HIV Medications

Drugs, Sexually Transmitted Diseases, Therapy & Procedures

Do I need to take medication if I’m HIV-positive?

Back in the mid-1980s — before doctors really knew what caused acquired immune deficiency syndrome (AIDS) and had even less of an idea how to treat it — an AIDS diagnosis was considered a death sentence. Today, there are many different medications that work against human immunodeficiency virus (HIV), the virus that causes AIDS. If you’re infected with HIV but don’t yet have AIDS, anti-viral medications can help you keep the disease from progressing. If you already have AIDS, the medications can help you stay alive longer by keeping your immune system as strong as possible.

But not everyone who is infected with HIV needs to start taking medications right away. For one thing, the drugs are expensive and can cause significant side effects, so doctors may not prescribe them unless they think patients can really benefit. Guidelines released by the International AIDS Society in 2008 recommend that doctors consider prescribing medications to all patients with a CD4 count — a measure of certain immune cells — below 350 (This was instead of the previous cutoff level of 200). If you’re still in overall good health, and your CD4 cell count is still above 350 (per microliter), you may not need HIV medication for now. However, your doctor will want to see you regularly, probably at least every three months to check your test results.

On the other hand, there is new evidence that starting treatment even earlier (CD4 counts between 350 and 500) can lead to 70 percent higher long-term survival rates. Early treatment may not be right for everyone, though because once you start taking HIV drugs, you must stick to your treatment strictly — and indefinitely.

What are the different types of HIV drugs?

The drugs used to treat HIV come in several different varieties. Most of them work by making it difficult for the HIV virus to make copies of itself, an approach called anti-retroviral therapy (ART). Different types of drugs will interrupt the copying process in different ways. Many people take a combination of three or more drugs — also called a drug cocktail or highly active antiretroviral therapy (HAART) — to fight the infection on more than one front. Here’s a look at the major types of HIV medications:

Fusion inhibitors: When HIV enters the body, it targets a certain type of immune cell called a T lymphocyte. The virus binds with CD4, a molecule on the surface of CD4-positive T lymphocytes. Once it binds, the virus fuses with the cell membrane and releases its genetic information into the cell. Fusion inhibitors block this process. Examples include Fuzeon (enfuvirtide) and Selzentry (maraviroc). The first fusion inhibitor was approved in 2003. These are relatively new drugs and they must be injected, so they are not a first-line treatment.
Reverse transcriptase inhibitors:HIV is a retrovirus. Its genetic material is RNA (a single stranded form, which is short-lived in our bodies) instead of DNA, a double-stranded (and very stable) form found in our own cells. In order to stay in our cells and use our cell’s machinery to replicate, the virus needs to convert its RNA into DNA. It does this with an enzyme called reverse transcriptase.

There are two types of reverse transcriptase inhibitor drugs:

Nucleoside reverse transcriptase inhibitors (NRTIs). Also called “nucleoside analogs,” these drugs are faulty versions of DNA building blocks. That way, the DNA copy of the virus is defective and isn’t able to replicate or function properly. Examples include Retrovir (zidovudine or azidothymidine, also known as AZT or ZDV), Epivir (lamivudine or 3TC), Viread (tenofovir or TDF), and Videx (didanosine). (AZT was the first HIV drug to be approved, back in 1987.)
Non-nucleoside reverse transcriptase inhibitors (NNRTIs). These drugs bind to reverse transcriptase and keep the enzyme from turning the RNA into DNA. Examples include Viramune (nevirapine), Sustiva (efavirenz), and Intelence (etravirine), approved in 2008. The first NNRTI was approved in 1996.
Integrase inhibitors: An HIV enzyme called integrase takes the DNA version of the virus and integrates it into the DNA of the human cell. That way, the HIV virus (now called a “provirus”) can stay inside the cells for a long time and make many copies of itself. Integrase inhibitors keep viral DNA from integrating with your DNA and disrupt the HIV life cycle. An example is Isentress (raltegravir), approved in 2007.
Protease inhibitors (PIs): Once HIV is part of the cell’s DNA, it can use the cell’s own enzymes to read its DNA and create the proteins that form the envelope or shell for new copies of the virus. These proteins are made in longer strings that must be chopped into smaller pieces. A viral enzyme named protease does this job after the new virus buds off the host cell. Protease inhibitors block this step, so that the copies don’t mature into their final form, and aren’t able to infect other cells. Examples include Crixivan (indinavir), Norvir (ritonavir), and Viracept (nelfinavir). (The first PI was approved in 1995.)
Combination pills: These simply include two or three drugs in fixed amounts, such as Trizivir (contains abacavir or ABC, zidovudine or AZT, and lamivudine or 3TC) and Truvada (contains emtricitabine or FTC and tenofovir or TDF). Combining medicines reduces the number of pills to take and can make it easier to stick to a treatment plan.

What are the possible side effects of HIV medications?

