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First trial of the HIV-1 vaccine in Africa: Ugandan experience



Problems in setting up the first trial of an HIV-1 vaccine in Uganda are described here by Mugerwa and colleagues. The authors explain how they solved these problems and give suggestions to help researchers who are starting future trials of HIV vaccines.
First trial of the HIV-1 vaccine in Africa: Ugandan
Roy D Mugerwa, Pontiano Kaleebu, Peter Mugyenyi, Edward Katongole-Mbidde, David L Hom,
Rose Byaruhanga, Robert A Salata, Jerrold J Ellner and the HIV-1 Vaccine Trial Group
Problems in setting up the first trial of an HIV-1 vaccine in Uganda are described here by Mugerwa
and colleagues. The authors explain how they solved these problems and give suggestions to help
researchers who are starting future trials of HIV vaccines
Trials of the HIV-1 vaccine have been conducted in
Europe, North America, Brazil, China, and Thailand.1
The first trial of a candidate vaccine in Africa was
recently completed in Uganda. It involved a ran-
domised, placebo controlled trial of a vaccine in
healthy volunteers at low risk of HIV infection.23The
vaccine, called “ALVAC-HIV,” uses a live recombinant
canarypox vector to express envelope and core genes
of HIV-1.
Many commentators predicted that it would be dif-
ficult to conduct trials of HIV vaccines in developing
countries because of scientific, sociobehavioural,
ethical, and logistical barriers.4–8 Before we started the
trial in Uganda, we gathered data to help us overcome
these potential barriers. We collected epidemiological9
and sociobehavioural10 data about people who had
participated in studies that looked at preparing for
trials of the HIV vaccine. These data showed the preva-
lence and incidence of HIV, behaviours placing people
at risk of becoming infected with HIV, and the social
acceptability of a vaccine against HIV.9–11 The people
received detailed education and counselling about
infection with HIV and about HIV vaccines, and we
recruited some for our trial.11 We organised three open
workshops at the HIV candidate vaccine trial
workshop in Kampala in 1996 to gain consensus from
scientists, policy makers, community representatives,
and the media about how to undertake research into
HIV vaccines.
Despite these initiatives to solve problems before
the trial began, we still encountered many barriers. In
this article, we discuss these barriers and the strategies
that we developed to overcome them.
Social, behavioural, and ethical issues
Public misconceptions and media misinformation
Despite elaborate preparations for the Ugandan trial
of the HIV vaccine, misconceptions arose about the
trial’s purpose among the general public and potential
volunteers. Between 20 and 30 people infected with
HIV, who mistakenly thought that the vaccine was
therapeutic, asked to be enrolled in the study. Three
themes recurred during weekly meetings of focus
groups held for the benefit of potential volunteers:
belief that the vaccine would protect against unsafe sex,
fear that volunteers were to be injected with HIV, and
fear that volunteers would be exposed deliberately to
people infected with HIV.
Most of the confusion was due to widespread
rumours and conflicting media reports about the
vaccine. Many media writers, reporters, and editors
seemed not to understand concepts such as the differ-
ence between drugs and candidate vaccines. One
report in a Ugandan newspaper (New Vision 22
September 1996) referred to ALVAC-HIV as a “candi-
date drug”; some journalists confused the vaccine with
the newly introduced combination of anti-HIV drugs.
The latter error led to false hopes of treatment and to
demands that ALVAC-HIV be given to as many people
as possible. Meanwhile, an ongoing campaign by the
Ministry of Health to increase vaccination of children
against polio was disrupted by allegations that the
polio vaccine was contaminated with HIV.
Political issues and intrigue
Such public stigmatisation of the trial meant that the
matter had to be openly debated in parliament and
approved by a ministerial cabinet before being
sanctioned by the president of Uganda. Many public
figures tried to make political gains from the situation,
by expressing concerns about Ugandans serving as
guinea pigs for experiments that could not be done in
Europe or the United States. On the day of the first
vaccination, a controversial but influential member of
the Ugandan parliament organised a rally, which was
broadcast live on a local radio station. “This vaccine
should be tried on animals in the National Parks. Presi-
dent Museveni has sanctioned its use on Ugandans in
exchange for money to finance his war in the Congo,
he declared, amid wild applause.
