attack (myocardial infarction). Recent data on this issue are described below.
Abacavir causes a hypersensitivity reaction in approximately 5% of people starting these drugs. A strong association between the hypersensitivity reaction and the B*5701 allele (genetic variant) has been established. A hypersensitivity reaction may be life threatening. Although the symptoms vary, most cases involve a fever. Other symptoms include rash, nausea, vomiting, diarrhoea and abdominal pain. (Keiser)
Less common symptoms include lethargy, muscle or joint pain, headache, numbness on the skin, puffiness of the throat, face and neck, swollen glands, conjunctivitis, mouth ulcers, and low blood pressure. Rash and gastrointestinal symptoms are more common in children experiencing a hypersensitivity reaction. The key difference between hypersensitivity and influenza is the presence of gastrointestinal symptoms in abacavir hypersensitivity, as well as the presence of more than two symptoms. (Keiser) (Phillips, 2006)
Typically, a pattern of symptoms builds up over a period of days, often worsening as successive doses are taken. A hypersensitivity reaction is most commonly seen in the first two to six weeks of taking the drug, although cases after only one dose have been reported. (de la Rosa) However, as hypersensitivity can occur at any time during abacavir treatment, everyone taking abacavir should familiarise themselves with the symptoms of the reaction and notify their doctor immediately if they develop.
Genetic testing for hypersensitivity
Testing for the genetic variant that can cause a hypersensitivity reaction to abacavir reduced the incidence of ‘immunologically confirmed’ hypersensitivity reactions to zero in a randomised controlled trial of nearly 2000 people. (Mallal)
The study was funded by the drug’s manufacturer, GlaxoSmithKline (GSK) to establish whether the presence of B*5701 was a necessary condition for the reaction and whether withholding abacavir from people with B*5701 would eliminate ‘true’ hypersensitivity reactions. The PREDICT study appears to show that this is the case.
All participants with immunologically confirmed hypersensitivity reactions had multiple symptoms: about two-thirds had the presence of at least three symptoms (fever, rash, plus another systemic symptom) and a third consisted of fever plus rash alone. In contrast, a high proportion of suspected hypersensitivity reactions that were not immunologically confirmed tended to consist of one or more constitutional symptoms such as diarrhoea or respiratory symptoms and lack one or both of the defining symptoms of fever or rash.
Apart from ethnicity, the only other factors strongly associated with a clinically suspected hypersensitivity reaction were either existing protease inhibitor therapy or starting therapy with an NNRTI at the same time as abacavir. In both cases, and especially with new NNRTIs, it would be easy to mistake a reaction to one of the other drugs in the regimen for an abacavir hypersensitivity reaction.
People of African descent report hypersensitivity to abacavir-containing regimens less frequently. The SHAPE (Study of Hypersensitivity to Abacavir and Pharmacogenetic Evaluation) study determined that gene screening is 100% sensitive for HLA-B*5701 in both White and Black people. In that study, only 14% of African Americans with suspected hypersensitivity reactions had the B*5701 variant as compared to 44% of White people. The study confirmed that suspected hypersensitivity reactions are more likely to prove to be ‘false positives’ in African-American people than in those of White ethnicity and more often lack the defining symptoms of fever and/or rash. (Phillips, 2007) (Saag)
Results of that trial suggest that genetic testing should be routine for people of all ethnicities and for all people starting abacavir to reduce instances of misdiagnosis of hypersensitivity reaction and situations in which abacavir is inappropriately withdrawn from patients who could have benefited from it. If screening for B*5701 is not possible, clinical vigilance needs to be relied upon.
Although over half of patients positive for B*5701 do not develop a hypersensitivity reaction, it is thought that they are at very high risk of developing one, and GSK recommends that no patient positive for B*5701 be given abacavir. If patients develop a hypersensitivity reaction and abacavir is stopped, regulators recommend that the drug is not restarted, even if the patient subsequently tests negative for B*5701.
The consequences of re-challenge are serious enough that the small chance of a false-negative test cannot be neglected. Although this study did not see any, the chance of rare immunological reactions to abacavir that are not related to B*5701 cannot be ruled out.
