PrEP Trial Design and Ethical Considerations

In January AVAC collaborated with the French AIDS organization Sidaction to host a meeting, Challenges of clinical trial design, degree of evidence and recommendations in the era of PrEP. The meeting provided a forum for local French researchers and advocates to discuss IPERGAY, the intermittent PrEP study currently underway with men who have sex with men in France. A number of international researchers, advocates and normative agencies were also on hand to broaden the discussion. Advocates on both sides of the Atlantic have questioned the use of a placebo arm in IPERGAY since the US FDA approved daily TDF/FTC (Truvada) for prevention last July. French and other European regulators, however, have yet to approve the use of Truvada as PrEP, therefore it is not currently available for prevention, only treatment.

The daylong gathering brought key stakeholders together to discuss the difficult questions of trial design and ethics—issues relevant not only to IPERGAY but to other current and future biomedical prevention trials. Presentations from the meeting are available at www.prepwatch.com/#sidaction.

While participants in the meeting highlighted the various perspectives on the actual IPERGAY trial design, there was general agreement on the important role of the trial in answering questions around intermittent PrEP, whether TDF/FTC could be taken “on demand”, meaning at the time of sex, and still reduce the risk of HIV transmission.

At the meeting the French organization AIDES called on the French regulatory agency (the National Security Agency of Medicines and Health Products, or MSNA) to approve Truvada via a compassionate use authorization for HIV prevention among most at-risk groups. For a copy of the press release, click here.

Continue following developments at www.prepwatch.org/#sidaction.

ARV-Based Prevention Research and Development Product Pipeline

The Px Wire centerspread from April-June 2013 Volume 6, No. 2 showcases the ARV-based HIV prevention pipeline from pre-clinical research to implementation projects.

Press Release

VOICE trial results underscore need to accelerate development of additional HIV prevention options for women; PrEP strategies remain valuable prevention tool

New York, NY – Results from a large-scale HIV prevention trial among African women known as VOICE (Vaginal and Oral Interventions to Control the Epidemic) provide an urgent reminder that products must meet the needs of the people using them. While disappointing, the results lend new urgency and direction to the search for additional safe and effective HIV prevention options for women, AVAC said today.

Researchers announced today that none of three pre-exposure prophylaxis (PrEP) and microbicide interventions tested in VOICE—daily oral tenofovir, daily oral TDF/FTC (Truvada), and daily 1% vaginal tenofovir gel—provided additional protection against HIV in the study, likely because few of the women in the trial used the products as directed. This low adherence explains the lack of benefit and is consistent with data from other antiretroviral (ARV)-based prevention trials that found a correlation between higher levels of adherence and protection from HIV. The new results were presented in Atlanta at the 20th Conference on Retroviruses and Opportunistic Infections (CROI).

“The VOICE results reinforce what we already know from previous trials—these interventions work when they are used, and they don’t work when they are not used,” said Mitchell Warren, AVAC Executive Director. “PrEP is still a valuable option for many women, and men, who recognize their risk and can take PrEP consistently. Now we have a dual responsibility to understand who might benefit from daily PrEP and ensure that they can access it, and to accelerate the development of additional options that can meet the urgent needs of others.”

A range of trials has shown varying levels of effectiveness of tenofovir-based prevention for heterosexual men and women, and for men and transgender women who have sex with men. The VOICE data do not invalidate the prior trial results, including the finding that daily oral tenofovir-based PrEP provided high levels of protection for women in stable relationships where one partner was HIV-positive, and that 1% vaginal tenofovir gel was modestly effective on a different dosing schedule.

“Previous trials of tenofovir-based gel and pills have shown that biologically this approach can work, but only if the product is used. HIV prevention is never just biomedical—behavior is key. What we’ve learned from VOICE and other trials is that adherence to the prescribed dose—the behavioral component—is the variable that determines effectiveness,” Warren added.

“Biomedical tools do not work in a vacuum but rather in the complex realities of women’s and girls’ lives. The women of VOICE and other prevention trials have much to tell us. Now we need to listen to what they are saying and design prevention options based on a better understanding of their reproductive and sexual health needs and desires, their perceptions of personal risk for HIV infection, and their interest in and ability to use the products offered in those trials,” Warren said.

VOICE showed a very high incidence of HIV in the trial—5.7 percent among all the women in the trial and 8.8 percent among unmarried women under the age of 25 in South Africa.

“The high rates of new HIV infections among women, especially young women, are the most shocking and disturbing data from this trial. They are a sobering reminder of how desperately women need new prevention options that they can and will use to protect themselves from HIV,” said Elizabeth Bukusi, Deputy Director (Research and Training) of the Kenya Medical Research Institute (KEMRI) and an AVAC Board Member. “The VOICE results teach us again that an urgent need for new prevention options does not mean women will automatically demand or use those products.”

Following the 2012 US Food and Drug Administration (FDA) approval of Truvada as PrEP for adults at risk of HIV, AVAC called for a comprehensive package of PrEP demonstration projects for all populations—including young women—that could benefit from the proven option of daily oral TDF/FTC. Demonstration projects and other studies in which participants know that they are taking an intervention that has been proven to work will provide important information about how adherence can be supported in real-world situations. AVAC is also working with advocacy partners in the US and internationally to push national health agencies to systematically determine how PrEP can be delivered to the women and men who will benefit from it. This includes a statement released today from a coalition of HIV and women’s health advocates calling on US agencies to coordinate a PrEP agenda to quickly and accurately answer questions about how PrEP can be made available to women in the US.

