What is LPV?
HIV infection is no longer a fatal condition that always results in death. HIV infections are caused by the human immunodeficiency virus, and if left untreated progresses into a condition called AIDS (Acquired Immunodeficiency Syndrome). AIDS is characterized by progressive weakening of the immune system that results in its ultimate failure, making the affected individual susceptible to infections and diseases that would not normally affect a person with a healthy immune system. Usually, patients with AIDS die from complications that arise due to their failed immune system. The first clinical case of AIDS was reported in 1981 in the United States. Since then, many years have been spent on research and drug discovery to find drugs that are effective and safe for the treatment of HIV. A major result of this was the discovery of a group of drugs that revolutionized HIV treatment called ‘anti-retroviral drugs’ of which many are currently available on the market.
Today, AIDS is still considered a global pandemic with an estimated 37.9 million people living with AIDS around the world, according to UNAIDS in 2018. In the same year, 77,000 people died of AIDS. According to global estimates, up to 21% of people infected with HIV are not aware of their status. This prevents them from getting treatment for their condition, and in most cases the infection progresses to symptoms of AIDS.
Certain regions of the world have a higher prevalence of AIDS. These include, Sub-Saharan Africa, West and Eastern Africa, some parts of Central Asia, Latin America and the Caribbean. In the United States, AIDS remains a consistent problem too. According to the Centers for Disease Control and Prevention (CDC), approximately 1.1 million people were living with HIV-infection in the U.S. as of 2016, which is the most current year for which data was available. In 2017, there were 16,350 AIDS-related deaths in the U.S. Importantly, the cause of death is usually not directly due to AIDS, but due to another health complication that arises due a failed immune system caused by AIDS.
How does HIV progress to AIDS?
HIV is spread from individual to individual most commonly by sexual transmission and by needles or syringes. Not all body fluids can spread the virus. Only blood, semen, pre-seminal fluids, breast milk, vaginal fluids and rectal fluids can transmit the virus from one person to another. Transmission of these fluids also depends on coming into contact with another mucous membrane or damaged skin through which the virus can enter.
HIV infects the cells of the immune system like macrophages, dendritic cells and helper-T cells. The specific T-cells that HIV mostly attacks are CD4+ T-cells, named after a specific protein on the surface of these cells. When the amount of CD4+ T-cells decreases below a certain amount, immunity is lost and the infection progresses to AIDS. After HIV infection, a person may remain symptom-less for many years and the average survival time without treatment is about 11 years. With treatment, survival time can be much longer, and in many cases the infection will never progress to AIDS as long treatment is continued for the rest of the infected individual’s life. What kinds of medication are available to treat AIDS?
Treating HIV infections with Antiretroviral Therapy (ART)
Anti-retroviral therapy has been a game-changer in the treatment of HIV-infections. According to UNAIDS 2019 data, 62% of all people infected with HIV are on ARTs to treat their condition, and 53% of all HIV-infected people are virally suppressed, meaning that their viral load is under a certain threshold level and will most likely not be transmitted to an uninfected individual. There are many ART medications available for treatment of HIV. Lopinavir is a major medication that is the only co-formulated ART of its subcategory that is approved by the Food and Drug Administration (FDA), and it is used worldwide to treat HIV infections.
How does Lopinavir work?
The HIV virus has a few major steps in its life cycle once it infects humans. Completion of these steps is how the virus produces hundred of new virus particles that can help the virus grow in the body. In the first step, the virus attaches to and enters the human cell. The virus then performs several steps to complete its replication process within human cells. In the last step, the newly produced virions must mature by budding off from the host human cell membrane. This requires the activity of an enzyme called HIV-1 protease. Lopinavir works as an inhibitor of this enzyme to prevent maturation of the budding virions by interfering with the activity of HIV-1 protease. The resulting virions are defective and non-infectious. This decreases the HIV viral load in patients taking lopinavir, and this reduced load ensures that the virus cannot be passed on to non-infected individuals. Inhibiting the production of new mature virus particles within human cells also prevents HIV infection from progressing to AIDS as long as the medication is taken regularly and long-term. What kind of inhibitor is lopinavir? Due to its mechanism of action, lopinavir is classified as a ‘Protease Inhibitor’ within the class of ARTs.
