CROI 2018: Highlights and what’s next for advocates

[UPDATED: slides and audio from our webinar series are now available below.]

Historically, the Conference on Retroviruses and Opportunistic Infections (more commonly known as CROI) is heavy on basic science and early-phase research. Data from these types of studies were still prominent in 2018 (see Jon Cohen’s excellent Science article on new animal data informing cure and vaccine research). This year the meeting also broadened its lens from the lab to the ways that different strategies are, or might, have an impact in the context of people’s complex lives.

Dapivirine Ring: Guess what, women use it when they know what works!

The dapivirine vaginal ring is a silicone ring containing an antiretroviral that is released slowly over time. It’s been designed to be worn by women for around a month. Two years ago, at CROI 2016, the ASPIRE and Ring Study results showed that the dapivirine vaginal ring is safe and reduces the risk of HIV infection by around 30 percent overall among women enrolled in the study. At CROI 2018, interim data from the open-label extension (OLE) trials of the ring—HOPE and DREAM—showed that the ring reduced risk by 50 percent. In the open-label studies, all participants have been given access to the dapivirine ring to use monthly for up to 12 months. There is no placebo and all participants are told about the safety and efficacy data. Presenting on behalf of the HOPE study team, Jared Baeten (MTN) remarked that the ring data are similar to the oral PrEP OLE data-in those studies too, people were more adherent once they knew the results from prior trials. Final data from HOPE and DREAM, including findings on how well it works in those who use it consistently, will be available in late 2018/early 2019.

What’s Next

The European Medicines Agency (EMA) is reviewing available data on the ring under a framework that allows it to provide regulatory guidance for developing countries. Its decision is expected in late 2018. Will the world be ready with investments, introduction plans and advocacy? Experience to date says: only if advocates work at local, regional and global levels to demand advance planning and action.

Women’s Vaginas: They’re amazing and important to HIV (duh!)

A biome is a large naturally occurring group of plants or animals in a given habitat. The vaginal microbiome is the naturally occurring group of bacteria that live in women’s vaginas and-depending on the proportion of different bacteria present at a given time-keep us healthy or may make us uncomfortable or even put us at risk. The relationship between the vaginal microbiome and HIV acquisition has been a focus at several recent conferences. It was highlighted again in a plenary presentation at CROI.

Nichole Klatt (University of Washington) presented data on what happens when there is an imbalance between good and bad bacteria, a condition known as vaginal microbiome dysbiosis. When researchers looked at vaginal bacteria and different antiretrovirals in lab studies (in vitro), they found that microbiomes with an imbalance towards bad bacteria showed some degradation of topical tenofovir and dapivirine. In other words: it could be that women with such imbalances who are adherent to a vaginal microbicide or the dapivirine ring might still have lower levels of drug in their genital tissue than what is needed for adherence.

It’s incredibly important to understand how the microbiome impacts HIV risk and vaginal health, including the presence of topically applied ARV-based prevention. It’s also incredibly important to remember that these data do not say anything about how oral tenofovir-based PrEP works for women. Oral PrEP arrives in genital tract cells in completely different ways than topical PrEP. To date, data from the human trials of both oral PrEP and dapivirine ring haven’t shown any difference in effect in women with bacterial vaginosis, which is good news. Additional data will continue to shed light on this important and continuing story. And in the meantime, the take-home is still that oral PrEP works for women and that so far there has been no difference in levels of protection in the ring studies linked to dysbiosis.

What’s Next

Advocates need to be on the frontlines of explaining what these vaginal microbiome data do and don’t tell us. We can’t afford misinformation suggesting that oral PrEP doesn’t work in women. We also can’t afford to ignore the complexities of all bodies-female, male and trans-and how they impact prevention and treatment.

Pregnant and Post-Partum Women Need HIV Prevention

A presentation from Renee Heffron (University of Washington) provided more evidence that pregnant and post-partum women are at increased risk of HIV infection. She and colleagues analyzed data from two studies of over 2,700 serodifferent couples. They found that women who were pregnant or post-partum were 3-4 times more likely to acquire HIV. Implications for care and prevention include counseling, more testing, treatment for male partners and woman-controlled prevention options like oral PrEP.

What’s Next

2018 will see many discussions of pregnancy, contraceptives and HIV risk as the many stakeholders prepare for data from the ECHO trial. ECHO is looking at three different methods (DMPA, copper IUD and Jadelle implant) to see if any have an impact on women’s HIV risk. These data are an essential reminder that HIV risk is driven by many things-including pregnancy. Advocates need to push for PrEP in the ante- and post-natal context, contraceptive choice, programs that diagnose male partners and link them to effective ART-and more. Data and global and national guidelines on the use of oral PrEP (e.g., the WHO technical brief on preventing HIV during pregnancy and breastfeeding in the context of PrEP) and the dapivirine ring for pregnant and post-partum women are essential.

