Webinar: “Time to Protection” on PrEP

UPDATE: The audio and slides from the webinar are now available. Or watch the webinar on YouTube.

Daily oral PrEP using TDF/FTC provides high levels of protection against HIV in people who take the pill regularly. But this protection doesn’t happen overnight. Instead, a person needs to take a number of doses to build up protective levels of the drug in the blood.

Just how many doses?

Right now, the answer to this question is an educated guess—and the World Health Organization (WHO) and the US Centers for Disease Control and Prevention (CDC) have different answers about “time to protection” in their respective guidelines for oral PrEP use.

Please join us for a webinar on the data behind “time to protection for PrEP” on Thursday, February 9, 11am–12:30pm US Eastern Time (visit www.timeanddate.com for the local time in your area) to learn more. This webinar will include pharmacologists who have studied drug levels in the blood and tissue of PrEP users, as well as representatives from the WHO who were involved in developing the guidance on this topic along with advocates and implementers.

Register here.

The primary difference between US CDC and WHO guidelines on time to protection relates to women. Specifically, US CDC guidelines recommend that women complete 20 doses of daily oral TDF/FTC to achieve protective levels of the drug in the vaginal tissue. WHO recommends seven days for men (penile and rectal exposure) and women (vaginal and rectal exposure).

Both of these recommendations are based on measurements of the amount of drug that accumulates in blood and/or tissue over a specific period of time. The studies of how drugs are taken into the body and how they leave the body is called “pharmacokinetics” and “pharmacodynamics” or “PK” and “PD” for short, as explained in our primer for advocates (www.avac.org/pharmacokinetics-and-pharmacodynamics). There isn’t a single PK measurement that is associated with PrEP protection—so both WHO and CDC guidelines are based on inference.

When indirect measures are used for direct conclusions, advocates need to understand the rationale. We hope this webinar will further the conversation. Please join us.

What’s New on AVAC.org

AVAC.org has a host of new resources providing concise updates, informed perspective and handy tools. Take a look at the highlights below and get up to speed on a range of strategic issues.

New Resources

  • AVAC, in partnership with the Clinton Health Access Initiative (CHAI), is taking on new work focused on supporting innovation in the prevention “market”—including the programs that deliver new products and the pipeline of products in trials. This two-page intro to the “HIV Prevention Market Manager” gives an overview of this new body of work.
  • To get a flavor of the work the Prevention Market Manager team is focused on, check out this new resource: End-User Research Landscape Mapping and Findings. The term “end user” is used by people who work on developing and marketing products. It refers to the individual who’s ultimately going to make the decision to seek out and use a given product or intervention. This resource gives a sense of the range of efforts trying to understand what is and isn’t known about one key set of “end users” for new prevention options—adolescent girls and young women in sub-Saharan Africa.

From the Infographics Gallery

  • Introduction to Long-Acting Injectables is an updated graphic to guide you through the basics of antiretrovirals that are being developed as long-acting injectables for both treatment and prevention.

Strong Voices in P-Values

  • Progress and justice for women and girls has come under attack by the new US administration via the reinstatement and proposed expansion of the Global Gag Rule. In Standing Together Against the Global Gag Rule the AVAC team reaffirms its commitment to the fight for bodily autonomy, for justice, for choice and voice for women and girls.
  • In New and Touted HIV bNAb: Big deal or news blip?, veteran science writer and HIV journalist Mark Mascolini delves into the nuances of vaccine research using broadly neutralizing antibodies. You will learn more than just what these are; Mascolini looks at the big promises and the small print.
  • Lindsay Roth, a long-time organizer and advocate for sex workers’ rights, gives any lay reader on the subject of sex work an opportunity to gain a deeper understanding of the issues at stake in Getting Set to Defend and Advance Sex Workers’ Rights in 2017 and Beyond. Roth’s reporting shows how HIV prevention, human rights and economic justice can only succeed together.

