Pharmacological Effects of Antiretroviral Medication in the Management of HIV Infection

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1 Jacqueline Sed Pharmacological Effects of Antiretroviral Medication in the Management of HIV Infection St. Thomas University Dr. Delia Leal April 19, 2024

2 Abstract Antiretroviral treatment (ART) should be started as soon as feasible following an HIV diagnosis. It is important to remove obstacles to care, such as those pertaining to obtaining ART and adherence assistance. Initial therapeutic regimens that involve integrase strand transfer inhibitors continue to be the standard. Long-acting injectable treatment with cabotegravir with rilpivirine administered as seldom as every two months is now an option for patients who have achieved viral suppression with a daily oral regimen. Certain antiviral drugs have been associated with weight gain and metabolic problems; new approaches to address these issues are required. People living with HIV are facing health difficulties associated with aging, making it more crucial than ever to manage comorbidities throughout their lives. Moreover, an integrated, evidence-based strategy is needed to address drug use disorders in HIV-positive individuals. Medications taken orally (tenofovir disoproxil fumarate or tenofovir alafenamide + emtricitabine) and, for the first time, an injectable long-acting drug, cabotegravir, are options for preexposure prophylaxis (Gandhi et al., 2023).

3 Introduction Methods for treating and preventing HIV infection are still being developed, forty years after the first cases were documented. As soon as an HIV diagnosis is made, a person should begin treatment. Antiretroviral therapy (ART) should be initiated as soon as possible if they have an opportunistic infection, in order to treat it. Daily oral medication is one of the initial alternatives for antiretroviral therapy (ART), typically in conjunction with an integrase strand transfer inhibitor (InSTI). Once viral suppression has been attained, patients may be ready to begin a long-acting injectable treatment, such as cabotegravir and rilpivirine [RPV], which can be administered every two months. Both new possibilities and difficulties exist as HIV treatment and prevention improve. HIV-positive individuals are living longer, which raises significant age-related issues that are needed for a comprehensive strategy. For the best results in HIV treatment and prevention, multidisciplinary and holistic care for individuals with drug use disorders is necessary. Clinicians and HIV-positive individuals are facing fast changing issues due to other infectious disease outbreaks, such COVID-19 and the recent monkeypox virus infection. Work has to be quadrupled, with equity serving as the driving principle, in order to successfully address these and other issues and to take advantage of the chance to end the HIV pandemic (Gandhi et al., 2023). Pathophysiology of HIV Infection HIV is an encapsulated virus that has a unique affinity for immune system cells, where it may multiply. The virus causes an acute infection, which in most HIV+ people continue as a relatively asymptomatic condition over time while having cumulatively detrimental

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4 consequences on immunological function. Early in an infection, HIV replication and direct viral cytopathic effects severely compromise gut mucosal immunity, causing the integrity of the gut barrier to be lost and permeability to microbial products and dysbiosis. The presence of translocated bacterial products in the bloodstream, even in patients receiving antiretroviral medication (ART), is intimately associated with the systemic chronic immune activation that propels the development of illness and persistent inflammation. Retention of HIV viral particles in lymphoid tissues triggers both innate and adaptive immune responses against HIV locally. Prolonged activation damages the architecture of the lymphoid tissue by scarring, which prevents these cells from accessing vital homeostatic substances. This process is linked to immune cell depletion and the inability of antiretroviral treatment (ART) to significantly boost populations of CD4(+) T cells. Early on in an infection, the HIV genome is formed as a latent virion in a variety of cell types and tissues. Perhaps the biggest obstacle to viral eradication is the latent virus's continued presence in these reservoirs (Huerta, 2020). Many people may merely get an illness without any symptoms following the encounter. Usually, symptoms appear two to four weeks after exposure, but occasionally, they take up to ten months. An acute retroviral syndrome is characterized by a cluster of symptoms that might manifest suddenly. All of these symptoms are not unique to HIV, but their greater intensity and length is a sign of a bad prognosis. Below is a list of these symptoms in decreasing order of frequency: The symptoms include joint pain, enlarged lymph nodes, sore throat, headache, muscular soreness, skin rash, fatigue, and diarrhea. In addition to an HIV virologic (viral load) test, the most sensitive screening immunoassay (preferably a combined antigen/antibody immunoassay) is carried out when there

