An Overview of Medications for HIV and AIDS

As few as 10 years ago, AIDS was considered an automatic death sentence. From the time a person developed full-blown AIDS to the time of death was generally a couple of years or less. Thanks to new HIV medications, the face of HIV/AIDS is changing dramatically. For a new generation, it has become a chronic condition rather than a terminal one. It can be difficult to live well with a chronic illness, but it is far from impossible.

HIV is the human immunodeficiency virus. It is the virus that can lead to acquired immune deficiency syndrome, or AIDS. CDC estimates that about 56,000 people in the United States contracted HIV in 2006.

There are two types of HIV, HIV-1 and HIV-2. In the United States, unless otherwise noted, the term "HIV" primarily refers to HIV-1.

Both types of HIV damage a person's body by destroying specific blood cells, called CD4+ T cells, which are crucial to helping the body fight diseases.

Within a few weeks of being infected with HIV, some people develop flu-like symptoms that last for a week or two, but others have no symptoms at all. People living with HIV may appear and feel healthy for several years. However, even if they feel healthy, HIV is still affecting their bodies. All people with HIV should be seen on a regular basis by a health care provider experienced with treating HIV infection. Many people with HIV, including those who feel healthy, can benefit greatly from current medications used to treat HIV infection. These medications can limit or slow down the destruction of the immune system, improve the health of people living with HIV, and may reduce their ability to transmit HIV. Untreated early HIV infection is also associated with many diseases including cardiovascular disease, kidney disease, liver disease, and cancer. Support services are also available to many people with HIV. These services can help people cope with their diagnosis, reduce risk behavior, and find needed services.

AIDS is the late stage of HIV infection, when a person's immune system is severely damaged and has difficulty fighting diseases and certain cancers. Before the development of certain medications, people with HIV could progress to AIDS in just a few years. Currently, people can live much longer - even decades - with HIV before they develop AIDS. This is because of "highly active" combinations of medications that were introduced in the mid 1990s.

We've come a long way since the early years of the HIV/AIDS epidemic. There are now over 20 individual HIV drugs, known as antiretrovirals (ARVs), on the market to treat this disease, along with 5 combination drugs (pills that combine two or three ARVs), and more are on the way. What's more, we've learned a lot about when and how to use available medications much more easily and effectively-and with fewer side effects. Most researchers and doctors believe that HIV can be effectively treated for decades, permitting a normal lifespan for many.

Antiretroviral drugs used in the treatment of HIV infection

Multi-class Combination Products

Brand Name	Generic Name	Manufacturer Name
Atripla	efavirenz, emtricitabine and tenofovir disoproxil fumarate	Bristol-Myers Squibb and Gilead Sciences

Nucleoside Reverse Transcriptase Inhibitors (NRTI)

Brand Name	Generic Name	Manufacturer Name
Epivir	lamivudine, 3TC	GlaxoSmithKline
Retrovir	zidovudine, azidothymidine, AZT, ZDV	GlaxoSmithKline
Ziagen	abacavir sulfate, ABC	GlaxoSmithKline
Emtriva	emtricitabine, FTC	Gilead Sciences
Videx	didanosine, dideoxyinosine, ddI	Bristol Myers-Squibb
Viread	tenofovir disoproxil fumarate, TDF	Gilead Sciences
Combivir	lamivudine and zidovudine	GlaxoSmithKline
Trizivir	abacavir, zidovudine, and lamivudine	GlaxoSmithKline
Zerit	stavudine, d4T	Bristol Myers-Squibb
Hivid	zalcitabine, ddC	Hoffmann-La Roche

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI)

Brand Name	Generic Name	Manufacturer Name
Intelence	etravirine	Tibotec Therapeutics
Rescriptor	delavirdine, DLV	Pfizer
Sustiva	efavirenz, EFV	Bristol Myers-Squibb
Viramune	nevirapine, NVP	Boehringer Ingelheim

Protease Inhibitors (PI)

Brand Name	Generic Name	Manufacturer Name
Aptivus	tipranavir, TPV	Boehringer Ingelheim
Crixivan	indinavir, IDV	Merck
Norvir	ritonavir, RTV	Abbott Laboratories
Lexiva	Fosamprenavir Calcium, FOS-APV	GlaxoSmithKline
Invirase	saquinavir mesylate, SQV	Hoffmann-La Roche
Viracept	nelfinavir mesylate, NFV	Agouron Pharmaceuticals
Kaletra	lopinavir and ritonavir, LPV/RTV	Abbott Laboratories
Agenerase	amprenavir, APV	GlaxoSmithKline
Prezista	darunavir	Tibotec, Inc.
Reyataz	atazanavir sulfate, ATV	Bristol-Myers Squibb

Fusion Inhibitors

Brand Name	Generic Name	Manufacturer Name
Fuzeon	enfuvirtide, T-20	Hoffmann-La Roche & Trimeris

Entry Inhibitors

Brand Name	Generic Name	Manufacturer Name
Selzentry	maraviroc	Pfizer

Integrase Inhibitors

Brand Name	Generic Name	Manufacturer Name
Isentress	raltegravir	Merck & Co., Inc.

The Importance of Adhering to Your Treatment Regimen

HIV treatment is a partnership. Just as you rely on your antiretrovirals (ARVs) to be proven safe and effective, your medications don't work alone-you need to take them correctly if they are to keep you healthy. This is called "treatment adherence."

Generally speaking, adherence means taking the correct dose of your medications every time you're supposed to take them, exactly as prescribed by your health care provider or recommended by your pharmacist (for example, on an empty stomach, before bedtime, etc.).

