c6 hiv 201 armas
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HIV 201
Laura N Armas-Kolostroubis MDClinical Director
Texas/Oklahoma AIDS Education and Training Center
Christine, 2008
• 40 yo AAF with asymptomatic HIV diagnosed in 2003
• No co-infections• HTN well controlled on
lisinopril/HCTZ 10/12.5• Cocaine dependence• CD 4 = 876 cells/mL• VL = <400• Had all her immunizations in
2004-2005
Christine 2008
• You consider this patient to be:
a)A long-term non-progressor
b)A elite controller
c)Not infected with HIV
d)Infected with non-HIV-1 virus
e)None of the above
Christine 2009
• Lost to follow up x 6 months (was in jail)• CD4=734 c/mL; VL=1,207 c/mL• AST= 156, ALT= 98; GGT = 389• Reports occassional etoh binging• No hepatomegaly• HBsAg (+); HBsAb (-); HBcAb (+)• HBcIgG (+), HBcIgM (+)• HBV Quant= 657,433 c/mL• HBeAg (+), HBeAb (-)
Christine, 2008
HBV HBsAg HBsAb
HBc Ab
HBeAg HBeAbIgG IgM
Incubating + - - - +/- -
Acute Infection + - +/- + + -Chronic Carrier + - + - - +Chronic Infection + - + - + -
Resolved Infection - + + - - +
Immune - + - - - -
Christine, 2008
HBV HBsAg HBsAb
HBc Ab
HBeAg HBeAbIgG IgM
Incubating + - - - +/- -
Acute Acute InfectionInfection ++ -- +/-+/- ++ ++ --
Chronic Carrier + - + - - +
Chronic Infection + - + - + -
Resolved Infection - + + - - +
Immune - + - - - -
Hepatitis B Vaccination
• Series of 3 vaccines– Baseline– 6 weeks– 6 months
• Recheck to verify immunity
• Double dose
Hepatitis B Vaccination
• Accelerated HBV Vaccine Schedule624
– Standard dose at T0,1 and 3 wks
– Non-inferior efficacy only for those with CD4 >500
• Alternate 4-part high dose HBV Vaccine Schedule623
– Double dose at T0,4,8,and 24 wks
– Better response than standard 3 dose series, especially:- Older age- VL >50- Males- CD4 <350
CROI 2010: Launay O #623; de Vries-Sluijs T #624
Christine 2008
• Do you start cART?
a)Yes
b)No
c)Maybe if she stops cocaine
d)Don’t know
http://www.aidsinfo.nih.gov/Guidelines/GuidelineDetail.aspx?GuidelineID=7
Indications for Treatment
• AIDS defining illness
• Asymptomatic with CD4 <350
• Hepatitis B co-infection– When HBV treatment is indicated
• HIV Associated Nephropathy (HIVAN)
• Pregnancy
ARV Initiation
• CD4 350-500– 55% Panel – Strong Recommendation– 45% Panel - Moderate Recommendation
• CD4 >500– 50% Panel recommend initiating– 50% Is ‘optional’
“Patients initiating ARV therapy should be able and willing to commit to lifelong treatmentand shouold
understand the benefits and risks of therapy and the importance of
adherence”
Christine 2008
• Agree to start, what would you use?
a)ABC/3TC/LPV/rtv
b)FTC/TDF
c)FTC/TDF/EFV
d)FTC/TDF/boosted PI
e)c or d
Christine 2010
• Started of FTC/TDF/EFV
• 70% adherent to medical appointments
• 100% adherent to cART
• CD4= 1126 c/mL; VL <48 c/mL
• HBV Quant <357 c/mL
• Hbe Ag (-), HBeAb (+)
Christine 2010
• Do you continue regimen?