All HIV medications can cause potentially serious side effects, so it’s important that you take your pills exactly as directed every day, and talk to your doctor about any complications you experience. Here are some of the possible downsides to HIV treatments:

Liver damage. NRTIs, NNRTIs, and PIs can all be toxic to the liver. Over time, the liver can become inflamed, and some liver cells can die. The liver may also start accumulating fat, a possible first step toward a dangerous condition called lactic acidosis (see below). Your doctor will run regular blood tests to check for signs of liver damage. Tell your doctor right away if you develop any symptoms of liver trouble including abdominal pain, nausea, vomiting, loss of appetite, diarrhea, fatigue, or jaundice (yellowing of the skin and eyes).
Lactic acidosis. Patients taking NRTIs are at increased risk for lactic acidosis, an extremely rare but potentially deadly complication caused by a buildup of lactic acid (a waste product of cells) in the bloodstream. Symptoms of lactic acid buildup include fatigue, shortness of breath, rapid breathing, liver swelling or tenderness, poor circulation to the hands or feet, irregular heart beat, unexplained weight loss, nausea, vomiting, and abdominal pain.
High blood sugar and diabetes. All PIs can put patients at risk for hyperglycemia (high blood sugar) and diabetes. These complications are especially common in patients who are overweight, older, or have a family history of diabetes. If you’re taking a PI, tell your doctor if you have a sign of hyperglycemia, including excessive hunger and thirst, excessive urination, or unexplained weight loss. If you develop hyperglycemia while taking a PI, your doctor may switch you to a different HIV medication or prescribe insulin or another medication to keep your blood sugar under control.
High cholesterol. A few HIV drugs, including the PI Norvir and the NNRTI Sustiva, can raise blood cholesterol and triglycerides. If your cholesterol or triglycerides get too high, you could be at risk for heart disease. Because of this danger, your doctor will want to check your lipid levels on a regular basis. There are many options for bringing down high cholesterol, including statin drugs such as Lipitor (atorvastatin).
Lipodystrophy. HIV medications can cause lipodystrophy, a fancy word for problems with fat metabolism or distribution. In some cases, fat can disappear from areas of the body including the face, arms, legs, or buttocks. In other cases, fat may start piling up in places such as back of the neck, belly, or breasts (in both men and women). Lipodystrophy seems to be most common in people taking both PIs and NRTIs. This condition isn’t especially dangerous, but it can be unsightly. In some cases, people get cosmetic surgery to correct it. It can also be a warning sign of other problems, including high blood sugar, or high cholesterol.
Weakened bones. Protease inhibitors can rob bones of minerals, potentially making them less dense (a condition called osteopenia). In advanced cases, bones become prone to breaking (a condition called osteoporosis). Some HIV patients also suffer from the death of bone cells (a condition called osteonecrosis), but it’s not clear if this is a drug side effect or a complication of the disease. Your doctor may want you to have regular scans to check bone density, as osteoporosis won’t cause any symptoms until you have a fracture. Fractures can cause pain and tenderness, and frequently occur in the spine, wrists, or hips. Calcium supplements, weight-bearing exercise, and medications can help prevent bone loss.
Skin rash. NNRTIs — and, to a lesser extent, NRTIs and PIs — can cause rashes. The rashes are usually mild, but they can also be severe, especially among patients taking Viramune. Tell your doctor if you develop sores with blisters in the center or if your skin starts peeling leaving behind painful sores.
Anemia. About 30 percent of HIV patients (and up to 80 percent of those with AIDS) develop anemia, or low red blood cell counts, which results in fatigue. Certain HIV drugs such as AZT can also contribute to anemia. Depending on your red blood cell count, your doctor may prescribe vitamins, drugs to boost red blood cell production, or even transfusions in extreme cases.

How should I take my HIV medications?

That depends. Each medicine will have its own timetable and directions. You’ll need to plan your medication schedule carefully. Some drugs should be taken with a meal, but others work better on an empty stomach. Your doctor or a pharmacist can help you come up with a system that works for you.

HIV treatments can be notoriously complicated. You could easily end up taking 15 or more pills each day. On the other hand, with some of the combination therapies, you may be able to start off with one or two pills taken just once or twice a day. If these work well and you’re able to stick to your treatment, you can remain on this very simple regimen for years at a time. The stakes are high, too: Even if you are taking 15 pills each day, missing even just a few pills in a week could give the virus a chance to start multiplying. Just as bacteria can become resistant to antibiotics, HIV can mutate (change) and develop defenses against your medications if you don’t take them exactly as directed.

How do I know if the drugs are working?

As part of your treatment, your doctor will have you get regular blood tests (usually at least every three months) to see if your HIV infection is in check. Some of the key factors are viral load (the amount of virus in the bloodstream), CD4 count (the number of CD4-positive T-lymphocytes, the type that HIV targets), and CBC (complete blood count). If the drugs are no longer working well, your doctor will consider prescribing you other medicines.

References

Hammer SM et al. Antiretroviral treatment of adult HIV infection: 2008 recommendations of the International AIDS Society-USA Panel. Journal of the American Medical Association. August 6, 2008. 300(5): 555-570.

US Department of Health and Human Services. AIDS Info. Approved medications to treat HIV infection. 2008.

FDA: Drugs Used in the Treatment of HIV Infection

US Department of Health and Human Services. AIDS Info. HIV Life Cycle. May 2005.

Gladstone Institute: Moving Basic HIV Discoveries Toward New Antiviral Therapies

US Department of Health and Human Services. AIDS Info. Side effects of anti-HIV medications. 2005.

US Department of Health and Human Services. AIDS Info. HIV and its treatment: what you should know. 2008

American Cancer Society. Types of immunotherapy. 2008.

US Food and Drug Administration. FDA approves new HIV drug after priority review. 2008.

American Academy of Family Physicians. How to take your medications for HIV. 2006.

National Anemia Action Council. Information Handout on AIDS.

Murphy RL. Antiretroviral therapy for advanced nave HIV-infected patients: current status and comparison of two different management strategies. Journal of Acquired Immune Deficiency Syndromes. Vol 46 Suppl 11 September 2007 p.S1-S2.

Merck Manuals Online Medical Library. Human Immunodeficiency Virus (HIV) Infection.

San Francisco General Hospital, published on thebody.com. How the protease inhibitors work; their mechanism of action, with schematic color illustrations. June 1996.