Closure of oral Tenofovir arm in VOICE Pre-Exposure Prophylaxis trial: PrEP as a “niche intervention”?

via Incidence, by Roger J. Tatoud

The Microbicides Trial Network (MTN) September 28th that its VOICE (Vaginal and Oral Interventions to Control the Epidemic, MTN003) HIV Pre-Exposure Prophylaxis (PrEP) prevention study will discontinue the daily oral tenofovir arm of the trial. The decision follows an interim review of the trial’s data by its Data Safety and Monitoring Board (DSMB) which recommended that VOICE stops evaluating the oral tenofovir tablet (TDF, brand name Viread), because it will not be possible for the study to show a difference in effect between the drug and the placebo tablet (futility) for the prevention of HIV infection in the context of that study. Importantly, the DSMB did not found any safety issues associated with the use of TDF in any arm of the trial.

This is the third PrEP trial, after FEM-PrEP and TDF2, for which an interim review of the trial’s data led to a change of course of the study. Because the four other arms of the VOICE trial continue, there are no data available publicly yet to explain why tenofovir would not show effectiveness in this study when three other studies showed a dramatic reduction in the risk of HIV infection with tenofovir alone or in combination with another antiretroviral (see table below). However, Sharon Hillier and Ian McGowan of the Microbicide Trials Network noted that the study’s population – predominately women in their 20’s, could be an important factor.

“If there’s one thing we’ve learned over the years it’s that unmarried women in their 20s are in a very different place in their lives than married women in their 30s. People in different circumstances will make different choices about their use of condoms, their choice of partners and whether or not to use a biomedical prevention product. As we continue the VOICE trial we recognize that there could be many factors that influenced the outcome with oral tenofovir, and even when we have more information available to us, understanding what exactly happened (or not) will not be simple.”

If confirmed (a full analysis of the data will not be available before several months) this would add to the challenge of defining a strategic use for PrEP in the general population or in populations at risk.

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[If an item is not written by an IRMA member, it should not be construed that IRMA has taken a position on the article's content, whether in support or in opposition.]

Washington D.C.: Public Meeting on Safety Issues in PrEP

An invitation from the Forum for Collaborative HIV Research:

Safety Issues in Pre-exposure Prophylaxis for HIV negative individuals, proposals for management of safety concerns, and pending plans for scale-up

Forum for Collaborative HIV Research

1608 Rhode Island Avenue, NW

Washington, DC 20036

August 19, 2011

8:30am - 4:00pm

The Forum for Collaborative HIV Research has been tasked by our collaborators in the public health community, including the US Food and Drug Administration, to convene an open public meeting to address safety issues that may surround the introduction of biomedical approaches to prevent HIV infection. Recent data from the iPrEx, Partners PrEP and CDC’s TDF2 studies support a conclusion that pre-exposure prophylaxis (PrEP) with antiretrovirals may be effective at preventing transmission of infection in otherwise healthy, vulnerable individuals upon exposure to HIV. This important finding may lead to scale-up, broad use of PrEP and, potentially, approval of a PrEP indication.

Recently, the drug development paradigm has also shifted with more focus on safeguarding individuals on medications. Premarket studies can miss important safety signals, either because the patient population is different and limited by enrollment criteria, too small to see low incidence events, or exposure is not long enough to identify latent effects. Compensatory behavioral issues may also be a concern upon scale-up. Appropriate communication strategies to reach the intended healthcare provider and the intended vulnerable populations must be identified and formulated. Mechanisms to anticipate and/or control the development of resistant HIV are also important. Finally, public focus as a result of our meeting may identify additional public health issues that should be addressed as well.

The Forum meeting will follow our usual format of panel discussions featuring stakeholders, including academics, trialists, clinicians, community advocates, public health professionals, and others. Each will be asked by a moderator to address a set of pre-prepared questions. Four panels are planned: (1) What are the safety issues of concern with pre-exposure prophylaxis?; (2) what are potential remedies to control safety risks and their pros and cons?; (3) what are the public health implications?; and (4) finally, a panel will summarize and identify next step.

Because of limited space, public participation in the meeting room will be limited to one participant per organization. An overflow room will be available for attendees on an as-needed basis. The meeting will be webcast to enhance national dissemination. Written supplementary questions can be directed to the panels. Webcast attendees can also submit written questions via instant messaging.