Monitoring for hypersensitivity
It is recommended that people starting abacavir be monitored very closely for the first two months of therapy, with consultation every two weeks. If a person who has recently started abacavir develops at least two symptoms associated with hypersensitivity, abacavir should be discontinued as soon as a doctor has made a formal diagnosis. Abacavir should not be stopped in the absence of medical advice.
In August 2000, a warning was issued about the potential for rapid onset of hypersensitivity reactions in people who restart abacavir after a period off the drug. In some cases, early symptoms of the hypersensitivity reaction may not have been diagnosed before treatment was stopped or treatment may have stopped very soon after abacavir was started.
Cases of hypersensitivity reaction after treatment interruptions have been reported in patients showing no signs of allergy despite taking abacavir for over a year before stopping the drug. (Sahly) In cases where symptoms of the hypersensitivity reaction may have occurred before interrupting abacavir, patients in whom restarting abacavir is necessary must do so in hospital to allow for immediate identification of a reaction.
Risk factors for a hypersensitivity reaction include:
- female sex
- not being of African origin
- no prior AIDS diagnosis (Brothers)
- a history of adverse drug reactions
- a history of allergic reactions, such as asthma, hay fever or eczema
- viral load above 100,000 copies/ml. (Leoty-Bernard)
Administration of the corticosteroid prednisolone, which suppresses immune activation, does not alleviate the risk associated with the hypersensitivity reaction. (Wit)
Risk of cardiovascular disease
There is conflicting evidence regarding the impact of abacavir use on the risk of cardiovascular disease.
In 2009, D:A:D (Data Collection on Adverse Events of Anti-HIV Drugs) investigators presented information collected from over 33,000 participants from eleven prospective cohorts. They found that recent abacavir use (in the past six months) increased the risk of myocardial infarction by 68%; that risk rose with correspondingly longer time on abacavir. (Lundgren)
Results from the SMART (Strategies for Management of Anti-Retroviral Therapy) study also found an excess risk of cardiovascular disease with abacavir use as compared to other NRTIs. Events included myocardial infarction, stroke, coronary artery disease, congestive heart failure, peripheral vascular disease, and death. Researchers believe that abacavir may cause vascular inflammation, increasing the risk of cardiovascular events, particularly in those already highly vulnerable. (Strategies for Management of Anti-Retroviral Therapy/INSIGHT, D:A:D Study Groups)
A subsequent systematic review of studies looking at the relationship between antiretroviral drugs and cardiovascular disease found that the evidence of an association between recent exposure and cumulative exposure to abacavir and heart attack was mixed. (Bavinger) The lack of consistency in findings is due to differing inclusion criteria, varying ages of cohorts and lack of statistical power to measure significant differences in events. Due to the uncertainty, the British HIV Association has concluded that abacavir should be avoided wherever possible by people with a higher risk of cardiovascular disease.
As with all other anti-HIV drugs, strains of HIV that are resistant to abacavir may emerge after a period of treatment. The emergence of drug-resistant strains coincides with a fall in the effectiveness of the drug.
There is considerable cross-resistance amongst the nucleoside reverse transcriptase inhibitors (NRTIs). This means that once a patient has HIV that is resistant to one NRTI, other NRTIs will have less effect on HIV viral load. Although people who have developed lamivudine resistance can still benefit from abacavir, if lamivudine resistance is combined with high-level zidovudine resistance, abacavir is unlikely to be effective. (Katlama, 2000) (Falloon)
Resistance to abacavir tends to emerge slowly, since a number of mutations must develop for the drug’s efficacy to decrease. Low-level (two- to sixfold) reductions in effectiveness can occur following development of mutation M184V, which is usually associated with lamivudine resistance. (Fenner) Subsequent mutations K65R, L74V and Y115F confer high-level (tenfold or greater) resistance to abacavir. (Harrigan) Similarly, the Q151M brings about low-level resistance to abacavir, but resistance is increased following additional mutations at positions 62, 75, 77 and 116.
Sixfold or greater resistance renders abacavir largely ineffective. (Lanier, CROI 2001)
Clearance of methadone hydrochloride is increased by 22% when combined with abacavir, but no dose modification of methadone hydrochloride is required. However, people taking both drugs should be monitored for methadone hydrochloride withdrawal symptoms.
