Treatment simplification in HIV-infected adults as a strategy to prevent toxicity, improve adherence, quality of life and decrease healthcare costs

Figures & data

Figure 1 1996 to 2011, from multiple drugs to once-daily and more potent antiretroviral therapy regimens: the long road to patient satisfaction and adherence.

Table 1 Avantages and disadvantages of fixed-doses combinations (FDCs)

Advantages of FDCs

Decreased pill burden

Better adherence

Prescription errors less likely

Patients unable to take partial regimen

Experience of FDCs with other diseases such as tuberculosis, malaria etc

Practical for management in large programs (improved drug supply systems)

Cheaper in generic form (eg, in resource-limited settings)

Disadvantages of FDCs

Does not accommodate lead-in dose

Difficult to use when dose adjustments are needed (eg, renal failure)

Need to stop FDC for adverse drug reaction to one component

Limited availability of pediatric formulations

More expensive if generic version of one or more components available (developed countries)

Table 2 Approved and under study antiretroviral therapy coformulations

	Type
Approved coformulations
AZT/3TC	Dual NRTI
d4T/3TC	Dual NRTI
ABC/3TC*	Dual NRTI
TDF/FTC*	Dual NRTI
TDF/FTC/EFV*	Dual NRTI + NNRTI
TDF/3TC/EFV	Dual NRTI + NNRTI
AZT/3TC/NVP	Dual NRTI + NNRTI
d4T/3TC/NVP	Dual NRTI + NNRTI
AZT/3TC/ABC*	Triple NRTI
LPV/r*	Boosted PI
Coformulations under study
TDF/FTC/rilpivirine	Dual NRTI + NNRTI
TDF/FTC/elvitegravir/cobicistat	Dual NRTI + boosted integrase inhibitor

Note:

* Available in United States.

Abbreviations: AZT, zidovudine; 3TC, lamivudine; d4T, stavudine; ABC, abacavir; TDF, tenofovir disoproxil fumarate; FTC, emtricitabine; EFV, efavirenz; LPV/r, lopinavir/ritonavir; NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.

Table 3 Summary of recent studies comparing QD to BID or TID HIV regimens

Author and ref.	Study design	n	Adherence endpoint	Duration	Results	Population
Bangsberg et al^Citation11	Prospective observational study assessing adherence and virologic response to EFV/TDF as single-tablet regimen (STR)	658	Adherence and viral suppression compared to historical controls from the same cohort	6 months	Adherence was higher in EFV/FTC/TDF STR regimen compared to multiple pill regimens (P = 0.006) after controlling for multiple confounders. Viral suppression (HIV RNA < 50 copies/mL) was greater in EFV/FTC/TDF STR than multiple pill regimens (69.2% versus 46.5%; P = 0.02). No difference in viral suppression after controlling for adherence.	Homeless and marginally housed HIV+ individuals
Airoldi et al^Citation13	ADONE: prospective, multicenter, open-label, comparative study with a within-patient analysis	202	Effect of simplification of the ARV regimen on adherence	6 months	One month after switch to the fixed-dose coformulation (FDC), adherence increased to 96.1% (baseline 93.8%) (P < 0.01), and was 96.2% at 6 months. QoL improved over time from 68.8% to 72.7% (P = 0.042). QoL was significantly associated with adherence (P < 0.0001). During FDR use the mean CD4 count increased from 556 to 605 cells/mm^3 (P < 0.0001).	Patients chronically treated with emtricitabine (FTC) + tenofovir (TDF) + efavirenz (EFV) or lamivudine (3TC) + TDF + EFV and with a HIV-RNA < 50 copies/mL.
DeJesus et al^Citation12	Randomized controlled trial comparing TDF/FTC/EFV QD versus BID versus TID	567	Adherence as measured by pill count	6 months	Improved adherence with single tablet regimen of TDF/FTC/EFV with QD as compare to BID or TID (P < 0.01 for all comparisons)	ART-naïve adults initiating HAART
Zajdenverg et al^Citation10	Randomized controlled trial LPV/r tab. QD versus BID + NRTIs in ART-experienced	599	Non-compliance (ingestion, correct dose, time of ingestion)	6 months	Through 24 weeks, QD dosing of LPV/r resulted in higher treatment compliance than BID dosing <50 copies/mL and 100% <400 copies/mL	HIV treatment-experienced patients
Maitland et al^Citation7	Randomized, open-label study comparing adherence, efficacy and safety of immediate versus delayed switching from ABC + 3TC BID to ABC/3TC FDC QD.	94	Patients’ satisfaction measured by HIVTSQ Questionnaire; Adherence by MEMS caps	8 weeks	Treatment compliance [BID versus QD] 99.2% (90.7%–100%) versus 96.6% (60.0%–100%) (P50.017); dosing compliance 97.1% (64.3%–100%) versus 91.9% (33.3%–100%) (P50.016); and timing compliance 95.5% (53.8%–100%) versus 86.3% (4.3%–100%) (P50.006). Treatment satisfaction increased significantly at week 4 with ABC/3TC QD [92% (82%–99%) versus 85% (75%–93%) (P50.004)].	UK-based single-center, open-label study in HIV-infected patients with VL < 50 copies/mL).
Boyle et al^Citation9	Open-label, randomized, multicenter, phase 3B noninferiority study to evaluate a BID + (twice daily or greater) regimen versus a QD regimen	320 QD = 213, BID = 107	Proportion of patients who maintained plasma HIV RNA < 50 copies/mL at Week 48 after switching to the QD arm compared with patients in the BID + arm.	48 weeks	The QD arm was noninferior to the BID + arm in the primary efficacy measure (proportion of patients who maintained suppression at Week 48; QD arm, 80.0% versus BID + arm, 75.8%). Adherence and treatment satisfaction significantly favored the QD arm, in which 91.0% of patients preferred the simpler regimen.	HIV– infected adult patients with a VL < 50 copies/mL on a twice-daily or more frequent ARV regimen.
Wright et al^Citation8	To evaluate the safety and antiviral activity of QD enfuvirtide (ENF) compared with BID ENF.	Total = 61; QD = 30, BID = 31	Proportion of patients achieving a HIV RNA <400 copies/mL	48 weeks	At Week 48, 23.3% of QD patients versus 22.6% of BID (P = 0.969) achieved HIV RNA < 400 copies/mL, and 13.3% and 22.6% (P = 0.323), respectively, achieved <50 copies/mL. No significant differences in AEs were noted. Adherence (95% of prescribed doses) was higher with once daily (80.0%) versus twice daily (58.1%) ENF.	Eligible patients were ENF-naive, on an unchanged pre-study regimen for ≥28 days with a VL of ≥5000 copies/mL, and had prior experience or documented resistance to 3 classes of approved ARVs (PIs, NRTIs, and NNRTIs).

