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Evolving Strategies in HIV Diagnosis and Treatment

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Title: Evolving Strategies in HIV Diagnosis and Treatment Author: Maine Medical Center Last modified by: Windows User Created Date: 10/16/2012 12:29:45 PM – PowerPoint PPT presentation

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Title: Evolving Strategies in HIV Diagnosis and Treatment


1
Evolving Strategies in HIV Diagnosis and Treatment
  • Rob Smith
  • September 27,2013

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Current Success Rate for cART
  • Undetectable viral load in 85 of treated
    patients
  • Reasons for treatment failure adherence
    (co-morbidities), access, drug resistance (lt5 of
    pts)
  • Not all treated patients achieve immune
    reconstitution (especially if CD4 nadir lt200)

6
NEJM Mar., 2010
7
HIV Stats in the US
  • 50,000 new cases/yr 18,000 deaths/yr
  • 20-30 do not know HIV status
  • These 20 account for ½ of new cases
  • By 2015, ½ of all HIV cases will be gt50 yo

8
HIV in Maine
  • 1800 HIV positive prevalence 0.1
  • 300-500 do not know their HIV status
  • 50 new cases per year gt50 late stage
  • 60 MSM 10 hetero w known positive partner 16
    hetero w/o known at risk partner 12 IVDU

9
Why Do We Still See AIDS in the US?
  • Late testers 30-40 present with AIDS or
    develop in one year this is true in Maine as
    well as nationally (NEJM 2006354438).
  • Retention in care, adherence to meds
  • (Psychiatric disease, substance use, other
    barriers to ongoing treatmentCID 2007441493)

10
CID Sept. 15, 2010
11
Recent MMC Case
  • 50 yo man seen in MMC ER w difficulty
    breathing.
  • Evaluated w BMP, CXR (interstitial
    infiltrates). Rx albuterol.
  • 3 wks later Admit to MMC - hypoxic.
  • Relevant Hx 25 lb weight loss since Jan cough x
    3-4 months. Single male. Not currently sexually
    active.

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  • Exam thrush oral hairy leucoplakia circular
    dermatophytic rash in axilla.
  • CT bilat ground glass opacities in upper and
    lower lobes
  • BAL Pneumocystis CMV
  • HIV VL 200,000 CD4 45

14
Another Recent MMC Case
  • 55 yo married man with fatigue, weight loss,
    intermittent fever x 6 months. Rx for chronic
    Lyme with 3 months oral doxycycline.
  • Refer to dermatology for Rx psoriasis with
    topical steroids
  • Refer to surgery for rectal fissure
  • Develops right facial droop, arm weakness
    thalamic brain mass on CT scan--?tumor. Admit to
    MMC.
  • HIV positive CD4 40

15
Newer Testing Strategies
  • CDC proposals (2006)
  • Routine testing on adults (13-64)
  • Annual testing in those at risk
  • Pregnancy, contemplated pregnancy
  • Opt out provision implied consent
  • Rapid Diagnostic Tests 6 approved
  • Point of care
  • Home testing
  • Confirm Positives!
  • (NEJM
    2006354438PLOS ONE 2012 7(9) e44417)

16
Maine HIV Testing Law 2007
  • Changes in state law
  • No pre-test counseling required
  • No written informed consent..BUT
  • Does require
  • A patient must be informed orally or in
    writing that an HIV test will be performed unless
    (they) decline
  • Information must include an explanation of
    what an HIV infection involves, and the meaning
    of positive and negative test results
  • If a test is positive, post-test
    counseling must be provided

17
Barriers to Routine HIV Testing
  • Lack of knowledge of CDC recommendations
  • USPHT DID not endorse DOES as of 2013
  • Assumptions re patient risk
  • Low prioritylack of time
  • Uncertainty re informed consent law

18
Traditional Diagnostic Tests-HIV 1
  • ELISA plus Western Blot
  • Sensitivity 99.5 post 3 months disease
  • Specificity 99.99
  • False negatives Window period
    agammaglobulinemia SubType O,N
  • False Positives autoantibodies