Alcohol is known to increase blood levels of abacavir, but this has been found not to be clinically significant. Dose adjustments are not required. (McDowell)
The combination of abacavir and lamivudine in combination with a third drug is a preferred option for first-line antiretroviral treatment in infants and children in European (PENTA), US and World Health Organization guidelines.
The recommended dose of abacavir for infants and children between three months and 12 years of age is 8mg/kg twice a day, up to a maximum dose of 600mg a day. (Kline) There are limited data to suggest that a dose of 2mg/kg twice daily may be suitable for infants 30 days or younger.
Children weighing between 14kg and 20kg may receive one 300mg tablet once daily or half of one 300mg tablet twice daily. Children weighing 20-25kg may receive one and a half 300mg tablets once daily, or a full tablet and a half tablet split between morning and evening doses.
Abacavir does not need to be dosed with food. Patients who are HLA-B*5701 positive should not use abacavir; testing should be considered prior to therapy initiation (see Hypersensitivity reaction above).
Abacavir can be used during pregnancy. There is no evidence that abacavir causes harm to the foetus.
Fischl M et al. Ziagen (abacavir) combined with 3TC and AZT is highly effective and durable through 48 weeks in HIV-1 infected antiretroviral-naive subjects. Sixth Conference on Retroviruses and Opportunistic Infections, Chicago, abstract 19, 1999
Staszewski S et al. Abacavir-lamivudine-zidovudine vs indinavir-lamivudine-zidovudine in antiretroviral naive HIV-infected adults: a randomized equivalence trial. JAMA, 285: 1155-1163, 2001.
de Jesus E et al. Efficacy and safety of abacavir versus zidovudine in antiretroviral naive adults with HIV-1 infection. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, abstract H-446, 2003. You can read more about this study in our news report.
Moyle G et al. Abacavir once or twice daily combined with once-daily lamivudine and efavirenz for the treatment of antiretroviral-naive HIV-infected adults: results of the Ziagen Once Daily in Antiretroviral Combination Study. Journal of Acquired Immune Deficiency Syndromes, 38: 417-425, 2005.
Sax PE et al. Abacavir/lamivudine versus tenofovir DF/emtricitabine as part of combination regimens for initial treatment of HIV: final results. Journal of Infectious Diseases, 204: 1191-1201, 2011.
Lanier R et al. HIV-1 reverse transcriptase sequence in plasma and cerebrospinal fluid of patients with AIDS dementia complex treated with abacavir. AIDS, 15: 747-751, 2001.
Hoy JF et al. Changes in mitochondrial DNA in peripheral blood mononuclear cells from HIV-infected patients with lipoatrophy randomized to receive abacavir. Journal of Infectious Diseases, 190: 688-692, 2004.
Podzamczer D et al. Less lipoatrophy and better lipid profile with abacavir as compared to stavudine: 96-week results of a randomized study. Journal of Acquired Immune Deficiency Syndromes, 4: 139-147, 2007.
Martin A et al. Reversibility of lipoatrophy in HIV-infected patients 2 years after switching from a thymidine analogue to abacavir: the MITOX Extension Study. AIDS, 18: 1029-1036, 2004. You can read more about this study in our news report.
Katlama C et al. Comparison of metabolic abnormalities 48 weeks after switching from highly active antiretroviral therapy containing non-nucleoside reverse transcriptase inhibitor to Trizivir versus continued highly active antiretroviral therapy. AIDS, 17: 1855-1856, 2003. You can read more about this study in our news report.
Moyle G et al. A 48 week, randomized, open label comparison of three abacavir-based substitution approaches in the management of dyslipidemia and peripheral lipoatrophy. Journal of Acquired Immune Deficiency Syndromes, 33: 22-28, 2003. You can read more about this study in our news report.
Keiser P et al. Comparison of symptoms of influenza A with abacavir-associated hypersensitivity reaction. International Journal of STD and AIDS, 14: 478-481, 2003.
