In this episode of AVAC’s Px Pulse podcast series, Slim Abdool Karim, co-principal investigator of the landmark CAPRISA 004 study, talks about why designing trials with oral PrEP is a must—scientifically and ethically.
PrEP and Trial Design — A no brainer for some
HIV Prevention in the Era of PrEP: The implications of TDF/FTC for biomedical prevention trials
On Thursday, October 26, colleagues from the Treatment Action Group (TAG), along with advocates, researchers and GPP practitioners, discussed the recommendations from the TAG’s recently released white paper, HIV Research in the Era of PrEP: The Implications of TDF/FTC for Biomedical Prevention Trials.
The effectiveness and increasing availability of oral PrEP raises questions about how it should be incorporated into clinical trial designs for next-generation HIV prevention options. This paper explores ethics, the scientific literature to date, and advocates’ views on the issue.
PrEP and Trial Design — A no brainer for some
Clinical trials for new HIV prevention methods offer participants counseling and access to the existing ways to protect oneself from HIV. It’s called the “standard of prevention” and is a package of prevention methods and services.
Now that oral PrEP is a proven HIV prevention method and WHO-recommended, some trials are adding it to the package. And that makes trials more complex. That’s a good problem to have, says Slim Abdool Karim, the director of the Centre for the AIDS Program of Research in South Africa, also known as CAPRISA. As the co-principal investigator of the landmark CAPRISA 004 tenofovir gel study and the recipient of multiple awards for his research, Karim brings incomparable perspective to this question. In this interview with AVAC’s Jeanne Baron, Karim talks about why designing trials with oral PrEP is a must—scientifically and ethically.
This interview is part of an ongoing series, and look out for our upcoming podcast—Px Pulse, which will feature interviews and discussions that explore vital topics in HIV Prevention research today. Tell us what you think!
Click on the links below to learn more about PrEP and standard of prevention in trials:
Px Wire July-September 2017, Vol. 10, No. 3
This issue of AVAC’s quarterly newsletter, Px Wire, is now available. Check it out for a deep dive into the data that suggest men who have sex with men may be able protected by oral PrEP, even if they don’t dose every day—and for the reasons why these data do not apply to women. You’ll also find out why messages about global AIDS are on our mind—and what we’d change about the current global conversation.
New Px Wire: PrEP, money and more
The latest issue of AVAC’s quarterly newsletter, Px Wire, is now available. Check it out for a deep dive into the data that suggest men who have sex with men may be protected by oral PrEP, even if they don’t dose every day—and for the reasons why these data do not apply to women. You’ll also find out why messages about global AIDS are on our mind—and what we’d change about the current global conversation.
Because money matters as much as messages, we’ve provided a centerspread that summarizes current investments, and trends over time, in HIV-prevention research and development. This full-color feature is excerpted from the recently-released report on HIV prevention research and development investment produced by AVAC and partners in the field.
Evolving Context for HIV Prevention Research (Map)
A global map showing selected HIV prevention research and oral PrEP status.
PrEP’s Entry into Kenya: Communities hold the key
On July 4, Kenyan civil society, including groups working on the frontlines of HIV prevention and treatment, called a meeting with the leaders and implementers of oral pre-exposure prophylaxis (PrEP) activities in the country. The meeting’s purpose was to have a frank discussion about the role of community support in the national PrEP program, and touch on progress with HIV self-testing implementation. Some of the civil society groups, like ISHTAR-MSM and Bar Hostess Empowerment Support Programme (BHESP), are also involved in implementation—they’ve partnered with Jilinde, a national-scale PrEP rollout project, or LVCT to help identify potential PrEP users, spread messages and deliver services.
Other CSOs in the room, such as Survivors, an NGO of female sex workers in Busia, Western Kenya, and the Kenya Legal & Ethical Issues Network on HIV and AIDS, aren’t delivering services, but, like BHESP and ISHTAR, represent advocates, activists and potential PrEP users. All were united by a common goal of shining a spotlight on community and civil society engagement as a critical link to successful PrEP rollout in the country.
In the months leading up to the May 4 launch of Kenya’s national program, many civil society groups gave inputs to the national PrEP technical working group (TWG), convened by the National AIDS & STI Control Program (NASCOP). This work is ongoing, with civil society represented on the various rollout committees.
But being invited to the table is not the same as setting the table—and at the July 4 meeting, the organizers structured a packed agenda in order to learn about progress and plans, as well as to express their views on priority issues.
