Ongoing Management of the HIV Patient in the Ambulatory ...ashpadvantagemedia.com/15-cem-hiv/files/handout-hiv.pdf · Dr. Schafer’s clinical practice site is an HIV specialty ambulatory
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Ongoing Management of the HIV Patient in the Ambulatory Care Setting: Strategies for
Achieving Long-term Viral Suppression
Presented as a Midday Symposium and Live Webinar at the
50th ASHP Midyear Clinical Meeting and Exhibition
Monday, December 7, 2015
New Orleans, Louisiana
www.cemidday.com
Sponsored by the American Society of Health-System Pharmacists (ASHP) and planned by ASHP Advantage, a division of ASHP.
Please be advised that this activity is being audio and/or video recorded for archival purposes and, in some cases, for repurposing of the content for enduring materials.
Ongoing Management of the HIV Patient in the Ambulatory Care Setting: Strategies for Achieving Long-term Viral Suppression
Agenda
11:30 a.m. – 11:40 a.m. Welcome and Introductions Jason J. Schafer, Pharm.D., M.P.H., BCPS, AAHIVP 11:40 a.m. – 11:50 a.m. HIV Epidemiology and Engagement in Care
Jason J. Schafer, Pharm.D., M.P.H., BCPS, AAHIVP 11:50 a.m. – 12:10 p.m. Acute HIV Infection
Joseph A. DeSimone, Jr. M.D., FIDSA, AAHIVS 12:10 p.m. – 12:30 p.m. Switching ART
Joseph A. DeSimone, Jr. M.D., FIDSA, AAHIVS 12:30 p.m. – 12:50 p.m. Hepatitis C Co-infection Jason J. Schafer, Pharm.D., M.P.H., BCPS, AAHIVP 12:50 p.m. – 1:00 p.m. Faculty Discussion and Audience Questions All Faculty
Faculty
Jason J. Schafer, Pharm.D., M.P.H., BCPS, AAHIVP, Activity Chair Associate Professor, Department of Pharmacy Practice Jefferson College of Pharmacy Clinical Pharmacy Specialist, HIV Ambulatory Care Jefferson Infectious Diseases Associates Thomas Jefferson University Philadelphia, Pennsylvania Joseph A. DeSimone, Jr. M.D., FIDSA, AAHIVS Professor of Medicine Director, Infectious Diseases Fellowship Program Sidney Kimmel Medical College Thomas Jefferson University Philadelphia, Pennsylvania
Ongoing Management of the HIV Patient in the Ambulatory Care Setting: Strategies for Achieving Long-term Viral Suppression
Jason J. Schafer, Pharm.D., M.P.H., BCPS, AAHIVP Associate Professor, Department of Pharmacy Practice Jefferson College of Pharmacy Clinical Pharmacy Specialist, HIV Ambulatory Care Jefferson Infectious Diseases Associates Thomas Jefferson University Philadelphia, Pennsylvania Jason J. Schafer, Pharm.D., M.P.H., BCPS, AAHIVP, is Associate Professor of Pharmacy Practice at the Jefferson College of Pharmacy and Clinical Pharmacy Specialist, HIV Ambulatory Care, at Thomas Jefferson University in Philadelphia, Pennsylvania. Dr. Schafer received his Doctor of Pharmacy degree from Duquesne University and completed a pharmacy practice residency at the Mercy Hospital of Pittsburgh and a second residency specializing in infectious diseases at the Ohio State University Medical Center. He received his Master of Public Health degree from the Jefferson School of Population Health. He is a board-certified pharmacotherapy specialist (BCPS) and is certified by the American Academy of HIV Medicine (AAHIVM) as a practicing HIV Pharmacist (AAHIVP). Dr. Schafer’s clinical practice site is an HIV specialty ambulatory care clinic in Philadelphia where he provides medication therapy management services. He also provides service to the AAHIVM on its Pharmacist and Credentialing Committees. Dr. Schafer has published numerous articles on HIV medicine and pharmacotherapy in the medical literature including the ASHP Guidelines on Pharmacist Involvement in HIV Care. He has also been active in ASHP most recently serving as the Infectious Diseases Network Facilitator and as Director at Large for the Section of Clinical Specialists and Scientist’s Executive Committee.
