Combination dolutegravir–abacavir–lamivudine in the management of HIV/AIDS: clinical utility and patient considerations

Figures & data

Table 1 Clinical trials of DTG in first-line treatment (naïve patients)

Study	Regimens	No of patients	Weeks of treatment	Rates (%) of patients with VL <50 copies/mL	Rates (%) of patients with AEs leading to discontinuation	Notes
SPRING-1^Citation48,Citation49	DTG (10, 25, or 50 mg od) vs EFV, both with ABC/3TC or TDF/FTC	155 vs 50	48^Citation48 and 96^Citation49	88 vs 72 82 vs 72	<1 vs 8 3 vs 10	RCT, partially blinded, Phase IIb dose-ranging trial
SPRING-2^Citation51,Citation52	DTG (50 mg od) vs raltegravir (400 bid) with NRTI backbone	411 vs 411	48^Citation51 and 96^Citation52	88 vs 85 81 vs 76	2 vs 2 2 vs 2	RCT, double-blind trial; DTG noninferior to raltegravir and no evidence of emergence of resistance in DTG arm
SINGLE^Citation50	DTG/ABC/3TC vs EFV/TDF/FTC	422 vs 422	48	88 vs 81	2 vs 10	DTG/ABC/3TV had a better safety profile and was more effective than EFV/TDF/FTC
FLAMINGO^Citation53	DTG vs DRV/r	242 vs 242	48	90 vs 83	2 vs 4	DTG superior to EFV (P=0.003) primarily because discontinuation rate greater in EFV

Abbreviations: DTG, dolutegravir; VL, viral load; AEs, adverse events; od, once daily; EFV, efavirenz; ABC, abacavir; 3TC, lamivudine; TDF, tenofovir; FTC, emtricitabine; RCT, randomized controlled trial; bid, twice daily; NRTI, nucleoside/nucleotide reverse transcriptase inhibitor; DRV/r, DRV + ritonavir.

Table 2 Clinical trials of DTG in second-line treatment (ARV-experienced patients, INSTI naïve or experienced)

Study	Regimens	No of patients	Weeks of treatment	Rates (%) of patients with VL <50 copies/mL	Rates (%) of patients with AEs leading to discontinuation	Notes
SAILING^Citation54	DTG 50 mg vs raltegravir 400 bid + OBT	354 vs 361	48	71 vs 64	1 vs 1	INSTI-naïve patients; RCT, double blind
VIKING (Cohort I)^Citation55	DTG 50 mg od + OBT	27	24	41	No severe AE related to DTG reported	Phase IIb, open label, single arm; INSTI resistant
VIKING (Cohort II)^Citation55	DTG 50 mg bid + OBT	24	24	75	No severe AE related to DTG reported	Phase IIb, open label, single arm; INSTI resistant
VIKING-3^Citation56	DTG 50 mg bid + OBT	183	24	69	2.7	Phase III, open label, single arm; INSTI resistant

Abbreviations: DTG, dolutegravir; VL, viral load; AEs, adverse events; bid, twice daily; OBT, optimized background therapy; INSTI, integrase strand transfer inhibitor; RCT, randomized controlled trial; od, once daily.

Figure 1 Comparative efficacy data of EFV/TDF/FTC and DTG/ABC/3TC at week 48, according to strata and subgroups. Data from.⁵⁰

Abbreviations: EFV, efavirenz; TDF, tenofovir; FTC, emtricitabine; DTG, dolutegravir; ABC, abacavir; 3TC, lamivudine; CI, confidence interval; HIV-1, human immunodeficiency virus type 1; RNA, ribonucleic acid.

Table 3 US guidelines – Department of Health and Human Services (May 2014).¹ Recommended initial combination regimens for all patients, regardless of initial viral load or CD4 count

Regimens	Rating*	Notes
NNRTI based
• EFV/TDF/FTC	A1
PI based
• ATV/r plus TDF/FTC	A1
• DRV/r plus TDF/FTC	A1
INSTI based
• DTG plus ABC/3TC	A1	Only for patients HLA-B*5701 negative
• DTG plus TDF/FTC	A1
• EVG/COBI/TDF/FTC	A1	Only for patients with pretreatment CrCl ≥70 mL/min
• RAL plus TDF/FTC	A1

Note:

* A1, strong recommendation from randomized clinical trials.

Abbreviations: NNRTI, nonnucleoside reverse transcriptase inhibitor; EFV, efavirenz; TDF, tenofovir; FTC, emtricitabine; PI, protease inhibitor; ATV/r, atazanavir + ritonavir; DRV/r, darunavir + ritonavir; INSTI, integrase strand transfer inhibitor; DTG, dolutegravir; ABC, abacavir; 3TC, lamivudine; EVG, elvitegravir; COBI, cobicistat; RAL, raltegravir; CrCl, creatinine clearance.

