Download 5-HIV-Pharmacotherapy-Update-2016-no

Document related concepts

Prescription costs wikipedia , lookup

Bad Pharma wikipedia , lookup

Pharmacogenomics wikipedia , lookup

Adherence (medicine) wikipedia , lookup

Discovery and development of ACE inhibitors wikipedia , lookup

Discovery and development of neuraminidase inhibitors wikipedia , lookup

Metalloprotease inhibitor wikipedia , lookup

Theralizumab wikipedia , lookup

HIV vaccine wikipedia , lookup

Bilastine wikipedia , lookup

Discovery and development of non-nucleoside reverse-transcriptase inhibitors wikipedia , lookup

Discovery and development of HIV-protease inhibitors wikipedia , lookup

Discovery and development of integrase inhibitors wikipedia , lookup

Transcript
1
HIV Pharmacotherapy
Focused Update
Drew Lambert, PharmD
[email protected]
Husson University School of Pharmacy
2
I have no conflicts of interest.
• However, I will be using brand names extensively
during the presentation
1. Majority of the drugs used are brand-only
2. Easier to say
3
Objectives
• Identify and describe new antiretroviral therapies
• Review most recent HIV guidelines
• Choose an appropriate antiretroviral regimen
4
Definitions
• HIV – Human Immunodeficiency Virus
• AIDS – Acquired Immune Deficiency Syndrome
• ARV – Antiretroviral
• ART – Antiretroviral Therapy
• HAART – Highly Active Antiretroviral Therapy
• NRTI – Nucleoside Reverse Transcriptase Inhibitor
• NNRTI – Non-nucleoside Reverse Transcriptase
Inhibitor
• PI – Protease Inhibitor
• INSTI – Integrase Strand Transfer Inhibitor
5
Quick Stats
• About 1.2 million infected with HIV in the US
• 1 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
6
7
8
http://www.niaid.nih.gov/SiteCollectionIma
ges/topics/hivaids/HIVvirion.jpg
9
Pathophysiology
• HIV attacks cells expressing the CD4+ receptor
(CD4+ or CD4 cells)
• T-helper cells
• Normal 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
10
Fauci A et al. Ann Intern Med 1996;124:654
12
13
HIV vs. AIDS
• Patients may be infected with HIV but not have AIDS
• Stage 1 – CD4 count ≥500 cells/mm3 or CD4% ≥29
• Stage 2 – CD4 count 200-499 cells/mm3 or CD4% 14-28
• AIDS
• Stage 3 – CD4 count <200 or CD4% <14 OR
• AIDS defining illness
• Only seen with severe immunodeficiency
14
New Drug Approvals
All FDA approved drugs:
https://aidsinfo.nih.gov/education-materials/factsheets/19/58/fda-approved-hiv-medicines
15
Stribild – August 2012
• Elvitegravir 150mg + cobicistat 150mg +
emtricitabine 200mg + tenofovir disoproxil
fumarate 300mg
• INSTI based single tablet regimen
• Common adverse events
• Nausea and diarrhea
• Take with food
• Take antacids 2 hours before or after Stribild
16
Tivicay – August 2013
• Dolutegravir 50mg daily
• Increase to 50mg twice daily when given with
UGT1A1 inducers (e.g., rifampin, efavirenz,
fosamprenavir, tipranavir) or with INSTI resistance
• 2nd generation INSTI
• Common adverse effects
• Headache, insomnia, fatigue
• No food effects
• Take 2 hours prior or 6 hours after antacids
17
Triumeq – August 2014
• Dolutegravir 50mg + abacavir 600mg +
lamivudine 300mg
• Integrase inhibitor based single tablet regimen
• 2nd generation INSTI
• Only combination with abacavir/lamivudine NRTI
backbone
18
Tybost – September 2014
• Cobicistat (cobi) 150mg daily
• Pharmacokinetic booster (3A4 inhibitor) approved
to be used in combination with
• Darunavir 800mg daily
• Atazanavir 300mg daily
• Elvitegravir 150mg as part of Stribild or Genvoya
• Not active against HIV
• Inhibits creatinine excretion but does not change
GFR
19
Vitetka – September 2014
• Elvitegravir 85mg or 150mg
20
Vitetka – September 2014
• Must be given with ritonavir boosted protease
inhibitors
• Take with food
• Diarrhea is the most common adverse event
• Avoid with CYP 3A4 inducers
• No data yet on taking it with…
21
Protease inhibitor + booster combinations
- January 2015
Prezcobix
Evotaz
• Atazanavir (Reyataz)
• Darunavir (Prezista)
300mg + cobicistat
(Tybost) 150mg
800mg + cobicistat
(Tybost) 150mg
• 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)
22
Genvoya – November 2015
• Elvitegravir 150mg + cobicistat 150mg +