Abbreviations: EFV, efavirenz; FTC, emtricitabine; TDF, tenofovir disoproxil fumarate; STR, single-tablet regimen; FDC, fixed-dose coformulation; ART, antiretroviral therapy; HAART, highly active antiretroviral therapy; LPV/r, lopinavir/ritonavir; NRTI, nucleoside reverse transcriptase inhibitor; ABC, abacavir; MEMS caps, Medication Monitor Event Systems (MEMS); ENF, enfuvirtide; 3TC, lamivudine; ARV, antiretroviral; NNTRI, non-nucleoside reverse transcriptase inhibitor; VL, viral load; PI, protease inhibitor; AE, adverse events; QoL, quality of life.

BangsbergDRRaglandKMonkAA single tablet regimen is associated with higher adherence and viral suppression than multiple tablet regimens in HIV+ homeless and marginally housed peopleAIDS201024182835284021045636

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AiroldiMZaccarelliMBisiLOne-pill once-a-day HAART: a simplification strategy that improves adherence and quality of life of HIV-infected subjectsPatient Prefer Adherence2010411512520517472

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DeJesusEPozniakAGallantJImprovement in Fasting Lipids but Minimal Recovery of Limb Fat Were Seen 96 Weeks After Switching from Lamivudine/Zidovudine Plus Efavirenz to Fixed-Dose Efavirenz/Emtricitabine/Tenofovir DF in HIV-Infected Patients49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC)September 12–15, 2009San Francisco, CA USA Poster# H-1572. Available from: http://www.hivandhepatitis.com/2009icr/icaac/pdfs/2_DeJesus.pdf. Accessed July 10, 2011.

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ZajdenvergRBadal-FaesenAndrade-VillanuevaJLopinavir/ritonavir (LPV/r) tablets administered once-(QD) or twice-daily (BID) with NRTIs in antiretroviral-experienced HIV-1 Infected subjects: results of a 48-week randomized trial (Study M06-802)5th IAS Conference on HIV pathogenesis, Treatment and PreventionCape Town, South Africa2009 Jul 19–22 Available from: http://www.ias2009.org/pag/Abstracts.aspx?AID=1249.

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MaitlandDJacksonAOsorioJSwitch Study TeamSwitching from twice-daily abacavir and lamivudine to the once-daily fixed-dose combination tablet of abacavir and lamivudine improves patient adherence and satisfaction with therapyHIV Med20089866767218631255

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BoyleBAJayaweeraDWittMDRandomization to once-daily stavudine extended release/lamivudine/efavirenz versus a more frequent regimen improves adherence while maintaining viral suppressionHIV Clin Trials20089316417618547903

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WrightDRodriguezAGodofskyEEfficacy and safety of 48 weeks of enfuvirtide 180 mg once-daily dosing versus 90 mg twice-daily dosing in HIV-infected patientsHIV Clin Trials200892738218474492

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