Nelfinavir is an antiretroviral medication used to treat human immunodeficiency virus (HIV) infection. It works to decrease the amount of HIV in the blood, which helps slow the progression of the disease. While nelfinavir does not cure HIV, its purpose is to manage the infection and reduce the likelihood of developing HIV-related illnesses.
How Nelfinavir Works and Its Primary Use
Nelfinavir belongs to a class of antiretroviral drugs known as protease inhibitors. These inhibitors target HIV protease, an enzyme within the HIV life cycle. This enzyme is responsible for cleaving large viral polyproteins into smaller, functional proteins necessary for new viral particle assembly.
By binding to the active site of HIV protease, nelfinavir inhibits its activity. This blockage prevents proper processing of viral polyproteins, leading to the production of immature, non-infectious HIV particles. These defective viruses cannot effectively infect new cells, reducing the overall viral load.
Nelfinavir’s primary medical use is treating HIV-1 infection in adults and children aged 2 years and older. It is almost always used in combination with other antiretroviral drugs, such as nucleoside reverse transcriptase inhibitors (NRTIs). This multi-drug approach, known as highly active antiretroviral therapy (HAART), targets different stages of the HIV replication cycle to maximize effectiveness and minimize drug resistance.
When used in combination therapies, nelfinavir can lead to substantial reductions in HIV viral load and increases in CD4+ cell counts. CD4+ cells are immune cells targeted by HIV, and an increase in their number indicates improved immune function. The medication is available in tablet and powder forms for oral administration, usually taken two or three times daily with food to enhance absorption.
Potential Side Effects and Drug Interactions
Nelfinavir, like other medications, can cause side effects, ranging from common and generally mild to more serious and less frequent. The most frequently reported adverse event is diarrhea, which affects up to 20% of patients. Other common gastrointestinal side effects include nausea, gas, stomach pain, and a loss of appetite.
Some individuals may also experience a skin rash or changes in the shape or location of body fat, particularly in areas like the arms, legs, face, neck, breasts, and waist. More serious side effects, though less common, can include low white blood cell counts, which may manifest as fever or mouth sores. Increases in blood sugar levels, even in individuals without a history of diabetes, have been reported, potentially leading to symptoms like increased thirst or urination.
Nelfinavir interacts with a significant number of other medications, and these interactions can be severe. It is metabolized in the liver by the cytochrome P450 enzyme system, specifically CYP3A4 and CYP2C19, which can affect the levels of other drugs. Co-administration with certain medications, such as some antiarrhythmics, rifampin, voriconazole, and certain benzodiazepines, is contraindicated due to the risk of increased toxicity or reduced effectiveness.
Patients should inform their healthcare providers about all medications, supplements, and herbal products they are taking, including St. John’s wort, as these can significantly alter nelfinavir’s effects or lead to adverse reactions. For instance, nelfinavir can decrease the effectiveness of hormonal birth control, necessitating the use of barrier methods to prevent pregnancy. Individuals with conditions like hemophilia or phenylketonuria also require careful consideration due to specific risks associated with nelfinavir.
Nelfinavir’s Evolving Role in HIV Treatment
Nelfinavir was approved for medical use in 1997, representing an important advancement in HIV treatment. It was among the first protease inhibitors available, offering a new mechanism to combat the virus. In its early use, nelfinavir showed strong activity against HIV-1 and was a component in first-line combination therapies.
Over time, newer antiretroviral drugs have been developed, offering improved efficacy, more convenient dosing schedules, and fewer side effects. For example, some newer protease inhibitors like darunavir and atazanavir are now recommended as first-line therapy choices. As a result, nelfinavir’s role has shifted from a primary first-line option to an alternative agent.
Despite the emergence of newer therapies, nelfinavir may still be used in specific clinical situations. It can be an option for patients who are unable to tolerate other protease inhibitors or for those with particular patterns of drug resistance. The development of resistance to nelfinavir often involves a specific mutation (D30N) that does not necessarily confer resistance to other protease inhibitors, preserving those agents for future treatment options.