АРТ в 2016-2017 гг: неизменная потребность в...

©2016 Academy of Managed Care Pharmacy

Antiretroviral Therapy 2016-2017: The Continuing Need for

Individualized Therapy to Optimize Outcomes Among Diverse HIV

Patients

Jointly presented by AMCP and CCO

FacultyDanielle Ciuffetelli, PharmD

Ambulatory Hepatology/Infectious Diseases Clinical PharmacistHospital of the University of Pennsylvania

Philadelphia, Pennsylvania 

Elly Fatehi, PharmD, BCPSDirector of Clinical Pharmacy

Amida CareNew York, New York 

Special Acknowledgement: Terry D. Leach, PharmD

Vice President of PharmacyAmida Care

New York, New York

Financial Relationship Disclosures

• Danielle Ciuffetelli, PharmD, reports having no financial relationships with any commercial interests during the past 12 months.

• Elly Fatehi, PharmD, BCPS, reports having no financial relationships with any commercial interests during the past 12 months.

• Terry D. Leach, PharmD, reports having no financial relationships with any commercial interests during the past 12 months.

*This educational activity is supported by an unrestricted educational grant from Janssen Therapeutics.*

©2016 Academy of Managed Care Pharmacy

Clinical Perspective on Treating Diverse HIV Patient Populations   

Danielle Ciuffetelli, PharmDAmbulatory Hepatology/Infectious Diseases

Clinical PharmacistHospital of the University of Pennsylvania

Philadelphia, Pennsylvania

Evolving HIV (Human Immunodeficiency Virus) Treatment Landscape

• Numerous effective regimens• Fewer toxicities• Increased lifespan leading to aging population

and increased duration on therapies• Opportunity to individualize treatment

Opportunities to Tailor a Regimen

Medications Factors• Efficacy• Safety profile

– Short- and long-term• Genetic barrier to

resistance• Rate of transmitted

resistance• Dosing frequency• Pill size

Individual Factors• Pretreatment viral load

and CD4+ cell count• Drug resistance results• HLA-B*5701 status

• Human leukocyte antigen• Comorbidities• Concomitant medications• Patient preferences

Antiviral Drug Potency and Genetic Barrier to Resistance

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ange

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FTC3TC

2log

3log

Genetic Barrier to Resistance (Approximate no. of mutations needed to fail)

1 2 3 4

RPV

EVGRALEFV

ABCTDF

DTG DRV/RTV

1log

ATV/RTV

Recommended Regimens

ABC: abacavir; 3TC: lamivudine; FTC: emtricitabine; TAF: tenofovir alafenamide; TDF: tenofovir disoproxil fumarate.

• ART recommended for all HIV-infected pts, regardless of CD4+ cell count

• Regimen recommendations may differ based on CrCl, eGFR, HLA-B*5701 status, HBsAg status, and osteoporosis status

Class DHHS IAS-USAINSTI DTG/ABC/3TC

DTG + FTC/(TAF or TDF) EVG/COBI/FTC/(TAF or TDF) RAL + FTC/(TAF or TDF)

DTG/ABC/3TC DTG + FTC/TAF EVG/COBI/FTC/TAF RAL + FTC/TAF

Boosted PI DRV + RTV + FTC/(TAF or TDF)

Alternative Regimens• For some patients, an alternative regimen may be the best

choice based on individual factors

• Recommendations may differ based on baseline HIV-1 RNA, CD4+ cell count, CrCl, eGFR, HLA-B*5701 status, HBsAg status, and osteoporosis status

Class DHHS IAS-USABoosted PI

ATV + RTV + FTC/(TAF or TDF) ATV/COBI + FTC/(TAF or TDF) DRV + RTV + ABC/3TC DRV/COBI + ABC/3TC DRV/COBI + FTC/(TAF or TDF)

DRV + RTV + ABC/3TC DRV/COBI + ABC/3TC DRV + RTV + FTC/(TAF or TDF) DRV/COBI + FTC/(TAF or TDF)

NNRTI EFV/FTC/TDF EFV + FTC/TAF RPV/FTC/TAF RPV/FTC/TDF

EFV/FTC/TDF RPV/FTC/TAF RPV/FTC/TDF

EFV: efavirenz; RPV: rilpivirine; ATV: atazanavir; COBI: cobicistat; DRV: darunavir; RTV, ritonavir.

