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C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
C6 HIV 201 Armas
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C6 HIV 201 Armas

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  • Answer is b, a elite controller
  • Second study provides additional information on possible utility of using double dose HBV vaccination in non-responders (also recommended by hepatologist speaker at RWCA clinical update conference 2009) First study – accelerated vaccine schedule proposed as option for thiose who are less likely to finish traditional dosing schedule
  • Answer is a
  • Answer is e
  • Correct answer is c
  • Since the introduction of HAART, an increase in STIs has been observed in MSMs who are aware of their HIV + status. Many of these STI may be asymptomatic. The question is whether regular STI screening should be considered for all HIV-infected MSM.
  • Correct answer is b
  • Correct answer is e
  • Correct answer is b
  • Correct answer is c
  • Correct answer is c
  • Answer is e (all of the above)
  • Answer is e (all of the above)
  • Slide #5: Challenges to Successful ART: Considerations When Initiating Therapy This Venn diagram illustrates the four interrelated components that play a role in determining successful outcomes with antiretroviral therapy and therefore should be addressed when initiating treatment.   Designing a general strategy for interventions specific to each of these components right from the beginning of treatment is a key factor in the overall success of anti-HIV therapy.
  • Correct answer is e
  • Collect the answers but no correct answer
  • A cumulative score of 0 to 2 is associated with a 74% response rate, whereas cumulative scores of 2.5 to 3.5 and 4.0 or greater are associated with response rates of 52% and 38%, respectively. 38 Presence of the K103N mutation at baseline is not associated with a reduced virological response. 39
  • Transcript

