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HIV Treatment 101
C. Ryan Tomlin, Pharm.D., BCPS, AAHIVPClinical Pharmacist – HIV Medicine
Outline
• What is HIV?• Common Labs• Life Cycle and Medication Targets• Building an HIV regimen• HIV Guidelines
– When to start treatment– What medications to start– When to change therapy
2
What is HIV?
• Human – Only found in humans• Immunodeficiency – Weakens immune system by destroying
CD4 cells• Virus – Reproduces by taking over a host cell
3
Common HIV Labs
• Viral Load– How much HIV is in the blood– Lower the better
• CD4 Count– How strong the immune system is– Higher the better
• Genotype– Has HIV found ways to avoid certain medications?– Resistance test
4
HIV Time Course
5
Goals of Therapy
• Increase the CD4– Above 200, preferably above 500
• Decrease the VL– Non-detectable
• Improve quality of life• Reduce secondary HIV related disease• Reduce transmission
– (Undetectable = Untransmittable)
6
HIV Life Cycle
NRTIs NNTRIs PIs Single TabletRegimens
Entry/Fusion Inhibitors
Combivir® Edurant® Aptivus® Atripla® Fuzeon®
Descovy® Intelence® Crixivan® Biktarvy® Rukobia®
Emtriva® Pifeltro® Evotaz® Complera® Selzentry®
Epivir® Rescriptor® Invirase® Delstrigo® Trogarzo®
Epzicom® Sustiva® Kaletra® Dovato®
Retrovir® Viramune® Lexiva® Genvoya®
Trizivir® Norvir® Juluca®
Truvada® INSTIs Prezcobix® Odefsey®
Videx® Isentress® Prezista® Stribild®
Viread® Tivicay® Reyataz® Symtuza®
Zerit® Vitekta® Viracept® Triumeq®
Ziagen®
FDA Approved Antiretrovirals
8
Building an HIV Regimen for a New Patient
• Three medications from at least 2 different classes (usually…)– Never mono therapy– NRTIs are the only class we routinely use more than 1 at a time– Ritonavir and Cobicistat do not count
• Number of medications does not have to match the number of pills
9
Example Single Tablet Regimens
• Biktarvy – 2018– Tenofovir alafenamide/Emtricitabine/Bictegravir– NRTI/NRTI/INSTI
• Symtuza – 2018– Tenofovir alafenamide/Emtricitabine/Darunavir/Cobicistat– NRTI/NRTI/PI/Booster
The Two Drug Rule Exceptions
• Juluca – 2017– Rilpivirine/Dolutegravir– NNRTI/INSTI– Only used in someone stable on another regimen for 6 months
• Dovato – 2019– Dolutegravir/Lamivudine– INSTI/NRTI
Simpler Regimens Over Time
Regimen Dosing Pill Burden
1996: q8h: 10 pills/d / /
1998 q12h: 5 pills/d /
2002 q12h: 3 pills/d /
2003 qd : 3 pills/d
2004 qd: 2 pills/d
2006 qd: 1 pill/d
12
Available Guidelines
• US DHHS : Department of Health and Human Services• IAS-USA : International AIDS Society• BHIVA : British HIV Association• EACS: European AIDS Clinical Society• WHO: World Health Organization
1
What the Guidelines Address
• Laboratory testing• When to start treatment• What medications to start• When to change therapy• Treatment of special populations• Treating co-infected patients• Medication side effects and drug interactions
1
When to Start Therapy
What to Start
When to Change Therapy
1
Treatment Initiation Over Time
1998 2001 2002 2004 2007 2009 2012
CD4 Count
Treat: <500
Treat: <200Offer:<350Indiv.>350
Treat: <200Offer:<350Indiv.>350
Treat: <200Offer:<350Indiv.>350
Treat:<350Indiv.>350
Treat:<350Rec:<500Indiv.>500
Treat everyone<350 (AI)<500 (AII)>500 (BIII)
VL >20,000 >55,000 >100,000
Other factors
PregnantHBVHIVAN
PregnantHBVHIVAN
PregnantHBVHIVANHigh risk of transmitting
1
START Study
• International Study– 215 sites in 35 countries
• 4,685 patients with CD4 counts above 500 enrolled– Half started medications right away– Half waited till CD4 dropped below 350
1http://www.niaid.nih.gov/news/newsreleases/2015/Pages/START.aspx
START Study Results
41
86
0102030405060708090
100
Start right away Start at 350
AIDS, Serious Non-AIDS Events, or Death
18http://www.niaid.nih.gov/news/newsreleases/2015/Pages/START.aspx
Benefits of Early Treatment
• Maintain higher CD4 count to prevent damage to the immune system
• Decrease risk of HIV associated complications– Opportunistic infections– Underlying inflammation
• Decrease risk of transmission– Undetectable = Untransmittable
19
Increase in CD4 Count
Gras L et al. J Acquir Immune Defic Syndr. 2007;45(2):183-192.