19
New HIV Diagnostic Algorithm-2012
  • HIV 1/2 Immunoassay screen (includes antibody
    screen and p24 antigen)
  • If positive, reflex to Multispot (HIV 1 vs 2
    assay) and HIV RNA (viral load)
  • If initial screen is negative, no additional
    testing UNLESS clinical concern of acute HIV
    disease in this event, do HIV RNA
  • Adapted from CLSI consensus guideline (June 2011)

20
HPI
  • 22 y.o. female with no hx illness who experienced
    HA and fever 1 week after returning from vacation
    to resort in Caribbean. Symptoms progressed to
    severe fatigue and fainting.
  • 9/19 went to ER. Febrile with UA showing 3-5 WBC.
    Diagnosed with UTI and given ciprofloxacin.
  • 9/22 back to ER for worsening dizziness, fever,
    HA, fatigue. WBC 4.8 with 29 bands. Monospot
    negative. Given IV hydration and sent home for
    unspecified viral illness.

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HPI continued
  • 9/24 Returned to ER. Fever, fatigue, dizziness,
    new right inguinal LAD, dry cough and mild
    diarrhea. Febrile to 101.4, marked orthostatic
    hypotension. WBC 2.6, platelets 105, CRP 3, CMP
    WNL
  • Admitted to an outside hospital with ? PID versus
    Lyme. ID and Gyn consulted and started on empiric
    Piperacillin/Tazobactam and Doxycycline.
  • Exam unremarkable --- ultrasound with 2 cm
    inguinal node. CT abd/pelvis negative except a
    question of inflammation in the right inguinal
    node. Cardiac echo negative. CXR LLL infiltrate
    versus atelectasis.

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HPI continued
  • Further workup revealed
  • Erhlichia serology negative
  • Lyme ELISA equivocal
  • Rapid strep negative
  • HIV ELISA (antibody) test negative
  • VDRL negative
  • C-diff and cryptosporidium negative
  • Chlamydia swab positive
  • Blood, stool, and urine cultures showed no
    growth.
  • WBC and platelet count improved and sent home
    9/27 to complete a 2 week course of doxycycline
    for presumptive chlamydia/LGV, ? atypical PNA, ?
    Lyme
  • Continued to feel lightheaded so saw her family
    physcian on 10/2. Afebrile WBC 5.6 (21 reactive
    lymphs), HCT 37, plat 354, ALT 69. Doxycycline
    extended 3 weeks. ID consulted.

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DDx Expanded
  • Hx of unprotected sexual intercourse while on
    vacation. No new findings on exam. Doxycycline
    discontinued.
  • HIV viral load gt750,000 copies/mL
  • Repeat HIV testing showed ELISA and Western
    blot
  • Pan-sensitive genotype
  • Pt started on anti-retroviral Rx for Acute
    retroviral syndrome or Primary HIV

24
Acute Retroviral Syndrome- Symptoms
  • Fever (96)
  • Lymphadenopathy (74)
  • Pharyngitis (70)
  • Rash (70)
  • Myalgia/arthralgia (54)
  • Headache
  • Diarrhea
  • Nausea and vomiting
  • Hepatosplenomegaly
  • Weight loss
  • Thrush
  • Neurologic symptoms

25
Baseline Tests HIV Dx
  • HIV viral load, CD4 count
  • HIV genotype
  • CBC, CMP, RPR, Hep B/C serologies, RPR, Toxo IgG
    (if CD4,200)
  • PPD (gt5mm) or IGRA assay
  • Immunizations PCV13 (Prevnar) followed 8 wks
    later by PPSV23 (Pneumovax) Hep A/B if indicated

26
OI Prevention Guidelines (CDC 2009)
  • CD4lt200 (or 14) PCPTM/SZ (daily), dapsone
    (/-pyrimethamine for toxo), atovoquone (),
    aerosol pentamidine
  • CD4lt100 Toxoplasmosisif seropositive tm/sz or
    dapsone plus pyrimethamine/leucovorin
  • CD4lt50 MAIazithromycin weekly or clarithromycin
    daily

