Abacavir is an FDA-approved drug used to treat HIV-1 infection in conjunction with other antiretrovirals. Like other nucleoside analog reverse-transcriptase inhibitors (NRTIs), abacavir use is typically in combination with other HIV medications. Abacavir is not recommended for use by itself. It can be taken by mouth as a tablet or solution and may is a treatment option in patients over the age of three months. Commonly, abacavir is dispensed together with other HIV medications such as abacavir/lamivudine/zidovudine, abacavir/dolutegravir/lamivudine, and abacavir/lamivudine.
Abacavir is a nucleoside reverse transcriptase inhibitor. Within this class, it is specifically a carbocyclic 2’-deoxyguanosine, also known as a guanosine analog. After oral ingestion, abacavir sulfate is rapidly absorbed and reaches peak concentrations at about 0.63 to 1 hour with an absolute bioavailability of about 83%. Abacavir displays linear pharmacokinetics and possesses dose proportionality over the range of 300 to 1200 mg/day. Taking abacavir with food has not had any clinically relevant effect on exposure to the drug and can be safely ingested in the presence or absence of food. The volume of administration by parental route is about 0.86 +/- 0.15 L/kg. Plasma protein binding is about 50% and has an independent relationship with the plasma concentration of the drug.
The liver accomplishes the majority of abacavir's metabolism. The remaining bioavailable 2% of the compound gets excreted as an unaltered product in the urine. Two major metabolic pathways are known as the uridine diphosphate glucuronyltransferase, and the alcohol dehydrogenase pathway processes abacavir within the liver. Enzymatic metabolism produces an inactive glucuronide metabolite (361W94, approximately 36% of the dose recovered in the urine) and an additional inactive carboxylate metabolite (2269W93, about 30% of the dose recovered in the urine) — the other 15% of the compound ends up in the urine as minor metabolites, which comprise less than 2% of the orally ingested amount. Elimination through stool makes up about 16% of the original dose. CYP450 metabolism of abacavir does not play a substantial role in abacavir, and no observable drug interactions that alter clinical decision making exist within recommended doses of methadone, or alcohol, zidovudine, abacavir, and lamivudine.
The antiviral effect of abacavir is due to its intracellular anabolite, carbovir-triphosphate, which interferes with HIV viral RNA-dependent DNA polymerase, leading to inhibition of viral replication. This intracellular anabolite has been shown to have a long elimination half-life of greater than 20 hours, allowing for once-daily dosing.
Abacavir is administered as 300 mg twice daily or as 600 mg once daily. It is also available as part of several co-formulated tablets. These different co-formulations are part of nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs).
There are no dosage adjustments recommended in patients with renal impairment, and abacavir is well-tolerated in patients that would benefit from NRTI use with renal pathology from other antiretrovirals. The recommendation is to dose-adjust in hepatic impairment. Mild hepatic impairment denoted as Child-Pugh class A is suggested at 200 mg twice daily as an oral solution. Contraindications to abacavir include moderate to severe hepatic impairment, Child-Pugh class B or C, due to lack of evidence.
The common toxicities of the NRTI class are mitochondrial toxicity, which can present as hepatic steatosis, lipoatrophy, pancreatitis, and peripheral neuropathy. Symptomatic lactic acidosis can also occur in patients, and these require monitoring due to an increased risk of mortality. Additionally, patients on long-term antiretroviral therapy (ART) may experience fat redistribution: lipodystrophy.
Clinicians should avoid abacavir should in people with coronary artery disease and those at increased risk of myocardial infarction due to an increased risk of hyperlipidemia and cardiovascular events.
Contraindications to the use of abacavir in ART therapy include hypersensitivity to abacavir or any formulation component, moderate to severe hepatic impairment, and patients who are positive for the HLA-B*5701 allele. Also, in patients with moderate to severe hepatic impairment, Child-Pugh class B or C, abacavir administration is relatively contraindicated due to lack of study.
Abacavir should also be avoided in patients and is relatively contraindicated in individuals who test positive for HLA-DR7 and HLA-DQ3 because evidence shows that withholding abacavir leads to a reduced incidence of hypersensitivity reactions.
There is some potential for drug-induced injury to the body that requires monitoring when administering abacavir to patients with HIV. Patients should receive screening for HLA-B*57101 genotype status before the start of therapy and before a continuation of therapy in patients with unknown HLA*B57101 status. Patients should have CBC with differential, serum creatinine kinase, CD4 count, HIV RNA plasma level, triglycerides, and serum amylases monitored periodically. Clinicians should be aware of the risk for acute and late-onset hepatotoxicity and monitor AST and ALT levels. Signs of central fat gain or lipoatrophy should be assessed for fat gain or fat loss to fine-tune ART therapy.