Further information
about contributors
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Summary points
During Africa’s first trial of a candidate HIV
vaccine, we encountered social, political, legal, and
ethical barriers to completing the trial
Widespread public and media fear existed about
the risks of participating in the trial, including the
risks of becoming infected and being
experimented on
The lack of adequate ethical guidelines and a
regulatory control mechanism for biomedical
research led to delays in approval of the study
Doctors planning trials of HIV vaccines need to
interact closely with representatives from the
communities involved, the media, volunteers, and
other stakeholders
Education and debate
See also Clinical
review p211
Department of
Medicine, Makerere
University Medical
School, Kampala,
Roy D Mugerwa
Medical Research
Council, Uganda
Virus Research
Institute, Entebbe,
Pontiano Kaleebu
scientific research
Joint Clinical
Research Center,
Kampala, Uganda
Peter Mugyenyi
Rose Byaruhanga
chief counsellor
Uganda Cancer
Institute, Kampala,
Clinical Research
Group of the New
Jersey Medical
School, University
of Medicine and
Dentistry of New
Jersey, Newark, New
Jersey 07107-3000,
David L Hom
assistant professor
Department of
Medicine, Division
of Infectious
Diseases, Case
Western Reserve
University Hospitals
of Cleveland,
Cleveland, Ohio
44106-5083, USA
Robert A Salata
continued over
BMJ 2002;324:226–9
226 BMJ VOLUME 324 26 JANUARY 2002
Ethical concerns
Before the study began, the Uganda network on law,
ethics, and HIV raised concerns about the informed
consent process, possible coercion of volunteers, reim-
bursement, and volunteers’ confidentiality. The net-
work wondered how we would ensure that volunteers
fully understood the risks inherent in participation
during the process of obtaining informed consent. To
resolve this potential problem, we translated the
consent form into the participants’ language and gave
them two weeks to read it and ask questions. We also
tested their understanding of the trial
volunteers who
failed to score at least 70% in these tests were referred
for further education at focus group discussions. We
felt that certain scientific terminology would be difficult
for the general public to understand, so we simplified
some research terms by using culturally and socially
familiar analogies
“air supply” was used for placebo,
“wrapping” for blinding, and “lottery” for random-
To avoid the possibility of coercion, all staff involved
in the study were civilian rather than from a military
background. The only incentives for participants were
treatments for simple conditions such as malaria, free
condoms, counselling, lunch, $10 (£7) for the time
spent in the trial, and reimbursement of transport
costs. With respect to confidentiality, we did not discuss
volunteers’ participation with their spouses, family
members, or friends
this decision was left to the
volunteers themselves.
Safety of the trial participants
The safety of participants in the trial became a lively
public issue. The annual expenditure on health in
Uganda is only $6 per person. Families already
overburdened with sick members would have neither
the motivation nor the resources to look after relatives
falling ill as a result of their participation in the vaccine
trial. A woman living with AIDS was reported in a local
newspaper as saying, “Researchers should take full
responsibility for any consequences of the trial. If
volunteers fall ill, let the scientists look after them.
The vaccine manufacturer had arranged insurance
for volunteers experiencing injuries related to the vac-
cine. Volunteers who tested positive for antibodies to
HIV because of the vaccine were to be offered special
participation cards to protect from being discriminated
against for immigration, insurance, and employment
purposes. Some potential volunteers declined to
participate because of fears about being ineligible for
future vaccine trials and the prospect of inadequate
compensation for their families if they died.
The high prevalence of infection with HIV in some
poor countries, combined with such countries’
inadequate resources for purchasing antiretroviral
medications, makes them ideal testing sites for
candidate vaccines. Ugandans were concerned about
reports in the foreign media that manufacturers might
choose to trial vaccines in poor countries to reduce
product liability in case of injury or to exploit weaker
legal, ethical, or regulatory mechanisms for conducting
biomedical research.
A newspaper report (New Vision 1 March 1997)
asked whether the trial was an example of “hit and run
research” by scientists from rich countries, in which a
poor country was chosen as the setting because the
study would be cheaper and fewer questions would be
asked about safety and ethics. A bishop of the Church
of Uganda warned that the church would resist trials of
HIV vaccines if safety measures for volunteers were not
guaranteed. “People made in the image of God are not
to be used as objects to be disposed of when
experiments fail,” he commented during a church
Scientific issues
The risks to volunteers
We believe that some objections raised in the research
community and among medical professionals were of
importance; others were due to jealousy on the part of
professionals not involved in the trial. For example,
three prominent Ugandan scientists
a geneticist, a
virologist, and an immunologist
raised fears that the
vaccine might undergo dangerous mutations that
could lead people to develop strange abnormalities.
They further argued that the virus might replicate in
vaccinated individuals, causing disseminated disease,
and that the individuals would then infect their
partners through sexual transmission, since the
vaccine uses a live vector.To these doctors, the trial was
comparable to the infamous Tuskegee experiment, in
which American researchers investigating the course
of syphilis denied treatment to African-American
patients deliberately and without the patients’ knowl-
edge. The three scientists claimed that the motive of
our trial was to spread HIV and other viruses among
uninfected Ugandans and eventually to wipe out the
African race, even though a major safety feature of
canarypox is its inability to replicate in mammals.12
The disagreements between scientists created
apprehension among the public. Attempts to clear up
the misunderstandings and allay the anxiety delayed
the start of the trial. The delay caused further specula-
tion about the worthiness of the vaccine, as the public
wondered why the trial was taking so long to start. On
11 September 1996, New Vision quoted experts as say-
ing that the candidate vaccine was safe; this seemed to
contradict an earlier report in the same paper, which
stated that the main aim of the trial was to evaluate
safety in local conditions. The public became
Election posters for President Museveni of Uganda, who was accused of sanctioning the use
of a trial HIV vaccine on Ugandans in exchange for money to finance war in the Congo
Education and debate
New Jersey Medical
School, Newark,
New Jersey
07103-2714, USA
Jerrold J Ellner
Correspondence to:
R D Mugerwa
227BMJ VOLUME 324 26 JANUARY 2002
distrustful, with some asking why, if the vaccine was
safe, were trials being conducted in Uganda. The pub-
lic could not understand that, although no adverse
effects had been found when the HIV vaccine was
tested elsewhere, its safety for the indigenous peoples
of Africa could not be assumed.
