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HIV Updates
Abdi Mohamed, Pharm.D
Assistant Professor o Pharmacy Practice
Husson University School of Pharmacy
Objectives
• Review of the history and epidemiology of
HIV/AIDS
• Diagnosis of HIV infection
• When to initiate therapy
• Overview of antiretroviral medications
• New DHHS adult and adolescent antiretroviral
treatment guidelines.
• Importance of adherence
What is HIV?
• HIV is a lentivirus
• HIV = Human
Immunodeficiency Virus
• It destroys CD4 cells (Tcells and macrophage)
• AIDS = Acquired
immunodeficiency
Syndrome
– CD4 count < 200/mm3 or
– CD4 % < 14%
History of HIV
•
•
•
•
First cases of AIDS were identified in 1981 in Los Angeles, CA
Believed to be a zoonosis (transmitted from animal)
HIV is a descendant of a Simian Immunodeficiency Virus (SIV)
SIVs bear a very close resemblance to HIV-1 and HIV-2 (two
types of HIV).
• HIV-2 is similar to SIVsm, a strain of SIV found in the sooty
mangabey (also known as the White-collared monkey), which is
indigenous to western Africa.
• HIV-1, was recently discovered to relate to SIVcpz, the SIV
strain found in chimpanzees
Chen Z, Telfier P, Gettie A, Reed P, Zhang L, Ho DD, Marx PA. J Virol. 1996 Jun;70(6):3617-27
Etiology
• HIV was identified as the etiologic agent of
AIDS until 1983
• Two types
– HIV-1
– HIV-2
• Both them cause similar condition
• They differ in transmission and progression
– HIV-1 more virulent and more easily transmissible
Barre-Sinoussi F, Chermann JC, et al. Science. 1983 May 20;220(4599):868-71.
5
Transmission
Epidemiology
• 2012 US HIV data
– Annually HIV infection 60,000
– People living with HIV 1.62 million
– HIV patients not in care ~55%
– 1 in 5 (20%) are unaware of their infection
– By race, blacks/African Americans face the
most severe burden of HIV
G.J. Stine. AIDS update 2012. Mc Graw Hill p152
7
Progression of HIV
2-3 wks
Viral transmission
2-3 wks
Acute retroviral syndrome
Recovery + seroconversion
Avg. 1.5yrs
Avg. 8 yrs
Asymptomatic chronic HIV inf
2-4 wks
Symptomatic HIV/AIDS
2007 The Hopkins HIV guide
Death
Diagnosis & Testing
• HIV antibody testing is performed by using an
enzyme-linked immunosorbent assay (ELISA)
• If positive repeat the test
• Use Western blot (WB) to confirm
• Rapid immunoassy (e.g OraQuick)
• Resistance test
– genotype (detects mutations that confers HIV drug
resistance)
– Phenotype (culture based on viral replication assays in the
absence or presence of drugs)
Use of CD4 Cell Levels to Guide
Therapy Decisions
• CD4 count
– The major indicator of immune function
– Most recent CD4 count is best predictor of
disease progression
– A key factor in determining urgency of ART or need for OI prophylaxis
– Important in determining response to ART
• Adequate response: CD4 increase 50-150 cells/µL per year
• CD4 monitoring
– Check at baseline (x 2) and at least every 3-6 months*
* May consider every 6-12 months in clinically stable patients on ART
with sustained HIV RNA suppression and CD4 status well above
threshold for opportunistic infection risk.
February 2013
www.aidsetc.org
Use of HIV RNA Levels to
Guide Therapy Decisions
• HIV RNA
– May influence decision to start ART and help
determine frequency of CD4 monitoring
– Critical in determining response to ART
• Goal of ART: HIV RNA below limit of detection (ie,
<20-75 copies/mL, depending on assay)
– Commercially available assays do not detect HIV-2
February 2013
www.aidsetc.org
Other Test
• HLA-B*5701 Screening
– Recommended before starting any regiment containing
abacavir, to reduce risk of hypersensitivity reaction (HSR)
– Positive patient should not receive ABC and ABC allergy
should be recorded in file
• Coreceptor tropism assay
– Should be performed to detect whether HIV-1 isolates use
CCR5 or CXR4 or both.