Rosemary Mburu, Executive Director of WACI Health, and Nelson Otuoma, Executive Director of the National Empowerment Network of People living with HIV/AIDS in Kenya (NEPHAK), co-facilitated the meeting.
Mburu noted that many issues remain to be worked out if PrEP is to achieve its true potential in the country: communities need to be continuously informed and engaged; sustainable financing that includes domestic resources has to be secured; and county-level plans have to be designed, with appropriate material for use at the community level.
Otuoma, who recently won the inaugural Maisha Conference Award for his work in community advocacy, reminded everyone of PrEP’s massive potential in Kenya, but only “if we can overcome barriers like stigma.”
“Just like ARVs changed the face of HIV from a killer disease to a chronic condition, PrEP can help the country move further and faster along the HIV prevention roadmap,” he said.
Jointly presenting the viewpoint of young women to the convening, 24-year-olds Anastacia Kendi and Grace Kamau, part of the youth-serving group Sauti Skika, welcomed the launch of PrEP, calling it “an empowering tool to women and girls.”
“I hope there will be more investments in ensuring the interventions are made to work for women and girls’ needs alongside the needs of boys and men.”
Three established PrEP implementation projects in Kenya—the Partners Scale Up Project; Introducing PrEP in Combination Prevention (IPCP); and Bridge to Scale (also known as Jilinde, Kiswahili for “protect yourself”)—shared updates and lessons learned.
Speakers from these projects reported excitement about PrEP as a new prevention method in the country. Yet they said that there were obstacles when it comes to actual use. While there are reports of high demand in some communities and programs, there are also places where the number of people signing up to use PrEP is lower than the expected enrollment.
Adherence (taking the pill daily as prescribed) stands out as challenge; and many people who are using PrEP have been “lost to follow-up”, public-health lingo for a participant who starts taking a medication such as PrEP or antiretroviral treatment (for people living with HIV) but along the way stops returning for their monthly refill visits without informing their clinic.
In all updates, community engagement stood out as a critical part of the solution.
Dr Elizabeth Irungu, the director of the Partners Scale Up Project in Thika and Kisumu in central and western Kenya respectively, said the project team is finding broad acceptance for PrEP among heterosexual, HIV-serodiscordant couples.
“We now have something to give the HIV-negative person,” she stated.
Partners dispenses PrEP from Comprehensive Care Centres (CCCs), clinics that are primarily involved with HIV prevention and treatment.
“We think that by adding PrEP for HIV prevention for HIV-negative people, there may be a reduction of the stigma associated with going to CCCs, as both positive and negative people can get services there. However, there is a lot of work to be done to reduce stigma around HIV, and around going to a CCC,” said Irungu.
By June 2017 the project, funded by the Bill & Melinda Gates Foundation, had enrolled 290 couples. They hope to reach 4,800 couples by 2019—200 in each of 24 centers.
Jhpiego’s Jilinde project, also funded by the Gates Foundation, is working among men who have sex with men, sex workers and adolescent girls and young women at high risk for HIV.
Tom Marwa, Senior Technical Advisor at Jhpiego, informed the convening that 2,300 users were enrolled between February and June 2017 through 17 Jilinde PrEP delivery centres in 10 counties of Kenya. The program is on track to reach 20,000 PrEP users by 2020, and its experiences will contribute important lessons to other African countries planning to introduce PrEP, he added.
Introducing PrEP in Combination Prevention (IPCP) consortium, led by LVCT Health, is implementing PrEP among the same populations as Jilinde. The project started before the national launch of PrEP and was designed to test whether PrEP could be delivered to these populations from standard healthcare facilities.
Dr Michael Kiragu, who leads IPCP, said he was heartened to see good support of PrEP during the formative studies phase of the project. Yet out of a target of 2100, only 1626 PrEP users (77 percent of target) were enrolled and retained into the program. He said that this was a sign that there were barriers to PrEP uptake and use.
The project team has learned that an individual’s community has a huge influence on their decision-making, and stigma remains a barrier to PrEP uptake and adherence, he noted.
“PrEP users at IPCP clinics complain about the rattling of pills in the bottle, the color of the pill (blue), and about disapproval from their husbands, boyfriends or parents.” To address some of these challenges clinics have started giving out cotton balls to mute the rattling of pills, holding community dialogues on PrEP with men, and offering couples counseling. In addition, people using PrEP have pointed to support groups as one of the most important resources they depend on to help them maintain good adherence.