Phillips E et al. Pharmacogenetics and clinical characteristics of patch-test confirmed patients with abacavir hypersensitivity. Seventh International Workshop on the Clinical Pharmacology of HIV Therapy, Lisbon, abstract 33, 2006.
de la Rosa R et al. Life-threatening reaction after first ever dose of abacavir in an HIV-1-infected patient. AIDS, 18: 578-579, 2004.
Mallal S et al. PREDICT-1: a novel randomised prospective study to determine the clinical utility of HLA-B*5701 screening to reduce abacavir hypersensitivity in HIV-1 infected subjects (study CNA106030). Fourth IAS Conference on HIV Pathogenesis, Treatment and Prevention, Sydney, abstract WESS101, 2007. You can read more about this study in our news report.
Phillips E et al. High sensitivity of HLA-B*5701 in Whites and Blacks in immunologically-confirmed cases of abacavir hypersensitivity (ABC HSR). Fourth IAS Conference on HIV Pathogenesis, Treatment and Prevention, Sydney, abstract WEAB305, 2007. You can read more about this study in our news report.
Saag M et al. High sensitivity of human leukocyte antigen-B*5701 as a marker of immunologically confirmed abacavir hypersensitivity in white and black patients. Clinical Infectious Diseases, 46: 1111-1118, 2008. You can read more about this study in our news report.
Sahly HM et al. Development of abacavir hypersensitivity reaction after rechallenge in a previously asymptomatic patient. AIDS, 18: 359-360, 2004. You can read more about this study in our news report.
Brothers C et al. Once-daily administration of abacavir is not a clinical risk factor for suspected hypersensitivity reactions in clinical trials, and rash alone is not sufficient to diagnose the reaction. 12th Conference on Retroviruses and Opportunistic Infections, Boston, abstract 836, 2005.
Leoty-Bernard M et al. Risk factors for hypersensitivity reaction to abacavir. Antiviral Therapy, 6: S53, 2001.
Wit FWNM et al. Prednisolone does not prevent hypersensitivity reactions in antiretroviral drug regimens containing abacavir with or without nevirapine. AIDS, 15: 2423-2429, 2001.
Lundgren J et al. Risk of myocardial infarction with exposure to specific ARV from the PI, NNRTI, and NRTI drug classes: The D:A:D Study. 16th Conference on Retroviruses and Opportunistic Infections, Montreal, abstract 44LB, 2009. You can read more about this study in our news report.
Strategies for Management of Anti-Retroviral Therapy/INSIGHT; D:A:D Study Groups. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients. AIDS, 22 : F17-24, 2008.
Bavinger C et al. Risk of cardiovascular disease from antiretroviral therapy for HIV: a systematic review. PLOS One, 8: e59551, 2013.
Katlama C et al. The role of abacavir (ABC, 1592) in antiretroviral therapy-experienced patients: results from a randomized, double-blind, trial. AIDS, 14: 781-789, 2000.
Falloon J et al. HIV-1 genotype and phenotype correlate with virological response to abacavir, amprenavir and efavirenz in treatment-experienced patients. AIDS, 16: 387-396, 2002.
Fenner TEO et al. Changes in codon 184 and phenotypic resistance of 65 different HIV-1 isolates to abacavir, 3TC and AZT. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy, Toronto, abstract 1272, 2000.
Harrigan PR et al. Resistance profile of the human immunodeficiency virus type 1 reverse transcriptase inhibitor abacavir (1592U89) after monotherapy and combination therapy. Journal of Infectious Diseases, 181: 912-920, 2000.
Lanier RE et al. Determination of a clinically relevant phenotypic resistance 'cutoff' for abacavir using the phenosense assay. Eighth Conference on Retroviruses and Opportunistic Infections, Chicago, abstract 254, 2001.
McDowell JA et al. Pharmacokinetic interaction of abacavir (1592U89) and ethanol in human immunodeficiency virus-infected adults. Antimicrobial Agents and Chemotherapy, 44: 1686-1690, 2000.
Kline MW et al. A phase I study of abacavir (1592U89) alone and in combination with other antiretroviral agents in infants and children with human immunodeficiency virus infection. Pediatrics, 103: E471-E475, 1999.