Drew Lambert PharmD lambertdhussonedu Husson University School of Pharmacy 1 I have no conflicts of interest However I will be using brand names extensively during the presentation Majority of the drugs used are brandonly ID: 737952
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Slide1
HIV Pharmacotherapy Focused Update
Drew Lambert, PharmDlambertd@husson.eduHusson University School of Pharmacy
1Slide2
I have no conflicts of interest.
However, I will be using brand names extensively during the presentationMajority of the drugs used are brand-onlyEasier to say
2Slide3
Objectives
Identify and describe new antiretroviral therapiesReview most recent HIV guidelinesChoose an appropriate antiretroviral regimen
3Slide4
Definitions
HIV – Human Immunodeficiency VirusAIDS – Acquired Immune Deficiency SyndromeARV – AntiretroviralART – Antiretroviral TherapyHAART – Highly Active Antiretroviral TherapyNRTI – Nucleoside Reverse Transcriptase InhibitorNNRTI – Non-nucleoside Reverse Transcriptase Inhibitor
PI – Protease Inhibitor
INSTI –
Integrase
Strand Transfer Inhibitor
4Slide5
Quick Stats
About 1.2 million infected with HIV in the US1 of every 265 people~13% undiagnosed (down from ~20% previously)
~50,000
new cases per year in the
US (2013)
~14
,000
deaths per year in the
US (2012)
Centers for Disease Control and Prevention. Results of the Expanded HIV Testing Initiative--25 jurisdictions, United States, 2007-2010.
MMWR
Morb
Mortal
Wkly
Rep. Jun 24 2011;60(24):805-810. http://www.cdc.gov/hiv/statistics/overview/ataglance.html
5Slide6
6Slide7
7Slide8
http://www.niaid.nih.gov/SiteCollectionImages/topics/hivaids/HIVvirion.jpg
8Slide9
Pathophysiology
HIV attacks cells expressing the CD4+ receptor (CD4+ or CD4 cells)T-helper cellsNormal range is 500-1600 cells/mm3 (
CD4 count)
40-70% of total lymphocytes
New viruses bud off from the cell and enter the bloodstream
The number of copies of HIV RNA per mL is known as
viral load
9Slide10
Fauci
A et al. Ann Intern Med 1996;124:654
10Slide11
Kahn JO, Walker BD. Acute human immunodeficiency virus type 1 infection.
NEJM.
1
998;339(1
):33-39.
11Slide12
12Slide13
HIV vs. AIDS
Patients may be infected with HIV but not have AIDSStage 1 – CD4 count ≥500 cells/mm3 or CD4% ≥29Stage 2 – CD4 count 200-499 cells/mm
3
or CD4% 14-28
AIDS
Stage 3 – CD4 count <200 or CD4% <14
OR
AIDS defining illness
Only seen with severe immunodeficiency
13Slide14
New Drug Approvals
All FDA approved drugs:https://aidsinfo.nih.gov/education-materials/fact-sheets/19/58/fda-approved-hiv-medicines
14Slide15
Stribild – August 2012
Elvitegravir 150mg + cobicistat 150mg + emtricitabine 200mg + tenofovir disoproxil fumarate 300mgINSTI based single tablet regimenCommon adverse events
Nausea and diarrhea
Take with food
Take antacids 2 hours before or after Stribild
15Slide16
Tivicay – August 2013
Dolutegravir 50mg dailyIncrease to 50mg twice daily when given with UGT1A1 inducers (e.g., rifampin, efavirenz, fosamprenavir, tipranavir) or with INSTI resistance2nd generation INSTI
Common adverse effects
Headache, insomnia, fatigue
No food effects
Take 2 hours prior or 6 hours after antacids
16Slide17
Triumeq – August 2014
Dolutegravir 50mg + abacavir 600mg + lamivudine 300mgIntegrase inhibitor based single tablet regimen2nd generation INSTIOnly combination with abacavir/lamivudine NRTI backbone
17Slide18
Tybost – September 2014
Cobicistat (cobi) 150mg dailyPharmacokinetic booster (3A4 inhibitor) approved to be used in combination with Darunavir 800mg dailyAtazanavir 300mg
