www.ncbi.nlm.nih.gov
Abstract
Abstract
The underpinning theme of the 2016 INTEREST Conference
held in Yaoundé, Cameroon, 3–6 May 2016 was ending AIDS as a public
health threat by 2030. Focused primarily on HIV treatment, pathogenesis
and prevention research in resource-limited settings, the conference
attracted 369 active delegates from 34 countries, of which 22 were in
Africa. Presentations on treatment optimization, acquired drug
resistance, care of children and adolescents, laboratory monitoring and
diagnostics, implementation challenges, HIV prevention, key populations,
vaccine and cure, hepatitis C, mHealth, financing the HIV response and
emerging pathogens, were accompanied by oral, mini-oral and poster
presentations. Spirited plenary debates on the UNAIDS 90-90-90 treatment
cascade goal and on antiretroviral pre-exposure prophylaxis took place.
Joep Lange career guidance sessions and grantspersonship sessions
attracted early career researchers. At the closing ceremony, the Yaoundé
Declaration called on African governments; UNAIDS; development,
bilateral, and multilateral partners; and civil society to adopt urgent
and sustained approaches to end HIV by 2030.
Introduction
The goal to end AIDS as a public health threat by 2030 [1]
was the underpinning theme of the 10th International Workshop on HIV
Treatment, Pathogenesis, and Prevention Research in Resource-Limited
Settings (2016 INTEREST Conference) held in Yaoundé, Cameroon, 3–6 May
2016. The meeting attracted 369 active delegates from 34 countries of
which 22 were in Africa (Cameroon, South Africa, Nigeria, Cote D’Ivoire,
Kenya, Uganda, Zambia, Zimbabwe, Botswana, Ghana, Senegal, Tanzania,
Benin, Burkina Faso, Congo, Gabon, Guinea, Liberia, Malawi, Namibia,
Rwanda and Swaziland). Spirited plenary debates on the UNAIDS 90-90-90
(90-90-90 refers to the targets of 90% of people living with HIV knowing
their serostatus, 90% of those who know they are HIV-positive being on
antiretroviral treatment [ART] and 90% of those on ART achieving viral
suppression. This translates into 73% of all people living with HIV
being virally suppressed) treatment cascade goal for 2020 [2]
and on antiretroviral pre-exposure prophylaxis (PrEP) took place. There
were presentations on treatment optimization, acquired drug resistance,
care of children and adolescents, laboratory monitoring and
diagnostics, implementation challenges, HIV prevention, key populations,
vaccine and cure, hepatitis C, mHealth, financing the HIV response and
emerging pathogens [3].
In
addition to oral, mini-oral and poster presentations, early morning
Joep Lange research career guidance sessions saw mid-career and senior
investigators explain how they got started on a research career and give
advice on how to get funded, choose a mentor and get published.
Parallel research grantspersonship sessions were presented by ANRS
(France Recherche Nord & Sud Sidahepatites); Fogarty International
Center, US National Institutes of Health; and EDCTP (European &
Developing Countries Clinical Trials Partnership).
HIV in Cameroon
Cameroon’s
Minister of Public Health, André Mama Fouda, opened the conference. Dr
JB Elat, Permanent Secretary of the National AIDS Programme, presented
an overview of HIV in Cameroon. HIV prevalence in 2011 was 4.3%, with
urban populations and women disproportionately affected: 5.6% of women
versus 2.9% of men. Compared to the general population, men who have sex
with men (MSM) have 8–14× higher (24–44%), truck drivers have 5× higher
(16%) and female sex workers (FSW) have 6× higher (36%) HIV prevalence.
Clients of FSW account for 36% of new HIV infections annually. After
Cameroon’s ART programme began in 2000, HIV prevalence fell by 20%
between 2004 and 2011 from 5.5% to 4.3%. Prenatal consultations for
prevention of mother-to-child transmission (PMTCT) increased steadily
from 2009, with attendance reaching 74% in 2015. Between 2005 and 2015,
the number of people on ART increased 10-fold and approximately 7,000
children now receive ART. In 2015, 882,639 Cameroonians were tested for
HIV. Cameroon aims to increase access to HIV testing and treatment
services, reduce stigma, strengthen supply chains, tailor HIV prevention
for key populations and build civil society capacity. Poor retention in
care remains a weak link in Cameroon’s progress towards 90-90-90 [4].
Achieving 90-90-90
Passionate
debate presenting opposing viewpoints on 90-90-90 saw pessimists
emphasize factors preventing achievement of the Fast-Track Initiative
targets: insufficient resources (human, infrastructure, financial),
inability to reach all people living with HIV (PLHIV) and retain them in
care, risk of emerging drug resistance and international donor fatigue.
Optimists highlighted the 17 million PLHIV on ART globally,
opportunities to halt the HIV epidemic now and examples of countries
close to achieving 73% viral suppression targets. Although achieving
90-90-90 is judged desirable, during the debate more conference
participants became convinced the proposed time frame is too short.