Ongoing Management of the HIV Patient in the Ambulatory Care Setting: Strategies for Achieving Long-term Viral Suppression
Joseph A. DeSimone, Jr. M.D., FIDSA, AAHIVS Professor of Medicine Director, Infectious Diseases Fellowship Program Sidney Kimmel Medical College Thomas Jefferson University Philadelphia, Pennsylvania Joseph A. DeSimone, Jr., M.D., FACP, FIDSA, is Professor of Medicine and Program Director for the Infectious Diseases Fellowship Program at the Sidney Kimmel Medical College, at Thomas Jefferson University in Philadelphia, Pennsylvania. Dr. DeSimone graduated from Hahnemann University School of Medicine where he also completed both his Internal Medicine residency and Infectious Diseases fellowship. He is a fellow of the Infectious Diseases Society of America (FIDSA) and a Practicing HIV Specialist (AAHIVS). He is responsible for teaching infectious diseases and HIV to medical students, internal medicine residents, and infectious diseases fellows at Thomas Jefferson University. Dr. DeSimone has provided clinical care for HIV-infected patients at Thomas Jefferson University for over 15 years and currently cares for over 300 HIV-infected patients in his practice. He has acted as the principal or co-principal investigator for dozens of clinical trials investigating antiretroviral therapy for persons with HIV infection. Dr. DeSimone has authored numerous publications in peer-reviewed journals and abstract presentations at national meetings. He has received numerous teaching awards while at Thomas Jefferson University including the Dean’s Award for Excellence in Education from the Sidney Kimmel Medical College and Induction into the Gold Humanism Honor Society.
CDC National HIV Surveillance System and Medical Monitoring Project.Skarbinski, et al. JAMA Intern Med. 2015;175(4):588‐596.
Diagnosed
0% 20% 40% 60% 80% 100%
86%
Engaged in Care 40%
HIV Infection in the USPatient engagement and Transmission of HIV
92% of new HIV infections are attributable to people with HIV who are not in medical care, including those who are not diagnosed
CDC National HIV Surveillance System and Medical Monitoring ProjectHIV Care Continuum. https://www.aids.gov/federal‐resources/policies/care‐continuum/
HIV Infection in the USPatient engagement in the continuum of HIV Care
Virally Suppressed
0% 20% 40% 60% 80% 100%
30%
66% diagnosed but not in care
A
B
C
D30%
• Of the 70% of people living with HIV who are not virally suppressed:
A. 66% are diagnosed, but not engaged in regular HIV careB. 20% do not know they are infectedC. 10% are prescribed ART, but have not yet achieved viral suppressionD. 4% are in HIV care, but are not prescribed ART
• Closing the gaps
– Improvements in HIV testing and diagnosis
– Emerging strategies for linking and retainingpatients in care
– Evolving recommendations for when to initiateantiretroviral therapy
– Achieving and maintaining viral suppression
CDC National HIV Surveillance System and Medical Monitoring ProjectHIV Care Continuum. https://www.aids.gov/federal‐resources/policies/care‐continuum/
HIV Infection in the USPatient engagement in the continuum of HIV Care
Note: new algorithm may not be uniformly adopted in all settings. If a rapid 3rd generation test is used with a positivie test result, confirmation is needed with a more specific test (eg, Western Blot).
Awareness of Serostatus Among People with HIV, and Estimates of Transmission
~20% Unaware
of Infection
~80% Aware of Infection
People Living with HIV/AIDS:1,200,000
New Sexual Infections Each Year: ~50,000
account for…
~49% of New
Infections
~51% of New
Infections
Hall HI et al. AIDS. 2012; 26;893‐6.
PT comes to office 5 days later to learn of confirmed diagnosis. HIV viral load is >10 million copies; CD4 count is 600 cells/mm3.Should this patient be treated with ART and when?
a. Yes, immediately (today)
b. Yes, in 4 weeks (after genotype available)
c. No, since CD4 count is >500 cells/mm3.
d. Not yet, since she needs time to process hernew diagnosis.
e. Not sure
New York State Department of Health AIDS Institute: www.hivguidelines.org.
U.S. Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents. http://aidsinfo.nih.gov/guidelines (accessed 2015 April).