Px Wire January-March 2017, Vol. 10, No. 1

This issue of Px Wire, AVAC’s quarterly update on HIV prevention research, looks ahead at a host of issues we are watching in 2017. Are we confronting “Fast Track” goals with the sober analysis they demand? Will oral PrEP guidelines translate into programs and will programs meet people’s needs? What progress can we expect from studies on the dapivirine vaginal ring, various vaccine candidates or on broadly neutralizing antibodies, which are garnering so much press attention of late? Will global leaders embrace policies that ensure data gaps on key populations will finally be filled?

Px Wire’s Take on 2017: #Onwards #UntilTheEpidemicIsOver

2017 promises to be a year of big changes, but how the political winds will touch the field of HIV is still unknown. Amidst the uncertainty, long hard work advancing HIV prevention is pushing frontiers all over the world from the lab to the clinic to the household medicine cabinet.

This issue of Px Wire, AVAC’s quarterly update on HIV prevention research, looks ahead at a host of issues we are watching in 2017. Are we confronting “Fast Track” goals with the sober analysis they demand? Will oral PrEP guidelines translate into programs and will programs meet people’s needs? What progress can we expect from studies on the dapivirine vaginal ring, various vaccine candidates or on broadly neutralizing antibodies, which are garnering so much press attention of late? Will global leaders embrace policies that ensure data gaps on key populations will finally be filled?

Check out AVAC’s round-up of these and other questions that we think will define the state of HIV prevention in 2017. And this issue’s centerspread extends the story beyond 2017 with an infographic showing the status of large-scale prevention trials through 2020.

AVAC Introduction to Long-Acting Injectables

A strategy that uses long-acting injectables is being tested now for treatment and prevention. Injected antiretrovirals that are being developed to remain effective for weeks or months could potentially simplify adherence. Our infographic explains the research underway and reviews some of the major questions that research must address.

Introduction to Long-Acting Injectables

This infographic details the process for developing long-acting injectables for PrEP and Treatment U=U.

PrEP Won’t Protect if it’s Priced Out of Reach

Kenneth is a 2015 AVAC Advocacy Fellow, hosted by HEPS-Uganda. He works with both grassroots communities and national level stakeholders in promoting health and the rights of people living with HIV in Uganda by advocating for consumer friendly policies. He’s currently the head of HEPS-Uganda’s advocacy program, and coordinates the Uganda Coalition for Access to Essential Medicines.

The cost of providing new tools for preventing HIV infections like oral PrEP is concerning. I hear cries about the sky-high prices of these new prevention options all the time. Unfortunately, after the lament, there’s little conversation about reducing these high costs and enabling access. Access is defined by 4 A’s: Affordability, Acceptability, Accessibility and Availability. Lose any one of them and you lose access – and impact – altogether. For anything and everything you ever wanted to know about PrEP, including information about costs as it becomes available, checkout PrEPWatch.org.

Globally, we have 37 million people living with HIV, but only 50 percent of these are enrolled on treatment. That’s despite the landmark study, HPTN 052, that showed early initiation of antiretroviral treatment in people living with HIV with a CD4 count between 350 and 550, not only improved their health but also reduced HIV transmission to HIV-negative partners by 96 percent.

There is a lot of public taxpayer’s money invested in research and development of new tools for preventing, and managing HIV. No doubt, a lot of innovation and brain power goes into the development of these products and I salute that work. But let’s not forget the ultimate goal of an AIDS-free generation. This can only happen if people, irrespective of their location, gender, race, sexual and political orientation, have access to affordable commodities.

The irony is once these products are out, few can afford them.

The latest prevention option, oral PrEP, has been adopted in guidelines, or is in the process of being adopted, by several countries, both middle and low income, as a prevention option for people at substantial risk HIV infection. However, there are already concerns that the cost of PrEP may be a barrier to access, and that’s partly the reason officials are dragging their feet as they consider adding it to their package of prevention.

Pricing PrEP is still underway, but looking at cost for the delivery of antiretrovirals for treatment may give us an idea. A July 2016 analysis of three ART delivery models in Uganda, published in the Journal of the International AIDS Society, showed that it costs $257 (facility-based model), $332 (a combination of community distribution and facility-based model) and $404 (community distribution model) to deliver ART annually per person. Like ART, the expectation is that most people taking PrEP will receive it for free, and if PrEP delivery costs about the same as ART delivery, this could be a big barrier to its access, especially for low income countries and populations at risk. Someone, somewhere, will have to pay, and $257 to $404 per person per year is quite a high cost.

