Supplementary memorandum submitted by
the National AIDS Trust
Stages of HIV vaccine developments and current
progress
| Phase | Objectives
| Size | Current Status1[6]
|
| Pre-clinical | Develop and test vaccine
concepts in the lab and in
animal studies
| — | Extensive basic science research
underway but;
— investigating a limited
range of possible strategies;
— most focused on types of
virus found in industrialised
countries;
— university/bio tech-based,
thus limited capital
|
Phase I
(12-18 months) | Safety trial with healthy
volunteers at low risk of HIV
infection
| 10-15 | 18 phase I trials underway
(14 of which are for types of
virus prevalent in
industrialised countries)
|
Phase II
(up to 2 years) | Safety/dosing trial with
healthy volunteers at low risk
of HIV infection
| 50-500 | 3 vaccine concepts have
reached Phase II
|
Phase III
(3-4 years | Efficacy trial with high-risk
populations—vaccine vs
placebo
| 5,000-8,000 | Only 2 very similar products in
Phase III trials (Vax Gen)
— low expectations as to
efficacy
|
| | High Cost:
— require site
infrastructure;
— require community
mobilisation and education;
— need voluntary
counselling and testing,
prevention and care
programmes.
| |
|
Shortening the development time for HIV vaccines
IAVI's Scientific Blueprint 2000[7]
makes several recommendations to reduce the time taken to develop
safe, effective and accessible HIV vaccines, including:
(a) Parallel development: move several different vaccine
concepts in to human trials simultaneously thus broadening the
research pipeline and maximising knowledge gained from each trial.
(b) Focus research on types of HIV that are prevelant
in the majority world (Clades A, C, D, E etc, depending on where
trials are planned).
(c) Develop protocols for combined phase I/II trials (ie
shorten development pipeline).
(d) Develop criteria for selecting most promising candidates
to move into Phase III trials.
(e) Conduct parallel Phase III efficacy trials in several
of the countries most heavily affected by HIV and AIDS.
Manufacturing, licensing, purchasing and delivering HIV vaccines
The scientific development and testing of successful HIV
vaccines are only the first stages of actually delivering vaccines
to the people who need them. The potential demand for an effective
HIV vaccine would be enormous and could pose logistical challenges
for manufacture, purchase and delivery. The simultaneous provision
of a vaccine across the world would also require the licensing
of the product by a large number of regulatory bodies. With an
additional 15,000 people becoming infected with HIV every day,
these potential delays need to be planned for now.
In AIDS Vaccines for the World: Preparing Now to Ensure
Access (IAVI, July 2000)[8]
IAVI addresses these issues and sets out a five point global access
plan;
(a) Establish effective pricing and global financing mechanisms
ensure rapid access to vaccines where they are most needed;
(b) Establish mechanisms to make more reliable estimates
of demand for specific vaccines and ensure the creation of appropriate
production capacity;
(c) Develop appropriate vaccine delivery systems, policies
and procedures for adolescents, sexually active adults and other
at risk groups;
(d) Harmonise national and international guidelines governing
vaccine approval;
(e) Demonstrate global commitment to the effective worldwide
deployment of important vaccines by immediately increasing efforts
to achieve maximum use of one or more currently under-utilised
non-HIV vaccines in developing countries (NB: this is part of
the rationale for GAVI).
Scaling up activity
The IAVI Scientific Blueprint 2000 suggests that maximising
the chance of success in finding a successful vaccine will require:
(a) 25 new vaccine designs to be moved into development
and evaluated in head-to-head Phase I/II trials;
(b) the most promising candidate vaccines should be taken
into six to eight parallel Phase III trials by 2007;
IAVI estimates that this level of scaling up will require
an additional $1 billion invested in vaccine R & D over and
above current projected expenditure.
CURRENT LEVELS
OF INVESTMENT
IN HIV VACCINE
RESEARCH
"Privately funded R&D on HIV vaccines (in 1999) was
in the range of $50-$124 million per year and fewer than 200 scientists
in the private sector are dedicated to AIDS vaccine-related work,
some of it subsidised by the public sector [ . . . ]. The incentive
for investing in AIDS treatment is far greater. Demand for treatment
is always more robust than for prevention."