Case 1• JS arrives to clinic after lost to follow up for 1 year.

• She is HIV treatment naive, her HIV genotype is pending, CD4+ cell count is 80 cells/mm3, HIV viral load 75,000 copies/mL and HLA-B*5701 negative.

• She reports difficulty remembering to take medications everyday.

• One of her friends has been on efavirenz/emtricitabine/tenofovir DF for years and JS would like to start this medication.

• How would you proceed?

Elvitegravir Efficacy

Phase III Trials Study 102 Study 103 GS-0104/0111

Design Non-inferiority, treatment-naive

Study Arms E/C/F/TDF(n = 348)

EFV/F/TDF (n = 352)

E/C/F/TDF(n = 353)

ATV/RTV + F/TDF

(n = 355)

E/C/F/TAF(n = 866)

E/C/F/TDF(n = 867)

HIV VL < 50 c/mL* 88% 84% 90% 87% 92% 90%

Overall E/C/F/TDF non-inferior through Week 144

E/C/F/TDF Non-inferior through Week 144

E/C/F/TAF non-inferior through Week 96

ATV: atazanavir; C: cobicistat; R: ritonavir; EFV: efavirenz; E/C/F: elvitegravir/cobicistat/emtricitabine.

*At Week 48, primary endpoint.

Dolutegravir, Raltegravir, Darunavir Studies

Phase III Trials

SPRING-2 SINGLE FLAMINGO ACTG A5257

Design Non-inferiority, treatment-naive Treatment-naive, open-label, equivalence

Study Arms

DTG + 2 NRTIs(n = 411)

RAL + 2 NRTIs

(n = 411)

DTG + ABC/ 3TC

(n = 414)

EFV/ FTC/ TDF

(n = 419)

DTG + 2 NRTIs

(n = 242)

DRV + RTV + 2 NRTIs

(n = 242)

ATV + RTV + FTC/ TDF

(n = 605)

RAL + FTC/ TDF

(n = 603)

DRV + RTV + FTC/ TDF

(n = 601)

HIV VL < 50 c/mL*

88% 85% 88% 81% 90% 83% - - -

VF† - - - - - - 12.6% 9.0% 14.9%

Overall DTG non-inferior through Week 96

DTG superior through Week 144

DTG superior through Week 96

All 3 regimens equivalent for primary efficacy endpoint.‡

*At Week 48, primary endpoint for SPRING-2, SINGLE, and FLAMINGO. †Cumulative incidence of virologic failure (VF) over 96 weeks, primary endpoint for ACTG A5257. Defined as confirmed VL > 1000 c/mL at or after 16 weeks and before 24 weeks, or > 200 c/mL at or after 24 weeks. ‡For combined efficacy and tolerability endpoint, RAL superior to both PIs and DRV superior to ATV.

Efavirenz Disadvantages

• Most commonly transmitted mutations are with non-nucleoside reverse transcriptase inhibitors – Protease inhibitors and integrase inhibitors have the

lowest rate of transmitted mutations• Low genetic barrier to resistance• Higher incidence of adverse effects

– Neurotoxicities: abnormal dreams, depression, dizziness, headaches

• Involved in Cytochrome P450 3A4 (CYP3A4) and 2D6

TAF vs. TDF• TAF has improved renal profile

– Smaller decreases in creatinine clearance– Fewer discontinuations due to significant renal events– Can be used with CrCl down to 30 mL/min (vs 50 or 60

mL/min with TDF, depending on other drugs in regimen)• TAF has improved bone profile

– Significantly smaller reductions in hip and spine bone mineral density

• TDF has better lipid profile– Higher increases in fasting lipids in the TAF arms; TAF

lacks lipid protective effects observed with TDF• Each can be combined with different classes (INSTIs,

NNRTIs, PIs) as FTC/TAF or FTC/TDF

Choosing Among Recommended First-line Regimens

Drug Advantages Disadvantages

DTG

Available as STR with QD dosing High barrier to resistance No food requirement Superior to EFV and DRV/RTV Superior to RAL in tx-exp’d pts Superior to ATV/RTV in women

Only coformulated with ABC/3TC Serum Cr increases (inhibits tubular secretion) Insomnia, headache more frequent in some studies Largest pill size of STRs