Providing same day, observed ART to newly diagnosed HIV+
outpatients is associated with improved virologic suppression
Christopher D. Pilcher, Hiroyu H. Hatano, Aditi Dasgupta, Diane Jones, Sandra Torres, Fabiola Calderon, Erin Demicco, Wendy
START Study:Initiation of ART in Early Asymptomatic HIV Infection
Lundgren J, et al. 8th IAS Conference. Vancouver, 2015. Abstract MOSY0301.The INSIGHT START Study Group. N Engl J Med. 2015;July 20. [Epub ahead of print].
Permission from Practice Point Communications.
Multicontinental Study (n=4685)
HIV‐positive adults
Treatment‐naive
CD4 >500 cells/mm3
Randomization1:1 Immediate ART (n=2326)
Deferred ART (n=2359)(CD4 Declined to <350 cells/mm3 or AIDS‐related event)
Primary outcome a composite outcome of 2 major components:
• Any serious AIDS‐related event
‐ Death from AIDS or any AIDS‐defining event, Hodgkin’s lymphoma
• Any serious non–AIDS‐related event
‐ CVD (myocardial infarction, stroke, or coronary revascularization) or death from CVD, end‐stage renal disease (initiation ofdialysis or renal transplantation) or death from renal disease, liver disease (decompensated liver disease) or death from liver disease, non–AIDS‐defining cancer (except for basal‐cell or squamous cell skin cancer) or death from cancer, and any death not attributable to AIDS
5//2015: DSMB recommends stopping trial:Deferred arm offered ART
START Study Outcomes:Composite Primary Endpoint and its Components
• Immediate ART was superior to deferral of ART
– Both for serious and non‐seriousAIDS events
• Majority (68%) of the primary endpoints occurred in patientswith a CD4 >500 cells/mm3
• Similar significant reductionswere noted across all patient subgroups
• No increase in adverse events associated with immediate versus deferred ART
Lundgren J, et al. 8th IAS Conference. Vancouver, 2015. Abstract MOSY0301.The INSIGHT START Study Group. N Engl J Med. 2015;July 20. [Epub ahead of print].Permission from Practice Point Communications.
0
20
40
60
80
100
Number of Even
ts
AIDS‐Related
Non‐AIDS Related
Components(Serious Events)
CompositeEndpoint
96Deferred ART (n=2359)
Immediate ART (n=2326)
42
50
14
47
29
Number of Serious Events
57%Reduction(P<0.001)
72%Reduction(P<0.001)
39%Reduction(P=0.04)
When to Start Therapy:Balance Now Favors Early ART
• Drug toxicity• Preservation of limited Rx options• Risk of resistance (and transmission
of resistant virus)
• ↑ potency, durability, simplicity, safety of current regimens
• ↓ emergence of resistance• ↓ toxicity with earlier therapy• ↑ subsequent treatment op ons• Risk of uncontrolled viremia at all CD4
Recommendations for Initiating ART: Considerations
• “Patients starting ART should be willing andable to commit to treatment and should understand the benefits and risks of therapy and the importance of adherence.”
• Patients may choose to postpone ART
• Providers may elect to defer ART, based on anindividual patient’s clinical or psychosocialfactors, but ART should be started as soon asit is feasible to do so
July 201540 www.aidsetc.org
Per the DHHS 2015 guidelines, which of the following is currently recommended as a first‐line regimen for this patient?
a. Efavirenz/tenofovir disoproxil/emtricitabine(EFV/TDF/FTC)
b. Rilpivirine/tenofovir disoproxil/emtricitabine(RPV/TDF/FTC)
c. Atazanavir/ritonavir (ATV/r) plus TDF/FTC
d. Elvitegravir/cobicistat/TDF/FTC (EVG/cobi/TDF/FTC)
e. Darunavir/ritonavir (DRV/r) plus abacavir/lamivudine (ABC/3TC)
U.S. DHHS Guidelines, April 2015: What to Start
• Non‐nucleoside reverse transcriptase inhibitors (NNRTIs) andAtazavavir/ritonavir (ATV/r), previously classified as “recommended,” are now “alternative regimens”
U.S. Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents. April 2015.
*Only for pts who are HLA‐B*5701 negative. †Only for pts with pre‐ART CrCl ≥ 70 mL/min.
