Thirty years ago, getting a diagnosis of HIV was like receiving a death sentence. But medical research has come a long way in the development of effective anti-HIV therapies. The availability of effective combination antiretroviral therapy (ART), the standard treatment strategy for HIV, has changed the game. Although some people still die from the long-term consequences of infection, today it’s more like living with a chronic disease. In fact, there are currently more than 1 million HIV-positive Americans living active, healthy lives. While it can still be a challenge, advances in HIV treatment continue to find new drugs and new ways to approach therapy.
Back in the 1980’s, there was one drug to treat HIV—zidovudine, also known as AZT (Retrovir). Now, more than 25 HIV medications are grouped into 6 different classes based on how they fight HIV. Two of the newer classes of HIV medications include:
Entry Inhibitors (also known as fusion inhibitors): these stop the HIV virus from entering CD4 cells—the immune cells that HIV attacks. They do this by blocking a protein on the cell’s surface that the virus needs to gain entry. Another name for this class is CCR5 antagonists. The first member of this class, maraviroc (Selzentry), was approved in 2007. Entry inhibitors like enfuviritide (Fuzeon) are often prescribed in addition to other antiviral drugs, especially in patients that have already been on different anti-HIV medications or harbor drug-resistant HIV strains.
Integrase Inhibitors: these block the HIV virus from making copies of itself. HIV produces an enzyme called integrase that allows its DNA to merge with the DNA of an infected person’s CD4 cells. When these infected cells reproduce, the virus spreads. Integrase inhibitors block integrase to prevent this from happening. The first member of this class—raltegravir (Isentress)—gained FDA approval in 2007. Other drugs in this class are dolutegravir (Tivicay), approved in 2013, and elvitegravir (Vitekta), approved in 2014.
In order for HIV to infect CD4 cells, it has to convert its RNA into DNA using an enzyme. An unique class of medications called non-nucleoside reverse transcriptase inhibitors (NNRTIs) prevents the enzyme from performing the conversion. NNRTIs have been around since the 1990’s, but there have been recent additions to this class that increase the options for combination therapy. They include:
- Etravirine (Intelence), which was approved in 2008.
- Rilpivirine (Edurant), which was approved in 2011.
- Nevirapine extended release (Viramune XR), which was approved in 2011. It’s a long-acting version of an older drug, nevirapine (Viramune).
- Delaviridine (Rescriptor) has been approved to treat HIV since 1997, however, newer NNRTIs offer better drug efficacy and dosage convenience.
Efavirenz (Sustiva) is prescribed as a once-daily capsule and has been FDA approved since 1998.
Cobicistat (Tybost) and ritonavir (Norvir) are pharmacokinetic enhancers, which boost the performance of other drugs. They don't actually directly affect the HIV virus; instead, they increase the levels of specific protease inhibitors in the blood. This makes the protease inhibitors—drugs that do fight the HIV virus—more effective.
HIV treatment, known as highly active antiretroviral therapy (HAART), usually involves at least three different drugs, and each medication might have its own specific instructions. The various combinations can be difficult to manage, depending on which drugs you take. Fortunately, five new combination products have gained FDA approval in the last 10 years. These simplify therapy by combining two to four medicines in one pill. One study showed that these combination pills reduced the virus and enhanced the immune system of 80% of HIV patients who participated. These representative combination antiviral formulations include:
Abacavir, dolutegravir and lamivudine (Triumeq)
Atazanavir and cobicistat (Evotaz)
Darunavir and cobicistat (Prezcobix)
Elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate (Stribild)
Emtricitabine, rilpivirine, and tenofovor disoproxil fumarate (Complera)
Current guidelines from the U.S. Department of Health and Human Services recommend starting HAART for everyone diagnosed with HIV. In the past, guidelines didn’t stress early therapy as much. It was more acceptable to wait until CD4 counts started declining, viral loads started increasing, or symptoms started appearing. That may still be the way to go in certain cases, and while the decision is ultimately up to patients and their doctors, there’s a good reason for starting early. Growing evidence suggests early treatment—regardless of CD4 count—results in fewer complications and possibly even fewer deaths.