– Requires plasma HIV RNA ≥ 1000 copies/mL
– Maraviroc is considered for patient with virologic failure
DHHS: Changing Criteria for
Initiating ART
CD4+
Count,
cells/mm3
> 500
350-500
200-350
< 200 or
symptomatic
disease
1998
2001
Offer if
VL
> 55,000
Consider if
Offer if
VL
VL > 20,000
> 55,000
Offer, but
Offer if
controversy
VL > 20,000
exists
Offer if
VL > 20,000
Treat
Treat
2006
2008
Consider if
VL
≥ 100,000
Consider if
VL
≥ 100,000
Offer after
discussion
with patient
Consider in
certain
groups
Consider in
certain
groups
Treat
clinicaloptions.com/hiv
2009
2012
Consider
Treat
Treat
Treat
Treat
Treat
Treat
Treat
Treat
Treat
Current Guidelines for Initiating ART
Guideline
Symptomatic/
AIDS
CD4+ Count
< 200
CD4+ Count
200-350
CD4+ Count
350-500
CD4+ Count
> 500
DHHS (2/2012)
Yes
Yes
Yes
Yes
Yes
IAS-USA (7/2012)
Yes
Yes
Yes
Yes
Yes
British HIV
Association
(9/2012)
Yes
Yes
Yes
Defer*
Defer*
European AIDS
Clinical Society
(11/2012)
Yes
Yes
Yes
Consider
Defer
WHO (7/2010)
Yes
Yes
Yes
No†
Not addressed
*If a patient with CD4+ count > 350 cells/mm³ wishes to start ART to reduce the risk of transmission to partners,
that wish should be respected and ART started.
†With the exception of an HIV-positive partner in a serodiscordant relationship, who should be offered antiretroviral
therapy at CD4+ count > 350 cells/mm³ to prevent transmission to the uninfected partner.
clinicaloptions.com/hiv
Recommendations for Initiating ART
ART is recommended for treatment
• “ART is recommended for all HIV-infected
individuals to reduce the risk of disease
progression.”
– The strength of this recommendation varies on the basis of
pretreatment CD4 count (stronger at lower CD4 levels)
February 2013
15
www.aidsetc.org
Recommendations for Initiating
ART: CD4 Count or Clinical
Category
Recommended for all CD4 counts:
CD4 count <350 cells/µL (AI)
CD4 count 350-500 cells/µL (AII)
CD4 count >500 cells/µL (BIII)
February 2013
www.aidsetc.org
16
Recommendations for Initiating
ART: Prevention
 Perinatal transmission
 Recommended for all HIV-infected pregnant
women (AI)
 Sexual transmission
 Recommended for all who are at risk of
transmitting HIV to sexual partners (AI for
heterosexuals, AIII for other transmission risk groups)
February 2013
www.aidsetc.org
17
Potential Benefits of Early
Therapy (2)
• Potential decrease in risk of many complications,
including:
–
–
–
–
–
–
HIV-associated nephropathy
Liver disease progression from hepatitis B or C
Cardiovascular disease
Malignancies (AIDS defining and non-AIDS defining)
Neurocognitive decline
Blunted immunological response owing to ART initiation at
older age
– Persistent T-cell activation and inflammation
February 2013
18
www.aidsetc.org
When to Start Therapy
 Drug toxicity
 Preservation of limited Rx
options
 Risk of resistance (and
transmission of resistant
virus)
Delayed ART
When to Start Therapy: Balance Now
Favors Earlier 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 options
 Risk of uncontrolled viremia at all
CD4+ cell count levels
 ↓ transmission
Delayed ART
Early ART
clinicaloptions.com/hiv
ANTIRETROVIRAL THERAPY
History of ART
22
Current ARV Classes
HAART
Protease inhibitors
