Highly active antiretroviral

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. 

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... 

Highly active antiretroviral therapy (HAART) based on protease inhibitors or nonnucleoside reverse transcriptase inhibitors was introduced in the industrialized world during the second half of the 1990s. The majority of studies are based on data from the United States of America. 

Beck et al. (2004) presented an analysis of the cost-effectiveness of highly active antiretroviral therapy in Canada. They compared the cost-effectiveness from 1991 to 1995 (pre-HAART period) with the period from 1997 to 2001 (HAART period) for non-Aids and Aids groups. For the first group, they calculate total cost of US 4265 in the pre-HAART period and US 9445 in the HAART-period, whereas 66% and 84% were spent on antiretrovirals. The incremental cost per life year gained was US 14,587, that is, the HAART technology is rather cost-effective. For the Aids patients, the total costs were US 9,099 in the pre-HAART period and US 11,764 in the HAART period, whereas 29% were for antiretrovirals in the pre-HAART era and 72% in the HAART era. The incremental cost per life year gained by introducing HAART was US 12,813, so that HAART seems cost-effective in Canada. 

Bozette et al. (2001) examined expenditures for the care of adult HIV-infected patients since the introduction of highly active antiretroviral therapy. They interviewed a representative random sample of 2,864 patients in early 1996 and followed them for up to 36 months. They estimated the average expenditure per patient per month on the basis of self-reported information. According to their calculations, the mean expenditure was US 1,792 per patient per month at base hne in early 1996, but it decbned to US 1,359 for survivors in 1997, since the increases in pharmaceutical expenditures were smaller than the reductions in hospital costs. After adjustments for the interview date, clinical status, and deaths, the estimated annual expenditure declined from US 20,300 per patient (1996) to US 18,300 (1998). 

Beck EJ, Mandalia S, Gaudreault M, Brewer C, ZowaU H, Gilmore N, Klein MB, Lalonde R, Piche A, Hankins CA (2004) The cost-effectiveness of highly active antiretroviral therapy, Canada 1991-2001, Aids 18 (18) 2411-2418... 

Borleffs JC, Jager JC, Marinus JJ (1990) Hospitalcost for patient with HIV infection in a university hospital in The Netherlands, Health Pohcy 16 43-54 Bozette S, Joyce G, McCaffrey DE et al (2001) Expenditures for the care of HIV-infected patients in the era of highly active antiretroviral therapy, N Engl J Med 344 817-823 Breidert C (2006) Estimation of wilhngness-to-pay theory, measurement, application, Deutscher Universitats-Verlag, Wiesbaden... 

Gebo KA, Chaisson RE, Folkemer JG et al (1999) Cost of HIV medical care in the era of highly active antiretroviral therapy, AIDS 13 963-969... 

Kimura H (2002) Cost of HIV treatment in highly active antiretroviral therapy in Japan, Nippon Rinsho 60(4) 813-816... 

Munakata J, Brenner JS, Becker S et al (2006) Chnical and economic outcomes of nonadherence to highly active antiretroviral therapy in patients with human immunodeficiency virus, Med Care 44 893-899... 

Yazdanpanah Y, Goldie SJ, Losina E et al (2002) Lifetime cost of HIV care in France during the era of highly active antiretroviral therapy. Antivir Ther 7 257-266... 

Brew BJ (2004) Evidence for a change in AIDS dementia complex in the era of highly active antiretroviral therapy and the possibility of new forms of AIDS dementia complex. Aids 18(Suppl 1) S75-S78... 

Sacktor N (2002) The epidemiology of human immunodeficiency virus-associated neurological disease in the era of highly active antiretroviral therapy. J Neurovirol 8(Suppl 2) 115-121... 

Morgello S, Estanislao L et al (2004) HIV-associated distal sensory polyneuropathy in the era of highly active antiretroviral therapy the Manhattan HIV Brain Bank. Arch Neurol 61(4) 546-551... 

Palella FJ Jr, Baker RK et al (2006) Mortality in the highly active antiretroviral therapy era changing causes of death and disease in the HIV outpatient study. J Acquir Immune Defic Syndr... 

Puthanakit T, Oberdorfer P et al (2006) Immune reconstitution syndrome after highly active antiretroviral therapy in human immunodeficiency virus-infected thai children. Pediatr Infect Dis J... 

Finzi D, Hermankova M, Pierson T, Carruth LM, Buck C, Chaisson RE, Quinn TC, Chadwick K, MargoUck J, Brookmeyer R, Gallant J, Markowitz M, Ho DD, Richman DD, SUiciano RF (1997) Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science 278(5341) 1295-1300... 

Zhu T, Muthui D, Holte S, Nickle D, Peng P, Brodie S, Hwangbo Y, Mullins II, Corey L (2002) Evidence for human immunodeficiency virus type 1 replication in vivo in CD14(-l-) monocytes and its potential role as a source of virus in patients on highly active antiretroviral therapy. J Virol 76(2) 707-716... 

Keane NM, Price P, Lee S et al (2001) An evaluation of serum soluble CD30 levels and serum CD26 (DPPIV) enzyme activity as markers of type 2 and type 1 cytokines in HIV patients receiving highly active antiretroviral therapy. Clin Exp Immunol 126 111-116 Khan MZ, Brandimarti R, Shimizu S et al (2008) The chemokine CXCL12 promotes survival of postmitotic neurons by regulating Rb protein. Cell Death Differ 15(10) 1663-1672... 

Ushio-Fukai M, Nakamura Y (2008) Reactive oxygen species and angiogenesis NADPH oxidase as target for cancer therapy. Cancer Lett 266 37-52 Valentin A, Rosati M, Patenaude DJ, Hatzakis A, Kostrikis LG, Lazanas M (2002) Persistent HIV-1 infection of natural killer cells in patients receiving highly active antiretroviral therapy. Proc Natl Acad Sci U S A 99(10) 7015-7020... 

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