NEJM Publishes Papers on PrEP

Last week, The New England Journal of Medicine published online papers on the Partners ("Antiretroviral Prophylaxis for HIV Prevention in Heterosexual Men and Women"), FEM-PrEP ("Preexposure Prophylaxis for HIV Infection among African Women") and TDF2 ("Antiretroviral Preexposure Prophylaxis for Heterosexual HIV Transmission in Botswana") studies.

There was also an editorial "Preexposure prophylaxis for HIV - Where Do We Go From Here," and a look at some interesting case vignetttes - would YOU prescribe PrEP in these circumstances?.

These are great resources, hope you check them out.

[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position. Please look for us on Facebook here www.facebook.com/MappingPathways and you can follow us on Twitter @mappingpathways as well.]

A Qualitative Study of Provider Thoughts on Implementing Pre-Exposure Prophylaxis (PrEP) in Clinical Settings to Prevent HIV Infection

via PLoS ONE, by Emily A. Arnold, Patrick Hazelton, Tim Lane, Katerina A. Christopoulos, Gabriel R. Galindo, Wayne T. Steward, Stephen F. Morin

ABSTRAST

Background

A recent clinical trial demonstrated that a daily dose tenofovir disoproxil fumarate and emtricitabrine (TDF-FTC) can reduce HIV acquisition among men who have sex with men (MSM) and transgender (TG) women by 44%, and up to 90% if taken daily. We explored how medical and service providers understand research results and plan to develop clinical protocols to prescribe, support and monitor adherence for patients on PrEP in the United States.

Methods

Using referrals from our community collaborators and snowball sampling, we recruited 22 healthcare providers in San Francisco, Oakland, and Los Angeles for in-depth interviews from May-December 2011. The providers included primary care physicians seeing high numbers of MSM and TG women, HIV specialists, community health clinic providers, and public health officials. We analyzed interviews thematically to produce recommendations for setting policy around implementing PrEP. Interview topics included: assessing clinician impressions of PrEP and CDC guidance, considerations of cost, office capacity, dosing schedules, and following patients over time.

Results

Little or no demand for PrEP from patients was reported at the time of the interviews. Providers did not agree on the most appropriate patients for PrEP and believed that current models of care, which do not involve routine frequent office visits, were not well suited for prescribing PrEP. Providers detailed the need to build capacity and were concerned about monitoring side effects and adherence. PrEP was seen as potentially having impact on the epidemic but providers also noted that community education campaigns needed to be tailored to effectively reach specific vulnerable populations.

Conclusions

While PrEP may be a novel and clinically compelling prevention intervention for MSM and TG women, it raises a number of important implementation challenges that would need to be addressed. Nonetheless, most providers expressed optimism that they eventually could prescribe and monitor PrEP in their practice.

Read the full text here.


[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position. Please look for us on Facebook here www.facebook.com/MappingPathways and you can follow us on Twitter @mappingpathways as well.]

Pause and Rewind with Jim Pickett: Triumphs and Trials in 2011

Original content from the Mapping Pathways blog team

“PrEP … is hard as hell to figure out. Hard as hell. But that’s what we have to do – we have to be right there, at the hardest place possible, trying to get the answers.”

MP: Was 2011 a significant year with regard to new HIV prevention methods?

JP: Definitely. I think it’s been a really dynamic year. The discussion around ARV-based prevention has been heated, it’s been passionate, and it’s been very broad. The field as a whole has received so much attention this year because of all the studies that were reported, beginning in 2010. The lively discussion has put the research and advocacy that’s been ongoing for years on so many people’s radar for the first time.

MP: What were some of the biggest highlights in the prevention landscape this past year?

JP: In terms of the actual science that was reported out this year, a couple of studies were really important. The HPTN 052 trial proved beyond a shadow of a doubt that providing treatment to people can be very effective as a means of prevention as well as for treating the individual with HIV. It was something we all pretty much knew but we didn’t have a randomized controlled trial to prove it. Now we have one – and that’s really powerful.

There have also been significant results on the use of pre-exposure prophylaxis (PrEP) in heterosexual individuals. The Partners PrEP study and the TDF2 Botswana study have brought further proof that oral prevention – taking a pill every day – can work to prevent HIV, and can work quite well.

On the other side, we’ve had some confounding results as well. The FEM-PrEP trial closure, due to the fact it was unable to prove the effectiveness of Truvada in preventing HIV infection among HIV-negative women, has left us scratching our heads. The VOICE trial, which is investigating both microbicides and PrEP, had to close the tenofovir gel and pill arms due to futility – they weren’t going to be able to show these interventions work to prevent HIV.