emtricitabine 200mg + tenofovir alafenamide 10mg
• INSTI based single tablet regimen
• Similar to Stribild
• Disoproxil fumarate 300mg
• Nausea is most common ADR
• Take with food
23
Odefsey – March 2016
• Rilpivirine 25mg + emtricitabine 200mg +
tenofovir alafenamide 25mg
• NNRTI based single tablet regimen
• Similar to Complera
• Disoproxil fumarate 300mg
• Take with food
• Depression, insomnia, headache, nausea are
common
24
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
Genvoya – A New 4-Drug Combination for HIV. The Medical Letter. 2016;15(1488):19-21.
25
Guidelines
(OLD) DRUGS
Drug Class & Individual Agent Overview
Nucleoside Reverse Transcriptase Inhibitors
Non-nucleoside reverse transcriptase inhibitors
Protease Inhibitors
Integrase strand transfer inhibitors
26
2007
1987
CCR-5 Antagonists &
Integrase Inhibitors
Nucleoside Reverse
Transcriptase Inhibitors
2003
Fusion
Inhibitors
1995
Protease
Inhibitors
1996
Non-Nucleoside Reverse
Transcriptase Inhibitors
July 12, 2006:
Atripla approved
27
NRTIs
Generic
Abbreviation
Brand
ABC
Ziagen
Didanosine*
ddI
Videx (EC)
Emtricitabine
FTC
Emtriva
Lamivudine*
3TC
Epivir
Tenofovir
TDF
Viread
Stavudine*
d4T
Zerit
Zidovudine*
AZT or ZDV
Retrovir
Abacavir*
* – generic (tablet dosage form)
28
Mechanism of Action and notes
• Nucleoside/nucleotide analogs
• Stop reverse transcriptase because of
replacement of 3’ end
• Actively compete with endogenous substrates
• Mimic different bases
• Choose two that mimic different base pairs
• Require phosphorylation for activation
• Generally renal elimination
• Form the backbone for HAART (highly active
antiretroviral therapy)
29
Class Adverse Reactions
• Headache
• N/V/D
• Rash
• Lipoatrophy—primarily caused by the thymidine
analogs zidovudine and stavudine
• Fatty liver
• Lactic acidosis
30
Nucleoside Reverse Transcriptase Inhibitors
• Abacavir (Ziagen, ABC)
• 600mg once daily or 300mg BID
• Must 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
31
Nucleoside Reverse Transcriptase Inhibitors
• Emtricitabine (Emtriva, FTC)
• 200mg daily
• May cause skin discoloration
• Generally well tolerated
• Active against HBV
• Lamivudine (Epivir, 3TC)
• 300mg daily
• Generally well tolerated
• Active against HBV
32
http://www.odermatol.com/wp-content/uploads/figure%201aj.jpg
33
Nucleoside Reverse Transcriptase Inhibitors
• Tenofovir disoproxil fumarate (Viread, TDF)
• 300mg daily
• NucleoTIDE 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
34
NRTI Combinations
• Combivir*
• Epivir (lamivudine) and Retrovir (zidovudine)
• Epzicom
• Epivir (lamivudine) and Ziagen (abacavir)
• Trizivir*
• Epivir (lamivudine), Retrovir (zidovudine), and Ziagen
(abacavir)
• Truvada
• Emtriva (emtricitabine) and Viread (tenofovir disoproxil)
* – generic (tablet dosage form)
35
NNRTIs
Generic
Abbreviation
Brand
Delavirdine
DLV
Rescriptor
Nevirapine*
NVP
Viramune (XR)
Efavirenz
EFV
Sustiva
Etravirine**
ETV
Intelence
Rilpivirine**
RPV
Edurant
* – generic
** – second generation NNRTI
36
Mechanism of Action and notes
• Inhibit reverse transcriptase directly
• Does not require activation
• Low genetic barrier to resistance
• Single mutation can cause resistance to multiple drugs
• Second generation NNRTIs have a higher barrier
to resistance
• Come in single tablet combinations
• Metabolized by and induce CYP 3A4
37
Adverse Reactions
• Rash (including SJS)
• N/V/D
• Increased LFTs
• Other drug-specific adverse reactions
• Newer NNRTIs are better tolerated
38
Non-Nucleoside Reverse Transcriptase Inhibitors
• Efavirenz (Sustiva, EFV)
• 600mg daily
• Do not use in moderate to severe hepatic impairment
• Pregnancy 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
39
Non-Nucleoside Reverse Transcriptase Inhibitors
• Rilpivirine (Edurant, RPV)
• 25mg daily
• Should be taken with food
• Higher barrier to resistance
• More virologic failures as compared to efavirenz in
patients with a viral load of >100,000 copies/mm3
• 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
40
NNRTI Combinations
• Atripla – 600/200/300mg
• Sustiva (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
41
PIs
Generic
Ritonavir
Indinavir
Abbreviation