PrEP Use Increases but Disparities Persist

Access to PrEP was woven throughout the CROI program, as data on PrEP programs and use continues to accumulate. Findings from San Francisco and Australia both showed a significant uptick in PrEP use and reduced infections (primarily in men who have sex with men) but across both of the studies racial and ethnic disparities in access remained largely unchanged. A new analysis from the US Centers for Disease Control and Prevention (CDC), also presented at CROI, found that two-thirds of those who could benefit from PrEP are African-American or Latino and yet prescriptions for these populations remain stubbornly low. Gaps in access were seen across racial groups but were most stark among non-white populations.

What’s Next

A continued fight for health equity as part of a broader social justice agenda in America-and around the world.

Undetectable=Untransmittable

In a meeting known for a focus on basic science, conversations about the Undetectable=Untransmittable campaign and its role in reducing stigma were frequent and welcomed. And for the first time there was a plenary session on mental health at which presenter Robert Remien (HIV Center for Clinical and Behavioral Studies, Columbia University) called for stepped up mental health services to achieve the 90-90-90 goals.

What’s Next

Advocates have consistently been at the frontlines of demanding a holistic approach to prevention and treatment—here’s more data to fuel the fight.

Products in the Pipeline

While there was an increased focus on implementation work this CROI, true to form the meeting also featured plenty on data from early-stage research. Among the hundreds of posters and oral abstract presentations a couple stood out including a non-ARV vaginal insert-designed to prevent HIV, HSV-2 and HPV infection-from PopCouncil and the long-acting ARV from Merck (MK-8591) to prevent HIV. Given favorable animal data, both products are being considered for clinical development.

What’s Next

A major scientific-literacy and agenda-setting push so that advocates can join researchers and product developers to guide decisions about how these trials will be designed and when and where they will happen.

Keep the Conversation Going

Join us for a post-CROI webinar series! Dig into the data with researchers and discuss with fellow advocates how these findings can inform our advocacy work moving forward. Register today!

And stay tuned for announcements on additional webinars!

The January Episode of Px Pulse is Up!

As the new year gets into full swing, we at AVAC look forward to assessing, untangling, confronting and calling on all of us to commit to HIV prevention in all its complexity. Building on the advocacy agenda we lay out in AVAC Report 2017, and a corresponding December episode of our Px Pulse podcast, our January episode expands on what we’re looking forward to in the year ahead.

Find Px Pulse on iTunes or listen at AVAC.org to hear AVAC Executive Director Mitchell Warren explore more of what’s got our attention—it’s no small list.

  • Major new vaccine and long-acting injectable PrEP trials are launching.
  • The dapivirine ring is under regulatory review, and could be the world’s next biomedical prevention option since oral PrEP.
  • Recent findings from the Rakai Community Cohort Study in Uganda confirmed what models predicted—bringing combinations of existing interventions, such as voluntary medical male circumcision and antiretroviral treatment, to scale slashes new HIV diagnoses. How can we leverage these findings to maximize prevention at the global level?
  • What will advocates need to do this year to prepare for results—anticipated in 2019—of a key trial called ECHO that’s looking at whether contraceptive methods affect HIV risk?

Hear all this and more in the January episode of Px Pulse, AVAC’s podcast on HIV prevention research today. Tell us what you think!

What Young Women Want

This letter comes from a group of young African women and reflects their HIV prevention research priorities. It was submitted to the National Institutes of Health’s (NIH) Division of AIDS (DAIDS) during the open-comment period concerning the structure and agenda for its next funding cycle (2021-2027).

Dear Dr. Carl Dieffenbach,

We are eight young women from South Africa, Uganda and Zimbabwe who were involved in recent consultations for planned HIV prevention trials with young women. We are interested in HIV prevention research because in each of our countries, young women are at high risk for HIV and we are so excited to hear that finally the needs of protecting young women are at the forefront of studies exploring new prevention tools. We understand that you and DAIDS are considering the research priorities for the next several years and we want to make sure that our voices are heard.

We are:
Sanele Ngulube – Zimbabwe, age 20
Irene Hware – Zimbabwe, age 22
Cleopatra Makura – Zimbabwe, age 21
Shakirah Green – Uganda, age 24
Catherine Nakkide – Uganda, age 22
Charity Twikirize – Uganda, age 22
Sinazo Peter – South Africa, age 24
Anelisa Madalane – South Africa, age 18

Please accept this as our feedback to you as you consider the research agenda that affects our future.