Recommendations based on the
Ugandan experience
Many countries lack regulatory mechanisms and a
legal framework for conducting biomedical research.
This, together with absent or inadequate ethical guide-
lines, poses problems that hinder reviews and approv-
als of research. Any country wishing to undertake
research into HIV vaccines needs to have a national
plan that clearly addresses these issues. The recently
formulated ethical guidelines by the joint United
Nations programme on HIV and AIDS (UNAIDS) can
be used as a basis for developing local guidelines.13
National regulatory agencies must be set up early
enough to assess the quality, safety, and potential
efficacy of new vaccines against HIV.
A related issue is the need to have at least two com-
mittees with appropriate representation to review ethi-
cal and scientific aspects of study protocols.In Uganda,
the protocol for the trial had to be approved by six dif-
ferent local committees
ethics, science, technology,
biosafety, drug authority, and social services
there was no national regulatory and control
mechanism for conducting research into HIV vaccines.
This meant that no single committee was considered
competent enough to handle this new and sensitive
subject. The time taken to form the committees
delayed the date that the first participant was enrolled
by one year.
The local population has confidence in trials when
national scientists are seen to participate actively in the
process of developing vaccines. These national
scientists should be involved, therefore, in all scientific
discussions, including those about the choice of
vaccine construct and study design and about
implementation of the study. Early negotiations with
funding and collaborating institutions should include
delicate issues such as patent rights, intellectual
property, compensation for injuries induced by the
vaccine, appropriate treatment for volunteers who
become infected with HIV naturally, and, where
relevant, availability of the vaccine for the participating
country once it is licensed.
Lack of information leads to misinformation.
Politicians and other community leaders should be
given information to encourage public support for
trials of vaccines and to reassure potential study volun-
teers. An information strategy for the public,
volunteers, and the media
who should be given regu-
lar progress reports on various aspects of the trial
essential. An information desk to issue periodic
bulletins and correct misinformation appearing in the
electronic or printed media can help avert crises. An
advisory board including representatives of the local
community may provide a critical link between
researchers and the public. Focus group discussions
provide an opportunity for trial volunteers to air their
concerns and for researchers to understand volun-
teers’ problems and provide information about the
ongoing study as well as about trials in other countries.
Before researchers start any trials of HIV vaccines, they
need to gain support from politicians, the media, and
the general public. Respected local scientists must be
involved in the planning and implementation of stud-
ies to enhance their credibility and to identify cultural
or logistical issues that might hinder recruitment. All
stakeholders must be involved in discussions about
important scientific, social, legal, ethical, and other
concerns before the study begins. The success of future
trials of HIV vaccines in poor countries depends
on adequate mechanisms of regulatory control as
well as a clearly defined approval process for research
We thank the study volunteers for their patience, understanding,
and enthusiasm about being involved in this landmark trial. We
thank the laboratory and clinical staff of the Joint Clinical
Research Center and the Uganda Virus Research Institute. We
acknowledge the support of the Ugandan Ministry of Health
and UNAIDS. We thank Dr Harriet Mayanja for her advice and
contribution to the drafting of this paper.
Funding: Funding was provided by the US National Institute
of Allergy and Infectious Diseases (AI-35173 and AI-36219) and
Fogarty International Center (TW-00011), Bethesda, Maryland,
with support from the Government of Uganda and UNAIDS,
Geneva, Switzerland. The vaccine was provided by Aventis-
Pasteur (formerly Pasteur Merieux Connaught), Lyons, France.
Competing interests: None declared.
Number of people
(15-49 years)
(15-49 years)
(10-14 years)
100 000
200 000
300 000
400 000
500 000
Estimated number of people living with HIV and AIDS in Uganda at
the end of 1999. Data from UNAIDS/WHO epidemiological fact sheet
on HIV/AIDS and sexually transmitted infections. Uganda. 2000
Number of people
Rural Urban Rural
Intercourse of risk Non-regular partner
Proportion of people reporting use of condom during most recent
“intercourse of risk” (left) and proportion of sexually active people
having at least one sexual partner other than their regular partner in
the past 12 months (right) in rural and urban areas of Uganda in
1995. Data from UNAIDS/WHO epidemiological fact sheet on
HIV/AIDS and sexually transmitted infections. Uganda. 2000 update
Education and debate
228 BMJ VOLUME 324 26 JANUARY 2002
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Africa, July 9-14, 2000.
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Sicard D, et al. Safety and immunogenicity of a live recombinant canary-
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(Accepted 22 November 2001)
How can HIV be prevented in South Africa? A social
Catherine Campbell, Yodwa Mzaidume
South Africa’s lack of government leadership in the fight against HIV and AIDS has resulted in
disunity in local HIV/AIDS circles. Catherine Campbell and Yodwa Mzaidume suggest that peer
with local people taking control of HIV prevention efforts
can be successful but depends
on collaboration between many stakeholder groups at local, national, and international level
HIV and AIDS prevention programmes often have
little impact because such programmes have tradition-
ally had a biomedical focus and an emphasis on
individual behaviour. Yet social and community level
factors influence the rate and method of HIV
transmission and can affect the success or failure of
prevention programmes.
In this paper we discuss the importance of these
factors with reference to a South African prevention
programme. We argue that HIV prevention efforts are
affected by the participation of a wide range of groups
and processes at local, national,and international level.
