YOU ARE HERE:
UNAIDS' guidelines
   Last updated: 19.05.03
 
In 1997-99, UNAIDS sponsored a series of consultations leading to the publication of a detailed eighteen-point guidance document in May 2000. The following section outlines and comments on this guidance, which can be read in full on the UNAIDS website (www.unaids.org).

HIV vaccines development (point 1)
UNAIDS begins with the need to develop vaccines and make them available: ‘it is imperative that they benefit the population at greatest risk of infection.’ It distinguishes between ‘investigators’, ‘host countries’ where trials might be held and ‘communities’ from which volunteers would be drawn, ‘donors and international agencies’ and ‘sponsor countries’ acknowledging that vaccines are being developed in public-private partnerships rather than on a purely commercial basis.

Vaccine availability (point 2)
Issues of availability including but not limited to availability in the country and population where a vaccine is tested need to be addressed throughout the process of vaccine development. ‘The discussions should include decisions regarding payments, royalties, subsidies, technology and intellectual property, as well as distribution costs, channels and modalities, including vaccination strategies, target populations, and number of doses.’

Capacity building (point 3)
A recurring theme, with the goal of enabling host countries and communities to participate as equal partners in the process.

Research protocols and study populations (point 4)
Any study must be scientifically sound and have the potential to benefit the population recruited into the study. An ethical trial must be capable of answering the questions it sets out to answer, using the most efficient and humane means of addressing scientific uncertainty, e.g. to show whether a candidate vaccine is immunogenic, safe and/or effective. The relevance of this point is greater for populations at high risk in host countries than for populations at low risk in sponsor countries, where exploitation is seen as less of a danger.

Community participation (point 5)
‘Community representatives should be involved in an early and sustained manner in the design, development, implementation, and distribution of results of HIV vaccine research.’ The guidance identifies categories of interested people who should be consulted in the course of setting up arrangements for community participation, including those eligible to volunteer for a specific study as well as care-givers and people living with HIV.

Scientific and ethical review (point 6)
Host countries must be capable of independent scientific and ethical review of research proposals, an area in which capacity building by agencies independent of vaccine developers may be needed.

Vulnerable populations (point 7)
This refers to the need to recognise and take steps to overcome social factors that may make research participants vulnerable to exploitation. This vulnerability is not solely economic, and may derive from inadequate respect for human rights on a variety of grounds.

Clinical trial phases (point 8)
This breaks with past guidance on international clinical research, which has required that early phase trials should be confined to the country in which a product is first developed. UNAIDS acknowledges that any country may legitimately decide to conduct phase I trials, provided there is sufficiently strong scientific, clinical, and ethical review infrastructure to protect the volunteers. The case for doing this is enhanced when a vaccine candidate is based on isolates of the virus from a particular community, country or region where trials will be carried out.

Potential harms (point 9)
Likely harms need to be identified in research protocols, and fully explained to trial volunteers in the informed consent process, including an explanation of how people will receive treatment and compensation if needed.

‘HIV infection acquired during participation in an HIV preventive vaccine trial should not be considered an injury subject to compensation unless it is directly attributable to the vaccine itself, or to direct contamination through research-related activities. In addition to compensation for biological/medical injuries, appropriate consideration should be given to compensation for social or economic harms, e.g. job loss as a result of testing positive following vaccine administration.’

A distinction is made here between the need for compensation for HIV infection and the need for access to treatment and care, which is addressed separately. It would seem better to prevent social or economic harms rather than merely to plan for compensation. This is why ‘consideration should also be given to setting up an ombudsperson who can intervene with outside parties, if necessary and requested, on behalf of participants, as well as to providing documentation to participants that they can use to show that their false positive is due to their participation in research.’

Benefits (point 10)
Potential benefits to trial volunteers from participation should be clearly explained to them, without presenting them in such a way as to unduly influence the decision to join a trial.

Control group (point 11)
‘As long as there is no known effective HIV preventive vaccine, a placebo control arm should be considered ethically acceptable in a phase III HIV preventive vaccine trial. However, where it is ethically and scientifically acceptable, consideration should be given to the use in the control arm of a vaccine to prevent a relevant condition apart from HIV.’ (The examples given are hepatitis B and tetanus.) The guidance might have pointed out that the failure to provide for a blinded control group in any trial involving high-risk volunteers might lead volunteers to assume that a vaccine protects them when it does not and increase their HIV risk, leading to real harm. If volunteers are to take part in a blinded trial they must remain ignorant for the duration of the trial of whether they have received an HIV vaccine, without losing the ability to check their own HIV status.

