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.]

PrEP: time to rethink prevention, effectiveness and ethics?

via Somatosphere, Marsha Rosengarten

One of the more controversial interventions proposed for HIV prevention in those who test HIV antibody negative and perceived to be at risk is pre-exposure prophylaxis (PrEP) – a daily pill comprising one or two antiretroviral drugs manufactured by Gilead Inc.  Besides the mixed results from multi-site randomised controlled trials (RCTs) seeking to establish the efficacy of PrEP (see iPrEX versus Fem-PrEP), concerns have been raised about PrEP’s potential to undermine condom use, its cost implications in locales where treatment provision is still lacking and elsewhere, its potential to cause unwanted drug side-effects as well as possible drug resistance in those it fails to protect.

Nevertheless, continuing new infections and evidence that high adherence produces a strong protective effect are mobilising many public health authorities to devise feasible implementation models.

Most remarkable about the growing interest in PrEP is the exclusion of the social sciences from major forums where this work is taking place.  One such example is a two-day forum held in the UK by IAPAC on the dual topics of treatment as prevention (TasP) and PrEP.  The only non-biomedical speakers listed on the programme were a psychologist (speaking on adherence), a bioethicist, activists and public health officials linked to various national epidemics.

Indeed it won’t come as a surprise to many to know that despite the millions of dollars to support RCTs for PrEP, the Bill and Melinda Gates Foundation have so far declined to support a substantial programme of social research on PrEP.  In fact if we consider the bioethical requirements imposed on the conduct of RCTs for PrEP and other biomedical interventions, there is no ethical requirement for research on the social dimensions of the intervention during or post RCTs. This applies even when RCTs demonstrate candidate efficacy.

Read the Rest.


[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.]

The Lancet:PrEP for HIV prevention reaches key milestone

via the Lancet.com, by Salim S Abdool Karim and Quarraisha Abdool Karim

On May 10, 2012, a US Food and Drug Administration (FDA) advisory committee voted in support of the use of tenofovir-emtricitabine for HIV prevention.1 If the FDA, which is scheduled to make its decision by June 15, adopts the committee's recommendations, tenofovir-emtricitabine will become the first antiretroviral drug to be approved as pre-exposure prophylaxis (PrEP) for the prevention of HIV, paving the way for implementation.

PrEP has a unique advantage in young women in southern Africa, who bear a disproportionate burden of the HIV epidemic. In much of this region, young women are often unable to convince their male partners to use condoms, remain faithful, or have an HIV test. To rely on her HIV- positive discordant male partner to come forward to test, to agree to take antiretroviral therapy (ART), and to take his ART with high adherence, all for her protection, puts a woman's risk of acquiring HIV back in the hands of men, thereby disempowering women and undermining their efforts to control their risk of HIV.

However, there are several criticisms and concerns about PrEP. First, that data on the effectiveness of PrEP, especially in women, are inconsistent. This concern is based on the results of two PrEP studies—the FEM-PrEP2 and VOICE3, 4 trials—which were stopped, at least partly, earlier than planned when they did not show efficacy. To some extent, this concern has been allayed by recent data from the FEM-PrEP trial5 which show that adherence to daily tenofovir-emtricitabine in the trial was too low allow assessment of efficacy. Data to explain the VOICE trial, which still has an ongoing tenofovir-emtricitabine group, are not expected until 2013.

Second, some suggest that antiretroviral drugs should be provided to HIV-negative people only when all eligible HIV-positive patients are receiving ART. Although it is a legitimate concern that eligible HIV-positive patients should be prioritised for ART for their own health and to save their lives, it is spurious to trade off treatment and prevention as if these drugs are being taken away from sick and dying patients to be given to healthy people. Treatment and prevention strategies are a continuum in their use of antiretroviral drugs—both are needed in conjunction with each other to ensure ART provision is sustainable in the long term and to realise the quest to end the HIV epidemic.

Read the Rest.


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

Microbicides 2012 Conference: “Someday, our ARV-prevention tools will be as sexy as the I-Phone!”

Original content from the Mapping Pathways blog team

This is the second part of a two-part blog series on highlights and discussions from the Microbicides 2012 conference that recently concluded in Sydney. Here, Jim Pickett re-emphasizes the importance of adherence in clinical trials (a big topic of discussion at the conference) and his optimism about the future of the HIV prevention and treatment landscape. Read Part I here.

MP: Can you give us some examples that illustrate the issues surrounding adherence?