Registration: Register online at http://prep-reg.com/ to attend the public meeting or to view the live webcast.

Location: 1608 Rhode Island Avenue NW, Washington, DC 20036
Date and Time: August 19, 2011 8:30 AM-4:00 PM

________________________________________
Forum Announcements

Studies show new progress in HIV testing in emergency departments

July 29

A CDC sponsored supplement released in the Annals of Emergency Medicine details new HIV testing efforts in Emergency Departments. "Emergency departments play a critical role in helping people learn their HIV status, connecting them to life-prolonging care, and helping them avoid transmitting the virus to others"said Jonathan Mermin, MD, Director of CDC's Division of HIV/AIDS Prevention. Click here to read more

Controlling the HIV Epidemic - The Promise of ARV-Based Prevention: Presentations now available

July 28

Presentations made at the Forum co-sponsored IAS Satellite Symposium "Controlling the HIV Epidemic - The Promise of ARV-Based Prevention" are now available. Click here to read more

Statistical Methods for Causal Inference in Observational and Randomized Studies: Course fees increase on August 1

7/26/11 This course concerns statistical methods for causal inference using observational and experimental longitudinal data. The course will focus on the application of methodological advances in statistical and causal research to improve the design and interpretation of safety analyses. These analyses will become increasingly important in the post-marketing safety environment for new drugs.

Dates: September 26-28, 2011.
Location: UC Washington Center, Washington, DC.

To register, please use the following link: www.hivforum.org/stats2011

[If an item is not written by an IRMA member, it should not be construed that IRMA has taken a position on the article's content, whether in support or in opposition.]

Open-Label Extension of iPrEX HIV PrEP Study Begins at 11 Sites in 6 Countries

Via iPrEX News.

The iPrEx Open-Label Extension Study (iPrEx OLE), the next phase of the first human study to report efficacy results on pre-exposure prophylaxis (PrEP) to prevent HIV infection, has begun at clinical trial sites around the world. Approximately 2,000 men and transgender women who have sex with men are expected to participate in the 72-week iPrEx OLE study. Study sites in the United States and South Africa are enrolling participants now, as other study sites finalize the regulatory approval process.

In PrEP, antiretroviral medications that are usually used to treat HIV are taken by uninfected people to reduce their risk of infection. The iPrEx study found that men and transgender women who have sex with men (MSM) who took a single daily tablet containing the HIV medications emtricitabine and tenofovir (FTC/TDF), known commercially as Truvada®, experienced an average of 44% fewer HIV infections than those who received a placebo (blank pill). HIV infection rates in the iPrEx study dropped by 90% among those who used PrEP consistently enough to have detectable drug in the body. The HIV risk reduction benefits of PrEP were in addition to those provided by safer sex counseling, condoms, HIV testing and the detection and treatment of sexually transmitted infections. iPrEx study results were published in the New England Journal of Medicine in November, 2010.

The news of the start of iPrEx OLE follows the announcements by two other major PrEP studies, Partners PrEP and the CDC study in Botswana, known as TDF2, which demonstrated the safety and efficacy of PrEP in heterosexual women and men.

AdvertisementiPrEx OLE is a continuation of the iPrEx study that will collect additional data on PrEP efficacy, safety and adherence. All HIV-negative participants who took part in the original iPrEx study and who wish to participate will receive FTC/TDF for HIV prevention for 72 weeks through iPrEx OLE. No placebo will be used in the Open Label Extension.

"We are in a critical moment in HIV prevention research," said iPrEx Protocol Chair Robert Grant, MD, MPH of the Gladstone Institutes and the University of California at San Francisco. "iPrEx provided the first proof of an important new method of HIV prevention that can help slow the global toll of 2.6 million new HIV infections each year. Partners PrEP and the TDF2 study have now expanded that finding by demonstrating the effectiveness of PrEP in heterosexual women and men. Developing and deploying proven HIV prevention methods -- including PrEP, microbicides, vaginal gels, clean needles, medical male circumcision, early treatment, counseling, testing, condoms and suppressive therapy for pregnant women will all be key to slowing the global epidemic."

Read the rest here.

[If an item is not written by an IRMA member, it should not be construed that IRMA has taken a position on the article's content, whether in support or in opposition.]