This WHO information sheet documents the burden of HIV/AIDS in infants and young children — particularly in sub-Saharan Africa — and the success of introducing programmes to prevent mother-to-child transmission (MTCT). It describes both general and specific interventions needed to reduce MTCT.

This review article charts the rise of the new discipline of HIV prevention science: a combination of different yet complementary approaches that tackles the HIV/AIDS epidemic on a broad scale, from community-based to global activities.

The authors explain that the various elements each involve their own social, clinical and scientific dimensions, and include behavioural measures (such as condom use and voluntary counselling and testing) as well as the use of antiretroviral drugs for prevention of HIV transmission.

This popular science feature describes in lay terms the rationale behind the research and development of microbicides, describes some of the lead candidates, and gives a brief account of the context in which microbicides are being developed.

The author, Alan Stone, is chairman of the International Working Group on Microbicides, an umbrella organisation established in 1994 to coordinate and galvanise research and development of microbicides.

Particularly useful for those in developing countries about to embark on an HIV vaccine trial, this article describes the social, behavioural and ethical issues that arose in 1996 when Uganda was preparing for Africa's first HIV vaccine trial (which ran from 1999-2000).

Most notable were misconceptions about vaccine safety and its effects, such as whether the vaccine itself could cause disease, or was a treatment for infection. The authors describe the strategies employed to overcome these barriers, for example, through public outreach education and media communication.

In this article, the coordinator of the WHO's HIV Vaccine Initiative, Jose Esparza, outlines the steps that need to be taken in order to develop a safe, effective and affordable preventive vaccine.

In addition to overcoming considerable scientific hurdles, the development of a successful vaccine will require that multiple clinical trials take place in parallel, in both developing and industrialised countries.

The article explains the nature of the three different levels of clinical trial that vaccines must undergo before they can be licensed for widespread use, and lists which countries have participated (up to 2001).

Written for lay people who are considering becoming trial volunteers, this brief guide outlines the purpose and nature of HIV vaccine trials, and stresses the varying benefits of a vaccine.
 
These range from preventing infection in most or just some people (a preventive vaccine), to delaying or preventing the onset of illness or AIDS in people who are already infected with HIV (a therapeutic vaccine). Even a vaccine that is only partially effective could decrease the number of people who get infected.

It also indicates the need for advice on issues such as insurance and travel, as routine blood tests for the presence of antibodies to HIV will not distinguish between whether a person has received a vaccine or is infected with HIV (although other tests can be used for this).

[The guide is also available in Spanish.]

A layperson's guide to the concept of an HIV vaccine, the nature of clinical trials, and the ethical questions that local community groups or non-governmental organiastions need to raise before getting involved in clinical trials.

The guide also includes recommended web links and resources, and a glossary of relevant terms, and is available in French and Spanish.

This anthology from the International AIDS Vaccine Initiative looks back at the global commitment to fight AIDS launched at the International AIDS Congress in Durban in 2000, and at the progress and challenges of vaccine development. It provides a developing world perspective to the HIV vaccine enterprise, through the eyes of individuals playing key roles in HIV vaccine programmes.

Highlights include: a Brazilian AIDS vaccine advocate who sees vaccine-based prevention and drug-based treatment and care as part of the same goal; a South African nurse who advises on a vaccine community advisory board that has helped to dispel many myths about HIV vaccines; and a Kenyan paediatrician who outlines the difficulties in recruiting women to volunteer in clinical trials.

This is a comprehensive, technically detailed, review of the scientific advances in vaccine design over the past two decades. With more than 20 vaccines in pre-clinical testing and clinical trials, there is now hope that antibody-based immunity and cellular immunity are achievable goals.

Recent data, including investigation of people who have been exposed to HIV but remain uninfected, are helping to point the way forward. The authors warn, however, that the current crop of clinical trials are unlikely to reveal an effective vaccine, and that several large-scale phase III trials of different vaccine combinations will need to take place, which will require an unprecedented level of international cooperation. Additionally, the extent to which such vaccines can protect or control HIV infection and disease progression remains to be seen.

A well-written layperson's guide to the science behind HIV vaccine research, starting with an introduction to the body's immune system and how HIV infection gradually destroys this important defence against other infections and cancer.

This 'primer' also explains the composition of the different types of vaccines now in clinical trials, and highlights the gaps in understanding that are impeding progress. It contains a glossary of relevant terms, and is also available in French and Spanish.

This feature article presents the progress and pitfalls made in HIV vaccine research up to May 2002 (before the company VaxGen announced the results of the first large-scale trial of an HIV vaccine in February 2003; as widely reported, and anticipated by this article, the VaxGen trial proved disappointing).

The article describes the scepticism some scientists had about the VaxGen vaccine design, and other strategies now underway.  But although many different vaccines are now in clinical trials, several hurdles remain, including a lack of understanding about what is needed in order to protect against infection, and the rapid mutation and 'escape' of the virus from immune attack. Also uncertain is the extent to which geographical variation in HIV strains – known as clades – are likely to help or hinder vaccine development.