Serious and sometimes fatal hypersensitivity reactions can potentially occur with abacavir. Patients who possess the HLA-B*5701 allele also carry a higher risk for a hypersensitivity reaction to abacavir; however, hypersensitivity reactions have occurred in those who do not carry the HLA-B*5701 allele. All patients should receive screening for the HLA-B*5701.
Managing the administration of abacavir to HIV patients requires an interprofessional team of healthcare professionals that includes a nurse, laboratory technologists, pharmacists, social workers, and several physicians in different specialties. After HIV diagnosis, prompt admission into HIV medical and adherence/retention in that care is fundamental to the administration of effective antiretroviral therapy. Adherence to ART is one of the top factors of favorable HIV treatment outcomes and is necessary to decrease the occurrence of drug resistance within the patient. Common obstacles to successful ART stem from an absence of social support and alcohol or substance abuse, which prevent patients from having sustained therapy.
The emphasis on compliance cannot be overemphasized. Clinicians, specialists, nurses, and pharmacists all must share in the effort to educate the patient and monitor compliance. For example, if the patient is chronically late in picking up their prescription, meaning there will be days without therapy, the pharmacist must call the physician's office and share this information with the nurse or prescriber. The pharmacist is also responsible for medication reconciliation and verifying dosing parameters. On follow-up visits, the nurse must verify compliance and should do so by asking open-ended questions that force the patient to reveal familiarity with their regimen. Failure to take the drugs in ART correctly can result in therapeutic failure for the entire drug class, as the virus can obtain adaptive immunity; this is why any type of ART absolutely requires open, interprofessional team communication to ensure the best chance for therapeutic success. [Level V]
Recommendations for increasing successful outcomes in antiretroviral therapy
|||Park MS,Yang YM,Kim JS,Choi EJ, Comparative study of antiretroviral drug regimens and drug-drug interactions between younger and older HIV-infected patients at a tertiary care teaching hospital in South Korea. Therapeutics and clinical risk management. 2018 [PubMed PMID: 30519031]|
|||Katlama C,Ingrand D,Loveday C,Clumeck N,Mallolas J,Staszewski S,Johnson M,Hill AM,Pearce G,McDade H, Safety and efficacy of lamivudine-zidovudine combination therapy in antiretroviral-naive patients. A randomized controlled comparison with zidovudine monotherapy. Lamivudine European HIV Working Group. JAMA. 1996 Jul 10 [PubMed PMID: 8656503]|
|||Greig SL,Deeks ED, Abacavir/dolutegravir/lamivudine single-tablet regimen: a review of its use in HIV-1 infection. Drugs. 2015 Apr [PubMed PMID: 25698454]|
|||Yuen GJ,Weller S,Pakes GE, A review of the pharmacokinetics of abacavir. Clinical pharmacokinetics. 2008 [PubMed PMID: 18479171]|
|||Anderson PL,Kakuda TN,Kawle S,Fletcher CV, Antiviral dynamics and sex differences of zidovudine and lamivudine triphosphate concentrations in HIV-infected individuals. AIDS (London, England). 2003 Oct 17 [PubMed PMID: 14523272]|
|||Saag MS,Benson CA,Gandhi RT,Hoy JF,Landovitz RJ,Mugavero MJ,Sax PE,Smith DM,Thompson MA,Buchbinder SP,Del Rio C,Eron JJ Jr,Fätkenheuer G,Günthard HF,Molina JM,Jacobsen DM,Volberding PA, Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2018 Recommendations of the International Antiviral Society-USA Panel. JAMA. 2018 Jul 24 [PubMed PMID: 30043070]|
|||Postorino MC,Quiros-Roldan E,Maggiolo F,Di Giambenedetto S,Ladisa N,Lapadula G,Lorenzotti S,Sighinolfi L,Castelnuovo F,Di Pietro M,Gotti D,Mazzini N,Torti C, Exploratory Analysis for the Evaluation of Estimated Glomerular Filtration Rate, Cholesterol and Triglycerides after Switching from Tenofovir/Emtricitabine plus Atazanavir/Ritonavir (ATV/r) to Abacavir/Lamivudine plus ATV/r in Patients with Preserved Renal Function. The open AIDS journal. 2016 [PubMed PMID: 27563366]|
