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This chapter summarizes the principal challenges of antiretroviral therapy (ART) in both resource-rich and developing world settings as of the end of year 2006 and discusses the options available to address them. It shows that long-term ART involves problems of adherence, resistance and toxicity as well as cost. It also shows how the successes of HAART have modified the clinical presentation of cancers in HIV-infected individuals and how the aging of HIV-positive patients is gradually increasing the development of geriatric syndromes that were rarely seen just a few years ago. Early detection and aggressive management of hepatitis co-infections are needed in order to avoid the severe complications and elevated mortality of end-stage liver disease.

Despite the government's intransigence regarding antiretroviral treatment, islands of access to such care began to materialize in the late 1990s. Clinical investigators capitalized on the interests of pharmaceutical firms in conducting research in South Africa. Appalled international humanitarian relief organizations, including Doctors Without Borders, sought to underwrite limited treatment efforts. And within the corporate sector, some of South Africa's largest firms extended medical coverage to include antiretroviral therapy, either through health insurance or directly through company clinics. Those who pressed for such innovations believed that by demonstrating the efficacy of treatment, they would not only meet the clinical needs of patients, but provide a powerful antidote to the stigmatization attached to HIV infection and a moral challenge to President Mbeki and his administration. They were aided in their efforts by an innovative and effective grassroots organization of HIV positive people and their supporters, the Treatment Action Campaign.

This chapter first portrays the rationing of care in the pre-antiretroviral era, as doctors and nurses confronted claims by administrators and colleagues that treating people with HIV represented a waste of limited resources. It captures the sense of despair or outrage among clinicians who faced financial obstacles to providing what they believed was appropriate care. It discusses the hope and anguish experienced by doctors and nurses when the personal fortunes of some patients permitted their access to new, powerful anti-HIV available in the United States and Europe, while other, less privileged patients continued to suffer and die. Finally, the chapter traces the sense of dismay among clinicians over President Thabo Mbeki; the government that bore the mantle of victory over apartheid had itself become the most important obstacle to providing life-extending treatment to millions with HIV in South Africa.

This chapter provides an overview of paediatric HIV management in the population entering adulthood after a decade of highly active antiretroviral therapy (HAART). Topics discussed include prevention of mother-to-child transmission of HIV and the evolution of antiretroviral management.

This chapter focuses on the impact of highly active antiretroviral therapy (HAART). Topics discussed include the HIV pandemic, evolution of the antiretroviral therapy, global response to the epidemic, and criteria for a successful HIV intervention.

This chapter discusses HIV in Australia. Topics covered include epidemiology of HIV infection in Australia, primary and newly diagnosed HIV infection in Australia, treatment strategies during the era of HAART in Australia, and the impact of HAART in Australia.

This chapter begins with a description of the epidemiology of HIV/AIDS in Thailand. It then discusses the early use of antiretrovirals, early use of highly active antiretroviral therapy (HAART), driving forces in the scale-up of HAART, antiretroviral therapy (ART) in children, and the Thai government's policy on HAART.

This chapter describes the epidemiological characteristics of HIV infection in Chile. It discusses the healthcare system and its approach to antiretroviral therapy from the advent of HAART until 2007, with a focus on the difficulties, the challenges and lessons learned. It also outlines the current status of the national treatment programme and evaluates its impact.

This chapter reviews the EurSIDA. The EuroSIDA study was initiated in 1994 to study the clinical implications of the HIV epidemic in Europe and provide a continued surveillance mechanism for detection of emerging problems at a European level. The study's primary objective remains to prospectively study demographic, clinical, therapeutic, virologic, and laboratory data from those infected with HIV across Europe in order to determine the long-term virologic, immunologic, and clinical outcomes.

This chapter reviews the Options in Management with Antiretrovirals (OPTIMA) study. OPTIMA study is the first tri-national collaboration between the US Department of Veterans Affairs (VA), Canadian Institutes for Health Research, and the UK Medical Research Council. It is a prospective, randomized, 2-factorial design study looking at the clinical utility of a three-month antiretroviral drug-free period (ARDFP), and whether there is a difference in effectiveness between standard and ‘mega-regimens’ (five or more active antiretroviral drugs).

This chapter begins with a discussion of the epidemiology of HIV in Germany. It then discusses subtypes and prevalence of drug resistance in Germany, treatment strategies, effects of HAART, and healthcare delivery.

