Current Issue
January-March 2012, Volume 5, Number
1
Click here for the PDF version.
Contents:
- AVAC's Take
- At a Glance
- Data Dispatch
- Gilead Sciences submits TDF/FTC for HIV prevention to FDA
- More surprises and disappointments for VOICE
- Recently Released
- Not to be Missed
AVAC's Take
In the first issue of Px Wire in 2012, AVAC’s take is simple: We must continue without delay to build on the momentum that gathered throughout last year, reaching a new height on World AIDS Day 2011, when US President Barack Obama committed the US leadership to make “the beginning of the end of AIDS” a reality.
Realizing the goal articulated by President Obama, US Secretary of State Hillary Clinton, and many other leaders worldwide, depends on full implementation of antiretroviral therapy for HIV-positive individuals to maximize the potential of “treatment as prevention,” taking voluntary medical male circumcision (VMMC) to scale in key countries, and ensuring that no infant is born with or infected with HIV during breastfeeding. It also requires a long-term view that supports these efforts, while continuing research on additional tools.
Achieving the beginning of the end of the epidemic requires logistical innovation, political commitment and secure funding. None of these are guaranteed. As 2011 came to a close, the Global Fund to Fight AIDS Tuberculosis and Malaria (GFATM) announced the cancellation of its Round 11 funding—underscoring what perilous financial times these are for the fight against AIDS.
This year could turn out to be a pivotal year for the long-term effort to end AIDS. Here are some of the key outcomes AVAC and our partners will be working towards in the coming months.
- PEPFAR Country Operating Plans, which guide activities at the country level, align with the emerging science of combination prevention.
- Donor commitment and restoration of GFATM Round 11 funding.
- Political leaders in developing and developed countries join the US and match funds to scientific innovation.
- Fast-track US Food and Drug Administration (FDA) review of daily oral PrEP using daily TDF/FTC for HIV-negative individuals and a clear community voice articulating the demand for this strategy as part of combination prevention (for more on this story, see Data Dispatch on back).
- Launch of PrEP demonstration projects in MSM in Miami and San Francisco, and, ideally elsewhere.
- Thorough analyses of data from FEM-PrEP and VOICE trials that shed light on why various tenofovir-based strategies (daily oral TDF/FTC in FEM-PrEP and daily 1% tenofovir gel and daily oral TDF in VOICE) did not show benefit for the women in those trials.
- Consultations with women worldwide that explore what is known and unknown about the interaction between injectable contraceptives and HIV risk.
- Intensive preparation and community engagement in anticipation of RV144 follow-on vaccine trials slated to begin in Thailand and South Africa in coming years. Launch of trials to evaluate the safety and efficacy of a vaginal ring carrying the ARV dapivirine for HIV prevention in HIV-negative women.
- Key countries implement strategic plans to achieve 80 percent VMMC among adult men by 2015—and new devices such as PrePex and the Shang Ring introduced as additional circumcision tools.
If there is progress in ticking off the items on this list, then, in one year’s time, we’ll be able to say that we are closer to the end of AIDS than ever before.
At a Glance
IPERGAY, the pilot phase of a planned efficacy trial of coitally-related oral PrEP in MSM and transgender women began enrolling participants in January. The trial is sponsored by the French research agency ANRS. In this initial phase, investigators say they will evaluate the feasibility of the trial design, and may expand to a full efficacy trial. The randomized, placebo-controlled trial will assign participants to either oral TDF/FTC or a placebo pill. They will be counseled to use an “on demand” dosing strategy, taking the drug daily during periods of sexual activity. Results from the pilot phase are expected in 2014. AVAC will be working with partners to explore the implications of and views of such a placebo-controlled trial, in light of Gilead Science’s submission to the FDA for a TDF/FTC prevention indication.
MTN 013/IPM 026 began enrolling participants in this Phase I safety study last November. Women in the trial are randomly assigned to use either a vaginal ring containing two ARV drugs (dapivirine and maraviroc), a ring containing maraviroc alone, a ring that contains dapivirine alone, or a ring with no active drug, inserted once every four weeks. This is the first ARV- combination vaginal ring to enter clinical trials. Results are expected in early 2013. MTN and IPM are also each planning to launch an efficacy trial of the ring containing dapivirine alone later this year.