|||Boubaker K,Flepp M,Sudre P,Furrer H,Haensel A,Hirschel B,Boggian K,Chave JP,Bernasconi E,Egger M,Opravil M,Rickenbach M,Francioli P,Telenti A, Hyperlactatemia and antiretroviral therapy: the Swiss HIV Cohort Study. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2001 Dec 1 [PubMed PMID: 11692306]|
|||Coghlan ME,Sommadossi JP,Jhala NC,Many WJ,Saag MS,Johnson VA, Symptomatic lactic acidosis in hospitalized antiretroviral-treated patients with human immunodeficiency virus infection: a report of 12 cases. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2001 Dec 1 [PubMed PMID: 11692304]|
|||Carr A, HIV lipodystrophy: risk factors, pathogenesis, diagnosis and management. AIDS (London, England). 2003 Apr [PubMed PMID: 12870540]|
|||Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients. AIDS (London, England). 2008 Sep 12 [PubMed PMID: 18753925]|
|||Sabin CA,Worm SW,Weber R,Reiss P,El-Sadr W,Dabis F,De Wit S,Law M,D'Arminio Monforte A,Friis-Møller N,Kirk O,Pradier C,Weller I,Phillips AN,Lundgren JD, Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: a multi-cohort collaboration. Lancet (London, England). 2008 Apr 26 [PubMed PMID: 18387667]|
|||Marcus JL,Neugebauer RS,Leyden WA,Chao CR,Xu L,Quesenberry CP Jr,Klein DB,Towner WJ,Horberg MA,Silverberg MJ, Use of Abacavir and Risk of Cardiovascular Disease Among HIV-Infected Individuals. Journal of acquired immune deficiency syndromes (1999). 2016 Apr 1 [PubMed PMID: 26536316]|
|||Lucas A,Nolan D,Mallal S, HLA-B*5701 screening for susceptibility to abacavir hypersensitivity. The Journal of antimicrobial chemotherapy. 2007 Apr [PubMed PMID: 17317695]|
|||Mallal S,Nolan D,Witt C,Masel G,Martin AM,Moore C,Sayer D,Castley A,Mamotte C,Maxwell D,James I,Christiansen FT, Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir. Lancet (London, England). 2002 Mar 2 [PubMed PMID: 11888582]|
|||Christensen ES,Jain R,Roxby AC, Abacavir/Dolutegravir/Lamivudine (Triumeq)-Induced Liver Toxicity in a Human Immunodeficiency Virus-Infected Patient. Open forum infectious diseases. 2017 Summer [PubMed PMID: 28748198]|
|||de Waal R,Cohen K,Maartens G, Systematic review of antiretroviral-associated lipodystrophy: lipoatrophy, but not central fat gain, is an antiretroviral adverse drug reaction. PloS one. 2013 [PubMed PMID: 23723990]|
|||Harrigan PR,Hogg RS,Dong WW,Yip B,Wynhoven B,Woodward J,Brumme CJ,Brumme ZL,Mo T,Alexander CS,Montaner JS, Predictors of HIV drug-resistance mutations in a large antiretroviral-naive cohort initiating triple antiretroviral therapy. The Journal of infectious diseases. 2005 Feb 1 [PubMed PMID: 15633092]|
|||Cohen MS,Chen YQ,McCauley M,Gamble T,Hosseinipour MC,Kumarasamy N,Hakim JG,Kumwenda J,Grinsztejn B,Pilotto JH,Godbole SV,Mehendale S,Chariyalertsak S,Santos BR,Mayer KH,Hoffman IF,Eshleman SH,Piwowar-Manning E,Wang L,Makhema J,Mills LA,de Bruyn G,Sanne I,Eron J,Gallant J,Havlir D,Swindells S,Ribaudo H,Elharrar V,Burns D,Taha TE,Nielsen-Saines K,Celentano D,Essex M,Fleming TR, Prevention of HIV-1 infection with early antiretroviral therapy. The New England journal of medicine. 2011 Aug 11 [PubMed PMID: 21767103]|
|||Metsch LR,Pereyra M,Messinger S,Del Rio C,Strathdee SA,Anderson-Mahoney P,Rudy E,Marks G,Gardner L, HIV transmission risk behaviors among HIV-infected persons who are successfully linked to care. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2008 Aug 15 [PubMed PMID: 18624629]|
|||Tripathi A,Youmans E,Gibson JJ,Duffus WA, The impact of retention in early HIV medical care on viro-immunological parameters and survival: a statewide study. AIDS research and human retroviruses. 2011 Jul [PubMed PMID: 21142607]|
|||Gardner LI,Metsch LR,Anderson-Mahoney P,Loughlin AM,del Rio C,Strathdee S,Sansom SL,Siegal HA,Greenberg AE,Holmberg SD, Efficacy of a brief case management intervention to link recently diagnosed HIV-infected persons to care. AIDS (London, England). 2005 Mar 4 [PubMed PMID: 15750396]|