Median CD4 Response in Patients ≥50 Years at the Start of ART
Years from Starting ART0 1 2 3 4 65 7
11001000
900800700600500400300200100
0Mea
n CD
4 Ce
ll Co
unt (
cells
/mm
3 )
<50 cells/mm3
50-200 cells/mm3
200-350 cells/mm3
350-500 cells/mm3
≥500 cells/mm3
Control (male, <50 years at start of ART)
≥ 50 years at start of ART
20
When to Start Therapy
What to Start
When to Change Therapy
21
Building An HIV Regimen
2 NRTIs
1 NNRTI
1 Protease Inhibitor
1 Integrase Inhibitor
or
or
Example Regimens
Abacavir Lamivudine Dolutegravir
Triumeq
NRTI NRTI Integrase Inhibitor
Tenofovir AF Emtricitabine Darunavir
Descovy
NRTI NRTI Protease Inhibitor
Cobicistat
Prezcobix
Booster
First Line Regimens For Most People
Tenofovir Emtricitabine RaltegravirNRTI NRTI Integrase Inhibitor
Tenofovir Emtricitabine DolutegravirNRTI NRTI Integrase Inhibitor
Abacavir Lamivudine DolutegravirNRTI NRTI Integrase Inhibitor
Tenofovir Emtricitabine BictegravirNRTI NRTI Integrase Inhibitor
Truvada®/Descovy® + Isentress®
Truvada®/Descovy® + Tivicay®
Biktarvy®
Triumeq®
Lamivudine DolutegravirNRTI Integrase Inhibitor
Dovato®
The Rational For Unboosted Integrase Inhibitors
• Fewer drug interactions than NNRTIs, PIs and Elvitegravir• No food requirement• Good tolerability• Reduce the HIV viral load very quickly
The differences between recommended regimens is getting more and more subtle…
Treatment Naïve – Treatment Selection Factors
• Baseline resistance testing and viral load• Patient anticipated adherence• Other health conditions
– Kidney disease, heart disease– Pregnancy– Hepatitis co-infections
• Side Effects• Drug interactions• Patient’s daily schedule and meal times
26
Treatment Experienced
• Resistance testing• Antiretroviral medication history
– Side effect history– Allergies– Adherence/possible resistance
• All treatment naïve factors
27
Building an HIV Regimen for a New Patient
• Three medications from at least 2 different classes (usually…)– Never mono therapy– NRTIs are the only class we routinely use more than 1 at a time– Ritonavir and Cobicistat do not count
• Two exceptions to the three medication rule – Juluca, Dovato• Number of medications does not have to match the number of
pills
28
Building A Salvage Regimen
• Three medications, each from a different class– Medications selected based on viral resistance– Can still use more than 1 NRTI
• Can have more than 3 medications if there are not enough fully active medications left
Medication 1Partial resistance
Medication 2Partial resistance
Medication 3No resistance
Medication 4No resistance
½ ½ 1 1 = 3Active
Medications
Appropriate or Not? Question #1
Tenofovir DF Emtricitabine Elvitegravir
Stribild
NRTI NRTI Integrase Inhibitor
CobicistatBooster
Yes Probably Not
Appropriate or Not? Question #2
Yes Probably Not
Tenofovir DF Darunavir
Viread
NRTI Protease Inhibitor
Cobicistat
Prezcobix
Booster
Only 2 Active Medications
Appropriate or Not? Question #3
Yes Probably Not
Abacavir Lamivudine Zidovudine
Trizivir
NRTI NRTI NRTI
Only 1 Class
Appropriate or Not? Question #4
Juluca
Rilpivirine Dolutegravir
NNRTI Integrase Inhibitor
Yes Probably Not
Two Drug-Rule Exception
When to Start Therapy
What to Start
When to Change Therapy
34
Reason For Therapy Changes
• Viral Failure• Side Effects• Drug Interactions• Comorbidities• Reduce Pill Burden• Pregnancy• Cost/Insurance
35
Viral Failure
• Possible Causes– Suboptimal adherence– Pharmacokinetic issues– Possible drug resistance
• New regimen selection is based on cause of regimen failure and remaining antiretroviral options
36
Can I Go Back To My Old Regimen?
• Resistance/Viral Failure– No
• Side Effects, Drug Interactions, Comorbidities– Depends on the clinical picture
• Pill burden, Pregnancy, Cost/Insurance– Likely
37
Interruptions in Therapy
• Stop all antiretrovirals at once– Spacing them out only leads to resistance
• In patients with hepatitis B, treatment interruptions can lead to a hepatitis flare
• Always refer patient back to their medication provider
38
Drug Holidays
• If a patient's immune system is strong is it possible to stop medication for a period of time to decrease medication side effects?
• Short answer: No
39
SMART Study
• 5,472 patients enrolled– Half took medications continuously– Half took medications till their CD4 count was >350, then stopped till
<250
• Results– Those who took medication holidays were 2.5x more like to have a
clinical event or death
40N Engl J Med. 2006;355:2283-96.
Summary
• All patient should be offered medications regardless of CD4 count
• Initial treatment regimens should have 2 or 3 active medications
• Regimens should be designed to fit the patient• Interruptions in therapy should be avoided
41
HIV Treatment 101
C. Ryan Tomlin, Pharm.D., BCPS, AAHIVPClinical Pharmacist – HIV Medicine
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