INDICATIONS

FORMS

• Abbreviations: ABC (abacavir), ZDV (zidovudine), DTG (dolutegravir), 3TC (lamivudine)
• Ziagen (ABC) 300 mg tablets, Epzicom (ABC + 3TC) 600 mg/300 mg tablets, and Trizivir (ABC + 3TC + AZT) 300 mg/150 mg/300 mg tablets are no longer available as of 11/27/23, 01/01/24, and 01/01/24, respectively
• Kivexa (ABC + 3TC) is only available in Europe and Canada

*Prices represent cost per unit specified, are representative of "Average Wholesale Price" (AWP).
^Dosage is indicated in mg unless otherwise noted.

USUAL ADULT DOSING

• ABC 300 mg PO twice daily or 600 mg once daily, administered with or without food
  • Once- vs. twice-daily dosing strategy has been evaluated in adult patients in clinical trials, which demonstrated a non-inferior clinical outcome.[15][14]
  • Note: assess for HLA-B*5701 allele first, as patients carrying this have a significantly higher risk of hypersensitivity reactions, which may be serious.
• ABC/3TC 600 mg/300 mg PO daily, administered with or without food
• DTG/ABC/3TC 50 mg/600 mg/300 mg PO daily, administered with or without food

ADULT RENAL DOSING

PEDIATRIC DOSING

ADVERSE DRUG REACTIONS

DRUG INTERACTIONS

Not a substrate, inducer, or inhibitor of CYP3A4. No interaction is likely with PIs, NNRTIs, MVC, and RAL. ABC is metabolized by alcohol dehydrogenase and glucoronyl transferase.

RESISTANCE

• Thymidine analog mutations including M41L (which usually occurs with T215Y), L210W (which usually occurs with M31L and T215Y), and T215Y/F confer reduced susceptibility to ABC.
• Y115F, K65R, Q151M, M184V/I confers intermediate/high-level resistance to ABC.

PHARMACOLOGY

COMMENTS

Current DHHS Panel’s Recommendations:

• ABC-containing regimens (DTG/ABC/3TC and ABC/3TC use with DRV/r or DRV/c) are considered as alternative options for initial combination ART in people with HIV.[2]

Pros:

• ABC/3TC has been studied in combination with other ARTs, including EFV, multiple PIs, and DTG, in ART-naive patients.
  • Trials comparing ABC/3TC to TDF/FTC: The ACTG 5202 study (both arms also received either EFV or ATV/r),[11] the ASSERT study (both arms also received EFV),[8] and the HEAT study (both arms also received LPV/r).[10]
  • Trial comparing ABC to IDV: CNA3005 (both arms also received 3TC + ZDV).[21]
  • Trial comparing ABC to ZDV: CNA30024 (both arms also received 3TC + EFV).[17]
• ABC is available as a single-dose daily tablet formulated with DTG/FTC[3][5][7]or coformulated with 3TC to be used in combination with other ART.
• ABC does not cause renal dysfunction.

Cons:

• HSRs associated with the presence of the HLA-B*5701 allele.
  • Screening should be conducted before initiation of any ABC-containing regimen. If test positive, ABC should not be given. Those with ABC discontinued due to suspected/confirmed HSR should never be rechallenged, regardless of their HLA-B*5701 status.[19][18][12]
• Cardiovascular risk: ABC should be used with caution or avoided in people with cardiovascular disease or known high cardiovascular risk based on the observed association between the use of ABC and an increased risk of cardiovascular events from multiple, extensive cohort studies.[4]

Basis for recommendation

1. Panel on Treatment of HIV During Pregnancy and Prevention of Perinatal Transmission. Recommendations for the Use of Antiretroviral Drugs During Pregnancy and Interventions to Reduce Perinatal HIV Transmission in the United States. Department of Health and Human Services. Available at https://clinicalinfo.hiv.gov/en/guidelines/perinatal. Accessed (September 3, 2025)

   Comment:
   DHHS guidelines
   
   
   

2. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents With HIV. Department of Health and Human Services. Available at https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv. Accessed (September 3, 2025).

   Comment: DHHS guidelines
   
   
   
   
   

References

3. Rabie H, Yin DE, Ward S, et al. Efficacy, Safety and Tolerability of Dispersible and Immediate Release Abacavir/Dolutegravir/Lamivudine Tablets in Children With HIV: IMPAACT 2019 Week 48 Results. Pediatr Infect Dis J. 2025;44(8):777-784.  [PMID:40440679]

   Comment: IMPAACT 2019 was a multicenter, phase I/II, open-label, noncomparative study that evaluated the use of dispersible and immediate-release DTG/ABC/3TC (n=55) in either ART-naive or ART-experienced HIV pediatric patients < 12 years of age and weighing 5 to < 40 kg. A total of 54/55 patients maintained HIV-1 RNA VL < 200 copies/mL through week 48. A total of 9 drug-related adverse side effects were reported, resulting in permanent discontinuation in 1 patient due to liver injury.
   