EVG

Available as STR with QD dosing Superior to ATV/RTV in women

Requires PK boosting (COBI) and food with dosing Only coformulated with FTC/(TDF or TAF) High drug-drug interaction potential Serum Cr increases (from COBI

RAL

Longest safety record of INSTIs Fewest drug-drug interactions No food requirement Superior to ATV/RTV and DRV/RTV Recommended in pregnancy

Currently BID Not available as STR

DRV

Long safety record Highest barrier to resistance Recommended in pregnancy

DRV not yet available as STR Requires PK boosting and food with dosing High drug-drug interaction potential Higher rate of toxicity discontinuation vs INSTIs

Adherence Concerns and/or Resistance Data Pending

• Based on high barrier to resistance, latest DHHS guidelines recommend the following regimens in the absence of drug resistance testing:

– DRV + RTV + (FTC/TAF or FTC/TDF) or

– DTG + (FTC/TAF or FTC/TDF)

• Guidelines also note low incidence of treatment-emergent resistance with DRV/RTV over extensive period of clinical experience as favorable characteristic in setting of adherence concerns

Case 1• JS arrives to clinic after lost to follow up for 1 year.

• She is HIV treatment naive, her HIV genotype is pending, CD4+ cell count is 80 cells/mm3, HIV viral load 75,000 copies/mL and HLA-B*5701 negative.

• She reports difficulty remembering to take medications everyday.

• One of her friends has been on efavirenz/emtricitabine/tenofovir DF for years and JS would like to start this medication. How would you proceed?

• Recommend darunavir/ritonavir- or dolutegravir- based therapies based on safety/efficacy data, potential for non-adherence and starting before genotype is determined

Case 2

• AJ is a 45 y/o male with CrCl 45 ml/min, CD4+ cell count 380 cells/mm3, HIV viral load 200,000 copies/mL, and HLA-B*5701 negative.

• He has no other comorbidities • He has strong desire for single-tablet once daily

regimen. • What recommended or alternative regimens are

available for AJ?

Case 2

• AJ is a 45 y/o male with CrCl 45 ml/min, CD4+ cell count 380 cells/mm3, HIV viral load 200,000 copies/mL, and HLA-B*5701 negative.

• He has no other comorbidities • He has strong desire for single-tablet once daily

regimen. • What recommended or alternative regimens are

available for AJ?

Single-Tablet Regimens (STRs)

STR Generic Names* Preferred Initial Regimen?

EFV/FTC/TDFRPV/FTC/TAFRPV/FTC/TDFDTG/ABC/3TC EVG/COBI/FTC/TAF EVG/COBI/FTC/TDF *Currently no PI-based STRs available. DRV- and TAF-based STR in clinical development.

Case 2

• AJ is a 45 y/o male with CrCl 45 ml/min, CD4+ cell count 380 cells/mm3, HIV viral load 200,000 copies/mL, and HLA-B*5701 negative.

• He has no other comorbidities • He has strong desire for single-tablet once daily

regimen. • What recommended or alternative regimens are

available for AJ?

Renal Dosing Antiretroviral Regimens Creatinine Clearance RecommendationsDTG/ABC/3TC < 50 mL/min: Use not recommendedEVG/COBI/FTC/TDF or DRV/COBI + FTC/TDF

< 70 mL/min: Do not initiate

DTG + FTC/TDF orRAL + FTC/TDF orDRV + RTV + FTC/TDF orATV + RTV + FTC/TDF or EFV/FTC/TDF orRPV/FTC/TDF

< 50 mL/min: Use not recommended

DRV + RTV or DRV/COBI + FTC/TAF orDTG + FTC/TAF orEFV + FTC/TAF orEVG/COBI/FTC/TAF orRAL + FTC/TAF orRPV/FTC/TAF

< 30 mL/min: Use not recommended

Case 2

• AJ is a 45 y/o male with CrCl 45 ml/min, CD4+ cell count 380 cells/mm3, HIV viral load 200,000 copies/mL, and HLA-B*5701 negative.