|||Deschamps AE,De Geest S,Vandamme AM,Bobbaers H,Peetermans WE,Van Wijngaerden E, Diagnostic value of different adherence measures using electronic monitoring and virologic failure as reference standards. AIDS patient care and STDs. 2008 Sep [PubMed PMID: 18754705]|
|||Molina JM,Podsadecki TJ,Johnson MA,Wilkin A,Domingo P,Myers R,Hairrell JM,Rode RA,King MS,Hanna GJ, A lopinavir/ritonavir-based once-daily regimen results in better compliance and is non-inferior to a twice-daily regimen through 96 weeks. AIDS research and human retroviruses. 2007 Dec [PubMed PMID: 18160008]|
|||Boyle BA,Jayaweera D,Witt MD,Grimm K,Maa JF,Seekins DW, Randomization to once-daily stavudine extended release/lamivudine/efavirenz versus a more frequent regimen improves adherence while maintaining viral suppression. HIV clinical trials. 2008 May-Jun [PubMed PMID: 18547903]|
|||Dejesus E,Young B,Morales-Ramirez JO,Sloan L,Ward DJ,Flaherty JF,Ebrahimi R,Maa JF,Reilly K,Ecker J,McColl D,Seekins D,Farajallah A, Simplification of antiretroviral therapy to a single-tablet regimen consisting of efavirenz, emtricitabine, and tenofovir disoproxil fumarate versus unmodified antiretroviral therapy in virologically suppressed HIV-1-infected patients. Journal of acquired immune deficiency syndromes (1999). 2009 Jun 1 [PubMed PMID: 19357529]|
|||Lester RT,Ritvo P,Mills EJ,Kariri A,Karanja S,Chung MH,Jack W,Habyarimana J,Sadatsafavi M,Najafzadeh M,Marra CA,Estambale B,Ngugi E,Ball TB,Thabane L,Gelmon LJ,Kimani J,Ackers M,Plummer FA, Effects of a mobile phone short message service on antiretroviral treatment adherence in Kenya (WelTel Kenya1): a randomised trial. Lancet (London, England). 2010 Nov 27 [PubMed PMID: 21071074]|
|||Mannheimer SB,Morse E,Matts JP,Andrews L,Child C,Schmetter B,Friedland GH, Sustained benefit from a long-term antiretroviral adherence intervention. Results of a large randomized clinical trial. Journal of acquired immune deficiency syndromes (1999). 2006 Dec 1 [PubMed PMID: 17091022]|
|||de Bruin M,Hospers HJ,van Breukelen GJ,Kok G,Koevoets WM,Prins JM, Electronic monitoring-based counseling to enhance adherence among HIV-infected patients: a randomized controlled trial. Health psychology : official journal of the Division of Health Psychology, American Psychological Association. 2010 Jul [PubMed PMID: 20658830]|
|||Sabin LL,DeSilva MB,Hamer DH,Xu K,Zhang J,Li T,Wilson IB,Gill CJ, Using electronic drug monitor feedback to improve adherence to antiretroviral therapy among HIV-positive patients in China. AIDS and behavior. 2010 Jun [PubMed PMID: 19771504]|
|||Altice FL,Maru DS,Bruce RD,Springer SA,Friedland GH, Superiority of directly administered antiretroviral therapy over self-administered therapy among HIV-infected drug users: a prospective, randomized, controlled trial. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2007 Sep 15 [PubMed PMID: 17712763]|
|||Macalino GE,Hogan JW,Mitty JA,Bazerman LB,Delong AK,Loewenthal H,Caliendo AM,Flanigan TP, A randomized clinical trial of community-based directly observed therapy as an adherence intervention for HAART among substance users. AIDS (London, England). 2007 Jul 11 [PubMed PMID: 17589194]|
|||Maru DS,Bruce RD,Walton M,Springer SA,Altice FL, Persistence of virological benefits following directly administered antiretroviral therapy among drug users: results from a randomized controlled trial. Journal of acquired immune deficiency syndromes (1999). 2009 Feb 1 [PubMed PMID: 19131891]|
|||Safren SA,O'Cleirigh C,Tan JY,Raminani SR,Reilly LC,Otto MW,Mayer KH, A randomized controlled trial of cognitive behavioral therapy for adherence and depression (CBT-AD) in HIV-infected individuals. Health psychology : official journal of the Division of Health Psychology, American Psychological Association. 2009 Jan [PubMed PMID: 19210012]|