4. Davies Smith E, Malvestutto C, Ribaudo HJ, et al. Cardiovascular Hazards of Abacavir- Versus Tenofovir-Containing Antiretroviral Therapies: Insights From an Analysis of the REPRIEVE Trial Cohort. Open Forum Infect Dis. 2025;12(4):ofaf177.  [PMID:40207047]

   Comment: In this subgroup analysis of the REPRIEVE trial cohort evaluating key cardiovascular risk factors in HIV-infected adults, the risk of major adverse cardiovascular events (MACE) was assessed for ABC (n=883), TDF (n=4274), and TAF (n=957). The groups were balanced with respect to age, sex, atherosclerotic cardiovascular disease risk, CD4 count, eGFR, and anchor antiretroviral therapy. In baseline-adjusted associations, the hazard of first MAC was significantly higher for ABC compared to either TDF (HR 1.4, 95% Cl 0.9 to 2.1) or TAF (HR 1.5, 95% Cl 0.9 to 2.1), but not TDF vs. TAF (HR 0.9, 95% Cl 0.6-1.5).
   Rating: Important
   

5. Ruel TD, Acosta EP, Liu JP, et al. Pharmacokinetics, safety, tolerability, and antiviral activity of dolutegravir dispersible tablets in infants and children with HIV-1 (IMPAACT P1093): results of an open-label, phase 1-2 trial. Lancet HIV. 2022;9(5):e332-e340.  [PMID:35489377]

   Comment: IMPAACT P1093 was a multicenter, phase I/II, open-label, noncomparative study that evaluated the use of dispersible and immediate-release DTG/ABC/3TC (n=73) in either treatment-naive or treatment-experienced HIV pediatric patients 4 weeks to < 6 years of age weighing at least 3 kg with HIV-1 RNA VL >1000 copies/mL and no prior exposure to INSTI. So far, a total of 26/36 patients achieved HIV-1 RNA VL < 50 copies/mL through week 48.
   

6. Musiime V, Kasirye P, Naidoo-James B, et al. Once vs twice-daily abacavir and lamivudine in African children. AIDS. 2016;30(11):1761-70.  [PMID:27064996]

   Comment: In this open-label, randomized trial, children who received more than 36 weeks of an ABC + 3TC-containing first-line regimen twice daily in the ARROW trial were randomized to continue the twice-daily regimen (n=333) or switch to once daily (n=336). At week 48, viral load suppression was comparable between the two groups (difference -1.6%, 95% Cl -8.4 to 5.2%, p=0.65).
   

7. Walmsley SL, Antela A, Clumeck N, et al. Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection. N Engl J Med. 2013;369(19):1807-18.  [PMID:24195548]

   Comment: SINGLE was a phase 3, multicenter, randomized, double-blind, noninferiority trial that compared once-daily DTG 50 mg + ABC 600 mg/3TC 300 mg (n=414) with EFV 600 mg/TDF 300 mg/FTC 200 mg (n=419) in ART-naive HIV-infected adults who were negative for the HLA-B*5701 screening. Virologic suppression (defined as HIV-1 RNA VL < 50 copies/mL at week 48) was significantly higher for those who received DTG + ABC/3TC than EFV/TDF/FTC (DTG + ABC/3TC 88 vs. EFV/TDF/FTC 81%, difference 7, 95% Cl 2 to 12) demonstrating superiority. Additionally, a shorter median time to viral suppression and a greater increase in median CD4+ cell count was observed in those who received DTG + ABC/3TC (DTG + ABC/3TC 28 vs. EFV/TDF/FTC 84 days, p< 0.001 and DTG + ABC/3TC 267vs. EFV/TDF/FTC 208 cells/mm³, p< 0.001, respectively). Rash and neuropsychiatric events were significantly more common in those who received EFV/TDF/FTC, while insomina was more common in those who received DTG + ABC/3TC.
   