Table 4 European AIDS Clinical Society (EACS) updated guidelines (November 2014), modified.² Recommended initial regimens for HIV-infected adult patients. A drug from column A should be combined with the NRTI backbone listed in column B

A	B	Notes
NNRTI	NRTI
• EFV	ABC/3TC or TDF/FTC*	ABC/3TC, TDF/FTC, EFV/TDF/FTC coformulated
• RPV**	ABC/3TC or TDF/FTC	RPV/TDF/FTC coformulated
PI/r
• ATV/r	ABC/3TC or TDF/FTC
• DRV/r	ABC/3TC or TDF/FTC
INSTI
• EVG + COBI	TDF/FTC	TDF/FTC/EVG/COBI coformulated
• DTG	ABC/3TC or TDF/FTC	ABC/3TC/DTG coformulated
• RAL	ABC/3TC or TDF/FTC

Notes:

* ABC contraindicated if HLA-B*5701 positive;

** RPV: only if HIV viral load <100,000 copies/mL.

Abbreviations: HIV, human immunodeficiency virus; NNRTI, nonnucleoside reverse transcriptase inhibitor; EFV, efavirenz; ABC, abacavir; 3TC, lamivudine; TDF, tenofovir; FTC, emtricitabine; EFV, efavirenz; RPV, rilpivirina; PI, protease inhibitor; ATV/r, atazanavir + ritonavir; DRV/r, darunavir + ritonavir; INSTI, integrase strand transfer inhibitor; COBI, cobicistat; DTG, dolutegravir; RAL, raltegravir.

van LunzenJMaggioloFArribasJOnce daily dolutegravir (S/GSK1349572) in combination therapy in antiretroviral-naïve adults with HIV: planned interim 48 week results from SPRING-1, a dose-ranging, randomised, phase 2b trialLancet Infect Dis201212211111822018760

 PubMed Web of Science ®Google Scholar

StellbrinkHReynesJLazzarinADolutegravir in antiretroviral- naïve adults with HIV-1: 96-week results from a randomized dose-ranging studyAIDS2013271771177823807273

 PubMed Web of Science ®Google Scholar

RaffiFRachlisAStellbrinkHJOnce-daily dolutegravir versus raltegravir in antiretroviral-naïve adults with HIV-1 infection: 48 week results from the randomised, double-blind, non-inferiority SPRING-2 studyLancet2013381986873574323306000

 PubMed Web of Science ®Google Scholar

RaffiFJaegerHQuiros-RoldanEOnce-daily dolutegravir versus twice-daily raltegravir in antiretroviral-naïve adults with HIV-1 infection (SPRING-2 study): 96 week results from a randomised, double-blind, non-inferiority trialLancet Infect Dis2013131192793524074642

 PubMed Web of Science ®Google Scholar

WalmsleySAntelaAClumeckNDolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infectionN Engl J Med2013369191807181824195548

 PubMed Web of Science ®Google Scholar

ClotetBFeinbergJvan LunzenJOnce-daily dolutegravir versus darunavir plus ritonavir in antiretroviral-naïve adults with HIV-1 infection (FLAMINGO): 48 week results from the randomised open-label phase 3b studyLancet201438399362222223124698485

 PubMed Web of Science ®Google Scholar

CahnPPozniakALMingroneHDolutegravir vs raltegravir in antiretroviral-experienced, integrase-inhibitor-naïve adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING studyLancet2013382989370070823830355

 PubMed Web of Science ®Google Scholar

EronJJClotetBDurantJSafety and efficacy of dolutegravir in treatment-experienced subjects with raltegravir resistant HIV type 1 infection: 24-week results of the VIKING studyJ Infect Dis2013207574074823225901

 PubMed Web of Science ®Google Scholar

CastagnaAMaggioloFPencoGDolutegravir in antiretroviral-experienced patients with raltegravir- and/or elvitegravir-resistant HIV-1: 24-week results of the phase III VIKING-3 studyJ Infect Dis2014210335436224446523

 PubMed Web of Science ®Google Scholar

Panel on Antiretroviral Guidelines for Adults and AdolescentsGuidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and AdolescentsDepartment of Health and Human Services Available at: http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdfAccessed January 27, 2015

 Google Scholar

European AIDS Clinical SocietyGuidelines Clinical Management and Treatment of HIV Infected Adults in Europe. 7.1112014 Available at: http://www.eacsociety.org/Portals/0/GUIDELINES/English%20PDF%20-%20Version%207.1.pdfAccessed January 27, 2015

 Google Scholar