While adherence may sound easy, sometimes it's not. Studies show that even doctors have enormous difficulty taking even short-term drug regimens strictly according to the rules.

Adherence is especially important when it comes to treating HIV infection. From the moment HIV enters the body, the virus is constantly active, finding CD4 cells to infect so that it can reproduce. The goal of HIV treatment is to keep a tight lid on this process, ultimately pushing (and keeping) viral loads undetectable and CD4 cell counts high.

To successfully halt HIV replication and keep viral load suppressed, levels of HIV medications in the blood need to be maintained at high enough levels, 24 hours a day, every day. If the levels become too low, HIV can begin replicating. And if this happens while there are low levels of HIV medication in the bloodstream, the virus can change its structure (mutate) and become resistant to one, or more, of the drugs you're taking. This is called "drug resistance" and it can cause your meds to stop working properly and may limit future treatment options. Drug-resistant HIV can also be transmitted to other people, making it harder for them to treat their own infection.

Learning everything you can about managing HIV and your medications will not only make adherence easier, it will help ensure treatment success on a number of levels.

Understanding Drug Resistance

In simple terms, drug resistance refers to the ability of disease-causing germs-such as bacteria and viruses-to continue multiplying despite the presence of drugs that usually kill them.

With HIV, drug resistance is caused by changes (mutations) in the virus's genetic structure. These mutations can lead to changes in certain proteins, most commonly enzymes, that help HIV reproduce (replicate).

Mutations are very common in HIV. This is because HIV replicates at an extremely rapid rate and does not contain the proteins needed to correct the mistakes it makes during copying.

Mutations occur randomly, on a daily basis, but many are harmless. In fact, most mutations actually put HIV at a disadvantage-they reduce the virus's "fitness" and slow its ability to infect CD4 cells in the body. However, a number of mutations can actually give HIV a survival advantage when HIV medications are used, because these mutations can block drugs from working against the HIV enzymes they are designed to target. These are the mutations we are concerned about when we talk about drug resistance.

HIV relies on many enzymes to replicate inside a human cell. It also relies on proteins, including gp41, to latch on to CD4 cells and infect them. Mutations can occur in any of these parts of the virus and cause drug resistance:

• Reverse transcriptase: nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) target this enzyme.

• Integrase: Integrase inhibitors target this enzyme.

• Protease: Protease inhibitors target this enzyme.

• gp41: Fusion inhibitors target this protein on HIV's outer wall.

For people infected with HIV, drug resistance can render drugs less effective or even completely ineffective, thus significantly reducing treatment options.

HIV drug-resistance mutations can occur both before and during HIV treatment. Here's a look at how this happens:

• Transmission of drug-resistant HIV. Many HIV-positive people now take HIV drugs. If someone has developed resistance to one or more of these HIV drugs and has unprotected sex or shares needles with someone who is not infected with the virus, it is possible that they can infect their partner with a drug-resistant variant-a strain of HIV containing mutations that can cause resistance.
  
  In the United States and other countries where HIV treatment is widely used, between 5 percent and 20 percent of new HIV cases involve strains of the virus that are resistant to at least one HIV medication.

• During treatment. Even if someone is infected with HIV that doesn't contain drug-resistance mutations ("wild-type" virus), genetic changes still occur over time, even before treatment is started. This ends up creating a large mixture of virus in the body. Some of these variants contain the necessary mutations that can partially, or fully, resist an antiretroviral drug-which explains why one-drug treatment (monotherapy) should never be used to treat HIV.
  
  Soon after combination HIV drug treatment is started, the amount of wild-type virus is dramatically reduced. However, if the amount of virus isn't pushed down and kept at very low levels, HIV variants can continue replicating, acquiring additional mutations. And once the virus has accumulated enough mutations, a high level of resistance to the drugs being used can occur, causing viral load to increase and CD4 cells to drop.

A major concern with these mutations is that they can result in cross-resistance. This means that HIV resistance to one drug can automatically become resistant to other drugs in the same class. For example, if you're on a drug regimen that contains the NNRTI Sustiva and your virus becomes resistant to it, chances are that your virus is also resistant to the NNRTIs Viramune and Rescriptor, even though you haven't taken these drugs.

There are a number of steps that HIV-positive people can take to prevent-or at least slow down-the development of resistance:

• Learn all you can about HIV treatment and the available options. The more you know, the easier it will be to make treatment choices that help you avoid drug resistance. Reading the information on this web site about HIV medicine is a good first step.

• Start treatment with a powerful HIV regimen. Your first shot at HIV treatment is probably your best chance at fully suppressing the virus and preventing the development of drug resistance.

• When switching treatments, pick the most potent new regimen. Whenever possible, it is best to switch to a regimen that has three drugs that resistance tests predict will work. If necessary, two active drugs are better than one.

• Be sure to follow instructions. It is very important that HIV-positive people take their HIV medications exactly as prescribed. Missing doses and not taking the right number of pills can cause viral load to increase and cause drug-resistance mutations to develop (see our lesson on adherence).

• Communicate with your doctor. Knowing how to take your medicine properly and reporting any problems to your doctor are important for avoiding drug resistance.

• Monitor the effects of your treatment. This means keeping an eye on your viral load and other lab tests after you begin treatment and for as long as you remain on therapy. Every three months is a standard recommendation. Often an increasing viral load-or a viral load that fails to go undetectable-is the first sign that drug resistance is developing. Monitoring viral load is a good way to guard against drug resistance.