The scope of research, interventions, and policies must
be widened to take this into account.
Community participation
Among marginalised groups in poor countries,
providing information about health risks changes the
behaviour of, at most, one in four people
those who are more affluent and better educated.1This
is because health related behaviours (such as condom
use) are determined not only by individual choice but
also by the extent to which social conditions enable
such behaviours. Health promoters need to develop
policies and interventions that promote “health
enabling” social conditions (conditions that enable and
support health enhancing behaviour).23
Concepts such as community participation and
stakeholder partnerships are increasingly included as
articles of faith in HIV prevention policies and
interventions worldwide. Community led peer educa-
tion and participation by local stakeholders are widely
used strategies.4Our understanding of the processes
through which participation might bring health
benefits, however, is still limited.5
We explored community participation through our
involvement in the evaluation and implementation of
the Carletonville project. This project is a community
led HIV intervention programme in a South African
Summary points
The participation of local community members is
a key element in HIV prevention worldwide
Despite the proliferation of community based
approaches to HIV prevention, few studies have
examined the role of social factors in a
programme’s success
In particular, little is known about why
community participation affects sexual health
Community led peer education involves training
local people to take control of HIV prevention
This type of peer education in marginalised
groups can create trusting and cooperative
relationships in homogeneous local peer groups
The success of peer education also depends,
however, on collaboration among diverse
stakeholder groups at local, national, and
international level
Education and debate
London School of
Economics, London
reader in social
Project, c/o
Hospital, Private
Bag X2023,
Carletonville, 2500,
South Africa
Yodwa Mzaidume
outreach coordinator
Correspondence to:
C Campbell
BMJ 2002;324:229–32
229BMJ VOLUME 324 26 JANUARY 2002
... Concernant, l'expérimentation médicale en milieu carcéral, elle est fortement suspectée vu le contexte (11). Le recours aux 'volontaires' de l'Afrique sub-saharienne dans de larges programmes internationaux de recherche médicale était récurent ces dernières années (12)(13)(14)(15), à l'instar des essais cliniques pour l'élaboration d'un vaccin contre le virus de l'Ebola (11,16), le virus de l'Immunodéficience Humaine (14), ou tout récemment la 'coronavirus disease 2019' (15). ...
Full-text available
The developing World has the largest number of prisoners globally, but their situation is considered «opaque». In recent years, there has been a growing interest from pharmaceutical companies in this part of the world. A growing number of voices is denouncing the spectrum of medical exploitation of prisoners. In Tunisia, there is a great legislative effort to ensure the protection of this vulnerable population. The present history note, the sixth in a series on medical experimentation on prisoners, intended to discuss the situation of medical experimentation in prisons in Africa, the Middle East and part of the Arab world, Tunisia in particular.
... In February 1996 the Minister for Health, while addressing an international network of scientists 9 , stated Uganda's readiness to participate in HIV vaccine clinical trials. The ALVAC (clade B) vCP205 was the first HIV vaccine clinical trial in Uganda and Africa, and formed the foundation for vaccine research in Uganda 4, 10 . ...
Full-text available
Introduction: Infectious diseases and neglected tropical diseases continue to be a major challenge in resource limited settings, causing significant morbidity and mortality. Although vaccines are a key biomedical prevention tool, resource limited settings often lack the infrastructure, regulatory frameworks, and skilled human resource to conduct vaccine clinical trials. To address this gap, the Makerere University Walter Reed Project (MUWRP) was established and has contributed to vaccine research in Uganda and globally. Methods: This was achieved through training a strong vaccine clinical trial workforce; development of requisite clinical trial infrastructure for research activities and management of investigational products; conducting phase I-III vaccine trials and contribution to national ethical and regulatory frameworks that protect participants. Results: As of 2022, MUWRP had successfully conducted and completed five phase I/II HIV vaccine clinical trials, five for Ebola and Marburg, while one phase I/II Schistosomiasis and one phase III COVTD-19 vaccine clinical trial are ongoing. Discussion: The completed vaccine trials provided critical scientific knowledge on the safety and immunogenicity of investigational products which informed the design of better vaccines for diseases of global health importance. Conclusion: Academia, through establishment of appropriate partnerships can contribute to the identification of solutions to complex public health challenges.
... It targets the neurological system in its most severe form, resulting in paralysis [1]. Vaccination is a critical tool for disease prevention and control, but its use has been fraught with controversy worldwide [2,3]. Vaccination is primarily accomplished by preventing infections during childhood, a comprehensive course of injections delivered to infants shortly after birth. ...
