Epidemiological summary
Assuming for the purposes of this discussion that countries in Western, Central and Eastern Europe are all being considered:
- Adult prevalence of HIV is relatively low in Europe and in 2005 was given as 0.3% (West); 0.1% (Central); and 0.8% (East). These figures are undoubtedly an underestimate.
- New diagnoses of HIV are not falling; however AIDS mortality has decreased due to the introduction of ART.
- New diagnoses in Europe now outnumber deaths, meaning that the numbers of people living with HIV is increasing with major implications for health care, economic growth, cost and suffering.
- Numbers infected per year (2004) were given as:
- 23,000 (West) – 9% IDU; 31% gay men
- 1,585 (Central) – high % of children
- 50,000 (East) – 65% IDU; 0.6% gay men.
Clearly some groups of women (CSW), HIV-negative partners in sero-discordant relationships and migrant community members originating from high prevalence countries are also at high risk.
Effect of a vaccine
On the basis of the effect of a potential vaccine, we would propose differentiating 3 different types of potential vaccines:
1. Vaccines reducing susceptibility to infection (prophylactic vaccines);
2. Vaccines slowing disease progression;
3. Vaccines reducing infectivity.
A prophylactic vaccine may offer sterilising cross protective immunity to the different clades of virus which are now circulating in Europe – in which case (providing the vaccine is safe, acceptable and cheap) – it should be offered to all, and in particular reach those individuals most in need / at highest risk as it seems likely that overall epidemiological benefit won’t be achieved without covering these groups.
Acceptability and uptake of vaccines cannot be taken for granted. Proper community preparedness, outreach plans and programmes will be needed, moreover when those at highest risk may be amongst the hardest to reach, particularly in Central and Eastern Europe. We understand this is not within the remit of the EMEA, but more likely an issue for community groups such as the EATG.
- Given the biological proximity between vaccine types #2 and #3, it seems likely that a vaccine protecting against disease progression will have an impact on infectivity of the vaccinated – but infected – individual. From a purely public health approach we may consider these just as ''transmission halters'', but the prospect of such a vaccine providing extra years of disease free/ARV free lives to HIV+, vaccinated individuals appears a very beneficial one, moreover from the viewpoint of the EATG.
A growing body of policy research work is deepening our knowledge of the potential impact of future AIDS vaccines. In the light of current pipeline candidates, and as part of a project to estimate global and country-level impact of AIDS vaccines, the International AIDS Vaccine Initiative and the Futures Group have recently produced a research paper on impact models for AIDS vaccines for developing countries that includes some results potentially relevant to this discussion.
Considering a hypothetic vaccine imperfectly achieving reduced susceptibility, reduced infectiousness and slowing progression of disease, and using 3 different levels of efficacy together with 3 different levels of coverage, the model predicts that the number of new HIV infections averted in 15 years could range from 5.5 million to 28 million from the most modest scenario (30% efficacy and 20% coverage), to the most optimistic (70% efficacy and 40% coverage).
More relevantly perhaps, the model ''plays'' with the 3 potential attributes of the vaccine and explores potential variations on impact depending of the ones we deprive the vaccine of. On the basis of the medium scenario (50% efficacy and 30% coverage), with a vaccine that would ''only'' achieve reduced infectiveness and slow progression of disease, we would still achieve a 38% reduction in the cumulative number of new infections in 15 years. A more targeted coverage, likely to be the case in countries with concentrated epidemics, could still achieve 85% of the impact of a high-coverage scenario. The paper indicates that cost-effectiveness discussions might be premature at this point but that given the high cost of the epidemic, any programme reducing the number of new infections by 10% to 50% may be expected to produce significant savings
- Vaccines need to be considered in conjunction with other prophylactic measures: drugs, microbicides and behaviour interventions.
Current vaccine pipeline
Looking at the current HIV vaccine pipeline, we may encounter three potential scenarios with the upcoming results of current proof of concept trials:
Proven effectiveness warranting further research towards approval:
This would a major step forward for preventive vaccine development. It would be important to consider all aspects from manufacturing to delivery and programme roll out in a timely and effective fashion.
Equivocal results:
Many potential scenarios are possible in such a situation. Some consider equivocal results to be rather likely. Data may take time to be understood, and depending on what is shown, different scenarios would be possible, including a push for partial efficacy vaccine models to be studied in relevant contexts, i.e. most severe epidemics.
Negative outcome:
The vaccine shows clear lack of effectiveness on both end points which are defined as diminished susceptibility to infection and reduced viral set points in infected and vaccinated individuals.
The field could still obtain critical information for the design of future trials while managing expectations about ongoing and upcoming research. .
Concluding remarks
The EATG would not assume that all we can expect from an HIV/AIDS vaccine is a modification of the course of disease. We should not become guilty of too much pessimism, as too many people in the past have been guilty of over-optimism.
On the other hand, if all that is possible to begin with is a vaccine that could alter the course of disease, then this is still a very exciting possibility as, while not preventing HIV infection, it could turn it into an essentially benign infection.
Importantly, such a vaccine also has the potential to do this for people who are already infected. The line between prophylactic and therapeutic vaccines is potentially a blurred one; if a candidate vaccine demonstrated real efficacy in modifying the course of disease in people who acquire HIV infection when already vaccinated, the EATG would advocate trials of such a vaccine as a therapeutic intervention in already infected people. Proof-of-concept studies have demonstrated that therapeutic vaccines are possible and can reduce viral replication for as long as a year, before patients need to re-start antiretroviral drug therapy. However, these pilot vaccine preparations are complex at present, as expensive as a year's worth of ARVs, and may only work for certain subtypes of HIV or in people with certain kinds of immune response (HLAs etc). We would certainly welcome simpler, cheaper and more convenient therapeutic vaccines to be tested in a timely fashion in the appropriate populations.
The EATG is aware of some fundamental scepticism amongst HIV clinicians about the idea of a therapeutic vaccine. We are not aware of immunologists sharing such concerns.
As a patient group, we advocate for continued public support for the development of therapeutic AND prophylactic HIV vaccines, not only because they are they the only answer to preventing HIV in the long term, but they may also be the only answer to not having to take antiretroviral treatments for a lifetime in people are already infected with HIV.