    • 1. HIV 201 Laura N Armas-Kolostroubis MD Clinical Director Texas/Oklahoma AIDS Education and Training Center
    • 2. 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
    • 3. Christine 2008
      • You consider this patient to be:
      • A long-term non-progressor
      • A elite controller
      • Not infected with HIV
      • Infected with non-HIV-1 virus
      • None of the above
    • 4. 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 (-)
    • 5. Christine, 2008 HBV HBsAg HBsAb HBc Ab HBeAg HBeAb IgG IgM Incubating + - - - +/- - Acute Infection + - +/- + + - Chronic Carrier + - + - - + Chronic Infection + - + - + - Resolved Infection - + + - - + Immune - + - - - -
    • 6. Christine, 2008 HBV HBsAg HBsAb HBc Ab HBeAg HBeAb IgG IgM Incubating + - - - +/- - Acute Infection + - +/- + + - Chronic Carrier + - + - - + Chronic Infection + - + - + - Resolved Infection - + + - - + Immune - + - - - -
    • 7. Hepatitis B Vaccination
      • Series of 3 vaccines
        • Baseline
        • 6 weeks
        • 6 months
      • Recheck to verify immunity
      • Double dose
    • 8. Hepatitis B Vaccination
      • Accelerated HBV Vaccine Schedule 624
        • Standard dose at T0,1 and 3 wks
        • Non-inferior efficacy only for those with CD4 >500
      • Alternate 4-part high dose HBV Vaccine Schedule 623
        • 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
    • 9. Christine 2008
      • Do you start cART?
      • Yes
      • No
      • Maybe if she stops cocaine
      • Don’t know
    • 10. http://www.aidsinfo.nih.gov/Guidelines/GuidelineDetail.aspx?GuidelineID=7
    • 11. Indications for Treatment
      • AIDS defining illness
      • Asymptomatic with CD4 <350
      • Hepatitis B co-infection
        • When HBV treatment is indicated
      • HIV Associated Nephropathy (HIVAN)
      • Pregnancy
    • 12. ARV Initiation
      • CD4 350-500
        • 55% Panel – Strong Recommendation
        • 45% Panel - Moderate Recommendation
      • CD4 >500
        • 50% Panel recommend initiating
        • 50% Is ‘optional’
    • 13.
      • “ 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”
    • 14. Christine 2008
      • Agree to start, what would you use?
      • ABC/3TC/LPV/rtv
      • FTC/TDF
      • FTC/TDF/EFV
      • FTC/TDF/boosted PI
      • c or d
    • 15. 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 (+)
    • 16. Christine 2010
      • Do you continue regimen?
      • Yes
      • Check HBsAg if negative and HBsAb (+) stop, her infection is resolved
      • Even if above is true, don’t stop, she could have a flare
      • Switch to FTC/TDF only
    • 17. 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
    • 18.  
    • 19. A few months ago noticed the following lesion, but did not seek medical attention
    • 20. Mark
      • Your diagnosis is
      • Disseminated Herpes
      • Acne
      • Secondary Syphilis
      • Lymphogranuloma Venreum
    • 21. 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 STD LOCATION TEST 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
    • 22. 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
    • 23. 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
    • 24. 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
    • 25. 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:
      • Overweight
      • Obesity class I
      • Obesity class II
      • Morbid Obesity
      • Normal
    • 26. 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
    • 27. 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
    • 28. Juan
      • Cardiovascular risk calculation
      • http://hp2010.nhlbihin.net/atpiii/calculator.asp?usertype=prof
    • 29.  
    • 30.  
    • 31.  
    • 32. Risk factors of MI in HIV infected patients Costagliola, IAS 2009 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)
    • 33. Rates of MIs
      • 3,851 HIV infected patients
      • 1,044,589 non-HIV infected controls
    • 34. Juan
      • Repeat fasting glucose is 102 and 107
      • After the second glucose you:
      • Order a 2 hr. oral glucose tolerance test
      • Stress diet and exercise
      • Change regimen
      • Check a HbA1c
      • a, b and c
      • All of the above
    • 35. 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:
      • Uncontrolled Diabetes
      • Pre-diabetes
      • Normal
    • 36. Juan
      • Your management is:
      • Glyburide 5 mg po bid
      • Change ARV regimen
      • Nutritionist referral for a 1,200 cal diet and 20 minutes aerobic exercise
      • Continue same medications, recommend to diet and exercise
    • 37. Lessons
      • Cardiovascular and metabolic changes are prevalent
      • Monitor
        • Weight/ BMI
        • BP
        • Lipids
        • Glucose
      • Diagnose early, treat aggressively
    • 38. 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
    • 39. Fred
      • Genotype shows:
      • NRTI: M184V, D67N, R211K
      • NNRTI: K103N
      • http://hivdb.stanford.edu/pages/algs/sierra_mutation.html
    • 40.  
    • 41.  
    • 42. Tools
      • IAS-USA Mutations Card
        • Updated Yearly
        • Published in Topics in HIV Medicin e
      http://www.iasusa.org/resistance_mutations/
    • 43. Three Pathways to NRTI Cross-Resistance
      • TAMs
        • 41L, 44D, 67N, 70R, 118 I , 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
    • 44. 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
    • 45. 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
    • 46. Fred
      • What happened?
      • He is cured from resistance
      • Lost resistant virus
      • Resistance mutations are archived and will express under drug pressure
      • He will respond to Atripla
    • 47. 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
    • 48. HIV REVERSE TRANSCRIPTASE CANNOT PROOF READ C HIV RNA T U T T A G A A G G A G C C T C HIV DNA
    • 49. Fred
      • When facing a patient with an HIV-resistant strain the following factors could be involved:
      • Patient non-adherence
      • Pharmaco-kinetic interactions
      • Time related prescription patterns
      • Transmission of resistant strain
      • All of the above
    • 50. RELATIONSHIP BETWEEN ADHERENCE AND VIRAL LOAD P <0.01 % of PI Doses Taken
    • 51. EFFECTS OF SPONTANEOUS MUTATIONS ON VIRAL SWARMS Wild Type HIV Dead End HIV Resistant HIV
    • 52. EFFECT OF SELECTIVE PRESSURE OF INSUFFICIENT ART Wild Type HIV Resistant HIV Dead End HIV
    • 53. 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
    • 54. Genotypic Testing Plasma Amplified HIV DNA HIV RNA RT/PCR
      • Sequence HIV protease and reverse transcriptase
      • Sequence Analysis
      • Translate into amino acids
      • Compare to reference sequences
      • Identify resistance and apply algorithm
      AAAAAAAAA AAAAAAAAA AAAAAAAAA AAAAAAAAA AAAAAAAAA AAAAAAAAA AAAAAAAAA AAAAA AAAAA AAAAA
    • 55. Fred
      • When facing a patient with an HIV-resistant strain the following factors could be involved:
      • Patient non-adherence
      • Pharmaco-kinetic interactions
      • Time related prescription patterns
      • Transmission of resistant strain
      • All of the above
    • 56. 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
    • 57. Adherence Access to care Access to medication Life situation Disease stage Challenges to Successful ART: Considerations When Initiating Therapy Replication rate (Viral load) Mutation rate (Resistance) Latent HIV reservoirs Potency Pharmacokinetics (dosage schedule) Tolerability Toxicity Convenience Resistance Clinician experience Communication skills Virus Drug Clinician Patient
    • 58. 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 30 31 34 39 42 40 0 10 20 30 40 50 1996 1997 1998 1999 2000 2001 2002 Patients (%)
    • 59. Fred
      • At this time you:
      • Order a tropism test
      • Start TMP/SMX
      • Refer to adherence counseling
      • Screen and treat for depression
      • All of the above
    • 60.  
    • 61. Fred
      • After discussing with patient you choose:
      • FTC/TDF/RGV/DRV/rtv
      • FTC/TDF/ETV/MVC
      • FTC/TDF/MVC/RGV
      • MVC/RGV/ETV
      • RGV/ETV/DRV/RTV
    • 62. 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 RNA < 50 copies/mL at Wk 24 (%) Weighted Score Category 0-2.0 2.5-3.5 > 3.5 0 10 20 30 40 50 60 70 80 100 74% 52% 38%
    • 63. Etravirine Score Response Rate 0-2 74% 2.5-3.5 52% 4 or greater 38%

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