8. Post FA, Moyle GJ, Stellbrink HJ, et al. Randomized comparison of renal effects, efficacy, and safety with once-daily abacavir/lamivudine versus tenofovir/emtricitabine, administered with efavirenz, in antiretroviral-naive, HIV-1-infected adults: 48-week results from the ASSERT study. J Acquir Immune Defic Syndr. 2010;55(1):49-57.  [PMID:20431394]

   Comment: The ASSERT study was a multicenter, randomized, open-label study that evaluated the safety and efficacy of a daily dose of ABC 600 mg/3TC 300 mg (n=192) vs. TDF 300 mg/FTC 200 mg (n=193) in ART-naive, HLA-B*5701-negative HIV-infected adults. Both groups also received daily EFV 600 mg. Virologic failure (defined as failure to achieve 1-log reduction by week 4, or a confirmed rebound to ≥400 copies/mL after confirmed reduction to < 400 copies/mL after week 24) at week 48 was lower in those who received TDF/FTC than ABC/3TC in respect to achieving VL < 400 copies/mL (TDF/FTC 77 vs. ABC/3TC 67%, difference 9.5, 95% Cl 0.6 to 18.4) and achieving VL < 50 copies/mL (TDF/FTC 71 vs. ACT/3TC 59%, difference 11.6, 95% Cl 2.2 to 21.1). Although the difference was primarily driven by investigator-reported lack of efficacy and early withdrawals before virologic suppression. Additionally, while there was no difference in changes in eGFR from baseline between the two groups, those who received TDF/FTC had a higher rate of increase in markers of tubular dysfunction which was measured by retinol-binding protein and β-2 microglobulin (+50% and +24%, respectively for TDF/FTC; no change and -47%, respectively for ABC/3TC).
   

9. Musiime V, Kendall L, Bakeera-Kitaka S, et al. Pharmacokinetics and acceptability of once- versus twice-daily lamivudine and abacavir in HIV type-1-infected Ugandan children in the ARROW Trial. Antivir Ther. 2010;15(8):1115-24.  [PMID:21149918]

   Comment: The ARROW crossover pharmacokinetic study included 41 children aged 3-12 years who received combination treatment contanining ABC + 3TC twice daily (300 mg/150 mg, 450 mg/225 mg, and 300 mg + 600 mg/225 mg, for 12-< 20, 20-< 25, and ≥25 kg, respectively) then switched to once-daily once steady state was achieved. The AUCs of both ABC and 3TC were comparable between once- and twice-daily dosing regimens.
   

10. Smith KY, Patel P, Fine D, et al. Randomized, double-blind, placebo-matched, multicenter trial of abacavir/lamivudine or tenofovir/emtricitabine with lopinavir/ritonavir for initial HIV treatment. AIDS. 2009;23(12):1547-56.  [PMID:19542866]

    Comment: The HEAT trial was a randomized, double-anonymized, placebo-matched, non-inferiority study comparing once-daily regimen of ABC 600 mg/3TC 300 mg (n=343) and TDF 300 mg/FTC 200 mg (n=345) in ART-naive, HIV infected adult patients with HIV-1 RNA VL ≥1000 copies/mL. Both groups also received once-daily LPV 800 mg/r 200 mg. Virologic suppression (defined as HIV-1 RNA VL < 50 copies/mL at week 48) was comparable between those who received ABC/3TC and TDF/FTC (ABC/3TC 68 vs. TDF/FTC 67%, diffference 1, 95 Cl -6.63 to 7.40) estalbishing non-inferiority. Additionally, a similar outcome was observed when stratified by baseline VL of ≥100K (difference 2% at 48 weeks) and VL < 100K (difference 2% at 48 weeks).
    

11. Sax PE, Tierney C, Collier AC, et al. Abacavir-lamivudine versus tenofovir-emtricitabine for initial HIV-1 therapy. N Engl J Med. 2009;361(23):2230-40.  [PMID:19952143]

    Comment: In this phase 3B, randomized, partially blinded study (ACTG 5202), once-daily ABC 600 mg/3TC 300 mg (n=398) was compared to TDF 300 mg/FTC 200 mg (n=399) in HIV infected individuals who were at least 16 years of age and had received at most 7 days of ARV previously. Both groups also received once-daily ATV 300 mg/r 100 mg or EFV 600 mg. At median follow-up of 60 weeks, those with HIV-1 RNA VL >100K copies/mL and received ABC/3TC had a significantly shorter time to virologic failure (defined as HIV-1 RNA VL ≥1000 copies/mL at 16 weeks and before 24 week, or ≥200 copies/mL after 24 weeks) than those who received TDF/FTC (HR 2.33, 95% Cl 1.46 to 3.72) even after adjusting for prespecified baseline factors as main effects (HR 2.08, 98% Cl 1.28 to 3.37). Additionally, the time to first adverse event was shorter in those who received ABC/3TC than in those who received TDF/FTC (HR 1.89, 95% CI 1.43 to 2.50), with more patients in the ABC/3TC group having higher fasting lipid levels.
    