RTV
IDV
Brand
Norvir
Crixivan
Nelfinavir
Saquinavir
Tipranavir
Fosamprenavir
NFV
SQV
TPV
FPV
Viracept
Invirase
Aptivus
Lexiva
Lopinavir/r
Darunavir
Atazanavir
LPV/r
DRV
ATV
Kaletra
Prezista
Reyataz
No generics
42
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 cells
• High barrier to resistance
• Strong CYP 3A4 inhibitors
• Many drug interactions
• Most require pharmacokinetic “boosting” with
ritonavir or cobicistat
43
Acosta, EP. Pharmacokinetic enhancement of protease inhibitors. JAIDS. 2002;29:S11-18.
44
Adverse Effects
• Most increase cholesterol and triglycerides
• Lipodystrophy
• Diabetes and insulin resistance
• Immune Reconstitution Inflammatory Syndrome
(IRIS)
• N/V/D
• Abdominal pain
• Elevated LFTs
45
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.
46
Protease Inhibitors
• Ritonavir (Norvir, RTV)
• Used to boost other PIs—100mg with each dose of the
other protease inhibitor
• Available as tablets and capsules—tablets much more
palatable
• Tingling or numbness of the hands or feet, or around
the mouth
47
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
48
Protease Inhibitors
• Darunavir (Prezista, DRV)
• 800mg daily boosted with ritonavir for treatment naïve
patients, 600mg BID boosted for treatment experienced
• Take with food
• Very high barrier to resistance
• Not recommended in severe liver disease
• Less metabolic side effects than older PIs
• Possible rash on initiation
49
PI Combinations
• Evotaz – 300mg/150mg
• Reyataz (atazanavir) + Tybost (cobicistat)
• Prezcobix – 800mg/150mg
• Prezista (darunavir) + Tybost (cobicistat)
• Kaletra – 800mg/200mg
• Lopinavir/ritonavir
• Lopinavir not available separately
• NOT single tablet regimens
50
Integrase Strand Transfer Inhibitors (INSTIs)
Generic
Raltegravir
Elvitegravir*
Abbreviation
RAL
EVG
Brand
Isentress
Vitekta
Dolutegravir*
DTG
Tivicay
* – Second generation
No generics
51
Mechanism of Action and notes
• Inhibits HIV integrase, which integrates the viral DNA into the host
cell’s DNA
• Lower barrier to resistance than the PIs
• Adverse Reactions
• Generally well tolerated
• N/D
• Headache
• Elevated LFTs
52
Integrase Strand Transfer Inhibitors (INSTIs)
• Raltegravir (Isentress, RAL)
• 400mg BID
• No food requirements
• No renal dose adjustments
• Not studied in severe hepatic impairment
• Metabolized by UGT1A1 mediated glucuronidation
• 800mg twice daily with rifampin
• Increased total bilirubin
• Elevated CK – myopathy and rhabdomyolysis
53
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)
54
HIV TREATMENT
GUIDELINES
55
Treatment Goals
• Suppression of HIV viral load
• Undetectable - <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.
59
Antiretroviral Treatment (ART)
• Current standard is minimum of 3 drug regimen
• Typically two (or more) classes
• Panel on Antiretroviral Guidelines for Adults and
Adolescents convened by the Department of
Health & Human Services (DHHS)
60
Who and When to Initiate ART
• “ART is recommended for all HIV-infected
individuals…”
• Especially in
• History 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
61
Why initiate ART immediately?
• Decreased risk of death
• START and TEMPRANO Trials
• Higher CD4 count (>500 cells/mm3)
• Higher incidence of 1 year viral suppression
• Lower viral load = decreased risk of transmission
• Public health benefit
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.
62
Starting HAART <12 months after
seroconversion improves immune health
• Median CD4 count in uninfected patients is
900 cells/mm3
• 38.4% of patients beginning HAART <12 months
after seroconversion achieved this
• 28.3% of patients beginning HAART >12 months
after seroconversion achieved this
• Better overall immune health
• Fewer patients progressed to AIDS
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.
65
Recommended Regimens for All
Treatment Naïve Patients (6 regimens)
NRTI Backbone
Combination drug
Darunavir/r
Emtricitabine +
Tenofovir (TDF)
Class
PI
Raltegravir
Elvitegravir/cobi*
Dolutegravir
Emtricitabine +
Tenofovir
alafenamide (TAF)
Elvitegravir/cobi*
Abacavir +
Lamivudine
Dolutegravir*
INSTI
* – Available as a single tablet regimen