At the same time, AVAC calls for accelerated research and development of additional HIV prevention options that are less dependent on adherence and may be easier and more desirable for women to use. These include different delivery mechanisms, such as long-acting rings and injections, and less-than-daily dosing schedules, such as that being tested in the FACTS 001 trial, which is looking at 1% tenofovir vaginal gel used around the time of sex. Renewed commitment and resources are also urgently needed for research to develop HIV vaccines, which would overcome many of the issues around adherence, and combined contraceptive and HIV prevention methods, which would address many women’s needs more comprehensively.

“The data presented today are only the beginning of what we will learn from VOICE. We need to make sure that we get all of the information we can from the VOICE participants to help us understand why women were dedicated to the trial and yet were not willing or able to use the products consistently. These women are at such high risk for HIV, we owe it to them to work with them to find the options that they can and will use to protect themselves,” Warren said.

For more information about the VOICE results and ARV-based prevention visit www.avac.org/prep and www.avac.org/microbicides. The Working Group on US Women and PrEP Statement is online at www.prepwatch.org/#women.

Contact:

Mitchell Warren, [email protected], +1-914-661-1536
Kay Marshall, [email protected], +1-347-249-6375

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About AVAC: Founded in 1995, AVAC is a non-profit organization that uses education, policy analysis, advocacy and a network of global collaborations to accelerate the ethical development and global delivery of AIDS vaccines, male circumcision, microbicides, PrEP and other emerging HIV prevention options as part of a comprehensive response to the pandemic.

Achieving the End: One Year and Counting

In AVAC Report 2012, Achieving the End: One Year and Counting we’ve identified five priorities for action.

Achieving the End

Recent breakthroughs in HIV prevention research have created unprecedented opportunities to curb new HIV infections, save lives and set the world on a path towards eliminating HIV transmission.

Plans and Missing Pieces in PrEP Demonstration Projects: USA

This infographic from AVAC Report 2012 identifies the design and key questions for ongoing or planned PrEP demonstration projects in the US.

Reaching the Tipping Point: The time to act is now

AVAC Playbook 2012-2013: Progress toward global goals

AVAC first published its Playbook of global goals for ending AIDS in late 2011. This infographic from the AVAC Report 2012 builds on the objectives from 2011 and identifies five priorities for action in 2013.

Momentum for PrEP and Other News from USCA

In October, AVAC’s Kevin Fisher and Deirdre Grant and a number of PxROAR program members descended on Las Vegas for the United States Conference on AIDS (USCA). USCA is a US-focused conference that largely attracts front-line providers from AIDS service organizations.

This was AVAC’s fourth year presenting on PrEP at USCA, but importantly the first time since the United States FDA approved an indication for daily oral TDF/FTC (Truvada) as PrEP in July. Kevin and Deirdre led a seminar session PrEP can protect women and men against HIV! What do we need to know and do so we can translate results into public health impact? Over 75 people engaged in discussions on the state of PrEP research/implementation—the largest audience AVAC has had for this type of session at USCA—highlighting the growing need for information about PrEP, especially in translating research to rollout.

The audience participated in an energetic debate about whether at next year’s USCA, they thought they would be talking about how their communities had integrated PrEP into local HIV prevention efforts. In a reversal from previous years, almost everyone in the room was supportive of the idea that PrEP would be a part of their local prevention efforts. Previous questions surrounding PrEP have begun to be answered and its potential as a new—and needed—HIV prevention option is seen.

PxROAR members were also busy at USCA. Nichole Little led a roundtable discussion on PrEP and women based largely on her ROAR work—Sex, Biomedical HIV Prevention & The New Millennium Woman: Is PrEP The Answer For Me? Kieta Mutepfa helped facilitate a session on Strategies for HIV Prevention Message Development in Specialized Populations: A Case Study of Empowering Young MSM of Color in Los Angeles as Advocates for PrEP. Ebony Johnson was a speaker at the Opening Plenary Breakfast addressing what can be done to turn the tide of the epidemic among women and ensure social and health equity for all women in the United States.

The Change We Need to End AIDS in Uganda

2012 AVAC Fellow Alice Kayongo played a leading role in developing a civil society report, “The Change We Need to End AIDS in Uganda”, which details concerns and recommendations for shaping the national AIDS response in Uganda. This report was presented at the Joint Annual Review (JAR) of the country’s five-year National Strategic Plan (NSP) for responding to HIV/AIDS, which was first launched about a year ago. The mid-October JAR meeting was an opportunity to review progress and gaps. In the weeks leading up to the JAR, civil society participated in reviews of draft assessments of progress on the various elements of the NSP, including prevention, treatment and care, and health systems strengthening.

Kayongo was joined in this coalition effort by Sylvia Nakasi and Bharam Namanya of UNASO (2011 Fellow and Host Supervisor, respectively), and Leonard Okello, Alice’s Fellowship supervisor and Lillian Mworeko of ICW-EA (2012 Host)—as well as a broad range of other advocates.

The report, presented at the JAR, included a 10-point plan to halt new infections, save lives and ensure leadership, and provided a detailed critique of the national AIDS response to date.

This advocacy comes on the heels of a dynamic and successful campaign to increase funding for and recruitment of more than 6,000 health care workers throughout Uganda.

For a copy of the report, reach out to [email protected].