human immunodeficiency virus (part ii)

Autoimmune Consequences of Treatment

The rapid rate of replication and mutation of HIV makes it a very robust and challenging disease. This is problematic for treatment as it is difficult to prescribe a single drug regime that effectively combats the virus. Instead, "Highly Active Antiretroviral Therapy" (HAART), a combination of three or more antiretroviral medications is prescribed, in an effort to reduce the replication (and mutation) rate of the virus[20]. Traditionally, this "cocktail", consists of Nucleoside Reverse Transcriptase Inhibitors (NRTIs) or protease inhibitors[21]. Recently, a new type of drug known as a fusion inhibitor has shown promising results by actually preventing the HIV virus from entering the CD4+ lymphocytes, and consequently, preventing the continuation of the virus life cycle[21].

The following figures show the mechanisms by which Enfuvirtide, the first HIV entry inhibition drug, performs its functions.

Since the introduction of HAART in 1996 it has led to a significant drop in the mortality rate due to HIV[22]. With the increased use of HAART, there has been an increase in the number of HIV patients with autoimmune disorders. For example, the frequency of rheumatological diseases such as rheumatoid arthritis increases from 1% - 60% in HIV patients[23]. Research has shown[23] that during the infection of HIV, the frequency of autoimmunity initially drops, a paradoxically beneficial side-effect of HIV, due to the drop in CD4+ cells. Following treatment with HAART CD4+, lymphocytes return to a normal level, but appear to have an altered immune regulation, leading to an increased susceptibility to autoimmune disease.


20) Bangsberg, David R, Perry, Sharon, Charlebois, Edwin D, Clark, Richard A, Robertson, Marjorie, Zolopa, Andrew R, Moss, Andrew. Non-adherence to highly active antiretroviral therapy predicts progression to AIDS. AIDS 2001, 15: 1181-1183.
21) Matthews T, Salgo M, Greenberg M, Chung J, DeMas, Bolognesi D. Enfuvirtide: The first therapy to inhibit the entry of HIV-1 into host CD4 lymphocytes. Nature Reviews Drug Discovery 2004, 3: 215-225.
22) Murphy E, Collier A, Lesli A, Kalish, Assmann S, Para M, Flanigan T, Kumar P, Mintz L, Wallach F, Nemo G. Highly active antiretroviral therapy decreases mortality and morbidity in patients with advanced HIV disease. Annals of Internal Medicine 2001, 135: 17-26.
23) Goddard-Zandman G, Shoenfeld Y. HIV and Autoimmunity. Autoimmunity Reviews 2002, 1: 329-337.