12. Mallal S, Phillips E, Carosi G, et al. HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med. 2008;358(6):568-79.  [PMID:18256392]

    Comment: In this double-blind, prospective, randomized study, the effectiveness of prospective HLA-B*5701 screening to prevent ABC hypersensitivity reaction was evaluated in 1956 HIV patients who were treatment-naive to ABC. Patients were randomized to either prosective-screening (prospective HLA-B*5701 screening followed by exclusion of positive patients from ABC treatment) or standard-of-care (use of ABC without prospective HLA-B*5701 screening). The prevalence of HLA-B*5701 was 5.6%. Screeening significantly reduced the incidence of ABC hypersensitivty reaction (difference 2.7%, p< 0.001), with a negative predicative valve of 100% and a positive predictive value of 47.9%.
    

13. D:A:D Study Group, Sabin CA, Worm SW, et al. 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. 2008;371(9622):1417-26.  [PMID:18387667]

    Comment: D: A:D study was an international collaboration of 11 cohorts with 33,347 HIV adult patients that evaluated the relationship between NRTI and risk of myocardial infarction. After adjusting for cardiovascular risk factors that are unlikely to be affected by ART, cohort, calendar year, and use of other ARTs, recent but not cumulative use of ABC and ddI was associated with an increased rate of myocardial infaraction (RR 1.90, 95% Cl 1.47 to 2.45, p=0.0001 and RR 1.49, 95% Cl 1.14 to 1.95, p=0.003, respectively). This results were consistent even after adjusting for predicted 10-years risk of coronary heart disease.
    

14. Lamarca A, Clumeck N, Plettenberg A, et al. Efficacy and safety of a once-daily fixed-dose combination of abacavir/lamivudine compared with abacavir twice daily and lamivudine once daily as separate entities in antiretroviral-experienced HIV-1-infected patients (CAL30001 Study). J Acquir Immune Defic Syndr. 2006;41(5):598-606.  [PMID:16652033]

    Comment: CAL30001 was a multicenter, randomized, open-label, parallel-group study that compared once-daily ABC/3TC and twice-daily ABC + 3TC in ART-experienced, HIV adult patients who were experiencing virologic failure. Both groups also received TDF and PI or NRTI. The primary endpoint was time-average change from baseline (AUC minus baseline) in HIV-1 RNA VL over 48 weeks, and there was no difference between the groups (Once-daily -1.65 vs. Twice-daily -1.83 log10 copies/mL, 95% Cl -0.13 to 0.38), demonstrating noninferiority.
    

15. Moyle GJ, DeJesus E, Cahn P, 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. J Acquir Immune Defic Syndr. 2005;38(4):417-25.  [PMID:15764958]

    Comment: CNA30021 was a multicenter, randomized, double-blind trial that compared twice-daily ABC 300 mg (n=380) to once-daily ABC 600 mg (n=384) in ART-naive, HIV adult patients. Both groups also received once-daily 3TC 300 mg and EFV 600 mg. Virologic suppression (defined as HIV-1 RNA VL < 50 copies/mL at week 48) was comparable between the two groups (Once-daily regimen 66% vs. Twice-daily regimen 68%; difference -1.7, 95% CI -8.4 to 4.9), demonstrating non-inferiority. Additionally, virologic suppression was comparable between the two groups when stratified by baseline HIV-1 RNA VL (≤100K vs. >100K). Change in median CD4+ cells/mm3 from baseline through week 48 was also comparable between the two groups (Once-daily regimen: 188 vs. Twice-daily regimen: 200 cells/mm³).
    

16. Bergshoeff A, Burger D, Verweij C, et al. Plasma pharmacokinetics of once- versus twice-daily lamivudine and abacavir: simplification of combination treatment in HIV-1-infected children (PENTA-13). Antivir Ther. 2005;10(2):239-46.  [PMID:15865218]

    Comment: The PENTA-13 crossover pharmacokinetic study included 24 children aged 2-13 years who received combination treatment containing ABC 8 mg/kg + 3TC 4 mg/kg twice-daily, then switched to once-daily once steady state was achieved. AUC and Cmax of both ABC and 3TC were comparable between once- and twice-daily dosing regimen.
    