Informed consent (point 12)
This is a ‘strategy and process’ arising from a ‘process of consultation between community representatives, researchers, sponsor(s) and regulatory bodies.’ Individuals must be free to decide for themselves whether to take part, on the basis of ‘complete, accurate, and appropriately conveyed and understood information.’ Furthermore, ‘efforts should be taken to ensure throughout the trial that participants continue to understand and to participate freely as the trial progresses.’ Informed consent is needed separately for HIV tests before, during or after the trial.

The guidance observes that in any preventive vaccine trial it must be possible to distinguish the effects of the vaccine from those of natural infection. The costs and feasibility of doing this will vary between different vaccines. Vaccines based on the fullest possible range of viral components may need special and costly provision.

The most obvious test of remaining virus-free is failure to isolate the virus from a blood sample. However, even with a well-equipped laboratory it can still be difficult to isolate HIV from some people who are clearly infected with it, so a negative result on this test may not be convincing. Alternatives like p24 antigen tests (moderately expensive) and PCR tests (more expensive) would not be triggered by most likely vaccines. Some vaccine designers have deliberately excluded the HIV protein gp41 from vaccine systems so that commercially available ELISA tests for antibodies to gp41 may be used for this purpose (Corey, 1996; Yao, 1996).

Informed consent special measures (point 13)
This lists categories of people whose ability to consent freely on their own account may be limited by their social, legal, economic or gender status, for whom additional protective measures may be needed.

Risk-reduction interventions (point 14)
‘Appropriate risk-reduction counselling and access to prevention methods should be provided to all vaccine trial participants, with new methods being added as they are discovered and validated.’

One issue, which has much exercised people, is a supposed conflict of interest between trial volunteers, who surely want to stay uninfected at all costs, and researchers 'needing' some people to become infected to prove that others those vaccinated are genuinely protected. In practice, this conflict can be resolved by implementing prevention programmes that in theory and practice reduce the HIV risk of trial volunteers, whether or not they receive a vaccine.

Monitoring informed consent and interventions (point 15)
This needs to be provided for, with plans made before the trial begins.

Care and treatment (point 16)
‘Sponsors need to ensure care and treatment for participants who become HIV-infected during the course of the trial.’ This does not imply an obligation for sponsors to provide care and treatment for everyone in a community where a trial is taking place, nor for everyone identified as HIV positive during the course of screening trial volunteers. UNAIDS found during its consultations that there was no consensus as to what level of care and treatment needs to be provided during a vaccine trial. As this issue has been one of the most contentious, it is worth quoting the guidance point in full:

‘Care and treatment for HIV/AIDS and its associated complications should be provided to participants in HIV preventive vaccine trials, with the ideal being to provide the best proven therapy, and the minimum to provide the highest level of care attainable in the host country in light of the circumstances listed below. A comprehensive care package should be agreed upon through a host/community/sponsor dialogue which reaches consensus prior to initiation of a trial, taking into consideration the following:
  • level of care and treatment available in the sponsor country

  • highest level of care available in the host country

  • highest level of treatment available in the host country, including the availability of antiretroviral therapy outside the research context in the host country

  • availability of infrastructure to provide care and treatment in the context of research

  • potential duration and sustainability of care and treatment for the trial participant.


Women (point 17)
This observes that as women including those who are potentially pregnant, are pregnant, or are breastfeeding, should receive future preventive HIV vaccines, women should be included in clinical trials. The implication is that there should not be an absolute exclusion of pregnant or breastfeeding women from the later stages of HIV vaccine trials, although the need to warn women of potential risks to their children as part of the informed consent process is clearly set out.

Children (point 18)
This states, ‘children should be included in clinical trials’ and discusses the circumstances in which adolescents need to give individual informed consent, noting that the requirement for additional consent by parents or guardians will vary between countries depending on their legal provisions. In the case of breastfed infants, the requirement would be for consent by a parent on behalf of the child, or both parents if required by national legislation.