Discovery of Lopinavir
Lopinavir was first discovered and marketed by the pharmaceutical company, Abbott Laboratories (AbbVie) as the brand name Kaletra. It was FDA-approved to treat and prevent HIV infections in 2000. Since the drug inhibits the HIV-1 protease enzyme that is essential for viral replication to occur within human cells, finding a drug that could inhibit the activity of this enzyme first depended on figuring out the structure of the viral HIV-1 protease enzyme. Abbott was among the first groups to examine the structure of HIV-1 protease and design synthetic drugs that could bind to the enzyme based on its structure. The approach proved to be highly successful with the creation of lopinavir. However, a major drawback of the drug was that it had very low bioavailability, meaning that very little of the drug would actually reach circulation and be active once it was orally taken.
Lopinavir combined with Ritonavir
To solve this problem, Abbott combined lopinavir with one of its previous HIV-protease inhibitors, called ritonavir. Clinical reports have indicated that lopinavir is three to four times more active against HIV than ritonavir. Alone, ritonavir can also interfere with the replicative cycle of the HIV virus using a similar mechanism as lopinavir, but is most often used as a ‘booster’ with other ARTs and anti-viral medications. Ritonavir can boost the activity of lopinavir and these other drugs by inhibiting drug metabolizing enzymes in the liver that would normally break down lopinavir quickly. By slowing down the metabolism of lopinavir, ritonavir can boost its activity and counteract its disadvantage of having low bioavailability if taken alone. Lopinavir was one of the first drugs to be only available as a co-formulation with another drug and not available to be prescribed alone. Several fixed combination doses are available for the co-formulation, such as lopinavir/ritonavir (80mg/20mg).
The creators of lopinavir/ritonavir at Abbott Laboratories faced some criticism within the first few years of releasing the drug for not making it more publicly available and affordable to the developing world where the prevalence of HIV infections and AIDS is higher. However, after 2007, Abbott offered the drug at a lowered price through a preferential pricing program to Africa, and later to more ‘lower-income’ nations around the world. Their patent for the brand name fixed dose combination of lopinavir/ritonavir, called Kaletra, expired in 2016. Today, generic versions of lopinavir/ritonavir are available, and the drug still resides on the World Health Organization’s List of Essential Medicines.
Lopinavir/Ritonavir in COVID-19 Clinical Trials
With an alarming increase in the number of cases due to the current COVID-19 pandemic, doctors and scientists around the world are searching for existing drugs that could work against the SARS-CoV-2 virus that causes the illness. Previous research from 2003 found that lopinavir/ritonavir was clinically effective at inhibiting the growth of SARS-CoV-1 virus, making the drug combination an eligible candidate to test for the treatment of COVID-19. However, results from clinical trials have not shown a proven therapeutic effect of lopinavir/ritonavir in patients suffering from the illness. One completed clinical trial of 199 patients that was published on March 18, 2020 in the New England Journal Of Medicine reported that no benefit was observed in patients treated with lopinavir/ritonavir beyond what was observed with standard care. Completion of additional ongoing clinical trials could provide more evidence on whether the drug combination could be effective, but currently lopinavir/ritonavir does not appear to work in treating COVID-19.
How to buy Lopinavir
If you need to purchase lopinavir to treat or prevent HIV, a valid prescription from a licensed physician is required. FDA-approved generic lopinavir/ritonavir has been available since early 2017, but your prescription might be for the brand Kaletra. Many health insurance companies will cover only a generic version of the drug if it is available. If you want to take the brand drug, Kaletra, you will probably find that the cost is higher than the generic version. If your insurance does cover brand drugs, you may have to pay a higher amount as co-pay. Kaletra can cost up to double the amount of generic lopinavir/ritonavir and since the drug has to be taken daily and is likely a long-term drug if taken to treat HIV infections, the cost of the drug can quickly add up. Pharmacy discount cards can help you save on the cost of Kaletra. The free card available from USA Rx can enable savings on both Kaletra and generic lopinavir/ritonavir that may exceed what you save with your insurance. Present the card at your pharmacy the next time you fill your prescription to find out how much you can save.