As we review the first year of the HIV/AIDS epidemic in the new millennium, three developments clearly stand out. First is the renewed interest and progress in the testing of HIV preventive interventions. Second is the price war that unfolded between generic and multinational producers of antiretroviral drugs. Third is the fact that, after 20 years in the epidemic, we have not been able to halt the spread of HIV, particularly in developing countries. The papers in this section were chosen to reflect these developments.
The ever-increasing number of HIV-infected people (5.3 million new HIV infections in the year 2000 alone) has made it absolutely clear that the epidemic cannot be stopped by social and behavioral interventions alone. There is a growing consensus that biomedical interventions for primary prevention of HIV infection are the best long-term solution to stop the HIV epidemic. After the lethargy of the mid-1990s, public pressure mounted to move the testing of preventive HIV vaccines and topical microbicides forward. A whole new range of candidate HIV vaccines and microbicidal products has become available and is waiting to be tested in phase III efficacy trials. Testing of these products requires careful identification and preparation of sites and populations as well as cautious consideration of the human subjects issues involved. The paper by Esparza and Burke provides a timely address of the epidemiological aspects of planning HIV vaccine trials. The need for careful and integrated planning is clearly demonstrated by the epidemiological waste that occurred in the early 1990s, when several prospective HIV vaccine cohorts were developed that were never used in phase III trials. The establishment and maintenance of vaccine cohorts is extremely expensive and time consuming. The availability of a candidate vaccine fine-tuned for the genetic characteristics of the circulating virus and the route of transmission in the study population is therefore absolutely necessary prior to the initiation of prospective cohorts. The long road of Thailand to phase I, II and III HIV vaccine testing described by Esparza and Burke is a good example.
The importance of HIV genetic variability not only for vaccine development is also illustrated by the extensive and excellent review of Tatt, Barlow, Nicoll and Clewley regarding the public health significance of HIV subtypes. They describe the ever-increasing diversity of HIV strains around the world and their consequences for the clinical testing of HIV vaccines, the development of antiretroviral drugs, and the surveillance of transmission patterns. Their review makes it clear that we need to keep our epidemiological locus fixed on the moving target that the genetic diversity of HIV provides to us.
As we move forward with the clinical testing of HIV preventive interventions, protection of the physical and mental integrity of human subjects in this research becomes more and more important. The review of Kilmarx, Ramjee, Kitayaporn and Kunasol discusses experiences and recommendations from Africa and Asia regarding the rights of human subjects in HIV preventive clinical trials. Their paper provides helpful guidelines for ensuring free and fully informed consent as well as methods to educate potential participants and to evaluate their understanding. The use of comprehension tests as a measure or tutoring tool to assess understanding among study subjects is a relatively new method and, to our knowledge, up to now only used in HIV preventive trials. The paper also provides recommendations for reducing and monitoring risk behavior among trial participants as well as guidelines for community participation.
While the 5.3 million new HIV infections in the year 2000 show the desperate need for preventive interventions, the more than 20 million HIV-infected people without access to antiretroviral therapy (ART) and prophylactic HIV drugs show the desperate need for affordable medication. Since mid-2000, the prices of ART and other prophylactic drugs in developing countries have decreased more than 10-fold, bringing these treatments within close reach of hundreds of thousands, if not millions, of HIV-infected people. Contributors von Schoen Angerer, Wilson, Ford and Kasper represent Médicins Sans Frontières, the non-governmental organization deserving much credit for bringing down the costs of ART. In their review regarding the ethics of the provision of ART in developing countries, they describe the role of advocacy groups in facilitating generic production and distribution of antiretroviral drugs. Some will argue that these developments will deter large pharmaceutical companies from engaging in the development of new and more powerful anti-HIV drugs. Others will say that it will only stimulate pharmaceutical giants to more rapidly and creatively look at differential pricing schemes to make their drugs available to people in less wealthy countries. Whatever the outcome is, it cannot be denied that the price war on antiretroviral drugs has been one of the most publicly visible and significant developments in HIV/AIDS in the past year.
While we have seen progress in the search for clinical interventions to prevent HIV infection and in the accessibility of ART for people in developing countries, Ghys, Bazant, Monteiro, Calvani and Lazzari alert us to the fact that HIV continues to spread at alarming rates in many parts of the world. They eloquently describe the dark picture of the spread of the twin epidemics of injection drug use and HIV infection in Asia. With more than one-half of the total global population of 6 billion, Asia provides an enormous potential for epidemic spread of HIV. Ghys et al. argue that primary prevention of injection drug use and unsafe injection practices needs to be intensified and expanded, possibly at the expense of the repressive measures on which most Asian governments currently rely. Such strategies should be accompanied by programs addressing the economic, social and cultural forces driving the epidemics of drug use and HIV infection. The effects of these interventions and structural changes, however, will not come about quickly and will be difficult to sustain over time. We therefore need to continue our work to develop clinical interventions to prevent HIV infection, such as vaccines and microbicides. These interventions need to be affordable to low-income countries, where most new HIV infections occur. In the case of HIV vaccines, they also need to be tailored to the circulating HIV genotypes as well as to the dominant routes of transmission. However, these interventions will come too late for the 30 million people currently living with HIV, most of whom have no access to antiretroviral drugs. For this group, the price reduction of antiretrovirals is a very important development and provides a glimpse of hope for a better future. This hope can become a reality if we are able to face up to the challenge to set up the infrastructure and systems to deliver and evaluate the use of these drugs by people in remote locations with a minimum of facilities. This should include monitoring of viral resistance and primary prevention activities among those enrolled in treatment programs. Whether this will be possible remains to be seen.