Evolution of HIV Treatments

Human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) have claimed 44.1 million lives since it became a recognized pandemic in 1983 (Sharp and Hahn 2011; Swinkels et al. 2026). Comparing this to smallpox, which had an estimated mortality of 500 million over the span of 3000-4000 years, AIDs is killing at a much higher rate (Berche 2022). Due to its initial prevalence in gay populations, HIV received large amounts of stigma within social and medical settings. In today’s world, that has spread to include injecting drug users and commercial sex workers who are predisposed to HIV/AIDs stigma due to present discrimination and stereotypes (Mahajan et al. 2008). HIV is a lentivirus transmitted through blood and genital secretions that infects CD4+ lymphocytes. The cells are then replicated, spreading the virus while triggering the immune system to attack CD4+ cells, ultimately leading to AIDS (Figure 1). The challenge with HIV is that it attacks our immune system, weakening our defence against all pathogens (Melhuish and Lewthwaite 2022).

Figure 1: Dendritic cells infected with the HIV virus infect CD4+ (T cells). The T cells will either undergo programed cell death (apoptosis) as a result of destructive changes to the cell, or undergo clonal activation. Replicated CD4+ cells are able to undergo differentiation into memory cells, preserving the virus long-term (Figure 1 | Cell Death & Differentiation | Cell Death & Differentiation, n.d.).

Due to its complex involvement with the immune system, HIV treatment has needed to evolve alongside our understanding. Initial treatment began as a monotherapy – a single type of treatment with Lenacapavir as a newer promising treatment (“Definition of Monotherapy – NCI Dictionary of Cancer Terms – NCI” 2011; Mehtani et al. 2025).  To improve treatment efficacy, a push was made for combination therapy. This began in the mid-1990s with three active drugs from a minimum of two drug classes. This, however, led to negative side effects and a shift to two antiretroviral drugs instead of three, with promising results (Gibas et al. 2022). Organizing treatment could be hard for patients, specifically those who were unhoused or had difficulty accessing treatment. As such, single-tablet regimens combined the antiretrovirals (either 2 or 3) of different classes into an individual daily pill (Cutrell and Bedimo 2016). The newest form of HIV treatment is known as long-acting options. Patients are given injections from two weeks to two months depending on the drug prescribed. The caveat with this form of treatment is that it must be performed by a healthcare professional rather than at home (“Long-Acting HIV Medicine | NIH,” n.d.). 

All HIV patients experience side effects related to their treatment, but that is still preferable to their other option, death. With the number of people who are affected by HIV, we must continue our research and fight stigma to help save lives.

References

Berche, Patrick. 2022. “Life and Death of Smallpox.” Presse Medicale (Paris, France : 1983) 51 (3): 104117. https://doi.org/10.1016/j.lpm.2022.104117. 

Cutrell, James, and Roger Bedimo. 2016. “Single-Tablet Regimens in the Treatment of HIV-1 Infection.” Federal Practitioner 33 (Suppl 3): 24S-30S. 

“Definition of Monotherapy – NCI Dictionary of Cancer Terms – NCI.” 2011. nciAppModulePage. February 2. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/monotherapy. 

Figure 1 | Cell Death & Differentiation | Cell Death & Differentiation. n.d. Accessed October 22, 2026. https://www.nature.com/articles/4401616/figures/1. 

Gibas, Kevin M., Sean G. Kelly, Jose R. Arribas, et al. 2022. “Two-Drug Regimens for HIV Treatment.” The Lancet. HIV 9 (12): e868–83. https://doi.org/10.1016/S2352-3018(22)00249-1. 

“Long-Acting HIV Medicine | NIH.” n.d. Accessed October 22, 2026. https://hivinfo.nih.gov/understanding-hiv/fact-sheets/long-acting-hiv-medicine. 

Mahajan, Anish P., Jennifer N. Sayles, Vishal A. Patel, et al. 2008. “Stigma in the HIV/AIDS Epidemic: A Review of the Literature and Recommendations for the Way Forward.” AIDS (London, England) 22 (Suppl 2): S67–79. https://doi.org/10.1097/01.aids.0000327438.13291.62. 

Mehtani, Nicky J., Janet Grochowski, Anthonia Chimezie, Alix Strough, Sarah Strieff, and Monica Gandhi. 2025. “HIV Viral Suppression With Unintentional Lenacapavir Monotherapy in Adherence-Challenged Patients: A Case Series.” Open Forum Infectious Diseases 12 (6): ofaf330. https://doi.org/10.1093/ofid/ofaf330. 

Melhuish, Anne, and Penny Lewthwaite. 2022. “Natural History of HIV and AIDS.” Medicine, Sexually Transmitted Infections and HIV & AIDS Part 2 of 2, vol. 50 (5): 298–303. https://doi.org/10.1016/j.mpmed.2022.02.011. 

Sharp, Paul M., and Beatrice H. Hahn. 2011. “Origins of HIV and the AIDS Pandemic.” Cold Spring Harbor Perspectives in Medicine: 1 (1): a006841. https://doi.org/10.1101/cshperspect.a006841. 

Swinkels, Helena M., Andrew D. Nguyen, Taraz Samandari, and Peter G. Gulick. 2026. “HIV and AIDS.” In StatPearls. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK534860/.