daily
Elvitegravir 150mg as part of Stribild or
Genvoya
Not active against HIV
Inhibits creatinine excretion but does not change GFR
18Slide19
Vitetka
– September 2014
Elvitegravir 85mg or 150mg
19Slide20
Vitetka – September 2014
Must be given with ritonavir boosted protease inhibitorsTake with foodDiarrhea is the most common adverse eventAvoid with CYP 3A4 inducersNo data yet on taking it with…
20Slide21
Evotaz
Atazanavir (Reyataz) 300mg + cobicistat (Tybost) 150mg
Prezcobix
Darunavir (
Prezista
) 800mg + cobicistat (
Tybost
) 150mg
21
Protease inhibitor + booster
combinations -
January 2015
Both approved for use in combination with other ARV drugs
Previously approved to be boosted with ritonavir
Take with food
Metabolic ADRs (diabetes, fat redistribution, dyslipidemia)Slide22
Genvoya – November 2015
Elvitegravir 150mg + cobicistat 150mg + emtricitabine 200mg + tenofovir alafenamide 10mgINSTI based single tablet regimenSimilar to Stribild
Disoproxil
fumarate
300mg
Nausea is most common ADR
Take with food
22Slide23
Odefsey – March 2016
Rilpivirine 25mg + emtricitabine 200mg + tenofovir alafenamide 25mgNNRTI based single tablet regimenSimilar to CompleraDisoproxil
fumarate
300mg
Take with food
Depression, insomnia, headache, nausea are common
23Slide24
Tenofovir alafenamide
(TAF) vs. Tenofovir disoproxil fumarate (TDF)TDF conversion to tenofovir occurs mainly in the plasma; TAF conversion occurs
intracellularly
Plasma levels 91% lower; intracellular levels 4.1x higher
Less serum creatinine increase
Less effects on BMD
Less proteinuria
Less renal dysfunction
Same price
More comparison studies are ongoing
24
Genvoya
– A New 4-Drug Combination for HIV. The Medical Letter. 2016;15(1488):19-21.Slide25
(Old) Drugs
Drug Class & Individual Agent OverviewNucleoside Reverse Transcriptase InhibitorsNon-nucleoside reverse transcriptase inhibitorsProtease InhibitorsIntegrase strand transfer inhibitors
25
GuidelinesSlide26
Nucleoside Reverse Transcriptase Inhibitors
1987
1995
Protease Inhibitors
1996
Non-Nucleoside Reverse Transcriptase Inhibitors
2003
Fusion Inhibitors
2007
CCR-5 Antagonists &
Integrase
Inhibitors
July 12, 2006: Atripla approved
26Slide27
NRTIs
Generic
Abbreviation
Brand
Abacavir
*
ABC
Ziagen
Didanosine
*
ddI
Videx
(
EC)
Emtricitabine
FTC
Emtriva
Lamivudine*
3TC
Epivir
Tenofovir
TDF
Viread
Stavudine
*
d4T
Zerit
Zidovudine
*
AZT
or ZDV
Retrovir
*
–
generic (tablet dosage form)
27Slide28
Mechanism of Action and notes
Nucleoside/nucleotide analogsStop reverse transcriptase because of replacement of 3’ endActively compete with endogenous substratesMimic different basesChoose two that mimic different base pairsRequire phosphorylation for activation
Generally renal elimination
Form the backbone for HAART (highly active antiretroviral therapy)
28Slide29
Class Adverse Reactions
HeadacheN/V/DRashLipoatrophy—primarily caused by the thymidine analogs zidovudine
and
stavudine
Fatty liver
Lactic acidosis
29Slide30
Nucleoside Reverse Transcriptase Inhibitors
Abacavir (Ziagen, ABC)600mg once daily or 300mg BIDMust test for HLA-B*5701 because of possible hypersensitivity reaction
May have higher rates of failure in individuals with an viral load of >100,000 copies/mL
Zidovudine (Retrovir, AZT or ZDV)
300mg BID
Possible anemias and fatigue
Renal dose adjustments with
CrCl
<15mL/min
Bone marrow suppression
Fingernail
Hyperpigmentation
30Slide31
Nucleoside Reverse Transcriptase Inhibitors
Emtricitabine (Emtriva, FTC)200mg dailyMay cause skin discoloration