Ainsworth et al (2000), Accelerating an AIDS Vaccine for Developing
Countries: Recommendations for the World Bank. World Bank Vaccines
Task Force, p 5
Of the $300 million invested by all sectors in HIV vaccine
research and development in 1999, IAVI estimates that only $5-$10
million per year was spent on vaccines based specifically on the
types of HIV prevalent in non-industrialised countries. The majority
of research has focused on the type of HIV found predominantly
in Europe, America and Australia, even though this accounts for
less than five per cent of the total number of people infected
in the world.
ADDITIONAL INFORMATION
ON NEED
FOR AND
CURRENT STATE
OF RESEARCH
INTO MICROBICIDES
TO PREVENT
THE TRANSMITTION
OF HIV
The Need for Woman Centred Prevention Methods
Women account for 45 per cent of people living with HIV globally,
and this proportion is increasing. In sub-Saharan Africa women
account for 55% of people infected.
— Women are biologically more susceptible to HIV
infection during heterosexual intercourse than men.
— In many countries pervasive gender inequalities
mean that women are more vulnerable to HIV infection—eg
70 per cent of the world's poorest people are women (see IDC report
Women and Development, November 1999).
— In many countries cultural (and often legislative)
norms situate men in a more powerful position in determining sexual
practices than women and this can undermine the opportunity of
individual women, to negotiate safer sexual practices.
As set out below, a safe, effective and accessible microbicide
that is acceptable to women would provide an important addition
to current HIV prevention efforts. However, as with vaccines,
microbicides must be seen as part of broader strategies to address
HIV and AIDS. Microbicides will require ongoing access, purchase
and use as part of sexual practices to be effective.
Potential advantages and challenges of Anti-HIV Mocrobicides
| Potential Advantages | Challenges
|
Woman controlled
— strengthens women's opportunity to protect themselves and their partners
| Unlikely to be "invisible" to woman's partner and so will still usually require discussion
|
| Possibly active against other STIs
|
| Possibility that products can be applied some time before intercourse takes place
| Options and logistics for application of product need to be addressed:
— how easy is product to apply and what is optimal time before sex?
— how to ensure optimal coverage of product consistently to ensure protection in vagina?
— hygiene issues
|
| Possibility of cheap product that is stable under field conditions
| — multiple applications required: does not confer immunity
— distribution and cost
— social acceptability (address through social marketing)
|
| Possibility of microbicide that is not a contraceptive
|
| Improved protection when used with condoms (male or female)
| — currently assumed that microbicides should be used in conjunction with condoms.
|
Current State of Microbicide Research[9]
The Case for Microbicides[10]
estimates that a total of $35 million was invested by the public
sector in microbicide-related research in 1999. Total private
sector investment is estimated to be in the region of $3 million.
No major pharmaceutical company has invested in microbicide research.
There are four main approaches to microbicides:
(a) Killing or inactivating infectious pathogens eg currently
existing spermicides.
(b) Blocking entry of pathogens into target cells.
(c) Preventing infection from taking hold eg by using
anti-HIV drug based compounds (although this may raise costs).
(d) Enhancing natural vaginal defence mechanisms.
Current Trials and Products
|
| Product (approach type) | Trial Status
|
|
| Nonoxynol-9 (a) | Phase III trials
|
— COL-1492
— Contracept Gel
| NB: Data released in Durban showed N-9 increased HIV risk, even at low dose.
|
|
|
| Buffer Gel (d) | Phase I (India, Malawi, Thailand, Zimbabwe)
|
| Pro 2000 (b) | Phase I (USA), Phase II planned (MRC)
|
| Savvy (a) | Phase I (USA) |
| Cellulose Sulphate GEl (b) | Successful Phase I, Phase II planned
|
| Dextrin 2 Sulphate (b) | Successful Phase I, Phase II planned (MRC)
|
PC-515 (b)
carrageenan gel) | Phase II, Phase III feasibility study (South Africa)
|
|
Microbicides and Vaccines
The development and distribution of microbicides faces many
of the same obstacles that HIV vaccines do eg low levels of private
sector investment, narrow research base, planning for issues of
access and delivery. the development of strategies to overcome
these difficulties may be complementary for each technology. However,
there is a danger that these two technologies will be seen as
competing for resources.
