Metabolic syndrome caused by HIV and its treatment

    Most people have heard of both HIV and AIDS and the implications that they can have on an infected individual's health, but they do not know much else about people living with them. The former is a sexually transmitted virus that is responsible for the latter, which is a disease that causes severe immunodefficiency. People who manifest the disease have a much shorter lifespan than other people because their immune systems cannot respond to pathogens and cancers that a normal person's immune system would easily take care of.  While this disease used to be a death sentence for the vast majority of people infected, there are now many treatments that allow for an individual to live a normal, healthy life. Many people, however, do not realize that these treatments can themselves cause physiological stress on the body, sometimes causing disease. While they are not nearly as harmful as AIDS, it is still important that people know how HIV treatment may affect their health. 

    There are several different kinds of drugs that help prevent the progression of HIV into AIDS which include CD4 mimics, CCR5/CXCR4 inhibitors, fusion inhibitos, reverse transcriptase inhibitors (RTIs), protease inhibitors (PIs), integrase inhibitors (INSTIs), and budding inhibitors. While I will not describe the mechanism of each, it is important to note that all of these drugs are designed to inhibit HIV's replication cycle. While important in stopping HIV, they may cause what is known as metabolic syndrome (MS). According to the WHO, MS is considered to be a presence of hyperglycemia/ insulin resistance, obesity, and dyslipidemia, all detrimental to human health.

    People with HIV (PWH) typically have increased lipogenesis, increased lipolysis, and decreased ability to metabolize free fatty acids in the blood. This leads to a fatty liver and lipotoxicity. This may be one mechanism as to why PWH have decreased adipose tissue around the extremities but an increased amount of visceral adipose tissue. Antiretroviral therapies(ARTs) also increase the prevalence of hypercholesterolemia, glucose metabolism alterations, and hypertriglyceridemia. The prevalence of these metabolic disorders also increased with how long patients were using ART. All these complications can be caused by either HIV infection, ART treatment, or a combination of both, leading to an overall increase in MS among PWH. Now that it is known that ART may cause these diseases, doctos can better monitor how they may affect their patients and properly treat them. 

Sources:

Bacchetti, P., Gripshover, B., Grunfeld, C., Heymsfield, S., McCreath, H., Osmond, D., Saag, M., Scherzer, R., Shlipak, M., Tien, P., & Study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM). (2005). Fat distribution in men with HIV infection. Journal of Acquired Immune Deficiency Syndromes (1999), 40(2), 121–131. [1] https://doi.org/10.1097/01.qai.0000182230.47819.aa

Bourgi, K., Wanjalla, C., & Koethe, J. R. (2018). Inflammation and Metabolic Complications in HIV. Current HIV/AIDS Reports, 15(5), 371–381. https://doi.org/10.1007/s11904-018-0411-2

[1] Price, J., Hoy, J., Ridley, E., Nyulasi, I., Paul, E., & Woolley, I. (2015). Changes in the prevalence of lipodystrophy, metabolic syndrome and cardiovascular disease risk in HIV-infected men. Sexual Health, 12(3), 240–248. https://doi.org/10.1071/SH14084

Savès, M., François, R., Jacqueline, C., Rozenbaum, W., Ragnaud, J.-M., Perronne, C., Basdevant, A., Leport, C., Geneviève, C., & Group, A. C. (APROCO) S. (2002). Factors Related to Lipodystrophy and Metabolic Alterations in Patients with Human Immunodeficiency Virus Infection Receiving Highly Active Antiretroviral Therapy. Clinical Infectious Diseases, 34(10), 1396–1405. https://doi.org/10.1086/339866