a)Yes
b)Check HBsAg if negative and HBsAb (+) stop, her infection is resolved
c)Even if above is true, don’t stop, she could have a flare
d) Switch to FTC/TDF only
Mark
• 26 yo AAM with HIV diagnosed in 2006
• Nadir CD4=265 c/mL VL 345,987 c/ml
• Started on FTC/TDF/EFV
• Undetectable by month 4
• CD4= 471 c/mL, VL<48
• Comes in complaining of rash
A few months ago noticed the following lesion, but did not seek medical attention
Mark
• Your diagnosis is
a)Disseminated Herpes
b)Acne
c)Secondary Syphilis
d)Lymphogranuloma Venreum
High Prevalence of Asymptomatic STI’s in
HIV-Positive MSM, Visiting HIV Outpatient Clinics i
• 659 MSM (median age 45.4) – HIV outpatient clinic
of 2 academic hospitals
– STI screening during a routine visit
• Patients spontaneously reporting STI symptoms were excluded
• MSM completed questionnaire about sexual behaviour previous 6 months.
Heiligenberg M; Netherlands; Poster 1022; CROI 2010
STDSTD LOCATIONLOCATION TESTTEST
C. tracomatis
Oral swabs, anal self
swabs, urine
PCR
N. gonorrhea
Oral swabs, anal self
swabs, urine
PCR
HBV serum ABs
HCV serum ABs
T. pallidum serum RPR
Syphilis and HIV 1
• Increasing prevalence• HIV does not alter course of Syphilis, but
– Multiple chancres more common in HIV infected vs. non-HIV infected individuals (70 % vs 25%)
– Have earlier neurological involvement– Rapid development of aortitis– May present as encephalitis or arteritis– Condyloma latum is more common– Other unusual and more systemic manifestations
Prevention and Management of STDs in People Living with HIV/AIDS; The Eastern Quadrant STD/HIV/AIDS Prevention Centers, 2002
Mark
• Treated with Benzathine PCN 2.4 Million Units x once
• Recommended treatment for partner (s)• Any CNS or ophthalmic symptom should prompt
CSF evaluation• If unknown duration or > 1 year treatment is
Benzathine G PCN 2.4 Million Units qweek x 3• RPR 3, 6, 9, 12 and 24 months after treatment
Juan
• 53 yo HM diagnosed 2 years ago with AIDS after an episode of CNS toxoplasmosis
• Nadir CD4= 12 c/mL, VL 267,998 c/mL at diagnosis
• Started on FTC/TDF/DRV/rtv qday• Tolerating well, suppressed within 5 months• CD4 now is 214 c/mL• Same regimen + leveteracitam 500 mg bid
Juan
• Initial Body Mass Index (BMI) was 22.2
• A year after treatment is 27.3, two years after treatment is 31
Your diagnosis is:a)Overweightb)Obesity class Ic)Obesity class IId)Morbid Obesitye)Normal
Juan
• Smoker, no CV Family history, BP 137/82
• Lipid panel at one and two years shows:– Total cholesterol 183 207– Triglycerides 267
356– HDL 37 28– LDL 98 113
• You start treatment of TG with omega 3 fatty acid
Juan
Cardiovascular Risk Factors• Hypertension: >140/90 or on treatment• Men >50, Women >60• Total Cholesterol >200• HDL <40 (if >60 deduct 1 point)• Smoking• Family History of premature CAD (men
<45, women <55)
ATP III NCEP Guidelines
Juan
Cardiovascular risk calculation
http://hp2010.nhlbihin.net/atpiii/calculator.asp?usertype=prof
Risk factors of MI in HIV infected patients
Controls N=1151
Cases N=278
OR [95% CI ]
CV risk factors
0 173 5 1
1 or 2 710 166 16.8 (5.9 – 48.4)
3 or more 268 107 49.4 (16.4 – 149,0)
Plasma HIV-1 RNA
<= 50 copies/ml 573 121 1
> 50 copies/ml 578 157 1.6 (1,1 – 2,1)
CD4 / CD8 ratio
>= 1 135 19 1
< 1 1016 259 1.8 (1,0 – 3,0)
