Antiretroviral therapy

Kaposi sarcoma (KS) - an angiogenic-inflammatory neoplasm - is the most prevalent cancer in HIV-infected patients and its appearance is preceded by infection with human Heipesvitus-8 (HHV-8). Although chemotherapy has become the treatment of choice approved by the FDA, there are also good response rates in patients treated with IFN-a. Fortunately, today highly active antiretroviral therapy (HAART) has dramatically decreased the incidence of KS in AIDS patients. 

So far, five different protease inhibitors have been approved by the FDA for the treatment of HIV infection [3, 4]. Clinical trials in which protease inhibitors were evaluated in monotherapy demonstrated the potency of this class of inhibitors (decrease in HIV RNA levels, increase in CD4 cell counts). Treatment regimens were subsequently broadened to include reverse transcriptase inhibitors in combination with protease inhibitors. The result of these clinical trials has led to a list of guidelines with recommendations for the optimal treatment options. Prolonged control of the infection with combination therapy (highly active antiretroviral therapy, HAART ) could be shown. 

Boffito M, Back DJ, Blaschke TF, Rowland M, Bertz RJ, Gerber JG, Miller V (2003) Protein binding in antiretroviral therapies. AIDS Res Hum Retrovimses 19 825-835 Bressanelli S, Tomei L, Roussel A, Incitti 1, Vitale RL, Mathieu M, De Francesco R, Rey FA (1999) Crystal stmcture of the RNA-dependent RNA polymerase of hepatitis C vims. Proc Natl Acad Sci USA 96 13034-13039... 

Consequently, S-1360, a triazole analogue of DKA, was the first integrase strand transfer inhibitor (INSTI) to enter clinical trials, but the development was stopped during phase Eli (Billich 2003). Subsequently, a novel series of potent INSTIs, which replaced the 1,3-diketo acid moiety by an isosteric 8-hydroxy-1,6-naphthyridine core, showed improved metabohc stabihty (Zhuang et al. 2003). The compound L-870,810 moved into clinical trials, where it provided proof of concept in antiretroviral therapy-experienced and antiretroviral therapy-naive... 

Louie M, Hogan C, Di Mascio M, Hurley A, Simon V, Rooney J, Ruiz N, Brun S, Sun E, Perelson AS, Ho DD, Markowitz M (2003) Determining the relative efficacy of highly active antiretroviral therapy. J Infect Dis 187 896-900... 

Lalezari JP, Eron JJ, Carlson M, Cohen C, DeJesus E, Arduino RC, Gallant JE, Volberding P, Murphy RL, Valentine F, Nelson EL, Sista PR, Dusek A, KUby JM (2003b) A phase II clinical study of the long-term safety and antiviral activity of enfuvirtide-based antiretroviral therapy. Aids 17 691-698... 

Lockman S, Shapiro RL, Smeaton LM, Wester C, Thior 1, Stevens L, Chand F, Makhema J, Moffat C, Asmelash A, Ndase P, Arimi P, van WE, Mazhani L, Novitsky V, Lagakos S, Essex M (2007) Response to antiretroviral therapy after a single, peripartum dose of nevirapine. N Engl J Med 356 135-147... 

The priorities in antiretroviral therapy may change according to specific characteristics of the patient s virus population. Primarily, therapy should be potent enough to maximize the chances of achieving undetectable viremia thereafter, other consid-... 

Table 7 Diagnostic tools used for monitoring and optimizing antiretroviral therapy...

Barreiro P, del Romero J, Leal M, Hernando V, Asencio R, de Mendoza C, Labarga P, Nunez M, Ramos JT, Gonzalez-Lahoz J, Soriano V (2006) Natural pregnancies in HIV-serodiscordant couples receiving successful antiretroviral therapy. J Acquir Immune Defic Syndr43(3) 324-326... 

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