This case series is presented by Darren Kurtzer, AuD, PhD on the topic of whether anti-retroviral drugs used to treat HIV cause hearing loss.

BACKGROUND ON ANTI-RETROVIRAL DRUGS

• For treatment of retroviruses, particularly HIV
• Typically, three to four of these medications are taken at once
• This is termed “Highly Active Antiretroviral Therapy” (HAART)
• One of the main reasons for using numerous medications is to prevent viral resistance by affecting different stages of the retroviral life cycle
• Antiretroviral (ARV) drugs are broadly classified by the phase of the retrovirus life-cycle that the drug inhibits.
• Nucleoside and nucleotide reverse transcriptase inhibitors (NRTI): inhibit reverse transcription by being incorporated into the newly synthesized viral DNA and preventing its further elongation
• Non-nucleoside reverse transcriptase inhibitors (NNRTI): inhibit reverse transcriptase directly by binding to the enzyme and interfering with its function
• Protease inhibitors (PI): target viral assembly by inhibiting the activity of protease, an enzyme used by HIV to cleave proteins for final assembly of new virons
• Integrase inhibitors: inhibit the enzyme integrase, which is responsible for integration of viral DNA into the DNA of the infected cell.
• There are several integrase inhibitors currently under clinical trial, and Raltegravir became the first to receive FDA approval in October 2007
• Early inhibitors (or fusion inhibitors) interfere with binding, fusion and entry of HIV-1 to the host cell by blocking one of several targets. Maraviroc and Enfuvirtide are the two currently available agents in this class
• Maturation inhibitors: inhibit last step in gag processing where viral capsid polyprotein is cleaved, block the conversion to mature capsid protein (p24)