JP: The Partners PrEP trial and the FEM-PrEP trial are good case studies to illustrate the issues surrounding adherence in an HIV prevention clinical trial. Partners PrEP reported very high levels of adherence while the FEM-PrEP trial had to be stopped in April 2011 due to “futility.” Studies later indicated that while many of the FEM-PrEP participants said they adhered to the medication schedule, blood tests indicated that many did not.

A built-in support system and the risk perception of participants are the key here. In Partners PrEP, serodiscordant couples were enrolled together into the trial. One partner was HIV positive while the other was negative. The HIV risk of the HIV-negative partner was not theoretical; it was real. HIV was in their life and they were in it together.

FEM-PrEP involved women recruited on their own, with no consideration whether they were in a serodiscordant relationship – or any relationship for that matter. The risk of HIV was not present in the form of a partner who already had it, but it was, in fact, present in their environment where there was very high HIV incidenceIV HIV . It is interesting that many of these women did not believe themselves to be at a high risk of HIV, despite this high incidence.

Human beings are very good at rationalizing risks and saying “it can never happen to us.” I can drive fast and will never get into a car accident. If I feel a certain behavior is not risky, or that I can “get away with it”, I will not take steps to protect myself.

We don’t want to create tools where only people who are married or in a relationship are able to use the tools successfully. That would be crazy. But we do have to think about how important those social relationships are and use the lessons learned to devise new tools and new trials that give us answers – and develop things that work for all kinds of people, regardless of relationship status, sexual orientation, or whether their potential HIV exposure comes from unprotected vaginal intercourse, unprotected anal intercourse, or from the sharing of syringes during injection drug use.

MP: Are there any trials coming up that you are excited about?

JP: I’m very excited by the upcoming MTN-017 rectal microbicide safety and acceptability trial that will enroll approximately 186 gay men, other men who have sex with men, and transgender women at trial sites in South Africa, Peru, Thailand, and the United States. Participants will go through three eight-week cycles: One cycle of having a daily Truvada tablet, another cycle of applying a “rectal friendly” reformulated tenofovir gel every day, and a cycle of applying the gel before and after having sex.

What impresses me is the level of community involvement sought and obtained to help design this trial. The trial team, and advocates such as myself, visited each of the sites mentioned, had day-long meetings with community members, captured all their observations, and made adjustments to the trial design from the input received. We have to listen to the voices of the communities. We can’t just show up and conduct trials.

MP: What are your other thoughts on the HIV prevention and treatment landscape?

JP: I always like to compare the HIV prevention and treatment landscape to the evolution of computers and phones. Years ago, computers were the size of a house. It took time for the computer to evolve from its clunky beginnings to its current look where we can carry it around in our pocket and it can do more things than we ever could have imagined. Now we have phones and computers that are completely intuitive and easy to use.

Similarly, the HIV landscape has evolved over the years. Before 1996, we had a handful of drugs that didn’t always work great. They were toxic and had to be taken multiple times a day. When protease inhibitors came out in 1996, people near death’s door were brought back to life. But they also had to suffer through a whole host of side effects like nausea, diarrhea, and body disfigurements.

Now, new-age ARV medication can combine three drugs into one pill that has to be taken just once a day. The side effects are minimal and you don’t have to worry about requirements like eating it on a full or empty stomach, or having it refrigerated.

We are now in the clunky computer stage of ARV-based prevention. But, things will keep getting better. We can’t get to the streamlined phase before going through the clunky phase. We have to learn to crawl before we can run. Someday, our ARV prevention tools will be as sexy as the iPhone.

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. Read Part I of Jim’s interview here.

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

Microbicides 2012 Conference: Adherence – the A-word on everyone’s lips

Original content from the Mapping Pathways blog team

In part I of this two-part blog series, Jim Pickett talks about his experiences at the recently concluded Microbicides 2012 conference in Sydney and the buzz among advocates and trial designers today.

MP: What were some of the highlights for you from the conference?

JP: The conference in itself was great with many interesting and informative presentations. A highlight for me was that conversations about rectal microbicides were integrated throughout the conference and not just in one or two presentations. Rectal microbicides got a lot of attention.

From a Mapping Pathways perspective, we submitted an oral abstract that was accepted and I think the presentation I did was well received. We generated a lot of conversations about the work we have been doing and are planning to do in the upcoming year.

A Canadian colleague presented on their country’s plans for integrating ARV-based prevention into their national prevention plan and one of their planned activities is to develop a Canadian version of Mapping Pathways. This stems from a consultation in Ottawa I participated in last year – so it was gratifying to see Mapping Pathways being picked up by others – and presented at an international conference.