Costagliola, IAS 2009
Rates of MIs
• 3,851 HIV infected patients • 1,044,589 non-HIV infected controls
Juan
• Repeat fasting glucose is 102 and 107After the second glucose you:a)Order a 2 hr. oral glucose tolerance testb)Stress diet and exercisec)Change regimend)Check a HbA1ce)a, b and cf) All of the above
Juan
• Two-hour glucose tolerance test showed a fasting glucose of 102 and a 2 hour after glucose challenge of 175
• HbA1c is 6.2
Your diagnosis is:
a)Uncontrolled Diabetes
b)Pre-diabetes
c)Normal
Juan
Your management is:
a)Glyburide 5 mg po bid
b)Change ARV regimen
c)Nutritionist referral for a 1,200 cal diet and 20 minutes aerobic exercise
d)Continue same medications, recommend to diet and exercise
Lessons
• Cardiovascular and metabolic changes are prevalent
• Monitor – Weight/ BMI– BP– Lipids– Glucose
• Diagnose early, treat aggressively
Fred
• 32 yo BM with AIDS, diagnosed in 2003
• ARV history include– AZT/3TC/EFV x 18 months– FTC/TDF/EFV
• Failed after 2 years of last regimen:
• VL= 6,457, CD4=245
Fred
• Genotype shows:
• NRTI: M184V, D67N, R211K
• NNRTI: K103N
http://hivdb.stanford.edu/pages/algs/sierra_mutation.html
Tools
• IAS-USA Mutations Card– Updated
Yearly
– Published in Topics in HIV
Medicine
http://www.iasusa.org/resistance_mutations/
Three Pathways to NRTI Cross-Resistance
• TAMs– 41L, 44D, 67N, 70R, 118I, 210W, 215Y/F, 219Q/E
• Selected by ZDV and d4T in sequential fashion• Associated with cross resistance to all NRTIs
• ABC/ddI/TDF cross-resistance– 65R: ddI, ABC, TDF– 74V: ddI, ABC
• Multi-nucleoside resistance– Q151M complex: all NRTIs– T69 insertion: all NRTIs + TDF
Two Groups of NRTIs
• Group 1: AZT, d4T, TFV– M184V mutation increases susceptibility to
these drugs
• Group 2: 3TC/FTC, ddC, ddI, ABC– M184V mutation decreases susceptibility to
these drugs
Fred
• Continue FTC/TDF
• Discontinue EFV
• Start DDI, LPV/rtv
• Well suppressed x 1 year, then lost to follow up for 15 months
• CD4=107, VL= 234,000
• Genotype shows: No major mutations
Fred
• What happened?
a)He is cured from resistance
b)Lost resistant virus
c)Resistance mutations are archived and will express under drug pressure
d)He will respond to Atripla
HIV Variability
Worldwide Single Worldwide Worldwide
Annual HIV+ Single All HIV
Influenza Person HIV Subtype Subtypes
Viral Genetic Sequence Diversity
Desrosiers Abstract 91, CROI 2008
HIV REVERSE TRANSCRIPTASE HIV REVERSE TRANSCRIPTASE CANNOT PROOF READCANNOT PROOF READ
HIV RNA
T U T
T
A
G
A
A
G
G A G
C C T
C
HIV DNA
CC
Fred
When facing a patient with an HIV-resistant strain the following factors could be involved:
a)Patient non-adherence
b)Pharmaco-kinetic interactions
c)Time related prescription patterns
d)Transmission of resistant strain
e)All of the above
0%
10%
20%
30%
40%
50%
60%
70%
100% 80% - 99% <80%
P<0.01
% of PI Doses Taken
RELATIONSHIP BETWEEN ADHERENCE AND VIRAL LOAD
EFFECTS OF SPONTANEOUS EFFECTS OF SPONTANEOUS MUTATIONS ON VIRAL SWARMSMUTATIONS ON VIRAL SWARMS
EFFECTS OF SPONTANEOUS EFFECTS OF SPONTANEOUS MUTATIONS ON VIRAL SWARMSMUTATIONS ON VIRAL SWARMS
Wild TypeHIV
Dead EndHIV
ResistantHIV
EFFECT OF SELECTIVE PRESSURE OF INSUFFICIENT ART
EFFECT OF SELECTIVE PRESSURE OF INSUFFICIENT ART
Wild TypeHIV
ResistantHIV
Dead EndHIV
WHAT IS RESISTANCE?
