The treatment of human immunodeficiency virus (HIV) has been revolutionary for the 20th and 21st century HIV patients. In the 1990s, patients who were diagnosed with HIV essentially had a death sentence given to them. Patients with HIV who develop a CD4 count less than 200 are diagnosed with acquired immunodeficiency syndrome (AIDS). Patients with AIDS are at risk for many different opportunistic infections. Patients with HIV and AIDS often do not die from the infection itself, but rather from the opportunistic infections that develop as a result of a low CD4 count. (1) During the 1980s, many patients were dying from this disease that was not well-known. There was not much information about where the disease came from, how it spread from person to person, and there was certainly no approved medications. In March 1987, the first antiretroviral medication was approved. Zidovudine was the first HIV medication on the market, and it changed how patients were treated. This disease no longer became one of supportive care. Although many people still died after the introduction of this therapy, it led to the rise of more clinical trials and more approved therapies. In 1990, zidovudine was approved for use in children who had been introduced to the virus through their mothers or through other means. During this time, many patients with hemophilia received blood contaminated with the HIV virus. In June of 1995, the first protease inhibitor was approved, thus initiating the HAART treatment. HAART is a combination approach using multiple HIV medications to treat the disease.(2)
The Food and Drug Administration approved the use of Cabenuva and Vocabria together for the treatment of HIV. Cabenuva is an extended-release injectable suspension that is administered once monthly. Before a patient is initiated on a treatment of Cabenuva, there is an initial regimen of oral cabotegravir. The patient will take the oral version of Cabenuva in order to ensure tolerability of therapy. After the patient tolerates the oral formulation, they will be switched to the injectable formulation. This new formulation and dosing regimen for the treatment of HIV is revolutionary. HIV is now a controllable disease, as there are so many medications and regimens on the market. The caveat to these treatments, however, is that adherence is essential for suppressing viral load and preventing CD4 depletion. Patients with HIV who are not adherent to their medications are still susceptible to the same effects as patients in the 1980s who had no available treatment. Patients with difficulty adhering to treatment regimens should be evaluated for treatment with Cabenuva and Vocabria. Once monthly intramuscular injections are much more tolerable for patients than taking anywhere from one to three pills daily.(3)
One of the issues to these new treatment regimens is, of course, cost. HIV medications are notorious for being expensive medications. Adherence is a matter of public health, and there are many programs and affiliations that allow patients access to these medications with no copay, even if they do not have any prescription coverage. It will be quite interesting to see how this issue develops over the next few months as this treatment is adopted into practice.
References:
Volberding PA. HIV Treatment and Prevention: An Overview of Recommendations From the IAS-USA Antiretroviral Guidelines Panel. Top Antivir Med. 2017;25(1):17-24.
History of HIV and AIDS overview. Avert. https://www.avert.org/professionals/history-hiv-aids/overview. Published October 10, 2019. Accessed December 16, 2021.
Cabenuva. Package insert. ViiV Healthcare; 2021.
Human immunodeficiency virus (HIV) is the pathogen responsible for HIV infection, which can progress to the disorder known as acquired immune deficiency syndrome (AIDS). The primary modes of HIV transmission include unprotected sexual contact, vertical transmission from mother to fetus during pregnancy, the use of contaminated hypodermic needles, and transfusions with infected blood. HIV continues to be a significant global public health challenge, having caused the deaths of approximately 40.4 million [32.9–51.3 million] people worldwide. Despite efforts to control the spread, new infections persist in all regions, with some countries experiencing a resurgence after periods of decline. By the end of 2022, an estimated 39.0 million [33.1–45.7 million] individuals were living with HIV. Treatment for HIV has advanced significantly, and developing safe and effective pharmacotherapy has been one of the greatest achievements in medicine, allowing people to lead normal to near-normal lives. Effective medications are now available to manage the virus and prevent its transmission, including the use of pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP).
HIV initiates infection by attaching to and entering host T cells through CD4+ molecules and chemokine receptors. Once inside the host cell, the virus releases its RNA and several HIV-encoded enzymes. Viral replication depends on reverse transcriptase, an RNA-dependent DNA polymerase, which converts HIV RNA into proviral DNA. This process is highly error-prone, leading to frequent mutations and the emergence of new HIV genotypes.