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.
Recommended Regimens for Treatment
Naïve Patients
• Stribild ………………. 70 mL/min minimum
• Triumeq …………….. 50 mL/min minimum
• Genvoya……………
30 mL/min minimum
• Prezista + Norvir +
Dose adjust
<50mL/min for Truvada
only
Truvada
• Tivicay + Truvada
• Isentress + Truvada
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.
67
Alternative Regimens for Treatment Naïve Patients
NRTI Backbone
Combination drug
Efavirenz*
Rilpivirine*
Emtricitabine +
Tenofovir (TDF)
Class
NNRTI
Atazanavir/r
Atazanavir/cobi**
Darunavir/cobi**
Abacavir +
Lamivudine
PI
Darunavir/r
Darunavir/cobi**
* - Available as a single tablet regimen
** - Co-formulated
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.
68
Other Regimens for Treatment Naïve Patients
NRTI Backbone
Abacavir +
Lamivudine
Emtricitabine +
Tenofovir
Lamivudine
NONE
Combination drug
Raltegravir
Class
INSTI
Efavirenz*
Atazanavir/r*
Atazanavir/cobi*
Lopinavir/r
NNRTI
PI
Lopinavir/r
Lopinavir/r
Darunavir/r +
Raltegravir*
PI + INSTI
* - Viral load <100,000 copies/mL (and CD4+ >200 for DRV/RAL)
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.
69
Regimen Notes
• Patients receiving any regimen with abacavir
must be HLA-B*5701 negative
• Patients receiving a regimen with cobicistat and
TDF must have a pre-treatment CrCl ≥70 mL/min
• Patients 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.
70
Regimen Notes
• Emtricitabine/tenofovir (Truvada) and
abacavir/lamivudine (Epzicom) are the preferred
NRTI backbones
• No CCR5 antagonists or fusion inhibitors are
Recommended, Alternative, or Other regimens
• There are a total of 6 single tablet regimens; 3
are preferred
• Genvoya, 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.
71
Regimen Notes
• Tenofovir disoproxil fumarate – use with caution
in patients with renal insufficiency
• Efavirenz 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.
72
Regimen Notes
• Rilpivirine is not recommended in patients with a
viral load > 100,000 copies/mL
• PPIs are contraindicated with RPV
• Do 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/min
73
Choosing a Regimen
• Least adverse effects
• INSTI-based
• Durability
• PI-based
• Drug interactions
• INSTI based (usually)
• Single tablet regimen
• INSTI- or NNRTI-based
74
Emphasize Benefits of Therapy
• 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. Feb 12, 2013
75
Interventions to Improve Adherence
• Delivery of prescriptions
• Often disadvantaged populations
• Automatic refills
• Paying for medications
• Ryan White programs
• PAPs
• Other state and federal programs
• Dealing with insurance issues to ensure there is not a
lapse in therapy
76
XY is a 45 year old patient newly diagnosed with HIV.
His CD4+ count is 373 cells/mm3 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?
A. Genvoya
B. Atripla
C. Triumeq
D. Stribild
E. Complera
77
Which of the following Patients with HIV
should begin therapy?
A. 16 year old pregnant female with a CD4 count of
B.
C.
D.
E.
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/mm3 and a viral load of 984
copies/mL
36 year old female with Kaposi’s sarcoma and a
CD4 count of 77 cells/mm3 and a viral load of
797,384 copies/mL
51 year old male with diabetes and a CD4 count of
501 cells/mm3 and a viral load of 97,384 copies/mL
All of these patients should begin therapy
78
Which set of the following drugs all
contain the pharmacokinetic booster
cobicistat (Tybost®)?
A. Prezista, Stribild, and Tivicay, Vitekta
B. Evotaz, Prezista, Tivicay, Vitekta
C. Genvoya, Kaletra, Prezcobix, Triumeq
D. Evotaz, Genvoya, Prezcobix, Stribild
E. Prezcobix, Triumeq, Tivicay, Vitekta
79
Summary & Questions?
• Many new therapies are available which give new
options to patients seeking alternatives
• All patients should be treated regardless of CD4+
count or viral load
• Regimens should be individualized based on
specific patient parameters
• Adherence
• Drug interactions
• Adverse effects
• Durability
80
Resources
• AIDSinfo
• http://www.aidsinfo.nih.gov
• Guidelines and other resources
• Centers 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