Generally well tolerated
Active against HBV
Lamivudine
(
Epivir
, 3TC)
300mg daily
Generally well tolerated
Active against HBV
31Slide32
http://www.odermatol.com/wp-content/uploads/figure%201aj.jpg
32Slide33
Nucleoside Reverse Transcriptase Inhibitors
Tenofovir disoproxil fumarate (Viread, TDF)300mg dailyNucleoTIDE
reverse transcriptase inhibitor
Possible decreases in BMD
Fairly well tolerated
Activity against HBV
May cause renal dysfunction
Dose adjustments needed for
CrCL
<50mL/min, <30mL/min, and is not recommended with CrCl <10 unless receiving
hemodialysis
33Slide34
NRTI Combinations
Combivir*Epivir (lamivudine) and Retrovir (zidovudine
)
Epzicom
Epivir
(lamivudine) and
Ziagen
(
abacavir
)
Trizivir
*
Epivir
(lamivudine),
Retrovir (zidovudine), and Ziagen (abacavir)TruvadaEmtriva (emtricitabine
) and
Viread
(
tenofovir
disoproxil
)
*
–
generic (tablet dosage form)
34Slide35
NNRTIs
Generic
Abbreviation
Brand
Delavirdine
DLV
Rescriptor
Nevirapine
*
NVP
Viramune
(XR)
Efavirenz
EFV
Sustiva
Etravirine
**
ETV
Intelence
Rilpivirine
**
RPV
Edurant
* – generic
** – second generation NNRTI
35Slide36
Mechanism of Action and notes
Inhibit reverse transcriptase directlyDoes not require activationLow genetic barrier to resistanceSingle mutation can cause resistance to multiple drugsSecond generation NNRTIs have a higher barrier to resistanceCome in single tablet combinationsMetabolized by and induce CYP 3A4
36Slide37
Adverse Reactions
Rash (including SJS)N/V/DIncreased LFTsOther drug-specific adverse reactionsNewer NNRTIs are better tolerated
37Slide38
Non-Nucleoside Reverse Transcriptase Inhibitors
Efavirenz (Sustiva, EFV)600mg dailyDo not use in moderate to severe hepatic impairmentPregnancy class D
CNS adverse effects
Depression
Insomnia/abnormal dreams or nightmares
Dizziness
May give a false positive test for marijuana
Generally given at bedtime
Available as a combination tablet
38Slide39
Non-Nucleoside Reverse Transcriptase Inhibitors
Rilpivirine (Edurant, RPV)25mg dailyShould be taken with foodHigher barrier to resistance
More virologic failures as compared to
efavirenz
in patients with a viral load of >100,000 copies/mm
3
Depressive disorders
Contraindicated with CYP 3A4 inducers and PPIs
Only NNRTI to not inhibit or induce CYP enzymes
Available as a combination tablet
Not studied in patients with severe hepatic impairment
39Slide40
NNRTI Combinations
Atripla – 600/200/300mgSustiva (efavirenz), Emtriva (
emtricitabine
),
Viread
(
tenofovir
)
Sustiva (efavirenz), Truvada (emtricitabine and tenofovir)
Complera
– 200/25/300mg
Emtriva
(
emtricitabine
), Edurant (rilpivirine), Viread (tenofovir)Edurant (rilpivirine), Truvada (emtricitabine and tenofovir)Odefsey – 200/25/25mg
Edurant (rilpivirine), Emtriva (emtricitabine), tenofovir
alafenamide
40Slide41
PIs
Generic
Abbreviation
Brand
Ritonavir
RTV
Norvir
Indinavir
IDV
Crixivan
Nelfinavir
NFV
Viracept
Saquinavir
SQV
Invirase
Tipranavir
TPV
Aptivus
Fosamprenavir
FPV
Lexiva
Lopinavir
/r
LPV/r
Kaletra
Darunavir
DRV
Prezista
Atazanavir
ATV
Reyataz
No generics
41Slide42
Mechanism of Action and notes
Inhibit HIV protease enzyme, which cleaves polyproteins into mature, active proteins. This results in production of immature, non-infections virus particles.Occurs post-translation, so PIs are active in acutely and chronically infected cellsHigh barrier to resistanceStrong CYP 3A4 inhibitors
Many drug interactions
Most require pharmacokinetic “boosting” with ritonavir or cobicistat
42Slide43
Acosta, E
P
.