(PI)
Reverse
Transcriptase
inhibitors (RTI)
Nucleotide/Nucleosi
de Reverse
Transcriptase
Inhibitors (NRTI)
Entry Inhibitors
Non-Nucleoside
Reverse
Transcriptase
Inhibitors (NNRTI)
Integrase Inhibitor
24
Current ARV Medications
NRTI
PI
 Abacavir (ABC)
 Didanosine (ddI)
 Emtricitabine (FTC)
 Lamivudine (3TC)
 Stavudine (d4T)
 Tenofovir (TDF)
 Zidovudine (AZT, ZDV)
 Atazanavir (ATV)
 Darunavir (DRV)
 Fosamprenavir (FPV)
 Indinavir (IDV)
 Lopinavir (LPV)
 Nelfinavir (NFV)
 Ritonavir (RTV)
 Saquinavir (SQV)
 Tipranavir (TPV)
NNRTI
 Delavirdine (DLV)
 Efavirenz (EFV)
 Nevirapine (NVP)
Etravirine (ETR)
Rilpivirine
(RPV)
February 2013
Integrase Inhibitor
(II)
 Raltegravir (RAL)
 Elvitegravir* (EVG)
Fusion Inhibitor
 Enfuvirtide (ENF, T-20)
CCR5 Antagonist
 Maraviroc (MVC)
* EVG currently available only
in coformulation with cobicistat
(COBI)/TDF/FTC
www.aidsetc.org
25
Nucleoside Reverse
Transcriptase Inhibitors (NRTI)
•
•
•
•
•
Backbone of HIV combination therapy
HIV-1&2
Minimal drug interactions
Renal excreted except ABC
Minimal cross resistance patterns
Abacavir(ABC, Ziagen)
• ABC 300mg PO twice day or
600mg PO daily
• Part of Epzicom and Trizivir
• HLA-B*5701-positive patients
should not receive ABC
– Positive status should be recorded as
an ABC allergy
• Life threatening if re-challenged
• Toxicity
– Hypersensitivity (HSR) ≈ 4%
•
•
•
•
Fever, rash, fatigue, malaise
Occur within 6 weeks
Don’t rechallenge
HLA-B*5701
300mg tablet or 20mg/ml solution
27
Zidovudine (AZT, Retrovir)
• ZDV 300mg BID
• Part of Combivir and
Trizivir
• First-line regimen for
pregnant women
• Toxicity
– Nausea, malaise, headache,
insomnia, lipoatrophy
– Anemia and neutropenia are
the most frequent doselimiting adverse effects
100mg tab, 300mg cap,
10mg/ml IV and 10mg/ml solution
28
Twin Drugs
Lamivudine (3TC)/ Epivir
• FDA approved for treatment
of HIV and HBV
• Dose
– 300mg PO daily
• Toxicity
– Minimal ≈ placebo
• headache
– Hepatitis flare (BB)
Emtricitabine (FTC)/ Emtriva
• Approved for HIV but also
used to treat HBV
• Dose
– 200mg PO daily
• Toxicity
– Minimal ≈ placebo
• headache
– Hepatitis flare (BB)
29
Tenofovir (TDF, Viread)
• FDA approved for HIV and HBV
• In 2012, Truvada was approved by the FDA for
pre-exposure prophylaxis (PrEP)
• Usually dose
– 300 mg daily
• Toxicity
– Well tolerated but rarely can lead to acute renal
failure, Fanconi’s syndrome, proteinuria,
– May contribute to decrease in bone mineral density
30
NRTI Co-formulated Regimen
• Truvada
– 1 tablet once a daily
• TDF 300mg + FTC 200mg
• Combivir
– 1 tablet twice a day
• 3TC 150mg + AZT 300 mg
• Epzicom
– 1 tablet once daily
• 3TC 300mg + ABC 600mg
• Trizivir
– 1 tablet twice a day
• 3TC 150mg + AZT 300mg + ABC 300 mg
31
Adverse Effects: NRTIs
• All NRTIs:
– Lactic acidosis and hepatic steatosis (highest incidence with
d4T, then ddI and ZDV, lower with TDF, ABC, 3TC, and
FTC)
– Lipodystrophy
(higher incidence with d4T)
February 2013
32
www.aidsetc.org
Non-Nucleoside Reverse
Transcriptase Inhibitors (NNRTIs)
• First Generation
– Delavirdine [DLV, RESCRIPTOR®]
– Efavirenz [EFV, SUSTIVA®]
– Nevirapine [NVP, VIRAMUNE®]
• Second Generation
– Etravirine [ETR, INTELENCE®]