We’ve come up against ‘futility’, and now there’s a huge question mark. We don’t yet know what is going on: Was it something biological? Was it because adherence was poor? Why did these products work in other trials? While there have been very encouraging results about PrEP, the jury is still out – for instance, is this a good intervention for heterosexuals, especially women? Both PrEP trials that have shown futility have been for women. These critical questions need to be addressed.

MP: What has the debate around PrEP been like? What are people saying?

JP: Like I mentioned, the debate around ARVs as prevention has been very dynamic. Wherever you are on the analysis of these new strategies, whether you are critical of these or really excited about them, much of the discussion has been fruitful and invigorating.

What has upset me, though, is that some people (whether they’re researchers, advocates, public health workers, or policymakers) have been drawing lines and pitting interventions against one other. For instance, PrEP, ARVs for HIV-negative people to prevent HIV acquisition, is being pitted against treatment, ARVs for HIV-positive people. There’s been a lot of discussion on who “deserves” the drugs and who doesn’t – I don’t think that’s helpful in any way. We should all be working to get ARVs to those who need them – HIV-positive people, of course, and also HIV-negative individuals who need them, can use them, and would find them very beneficial. It’s about ARV access writ large.

MP: Why do you think this has happened?

JP: This is what happens in times of scarcity and economic trauma. People say, “We can’t possibly do everything, so we should do only this and not that.” It’s not surprising, but it’s still disheartening. We need to think broadly, globally and not dismiss new interventions because they’re challenging or bring up lots of questions. PrEP does bring a ton of issues: It’s brand new, it’s just out of the box, we’ve never done this before, and it’s hard as hell to figure out. Hard as hell. But that’s what we have to do – we have to be right there, at the hardest place possible, trying to get the answers. That’s where we should be spending our energy.

When the female condom was first introduced, it wasn’t given the attention and support it needed and a lot of people dismissed it. I think that really hobbled its potential for a long time. I don’t want to see PrEP in the same place – being disparaged before we’ve had a chance to explore and fully understand its potential.

MP: How can the Mapping Pathways project help in this context?

JP: The Mapping Pathways project will be offering a synthesis of literature, real-world experience, and key stakeholder opinions from vastly different perspectives and regions of the world. This is going to be extremely helpful because we know that just having great science isn’t going to get any of these interventions rolling. This project is helping create and disseminate information that countries, regions, states, and cities can use to make informed decisions about how they engage with these new prevention technologies – or not. I think the key word here is “informed”. What we’re all hoping is that these decisions are made based on a combination of science, feasibility, and acceptability in each region.

The fact that we’re going to be able to play a role in that process is very exciting. Wearing my Mapping Pathways hat, I’m really proud of the work we’ve done this year. The first wave of data collection is done – we’re now analyzing our literature review, our survey results and stakeholder interviews, and results from our ExpertLens process. I’m very excited about the data and analysis that we’ve been able to pull together as a multinational team. And now we get to start sharing these great insights with the world!

Jim Pickett is the Director of Prevention Advocacy and Gay Men's Health at the AIDS Foundation of Chicago. He is chair of IRMA (International Rectal Microbicide Advocates), and a member of the Mapping Pathways team.

[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position.]

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.

Read the rest.


[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position.]

From iPrEx to TDF2: A Quick Look at the Prevention Journey this Past Year

Starting in July 2010, encouraging results from a number of HIV prevention studies have revolutionized the HIV prevention landscape over this past year – from using oral PrEP and microbicides among HIV-negative people to reduce the risk of infection, to providing early antiretroviral treatment to people with HIV to reduce the risk of transmitting the infection to their uninfected partners.

Here is a quick look at six of the most significant trials: CAPRISA 004, iPrEx, FEM-PrEP, HPTN 052, Partners, and TDF2 that, together, are radically changing the way we look at prevention.

July 2010: CAPRISA 004 – a microbicide study

Background: Conducted by the Centre for the AIDS Programme of Research in South Africa (CAPRISA), Family Health International (FHI), and CONRAD. Funded by the United States Agency for International Development (USAID) and Technology Innovation Agency (TIA).

Who: 889 sexually active women.

Where: South Africa.

What: 1% tenofovir vaginal gel, applied within 12 hours before and after sexual intercourse.

Key results: The microbicide provided 39% protection from HIV acquisition. In women who used the gel more than 80% of the time, there was 54% efficacy. The gel also halved the women’s risk of acquiring HSV-2, the virus that causes genital herpes and also increases the risk of contracting HIV.

To know more about this study, click here and here.

November 2010: iPrEx – a large-scale, Phase III PrEP study

Background:Funded by the U.S. National Institutes of Health (NIH) through a grant to the J. David Gladstone Institutes, a non-profit independent research organization affiliated with the University of California at San Francisco (UCSF). Additional funding provided by the Bill & Melinda Gates Foundation.

Who: 2,499 men who have sex with men and transgender women who have sex with men.