• He has no other comorbidities • He has strong desire for single-tablet once daily

regimen. • What recommended or alternative regimens are

available for AJ?– RPV/FTC/TAF and EVG/COBI/FTC/TAF remaining

Baseline Considerations

Baseline Characteristic RecommendationsCD4+ cell count < 200 cells/mm3

Do NOT use:•Rilpivirine-based therapies

HIV Viral load > 100,000 copies/mL

Do NOT use:•Rilpivirine-based therapies•ABC/3TC with ritonavir- boosted atazanavir•ABC/3TC with efavirenz

HLA-B*5701 Positive Do NOT use:•Abacavir

Case 2

• AJ is a 45 y/o male with CrCl 45 ml/min, CD4+ cell count 380 cells/mm3, HIV viral load 200,000 copies/mL, and HLA-B*5701 negative.

• He has no other comorbidities • He has strong desire for single-tablet once daily

regimen. • What regimen is the best option for AJ?

– EVG/COBI/FTC/TAF appropriate regimen

Case 3

• PB is a 31 y/o female newly diagnosed with HIV. She wants a single-tablet regimen. Her CD4+ cell count is 650 cells/mm3, HIV viral load 50,000 copies/mL, and HLA-B*5701 negative.

• She has hepatitis C virus (HCV), genotype 1a, and is HCV treatment naive.

• Also, on lovastatin 20 mg daily for hyperlipidemia.

• What is the best recommended option for PB?

Case 3

• PB is a 31 y/o female newly diagnosed with HIV. She wants a single-tablet regimen. Her CD4+ cell count is 650 cells/mm3, HIV viral load 50,000 copies/mL, and HLA-B*5701 negative.

• She has hepatitis C virus (HCV), genotype 1a, and is HCV treatment naive.

• Also, on lovastatin 20 mg daily for hyperlipidemia.

• What is the best recommended option for PB?

Drug Interactions

Medication Potential for interactionsDarunavir Substrate/Inhibitor: CYP3A4, P-gp; Inducer: 2C9 Ritonavir Substrate: CYP3A4, 2D6, P-gp; Inhibitor:

CYP3A4, 2D6, P-gp; Inducer: CYP1A2, 2C8, 2C9, 2C19

Cobicistat Substrate/Inhibitor: CYP3A4, 2D6, P-gp (inhibit)Elvitegravir Substrate: CYP3A4; Inducer: CYP2C9 Tenofovir Substrate: P-gpDolutegravir Substrate: CYP3A4, P-gpRaltegravir No involvement in P-gp or CYP450

P-gp: P- glycoprotein.

Statin Interactions with Antiretrovirals (ARVs)

Statin DRV/r RAL DTG EVG NRTIsSimvastatinLovastatinAtorvastatinPitavastatinPravastatinRosuvastatin

Do not co-administerDose limit and/or statin titrationNo significant interaction anticipated

Case 3

• PB is a 31 y/o female newly diagnosed with HIV. She wants a single-tablet regimen. Her CD4+ cell count is 650 cells/mm3, HIV viral load 50,000 copies/mL, and HLA-B*5701 negative.

• She has hepatitis C virus (HCV), genotype 1a, and is HCV treatment naive.

• Also, on lovastatin 20 mg daily for hyperlipidemia.

• Eliminates darunavir/ritonavir and elvitegravir regimens due to drug interaction with lovastatin

Case 3

• PB is a 31 y/o female newly diagnosed with HIV. She wants a single-tablet regimen. Her CD4+ cell count is 650 cells/mm3, HIV viral load 50,000 copies/mL, and HLA-B*5701 negative.

• She has hepatitis C virus (HCV), genotype 1a, and is HCV treatment naive.

• Also, on lovastatin 20 mg daily for hyperlipidemia.

• What is the best recommended option for PB?

HCV and HIV

• HIV/HCV co-infected individuals are at increased risk for progression to cirrhosis

• Comparable HCV treatment response rates in HIV-infected and HIV-uninfected patients

• Drug-drug interaction considerations

HCV/ARV DDIs

DRV/r RAL DTG EVG TDFSofosbuvir Ledipasvir/sofosbuvir Daclatasvir Elbasvir/grazoprevir Ombitasvir/paritaprevir/ ritonavir + dasabuvir

Simeprevir Sofosbuvir/velpatasvir

OK to co-administerDose modification needed or toxicity monitoringCombination not recommended

Case 3

• PB is a 31 y/o female newly diagnosed with HIV. She wants a single-tablet regimen. Her CD4+ cell count is 650 cells/mm3, HIV viral load 50,000 copies/mL, and HLA-B*5701 negative.