– Rilpivirine [RPV, EDURANT]
33
Non-Nucleoside Reverse
Transcription Inhibitors (NNRTI)
• HIV-2 is resistant
• Limitation of first generation NNRTI
– Low genetic barrier to resistance
• Long half-lives
Efavirenz (EFV, Sustiva)
• Dosing recommendation
–
–
–
–
600mg PO once daily at or before bedtime
Take on empty stomach to reduce side effects
Co-formulated with TDF/FTC (Atripla)
No hepatic (caution) or renal dose adjustment
• Toxicities
– CNS side effects (4 weeks)
• drowsiness, insomnia, vivid dreams, and impaired concentration
– Rash
– Hyperlipidemia
– Potentially teratogenicity to humans
• Pregnancy category D
35
Nevirapine (NVP, Viramune)
• Extended release formulation was approved in 2011
• Dose recommendation
– 200mg PO QD x 2 weeks; 200mg PO BID
• Toxicity
– Rash including SJ syndrome
– Hepatotoxicity (BB)
• Female with CD4 > 250 or male with CD4> 400
• Liver disease (HBV, HCV or alcoholics)
– Child Pugh class B or C is contraindicated
36
Rilpivirine (RPV, Edurant)
• Approval: FDA-approved May 20, 2011for
treatment-naïve adults
• 25 mg tablet daily
– Take with 400 Kcal food
• Fixed dose
– Tenofovir-Emtricitabine-Rilpivirine (Complera)
• Toxicity (low): depression, insomnia, headache, and
rash
• Pregnancy : category B
37
ANTIRETROVIRAL THERAPY
Rilpivirine (TMC-278) vs. Efavirenz in ARV-Naive
ECHO and THRIVE: Study Design
Rilpivirine: 25 mg qd + TDF/FTC
(n = 346)
Study Features
Protocol
- Randomized, double-blind trial
- Phase 3
- N = 690 (ECHO) and 678 (THRIVE)
- Age > 18
- ARV-naïve
- HIV RNA > 5,000 copies/ml
- No baseline NNRTI mutations
- Randomized to one of 2 arms
- All given 2 NRTIs*
ECHO
1x
Efavirenz: 600 mg qd + TDF/FTC
(n = 344)
Rilpivirine: 25 mg qd + 2NRTIs*
(n = 340)
THRIVE
1x
*2 NRTIs:
ECHO: Tenofovir + Emtricitabine (TDF/FTC)
THRIVE: Tenofovir + Emtricitabine; Zidovudine + Lamivudine;
Efavirenz: 600 mg qd + 2NRTIs*
(n = 338)
Abacavir + Lamivudine
Source: Cohen C, et al. 17th International AIDS Conference. 2010:THLBB206.
ANTIRETROVIRAL THERAPY
Rilpivirine (TMC-278) vs. Efavirenz in ARV-Naive
ECHO and THRIVE: Week 48 Results
Pooled ECHO and THRIVE: Virologic Response ( ITT-TLOVR)
84.3%
82.3%
2NRTIs+ Rilpivirine (n = 686)
2NRTIs+ Efavirenz (n = 682)
Source: Cohen C, et al. 17th International AIDS Conference. 2010:THLBB206.
ANTIRETROVIRAL THERAPY
Rilpivirine (TMC-278) vs. Efavirenz in ARV-Naive
ECHO and THRIVE: Results
48 Week Data: Virologic Failure
All regimens included 2 NRTIs
Source: Cohen C, et al. 17th International AIDS Conference. 2010:THLBB206.
ANTIRETROVIRAL THERAPY
Rilpivirine (TMC-278) vs. Efavirenz in ARV-Naive
ECHO and THRIVE: Results
48 Week Data: Discontinuation Due to Adverse Effects
All regimens included 2 NRTIs
Source: Cohen C, et al. 17th International AIDS Conference. 2010:THLBB206.
ANTIRETROVIRAL THERAPY
Rilpivirine (TMC-278) vs. Efavirenz in ARV-Naive
ECHO and THRIVE: Results
Conclusions:
• Rilpivirine demonstrated high response rate
• Rilpivirine virologic failure rate higher than efavirenz (9.0% vs 4.8%)
• Rilpivirine had significant tolerability advantage over efavirenz
Source: Cohen C, et al. 17th International AIDS Conference. 2010:THLBB206.
