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Introduction

The use of highly active antiretroviral therapy (HAART) has resulted in dramatic reductions in morbidity and mortality for patients infected with HIV.¹Current guidelines for the use of initial antiretroviral (ARV) therapy reflect the multitude of clinical trial data that have helped to shape the appropriate treatment of HIV infection.² Despite the widespread availability of the guidelines in print and web format, contraindicated regimens may still be used by providers. This article will address regimens and combinations to be avoided in HIV treatment.

HIV medical care providers must constantly update their knowledge of current medication guidelines, based on the findings of patients taking these medications in clinical trials and once they have been released on the market. The New Jersey Department of Health and Senior Services (NJDHSS), through the AIDS Drug Distribution Program (ADDP) conducts periodic reviews of prescription patterns to identify errors and patterns of prescribing suboptimal combinations. In 2002, NJDHSS became aware that some providers were prescribing combinations including: stavudine + zidovudine; invirase + 2 nucleoside analog reverse transcriptase inhibitors (NRTIs); zalcitabine + didanosine; zalcitabine + stavudine; and zalcitabine + lamivudine.³ According to Sindy Paul, MD, MPH, Medical Director for the NJDHSS Division of HIV/AIDS Services (written communication, January 2007), NJDHSS and ADDP responded to this finding by initiating a system of “hard edits” that require the pharmacist to contact the prescribing provider to clarify the regimen, to minimize the risk of a patient receiving a contraindicated combination of antiretroviral agents.

We recommend that clinicians and pharmacists read this article for a summary of recommended and contraindicated regimens, and refer to the most recent DHHS antiretroviral treatment guidelines online at www.aidsinfo.nih.gov. In addition, a free continuing medical education lecture on diagnosis and management of HIV disease funded by NJDHSS, is available through the UMDNJ-Center for Continuing and Outreach Education here.

Preferred Regimens in DHHS Guidelines

The DHHS Guidelines were recently updated in October 2006, expanding the list of preferred antiretroviral therapy regimens.² For providers initiating patients on a nonnucleoside reverse transcriptase inhibitor (NNRTI) based regimen, the preferred NNRTI is efavirenz, in combination with either zidovudine/lamivudine or tenofovir/ emtricitiabine. When initiating therapy with a protease inhibitor (PI) based regimen, the ritonavir boosted protease inhibitors atazanavir/ritonavir, fosamprenavir/ritonavir, or lopinavir/ritonavir, in combination with either zidovudine/lamivudine or tenofovir/ emtricitabine are preferred.

ARV Regimens/Components Not to be Offered at ANY Time

Amprenavir liquid in pregnancy, children <4 years old, patients with renal and/or hepatic dysfunction, patients treated with disulfiram or metronidazole or in combination with ritonavir liquid

Although amprenavir capsules were recently taken off the market, the solution is still available from the manufacturer. Due to the large amount of propylene glycol in the formulation, it should not be used in the following patients: women who are pregnant, children less than four years old, and in those with renal or hepatic dysfunction. The propylene glycol in the liquid formulation may accumulate, leading to glycol toxicity in these patient populations. Patients may also experience an antabuse-like reaction when combining the amprenavir liquid with disulfiram or metronidazole. Large amounts of ethanol in the ritonavir liquid formulation may also accumulate in patients receiving amprenavir and ritonvair liquids concurrently. ²

Atazanavir and Indinavir

The protease inhibitors atazanavir and indinavir are both associated with the development of hyperbilirubinemia. Concurrent use of these medications has the potential to cause additive increases in bilirubin levels, and they should not be used together.

Didanosine and Stavudine

Didanosine and stavudine were commonly used in many of our combination regimens in the mid to late 1990s. However, our understanding of the toxicities of these medications has led to recommendations that concurrent use of didanosine and stavudine in any ARV regimen be avoided. Both stavudine and didanosine have been associated with peripheral neuropathy, pancreatitis and hyperlactatemia.^4,5 Their use together should be avoided because of the risk of overlapping toxicities. In pregnant women, concurrent stavudine and didanosine has been associated with reports of serious,even fatal cases of lactic acidosis and hepatic steatosis.⁶ Providers should avoid this combination in HIV infected pregnant patients.

Efavirenz in 1st trimester of pregnancy or in women of significant child bearing potential

Efavirenz has been shown to be teratogenic in nonhuman primates and is classified as Pregnancy Category D.^7,8 In patients who are pregnant or of significant child bearing potential, including those who are unreliable in using barrier contraception, efavirenz should be avoided. For women who are pregnant, recent updates to the DHHS Guidelines for ARV use in pregnancy recommend either lopinavir/ritonavir, nelfinavir, or nevirapine, in combination with zidovudine/lamivudine.⁹ Though the DHHS guidelines do not include saquinavir in pregnancy, the IAS guidelines do include this agent as an acceptable medication to be used in pregnancy. Current IAS guidelines are posted at http://www.iasusa.org/pub/arv_2006.pdf