Where: Peru, Ecuador, South Africa, Brazil, Thailand and the US.

What: Once-daily does of Truvada (oral FTC-TDF – emtricitabine and tenofovirdisoproxilfumarate), as well as monthly HIV testing and risk-reduction counseling.

Key results: PrEP provided 42-44% protection from HIV acquisition. The protective effect was even higher among those with good pill adherence. According to the initial findings, with 50% adherence reported, the efficacy was 50%; with 90% adherence reported, there was 73% efficacy. Updated findings were presented at the International AIDS Society conference in Rome: the drug had 92% efficacious in preventing HIV infection amongst those who had detectable drug levels; overall efficacy was 42%.

To know more about this study, click here and here.

April 2011: FEM-PrEP – a Phase III PrEP study

Background: Implemented by Family Health International (FHI) in partnership with research centers in Africa. Funded by the United States Agency for International Development (USAID), with early funding from the Bill & Melinda Gates Foundation.

Who: 1,951 sexually active women.

Where: Kenya, South Africa, and Tanzania.

What: Once-daily does of Truvada (oral FTC-TDF – emtricitabine and tenofovirdisoproxilfumarate), as well as HIV testing and counseling.

Key results: The interim FEM‐PrEP study results were inconclusive. As determined by a preliminary data review, the study would not have been able to demonstrate whether or not Truvada was effective in preventing HIV in women in this study. FHI, therefore, decided to close the trial early due to futility.

To know more about this study, click here and here.

May 2011: HPTN 052 – a Phase III antiretroviral study

Background:Conducted by the HIV Prevention Trials Network (HPTN). Funded by the National Institute for Allergy and Infectious Diseases (NIAID) at the US National Institutes of Health (NIH). Additional support provided by the NIAID-funded Adult Clinical Trials Group.

Who: 1,763HIV serodiscordant couples, in which the HIV-infected partner had a CD4+ cell count of 350-550 cells/mm^3.

Where: Botswana, Brazil, India, Kenya, Malawi, South Africa, Thailand, United States and Zimbabwe.

What: Initiation of early antiretroviral treatment, as well as regular counseling.

Key results:The interim review showed that antiretroviral treatment reduced the risk of HIV transmission from treated partner to uninfected partner by 96%.

To know more about this study, click here and here.

July 2011: Partners – a Phase III PrEP study

Background: Funded by the Bill & Melinda Gates Foundation.  The University of Washington International Clinical Research Center is the study sponsor and coordinated the trial in collaboration with investigators at the study sites.

Who: 4,758 heterosexual African HIV serodiscordant couples, that is, in which one partner had HIV and the other did not. 

Where: Kenya and Uganda.

What: Once-daily does of Truvada (oral FTC-TDF – emtricitabine and tenofovirdisoproxilfumarate) or tenofovir (oral TDF), as well as HIV testing and counseling.

Key results: The risk of infection was reduced by 73% in those who received Truvada, and by 62% in those who received tenofovir alone. Adherence was extremely high: more than 97% of doses dispensed were taken, and 95% of participants stayed in the study.

To know more about this study, click here and here.

July 2011: TDF2 – a PrEP study

Background: Conducted by BOTUSA, a partnership between the Botswana Ministry of Health and the US Centers for Disease Control and Prevention.

Who: 1,200 sexually active men and women.

Where: Botswana.

What: Once-daily does of Truvada (oral FTC-TDF – emtricitabine and tenofovirdisoproxilfumarate), as well as HIV testing and counseling.

Key results: In the primary analysis, it was seen that Truvada reduced the risk of infection by 63%. In the secondary analysis, excluding infections that occurred amongst people who had run out of their Truvada pills and had not taken one for at least 30 days, there was 78% efficacy.

To know more about this study, click here and here.

To stay abreast of research into new prevention technologies, check out AVAC and IRMA.

[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position.]

Antiretroviral prevention methods 'not in competition' with each other

Via AIDSMap, by Keith Alcorn.

Antiretroviral prevention methods are not in competition, and policy makers and providers need to start to thinking about how antiretrovirals, pre-exposure prophylaxis and microbicides will be provided as part of a combination prevention package – and who will benefit most from each method, delegates heard at a satellite meeting on the opening day of the Sixth International AIDS Society Conference (IAS 2011) in Rome.

“You don’t want to have the family planning clinic here, the pills clinic here, the injections clinic here, and the microbicides clinic over here,“ said Dr Stephen Becker of the Bill and Melinda Gates Foundation.

Delegates were discussing the rapidly changing landscape of HIV prevention methods that use antiretroviral drugs. One year ago, at the International AIDS Conference in Vienna, the world heard the results of the CAPRISA study, which showed that a microbicide gel containing tenofovir halved the risk of HIV infection in women who used the vaginal gel consistently.