This chapter looks back at some of the milestones on the road to highly active antiretroviral therapy (HAART) in the developed and developing world, recognizing the remarkable progress that has been achieved. It also acknowledges that the accumulated short-term experience may be neither sufficient nor appropriate when facing the long-term challenges raised by the epidemic, and the need for effective large-scale access to prevention, treatment, and care for all those in need worldwide.

This chapter begins with a description of the epidemiology of HIV in South Africa. It then discusses government policy on universal access to ART, treatment access in South Africa, the Southern African HIV Clinicians Society, and the importance of HAART on control of viraemia, opportunistic infections, and survival.

This chapter reviews the HIV Netherlands-Australia-Thailand Research Collaboration (HIV-NAT). HIV-NAT is an HIV-related clinical trials research centre under the aegis of the Thai Red Cross AIDS Research Centre (TRC-ARC). It was established in 1996 by collaboration between three organizations: the Thai Red Cross AIDS Research Centre in Bangkok; the National Centre in HIV Epidemiology and Clinical Research (NCHECR) in Sydney; and the International Antiviral Therapy Evaluation Centre (IATEC) in Amsterdam. The main missions of HIV-NAT are to conduct clinical trials of antiretroviral drugs according to the International Conference on Harmonisation/WHO Good Clinical Practice (ICH GCP) standards and to address research questions that are relevant and have a high impact on developing countries.

This chapter describes the epidemiological characteristics of HIV infection in Malawi. It then presents the antiretroviral therapy (ART) scale-up programme and analyses the reasons why the country was able to achieve a good degree of success and to discuss challenges of the programme.

This chapter describes the implementation and rapid scale-up of antiretroviral therapy (ART) services in Zambia, and reports early patient outcomes from a large programmatic cohort. Although the history of ART in Zambia is limited thus far, the country's experience provides unique insight into the potential impact of HIV treatment in settings of high prevalence and low resources.

This chapter presents an overview of HIV Outpatient Study (HOPS) and Multicenter AIDS Cohort Study (MACS). HOPS is a prospective observational cohort study that was initiated in 1993 by the US Centers for Disease Control and Prevention (CDC), and is currently expected to continue collecting and analyzing longitudinal data on HIV-infected outpatients until mid-2011. It is the longest-running and only remaining US government-sponsored multi-site prospective cohort of a diverse spectrum of people living with HIV infection and receiving routine clinical care in the United States. MACS was funded in 1983 by the US National Institute of Allergy and Infectious Disease (NIAID), and recruitment of participants began in early 1984. The initial rationale for funding this epidemiological investigation was to collect specimens that could potentially be of use in identifying an infectious agent as the cause of AIDS and to delineate the natural history of pre-AIDS in men who have sex with men (MSM), the first epidemiologically identified group at high risk of developing the syndrome.

This chapter begins with a description of the epidemiology of AIDS and HIV in Brazil. It then discusses treatment, results of free access to antiretroviral drugs, co-infection, and prevention. The HIV/AIDS epidemic in Brazil was detected early in the 1980s. Its progress seems to have been at least partially curbed by early and integrated response, including the establishment of an inclusive epidemiological surveillance system. The epidemic is characterized as concentrated since the prevalence among certain vulnerable groups is higher than 5%, but it is below 1% in the general population.

This chapter reviews the Projeto Praça Onze. The Projeto Praça Onze was a prospective cohort study conducted in Rio de Janeiro between 1995 and 1998 to estimate the incidence of HIV infection in high-risk seronegative men who have sex with men (MSM), and to determine whether this population would be suitable for vaccine and non-vaccine intervention studies.

This chapter discusses the quest for an effective treatment for AIDS and efforts to provide universal access to treatment. In the early 1980s there were no effective treatments against viruses on the market, except acyclovir for herpes simplex and amantadine for influenza. The discovery of antiretroviral therapy in the 1990s changed the lives of millions of people living with HIV, as well as how the world perceived AIDS and the epidemic. HIV infection was no longer a death sentence, and there was hope that one day the epidemic could be stopped. Since then more than thirty antiretroviral drugs have been marketed. In 1999 and 2000 the first generic antiretrovirals arrived on the world market, mainly produced in India by companies such as Cipla and Ranbaxy. This move by the Indian generic industry fundamentally changed access to medicines in low-income countries, in particular sub-Saharan Africa, by introducing generic price competition of drugs still under patent. In 2000 major pharmaceutical laboratories also agreed to lower the price of antiretrovirals for low-income countries as part of the UNAIDS-WHO Accelerating Access Initiative.