NRTI+NNRTI Co-formulated
Regimen
• Atripla
– EFT 600mg + FTC 200mg + TDF 300mg
• FTC+TDF= Truvada
– 1 tablet once daily at or before bedtime
• Complera
– RPV 25mg + FTC 200mg + TDF 300mg
• FTC+TDF= Truvada
• 1 tablet once daily with a meal
– Avoid antacids
– PPI is contraindicated
43
Adverse Effects: NNRTIs
• All NNRTIs:
– Rash, including Stevens-Johnson syndrome
– Hepatotoxicity (especially NVP)
– Drug-drug interactions
44
Protease Inhibitors
•
•
•
•
•
•
•
•
•
Atazanavir [ATV, REYATAZ®]
Darunavir [DRV, PREZISTA®]
Fosamprenavir [FPV, LEXIVA®]
Indinavir [IDV, CRIXIVAN®]
Lopinavir/Ritonavir [LPV/r, KALETRA®]
Nelfinavir [NFV, VIRACEPT®]
Ritonavir [RTV, NORVIR®]
Saquinavir [SQV, INVIRASE®]
Tipranavir [TPV, APTIVUS®]
45
ARV Components in Initial
Therapy: PIs
ADVANTAGES
• Higher genetic barrier to
resistance
• PI resistance uncommon
with failure (boosted PI)
• NNRTIs and II preserved
for future use
February 2013
DISADVANTAGES
• Metabolic complications
(fat maldistribution,
dyslipidemia, insulin
resistance)
• GI intolerance
• Potential for drug interactions
(CYP450), especially with
RTV
46
www.aidsetc.org
Atazanavir (ATV, Reyataz)
• Recommended dose
– Naïve patient
• 400 mg once daily or
• 300 mg + 100mg RTV once daily
– Take with food
– Avoid acid suppressing agents
• Toxicity
– Hyperbilirubinemia
– PR prolongation
– Nephrolithiasis, cholelithiasis
47
Darunavir (DRV, Prezita)
• Dose
– ARV naïve or experienced patients with no mutation
• 800mg + 100 mg RTV once daily
– ARV experienced patient with at least one mutation
– DRV must be boosted with RTN
– Take with food
• Toxicity
– DRV contains a sulfonamide moiety,
• Avoid patients with a sulfa allergy→ Rash
– GI (N/V/D)
– Hyperlipidemia
48
Lopinavir/Ritonavir (LPV/r, Keletra)
• The only boosted PI that is coformulated with
low-dose ritonavir
– LPV 200mg + RTV 50mg or LPV 100mg + RTV
25mg
• preferred regimen for pregnant women
• Toxicities
– GI (N/V/D)
– Hyperlipidemia (especially ↑triglycerides)
– Potential increased MI risk
49
Ritonavir (RTV, Norvir)
• Booster for other PI
– 100-400mg per day in 1-2 divided doses
• Formulation
– 100mg soft gel capsules, 100mg tablet
– 80mg/mL solution
• 43% alcohol
• Toxicities
– GI (N/V/D)
– Hyperlipidemia
– Hyperglycemia
50
Integrase Inhibitors
• Raltegravir
• Elvitegravir* (EVG)
• Currently being studied in phase III clinical trials
– Dolutegravir (S/GSK1249572)
* EVG currently available only
in coformulation with cobicistat
(COBI)/TDF/FTC
51
Integrase Inhibitors
•
•
•
•
Virologic response noninferior to EFV
appears to be active against HIV2
Fewer adverse events than with EFV
RAL has fewer drug-drug interactions than with
PIs or NNRTIs (not true of EVG/COBI)
• NNRTIs and PIs preserved for future use
February 2013
www.aidsetc.org
52
Raltegravir (RAL, Isentress)
• Indicated for both naïve and experienced pt
• Dose recommendation
– 400mg po twice a day with or without food
– When combined with other ART dose stays same
• Toxicities
–
–
–
–
Diarrhea, Nausea
Fatigue
Myalgia
Abnormal liver function
53
Stribild (Quad Pill)
• Approved August 2012
• Elvitegravir 150mg + cobicistat 150mg +
emtricitabine 200mg + tenofovir 300mg
• Stribild PO daily with food
• Cobicistat is used to increase the levels of
elvitegravir
• AE
– Decreased CrCl
– Nausea, diarrhea
EVG/COBI/TDF/FTC: “Alternative”
First-line Regimen
• EVG/COBI/TDF/FTC recommended as “alternative” regimen in
treatment-naive patients with ClCr > 70 mL/min (BI)[1]
• Benefits
– Noninferior to EFV/TDF/FTC,[2] ATV/RTV + TDF/FTC[3]
