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Managing Adverse Effects of HAART

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Despite the 'revolution' of HAART transforming natural ... 'Retinoid Syndrome' Hyperlipidemia (particularly with RTV) Other renal issues. Hyperbilirubinemia ... – PowerPoint PPT presentation

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Title: Managing Adverse Effects of HAART


1
Managing Adverse Effects of HAART
  • David Rubin, MD
  • Clinical Assistant Professor of Medicine
  • Weill Cornell Medical College
  • Medical Director, AIDS Center
  • New York Hospital Queens

2
Introduction
  • Despite the revolution of HAART transforming
    natural history of HIV infection, issues related
    to side effects confront patients and providers
    in doing it right
  • Focused management of these issues maximizes
    patients ultimate adherence to a given HAART
    regimen

3
Understanding the Scope of the Problem
  • Broad treatment-related AEs
  • Lipodystrophy
  • Metabolic abnormalities
  • Bone disease
  • Drug-specific AEs
  • NRTIs
  • NNRTIs
  • PIs

4
Importance of Adverse Effect Management
  • Increasing complexity of HAART
  • Increasing number of agents
  • Drug-drug interactions
  • Value of close monitoring to help patients
    ultimately tolerate difficult effects of certain
    agents
  • ie, ABC, NVP, EFV
  • Helping patients to tolerate the maximum number
    of agents preserves options for the future for
    that particular patient

5
General Considerations
  • Many questions regarding effects of using
    antiretrovirals in current combinations remain
    unanswered, are there associations with
  • Cardiovascular disease
  • Diabetes mellitus
  • Chronic metabolic and morphologic changes (
    a.k.a. Lipodystrophy)

6
Pro-Active Approachto Initiating HAART
  • Important to discuss potential adverse effects
    with patient
  • Important to support the patient on starting
    meds, ie, inform patient on ways to contact you
    for hand holding
  • Adherence issues clearly are associated with this
    initial patient-provider interaction
  • Must frequently follow laboratory parameters,
    CBC, SMAC (chemistries including LFTs)

7
Nucleoside Analogs (NRTIs)
  • Emerging data on class adverse rxns
  • Lactic acid level (lactic acidemia)
  • Rare lactic acidosis
  • Steatosis
  • Association of lactic acidemia with common NRTI
    side effects (?)
  • Theories of mitochondrial toxicity of agents
    explaining all AEs including lipodystrophy
  • Peripheral neuropathy rapid/progressive Sx
    discontinuation vs mild/intermittent

8
Zidovudine (Retrovir, AZT)
  • Primary side effects short term
  • Initial nausea
  • Initial headache
  • Ongoing nausea
  • Ongoing dysphoria
  • Primary side effects long term
  • Anemia usually noticed by 6 weeks
  • Leukopenia

9
D-Drugs
  • d4T (Zerit, stavudine)
  • Peripheral neuropathy
  • Hepatitis
  • Pancreatitis
  • ddI (Videx, didanosine) new EC vs tablets,
    with better tolerability, issue for adherence
  • Pancreatitis
  • Peripheral neuropathy
  • ddC (Hivid, zalcitabine)
  • Peripheral neuropathy
  • Pancreatitis

10
Abacavir Hypersensitivity
  • Initial discussion with patient
  • the card
  • Warningnot scaring, re reintroduction
  • Description of syndrome
  • Clinical diagnosis only with varied
    presentation
  • Important to alert patient to contact you before
    stopping it, otherwise high likelihood of losing
    it

11
Non-Nucleoside RTI (NNRTI)
  • Nevirapine
  • Rash
  • Management takes frequent monitoring to assess
    whether patient may continue or must stop, rash
    in up to 1/3 of patients
  • Keep in mind concern of Stevens-Johnson with
    desquamation of cutaneous and mucus membranes
    (lt1)
  • Hepatitis
  • May develop relatively quickly after start
  • Pay particular attention to co-infected patients
    with Hepatitis C in women

12
NNRTIs
  • Efavirenz
  • CNS Side Effects
  • Dizziness reason for QHS dosing
  • Vivid dreams
  • Depression
  • Think twice in patients with Hx of serious
    mental illness
  • Rash
  • Generally mild and self-limited
  • Delavirdine
  • Rash similar to NVP

13
Protease Inhibitors (PIs)
  • General
  • GI side effects
  • Size and number of pills
  • But never forget they first revolutionized
    HAART and currently clearly change progression
    rates to AIDS and death in the sickest patients,
    ie, CD4 lt100

14
Indinavir
  • Dosing
  • Crix q8 vs IDV/RTV
  • Hydration!
  • 3 periods of food restriction vs none
  • Nephrolithiasis
  • Retinoid Syndrome
  • Hyperlipidemia (particularly with RTV)
  • Other renal issues
  • Hyperbilirubinemia

15
Nelfinavir
  • Diarrhea!
  • Usual course after initial dosing, presents in
    intermittent pattern
  • Best advice is to take after a substantial meal
  • Usually not accompanied with any other complaint
  • Responds to loperamide well, some use calcium
    carbonate

16
Saquinavir
  • GI complaints nausea, gas, bloating, cramps,
    and diarrhea
  • Symptomatic treatment
  • If occurs, becomes more tolerable over time
  • Amount of food prior to Rx
  • Size of pill issue
  • GERD-type symptoms may occur
  • Responds to Rx for GERD
  • Must be refrigerated

17
Amprenavir
  • Size of pills
  • GERD and mechanical issues
  • GI Complaints
  • nausea, cramps, bloating, gas, and diarrhea
  • Rash (small but important)

18
Ritonavir
  • Full dose is rarely used due to intolerable taste
    issues along with GI Sx
  • Combination with IDV, SQV, and LPV
  • Allows for BID dosing of all above with food
  • Hyperlipidemia hyperglycemia
  • Must be refrigerated
  • Drug-drug interactionsmany!

19
Kaletra
  • First fixed-dose PI containing RTV, ie, LPV
    gets boosted to very high blood levels
  • GI side effects relatively mild, mostly
    bloating and gas
  • Taken with food
  • Must be refrigerated

20
Conclusion
  • Side effect management clearly key element for
    maintaining high rate of adherence, thus frequent
    monitoring, including laboratory, is necessary
  • By maximizing support for patient to tolerate
    each potentially troublesome agent, you maximize
    the patients long-term options
  • Knowledge and wisdom play a large role in
    helping patients reach their goals as to managing
    AEs
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