Background: Immunization has been shown to be an effective technique for managing and eliminating life-threatening infectious diseases, averting about two million deaths per year. This study aims to assess the knowledge, attitudes, and uptake of polio vaccines among Nigerian women. Study Design: Cross-sectional descriptive design that involved applying an interviewer-administered questionnaire. Place of study: The impact assessment was conducted in the 11 National Stop Transmission of Poliomyelitis Program (NSTOP) intervention states in two geopolitical zones of Northern Nigeria, Northwest and Northeast. Methodology: A total of 2592 caregivers/mothers were interviewed from 262 households in the states. Data collections were done at households in all the intervention states in the two geopolitical zones. The data were analyzed with IBM-SPSS version 25.0. Results: Mothers/caregivers showed high awareness of poliomyelitis vaccines (>99%). A significantly higher proportion (58.4%) of mothers from intervention states said the recent routine immunization section was less than a month ago than 45.7% of women in non-intervention states (P<.05). Mothers/caregivers' attitude to immunization was excellent as 98.8% said all children be fully vaccinated at 12 months. A higher proportion (96.6%) of women from the intervention regions said the time spent on vaccination is worth it than 93.8% of those without the interventions (P=.05). More mothers (95.5%) from the intervention areas have immunized their children within the last years than 91.7% of non-intervention mothers (P<.05). A significantly higher proportion of mothers from intervention regions (96.1%) said their children were immunized as scheduled than 94.4% of those from non-intervention areas (P<.05). Conclusion: Given its success thus far, it is recommended that the NSTOP program be sustained and, if possible, expanded geographically to cover the entire country when resources permit. This step will help keep polio permanently out of the country and reduce mortality among under-five children.
... Taking all information into consideration, we proposed a 'lite' valuation protocol, which requires a reduced sample size by collecting more cTTO data from each respondent. The valuation study was undertaken in Uganda, one of the major focuses of clinical trial research for low-to-middle income countries, specialising particularly, though not only, in human immunodeficiency virus research [30][31][32]. The availability of a value set would promote the use of the EQ-5D-5L tool in trials to measure and quantify health benefits. ...
Full-text available
Objective A ‘lite’ version of the EQ-5D-5L valuation protocol, which requires a smaller sample by collecting more data from each participant, was proposed and used to develop an EQ-5D-5L value set for Uganda. Methods Adult respondents from the general Ugandan population were quota sampled based on age and sex. Eligible participants were asked to complete 20 composite time trade-off tasks in the tablet-assisted personal interviews using the offline EuroQol Portable Valuation Technology software under routine quality control. No discrete choice experiment task was administered. The composite time trade-off data were modelled using four additive and two multiplicative regression models. Model performance was evaluated based on face validity, prediction accuracy in cross-validation and in predicting mild health states. The final value set was generated using the best-performing model. Results A representative sample ( N = 545) participated in this study. Responses to composite time trade-off tasks from 492 participants were included in the primary analysis. All models showed face validity and generated comparable prediction accuracy. The Tobit model with constrained intercepts and corrected for heteroscedasticity was considered the preferred model for the value set on the basis of better performance. The value set ranges from − 1.116 (state 55555) to 1 (state 11111) with ‘pain/discomfort’ as the most important dimension. Conclusions This is the first EQ-5D-5L valuation study using a ‘lite’ protocol involving composite time trade-off data only. Our results suggest its feasibility in resource-constrained settings. The established EQ-5D-5L value set for Uganda is expected to be used for economic evaluations and decision making in Uganda and the East Africa region.
... In the current study, the reported misperception is in line with eagerness amongst most respondents wanting to know more about HIV vaccine studies. Similarly, several studies suggest more basic HIV vaccine education to increase understanding of vaccine related concepts (Flynn, et al., 2005;Jaoko, et al., 2008;Kibuuka, et al., 2009;Mugerwa, et al., 2002;Mugyenyi, 2002;Omosa-Manyonyi, et al., 2011). To promote future participation in HIV vaccine trials, various strategies are needed to suppress this misperception, one being educational campaigns that had been predicted to have a substantial impact on individual willingness to participate in research (Smit, et al., 2006). ...
Background: Despite the successful conduct of three Phase I/II HIV vaccine trials in Dar es Salaam, Tanzania, misperception around the trials has been reported. In this study, misperception means incorrect understanding that in Phase I/II HIV vaccine trial, the researchers infected the volunteers with HIV. We describe the magnitude of misperception around HIV vaccine trials and associated factors among participating communities in Dar es Salaam, Tanzania. Methods: We conducted a cross-sectional study that included 605 respondents aged ³18 years from the communities that participated in Phase I/II HIV vaccine trials. These communities comprised of youths, Police and Prison officers. Respondents were interviewed using a pre-tested questionnaire on socio-demographic characteristics, HIV knowledge, and responses to HIV vaccine trial related questions. Results: Of the 605 respondents, 156 (26%) had misperception that the researchers infected the volunteers with HIV during the trials, while 58% weren’t sure whether the researchers infected the volunteers with the HIV or not. Awareness about progress in HIV vaccine development (adjusted risk ratio (RR)=1.50; 95% CI=1.11 – 2.04), participation in an HIV vaccine sensitization meeting (adjusted RR=1.50; 95% CI=1.14-1.97) and advanced secondary education (adjusted RR=1.92; 95% CI=1.19 – 3.09) were associated with an increased likelihood of having the misperception that researchers infected the volunteers. Nevertheless, the majority (94.5%) of respondents showed a willingness to know more about ongoing HIV vaccine studies while about 44.3% had reservations of taking part in HIV vaccine trials due to fear of getting HIV from the vaccine. Conclusions: The misperception that researchers infected volunteers with HIV in Phase I/II trial is significant and was associated with respondents’ awareness about HIV vaccine development, participation in sensitization meetings and advanced education. Partial knowledge about HIV vaccine trials was of note. Future HIV vaccine trials should strive to address the knowledge gap.