We have arranged our suggestions to you based on the themes we discussed together as a group. Here is what we want.

1) We want choice. The feeling that young women have when we know we have choices on how to protect ourselves, gives us power within and we get confident. The power and confidence means there are less chances that we become reckless about our sexual reproductive health. Choice frees us from slavery of any type because we are able to say yes or no, or even pick from a variety without being judged.

Most of all, we, young women, love experiencing new things and we love pushing boundaries. We want fun and exciting things and we shouldn’t be scared of using other methods because they are not of equal standard. Simply put, choice makes our life better.

2) We want products that are safe for our bodies and discrete. We, young women, are delicate, and you know how sensitive our vagina is. Not only that, but we have to fight social norms and cultures in our communities. We know that social norms should not dictate how we should take care of ourselves, but we also realise that most young women are oppressed by their partners, communities and culture.

We want something that will not attract people’s eyes and judgement. We need something that doesn’t require us to close our eyes, and clench our teeth when we use it. Again, it means we need different choices.

3) We want both systemic and non-systemic options. We have different opinions on what can work for us. Some of us like the idea of having to go to the clinic only once and be protected with a long-acting product—and it would be great if that could be for 6 months. Some of us like the convenience of systemic coverage. But others of us are nervous about side effects and the interaction with our sensitive bodies. We don’t want something that requires constant check-up. We want something that doesn’t stay in our bodies for a long time.

So, if you want to prioritise long-acting systemic methods, please make sure that it is easy and has no side effects for us. But remember our first point, that we want choices—we are all different and we want different tools at the table so we can choose what suits us best. We are all from different environments and cultures.

4) We want something other than injections. Some of us are okay with injections, but for others, injections don’t work and we want something we can take without pain. Some of us think twice about even going to the hospital when we are sick because we are scared of injections. Also, injections mean going to a clinic—and we have to deal with judgmental nurses who think we are too young for sex.

A visit to the clinic is really something else. So, if you plan on only giving us injections, it is not okay with us. We are not all good with the injections—please ensure that the research gives us something else too.

5) We want the ring: We love the idea of the ring. You insert it and you are done. It is like our secret weapon, painless but protective. We would use it because it’s in and doesn’t bother us for a while, and we can watch out for ourselves. We would even love the ring more if you added a contraceptive. We understand that DAIDS is thinking not to put more research into other forms of rings like this and we don’t think that’s a good idea. We have seen it works for some women and that’s okay that it doesn’t work for all because it’s another tool, another choice.

We want to thank you for the research you and your team have done. Thank you for the time you have put in and done for us, so far. However, we want you to know that we want more and we need more from you. We want to challenge you to do more for us and we want you to involve us more. We don’t want to be terrified of the products we are using (and please, if you come up with a new product, make it smell good). We don’t want side effects. And please, don’t forget about the potentially expensive costs of these methods. Most of all, we want products that will be safe and protect us as much as possible.

We hope our views will be heard and considered because we don’t want our issues to go unnoticed. We would love if—in the future—we were asked first about our needs instead of just coming with the products researchers think will be best and then asking us if we would use them. There is a South African saying, “it’s better to hear it from the horse’s mouth.”

—Sanele, Charity, Irene, Cleo, Shakirah, Catherine, Sinazo and Anelisa

NIH-Funded HIV Trial Networks: A family tree

This graphic provides a visual history of the DAIDS Networks and a look at what’s proposed for the next funding cycle. It appears in AVAC Report 2017: Mixed messages and how to untangle them.

Total Global HIV Prevention R&D Investment by Prevention Option, 2015–2016

This graphic shows the percentage of total global investment in HIV prevention spent on different interventions in 2015 and 2016. For much more on HIV prevention research & development funding, visit www.hivresourcetracking.org.

US HIV Research: A family tree

This graphics shows a family tree representing HIV research in the United States. It appears in AVAC Report 2017: Mixed messages and how to untangle them.

Timeline for DAIDS HIV Trials Network Recompetition

This graphic looks ahead from 2017 through 2027 at the DAIDS HIV Trials Network Recompetition process. It appears in AVAC Report 2017: Mixed messages and how to untangle them.

Evolving Context for HIV Prevention Research (Map)

A global map showing selected HIV prevention research and oral PrEP status.

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.

Global HIV Prevention R&D Investment by Technology Category

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.

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!