HIV Drug Guide Introduction

Antiretroviral drugs are classified based on the stage of the HIV life cycle they target. In the end, they all do the same thing -- prevent the virus from replicating -- but they do it in different ways. 2007 brought us two new drug classes: the CCR5 antagonists (a type of entry inhibitor) and the integrase inhibitors, so there are now six classes to choose from (if you count CCR5 antagonists and fusion inhibitors, both types of entry inhibitors, as separate classes). With few exceptions, most antiretroviral regimens include drugs from at least two classes, because attacking the virus with drugs that work in different ways is thought to help prevent resistance. The traditional combinations, especially for initial therapy, have been combinations of nucleoside analog reverse transcriptase inhibitors (NRTIs) plus either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI), but with more classes, we'll begin to see the emergence of new approaches and more options for therapy.

Nucleoside Analog Reverse Transcriptase Inhibitors (NRTIs) or "Nukes"

Nucleoside analogs, or "nukes," work by preventing reverse transcriptase, a viral enzyme, from turning HIV RNA into DNA. The nukes mimic the normal building blocks of DNA, but when they get pulled into the growing DNA chain, they screw up the process and keep the chain from being completed. The nukes were the only drugs we had until 1996, and they've been components of just about every drug regimen since the approval of Retrovir (AZT) in the mid-80's. Most ART combinations today consist of a combination of at least two nucleosides (the "backbone") plus one or more drugs from a different class. The popularity of nukes took a hit when we learned they caused lipoatrophy, which we'd been blaming on protease inhibitors. But it turned out that lipoatrophy (and other related toxicities) were caused primarily by the thymidine analogs (Zerit and Retrovir) but not by Epivir, Emtriva, Ziagen or Viread. As a result, we're not as afraid of nukes as we used to be.

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) or "Non-Nukes"

The NNRTIs, or "non-nukes," are powerful, convenient drugs with little long-term toxicity. Side effects occur early on, usually in the first few weeks, and include nervous system side effects with Sustiva, liver toxicity with Viramune, and rash with both. In contrast to boosted PIs, resistance to NNRTIs can occur easily and quickly if the viral load isn't suppressed. These are great drugs for people who are good at taking meds and want a simple combination, but they're not the best choice for those who start and stop meds frequently.

Protease Inhibitors (PIs)

The PIs are the drugs that changed everything. It was the combination of NRTIs plus PIs that first allowed us to completely suppress HIV viral load. Suddenly, we could do more than just temporarily boost the CD4 count for a year or two. HIV infection quickly went from being a progressive fatal disease to one that was chronic and manageable. Management wasn't easy, though. The early PIs were hard drugs to take: lots of pills, lots of doses, and lots of side effects and long-term toxicity. That's changed, in part because of ritonavir "boosting." Almost all PIs are now taken with a low dose of ritonavir (Norvir), which boosts drug levels and simplifies dosing (see "Norvir"). New PIs and new formulations of old PIs have also expanded options and have made PIs a lot easier to take than they used to be. Still, it's important to be aware of PI toxicity. To varying degrees, the PIs can raise lipids (cholesterol and triglycerides), can cause insulin resistance (which can lead to diabetes), and may cause body shape changes, specifically fat accumulation. PIs can sometimes cause diarrhea or loose stools that typically disappear with fiber supplements like Metamucil, Fibercon, or Citrucel. (Don't be put off by the word "laxative" on the bottle -- fiber helps whether you've got diarrhea or constipation.)

Entry Inhibitors

Entry inhibitors block entry of the virus into the CD4 cell. There are several stages of viral entry. The first is attachment of the virus to the CD4 receptor. There aren't any attachment inhibitors available yet, but this is a potential target for drug development. The next step is binding of the virus to a coreceptor (either CCR5 or CXCR4). In 2007, the first CCR5 antagonist, Selzentry, was approved by the FDA. The final step involves fusion of the envelope of the virus with the membrane of the CD4 cell, a step blocked by Fuzeon, a fusion inhibitor. For more information, see the Selzentry and Fuzeon drug pages.

Integrase Inhibitor

Integrase inhibitors, the newest class of drugs, block the insertion of HIV DNA into human DNA. For more information, see the Isentress drug page.

Patient Assistance and Drug Co-Pay Programs

Most, if not all, HIV pharmaceutical companies provide some level of patient assistance to individuals who are unable to afford their HIV medications; ask your health care provider or contact the manufacturer directly (see manufacturer contact on individual drug page) for details on a specific drug.

Several companies have also recently instituted co-pay assistance programs, which may cover all or part of the drug co-pay for many privately-insured patients, up to a specified amount, and for a pre-determined period of time (for example, up to one year). Certain restrictions and eligibility requirements apply (for example, Medicare, and Medicaid not accepted); eligibility requirements may vary from program to program. Once eligible, most companies will then provide you with a co-pay card which you can bring to your pharmacist or provide to your mail-order pharmacy when filling your prescription.

The following companies currently have HIV drug co-pay assistance programs.

Abbott: Positive Partnership PLUS Card -- In 2009, Abbott is launching a pilot program which will expand to the Positive Partnership PLUS Card. Includes 12 months of co-pay savings to cover Kaletra plus other ARVs, no income or co-pay eligibility criteria. Patients can save up to $50 toward their Kaletra co-pay, plus up to $100 of the cost of other HIV medications (up to $50 for each additional ARV with a limit of $100 total -- must be part of a Kaletra regimen.) Visit www.kaletra.com for more information.

GSK: MySupportCard -- Card is valid for the amount of your actual out-of-pocket cost up to a maximum of $100 for each prescription. All HIV drugs (Combivir, Epivir, Epzicom, Lexiva, Retrovir, Trizivir, and Ziagen) are covered. Go to www.mysupportcard.com for more information and to print out the card.

Gilead: Truvada Co-pay Assistance Program -- Covers Truvada, Emtriva, and Viread. For high co-pays only -- kicks in above $50 and up to $200/month. If health care provider does not have the card, you can call toll-free 1-888-358-0398 and it will be mailed to you. Atripla is currently not part of this program.

Tibotec: Tibotec Therapeutics Patient Savings Program -- Covers Prezista and Intelence. Saves up to 80% of the amount of your actual out-of-pocket cost up to $100 per drug, per month. Visit www.prezista.com or call toll-free 1-866-961-7169.

To view table of contents for The 13th Annual HIV Drug Guide, click here.

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