5 is a chance of acute or early HIV infection. Viral load testing based on RT-PCR is preferred. In general, HIV infection is indicated by a positive HIV virologic test. It takes between 10 to 15 days after infection for detectable viremia to manifest, and even very sensitive immunoassays do not show a positive result until 5 days later. Hence, if there is a high clinical suspicion of recent HIV exposure, repeat testing is performed one to two weeks after the first negative immunoassay and virologic results, which may have been deceptive (Vaillant & Gulick, 2022). Treatment for HIV Infection Pre-exposure prophylaxis (PrEP) is still not widely used effectively, despite significant advancements in the prevention of HIV-1 transmission. In order to prevent HIV-1 infection, those who do not currently have the virus must take an approved daily oral PrEP medication. Especially for high-risk patients, the availability of long-acting injectable PrEP that does not require daily administration may enhance uptake and adherence. Given intramuscularly as little as six times a year, capetecvir extended-release (ER) injectable suspension is the first long-acting injectable alternative licensed for PrEP. Adults who are at risk of acquiring HIV-1 through sexual activity might benefit more from injectable cabotegravir ER suspension than from daily oral emtricitabine/tenofovir disoproxil fumarate. As well as a preventative measure for potential HIV exposure, post-exposure prophylaxis (PEP) entails taking HIV medicine daily for a month. It is advised to begin within 72 hours after possible exposure and to continue after exposures that carry a greater risk, including having sex with an HIV-positive partner. PEP is available from genitourinary medicine (GUM) clinics, hospitals, accident, and emergency (A&E) departments, and sexual health clinics. Your HIV clinic could provide PEP for a person you've had intercourse with if you already have HIV. Antiretroviral medications interrupt the virus's ability to replicate in the body and enable the

6 immune system to heal itself, which is the treatment for HIV. Because HIV adapts fast and develops resistance, a combination of these medications is utilized. Depending on their requirements, newly diagnosed HIV patients usually take one to four medications daily. A viral load that is undetectable shows that therapy is working; the amount of HIV virus in the blood is analyzed to determine this (Blair, 2022). Conclusion Thus, it is more crucial than ever to provide comprehensive evidence-based primary care guidelines on HIV. For care involvement, it is imperative to provide a stigma-free, patient- centered care environment. Care access barriers need to be reduced at the clinic, social, health system, and individual levels. It is becoming more difficult to provide complete treatment for people with HIV, including managing many comorbidities and the attendant issues of polypharmacy, while also attending to HIV-related health concerns as the population ages and noncommunicable illnesses emerge. Healthcare professionals need to handle concerns that are unique to women and men, children, adolescents, transgender people, and people from varied gender backgrounds. These concerns include treatment throughout preconception and pregnancy. This update to the 2013 primary care recommendations comes from an expert panel of the HIV Medicine Association of the Infectious Diseases Society of America (Thompson et al., 2022). Supporting people living with HIV or at high risk for HIV requires a healthcare team approach, as does ensuring that organizational, community, and policy contexts promote HIV prevention. In the whole of their areas of competence, many of these are the roles that doctors play. Others include the individual or combined responsibilities of community agencies, academics, administrators of healthcare, and public health agencies. A key component of primary HIV prevention is still patient and public education, in which community partners,

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7 public health authorities, and doctors all have a responsibility to play. Every adult and teenager who engages in sexual activity or injects illegal substances should know how to avoid contracting HIV (Huynh et al., 2024).

8 References Blair H. A. (2022). Cabotegravir Extended-Release Injectable Suspension: A Review in HIV-1 Pre-Exposure Prophylaxis. Drugs, 82(14), 1489–1498. https://doi.org/10.1007/s40265-022- 01791-3 Gandhi, R. T., Bedimo, R., Hoy, J. F., Landovitz, R. J., Smith, D. M., Eaton, E. F., Lehmann, C., Springer, S. A., Sax, P. E., Thompson, M. A., Benson, C. A., Buchbinder, S. P., Del Rio, C., Eron, J. J., Jr, Günthard, H. F., Molina, J. M., Jacobsen, D. M., & Saag, M. S. (2023). Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2022 Recommendations of the International Antiviral Society-USA Panel. JAMA, 329(1), 63–84. https://doi.org/10.1001/jama.2022.22246 Huerta L. (2020). Editorial: Anti-infective 2020: HIV-From pathogenesis to treatment. Current opinion in pharmacology, 54, x–xii. https://doi.org/10.1016/j.coph.2020.12.001 Huynh, K., Vaqar, S., & Gulick, P. G. (2024, January 10). HIV Prevention. StatPearls - NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK470281/ Thompson, M. A., Horberg, M. A., Agwu, A. L., Colasanti, J. A., Jain, M. K., Short, W. R., Singh, T., & Aberg, J. A. (2021). Primary Care Guidance for Persons With Human Immunodeficiency Virus: 2020 Update by the HIV Medicine Association of the Infectious Diseases Society of America. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 73(11), e3572–e3605. https://doi.org/10.1093/cid/ciaa1391 Vaillant, A. A. J., & Gulick, P. G. (2022, September 20). HIV and AIDS Syndrome. StatPearls - NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK534860/

Pharmacological Effects of Antiretroviral Medication in the Management of HIV Infection

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