As we prepare to deliver PrEP, we need to mirror the solidarity and teamwork exhibited when these products were developed. A multi-disciplinary collaboration between potential PrEP users, healthcare providers, government and funders should characterize how we make PrEP accessible to everyone who needs it.

In October, I attended the 2016 HIV Research for Prevention (R4P) Conference in Chicago. Being the only conference focused solely on biomedical HIV prevention, I was really looking forward to hearing new ways to address the access issues I highlighted above. Unfortunately, even here there was too little conversation about protecting public health interests over private commercial interests, which hike prices for new HIV prevention tools. I’m excited by the potential of PrEP to drive new infections down, but I worry that if the high cost of its delivery isn’t checked, PrEP may not realize this potential, especially not in the developing countries where it’s needed most.

To Be PrEP-ared for the Future, We Must Learn from the Past

Simon K’Ondiek is a 2011 AVAC Advocacy Fellow, hosted by the Nyanza Reproductive Health Society in Kisumu, Kenya. He is an HIV prevention research advocate with vast experience in the mobilization of communities to effectively engage with HIV prevention research and educating these communities on clinical trials around them.

Five years ago, I was an AVAC Advocacy Fellow. At the time, voluntary medical male circumcision (VMMC) was just beginning to be rolled out in sub-Saharan Africa. Kenya, where I live, was out in front of many other countries but even then, there were problems and challenges—getting information out about what the intervention did and didn’t do, encouraging adult men to take up the procedure, fostering support from female partners, spreading the word, persuading traditional leaders to take it up—I spent my fellowship working on these things. The year culminated in a documentary photography series, exploring themes centered on the knowledge, attitudes, communication and behavioral intentions of young men and women as VMMC rolled out in Nyanza Province. I also built an advocacy task force to work in the province and monitor the rollout.

All of that work was triggered by a joint recommendation in 2007 from the World Health Organization (WHO) and UNAIDS. It called for the adoption of VMMC as an additional strategy for HIV prevention in priority countries. A subsequent document, Joint Strategic Action Framework to Accelerate the Scale-Up of Voluntary Medical Male Circumcision for HIV Prevention in Eastern and Southern Africa, identified key success factors for VMMC. These include leadership and governance. Steadfast political support, if sustained through the entire process of implementation, results in much greater uptake. Engaging national champions (such as Prime Minister Raila Odinga who became one of the key faces of VMMC in the region), developing national policy and operational plans, and designating a spokesperson for the national program helped bolster VMMC uptake in Kenya. I focused on community-level work and can say from first-hand experience that rollout without comprehensive community engagement beforehand almost brought VMMC to its knees. Few men showed up at clinics to be circumcised, and local leaders balked at the idea of circumcision, considering it a foreign intrusion. Something had to change to address these and other challenges. And when communities and traditional leaders were more meaningfully engaged, the pace of rollout intensified.

So much of what I did in that fellowship is applicable today—especially when it comes to PrEP. Here is what I wish everybody knew, and would carry forward as they plan for the kind of comprehensive engagement that made VMMC a reality in Kenya.

For PrEP to be effective community-wide, it will take strong leaders, resources, and the engagement of multiple stakeholders, including health service providers, clinic by clinic. Pre-exposure prophylaxis, or PrEP, for HIV prevention involves the use of antiretroviral medications, known as ARVs, to reduce the risk of infection in HIV negative people. Oral PrEP uses a two-in-one antiretroviral (ARV) pill, containing the ARVs tenofovir and emtricitabine under the brand name Truvada. These ARVs were originally developed to treat people who have already acquired the virus. As a pill taken as HIV prevention, several trials have found PrEP to be safe and effective if taken correctly.

