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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”
— Warning—not 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 (<1%)
— 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 <100
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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 interactions—many!
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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 patient’s long-term options
Knowledge and “wisdom” play a large role in helping patients reach their goals as to managing AEs
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For more HIV-related resources, please visit
www.hivguidelines.org