Dr Sarah Masyuko, NASCOP’s HIV testing and PrEP Manager, gave a keynote at the convening.
The first phase of communications and advocacy on PrEP had been hugely successful, she noted, with widespread media and social media engagement reaching all corners of the country. On the sustainability question raised by civil society, Dr Masyuko said the Ministry of Health is holding consultations with PEPFAR, The Global Fund, and private companies in Kenya to secure long-term financing for PrEP.
“PrEP rollout is unlike any other,” she noted, citing difficulties with gathering reliable data for an intervention that people can get on and off at will. She said the government is looking into an electronic system with unique identifiers that will help better track users nationwide. She challenged implementing partners to do even more to reach communities with accurate messages on PrEP and HIV self-testing, and that dispel rumours and misconceptions that stand in the way of uptake among eligble persons, defined in the Kenya national guidelines as anyone at substantial ongoing risk of HIV infection.
This background information provided the platform for a robust discussion of what’s working—and what else is needed. Civil society representatives were clear that PrEP messages needed to be highly tailored and that organizations with different positions in the communities needed to have the right infomation to deliver through trusted channels. This could mean fine-tuned messages that go beyond the category of “adolescent girl or young woman,” “sex worker,” or “MSM” to consider other life circumstances—how openly a person is living with his or her identity, their community support, their influencers, et cetera. Some of this work is underway; much more will come from civil society groups leading work on the ground and feeding back on what works and what doesn’t.
From the convening, Peter Mogere, lead pharmacist at the Partners Scale Up Project and 2017 AVAC Fellow, presented a 9-point list of ‘Civil Society Asks’ to the National Technical Working Group (TWG) on PrEP, on 7 July. Along with allocating domestic resources for PrEP, the asks focus on community engagement at the grassroots level; health care provider training; and combating human rights violations, stigma and discrimination.
Mogere said the TWG was highly receptive to the civil society asks; “The TWG Chair said she was looking forward to involving the civil society in reaching out to all communities that would benefit from PrEP. She noted that civil society works on the ground in all regions of the country, including rural areas, and reaching all people at risk of HIV infection is high on the priorities of the national PrEP program.”
As a next step, the advocates are planning to stay connected and to develop and advance priorities that they can pursue through meetings where civil society sets the agenda. The history of the epidemic tells us this is how things change.
AVAC provided technical and financial support for the convening, which was co-hosted by AVAC partners WACI Health and the National Empowerment Network of People living with HIV/AIDS in Kenya (NEPHAK), in collaboration civil society organizations ISHTAR-MSM; Survivors; International Network of religious leaders living with or personally affected by HIV (INERELA+)-Kenya; National Organization of Peer Educators (NOPE); I Choose Life; Health Gap; Bar Hostess and Empowerment Programme (BHESP); Keeping Alive Societies Hope (KASH); Persons Marginalized and Aggrieved (PEMA); Kenya Legal and Ethical Issues Network on HIV and AIDS (KELIN); and Sauti Skika, a project affiliated with NEPHAK.
Global HIV Prevention R&D Investment by Technology Category, 2000-2016
In 2016, funding for HIV prevention R&D decreased by 3 percent (US$35 million) from the previous year, falling to US$1.17 billion. Funding in 2016 signals the lowest annual investment in HIV prevention R&D in more than a decade.
New Report: Investment trends for HIV prevention and cure R&D
It is said success breeds success. 2016 was a year of encouraging progress, indeed success, on a number of HIV prevention fronts. Two trials of the dapivirine vaginal ring showed efficacy, a spate of new vaccine and antibody trials began, and a trial of long-acting injectable PrEP launched.
Those developments are successes by any measure, and yet this year’s funding report from the Resource Tracking for HIV Prevention Research & Development Working Group (Working Group) shows that prevention funding continues to slowly decline overall. Over the same time, cure research got a big bump from global funders. A separate cure-focused brief from the Working Group, developed in partnership with the International AIDS Society (IAS), showed investment in cure research tripled since 2012.
Released today, the Working Group’s latest annual report on global investment in biomedical HIV prevention shows that overall funding for HIV prevention research and development (R&D) has fallen to its lowest level in a decade.