While vaccines provide the best long-term prospect for stopping
HIV transmission (and doing so in a way which provide many potential
benefits to women) the timeline for their development is probably
in the range of 8-15 years if action is taken now. Microbicides
may provide provide an important mid-term intervention if resources
are made available and work to address practical and policy issues
is undertaken now.
The Alliance for Microbicide Development estimates that a
global investment of $100 million is required over the next five
years to move microbicide development significantly forward.[11]
INFORMATION REGARDING
THE PROVISION
OF "CARE
PACKAGES" TO
PEOPLE LIVING
WITH HIV AND
AIDS[12]
Continuum of Care
The notion of a continuum of care recognises that
anti-retroviral therapy (ART) for people living with HIV forms
just one part of the care and support that people with HIV need.
ART must be situated within the context of other services, some
of which provide the essential infrastructure that make ART possible
(such as diagnostic services).
A continuum of care would include: access to primary care
services, access to voluntary counselling and testing (VCT), access
to pain management drugs and palliative care, access to opportunistic
infection control, access to ARVs.
See Attachment
Focusing exclusively on the provision of ART may distract
policy makers from making available other forms of essential care
that can contribute to the quality of life of people living with
HIV, and which may contribute towards building the infrastructure
and expertise required for effective use of ART. However, as a
matter of principle access to ART, and the support necessary for
its effective use, should be taken as the goal of developing care
services for people with HIV.
Cost of drugs is not the only barrier to their use in the
majority world. Effective use of drugs requires: consistent supply
and distribution, diagnostic and testing capacity, prescribing
expertise, access to additional conditions for treatment such
as clean water or appropriate nutrition. However, drugs costs
are a major obstacle, and would remain so even if the issues above
were addressed. Reducing the cost of drugs will be an essential
component of any care strategy. Reducing the cost of drugs now
would:
— demonstrate a commitment to providing equitable
care for people with HIV and encourage infrastructure issues to
be addressed;
— increase access to non-ARV drugs, such as pain
killers and drugs for opportunistic infection prophylaxis;
— increase potential access to ARVs for use in existing
distribution networks (eg UNAIDS pilot treatment schemes or private
sector schemes).
The provision of a continuum of care will require input from
a variety of stakeholders including: donors, UN agencies, national
governments, pharmaceutical companies, NGOs, CBOs and people with
HIV.
See example table below:
|
| Potential roles within continuum of care for pregnant women with HIV
|
|
| Government | Hospitals
| NGOs | CBOs |
PWHIV |
voluntary testing
policy | laboratory support
| counselling | counselling |
basic information
provision |
subsidised or free
access to AZT or NVP
| counselling | infant feeding
| home-based care | counselling
|
| delivery of services
without
discrimination
| home visits | strengthen families
of PWHIV
| legal rights
awareness |
| | traditional birth
attendant services
| transport to clinics | |
| | |
home visits | |
|
Reference: Report of "Mobilising Care, Community Support
and the Involvement of People with HIV and AIDS in Asia,"
Thailand, October 1998. Available from the International HIV/AIDS
Alliance.
To develop and implement prevention strategies such as vaccines,
microbicides or mother-to-child transmission programmes requires
access to and community acceptance of voluntary counselling and
testing (VCT). VCT is only sustainable if people found to be positive
can access some levels of care and support and live in an environment
in which their rights are protected. In this sense, prevention
services are intrinsically linked to care provision.
Saul Walker and Julian Meldrum
National AIDS Trust
July 2000
6
Scientific Blueprint 2000: Accelerating Global Efforts in
AIDS Vaccine Development. IAVI, July 2000. (available at www.iavi.org). Back
7
ibid. Back
8
available at www.iavi.org. Back
9
See The Case for Microbicides: A Global Priority, Population
Council and International Family Health, July 2000. Back
10
Ibid. Back
11
ibid. page 13. Back
12
Provided with the support of Dr Mandeep Dhaliwal at the International
HIV/AIDS Alliance. Back
| 