27
Who to Rx DHHS Guidelines 2012
  • Rx recommended for all HIV-infected individuals.
    Strength of recommendation varies on the basis of
    preRx CD4 count.
  • CD4 lt350 AI
  • CD4 350 to 500 AII
  • CD4 gt500 BIII
  • Astrong evidenceBmoderate

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Why Rx Everyone with HIV
  • Rx reduces HIV-related events, HIV-unrelated
    events and malignancies
  • (Note that CD4 nadir and viremia copy years
    predict adverse outcomes)
  • Public health benefit with reduced HIV
    transmission (HPTN 052 Nejm 2011)
  • Timing may depend on presence of opportunistic
    infections
  • (Inconclusive evidence for elite controllers,
    long-term non-progressors)

29
Preferred Regimens (DHHS-2012)
  • Efavirenz/tenofovir/emtricitabine
  • Ritonavir-boosted atazanavir and
    tenofovir/emtricitabine (truvada)
  • Ritonavir-boosted darunavir and
    tenofovir/emtricitabine
  • Raltegravir and tenofovir/emtricitabine
  • (http//www.aidsinfo.nih.gov/ContentFiles/Adultand
    AdolescentGL.pdf)

30
Alternative Regimens
  • Rilpivirine/tenofovir/emtricitabine
  • Eltegravir/cobicistat/tdf/ftc
  • Lopinavir/r (Kaletra)/tdf/ftc
  • May substitute abacavir/lamivudine (Epzicom)
    for tenofovir/emtricitabine in patients with
    renal disease, osteoporosis

31
Factors to Consider
  • Underlying drug resistance
  • Potential adverse effects of drugs, drug-drug
    interactions
  • Pregnancy or significant child bearing potential
  • Co-morbid conditions (Hepatitis B/C, psychiatric,
    substance abuse)
  • Post-menopausal women or other risk osteoporosis
  • Convenience

32
Always check for drug resistance first
  • HIV genotype for everyone, as a baseline and if
    there is viral breakthrough (gt500 copies HIV)
  • If treatment is failing, obtain genotype while on
    their regimen to detect resistance mutations
  • HIV phenotype for known or suspected complex drug
    resistance mutation patterns ()

33
Management of HIV (DHHS 2011)
  • Goal is undetectable (lt48 copies/mL) HIV viral
    load (Assays vary on limit of detection from lt75
    to lt20 copies/mL)
  • Monitor the HIV viral load q 3 months once goal
    is achieved
  • CD4 counts can be repeated q 6-12 months if viral
    load controlled

34
Continue to Monitor For
  • New STDs (annual RPR/syphilis screen)
  • New onset Hep C (annual)
  • TB (Risk dependent on community context)
  • Metabolic disordersie fasting glucose, lipids
    creatinine and urinalysis testosterone in
    symptomatic males ?bone density

35
Be Aware of.
  • Increased CAD risk
  • Increased risk for liver disease (fatty liver)
  • Increased risk for renal disease
  • Neuro-cognitive disorders-10x reduction in HIV
    dementia with ARVs, but ?increased risk over time
  • AIDS (lymphoma, cervical) and Non-AIDS
    malignancies (anal, lung, liver)related to CD4

36
NEJM 3521 January 6, 2005
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Post-Exposure Prophylaxis
  • OccupationalCDC algorithm UCSF PEPline
    (888-448-4911 or www.nccc.ucsf.edu/Hotlines/PEPlin
    e.html) risk if needlestick exposure to an HIV
    infected pt0.33 if mucosal, 0.09 risk
  • Needlestick risk factors index patient status
    hollow vs solid needle visible blood deep
    puncture needle into vessel
  • Treat ASAP (within 2 hours if possible)
  • Risk reduction of 80

38
Post-Exposure Prophylaxis Non-Occupational
  • CDC recommends nPEP if
  • Substantial risk of exposure w/in 72 hrs
  • Mucosal or non-intact skin exposed to body
    fluids (not saliva, urine etc unless visibly
    contaminated w blood) from known HIV source
  • Case by case if HIV status unknown
  • Should not be used as a frequent intervention for
    any one patient