• She has hepatitis C virus (HCV), genotype 1a, and is HCV treatment naive.

• Also, on lovastatin 20 mg daily for hyperlipidemia. • Dolutegravir/abacavir/lamivudine is the best option

based on considerations such as patient preference, comorbidities and drug interactions

Case 3: What if… Pregnancy?

• PB is a 31 y/o female newly diagnosed with HIV. Her CD4+ cell count is 650 cells/mm3, HIV viral load 50,000 copies/mL, and HLA-B*5701 negative.

• Her workup reveals that she is in her first trimester of pregnancy (~ 7 wks).

• She does not have a preference regarding dosing frequency, but when you discuss options she expresses concern about potential jaundice because she works with the public as a sales rep

• What is the best recommended option for PB?

DHHS Recommendations: ART Initiation in Pregnant Women

Guideline Status NRTIs PIs Integrase

Inhibitors NNRTIs

Preferred3TC/ABCFTC/TDF3TC + TDF

Atazanavir/RTV*Darunavir/RTV*† Raltegravir*§

Alternative 3TC/ZDV Lopinavir/RTV* Efavirenz*Rilpivirine*‡

Insufficient data to recommend

FTC/TAF FosamprenavirDolutegravirEVG/COBIEVG/COBI

*In addition to 2-NRTI backbone. †Must be used twice daily in pregnancy. ‡Only if retreatment HIV-1 RNA ≤ 100,000 copies/mL and CD4+ cell count ≥ 200 cells/mm3. §If adherence concerns or potential for ART discontinuation postpartum, a PI is preferred over INSTI to reduce resistance risk.

Case 3: What if… Pregnancy?

• PB is a 31 y/o female newly diagnosed with HIV. Her CD4+ cell count is 650 cells/mm3, HIV viral load 50,000 copies/mL, and HLA-B*5701 negative.

• Her workup reveals that she is in her first trimester of pregnancy (~ 7 wks).

• She does not have a preference regarding dosing frequency, but when you discuss options she expresses concern about potential jaundice because she works with the public as a sales rep

• Darunavir + RTV or RAL in combination with ABC/3TC or FTC/TDF are the best options based on patient preference and pregnancy

©2016 Academy of Managed Care Pharmacy

Managed Care Perspective on Treating Diverse HIV

Patient Populations

Elly Fatehi, PharmD, BCPSDirector of Clinical Pharmacy

Amida CareNew York, New York 

Amida Care Overview• HIV SNP

– ~6200 Medicaid Members in New York City (NYC)

– 1000 Medicare Members• Top Co-morbid Conditions

– Severe Mental Illness– Substance Abuse Disorder– HCV

• Regulatory Challenges– Ending the Epidemic– Specialty Pharmacy Limits– Pharmacy Efficiency Edits– Rebates - HIV & HCV

• Fraud, Waste & Abuse (FWA) Concerns

SNP= Special Needs Population

HIV DistributionRates of HIV Diagnoses Among Adults and Adolescents in the US in 2014

Source: CDC. Diagnoses of HIV infection in the United States and dependent areas, 2014(http://www.cdc.gov/hiv/pdf/library/reports/surveillance/cdc-hiv-surveillance-report-us.pdf). HIV Surveillance Report 2015;26

Current Status of Medicaid Expansion

41

HIV Care Continuum

Goal = Viral Suppression

Viral Suppression

Definition • Viral Load (VL)

– Goal is maximum suppression (below lower limits of detection of current assays)

• CD4+ cell count– Goal is to maximize restoration of

immunologic function

Influencing Factors

• Concomitant Diseases– Psychiatric Disorders– Substance Use Disorders– Hepatitis

• Adherence– MPR - Medication possession ratio– PDC - Proportion of days covered

• Opportunistic Infection Prophylaxis– E.g. Pneumocystis Pneumonia

©2016 Academy of Managed Care Pharmacy

Managed Care Pharmacy Strategies

Formulary ConsiderationsFormulary Considerations• Pharmacy & Therapeutics Committee

– HIV Expertise/Experience– Subcommittee

• Open Formulary– Time until new product coverage

• Rebates

HIV Formulary Considerations• Incentive or Closed Formularies

– Cover a minimum of 2 drugs per category– Exception process for stable members

• Single-tablet vs multi-tablet regimens– Consider member contribution– Adherence

• TAF vs TDF products• Generics

Antiretroviral Formulary ExampleTDF vs TAF• Elvitegravir/cobicistat/emtricitabine/tenofovir DF -

(containing TDF)– Mfg. increase WAC to $3469/month

• Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide - (containing TAF)– Mfg. set WAC at $2578/month

• Encourages switch to less costly– Proposed reduced bone and renal toxicity?

