When the human immunodeficiency virus (HIV) emerged in the early 1980s, it was considered a death sentence. There were few drugs to treat the virus. Resulting opportunistic infections or other AIDS-related conditions led to death. Since then, many drugs have been developed and approved to treat both HIV and its opportunistic infections.
These antiretroviral medications, also known as antiretroviral therapy or ART,
have greatly extended the lives of many people living with HIV, including children. However, none of the medications cures HIV disease. The drugs are also expensive, costing $3,000 or more per month. They must be taken every day indefinitely and may cause side-effects and toxic effects to the body.
If people frequently miss or skip doses of ART, the virus will become "resistant" to the medications and will no longer be effective.
HIV treatment continues to change rapidly. New therapies, different combinations of drugs and improved methods for monitoring infection make treatment increasingly effective but also complex.
Here are three important facts about ART for HIV:
- It is now recommended that everyone with HIV take ART, regardless of their CD4/T-cell counts and even if they are not having any symptoms or complications related to the virus.
- ART will stop or greatly delay progression to AIDS and prolong life.
- ART has changed over the past several years and will continue to change, so if you have HIV, it is important that you and your health care providers stay up to date about the most effective and least toxic medications.
It is very important that you find an HIV specialist to care for you. Given the speed with which the field changes, many primary care physicians and other providers, such as nurse practitioners and physician assistants, cannot keep up with the latest treatment advances.
Being HIV-positive, you may also face unique psychological and social challenges, such as whom to notify, how to handle your feelings, when to start treatment and where to find financial assistance. These are issues that HIV specialists and their staff and medical practices are most familiar with.
An HIV specialist, whether he or she is a primary care or infectious disease doctor, should know the unique ways in which HIV infection affects a woman's health. For example, HIV-infected women are more likely to experience certain gynecological disorders than HIV-negative women and are much more likely to have abnormal Pap tests. HIV-positive women should have a Pap test twice within the first year after their initial HIV diagnosis. If both Pap tests are normal, they can then usually resume getting annual Pap tests.
The overall goal of HIV treatment is to reduce the amount of virus in the bloodstream to a level so low it cannot be detected. Indeed, having "undetectable" virus is the benchmark for measuring a successful therapy regimen. It is important to know that an "undetectable" virus does not mean that you're cured or that the virus is completely out of your body.
Another benefit from HIV treatment is its potential to prevent the serious opportunistic infections that make AIDS a debilitating condition.
With the advent of a class of drugs called protease inhibitors in the mid-1990s, a new model was introduced for treating HIV infection. Drug therapy with protease inhibitors works to interrupt HIV replication by interfering with an enzyme known as HIV protease. By keeping the virus in check, the drugs can delay the gradual weakening of the immune system.
These powerful drugs used in different combinations have allowed people once disabled by AIDS to return to work and remain free from serious symptoms. This model uses a combination of at least three drugs from two or more classes. It was originally referred to as highly active antiretroviral therapy, or HAART, but is now simply called ART.
Before the development of new HIV drugs, the only treatment was zidovudine, usually known as AZT. Patients typically responded to AZT for several month but became sick again once the virus mutated and could overcome survive the drug's effects. These viral mutations also occur with other drugs used to treat HIV but less often with the new, more potent drugs.
Studies also show that HIV treatments reduce the chance that an infected person will transmit the virus. The combination HIV drugs not only reduce the amount of virus in the blood but in other body fluids as well, including semen and vaginal secretions.
Finally, people who start early treatment with powerful drug combinations can delay symptoms of infection longer than those not receiving treatment. This is why it is recommended that everyone infected with HIV start treatment as soon as possible.
There may be reasons you consider delaying treatment, such as lack of health insurance, difficulty accepting the HIV diagnosis, depression or substance abuse, but these should be worked through with your HIV specialists and their care team with the goal of starting ART soon as possible.
If you have HIV/AIDS, you should be active in your treatment—discuss the risks and benefits of all therapy options with your health care professional so you can make the most informed decision. There are several options for treatment available, so your HIV specialist should help determine which combination of ART may be best for you. Factors to consider will include your age, what other medications you may be taking or if you are considering pregnancy.