... Communicating risk is complicated [23]; key questions regard the right level of information, how to couch uncertainty and the risk of introducing doubt or legitimising rumours by attempting to counter them. In the context of African vaccine trials, it is suggested that limited knowledge can elevate concerns among participants [24][25][26][27]. However, retention in the DoRIS trial has been very high with >95% attending their clinic visit scheduled for 24 months after the first vaccine dose. ...
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(198) Background The multi-dose regimen is a known barrier to successful human papillomavirus (HPV) vaccination. Emerging evidence suggests that one vaccine dose could protect against HPV. While there are clear advantages to a single dose schedule, beliefs about vaccine dosage in low and middle income countries (LMICs) are poorly understood. We investigated acceptability of dose-reduction among girls, and parents/guardians of girls, randomised to receive one, two or three doses in an HPV vaccine dose-reduction and immunobridging study (DoRIS trial) in Tanzania. Methods Semi-structured interviews with girls (n=19), and parents/guardians of girls (n=18), enrolled in the study and completing their vaccine course. Results Most participants said they entrusted decisions about the number of HPV vaccine doses to ‘experts’. Random allocation to the different dose groups did not feature highly in the decision to participate in the trial. Given a hypothetical choice, girls generally said they would prefer fewer doses in order to avoid the pain of injections. Parental views were mixed, with most wanting whichever dose was most efficacious. Nonetheless, parents sometimes equated a higher number of doses with greater protection. Conclusion Vaccine trials and programmes will need to employ careful messaging to explain that one dose offers sufficient protection against HPV should emerging evidence from ongoing dose-reduction clinical trials support this.
... Although only five discrete vaccine trials are ongoing/ planned for implementation in several countries, sub-Saharan Africa has the human and institutional resources required to host and participate in many more COVID-19 trials, based on current and past experiences with HIV, Ebola, malaria, and tuberculosis vaccine trials [37][38][39][40][41][42][43]. The region also has human-vaccine production plants in Senegal (prequalified yellow fever vaccine) and South Africa (fill-finish) [44,45]. ...
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Objective The COVID-19 pandemic is a biosecurity threat, and many resource-rich countries are stockpiling and/or making plans to secure supplies of vaccine, therapeutics, and diagnostics for their citizens. We review the products that are being investigated for the prevention, diagnosis, and treatment of COVID-19; discuss the challenges that countries in sub-Saharan Africa may face with access to COVID-19 vaccine, therapeutics, and diagnostics due to the limited capacity to manufacture them in Africa; and make recommendations on actions to mitigate these challenges and ensure health security in sub-Saharan Africa during this unprecedented pandemic and future public-health crises. Main body Sub-Saharan Africa will not be self-reliant for COVID-19 vaccines when they are developed. It can, however, take advantage of existing initiatives aimed at supporting COVID-19 vaccine access to resource-limited settings such as partnership with AstraZeneca, the Coalition for Epidemic Preparedness and Innovation, the Global Alliance for Vaccine and Immunisation, the Serum Institute of India, and the World Health Organization’s COVID-19 Technology Access Pool. Accessing effective COVID-19 therapeutics will also be a major challenge for countries in sub-Saharan Africa, as production of therapeutics is frequently geared towards profitable Western markets and is ill-adapted to sub-Saharan Africa realities. The region can benefit from pooled procurement of COVID-19 therapy by the Africa Centres for Disease Control and Prevention in partnership with the African Union. If the use of convalescent plasma for the treatment of patients who are severely ill is found to be effective, access to the product will be minimally challenging since the region has a pool of recovered patients and human resources that can man supportive laboratories. The region also needs to drive the local development of rapid-test kits and other diagnostics for COVID-19. Conclusion Access to vaccines, therapeutics, and diagnostics for COVID-19 will be a challenge for sub-Saharan Africans. This challenge should be confronted by collaborating with vaccine developers; pooled procurement of COVID-19 therapeutics; and local development of testing and diagnostic materials. The COVID-19 pandemic should be a wake-up call for sub-Saharan Africa to build vaccines, therapeutics, and diagnostics manufacturing capacity as one of the resources needed to address public-health crises.
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Introduction Vaccine efficacy testing requires engagement of willing volunteers with high disease incidence. We evaluated factors associated with willingness to participate in potential future HIV vaccine trials in Maputo, Mozambique. Methods Adults aged 18–35 years without HIV and who reported at least two sexual partners in the 3 months prior to screening were enrolled into a 24-month observational study. They were asked at screening and exit if they would be willing to participate in a theoretical HIV vaccine study. Bivariate and multivariate logistic regression analyses were done between willingness to participate, demographic, sexual behavior, and motivational factors for screening visit data. Logistic regression with generalized estimating equations (GEE) was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for factors potentially associated with willingness to participate for data from both visits. Results A total of 577 participants without HIV were eligible, including 275 (48%) women. The mean age was 22.2 (SD ± 3.9) years. At screening 529 (92%) expressed willingness to participate and the proportion remained stable at 378 (88%) of the 430 participants retained through the exit visit (p = 0.209). Helping the country (n = 556) and fear of needles (n = 26) were the top motive and barrier for willingness to participate, respectively. Results from the GEE binary logistic regression (screening visit and exit visit) showed that wanting to learn how to avoid risk behaviors (aOR 3.33, 95% CI: 1.61–6.86) and feeling protected against HIV infection (aOR 2.24, 95% CI: 1.07–4.7) were associated with willingness to participate in HIV vaccine studies. Conclusion The majority of our study population in Mozambique expressed willingness to participate in a theoretical HIV vaccine trial. Participation in a HIV vaccine trial was seen as a way to contribute to the fight against HIV but was associated with some unrealistic expectations such as protection against HIV. This reinforces the need for continuous mobilization and awareness of potential participants to HIV vaccine trial.