- Download HIV Prevention Research & Development Investments, 2016: Investment priorities to fund innovation in a challenging global health landscape
- Download graphics from the report
- Download the press release
- Download Global Investment in HIV Cure Research and Development in 2016: Funding for a cure remains a priority
The prevention research report notes that funding for preventive vaccine research constituted the bulk of all investments, followed by investments in cure, microbicides, prevention of mother-to child transmission (PMTCT), PrEP, medical male circumcision (VMMC), treatment as prevention (TasP) and female condoms. Over half of the HIV prevention option tracked by the working group experienced a decline. These trends are somewhat reflective of the cyclical nature of large-scale clinical trials—when trials end, funding drops off. Likewise, as some interventions enter full-scale rollout, like PrEP, VMMC and TasP, research in this area can be expected to slow down. Nevertheless, the overall trends bear close watching and strong advocacy to ensure that research continues. The progress of this research in the context of flat funding should not be misconstrued. Flat funding will not get us where we need to go next.
Taking stock of all that’s been accomplished with a decade of flat funding, it’s important to note that two million people continue to be infected each year. To achieve control of the epidemic, the field must also take stock of what could be achieved with the right priorities.
The right products need to be tested in the populations who need them most, and research does not always connect well to the people who are most at risk. The report explores the demographic breakdown of almost 700,000 participants in ongoing HIV prevention trials in 2016, with the majority of these volunteers residing in sub-Saharan Africa, most notably in treatment as prevention trials in Botswana, Uganda, Kenya and South Africa. Only one in eight trial participants in 2016 belonged to a population most affected by HIV, including MSM and transgender women, injection drug users and cisgender women.
An intensifying trend towards a small number of large investors is concerning. Together, the US public sector and the Bill & Melinda Gates Foundation (BMGF) represented 88 percent of the total global investment in 2016, compared to 81 percent in 2015. Simply put, for every dollar spent on HIV prevention R&D in 2016, 88 cents came from just two donors.
On a hopeful note, global investment in research toward an HIV cure increased to US$268 million, a 33 percent increase over 2015 levels, with a number of new funders, and an expanded research portfolio at the US National Institutes of Health. The majority of investments (US$253.2 million) came from the public sector with US$13.8 million invested by philanthropies such as Aids Fonds, amfAR, CANFAR, the Bill and Melinda Gates Foundation, Sidaction and Wellcome Trust.
This is a vigorous period in research and development, reflecting a growing recognition from the global community that research has to be part of the long-term fight to end the HIV epidemic. Now is the time to support continued progress with additional, well-targeted resources.
The Resource Tracking Working Group hopes these reports will serve as tools for advocacy and be used to develop public policy that accelerates scientific progress. We thank all of the individuals who contributed data to the report and who gave time and effort as trial participants.
Check out the report, share it with your fellow advocates, and be sure to let us know if your organization is either a funder or recipient of HIV prevention grants or if you have further questions or information about resource tracking at all!
Press Release
Declining Funding and Shrinking Donor Base Imperils Continued Success of HIV Prevention Research; European Countries Called to Renew Support
Contacts
AVAC: Kay Marshall, [email protected], +1-347-249-6375
IAVI: Rose Catlos, [email protected], +1-212-847-1049
New York and Paris —
A new report released today ahead of the 9th IAS Conference on HIV Science documents 2016 funding and highlights a continuing trend of flat or declining funding and its potential impact on further innovation in HIV prevention research and development (R&D).
The Resource Tracking for HIV Prevention R&D Working Group’s (RTWG) 13th annual report, HIV Prevention Research & Development Investments, 2016: Investment priorities to fund innovation in a challenging global health landscape, documents the lowest annual investment in HIV prevention R&D in more than a decade. In 2016, funding for HIV prevention R&D decreased by three percent (US$35 million) from the previous year, falling to US$1.17 billion.
At a time when the field is moving towards a new slate of efficacy trials across the prevention pipeline and follow-on research for successful antiretroviral-based prevention options is underway or planned this trend is worrisome, particularly in light of uncertainties around the sustainability of public sector support from the US and other funders. Even small declines in funding can delay or sideline promising new HIV prevention options that are needed to end the HIV epidemic.
The US continued to be the major funder of HIV prevention research. In fact, 88 cents of every dollar spent on HIV prevention R&D in 2016, came from just two donors: the US public sector and the Bill & Melinda Gates Foundation. In contrast, European public sector funding fell by US$10 million from 2015, and at US$59 million, accounted for just six percent of all public sector investment. This is the lowest European funding recorded in the last decade and marks a 52 percent decrease from the peak funding (US$124 million) in 2009. In addition, the number of philanthropic donors fell sharply from a total of 27 in 2015 to just 12 in 2016.
