HAART

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. 

HAART Highly active anti-retroviral therapy... 

Of the NNRTIs that were first approved, nevirapine and, even more so, efavirenz became cornerstones of HIV therapy because of their potential as a component of HAART (Staszewski et al. 1999). The most commonly used NNRTl drug is efavirenz. In addition, nevirapine was shown to effectively prevent HIV transmission from mother to baby. NNRTIs have proven beneficial when included in drug combination (triple or quadruple) therapy, preferably in the presence of protease inhibitors and NRTIs. 

The dramatic decrease in the morbidity and mortality of HIV-infected individnals in the last decade, due to the wide use of HAART, has been somewhat tempered by the emergence of mid-long term toxicities. A characteristic body fat redistribntion and metabolic changes, inclnding dyslipidemia and insnlin resistance, are amongst the most prevalent and worrisome consequences (Carr et al. 2003). As HIV-infected individnals have increasing life expectancies, the risk for cardiovascnlar complications has emerged as an important canse of morbidity and mortality and preventive measnres should be considered to minimize their impact (Weber et al. 2006). 

Even under these conditions we can state that in highly developed countries HAART is cost-effective. Because of an increase of life expectancy, the life-time provider costs increase under this drug regime. But, on the contrary, the indirect... 

As discussed previously, direct COI are the economic representation of resource consumption and have a natural monetary value. They can occur on the provider and the household side. This chapter analyses the direct COI in four steps Provider cost before HAART (Sect. 2.1.1), provider cost in the HA ART era (Sect. 2.1.2), lifetime provider costs (Sect. 2.1.3), and direct household cost (Sect. 2.1.4). 

Table 2 Examples of provider cost-of-rUness in the pre-HAART era [US p.a.]...

Table 2 summarizes these basic studies before the era of HAART. It is obvious, that there is a wide range between the results of these studies and we have to admit that we have little reliable data on the provider costs before 1995. The methodologies used are very different, so that comparison of results becomes difficult. In particular, the extent of considering special cost categories and the quality of data might have influenced the corresponding results. Borleffs et al. (1990) supposed that precise data on the utilization of health care facihties by HIV patients were often not available. 

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. 

To compare the epidemiological, clinical, and economic impacts of the HIV epidemic in Italy prior to and after the introduction of HAART, Tramarin et al. (2004) conducted a prospective and observational study with a multi-center design. They used data collected on an AIDS cohort from 1994 and updated data from a comparable cohort in 1998. Mortality and medical costs of 251 patients were measured in 1994 and in 1998, respectively. A considerable difference was observed in mortality (33.9% in 1994 vs. 3.9% in 1998). The cost per patient per year was US 15,515 in 1994 and US 10,312 in 1998. Based on the comparison of the two cohorts between both years, the authors concluded that after the introduction of HAART, hospital-based provision shifted from an inpatient-based to an outpatient-based service, with major focus on pharmaceutical care. 

Stoll et al. (2002b) examined provider costs in a German monocentric cohort of HIV-infected patients after the introduction of HA ART. According to their findings, mean provider costs per capita decreased from US 31,812 in 1997 to US 21,926 in 2001. The costs of HA ART per capita decreased significantly from US 15,739 in 1997 to US 14,336 in 2001. Also quite impressive was the continuous decrease of expenditures for additional drug therapy (-43.3%) and hospitalization (-52.1%), respectively. However, the costs caused by HAART increased from 49.5% of all provider costs in 1997 to 65.4% in 2001. 

With these findings we can conclude that the drug costs strongly increased since the introduction of HAART. However, other provider costs strongly declined with the introduction of this drug regime, so that the total costs remained stable or declined. HAART is - at least in the short-term analysis given in this literature review - cost-effective. 

A final assessment is difficult as the number of studies on lifetime costs of HIV/AIDS is very small, and the last few years have seen only few publications in that field. However, with an increasing life expectancy due to HAART, we can expect that the provider lifetime COI will strongly increase. 

In a nut-shell Out knowledge of the direct COI of HIV/AIDS has strongly increased in the last 10 years. Depending on the level of care in a particular country, provider cost per case might be as high as US 25,000 p.a., and the discounted lifetime costs in the HAART era will be more than 100,000 US per case. There can be no doubt that AIDS will cause higher costs for the patients and his household, but we know almost nothing about these costs. 

Beside their calculation of direct costs, Stoll et al. (2002a) also examined indirect costs in a German sample of HIV-infected patients after the introduction of HAART. To emphasize the implications of different approaches of indirect costs, the authors determined both costs based on the human capital approach and costs calculated on the friction cost approach. They concluded that indirect costs based on the friction approach per patient in 1997 (US 2,421) add up to only one-tenth of the amount derived from the human capital approach (US 24,639). 

Gable CB, Tierce JC, Simison D et al (1996) Costs of HIV-f/AIDS at CD4+ counts disease stages based on treatment protocols, J Acquir Immune Defic Syndr Hum Retrovirol 12 413 20 Gebo K, Fleishman J, Conviser R et al (2(X)6) Contemporary costs of HIV health care in the HAART era. In Presentation at the 13th conference of retroviruses and opportunistic infections,... 

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