Recommended Regimens
Integrase strand transfer inhibitor (INSTI)‐based
Dolutegravir/abacavir/lamivudine (DTG/ABC/3TC)*DTG plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC)
*Only for pts with pre‐ART HIV‐1 RNA < 100,000 copies/mL and CD4+ > 200 cells/mm3.†Only for pts with pre‐ART CrCl ≥ 70 mL/min.‡Only for pts who are HLA‐B*5701 negative.
• An alternative regimen may be the preferred regimen for some patients
U.S. Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents. April 2015.
Alternative Regimens
NNRTI based EFV/TDF/FTCRPV/TDF/FTC*
PI based ATV/COBI + TDF/FTC†
ATV/r + TDF/FTC DRV/COBI + ABC/3TC‡
DRV/r + ABC/3TC‡
DRV/COBI + TDF/FTC†
Difference in 96‐wk cumulative incidence (97.5% CI)
-20 0-10 10 20
15% (10% to 20%)
7.5% (3.2% to 12%)
7.5% (2.3% to 13%)
ATV/r vs RAL
DRV/r vs RAL
ATV/r vs DRV/r
Favors RAL
Favors DRV/r
Lennox JL, et al. Ann Intern Med. 2014;161:461‐471.
*Plus TDF/FTC.
ATV/r*RAL*DRV/r*
ACTG 5257: Cumulative Incidence of Virologic or Tolerability Failure
1.00
0.75
0.50
0.25
0.00
Cumulative Inciden
ce
Weeks Since Study Entry
0 24 48 64 80 96 112 128 144
Favors RALFavors RAL
SINGLE: DTG + ABC/3TC Superior to EFV/TDF/FTC in ART‐Naive Pts to Wk 144
• Open‐label extension, excluding pts with hepatitis B virus (HBV)• Emergent resistance in those with VF: 0/39 (DTG) vs 7/33 (EFV)
Virologic Success* Virologic Nonresponse No Virologic Data
FLAMINGO: DTG Superior to DRV/r in ART‐Naive Pts to Wk 96
Virologic Success Virologic Nonresponse No Virologic Data
FavorsDRV/r
95% CI for Difference
0%-12%
Wk 48
Wk 96
7.1%
12.4%
0.9%
4.7% 20.2%
13.2%
Subjects (%
)
FavorsDTG
25%
DTG 50 mg QD + 2 NRTIs (n = 242)
DRV/r 800 mg/100 mg QD + 2 NRTIs (n = 242)
Molina et al. HIV Drug Therapy Glasgow 2014; Glasgow, UK. Slides O153.
0
20
40
60
80
100
W48 W48 W48W96 W96 W96
90
8380
68
6 7 812
410 12
21
Comparing the Integrase Inhibitors
Together, the results of STARTMRK, GS 102 and 103, SINGLE, FLAMINGO, and ACTG 5257 suggest that integrase inhibitor–based regimens are the preferred starting regimens in
PT starts EVG/c/TDF/FTC. One year later: Viral load undetectable; CD4 count 900 cells/mm3; GFR now 70 mL/min/1.73 m2; HLA B‐5701 is positive. Next step?
a. Observe on EVG/c/TDF/FTC until GFR drops below
30 mL/min/1.73 m2
b. Switch EVG/c/TDF/FTC to Raltegravir (RAL) plusTDF/FTC
U.S. Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents. http://aidsinfo.nih.gov/guidelines (accessed 2015 April).
1. Mills A, et al. HIV Clin Trials. 2014;15:51‐56. 2. Mills A, et al. HIV Clin Trials. 2013;14:216‐223. 3. Pozniak A, et al. Lancet Infect Dis. 2014;14:590‐599. 4. Arribas JR, et al. Lancet Infect Dis. 2014;14:581‐589. 5. Brunetta J, et al. Patient. 2015;[Epub ahead of print]. 6. Martínez E, et al. AIDS. 2010;24:1697‐1707. 7. Perez‐Molina JA, et al. AIDS2014. Abstract LBPE18. 8. Gatell J, et al. AIDS 2014. Abstract LBPE17. 9. Eron JJ, et al. Lancet. 2010;375:396‐407. 10. van Lunzen J, et al. AIDS 2014. Abstract LBPE19.