Pharmacokinetic
enhancement of protease
inhibitors.
JAIDS.
2002;29:S11-18
.
43Slide44
Adverse Effects
Most increase cholesterol and triglyceridesLipodystrophyDiabetes and insulin resistanceImmune Reconstitution Inflammatory Syndrome (IRIS)N/V/DAbdominal painElevated LFTs
44Slide45
What is the difference between lipoatrophy and lipodystrophy?
In lipoatrophy, there is wasting of the subcutaneous fat, often accompanied by an increase in triglycerides. This occurs most commonly with the NRTIs, specifically stavudine and
didanosine
.
In
lipodystrophy
, there is accumulation of visceral fat. This occurs most commonly with the protease inhibitors.
45Slide46
Protease Inhibitors
Ritonavir (Norvir, RTV)Used to boost other PIs—100mg with each dose of the other protease inhibitorAvailable as tablets and capsules—tablets much more palatableTingling or numbness of the hands or feet, or around the mouth
46Slide47
Protease Inhibitors
Atazanavir (Reyataz, ATV)300mg daily boosted, or 400mg daily unboosted
Use boosted regimen when given with
tenofovir
or in treatment experienced patients
Take with food
Least metabolic side effects of the PI class
Dizziness and lightheadedness
Jaundice
Total bilirubin will likely increase, and can be a marker of adherence
PR prolongation
Interaction with PPIs and acid-decreasing agents
47Slide48
Protease Inhibitors
Darunavir (Prezista, DRV)800mg daily boosted with ritonavir for treatment naïve patients, 600mg BID boosted for treatment experiencedTake with food
Very high barrier to resistance
Not recommended in severe liver disease
Less metabolic side effects than older PIs
Possible rash on initiation
48Slide49
PI Combinations
Evotaz – 300mg/150mgReyataz (atazanavir) + Tybost (cobicistat)
Prezcobix
– 800mg/150mg
Prezista
(darunavir) +
Tybost
(cobicistat)
Kaletra
– 800mg/200mg
Lopinavir/ritonavir
Lopinavir not available separately
NOT single tablet regimens
49Slide50
Integrase
Strand Transfer Inhibitors (INSTIs)
Generic
Abbreviation
Brand
Raltegravir
RAL
Isentress
Elvitegravir*
EVG
Vitekta
Dolutegravir*
DTG
Tivicay
*
–
Second generation
No generics
50Slide51
Mechanism of Action and notes
Inhibits HIV integrase, which integrates the viral DNA into the host cell’s DNALower barrier to resistance than the PIsAdverse ReactionsGenerally well tolerated
N/D
Headache
Elevated LFTs
51Slide52
Raltegravir (Isentress
, RAL)400mg BIDNo food requirementsNo renal dose adjustmentsNot studied in severe hepatic impairmentMetabolized by UGT1A1 mediated glucuronidation
800mg twice daily with rifampin
Increased total bilirubin
Elevated
CK – myopathy and
rhabdomyolysis
Integrase
Strand Transfer Inhibitors (INSTIs)
52Slide53
INSTIs Combinations
Stribild - 150/150/300/200mg daily
Elvitegravir/cobicistat/tenofovir/emtricitabine (EVG/
cobi
/
TDF
/FTC)
Genvoya
- 150/150/
10
/200mg
daily
Elvitegravir/cobicistat/tenofovir
alafenamide
/emtricitabine (EVG/cobi/TAF/FTC)Triumeq
-
50/600/300mg
Dolutegravir/abacavir/lamivudine (DTG/ABC/3TC)
53Slide54
HIV Treatment guidelines
54Slide55
Treatment Goals
Suppression of HIV viral loadUndetectable - <50 copies/mL or the lower limit of detection (some assays detect a few as 20 copies/mL)“The goal of ART is to suppress
HIV replication to a level where drug-resistance mutations do not emerge
.”