Project ARM (Africa for Rectal Microbicides) held its first meeting in Addis Ababa, Ethiopia, last December. Initiated by IRMA (International Rectal Microbicide Advocates), in partnership with AVAC and others, the meeting developed a rectal microbicide research advocacy agenda specific to Africa. IRMA will release the Project ARM strategy report at the 2012 International Microbicides Conference in April.
Data Dispatch
Gilead Sciences submits TDF/FTC for HIV prevention to FDA
This past December, Gilead Sciences submitted a dossier to the FDA requesting a prevention indication for TDF/FTC (marketed as Truvada). If this supplemental new drug application (sNDA) is approved, TDF/FTC will be the first antiretroviral approved for use as a prevention tool in HIV-negative people.
Howard Jaffe, Chairman of the Gilead Foundation, told AVAC, “Per our discussions with FDA, the submission is based on data from the two large clinical trials that support Truvada for PrEP [iPrEx and Partners PrEP], as well as supporting data from several other clinical trials, including CDC 4323 [a TDF as PrEP safety study in MSM in the US] and TDF2 [a CDC-funded trial in heterosexual men and women in Botswana].”
It is also expected that the FDA will review data from trials that did not find effectiveness of tenofovir-based PrEP, such as VOICE and FEM-PrEP. For details on all of these trials and more PrEP research, see www.avac.org/prep.
This development is an exciting one, as it could simplify access to and potential insurance coverage of TDF/FTC as PrEP in the US. It could also be used as a regulatory precedent in other countries. If the FDA grants a “priority review” of the application, as is expected, it will take place in the first half of 2012. In the coming months, AVAC will work with partners to bring an informed community voice to the public advisory committee hearings anticipated in May or June. To get involved in this effort, please contact avac@avac.org.
More surprises and disappointments for VOICE
Last November, the Data and Safety Monitoring Board for the VOICE trial met for a scheduled review and recom- mended that the daily 1% tenofovir gel arm of the trial be discontinued. At the time of the review, the incidence rates (rate of new HIV infections) were equivalent in the group of women who received 1% tenofovir gel plus a standard prevention package compared to the group who received an identical prevention package and placebo gel with no active ingredient. (Neither the women nor the trial investigators or site staff knew who was receiving placebo or active gel.) The development was a further disappointment to VOICE, which had discontinued the daily oral TDF arm of the trial in September following a similar recommendation. The third active arm of VOICE, which is testing daily oral TDF/FTC, continues—and data are expected by 2013.
In 2010, the CAPRISA 004 trial of 1% tenofovir gel found that the gel reduced HIV risk in HIV-negative South African women by 39 percent overall. This trial tested a coitally- related dosing strategy, known as “BAT-24”.
The FACTS 001 trial of 1% tenofovir gel continues to evaluate the safety and effectiveness of the 1% tenofovir gel using the same dosing strategy evaluated in CAPRISA 004. The results of this trial are expected in 2014.
One key message from all stakeholders is: Research on oral ARV-based prevention (PrEP) and ARV-containing gels and rings continues. Conflicting results are not a sign to stop research but to intensify it.
Recently Released
AVAC Report 2011: The
End?
AVAC’s annual review of the field offers a
comprehensive agenda for ending AIDS and was
launched online with a variety of multi-media
components at www.avac.org/report2011.
P-Values
AVAC’s new bulletin on our partners’
activities worldwide is an opt-in newsletter.
You can subscribe and check out past issues at
www.avac.org/pvalues.
Not to be Missed
Jan 9–10: 2nd International
Workshop on HIV & Women, Bethesda,
MD
Jan 17–18: 2012 Black Gay
Research Summit, New Orleans, LA
Jan 19–20: National AAMSM
Leadership Conference on HIV/ AIDS and other
Health Disparities, New Orleans,
LA
Feb 15: AIDS 2012 abstract
submissions close (aids2012.org)
Feb 20–24: MTN Annual
Meeting, Washington, DC
March 5–8: Conference on
Retroviruses and Opportunistic Infections
(CROI), Seattle, WA
April 15–18: 2012
International Microbicides Conference (M2012),
Sydney, Australia