One of a series of WHO case studies Perspectives and Practice in Antiretroviral Treatment, this report features the HIV Equity Initiative established in Haiti in collaboration with Harvard University's Partners for Health.

The paper highlights how existing healthcare infrastructure (a TB control programme) can be adapted to HIV/AIDS treatment, with the lessons learned now being applied in other countries, including Peru, Russia, and the United States.

Advocating a public health approach to HIV/AIDS, the WHO describes antiretroviral (ARV) treatment programmes in developing countries as powerful demonstrations that expanded access to ARVs is both feasible and essential.

This paper outlines the elements of such a public health approach, in particular noting the participation of family and community members in support and monitoring of treatment adherence, and other tasks that in other settings may rely on more specialised healthcare personnel.

It follows on from the release of a set of standardised guidelines for the scaling up of treatment access, Scaling Up Anti-retroviral Therapy in Resource-Limited Settings in April 2002, and highlights the need for community partnership and capacity building.

This scientific review paper systematically covers the history of HIV drug development, from the initial identification of the AIDS virus and the appearance of the first antiretroviral drug, AZT, to the successes and limitations of today's Highly Active Antiretroviral Therapy (HAART).

The review includes a timeline of events, clear graphical illustrations of the HIV life cycle and mechanisms of drug action, and a list of the 21 drugs currently approved by the US Food and Drug Administration.

The authors express considerable optimism that future drugs targeting different steps in the HIV life cycle will help lead to more potent therapies. While the ultimate goal of complete cure remains a considerable challenge, they conclude, "the potential to completely control or suppress the virus in infected individuals is likely to become achievable in the near future".

This issue of the ACRIA Update gives an introduction to the science underlying HIV drug development, with a description of the stages of the HIV life cycle at which drugs are currently being targeted. 

It also includes useful articles (written by US- and South Africa-based authors) on the actions and side effects of existing brand-named drugs, dosing regimens, an outline of the drug development process, and an individual's experience of surviving more than a decade on HIV treatment.

This feature article - timed to coincide with the AIDS 2002 meeting in Barcelona - documents the prevailing mood about the successes and limitations of antiretroviral drugs. Jon Cohen charts the development of different drug strategies since 1996 (when a cocktail of drugs was first shown to control HIV), and canvasses expert opinion on their successes and limitations.

The 16 anti-HIV drugs approved by the US Food and Drug Administration at the time are listed (the total is now 21). These have had enormous impact on AIDS-related disease and mortality in wealthy nations, changing HIV/AIDS from an imminently fatal to a chronic manageable disease. But the rise of drug resistance and long-term side effects are now increasingly apparent, although, as Cohen reports, developing nations have yet to have the advantage of experiencing these 'limits of success'.

This study examined the effectiveness of two different methods of informing prospective participants about HIV research in Haiti. The first group of participants received information in a single interview with a physician. In a subsequent assessment of their understanding, only 20 per cent passed a questionnaire test.

The consent procedure was then modified to include three meetings with a Haitian social worker over 7-10 days before a final meeting with a physician-researcher. Of those participants agreeing to take part in the research, 80 per cent passed the comprehension test.

Noting the lack of practical guidelines on how best to inform and test the understanding of research participants in developing countries, Fitzgerald and colleagues conclude that a formal assessment of comprehension should be a routine part of the consent process.

Click here for a related commentary article.

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This article from the Gambia Government / Medical Research Council Joint Ethical Committee is an early response to the criticisms in the New England Journal of Medicine and The Lancet that placebo-controlled trials to prevent mother-to-child transmission of HIV were unethical.

The authors express concern that important research in developing countries would be threatened if research practice were changed in response to such criticisms. In particular, research that only compared new interventions with the best available therapy in developed countries would fail to provide information about interventions that are relevant and affordable for the local situation.

The authors note that there is sometimes a need to re-examine interventions that have proved effective in developed countries before it is possible to make an informed public health decision about introducing them in the developing world. They conclude that "stopping trials in Africa that are trying to help improve the health of poor people so that those in affluent countries can have peace of mind seems a tortured form of ethical logic".

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In this article Lindegger and Richter focus on two contentious aspects of informed consent. The first is the problem of 'social desirability' whereby participants may consent to take part in research because they wish to impress researchers or to please others in the community. The second is ways to determine whether participants' comprehension of the research is adequate to enable them to make an informed choice.

Other topics that are covered are conflicts that can occur between ethical principles and cultural practices when consent to research is sought, and how decisions about whether or not to take part in research should be made by communities and individuals. While consideration of these issues takes place within the context of South African HIV vaccine trials, the issues raised and the useful discussion that follows have a much wider relevance.

This background paper describes the basic principles behind two strategies that could be used to bring down the price of drug therapies: parallel importing (bringing drugs from another country) and compulsory licensing (restricting the monopoly rights of existing patent holders to permit generic drug production).

Other means of lowering drug prices are also briefly discussed. The paper aims to provide people with sufficient information to participate fully in the debate surrounding international trade laws and access to essential drugs (especially HIV-related medications).

The report is also available in French and Spanish.