Preserve and restore immunologic function
Reduce morbidity and prolong survival
Prevent HIV transmission
Improve quality of life
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at
http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf
.
55Slide56
Predictors of Treatment Success
High potency antiretroviral regimenMultiple active drugsAdherence to antiretroviral regimen (>95%)TolerabilityConvenienceLow baseline viral loadHigher (>200 cells/mm
3
) baseline CD4 count
Rapid reduction of
viremia
in response to therapy
56Slide57
Therapy Initiation Risk vs. Benefit
RisksDrug related toxicitiesLong-term effects may not be knownResistance with
nonadherance
Treatment fatigue
Less time for education and preparation for adherence
Transmission of resistant virus
Benefits
Reduces AIDS-related complications
Prolongation of disease-free survival
Viral suppression
Preservation of immune function
Decreased risk of disease transmission
Reduction of HIV-associated nephropathy, cardiovascular disease, malignancies,
neurocognitive
decline
DHHS Guidelines: Adults & Adolescents.
Nov 2014
57Slide58
Considerations for Treatment Selection
Underlying conditionsLiver/renal diseaseChemical dependencyCardiovascular diseaseUnderlying viral resistance
Potential medication toxicities
Drug interactions
Pregnancy or potential pregnancy
Lifestyle changes required
Dosing schedule, pill burden and food/fluid requirements
DHHS Guidelines: Adults & Adolescents.
Nov 2014
58Slide59
Antiretroviral Treatment (ART)
Current standard is minimum of 3 drug regimenTypically two (or more) classesPanel on Antiretroviral Guidelines for Adults and Adolescents convened by the Department of Health & Human Services (DHHS)
59Slide60
Who and When to Initiate ART
“ART is recommended for all HIV-infected individuals…”Especially inHistory of AIDS-defining illness (including opportunistic infections)Pregnancy
HIV-associated nephropathy
Hepatitis B & C
coinfection
Low CD4+ counts
Acute HIV infection
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health
and Human
Services. Available at
http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf
60Slide61
Why initiate ART immediately?
Decreased risk of deathSTART and TEMPRANO TrialsHigher CD4 count (>500 cells/mm3)Higher incidence of 1 year viral suppressionLower viral load = decreased risk of transmission
Public health benefit
61
INSIGHT START Study Group. Initiation of antiretroviral therapy in early asymptomatic HIV infection.
N
Engl
J
Med
. 2015
;373(9):
795-807.
TEMPRANO
ANRS Study Group,
Danel C, Moh R, et al. A trial of early antiretrovirals and isoniazid preventive
therapy in Africa
.
N
Engl
J Med
.
2015;373(9
):808-822.Slide62
Starting HAART <12 months after
seroconversion improves immune healthMedian CD4 count in uninfected patients is 900 cells/mm
3
38.4%
of patients beginning HAART
<12 months
after
seroconversion
achieved this
28.3%
of patients beginning HAART
>12 months
after
seroconversion
achieved thisBetter overall immune healthFewer patients progressed to AIDS62
Okulicz
, Jason F., et al. "Influence of the Timing of Antiretroviral Therapy on the Potential for Normalization of Immune Status in Human Immunodeficiency Virus 1–Infected Individuals."