CE IN THE MIDDAY
Hepatitis C Co‐Infection
Jason J. Schafer Pharm.D., M.P.H, BCPS, AAHIVP
Activity Chair
Associate Professor, Department of Pharmacy Practice
Hepatitis C InfectionTreatment is NOT what it used to be…
SVR Rates for Approved Therapies in HCV GT 1 Patients
1986
1998
2015
2013
1991
2001
MannsM et al. Lancet. 2001; 358:958‐965. Fried MW et al. N Engl J Med. 2002; 347:975‐982. Poordad F et al. N Engl J Med. 2011; 364:1195‐1206. Jacobson IM et al. N Engl J Med. 2011; 364:2405‐2416. Afdhal N et al. N Engl J Med. 2014; 370:1889‐1898.
Chung RT et al. N Engl J Med. 2004; 351:451‐9.Torriani FJ et al. N Engl J Med. 2004; 351:438‐450.
Carrat F et al. JAMA. 2004; 292:2839‐48.
Treating Co‐infection is NOT what it used to be…
SV
R (
%)
HCV mono
APRICOT* (n=289)
Ribavic* (n=205)
ACTG 5071* (n=66)
SVR according to genotype for HIV/HCV Co‐infected patients receiving Peg‐interferon plus ribavirin for 48 weeks
80
60
40
20
10
0
42
73
17
44
1429
62
8290
Genotype 1
Genotype 2/3
*80‐85% receiving ART*60‐65% with undetectable HIV RNA
100
Dieterich D et al. CROI 2014; P#24; Rodriguez‐Torres M et al. IDWeek 2013; P#714; Sulkowski M et al. Lancet Infect Dis 2013;13:597–605; Sulkowski M et al. Ann Intern Med 2013;159:86–96; Sulkowski M et al. Lancet 2014;314:653–61; Sulkowski M et al. AIDS. 2014; P#104 LB; Torriani FJ, et al. N Engl J Med. 2004;351:438–50;
AASLD/IDSA/IAS–USA. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org. (accessed 2015 Oct 15).
HIV/HCV Co‐infectionTreating Co‐infection is NOT what it used to be…
100
80
60
40
20
0
SVR (%)
29
14
7
74
89
7463
76
9496
SVR Rates for Approved Therapies in HCV GT 1 Patients Co‐infected with HIV
Afdhal N et al. N Engl J Med. 2014; 370: 1889‐98; Afdhal N et al. N Engl J Med. 2014; 370: 1483‐93; Kowdley K et al. N Engl J Med. 2014; 370: 1879‐88; Naggie et al CROI 2015, Oral #LB‐152;
Osinusi A et al. JAMA. 2015; Sulkowski M et al. JAMA. 2015; 313:1223‐1231; Feld JJ et al. N Engl J Med. 2014; 370:1594‐603.
HIV/HCV Co‐infectionSimilar response rates in HCV/HIV co‐infected patients compared to
Poordad F et al. EASL 2015, Abstract L08; Wyles DL et al. N Engl J Med. 2015; 373:714‐25. Kwo P et al. EASL 2015, Abstract S270; Del Bello DP et al. AASLD 2014, Abstract 994.
HIV/HCV Co‐infectionSimilar response rates in HCV/HIV co‐infected patients compared to
HCV mono‐infected patients
SVR‐12 (%)
80
60
40
20
10
0
90
100
HCV Monoinfection
HIV/HCV Co‐infection
DCV/SOF x 12 Weeks SOF/SIM ± RBV x 12 Weeks
ALLY‐1* ALLY‐3**
ALLY‐2
123/127235/265
96-98%
83-94%92%
Del BelloStudy
11/12150/155
95-97%
OPTOMIST‐1
*ALLY‐1 was conducted in patients with advanced cirrhosis and post‐transplant patients**ALLY‐3 was conducted for genotype 3 patients with and without cirrhosis
HIV/HCV Co‐infection
• HIV co‐infection accelerates fibrosis progressionamong HCV‐infected persons
• Controlling HIV may mitigate progression to some extent, but ART is not a substitute for HCV treatment
• Co‐infected patients have more liver‐related and overall mortality than HCV‐monoinfected patients
• Achieving SVR reduces the incidence of liver relateddeath and improves survival in co‐infected patients
AASLD/IDSA/IAS–USA. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org. (accessed 2015 Oct 15). Lee MH et al. J Infect Dis. 2012; 206:469‐477; Ly KN et al. Ann Intern Med. 2012; 156:271‐8; Ragni MV et al. Haemophilia. 2009; 15:552‐8; Aghemo A et al. Hepatology. 2012;
56:1681‐7.