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Background Health experts agree that widespread use of safe and effective vaccines will rapidly contain the COVID-19 pandemic. The big question is whether these vaccines can easily be accepted by their end-users. Our study aimed at determining sociodemographic factors associated with acceptance of vaccines and clinical trials of COVID-19 in western Uganda. Method A simplified snowball sampling technique was used to select 1067 respondents of 18–70 years in western Uganda using an online questionnaire from July to September 2020. Vaccine acceptability and risk perception were assessed using odds ratio at 95% confidence interval in R software version 3.6.3. Results There were 1067 participants in the study. The majority were males (73.2%) and age group 31–40 years (32.6%). The acceptance rate for COVID-19 vaccination was (53.6%; 572/1067) with those aged 18–20 years, males, elites at tertiary level of education (degree or diploma), students, Muslims, married, non-salary earners and rural dwellers having better odds and likeliness to accept vaccination. Only 44.6% (476/1067) showed interest in clinical trials among which; males, primary school leavers, students, Christians, un-married, respondents who didn’t earn any salary and rural dwellers had better odds and likelihood to participate in clinical trials. Conclusion There was a low level of vaccine acceptance and clinical trial interest in western Uganda. Minority groups in the study i.e., Muslims, students, primary school leavers, un-married rural dwellers among others showed more interest in vaccination and clinical trials. We anticipated fears in the larger part of this community that health experts need to address through reassurance of the community that vaccines are tested and that they are safe and important if we are to rapidly contain the COVID-19 pandemic.
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Following the discovery of HIV as a causative agent of AIDS, the expectation was to rapidly develop a vaccine; but thirty years later, we still do not have a licensed vaccine. Progress has been hindered by the extensive genetic variability of HIV and our limited understanding of immune responses required to protect against HIV acquisition. Nonetheless, valuable knowledge accrued from numerous basic and translational science research studies and vaccine trials has provided insight into the structural biology of the virus, immunogen design and novel vaccine delivery systems that will likely constitute an effective vaccine. Furthermore, stakeholders now appreciate the daunting scientific challenges of developing an effective HIV vaccine, hence the increased advocacy for collaborative efforts among academic research scientists, governments, pharmaceutical industry, philanthropy, and regulatory entities. In this review, we highlight the history of HIV vaccine development efforts, highlighting major challenges and future directions.
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Several investigators are preparing to conduct efficacy trials of human immunodeficiency virus (HIV) vaccines in the developing world. Failure to adequately address the unique ethical, behavioral, and social issues that surround vaccine testing in that setting will jeopardize the success of these trials and future acquired immunodeficiency syndrome (AIDS) research in the host nation. Twelve investigators from Africa, Asia, North America, and South America reviewed previous experience with HIV trials in developing countries and explored potential solutions to these issues. Host country scientists, government officials, and media must be actively involved in all aspects of the trials. Minimum prerequisites for conducting the trial include the following: (1) researching vaccines active against developing world HIV isolates; (2) establishing and maintaining an adequate technological infrastructure; (3) assessing the feasibility of recruitment in countries where the existence of HIV may be denied; (4) designing methods to obtain informed consent from each individual subject, rather than exclusively from family members or community elders; (5) creating locally appropriate instruments to measure risk behavior; (6) identifying a behavioral intervention for placebo and treatment groups; (7) making available laboratory methods to distinguish between natural HIV infection and vaccine-induced seropositivity; and (8) guaranteeing that an effective vaccine is available free of charge to the placebo group and at affordable prices to other host country residents.
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The implementation of human immunodeficiency virus (HIV) vaccine efficacy trials in developing countries represents an unprecedented series of challenges for the medical and scientific communities, health authorities, policy makers, and the populations of diverse countries. Such trials require great attention, dedication, and information at the earliest possible time from many groups in these communities, as well as the clear and full collaboration of all the national and international institutions and agencies involved. This article discusses suggestions and makes recommendations regarding multiple hurdles to trial implementation, including access to appropriate populations, incidence and natural history of HRV type 1 (HIV-1) infection, definition of efficacy endpoints, and logistical, ethical, regulatory, political, and media issues. The conduct of phase I and II trials in developing countries will be a critical step for appropriate vaccine selection and in helping to identify the country- and community-specific issues and the needs for further implementation. Some countries have already established their own national HIV vaccine development plans. Additional operational and action plans with special emphasis on efficacy trial implementation would be strongly recommended after country-specific preparedness workshops and constitution of national or regional task forces.