JAMA internal medicine
175.1 (2015): 88-99.Slide63
Monitoring Parameters
Viral Load = Amount of virus per mL of bloodGoal: As low as possible!<50 copies/mL correlates with durable response to HIV medications and is considered “undetectable”
Newer assays may detect < 20 copies/mL
CD4 count = Number of immune cells in blood
Goal: As high as possible!
>200 cells/mm
3
to prevent most opportunistic infections
DHHS Guidelines: Adults & Adolescents.
Nov 2014
63Slide64
Definitions of Guideline Regimens
Recommended RegimenOptimal and durable efficacy, favorable tolerability and toxicity profile and ease of useAlternative RegimenEffective and tolerable but have potential disadvantages compared with preferred regimens. An alternative
regimen may
be the preferred regimen for some patients
.
DHHS Guidelines: Adults & Adolescents.
Nov. 2014
64Slide65
Recommended Regimens for All Treatment Naïve Patients (6 regimens)
NRTI Backbone
Combination drug
Class
Emtricitabine + Tenofovir (TDF)
Darunavir
/r
PI
Raltegravir
INSTI
Elvitegravir/
cobi
*
Dolutegravir
Emtricitabine + Tenofovir
alafenamide
(TAF)
Elvitegravir/
cobi
*
Abacavir
+ Lamivudine
Dolutegravir*
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at
http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf
.
* –
Available as a single tablet regimen
65Slide66
Recommended Regimens for Treatment Naïve Patients
Stribild ……………….Triumeq ……………..Genvoya……………Prezista
+
Norvir
+ Truvada
Tivicay
+ Truvada
Isentress
+ Truvada
70 mL/min minimum
50 mL/min minimum
30 mL/min minimum
Dose adjust <50mL/min for Truvada only
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available
at
http
://
aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf
.Slide67
Alternative Regimens for Treatment Naïve Patients
NRTI Backbone
Combination drug
Class
Emtricitabine + Tenofovir (TDF)
Efavirenz*
NNRTI
Rilpivirine*
Atazanavir/r
PI
Atazanavir/
cobi
**
Darunavir/
cobi
**
Abacavir
+ Lamivudine
Darunavir/r
Darunavir/
cobi
**
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available
at
http
://
aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf
.
AIDSInfo
. Recommendation
on
Integrase
Inhibitor Use in Antiretroviral Treatment-Naive HIV-Infected Individuals from the HHS Panel on Antiretroviral Guidelines for Adults and
Adolescents. Dec. 30, 2013. Available at
http
://
aidsinfo.nih.gov/contentfiles/upload/AdultARV_INSTIRecommendations.pdf
.
* - Available as a single tablet regimen
** - Co-formulated
67Slide68
Other Regimens for Treatment Naïve Patients
NRTI Backbone
Combination drug
Class
Abacavir
+ Lamivudine
Raltegravir
INSTI
Efavirenz*
NNRTI
Atazanavir/r*
PI
Atazanavir/
cobi
*
Lopinavir/r
Emtricitabine + Tenofovir
Lopinavir/r
Lamivudine
Lopinavir/r
NONE
Darunavir/r
+
Raltegravir
*
PI + INSTI
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at
http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf
.
68
* - Viral load <100,000 copies/mL (and CD4+ >200 for DRV/RAL)Slide69
Regimen Notes
Patients receiving any regimen with abacavir must be HLA-B*5701 negativePatients receiving a regimen with cobicistat and TDF must have a pre-treatment CrCl ≥70 mL/minPatients must have a viral load <100,000 when initiating Complera (RPV/FTC/TDF) and the 2 other regimens noted in the Other Regimens slide
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at
http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf
.