The first 90: HIV testing
More
than 150 million HIV tests are conducted in low- and middle-income
countries annually and although the goal of diagnosing 90% of PLHIV is
achievable, testing must be performed with 100% accuracy because of the
profound consequences of misdiagnosis at both the individual and
population level [5].
Outreach programmes are necessary for marginalized, stigmatized, often
criminalized and hard to reach key populations. Community-based testing
can reach healthy people early in their infection and link them to care [6].
Identifying all HIV+ children and adolescents requires case-finding
approaches for chronic HIV survivors, intensified facility-based testing
and decentralized and simplified HIV testing at point of care [7].
The second 90: ART
The
World Health Organization recommends ART be offered immediately to
everyone diagnosed with HIV infection, regardless of their CD4+ T-cell count measuring immune status [8]. Globally, 17 million people (46% of PLHIV) are on ART [9].
Voluntary licensing is enabling generic companies to provide
antiretroviral (ARV) drugs in effective, well tolerated, and
quality-assured individual or combination formulations for 100–130 USD
per year. Voluntary licensing of drugs such as dolutegravir and
tenofovir alafenamide may reduce this cost to 60 USD/year; however, more
efficacy and safety data in pregnant women and HIV–TB-coinfected
patients are needed [10].
Robust supply chains are essential to prevent stock-outs and ensure
continuity of ART. Fulfilling high-income countries’ commitment to spend
0.7% of gross national income on overseas development assistance [11]
can assist resource-limited countries but increasing domestic
health-care funding in sub-Saharan Africa to reach the Abuja target of
15% of annual government expenditures being devoted to health will
reduce donor dependency and facilitate sustainable programmes [12].
Building on the global success of generic ART, generic versions of
drugs for tuberculosis, cancer and hepatitis B and C could facilitate
drug access for people in resource-limited settings around the world at
very affordable prices.
The third 90: viral suppression
Tracking
viral suppression requires rapid scale-up of viral load monitoring,
necessitating improved efficiencies in sample collection, transportation
and laboratory performance; timely transmission of results to clinics
and patients; and rapid appropriate action [13]. Treatment retention in Africa at 36 months is estimated at only 65% [14]. Poor adherence leads to drug resistance [15],
requiring effective interventions, including mHealth and group
delivery, to support retention in care and adherence. Innovations must
be anchored in a comprehensive understanding of the multiple barriers
facing people on ART, including adolescents who have important retention
and adherence challenges.
The WHO
recommends that ART scale-up be accompanied by high-quality HIV drug
resistance surveillance, achieved by investing in human and laboratory
resources, innovative and efficient technical approaches, robust supply
chains and quality assurance measures. Political and community
commitment is needed to overcome limited laboratory capacity in
sub-Saharan Africa and support studies identifying suitable ARV options.
These include the ultra-deep pyrosequencing work showing that protease
inhibitors and mara-viroc are likely to be effective in young
Cameroonian children (the author of this abstract received the Joep
Lange award for the top-scoring abstract by an African scientist at the 10th INTEREST Conference) [16], as are protease inhibitors in Ugandan children [17].
HIV prevention
More
than 10 million voluntary medical male circumcisions (VMMC) have been
performed, with high adult MC prevalence countries moving to establish
sustainable VMMC HIV prevention programmes focused on early infant and
early adolescent MC [18].
PrEP
with ARV drugs has achieved regulatory approval in South Africa and
Kenya, following WHO guidance recommending PrEP when HIV incidence is 3%
or more [8].
Follow-on studies and demonstration projects of oral PrEP among
serodiscordant couples and MSM have shown higher adherence than in trial
settings, possibly because people know that they are taking an
effective product [19].
Novel products and delivery options under investigation include
injectables that would be taken every 2 to 3 months, vaginal gel and
ring formulations, and monoclonal antibodies. PrEP works for anyone
experiencing a high risk of HIV exposure during a specific time of his
or her life. A debate on whether Africa was ready for PrEP persuaded
some who were sure it was ready to wonder whether regulatory,
logistical, equity and other issues had all been adequately addressed.
Importantly, PrEP implementation requires intensified investment in HIV
testing strategies across Africa, which would result in the increased
knowledge of serostatus that can improve entry into the 90-90-90
treatment cascade.
Vaccine and cure
The search for a vaccine, following the promising results of RV 144 [20],
includes active and passive approaches to HIV prevention.
Clade-specific trials in South Africa and elsewhere are part of the
pox-protein public-private partnership (P5) evaluating pox-protein
candidates. Hypothesis-generating Phase IIb trials are underway of
passive immunisation strategies involving monoclonal antibodies using
trivalent and tetravalent vectors to obtain broader coverage against HIV
[21].
Research to understand differences in viral reservoirs with
implications for cure strategies has found that Ugandans without HIV
infection have increased immune activation and lymph node pathology that
resembles early HIV infection among patients in Minnesota, USA [22].
If they acquire HIV in an environment where life-long exposure to
various pathogens already predisposes them to high levels of T-cell
activation, they may develop a larger HIV reservoir leading to
persistent immune activation, subsequent lymph node fibrosis and reduced
immune reconstitution. Pre-existing T-cell activation thus may account
for population differences in responsiveness to immune therapy
strategies, with fibrosis limiting diffusion of therapeutic agents into
lymph nodes where the virus replicates.