Since then results from four studies have added to the array of prevention methods that exploit antiretroviral drugs to prevent transmission or acquisition of HIV infection:

• The iPrEx study showed that taking the antiretroviral combination Truvada (tenofovir and emtricitabine (also known as FTC) reduced the risk of HIV infection in men who have sex with men by 44%.
• The HPTN 052 study showed that early treatment reduced the risk of HIV transmission to an uninfected regular partner by at least 96%.
• The Partners study showed pre-exposure prophylaxis with Truvada or with tenofovir alone reduced the risk of HIV infection by between 62% and 73%.
• The TDF2 study showed that  pre-exposure prophylaxis with Truvada reduced the risk of infection by between 62% and 78%.

The first tenofovir-containing microbicide could receive regulatory approval by the end of 2013, subject to positive results from a confirmatory trial now taking place in South Africa. That study is testing exactly the same dosing regimen as that used in the CAPRISA study, the so-called BAT 24 dosing schedule: one dose Before, one After, and no more than Two doses in 24 hours.

A second CAPRISA study (008) is testing the roll-out of tenofovir gel through family planning clinics in KwaZulu-Natal, comparing the monthly testing and follow-up schedule used in the original CAPRISA study with a three-monthly schedule, in order to examine the feasibility and acceptability of providing a microbicide through existing health services that target sexually active women.

Although the South African government has already begun investing in the scale-up of production facilities to manufacture the gel, the extent of demand for the microbicide is still unclear. Studies of women’s’ attitudes towards the microbicide will be needed to gauge demand, but a lot of work will also be needed to develop demand – and to make sure that women understand how they could benefit from using the microbicide.

“We need to reach out to women who don’t perceive themselves to be at risk, and we should be getting communities to rally round to be early adopters of tenofovir gel,” said Samu Dube of the Global Campaign for MIcrobicides.

“We need to get the product to the places where women are: the family planning clinics, the immunisation centres, antenatal clinics. We also need to target the school health system.”

However, work will also be needed to convince the providers of those services that they have a role to play in expanding women’s opportunities to protect themselves from HIV infection.

Read the rest here.

[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position.]

Safety Issues in PrEP: A Public Meeting

 You are invited to a public meeting with the Forum for Collaborative HIV Research in Washington D.C.:

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

[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position.]

Models: Tools to Improve Decision Making about HIV

Via AIDS.gov, by Ronald Valdiserri, M.D., M.P.H.

For those of us who work in the HIV/AIDS field, the month of July was dominated by exciting HIV prevention news coming out of the International AIDS Society meeting in Rome. Results from the HPTN 052 study showed that early, compared to delayed, antiretroviral treatment resulted in a 96% reduction in HIV transmission to uninfected partners. The TDF2 study conducted by CDC in partnership with the Botswana Ministry of Health, found that a once-daily pill containing two anti-HIV drugs reduced the risk of acquiring HIV infection by about 63% in a study population of healthy, heterosexual men and women. These and other study findings continue to add weight to the notion that HIV treatment is prevention. All of us are encouraged when we think about how these findings could be translated into real world settings in a way that would bring us closer to achieving the goals of the National HIV/AIDS Strategy.

Without minimizing the tremendous enthusiasm that rightly attends the prevention breakthroughs that were presented in Rome, I would like to talk about another scientific discussion that took place in July. As it turns out, this meeting was also held in a world capital, although to a much smaller audience. And while the results of this two-day meeting didn’t garner media attention the same way as the Rome meeting did, the topics under discussion were no less consequential.  In mid-July, I was very fortunate to attend a two-day workshop on “Modeling and Evidence-Based Decision Making” sponsored by amfAR, the Foundation for AIDS Research and cosponsored by the Kaiser Family Foundation, the National Alliance of State and Territorial AIDS Directors, and the Urban Coalition for HIV/AIDS Prevention Services. Meeting participants included colleagues from state and local departments of health, academia, federal government, and professional and community-based organizations.

Colleagues from Los Angeles, San Francisco, Maryland, and New York City shared with us their experiences with using various models to assist in making decisions about “optimizing” HIV prevention investments. Using different approaches, each of these health departments was trying to answer the same question, “What combination of prevention services and activities will result in the greatest reduction of the number of new HIV infections?”

At the onset of the meeting, we were reminded that modeling is used in other areas of health and public policy decision-making, especially when leaders are trying to combine diverse information from a variety of sources in order to make sound decisions at a population level.  However, even the biggest fans of modeling reminded us that a model is not a “crystal ball” nor is it infallible.  Instead, what models do is provide a tool to help us make better decisions about complex realities. Good models should always be clear about the inputs and assumptions that were used to generate the results. And perhaps most importantly, they should be used to guide rather than to conclude any discussions about how best to allocate resources.

Read the rest here.

[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position.]