69Slide70
Regimen Notes
Emtricitabine/tenofovir (Truvada) and abacavir/lamivudine (Epzicom) are the preferred NRTI backbonesNo CCR5 antagonists or fusion inhibitors are Recommended, Alternative, or Other regimensThere are a total of 6 single tablet regimens; 3 are preferredGenvoya,
Triumeq
, Stribild
Other 3 are alternatives
Atripla, Complera,
Odefsey
(anticipated by me)
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at
http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf
.
70Slide71
Regimen Notes
Tenofovir disoproxil fumarate – use with caution in patients with renal insufficiencyEfavirenz is teratogenic; do not include in regimens for women who may become pregnant
Atazanavir
should not be used with >20mg of omeprazole (or equivalent PPI dose). Administer ATV >12 hours after a dose of a PPI
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at
http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf
.
71Slide72
Regimen Notes
Rilpivirine is not recommended in patients with a viral load > 100,000 copies/mLPPIs are contraindicated with RPVDo not start EVG/cobi/TDF/FTC (Stribild) in patients with
CrCl
<70mL/min
Change
regimen if
CrCl
falls below 50mL/min
EVG/
cobi
/TAF/FTC (
Genvoya
) may be used in all patients with
CrCl
>30mL/min72Slide73
Choosing a Regimen
Least adverse effectsINSTI-basedDurabilityPI-basedDrug interactionsINSTI based (usually)Single tablet regimenINSTI- or NNRTI-based
73Slide74
Emphasize Benefits of Therapy
DHHS Guidelines: Adults & Adolescents. Feb 12, 2013
Reduces
AIDS-related complications
Prolongation of disease-free survival
Viral suppression
Preservation of immune function
Decreased risk of disease transmission
Reduction of HIV-associated nephropathy, cardiovascular disease, malignancies, neurocognitive
decline
74Slide75
Interventions to Improve Adherence
Delivery of prescriptionsOften disadvantaged populationsAutomatic refillsPaying for medicationsRyan White programsPAPsOther state and federal programs
Dealing with insurance issues to ensure there is not a lapse in therapy
75Slide76
XY is a 45 year old patient newly diagnosed with HIV. His CD4+ count is 373 cells/mm
3 and viral load is 210,794 copies/mL. He also has CKD with a CrCl of 40mL/min. What is the only first line single tablet regimen recommended for XY?
Genvoya
Atripla
Triumeq
Stribild
Complera
76Slide77
Which of the following Patients with HIV should begin therapy?
16 year old pregnant female with a CD4 count of 797 cells/mm3 and a viral load of 7,384 copies/mL
26 year old otherwise healthy male with a CD4 count of 797 cells/mm
3
and a viral load of 984 copies/mL
36 year old female with Kaposi’s sarcoma and a CD4 count of 77 cells/mm
3
and a viral load of 797,384 copies/mL
51 year old male with diabetes and a CD4 count of 501 cells/mm
3
and a viral load of 97,384 copies/mL
All of these patients should begin
therapy
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Which set of the following drugs all contain the pharmacokinetic booster cobicistat (
Tybost®)?Prezista, Stribild, and Tivicay
,
Vitekta
Evotaz
,
Prezista
,
Tivicay
,
Vitekta
Genvoya
,
Kaletra
, Prezcobix, TriumeqEvotaz, Genvoya, Prezcobix, Stribild Prezcobix
,
Triumeq
,
Tivicay
,
Vitekta
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Summary & Questions?
Many new therapies are available which give new options to patients seeking alternativesAll patients should be treated regardless of CD4+ count or viral loadRegimens should be individualized based on specific patient parametersAdherenceDrug interactionsAdverse effects
Durability
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Resources
AIDSinfohttp://www.aidsinfo.nih.govGuidelines and other resourcesCenters for Disease Control and Prevention (CDC)
http://www.cdc.gov/hiv/
Fact sheets, slide sets, testing and surveillance
World Health Organization
http://www.who.int/topics/hiv_aids/en/
International data, facts and statistics
Positively Aware
http://positivelyaware.com/
Annual HIV Drug Guide and other resources
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