Select Committee on International Development Minutes of Evidence

Supplementary memorandum submitted by the National AIDS Trust

Stages of HIV vaccine developments and current progress

PhaseObjectives SizeCurrent Status1[6]
Pre-clinicalDevelop 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
—  university/bio tech-based,
thus limited capital
Phase I
(12-18 months)
Safety trial with healthy
volunteers at low risk of HIV
10-1518 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
50-5003 vaccine concepts have
reached Phase II
Phase III
(3-4 years
Efficacy trial with high-risk
populations—vaccine vs
5,000-8,000Only 2 very similar products in
Phase III trials (Vax Gen)
—  low expectations as to
  High Cost:
—  require site
—  require community
mobilisation and education;
—  need voluntary
counselling and testing,
prevention and care

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.


    "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.


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 AdvantagesChallenges
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]


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

GovernmentHospitals NGOsCBOs PWHIV
voluntary testing
laboratory support counsellingcounselling basic information
subsidised or free
access to AZT or NVP
counsellinginfant feeding home-based carecounselling
delivery of services
home visitsstrengthen families
legal rights
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 Back

7   ibid. Back

8   available at 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

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