PrEP implementation shares similarities with other sexual and reproductive health products being implemented across sub-Saharan Africa. Contraceptives, like PrEP, are also safe and very effective if used. Adherence in both cases is essential. PrEP is highly protective for both men and women. Similarly, a condom also protects both men and women from contracting sexually transmitted diseases (STIs) and prevents unintended pregnancies. Voluntary medical male circumcision (VMMC), PrEP, condom use and other safe sex practices represent a range of options that can be used in combination and tailored to individual needs.

Numerous demonstration projects aim to establish the benefit of PrEP in the real world, outside the controlled environment of a clinical trial. As access expands, oral PrEP will surely face several challenges.

One example, a lack of awareness of available options, and lack of access to services adversely impacts the health of women, and children too. For PrEP implementation to be effective, administrators must overcome a similar lack of awareness and create access for those most vulnerable to HIV. Key populations need to know it’s available and effective. These groups, including sex workers, adolescent girls and young women, men who have sex with men (MSM) and discordant couples, must be engaged.

Consider this: in places where family planning needs are great, common explanations given for not using family planning methods include health concerns, side effects, poor access to products and services, partner reluctance and prohibitive costs. In some place, family planning challenges have been overcome by integrating HIV treatment and maternal and child health (MCH) services, training healthcare workers, engaging male partners, and continually building awareness of the availability of family planning services through TV and radio to reach a wider community.

It’s also important to note two other factors shaping local context: poor attitudes among health care workers hold back the uptake of family planning services, especially for adolescents and young women. And the involvement of men in family planning plays an important role, as women in many developing countries are not empowered to take family planning decisions on their own.

Therefore, successful PrEP implementation at the community level depends upon engaging those most vulnerable to HIV, and address these real-world challenges. They need to be aware of the availability, the side effects, the benefits. Unforeseen obstacles must be addressed as they arise to ensure successful rollout and uptake.

At the national level, we must operationalize PrEP guidelines and work with politicians to secure political will for a sustained delivery model. Well-coordinated community education and literacy programs are needed at the outset to explain PrEP and identify challenges such as stigma and the under-use of reproductive health services.

Government campaigns on TV, radio and posters, with support from local NGOs and local opinion leaders, should be considered. Such campaigns increase knowledge of PrEP, and influence social and cultural attitudes. Health care workers must be trained and provided with materials on PrEP as prevention, and their training must be integrated with reproductive health services to reach women and speed the delivery of PrEP to everyone who needs it.

As Kenya again leads in HIV prevention, this time with PrEP, we cannot repeat the mistakes of the past, which seriously hampered the roll out of VMMC. The potential public health benefits are enormous. There must be a pragmatic approach of integrating existing HIV prevention efforts, especially PrEP, into broader sexual reproductive health services. Overall, increasing PrEP access and acceptance requires effort to make sure those most vulnerable to HIV—including adolescents, sex workers and MSM learn about PrEP and can get it in a safe, culturally sensitive and cost-effective manner.

What’s New and What’s Needed: Updates in research results and advocacy

Welcome to our first post-US election update! Many of us, in the US and around the globe, continue to be moved, activated and concerned by the recent US election. We have been grateful for forums exploring how our work may be affected by various political scenarios, including this call on the future of Global AIDS Funding, hosted by GNP+. At the same time, we want to restate our long-standing and vigorous commitment to our ongoing work, which will continue with the same rigor as ever, in pursuit of our mission.

In that spirit, this update highlights recent developments in biomedical prevention research. Together they serve as a great example for why a pro-science, pro-research, pro-stakeholder engagement agenda is a non-negotiable necessity, irrespective of politics and political parties.

New basic science provides clues on cure and vaccines. Earlier in the month, two papers were published regarding new innovations in HIV prevention and cure.

A paper authored by Katharine Bar at UPenn and colleagues reported on the effect of the antibody VCR01 in people living with HIV. In these trials, people living with HIV stopped their antiretroviral treatment (ART) while receiving infusions of VRC01, a broadly neutralizing antibody that blocks the activity of many strains of HIV. The study measured the safety of VRC01 and sought to determine if it helped people control their virus while off treatment. Researchers compared viral “rebound” (the reappearance of virus in the body after ART is stopped) between people who received VRC01 and people who did not. Findings show VRC01 only slightly delayed viral rebound. This shows the value of the scientific research field in action, testing and narrowing the field of solutions until we hit the bullseye. VRC01 is also under study as a tool for HIV prevention in the ongoing AMP trials (HVTN 703/HPTN 081 and HVTN 704/HPTN 085), and a number of other antibodies are in various stages of both prevention and therapeutic research.