39
PEPChoice of Meds
  • New recommendations (2013) truvada plus
    raltegravir (well toleratedJ AIDS 2012)
  • If source pts viral resistance pattern is known,
    choose effective alternatives
  • Do not use abacavir/3TC
  • 28d course of treatment

40
Pre-Exposure Prophylaxis (PrePEP)?
  • Effectiveness demonstrated in MSM trial 44
    overall, 73 if adherent 66 in heterosexual
    females
  • Cost effective (lt100K per QALY)but could result
    in annual expenditures of 4 billion (Ann Intern
    Med 2012 156 541)
  • Concerns How to stratify risk who pays drug
    resistance long term risks of Rx
  • CDC interim guidelines for MSM (2011),
    heterosexuals at high risk (2012) IVDU

41
Real or Functional Cures?
  • Berlin patient stem cell transplant donor was
    CCR5 mutation homozygousoff ARV x 5yrs
  • Activate resting memory cells with latent
    infection and Rx? Use of vorinostat (Nature 2012
    487 482)

42
Resources
  • Primary Care Guidelines (IDSA-2009)
  • CID 2009 49 651-681.
  • Pregnancy http//aidsinfo.nih.gov/guidelines
  • Opportunistic Infections
  • http//aidsinfo.nih.gov/guidelines
  • Occupational Exposure
  • http//www.cdc.gov/mmwr
  • PEPline 1-888-448-4911

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How to Treat HIV
  • Preferred RegimensTreatment Naïve (DHHS
    01/10/2011)
  • Efavirenz plus tenofovir/emtricitabine
  • Atazanavir/r plus same
  • Darunavir/r plus same
  • Raltegravir plus same

46
HIV in Refugee Populations
  • Less likely to start ARV therapy
  • Similar CD4 at time of presentation
  • Higher likelihood co-infection with latent TB,
    Hepatitis B
  • Higher prevalence of a mental health disorder
    (especially PTSD)
  • Acquisition by heterosexual exposure rather than
    IVDU or MSM
  • Beckwith et al 200913186. Internat J Inf
    Dis.

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Science Vol. 332 May 13, 2011
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Science Vol. 333 July 1, 2011
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Prevention of HIV Infection
  • Reduce high risk behaviors education re safer
    sex, clean needles (needle exchange programs)
  • Pre and post-exposure chemo-prophylaxis
  • Test and treatlower the community viral load

52
  • It has also become clear that finding the
    cause of an infectious disease is the alpha but
    not the omega of its eradication.
  • R.C. Gallo MD and Luc Montagnier MD
  • (The Discovery of HIV as the Cause of AIDS,
    NEJM 2003 349 24)

53
Test and Treat?
  • More effective identification of HIV
    positivescan be targeted to higher risk groups
  • Lower community viral load leads to lower high
    transmission
  • Models San Fran--MSM (CID 2011) DC--community
    (modest impact on HIV transmission-CID 2010)

54
Rapid HIV Testing in the ER
  • N849 adults oral test Oraquick
  • Brigham and Womens Hospital ER
  • 39 with positive results 5 positive on
    confirmation26 non-infected (8 declined)
  • 8-30 fold increased odds of HIV with positive
    test, but specificity less than predicted
    (Ann Int Med 2008 149 153-160)
  • Increased false positives as kits near expiration
    date (PLOS ONE 2009)

55
NEJM Mar. 18, 2010
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NEJM April 10, 2008
57
Timing of HIV Rx in Pts with Opportunistic
Infections
  • Medication reactions and interactions
  • (ie 2/3 pts with PCP may develop rash with
    TM/SZ)
  • IRIS reactions
  • In general, start within 2 wks in pts with
    AIDSexceptions include TB in patients with
    CD4gt200 cryptococcal or TB meningitis

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Interpreting HIV Serology
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New Responses to Old Questions
  • How is HIV diagnosed in 2012 (ie there is a new
    algorithm)
  • Who should be treated?
  • What medications should be used and what adverse
    effects might we expect?
  • How is timing of treatment affected by presence
    of opportunistic infections?
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