MP: Are there any major themes that emerged from this conference?

JP: Adherence, the A-word, was a very big topic throughout the entire conference. We realized that we have to make HIV-prevention or treatment products people like and will want to adhere to. We have to figure out how tools like PrEP and microbicides fit in people’s lives, and funding should be put in place to better understand what people want, how they have sex, and the role of pleasure, love and intimacy, among many other “real world” realities. Right now, only about two percent of the budget of any study is used for the socio-behavioral aspect – that is, understanding participants’ motivations, documenting adherence, and exploring the communities they are a part of.

Adherence is especially crucial for PrEP to move into the real world. Participants in trials come to the clinic for monthly visits that include a host of prevention services and counseling on condom use and adherence to the study product. If adherence is an issue in such a controlled environment, how big of an issue will it be in the real world where they are not getting that level of intensive support?

A scenario where a trial has to be stopped because people did not take the drug is a major concern because it leaves us more questions than answers. We get no answers on the efficacy of the drug – we are left thinking “what if the person had taken it as instructed?”  We cannot afford to spend millions on trial after trial where we find out finally that people did not take the drug as instructed.

Sure, the lack of adherence could be telling us about acceptability – and if we are making products that people are having a hard time adhering to, is this product really acceptable? By the same token, this is an iterative process – what we have is what we have right now, and the only way to determine if the drug works is if people take it. We can’t improve on the delivery if we can’t answer that question. It is a bit of a conundrum.

MP: What are some of the strategies discussed to tackle the issue of low adherence?

JP: The first step, as mentioned, is to increase funding for the socio-behavioral components of the trial. We need to do better at finding the “right” trial participants. Imagine a case where two people are being recruited for an HIV study trial. One is a person who wants to do the study to the best of his or her abilities and is motivated by the aims of the study. The other person is motivated by the access to healthcare and the little monetary incentive provided by participation in the study. Would both their levels of adherence be the same? This isn’t to cast judgment on anyone – but really, we need to answer the study question – and we can’t do that if people don’t follow the study protocol.

Another interesting strategy being discussed more and more is separating the people who counsel the participants during the trial (adherence counseling) from the people who record user experiences taking, or not taking, the study product. If the same person performs these two functions, participants who form a bond with their adherence counselors during the course of the trial may be unwilling to disclose exactly how well they adhered to the program. The end goal is to find better ways to capture the data and make participants feel completely relaxed about being honest about their user experience. If they did not take the drugs as instructed, that’s ok. But we want to know why.

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. Stay tuned for part II of the blog.

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

Adherence – the key to success?

Original content from the Mapping Pathways blog team

A recent Mapping Pathways post talked about how the Partners PrEP study helped some couples work through their relationship problems – these couples saw the trial as a way to save their strained marriages. A key finding from the trial was the high level of adherence observed amongst the participants. The HIV-negative partner would remind the HIV-positive partner to take medication on time, replenish pill supplies, and keep follow-up appointments with counselors.

Adherence was also a key issue that came up at the Conference on Retroviruses and Opportunistic Infections (CROI) held recently in Seattle, Washington. Adherence is critical to interpreting the results in any trial, since a study pill, if not taken as directed, can make a highly effective pill appear ineffective.

A case in point is the FEM-PrEP study that involved 2,056 HIV-negative women in South Africa, Kenya and Tanzania who were randomly assigned to take either a daily Truvada pill or a placebo pill. However, the trial was stopped in April 2011 due to “futility” when an interim analysis discovered both trials arms having near-identical HIV infection rates. There were 33 HIV infections in women taking Truvada and 35 in women taking placebo.

While the participants in the study stated that they took their pills 95% of the time, drug levels found in the blood of women assigned to the Truvada study wing indicated that less than 50% of the women had actually taken the drug in the last 12 days.

In contrast, the Partners PrEP study, which enrolled 4,758 seriodiscordant (one partner HIV-negative and the other HIV-positive) couples in Kenya and Uganda, indicated adherence to medication at almost 97%. 

Why was there such a drastic difference in the levels of adherence in the two trials? Investigators suggested that the differences in population between the two studies could be one reason. The Partners PrEP study involved couples who defined themselves as being in long-term, stable relationships, which was one of the pre-requisites for lasting through the two-year-long trial.

On the other hand, the women recruited for the FEM-PrEP study were much younger and there was no such requirement of being in a stable relationship. Initial qualitative surveys indicated these women did not believe themselves to be at a high risk of HIV, despite high incidence in the community around them. 