The proviral DNA enters the host cell’s nucleus and becomes incorporated into the host DNA with the help of integrase, another enzyme produced by HIV. During cell division, this integrated proviral DNA is duplicated along with the host DNA. The proviral DNA can then be transcribed into HIV RNA and translated into HIV proteins, such as envelope glycoproteins 41 and 120. These proteins are assembled into new HIV virions at the inner membrane of the host cell and then bud from the cell surface, enclosed within a modified human cell membrane. Following budding, protease, another HIV enzyme, cleaves viral proteins, transforming the immature virion into a mature and infectious virion.
Choosing antiretroviral therapy (ART) for HIV involves a comprehensive assessment of several factors to tailor the treatment to the individual patient's needs. Key considerations include the patient’s clinical status, CD4 count (a measure of immune function), and viral load (the amount of virus in the blood). Prior therapy resistance must be evaluated to ensure the selected drugs will be effective. Patient acceptance and readiness are critical, as adherence to the regimen is essential for success. Baseline laboratory tests and an inventory of concomitant medications, including herbs and over-the-counter drugs, help to avoid potential drug interactions. The efficacy and toxicity of highly active antiretroviral therapy (HAART) also influence the choice of regimen. The goals of ART are durable suppression of the viral load, restoration and preservation of immunologic function, reduction in HIV-related morbidity and mortality, and prevention of HIV transmission. A patient-centered approach, considering all these factors, is vital for optimizing treatment outcomes.
Pharmacotherapy options for HIV encompass a diverse range of drug classes designed to inhibit various stages of the viral replication cycle. Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) such as Zidovudine, Lamivudine, Abacavir, Tenofovir, and Emtricitabine, function by incorporating themselves into the viral DNA and terminating its elongation. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) including Delavirdine, Efavirenz, Nevirapine, Etravirine, Rilpivirine, and Doravirine, bind directly to the reverse transcriptase enzyme, causing a conformational change that inhibits its activity. Protease inhibitors (PIs) like Saquinavir, Ritonavir, Lopinavir, Atazanavir, Fosamprenavir, and Darunavir prevent the protease enzyme from cleaving viral polyproteins into functional proteins, thereby blocking viral maturation. Entry inhibitors, such as fusion inhibitors, CCR5 antagonists, post-attachment inhibitors, and attachment inhibitors, obstruct the virus from entering host cells by targeting various stages of the entry process. Lastly, integrase inhibitors hinder the integration of viral DNA into the host genome, effectively stalling viral replication. Together, these pharmacotherapy options form a comprehensive approach to managing HIV infection.
The advancements in pharmacotherapy for HIV have significantly transformed the management and prevention of the virus. The development of various antiretroviral drug classes has enabled effective suppression of viral load, restoration and preservation of immune function, and reduction in HIV-related morbidity and mortality. Preventive strategies such as pre-exposure prophylaxis (PrEP), using medications like Truvada and Descovy, and post-exposure prophylaxis (PEP), which should be administered ideally within 2 hours and not later than 72 hours after exposure, have further enhanced our ability to combat HIV. The progress in HIV pharmacotherapy offers hope for improved health outcomes and a substantial decrease in HIV transmission rates, highlighting the critical role of ongoing research and innovation in the fight against HIV/AIDS.
References:
https://accesspharmacy-mhmedical-com.jerome.stjohns.edu/content.aspx?sectionid=124496669&bookid=1810&Resultclick=2#1127554297. (n.d.-b). https://accesspharmacy-mhmedical-com.jerome.stjohns.edu/content.aspx?sectionid=124496669&bookid=1810&Resultclick=2#1127554297
U.S. Department of Health and Human Services. (n.d.). HIV and AIDS: The basics. National Institutes of Health. https://hivinfo.nih.gov/understanding-hiv/fact-sheets/hiv-and-aids-basics
Human immunodeficiency virus (HIV) infection - human immunodeficiency virus (HIV) infection. Merck Manual Professional Edition. (n.d.). https://www.merckmanuals.com/professional/infectious-diseases/human-immunodeficiency-virus-hiv/human-immunodeficiency-virus-hiv-infection
Kemnic, T. R. (2022, September 20). HIV antiretroviral therapy. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK513308/
Gupta, P. K., & Saxena, A. (2021). HIV/AIDS: Current updates on the disease, treatment and prevention. Proceedings of the National Academy of Sciences, India. Section B. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063169/
World Health Organization. (n.d.-b). HIV. World Health Organization. https://www.who.int/news-room/facts-in-pictures/detail/hiv-aids