Between July and October 1993, 570 19- to 22-year-old volunteers were screened for HIV-1, with a resulting seroprevalence rate of 18.3% (95% CI: 14.0%, 22.6%). A cohort of 249 HIV-1-noninfected military recruits in the Ugandan Peoples' Defense Forces was followed prospectively for up to 18 months to document rates of HIV-1 seroprevalence, seroconversion, and knowledge and attitudes related to vaccine acceptability. The HIV-1 seroincidence rate was 3.56 per 100 person-years (95% CI: 1.49, 5.62) over 309 person-years of observation. At the 3- and 12-month visits, subjects were interviewed on issues of acceptance and knowledge about vaccines, including anti-HIV vaccines in particular. More than 90% believe that HIV vaccines will not cause HIV infection, and if offered, 88% report that they would take the vaccine if they were not already infected. Nonvaccine prevention methods were considered less reliable; monogamy and condom use were considered effective by only 33.5% and 69.3% of the cohort respectively. After completing the vaccine acceptability questionnaire at the 12-month visit, subjects were offered an approved polyvalent meningococcal vaccine as an indicator of general vaccine acceptance. All subjects reported receiving at least one previous vaccination, and 95% willingly accepted the meningococcal vaccination. The Ugandan military is a stable population at substantial risk for HIV-1 infection and may be a suitable population for vaccine efficacy trials.
ALVAC recombinants have been administered to humans and animals by parenteral and oral routes without giving signs of replication, systemic dissemination or severe reaction. In principle, it should be impossible for canarypox recombinants to disseminate in the environment as they would not be synthesised in mammalian cells as complete virus. Canarypox vectors have been safe for humans, in whom there has been no evidence of replication, but more work needs to be done to prove absence of replication. Recombinants are immunogenic by the intramuscular and subcutaneous routes. They are also immunogenic when given orally, but the dose required is still under study. Canarypox recombinants effectively prime the immune system for induction of antibodies and CD8 cell-mediated cytotoxicity by protein antigens. Antibody responses are not influenced by prior inoculation of canarypox, of subunit vaccine corresponding to the gene insert, or of vaccinia. Canarypox virus is attenuated for canaries, in which species it is already widely used. In principle, it is non-infectious for humans or other mammals. It may be infectious for other birds.
Between July and October 1993, 570 19- to 22-year-old volunteers were screened for HIV-1, with a resulting seroprevalence rate of 18.3% (95% CI: 14.0%, 22.6%). A cohort of 249 HIV-1-noninfected military recruits in the Ugandan Peoples' Defense Forces was followed prospectively for up to 18 months to document rates of HIV-1 seroprevalence, seroconversion, and knowledge and attitudes related to vaccine acceptability. The HIV-1 seroincidence rate was 3.56 per 100 person-years (95% CI: 1.49, 5.62) over 309 person-years of observation. At the 3- and 12-month visits, subjects were interviewed on issues of acceptance and knowledge about vaccines, including anti-HIV vaccines in particular. More than 90% believe that HIV vaccines will not cause HIV infection, and if offered, 88% report that they would take the vaccine if they were not already infected. Nonvaccine prevention methods were considered less reliable; monogamy and condom use were considered effective by only 33.5% and 69.3% of the cohort respectively. After completing the vaccine acceptability questionnaire at the 12-month visit, subjects were offered an approved polyvalent meningococcal vaccine as an indicator of general vaccine acceptance. All subjects reported receiving at least one previous vaccination, and 95% willingly accepted the meningococcal vaccination. The Ugandan military is a stable population at substantial risk for HIV-1 infection and may be a suitable population for vaccine efficacy trials.
The ethics of the design of clinical trials to prevent transmission of HIV-1 from mother to child in developing countries have been criticized.[*][1] However, a discussion of ethical principles in biomedical research that ignores the socioeconomic heterogeneity of society is not ethical and not
A live recombinant canarypox vector expressing HIV-1 gpl20 MN tm/gag/protease LAI (ALVAC-HIV, vCP205) alone or boosted by a p24E-V3 MN synthetic peptide (CLTB-36) was tested in healthy volunteers at low risk for HIV infection for their safety and immunogenicity. Both antigens were well tolerated. ALVAC-HIV (vCP205) induced low levels of neutralizing antibodies against HIV-1 MN in 33% of the volunteers. None of them had detectable neutralizing antibodies against a nonsyncytium-inducing HIV-1 clade B primary isolate (Bx08). After the fourth injection of vCP205, CTL activity was detected in 33% of the volunteers and was directed against Env, Gag, and Pol. This activity was mediated by both CD4+ and CD8+ lymphocytes. On the other hand, the CLTB-36 peptide was poorly immunogenic and induced no neutralizing antibodies or CTLs. Although the ALVAC-HIV (vCP205) and CLTB-36 prime-boost regimen was not optimal, further studies with ALVAC-HIV (vCP205) are warranted because of its clear induction of a cellular immune response and utility as a priming agent for other subunit antigens such as envelope glycoproteins, pseudoparticles, or new peptides.
An HIV-1 vaccine offers the best long-term hope to control the AIDS pandemic, especially in less-developed countries. To ensure its future availability we need to increase our research efforts today, including clinical trials. Although small-scale clinical trials of HIV-1 vaccines have been underway since 1987, the first phase III efficacy trials started only recently in the USA and Thailand. Initial results from these trials will be available within the next 2-3 years, and we must start planning now how vaccines should be used if found to be effective. In the meantime, the continuing promotion of the parallel development and assessment of other candidate vaccines is important. Financial mechanisms should also be developed as an incentive to industry and to ensure equitable distribution of future vaccines in less-developed countries. Moreover, a concerted effort is needed to ensure the development and future availability of appropriate vaccines for Africa.