• Monitor the price of elvitegravir/cobicistat/emtricitabine/ tenofovir alafenamide if preferred product– Consider price protection

ART Generic PipelineDrug Anticipated AvailabilityAbacavir/Iamivudine/zidovidine Generic: now availableAbacavir/lamivudine September 2016Lopinavir/ritonavir December 2016Ritonavir December 2016Darunavir November 2017Atazanavir December 2017Efavirenz December 2017Emtricitabine/tenofovir disoproxil fumarate December 2017Tenofovir disoproxil fumarate December 2017Fosamprenavir June 2018Efavirenz/emtricitabine/tenofovir disoproxil fumarate August 2018

Source: Pharmacist’s Letter/Prescriber’s Letter September 2016 – Resource #320947

Benefit Design Considerations• Out of pocket costs

– Single tablet vs combination tablets• Impact of costs on adherence• Actuarial impact

• Incentive copayment for viral suppression• Preferred Pharmacy incentive• Generic incentives• Medication Therapy Management (MTM) offering

Utilization Management

Utilization Management (UM)

• Prior Authorization• Step Therapy• Quantity Limits

– Per day– Per month– Refill-to-soon

• Duplicate Therapy

Management Strategies

• Timely access to care• Investigate ART regimens

with:– < 3 ARVs– 4 or more ARVs

• Monitor Resistance Testing

UM Opportunity

Maraviroc

• Indicated in combination with other ARTs

• With CCR5-tropic HIV

Amida Care - Evaluation

• 66 maraviroc members• Only 9.1% had confirmed

CCR5-tropic testing• Opportunity

– Provider Education– Prior Authorization

Pharmacy Network Considerations• Retail• Mail Order• Specialty Pharmacy• Performance Network

– HIV Management• New member education• Support group education• Adherence monitoring – VL & CD4• Activity reporting• Not dispensing in original container• Monitoring quantity on hand

– Value based on viral suppression

Pharmacy Certification• Pharmacist Credential – AAHIVP

(American Academy of HIV Medicine)• Pharmacy Accreditation

Pharmacy Considerations (cont)• Monitor Fraud, Waste & Abuse (FWA) activities

– Pharmacy incentives/buy back• Restrict prescriber and/or pharmacy use• Notify authorities

– Card sharing• Restrict prescriber and/or pharmacy use

– Overuse• Ignoring duplicate therapy DUR (Drug Utilization Review) messaging• Lost/stolen

– Require police reports• Quantity limits set daily and/or monthly

Prescriber Considerations

• Value based pricing• Provider profiling

– Cost Per-Member-Per-Month (PMPM)– # of drugs PMPM– VL Suppression rates– Visits Per-Member-Per-Year (PMPY)

• Prescriber Qualifications– Gold Carding

• Quality audits

Quality Standards• Data Requirements

– Total number of HIV members– Total number of members connected to care– Total number of members engaged in care– Total number of members on ART

• Adherence to ART – MPR

– Total number of members virally suppressed• VL and CD4

• HCV/HIV Co-infected– Number of identified co-infected members being treated

Business Considerations

• Medicaid– Largest number of HIV+ enrollees

• Commercial – Copayment/Coinsurance significant barrier

Medicare Considerations

• Protected Classes• Transition Fills allowed• Formulary/UM changes• HIV Adherence Display Measure• Aging HIV population

References - 1• HIV/AIDS Care Continuum. Available at https://www.aids.gov/federal-resources/policies/care-

continuum/. Accessed January 4, 2017. • Department of Health and Human Services. Guidelines for the use of antiretroviral agents in HIV-1-

infected adults and adolescents. Available at: http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Accessed January 4, 2017.

