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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