Types of Drugs
Today, there are six main classes of antiretroviral drugs approved for HIV therapy. They include the following:
- Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) were the first antiretrovirals developed for treatment of HIV. These drugs interfere with an enzyme that enables the virus to replicate. There are eight NRTIs that have been approved for HIV treatment. These include AZT, lamivudine (Epivir), abacavir (Ziagen), didanosine (Videx) and tenofovir (Viread). Several of these, including tenofovir, lamivudine and emtricitabine, are also active against hepatitis B virus. These medications must always be used with one or two drugs from one of the other classes listed below.
- Non-nucleoside reverse transcriptase inhibitors (NNRTIs) bind to the enzyme reverse transcriptase to prevent the virus from copying itself. They include efavirenz (Sustiva), rilpivirine (Edurant), nevirapine (Viramune) and etravirine (Intelence).
- Protease inhibitors (PIs), work by interfering with an enzyme called HIV protease, they prevent the virus from replicating at a later stage in its life cycle. There have been eight PIs developed, though currently only darunavir (Prezista) and atazanavir (Reyataz) are recommended for use in the United States. These drugs are almost always prescribed with two of the NRTI medications noted above.
- Fusion inhibitors block HIV from entering the CD4 cells of the immune system. There is one drug in this class, called enfuvirtide (Fuzeon). This drug must be given as an injection and is generally no longer recommended for use in the United States due to better and safer therapies.
- CCR5 antagonists (also called entry inhibitors) block the virus from replicating by preventing its membrane from fusing with healthy white blood cells. They appear to suppress the most drug-resistant strains of HIV. There is only one FDA-approved entry inhibitor, called maraviroc (Selzentry). This drug, which is prescribed with other HIV drugs, is used for people who have developed resistance to other HIV drugs or who have an advanced HIV infection.
- Integrase inhibitors, are the newest class of antiviral medications and are highly effective at shutting down the virus. They work by preventing HIV DNA from integrating into human DNA. There are three drugs in this class: raltegravir (Isentress), elvitegravir (Vitekta) and dolutegravir (Tivicay). The integrase inhibitors have become the most commonly recommended drugs for HIV treatment and are included in five of the six regimens recommended in the United States for first-line treatment. They are also prescribed in combination with two NRTIs.
In the past, people infected with HIV patients had to take eight to 15 pills a day for their treatment. Many of the newer drugs are combined into one or two pills that can be taken just once a day, which makes it much easier for people who need ART. There are now six single-tablet-regimens approved by the FDA for use in the United States. These include:
- Odefsey (emtricitabine, rilpivirine and tenofovir alafenamide)
- Genvoya (elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide fumarate)
- Triumeq (dolutegravir, lamivudine, abacavir)
- Stribild (elvitegravir/cobicistat/FTC/tenofovir)
- Complera (rilpivirine/tenofovir/FTC)
- Atripla (efavirenz/tenofovir/FTC)
These multiclass, one-dose medications combine two or more of the six classes of HIV drugs described above.
Medication Side Effects
All HIV medications carry the potential for toxicity or side effects. These are often referred to as adverse drug reactions. For example, protease inhibitors can redistribute fat cells in some patients. This condition, called lipodystrophy, causes paunches or humps to form in the abdomen or back. Some side effects are life threatening, such as the hypersensitivity reaction associated with abacavir.
More common side effects from antiviral drugs are headache, rash, nausea and vomiting. In most cases, these side effects are mild and will go away within one to two weeks. Your HIV specialist or one of their team should always discuss possible medication side effects with you before starting therapy.
If you are taking other medications, including prescription or over-the-counter (such as alternative medicines, supplements, vitamins and minerals), it is important to let your HIV specialist know this. There may be drug interactions or restrictions on what medications can be taken together.
Your HIV specialist will monitor your HIV treatment response with a blood test called a viral load test. This test measures the amount of HIV in your blood—in medical terms, "plasma HIV RNA"—and is quantified as "copies per milliliter." This test will be done one or two times before you start HIV medications and then usually about once a month after ART is started.
Before treatment, the viral load can be in the thousands or even millions. The goal with ART is to get the viral load below 20 copies per milliliter of blood. It may take about four to six months of ART to get the virus load to an undetectable level. Once the viral load is undetectable, the test only has to be done every three to six months.
The CD4+/T-cell count is another test your HIV specialist will monitor during treatment. A normal T-cell count is about 500 and, depending on how long someone has been infected with the virus, it may be much lower, sometimes even under 50. Historically, if T-cell count fell below 200, the person was given a diagnosis of AIDS. Effective ART will usually return the T-cell count to normal, although this can take one to two years of treatment or longer depending on how low the number is when ART is first started. This process is often called immune recovery.