– 1-tablet, once-daily dosing
• Limitations
– Potential for drug–drug interactions
– Limited safety data; limited data in advanced disease, women
– Possible increased risk proximal renal tubulopathy
– Food requirement
1. DHHS Panel Statement. September 18, 2012. 2. Sax PE, et al. Lancet. 2012;379:2439-2448.
3. DeJesus E, et al. Lancet. 2010;379:2429-2438.
DISADVANTAGES II
•
•
•
•
•
Twice-daily dosing
Lower genetic barrier to resistance than PIs
COBI has many drug-drug interactions
COBI may cause or worsen renal impairment
Myopathy, rhabdomyolysis, skin reactions
reported with RAL (rare)
February 2013
www.aidsetc.org
56
Entry Inhibitors
Enfuvirtide (T-20, Fuzion)
• Use for experienced patients
• 90mg subcutaneous injection
twice a day
– Reconstitute with 1.1ml sterile
water
• Adverse effects
– Injection-site reactions
– HSR
– Increased risk of bacterial
pneumonia
Maraviroc (MVC, Selzentry)
• Block the binding of gp120
to the chemokine receptor
(CCR5)
• Coreceptor tropism assay
– CCR5 or CXCR4
• Adverse Effects
– Drug-drug interactions
– Rash
– Abdominal pain
– Upper respiratory tract
infections
New DHHS Treatment
guidelines
Feb, 2013
Initial Treatment: Choosing
Regimens
• 3 main categories:
– 1 NNRTI + 2 NRTIs
– 1 PI + 2 NRTIs
– 1 II + 2 NRTIs
• Combination of NNRTI, PI, or II + 2 NRTIs preferred for
most patients
• Fusion inhibitor, CCR5 antagonist not recommended in
initial ART
• Few clinical end points to guide choices
• Advantages and disadvantages to each type of regimen
• Individualize regimen choice
DHHS guideline; February 2013
59
www.aidsetc.org
Initial Regimen:
Recommended/Preferred Agents
EFV
ATV/RTV
TDF/FTC +
DRV/RTV
RAL
DHHS Guidelines . Feb 2013; Thompson MA, et al. JAMA. 2010;304;321-333.
Initial Regimen:
Recommended/Alternative
RPV
LPV/RTV
TDF/FTC or ABC/3T
+
FPV/RTV
EVG/COBI/TDF/FT
C
9. DHHS Guidelines for Antiretroviral Therapy in Adults and Adolescents. March 2012.
10. DHHS Panel Statement. September 18, 2012.
CYP450 and Drug Metabolism
CYP2E1
CYP1A2
CYP2C
CYP2D6
Key points
•Majority of drugs metabolized
by CYP3A4 and CYP2D6
•CYP3A4 and CYP2D6
extensively involved with
PI/NNRTI metabolism
•Enzymes can be induced or
inhibited
Adapted from Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 9th ed.
Effect of ARV on Drug Metabolism
Induced by:
3A4
Inhibited by: RTV
Induced by:
Induced by:
Inhibited by: RTV, NFV, IDV,
SQV, DLV
RTV, NFV
Inhibited by: EFV, DLV
RTV,
NFV ?
RTV, NFV, TPV
EFV, NVP
Induced by:
2C19 2D6 2C9
RTV, NFV
Inhibited by: DLV
Induced by:
1A2 2E1 2A6 2B6 2C8
From Fichtenbaum CJ. Clin Pharmacokinet 2002:41(14):1195-1211.
EFV,
NVP
Recommendations for Initiating
ART: Considerations
 “Patients starting ART should be willing and able 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 an
individual patient’s clinical or psychosocial factors
February 2013
www.aidsetc.org
64
Immunization
MMWR / February 4, 2011 / Vol. 60 / No. 4
65
ART Approved & Unapproved Drugs
66
References
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Chen Z, Telfier P, Gettie A, Reed P, Zhang L, Ho DD, Marx PA. J Virol. 1996 Jun;70(6):3617-27
G.J. Stine. AIDS update 2012. Mc Graw Hill 2012
Thompson MA, et al. JAMA. 2012;308:387-402.
Williams I, et al. HIV Med. 2012;13(suppl 2):1-85.
EACS Guidelines for the Treatment of HIV Infected Adults in Europe. November 2012.
WHO Guidelines for Antiretroviral Therapy for HIV Infection in Adults and Adolescents. July 2010.
DHHS Guidelines for Antiretroviral Therapy in Adults and Adolescents. March 2012.
DHHS Guidelines for Antiretroviral Therapy in Adults and Adolescents. March 2012.
DHHS Guidelines for Antiretroviral Therapy in Adults and Adolescents. Feb 2013
Cohen M, et al. N Engl J Med. 2011;365:493-505.
DHHS Panel Statement. September 18, 2012.
Sax PE, et al. Lancet. 2012;379:2439-2448.
DeJesus E, et al. Lancet. 2010;379:2429-2438
ww.hivinsite.com
www.clinicaloptions.com
www.hivguidelines.org
www.hopkins-aids.edu