• Günthard HF, Saag MS, Benson CA, et al. Antiretroviral drugs for treatment and prevention of HIV Infection in adults: 2016 recommendations of the International Antiviral Society–USA Panel. JAMA. 2016;316:191-210.

• Clutter DS, Jordan MR, Bertagnolio S, Shafer RW. HIV-1 drug resistance and resistance testing. Infect Genet Evol. 2016;46:292-307.

• Nachega JB, Parienti JJ, Uthman OA, et al. Lower pill burden and once-daily dosing antiretroviral treatment regimens for HIV infection: a meta-analysis of randomized controlled trials. Clin Infect Dis. 2014;58:1297-1307.

• Milburn J, Jones R, Levy JB. Renal effects of novel antiretroviral drugs. Nephrol Dial Transplant. 2016;[Epub ahead of print].

• Wohl D, Oka S, Clumeck N, et al. Brief Report: A randomized, double-blind comparison of tenofovir alafenamide versus tenofovir disoproxil fumarate, each coformulated with elvitegravir, cobicistat, and emtricitabine for initial HIV-1 treatment: Week 96 results. J Acquir Immune Defic Syndr. 2016;72:58-64.

• Gallant JE, Daar ES, Raffi F, et al. Efficacy and safety of tenofovir alafenamide versus tenofovir disoproxil fumarate given as fixed-dose combinations containing emtricitabine as backbones for treatment of HIV-1 infection in virologically suppressed adults: a randomised, double-blind, active-controlled phase 3 trial. Lancet HIV. 2016;3:e158-e165.

References - 2• Sax PE, Wohl D, Yin MT, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate,

coformulated with elvitegravir, cobicistat, and emtricitabine, for initial treatment of HIV-1 infection: two randomised, double-blind, phase 3, non-inferiority trials. Lancet. 2015;385:2606-2615.

• Mills A, Arribas JR, Andrade-Villanueva J, et al. Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in antiretroviral regimens for virologically suppressed adults with HIV-1 infection. Lancet Infect Dis. 2016;16:43-52.

• Pozniak A, Arribas JR, Gathe J, et al. Switching to tenofovir alafenamide, coformulated with elvitegravir, cobicistat, and emtricitabine in HIV-infected pateitns with renal impairement. J Acquir Immune Defic Syndr. 2016;71:530-537.

• Wohl D, Thalme A, Finlayson R, et al. Renal safety of tenofovir alafenamide in patients at high risk of kidney disease. Program and abstracts of the 2016 Conference on Retroviruses and Opportunistic Infections; February 22-25, 2016; Boston, Massachusetts. Abstract 681.

• Raffi F, Jaeger H, Quiros-Roldan E, et al. Once-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 trial. Lancet Infect Dis. 2013;13:927-935.

• Pappa K, Baumgarten A, Felizarta F, et al. Dolutegravir (DTG) + abacavir/lamivudine once daily superior to tenofovir/emtricitabine/efavirenz in treatment naive HIV subjects: 144-week results from SINGLE (ING114467). Program and abstracts of the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 5-9, 2014; Washington, DC. Abstract H-647a.

References - 3• Wohl DA, Cohen C, Gallant JE, et al. A randomized, double-blind comparison of single-tablet regimen

elvitegravir/cobicistat/emtricitabine/tenofovir DF versus single-tablet regimen efavirenz/emtricitabine/tenofovir DF for initial treatment of HIV-1 infection: analysis of week 144 results. J Acquir Immune Defic Syndr. 2014;65:e118-e120.

• Clumeck N, Molina JM, Henry K, et al. A randomized, double-blind comparison of single-tablet regimen elvitegravir/cobicistat/emtricitabine/tenofovir DF vs ritonavir-boosted atazanavir plus emtricitabine/tenofovir DF for initial treatment of HIV-1 infection: analysis of week 144 results. J Acquir Immune Defic Syndr. 2014;65:e121-e124.

• Wohl DA, Cohen C, Gallant JE, et al. A randomized, double-blind comparison of single-tablet regimen elvitegravir/cobicistat/emtricitabine/tenofovir DF versus single-tablet regimen efavirenz/emtricitabine/tenofovir DF for initial treatment of HIV-1 infection: analysis of week 144 results. J Acquir Immune Defic Syndr. 2014;65:e118-e120.

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