Human immunodeficiency virus treatment

The first lead compounds for non-nucleoside reverse transcriptase (RT) inhibitors (NNRTl) were discovered about 15 years ago (Pauwels et al. 1990 Merluzzi et al. 1990 Goldman et al. 1991 De Clercq 1993 Riibsamen-Waigmann et al. 1997). Since then they have become an important ingredient of the dmg combination schemes that are currently used in the treatment of human immunodeficiency virus type 1 (HlV-1) infections. Starting from the HEPT and TIBO derivatives, numerous classes of compounds have been described as NNRTIs. Four compounds (nevirapine, delavirdine, efavirenz and etravirine) have so far been approved for clinical use and several others are the subject of clinical trials (Balzarini 2004 Stellbrink 2007). 

Mink M, Mosier SM, Janumpalli S, Davison D, Jin L, Melby T, Sista P, Erickson J, Lambert D, Stanfleld-Oakley SA, Salgo M, Cammack N, Matthews T, Greenberg ML (2005) Impact of human immunodeficiency virus type 1 gp41 amino acid substitutions selected during enfuvirtide treatment on gp41 binding and antiviral potency of enfuvirtide in vitro. J Virol 79 12447-12454... 

A variety of other clinically important infections, such as brucellosis, listeriosis, salmonellosis, and various Mycobacterium infections, are of interest as these are often localized in organs rich in MPS cells. Liposome encapsulation has been demonstrated to improve therapeutic indices of several drugs in a number of infectious models. The natural avidity of macrophages for liposomes can also be exploited in the application of the vesicles as carriers of immunomodulators to activate these cells to an microbicidal, antiviral, or tumoricidal state. These studies were recently reviewed by Emmen and Storm (1987), Popescu et al. (1987), and Alving (1988). In addition to the treatment of "old" infectious diseases, the concept of MPS-directed drug delivery is of considerable interest for the therapy AIDS, possibly enabling control of human immunodeficiency virus replication in human macrophages. 

Cornblath DR (1988) Treatment of the neuromuscular complications of human immunodeficiency virus infection. Ann Neurol 23(Suppl) S88-S91... 

Coinfection with human immunodeficiency virus (HIV) and tuberculosis accelerates the progression of both diseases, thus requiring rapid diagnosis and treatment of both diseases. 

There are a few key enzymes for the proliferation of human immunodeficiency virus (HIV). Reverse transcriptase is one of them since HIV is a member of the DNA viruses. Efavirenz (1) is an orally active non-nucleoside reverse transcriptase inhibitor (NNRTI) and was discovered at Merck Research Laboratories [1] for treatment of HIV infections. Efavirenz was originally licensed to DuPont Merck Pharmaceuticals which was later acquired by Bristol-Myers Squibb.11 The typical adult dose is 600 mg once a day and 1 is one of three key ingredients of the once-a-day oral HIV drug, Atripla (Figure 1.1). 

Balzarini J, Karlsson A, Perez-Perez M-J, Camarasa M-J, Tarpley WG, De Clercq E. Treatment of human immunodeficiency virus type 1 (HlV-l)-in-fected cells with combinations of HIV-l-specific inhibitors results in a different resistance pattern than does treatment with single-drug therapy. J Virol 1993 67 5353-5359. 

GENERAL APPROACH TO TREATMENT OF HUMAN IMMUNODEFICIENCY VIRUS INFECTION ... 

Treatment of Human Immunodeficiency Virus Infection Antiretroviral Regimens Recommended in Antiretroviral-Naive Persons-... 

Live vaccines rarely may cause severe or fatal reactions as a result of uncontrolled replication (growth) of the vaccine virus. This may occur in persons with weak immune systems, including persons with leukemia or human immunodeficiency virus (HIV) infection or persons undergoing treatment with certain drugs. This is why it is so important to know a person s health status before giving a live vaccine. 

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