While there is no cure for HIV/AIDS, science has come a long way from the HIV epidemic of the 1980s to today. Prior to 1996, when new AIDS drugs were introduced, life expectancy after diagnosis was just 18 months. Now, patients with HIV/AIDS routinely live for decades.
How HIV Medications Work
The HIV virus attacks and kills infection-fighting CD4 cells that comprise the human immune system. This loss of CD4 cells makes it very difficult for the body to fight off infection and some types of HIV-related cancer. HIV drugs work by preventing the virus from multiplying in the body to reduce the amount of the virus. This gives the immune system the chance to recover and remain strong enough to fight infection.
There are a variety of drugs now used to control HIV/AIDS, but each type of anti-HIV medication blocks the virus in its own way. This is why these drugs are usually prescribed in a “cocktail” to prevent the creation of HIV strains that are immune to a single drug. There are currently six classes of HIV drugs based on how they fight the virus. Most people begin HIV treatment with a regimen that includes three drugs from at least two classes.
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) were first approved in 1996. NNRTIs work by disabling a protein the HIV virus needs to copy itself. There are two generations of NNRTIs including nevirapine (Viramune), etravirine (Intelence), and efavirenz (Sustiva).
Nucleoside reverse transcriptase inhibitors were the first drugs available to treat HIV. While these drugs are less effective than NNRTIs and other drugs, they play a very important role in treatment and are still part of the standard care. NRTIs are actually faulty versions of the building blocks the HIV virus needs to copy itself. NRTIs on the market include Abacavir (Ziagen), lamivudine (Epivir), and stavudine (Zerit). This drug is also part of combination drugs lamivudine-zidovudine (Combivir) and emtricitabine-tenofovir (Truvada).
Additionally, Biktarvy is a newly released combination medicine that is taken as a once-daily tablet to treat HIV. It is a combination of an integrase inhibitor called bictegravir and two nucleoside reverse transcriptase inhibitors, emtricitabine and tenofovir alafenamide. The latter two had already been combined in the past into a separate drug called Descovy. It’s meant to be used without any other anti-HIV-1 medicines.
Protease inhibitors (PIs) were first introduced in 1995 and they play an important role in the treatment of HIV. HIV protease is an amino acid protein that works in the maturation of HIV particles later in the viral life cycle. Protease inhibitors work by disabling protease, which is a protein the HIV virus needs to copy itself. There are 8 PI compounds approved for use, include indinavir (Crixivan), fosamprenavir (Lexiva), darunavir (Prezista), and atazanavir (Reyataz).
Evotaz is a once-daily tablet that contains atazanavir, a protease inhibitor, as well as cobicistat, a CYP3A inhibitor. It’s meant to be taken with other antiretroviral medicines. When it’s taken correctly, Evotaz may help to decrease the viral load in the blood, as well as increase the amount of T cells, to better fight off infection.
Integrase inhibitors were first approved by the FDA in 2007, although a once-daily dosage form of Isentress was approved in 2017. An integrase inhibitor works by blocking integrase, the protein HIV needs to insert its RNA genetic information into CD4 cells. Integrase inhibitors include dolutegravir (Tivicay), raltegravir (Isentress), and elvitegravir (Vitekta). Isentress is meant to be taken with other antiretroviral medicines. There are three tablet options to choose from (oral suspension, film-coated, and chewable). Tell your doctor if you’ve ever had a muscle disorder (rhabdomyolysis or myopathy) before taking Isentress.
Tivicay should also be taken with other antiretroviral medications. In adults, Tivicay may be paired with rilpivirine to replace the HIV-1 medication that they are currently taking.
Fusion inhibitors were the first type of antiretrovial drug to target HIV’s replication outside the cell and they were approved by the FDA in 2003. A fusion inhibitor works by blocking the virus’s entry into CD4 cells in the body. Fusion inhibitors on the market include maraviroc (Selzentry) and enfuvirtide (Fuzeon). Fusion inhibitors work in a unique way that offers a therapeutic solution for patients who are very treatment resistant.
Fusion inhibitors are not widely used in HIV treatment for several reasons, including the cost and time associated with production, limited coverage by HIV drug assistance programs and insurance companies, adverse side effects, and inconvenient subcutaneous injection administration.
Chemokine Receptor Anagonists
The first chemokine receptor antagonist was approved by the FDA in 2007. Also known as CCR5 antagonists, these drugs work similarly to fusion inhibitors to deny IV entry. The process by which HIV binds with CD4 cells is complex, but it starts with binding of a specific HIV surface protein to a CD4 receptor, which causes structural changes in the protein’s V3 loop. This V3 loop then binds with a chemokine receptor to allow the protein to insert itself into the CD4 cell. Maravicoc (Selzentry) is a CCR5 antagonist that works by binding the CCR5 coreceptor to block interaction with the V3 loop and prevent fusion.
Common side effects of CCR5 antagonists include rash, abdominal pain, dizziness, cough, upper respiratory infections, musculoskeletal symptoms, and fever.
Side Effects of HIV Cocktails
New HIV medications have dramatically extended lifespan for patients, but these medications do have unanticipated side effects. Researchers have discovered that patients who live longer with the HIV/AIDS virus begin to suffer from maladies that normally affect people in their 70s and 80s. This includes cognitive problems, various forms of cancer, kidney disease, cardiovascular disease, and osteoporosis.
Researchers are still unsure if these symptoms are caused by the disease or the drugs used to treat HIV. Some symptoms are largely attributed to the medication, though, including bone loss and neuropathy.