The RTWG renewed a call for a greater range of donors to increase the stability of R&D financing and cushion potential impact if any of the major funders were to reduce their investments. Noting increases in public sector funding from the Netherlands and Sweden, the RTWG called on other European countries to increase investment in critical HIV prevention tools to help end the epidemic.
The past year has seen one new HIV vaccine efficacy trial begin and another planned to begin later in 2017; a novel proof-of-concept trial of antibody-mediated prevention underway; a monthly vaginal ring with the antiretroviral (ARV) drug dapivirine proven effective and under review by the European Medicines Agency; a multipurpose technology combining dapivirine and a contraceptive has launched early-stage trials; a long-acting ARV-based injectable PrEP formulation is beginning efficacy trials; and, finally, daily oral PrEP delivery programs are being scaled up in multiple countries. And behind these more advanced R&D activities come many other different HIV prevention modalities poised to prove themselves in early-stage research.
“The latest figures from UNAIDS show us that there has been progress toward meeting the 90 90 90 treatment goals, but there has been less progress – and less reporting – on meeting the prevention goals that are critical to epidemic control,” said Mitchell Warren, AVAC executive director. “We need to not only vastly accelerate roll out of HIV treatment and existing prevention options, we need continued and sustained investment to keep HIV prevention research on track to provide the new tools that will move the world closer to ending AIDS.”
The RTWG has tracked more than US$17 billion in investment towards biomedical HIV prevention since 2000 and warned that the greatest impact of this investment could be lost without continued and sustained support to move promising prevention options from laboratories and clinics into the lives of those who most need them.
“We are at an incredibly exciting time in the field of HIV prevention research and development with more life saving innovations, science and technology coming to the forefront than ever before,” said Luiz Loures, Deputy Executive Director of UNAIDS. “We cannot allow a lack of funding to set back progress. Invest now and we can end AIDS by 2030.”
The report documents some critical increases in funding, including the highest annual investment in preventive HIV vaccines since 2007, which includes the highest investment by the US public sector in preventive vaccine research since 2000, in part because of the start of the first vaccine efficacy trial in almost a decade. Yet European public sector investment in vaccine research was the lowest since 2001. The increase in support for vaccine research comes at a critical time in vaccine R&D and is an example of funders responding to the need for investment to keep promising research moving forward. The RTWG noted this level of investment should be occurring across the field to support the broadest possible pipeline of promising new HIV prevention options.
“A true end to AIDS will only be possible if we can develop and deploy an effective HIV vaccine and other innovative biomedical products for HIV prevention” said Mark Feinberg, President and CEO of the International AIDS Vaccine Initiative (IAVI). “With growing risk of increasing rates of HIV infection due to demographic trends and incomplete reach of HIV treatment programs, advances being made in HIV R&D needs support and acceleration. Progress can only happen with sustained public and private sector investment in HIV prevention R&D.”
The HIV field comes together in Paris next week at IAS2017 at a time when there is both much to be optimistic about in HIV science and in the accumulated knowledge of what and how we need to deliver treatment, prevention and care to the people who need it most. Yet, as the title of the report notes, this optimism faces a volatile global health landscape. Funding constraints, policy changes, shifting donor priorities and shifting demographics will all play a role in the world’s ability to respond to the continued challenges that HIV presents.
“After years of prudent and increasingly high-impact investment in HIV prevention and treatment, we have seen amazing dividends in lives saved, families kept together, communities revitalized and economies boosted,” added Warren. “We cannot lose that momentum. We have the innovative science. Now we need an expanded cadre of innovative funders who will work with us to ensure a continued return on investment in more lives saved and more infections averted.”
The report and infographics on prevention research investment are online at www.hivresourcetracking.org and on social media with #HIVPxinvestment.
###
Since 2000, the Resource Tracking for HIV Prevention R&D Working Group (formerly the HIV Vaccines & Microbicides Resource Tracking Working Group) has employed a comprehensive methodology to track trends in research and development (R&D) investments and expenditures for biomedical HIV prevention options. AVAC leads the secretariat of the Working Group, that also includes the International AIDS Vaccine Initiative (IAVI) and the Joint United Nations Programme on HIV/AIDS (UNAIDS). This year’s report is additionally made possible by the support of several donors, including the Bill & Melinda Gates Foundation and the American people through the US President’s Emergency Plan for AIDS Relief (PEPFAR) and the US Agency for International Development (USAID). The contents are the responsibility of AVAC and the Working Group and do not necessarily reflect the views of PEPFAR, USAID or the United States Government.