A paper authored by Dan Barouch of the Ragon Institute and colleagues looked at a strategy for a cure that combines a therapeutic vaccine with a TLR7-agonist. TLR7 is a protein that controls and activates human immune responses. This study looked at non-human primates (NHP) with SIV (the simian version of HIV). The study used the vaccine vector Ad26/MVA from Janssen Pharmaceuticals to instruct immune cells to recognize SIV, and the TLR7-agonist to activate those immune cells. This strategy tested whether the Ad26/MVA/TLR-7 combination would be able to marshal immune cells to eradicate SIV. In the study, non-human primates were put on ART immediately after infection. One group of NHPs received the vaccine alone, another received only TLR7, a third received a placebo and the last received a combination of Ad26/MVA and TLR7. All were then taken off of ART. Those that received the combination had the largest drop in SIV and the longest delay in viral rebound. There are a lot of caveats with animal models, but this finding could add to optimism for the scientific pursuit of an HIV cure. The Ad26/MVA vaccine vector is also being tested as a preventative vaccine, and a large-scale efficacy study of the regimen could begin in 2017.

Community mobilization on the DISCOVER trial of Gilead’s F/TAF as oral PrEP.

An article published on TheBody.com by long-time advocates Anna Forbes and Marc-André LeBlanc outlined the latest developments related to Gilead’s Phase III trial of the drug F/TAF for oral PrEP. The trial, known as DISCOVER, has raised concerns among advocates that stakeholder engagement has been insufficient. The study plans to enroll 5,000 participants from 92 sites across the US and Europe. Participants will be randomized to receive either daily TDF/FTC (Truvada), which is a proven prevention option approved by the US FDA for PrEP in 2012, or daily F/TAF, which is a different version of the drug combination that has been approved for treatment but the efficacy for prevention is unproven. Given the complex messaging of this trial—one that compares an approved option with an experimental one—community engagement over the course of trial planning and execution is imperative. The standards for stakeholder engagement, outlined in the Good Participatory Practice Guidelines, are designed to address this type of trial and should be met. While Gilead has engaged a limited subset of community stakeholders, a group of advocates, representing a range of organizations, submitted a public letter to Gilead on November 16 demanding substantial and meaningful improvements to the process of community engagement. This is the right thing to do and history has shown this process improves the chances for the trial’s success.

Decades of testing and research reflected in studies like these are doing the painstaking, instrumental work it takes to move us toward our goal, the end of AIDS. Let’s keep our eyes on the prize.

Achievements and Disappointments: From Cape Town to Chicago

Teresia is a seasoned advocate for gender equality and sexual reproductive health and rights, especially for HIV-positive women. She is passionate about promoting HIV prevention strategies that work for women and girls. Teresia was a 2014 AVAC Advocacy Fellow and a founding member of the Personal Initiative for Positive Empowerment (PIPE Kenya). She is the vice chairperson of ICW-EA and represents the region in the ICW Global International Steering committee. She is a counselor by profession and currently volunteering with ATHENA Network in community engagement on gender eqality and HIV.

In 2014, at the peak of my excitement as an HIV prevention advocate and an AVAC Fellow, the first Research for Prevention (R4P) Conference was held in Cape Town. I left that conference anxious but hopeful about a few things: The outcome of the FACTS 001 microbicides trial, the outcome of PrEP demonstration projects in different countries, how implementation in the real world would look, and the start of the much-talked-about ECHO trial that will answer key questions about whether certain hormonal contraceptives increase the risk of HIV acquisition.

In the time in between Cape Town and Chicago a lot has happened in all of these areas, and so much remains to be done.

A few months after leaving Cape Town, new findings came out about FACTS 001. There was no evidence of overall protection associated with the gel tested. Younger women were not correctly and consistently using the gel, and therefore were not protected.