17. DeJesus E, Herrera G, Teofilo E, et al. Abacavir versus zidovudine combined with lamivudine and efavirenz, for the treatment of antiretroviral-naive HIV-infected adults. Clin Infect Dis. 2004;39(7):1038-46.  [PMID:15472858]

    Comment: CNA30024 was a multicenter, double-blind, controlled, non-inferiority trial that compared twice-daily ABC 300 mg (n=324) to ZDV 300 mg (n=325) in ART-naive, HIV adult patients. Both groups also received 3TC 150 mg twice daily and EFV 800 mg once daily. Virologic suppression (defined as HIV-1 RNA VL ≤50 copies/mL at week 48) was comparable between the two groups (ABC 70% vs. ZDV 69%; difference 1, 95% CI -6.3 to 7.9), demonstrating non-inferiority. Virologic suppression did not differ between the two groups when stratified by baseline HIV-1 RNA VL (≤100K vs. >100K copies/mL). Those who received ABC had a greater increase in median absolute CD4+ count at week 48 (ABC 209 vs. ZDV 155 cells/mm³, p=0.005). Those who received ZDV had a higher incidence of nausea, vomiting, and fatigue. Those who received ABC had a higher incidence of allergic reaction.
    

18. Mallal S, Nolan D, Witt C, et al. Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir. Lancet. 2002;359(9308):727-32.  [PMID:11888582]

    Comment: This study found an extraordinary association between the presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 alleles and HSR to ABC (OR 822 [43-15675], p< 0.0001). The authors concluded that withholding ABC in the presence of these alleles would decrease the prevalence of HSR from 9% to 2.5%. Positive predictive value for HSR 100%, negative predictive value 97%.
    

19. Hewitt RG. Abacavir hypersensitivity reaction. Clin Infect Dis. 2002;34(8):1137-42.  [PMID:11915004]

    Comment: This review article provides an overview of abacavir hypersensitivity reaction, including epidemiology, proposed pathogenesis, clinical presentation, and management.
    

20. Izzedine H, Launay-Vacher V, Aymard G, et al. Pharmacokinetics of abacavir in HIV-1-infected patients with impaired renal function. Nephron. 2001;89(1):62-7.  [PMID:11528234]

    Comment: This is a pharmacokinetic study on the use of abacavir 600 mg or 300 mg q12-24h in HIV-infected patients with renal dysfunction, including those on chronic hemodialysis (4-hour session with a high permeability membrane).
    

21. Staszewski S, Keiser P, Montaner J, et al. Abacavir-lamivudine-zidovudine vs indinavir-lamivudine-zidovudine in antiretroviral-naive HIV-infected adults: A randomized equivalence trial. JAMA. 2001;285(9):1155-63.  [PMID:11231744]

    Comment: CNA3005 was a multicenter, double-blind, controlled trial that compared ABC 300 mg twice daily (n=262) to IDV 800 mg three times per day (n=265) in ART-naive, HIV adult patients. Both groups also received twice-daily 3TC 150 mg + ZDV 300 mg. Virologic suppression (defined as HIV-1 RNA VL < 400 copies/mL at week 48) was comparable between the two groups (ABC 51% vs. IDV 51%; difference -0.6, 95% CI -9 to 8). However, those with baseline VL >100K copies/mL and received IDV had a higher rate for achieving virologic suppression of < 50 copies/mL by week 48 than ABC (IDV 45 vs. ABC 31%, difference 14, 95% Cl -27 to 0). The increase in median absolute CD4+ count at week 48 was comparable between the two groups (ABC 107 vs. IDV 93 cell/mm³; difference of 3; 95% CI -24 to 19). The incidence of adverse side effects was comparable between the two groups.
    

22. Sáez-Llorens X, Nelson RP, Emmanuel P, et al. A randomized, double-blind study of triple nucleoside therapy of abacavir, lamivudine, and zidovudine versus lamivudine and zidovudine in previously treated human immunodeficiency virus type 1-infected children. The CNAA3006 Study Team. Pediatrics. 2001;107(1):E4.  [PMID:11134468]

    Comment: CNAA3006 was a multicenter, double-blind, randomized, placebo-controlled trial that compared triple-therapy, twice-daily ABC 8 mg/kg + 3TC 4 mg/kg + ZDV 180 mg/m² to dual-therapy, twice-daily 3TC 4 mg/kg + ZDV 180 mg/m2 in ART-experienced HIV pediatric patients. Virologic suppression (defined as HIV-1 RNA VL ≤10K copies/mL at week 48) was significantly higher in those who received triple-therapy (triple-therapy 33 vs. dual-therapy 21%). Additionally, virologic suppression was considerably greater in those with baseline HIV-1 RNA VL >10K copies/mL who received triple therapy (29% vs. 12% with dual treatment); however, this difference was not observed when baseline HIV-1 RNA VL was ≤10K copies/mL. Lastly, the median change in CD4+ count from baseline was also greater for triple-therapy.