Key populations
Success
in bringing down HIV prevalence among sex workers in Rwanda, Burkina
Faso, Kenya and Namibia highlights data gaps on successful interventions
among men involved in sex work, regular partners of female sex workers
and girls under 18 years who receive money or goods in exchange for
sexual services. Exciting new developments include studies of PrEP use,
integration of HIV and sexual and reproductive health services, and use
of mobile technology, social media and biometric measures to assist in
studying mobile sex work populations. Striking data on the use of
heroin, tramadol and other opioids have led to the African Union Plan of
Action on Drug Control that recognizes the burden of HIV and hepatitis C
among people who inject drugs in Africa. Political barriers to holistic
harm reduction remain for illicit drugs and for alcohol, a psychoactive
substance with dependence-producing properties that has been strongly
linked to HIV risk in Africa and around the world [23].
MSM have high HIV risks and continue to be criminalized in many African
countries, making it difficult to reach them with services. In eight
African countries, between 25 and 65% of these men aged 18–19 years are
meeting male sexual partners online [24], suggesting that social media and mobile platforms could help increase their access to HIV prevention and treatment.
Emerging pathogens – lessons learned for and from HIV
The
Ebola epidemic of 2014–2015 and epidemics of re-emerging pathogens,
such as Zika and Lassa Fever, have shown that high-quality studies can
run alongside the outbreak response, but health-care systems must be
strengthened now before more epidemics occur. Designing and running
Ebola clinical trials proved challenging in Guinea, Liberia and Sierra
Leone. In Guinea, a ‘ring vaccination’ trial design was used to evaluate
a vaccine candidate, with real-time modifications to take account of
the rapidly changing epidemic and logistical issues [25].
The impact of favipiravir on Ebola virus disease was evaluated in a
single arm, proof-of-concept trial that found it well-tolerated but
could not draw firm conclusions about efficacy [26].
Ideally, outbreaks of emerging and re-emerging pathogens should be
anticipated and potential drugs and vaccines for them investigated on an
ongoing basis so that efficacy trials can be initiated quickly when an
outbreak occurs. Engaging stakeholders, including community
stakeholders, at all stages of a clinical trial contributes to robust
trial design, facilitates trial conduct by addressing rumours and
enhancing participant retention, and helps ensure ownership of the
results for action [27].
Addressing ethical issues is key to ensuring that studies are conducted
ethically, communities support them and post-trial legacies are assured
[28].
Robust public health infrastructure, appropriate legislation and
community involvement were key in containing an Ebola outbreak of 20
cases in Nigeria and subsequent health-care system investments have
upgraded disease surveillance, research infrastructure and treatment
facilities [29].
Conclusions
Although
ART coverage in sub-Saharan Africa increased from 24% in 2010 to 54% in
2015, reaching a regional total of 10.3 million people [9],
late diagnosis of HIV infection, loss to follow-up and poor ART
adherence contributed to 790,000 people dying of AIDS-related causes in
2014. New adult HIV infections remain a concern: 25% are adolescent
girls and young women and more than 20% are from key populations. An
estimated 25.5 million people are living with HIV in sub-Saharan Africa,
with women accounting for 56% [9]. There has been a 48% decline in new HIV infections among children in the 21 Global Plan priority countries [30], but 190,000 African children acquired HIV infection in 2014 [31].
The 10th INTEREST Conference
heard a call for leadership and activism among HIV investigators and
physicians to show global solidarity with PLHIV worldwide and to ensure
that resources are used effectively. Sub-Saharan Africa loses over 150
billion USD/year through illicit financial flows [32], corruption and money laundering [12].
This money could replace international donations and fund health care
throughout the continent. At the closing ceremony, the Yaoundé
Declaration [33]
(Additional file 1) was read out, calling on African governments;
UNAIDS; development, bilateral, and multilateral partners; and civil
society to adopt urgent and sustained approaches to end HIV by 2030 [34,35].
Acknowledgments
The
authors thank Wendy Smith (Wordsmiths International Ltd, Wells, UK) for
providing meeting notes that were used as background materials for
writing the manuscript. The INTEREST 2016 organizers
acknowledge the support of the Ministry of Public Health, Cameroon; the
National Institutes of Health and the Fogarty International Center, USA;
the ANRS (France Recherche Nord & Sud Sidahepatites); and the
following companies: Gilead Sciences, Janssen Pharmaceuticals, AbbVie,
ViiV Healthcare, Roche and Mylan.
See also
The History of AIDS in Africa
AIDS (tag in our blog)
The History of AIDS in Africa
AIDS (tag in our blog)
Footnotes
Additional file
Additional file 1: The Yaoundé Declaration can be found at https://www.intmedpress.com/uploads/documents/3939_Hankins_Addfile1.pdf
Disclosure statement
All
12 authors reviewed previous drafts of the manuscript and approve its
contents. None of the authors have a conflict of interest, with the
exception of CABB of the company Virology Education that provided
logistical support for the conference.
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