Results from PrEP demonstration projects showed that discordant couples using oral PrEP had very low levels of HIV transmission – reducing the risk by up to 96 percent. More demonstration projects with different populations are currently underway and will answer questions related to implementation. In Kenya and Uganda, the open-label demo projects continue to record high adherence rates among discordant couples.

We know PrEP works but availability is limited. In most African countries, PrEP is not yet part of public health programs. In a few places it can be obtained at demonstration sites that target specific populations. Kenya and South Africa are the only African countries where Truvada (the brand name for drugs used as PrEP) has been approved and it is now available in South Africa’s public health system for certain high-risk populations. Regulatory applications have been submitted in Botswana, Lesotho, Malawi, Mozambique, Swaziland, Tanzania, Uganda and Zambia (see complete global map here).

“People at high risk of HIV are more likely to take PrEP if [they are] drawn out,” said Dr. Elizabeth Irungu of the Kenya Medical Research Institute who was in Chicago for R4P. Drawing out people at high risk means many things including outreach, reducing stigma, and using innovative approaches to overcome structural barriers such as distant or understaffed clinics, prejudiced service providers. It also calls for training health workers and strengthening health and community systems. We still don’t have PrEP guidelines in most countries; Kenya for example has made big strides in PrEP and other prevention tools, yet policy makers are yet to develop guidelines, which instruct health workers on how to administer PrEP. At R4P 2016, Kenyan policy makers promised to do so by 2017.

In the US, PrEP is widely available to those at risk. However, there are disparities in access there too: 70 percent of those accessing PrEP are men; although 75 percent of new infections are among people of color, only 25 percent of them are accessing PrEP. And the disparities go on and on. Communication campaigns should reach out to women and people of color who are at higher risk of acquiring HIV.

The discussion around hormonal contraception and the risk of HIV acquisition was filled with uncertainty in Cape Town. The World Health Organization (WHO) had issued a statement that women at high risk of HIV should be encouraged to use condoms alongside the hormonal contraceptive known as Depo-Provera. The uncertainty about Depo’s effect on HIV risk stems from conflicting and unclear observational data. Only a randomized controlled trial can resolve the question, “Do hormonal contraceptives like Depo-Provera increase the risk of HIV acquisition?” When ECHO was initiated advocates called for a four-arm trial but with not enough resources ECHO kicked off as a three-arm trial of Depo-Provera (or depo), a copper intrauterine device (IUD) and Jadelle (an implant). NET-EN, another injectable and potential fourth arm of the trial, was omitted from ECHO. What do we do in the meantime as we wait for ECHO results?

For me, the human rights issues are striking. Women considering Depo-Provera need accessible and complete information about this issue so they can make informed decisions. WHO is slow to respond to additional data about Depo’s potential for increasing risk and inconsistent in continued engagement with local communities in Africa.

Civil society organizations and advocates will continue to push for a mix of birth control methods and the funding to support it in all settings, including rural areas so that women will have a range of options to choose from. Engagement and consultations between WHO and advocates must continue. Conversations should be brought to communities; leaving no one behind. Most importantly, the conversation should be taken to the broader movement for sexual and reproductive health and rights (SRHR). All stakeholders should work and collaborate with sites that deliver reproductive health services, keeping PrEP access a high priority along with other SRHR services.

Sitting in a Chicago conference center, R4P’s home this year, I heard calls for innovation, with more and better tools that women can use and control. And leaders were calling for engagement across the biomedical frontier. “We need to work towards an HIV cure,” urged Ambassador Deborah Birx of PEPFAR, while also calling for the delivery and implementation of what we have. In short, Birx said we need to integrate programs, disseminate science, and engage communities meaningfully to shape the agenda for research and implementation.

Although there’s a lot that needs to be done to make Amb. Birx’s hope a reality, I’m more hopeful after Chicago than I was after Cape Town. Science continues to deliver – now it’s time for us as advocates, service providers, governments and funders to effectively implement what’s been delivered to us as we work towards new possibilities for tomorrow.