Delaying HCV Treatment Leads to Liver Disease Progression
HIV/HCV Co‐infection
• CD4+ guided ART interruption was associated with significantly greater riskof disease progression and death compared to continuous ART
– RR 2.5 (95% CI: 1.8‐3.6; p<.001)
• Includes increased CVD, liver, and renal‐related deaths:
• All co‐infected patients are candidates for HCV therapy
• HIV disease must be stable before initiating HCV treatment
• Interrupting HIV treatment to manage HCV infection is not recommended
• Recommended ART regimens for co‐infected patients are the same as those recommended for patients without HCV
• Co‐infected persons should be treated the same as persons without HIV infection, after recognizing and managinginteractions with antiretroviral medications
AASLD/IDSA/IAS–USA. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org. (accessed 2015 Oct 15).
HIV/HCV Co‐infectionAASLD/IDSA/IAS‐USA Hepatitis C Guidelines
Which HCV treatment strategy do you recommend?
a. Keep ART and start sofosbuvir/ledipasvir
b. Change ART and start sofosbuvir/ledipasvir
c. Keep ART and start daclatasvir + sofosbuvir
d. Change ART and start simeprevir + sofosbuvir
e. Keep ART and startparitaprevir/ritonavir/ombitasvir plusdasabuvir (PrOD)
AASLD/IDSA/IAS–USA. Recommendations for testing, managing, and treating hepatitis C.http://www.hcvguidelines.org. (accessed 2015 Oct 15).
HIV/HCV Co‐infectionRecommended HCV Treatment Regimens in Patients
AASLD/IDSA/IAS–USA. Recommendations for testing, managing, and treating hepatitis C.http://www.hcvguidelines.org. (accessed 2015 Oct 15).
SOF/SMV SOF/LDV SOF/DCV OMV/PTV/RTV + DSV
DRV/RTV/TDF/FTCSMV↑
DRV↔
SOF↑, LDV↑
DRV↔, TDF↑↑
SOF↑, DCV↑,
DRV↔
PTV↓/↑
DRV↓
RAL/TDF/FTCSOF↔, SMV↔
RAL↔
SOF↔, LDV↔
RAL↔, TDF↑
SOF↔, DCV↔
RAL↔
PrOD↔
RAL↑
EVG/COBI/TDF/FTC No dataSOF↑, LDV↑
COBI↑, TDF↑↑
SOF↑DCV – No data
COBI↑
No data
DTG/TDF/FTC No data
SOF – no dataLDV↔
DTG↔, TDF↑
SOF – no data DCV↔
DTG↑
PTV↓
DTG↑
DTG/ABC/3TC No data
SOF – no data LDV↔
ART: No data
SOF – no data DCV↔
DTG↑
PrOD↔
DTG↑
Tenofovir Absorption
Gut Lumen Blood Stream
Tenofovir DF
BCRP
P‐gp
P‐gp
BCRP
ӾLedipasvirRitonavirCobicistat
Enterocytes
BCRP: Breast Cancer Resistance Protein
Custodio J et al. ID Week 2015, Abstract 727.
SOF/SMV SOF/LDV SOF/DCV OMV/PTV/RTV + DSV
EVG/COBI/TAF/FTC No dataSOF↑, LDV↑
COBI↑, TDF↑
SOF↑DCV – No data
COBI↑
No data
HIV/HCV Co‐infectionWhat about TAF??
• TAF is a p‐glycoprotein substrate (like TDF)
• TAF bioavailability increases with cobicistat which increases TFV plasma levels • The TAF dose is adjusted down to 10mg in EVG/COB/TAF/FTC to compensate
• LDV and TAF co‐administration also leads to mild increases in TFV exposure through p‐glycoprotein inhibition.
• Despite increases in TFV with LDV, TFV plasma levels remain much lower with TAF versus TDFand within the range that has not lead to adverse renal effects or bone loss
• E/C/F/TAF may be co‐administered with LDV/SOF without dose modification
Note: new algorithm may not be uniformly adopted in all settings. If a rapid 3rd generation test is used with a positivie test result, confirmation is needed with a more specific test (eg, Western Blot).