Managing Adverse Effects of HAART

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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

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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

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Understanding the Scope of the Problem

• Broad treatment-related AEs
• Lipodystrophy
• Metabolic abnormalities
• Bone disease
• Drug-specific AEs
• NRTIs
• NNRTIs
• PIs

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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

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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)

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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)

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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Amprenavir

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

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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!

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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

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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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