• Genotypic– Point mutations in HIV genome associated with failure of anti-
retroviral drugs
• Phenotypic– Ability of HIV to grow in the presence of therapeutic levels of
drug
• Virtual Phenotype– Prediction of phenotype bases on mutations using linear
regression
• Clinical– Clinical deterioration despite the patient taking the medication
Genotypic Testing
Plasma Amplified HIV DNAHIV RNA
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AAAAA
• Sequence HIV protease and reverse transcriptase
Sequence Analysis• Translate into amino
acids• Compare to reference
sequences
• Identify resistance and apply algorithm
Fred
When facing a patient with an HIV-resistant strain the following factors could be involved:
a)Patient non-adherence
b)Pharmaco-kinetic interactions
c)Time related prescription patterns
d)Transmission of resistant strain
e)All of the above
Fred
• Tolerated ARV regimen well, intermittent diarrhea
• Was on fenofibrate for elevated TG
• Self discontinued because of development of lipo-dystrophy
• Got injections for lipo-atrophy of cheeks
AdherenceAccess to care
Access to medicationLife situationDisease stage
Challenges to Successful ART:Considerations When Initiating Therapy
Replication rate (Viral load)
Mutation rate (Resistance)
Latent HIV reservoirs
PotencyPharmacokinetics (dosage schedule)
TolerabilityToxicityConvenienceResistance
Clinician experienceCommunication skills
Virus Drug
Clinician
Patient
Declining Incidence of Initial ART Failure During 1st Year of
Treatment
• 5 observational cohorts from Europe and North America
• Started 3-drug ART between 1996 and 2002 (N = 4143)
• Incidence of virologic failure (VL > 500 c/mL 6-12 months after initiating ART) evaluated by calendar year
• VL failure declined significantly from 1996 to 2002 (P < .001)
• Risk of VL failure was lower with
– Older age– MSM– Lower baseline VL– Absence of AIDS diagnosis at time
of ART initiation
Lampe F, et al. CROI 2005. Abstract 593.
Patients With Virologic Failure by
Year of Starting ART
25
303134
3942
40
0
10
20
30
40
50
1996 1997 1998 1999 2000 2001 2002
Pat
ien
ts (
%)
Fred
At this time you:
a)Order a tropism test
b)Start TMP/SMX
c)Refer to adherence counseling
d)Screen and treat for depression
e)All of the above
Fred
After discussing with patient you choose:
a)FTC/TDF/RGV/DRV/rtv
b)FTC/TDF/ETV/MVC
c)FTC/TDF/MVC/RGV
d)MVC/RGV/ETV
e)RGV/ETV/DRV/RTV
DUET-1 & -2: Predictors of ETR Response
ETR mutations (n = 17) weighted based upon impact on response (weighting factor)– 3.0: Y181I/V– 2.5: L100I, K101P, Y181C,
M230L– 1.5: V106I, V179F, E138A,
G190S– 1.0: V90I, A98G, K101E/H,
V179D/T, G190A
Vingerhoets Resistance Workshop 2008 #24
HIV
-1 R
NA
< 5
0 co
pie
s/m
L
at W
k 2
4 (%
)
Weighted Score Category
0-2.0 2.5-3.5 > 3.50
10
20
30
40
50
60
70
80
100
74%
52%
38%
Etravirine
ScoreScore Response RateResponse Rate
0-2 74%
2.5-3.5 52%
4 or greater 38%