In short, the Partners PrEP study had in-built adherence motivators, in the form of committed partners, many of who participated in the whole process and actively helped their companions adhere to pill intake.

Could similar intrinsic motivators have improved the rate of adherence to medication in the FEM-PrEP study? And could similar subtle motivators be incorporated in other studies to improve the rates of adherence?

“Adherence is the word on everyone’s lips and minds these days – at CROI, at M2012, among trial designers, program implementers and advocates,” says Jim Pickett, Director of Prevention Advocacy and Gay Men's Health at the AIDS Foundation of Chicago and a Mapping Pathways member.

Stay tuned to the Mapping Pathways blog for more interesting posts on the important issue of adherence.


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

Researchers Explain the Role of Adherence in PrEP Trials at CROI 2012

via AidsMap.com, by Gus Cairns

Adherence makes all the difference to the efficacy of pre-exposure prophylaxis (PrEP), the 19th Conference on Retroviruses and Opportunistic Infections (CROI) heard today.

Further data were presented from two trials of PrEP (giving anti-HIV drugs to HIV-negative people to prevent infection), which announced dramatically different results last year.

In April 2011, the FEM-PrEP study found that giving HIV-negative women tenofovir/FTC (Truvada) pills to prevent their acquiring HIV was totally ineffective: there was no difference in HIV incidence between women taking Truvada and women taking placebo.

In July 2011, however, the Partners PrEP study found that Truvada was 73% effective in preventing HIV transmission between heterosexual partners of different HIV status.

How do we explain why giving HIV-negative women antiretroviral pills made no difference to the HIV infection rate in one trial, but prevented at least two in every three infections in the other? The difference, it appears, is that in the Partners PrEP trial, adherence to the study medication was very high, whereas in FEM-PrEP, despite counselling and support, less than half the women took their PrEP pills regularly.    

The Partners PrEP study

The Partners PrEP study enrolled 4758 serodiscordant couples in Kenya and Uganda; the HIV-negative partner was female in 38% of couples. This study had three arms: a daily tenofovir pill, a daily Truvada pill, or placebo.

There were 17 infections in participants on tenofovir, 13 on Truvada and 52 on placebo. Efficacy overall was 75% in those assigned Truvada and 67% in those assigned tenofovir, though confidence intervals (44% to 81% in tenofovir and 55% to 87% for Truvada) overlapped, so the efficacy of the two regimens was the same statistically. The same was true of efficacy observed in women (65%) and men (70.5%).     

Adherence according to pill counts of unused medication was 97%. A substudy (Donnell) compared tenofovir levels in the blood of 29 out of the 30 people who became infected in the two PrEP arms with levels in a random selection of 198 people who did not become infected.

Tenofovir was undetectable in the blood of 70% of the people who became infected but only 18% of the people who did not, indicating a ‘true’ adherence level of about 80% – and having a detectable level of tenofovir in the blood was associated with an 86% reduction in HIV risk in those taking tenofovir and a 90% reduction in those on Truvada.  

The FEM-PrEP study

In the FEM-PrEP study, 2056 HIV-negative women in South Africa, Kenya and Tanzania were randomised to take a daily Truvada pill or a placebo. The trial was stopped when an interim analysis found near-identical HIV infection rates in both trial arms. There were 33 HIV infections in women taking Truvada and 35 in women taking placebo; this translates into annual incidence rates of 4.7% and 5.0% respectively. This 0.3% difference is no difference at all, statistically speaking (hazard ratio 0.94, 95% confidence interval 0.59 to 1.52, p = 0.81). 

Participants in the study said they took their pills 95% of the time and adherence as measured by pill count was 85%. However when drug levels of tenofovir and FTC were measured in the blood of women assigned to Truvada, the investigators found that less than 50% of the women who should have been taking the drug had actually done so in the last 12 days, and less than 40% within the last 48 hours.

In infected participants, 26% had detectable levels of tenofovir in their blood in the last visit before they tested HIV positive, 21% at the visit they tested positive, and 15% at both visits; in non-infected participants whose samples were taken at the same visits they were 35%, 38% and 26% respectively.

Read the Rest.


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

CROI 2012: Researchers Present FEM PrEP Results

via MedPage Today, by Ed Susman

Pre-exposure prophylaxis with antiretroviral drugs failed to prevent women in Africa from becoming infected with human immunodeficiency virus (HIV) – apparently because more than half the women failed to take their medication.

The incidence of HIV infection among previously uninfected women treated with a co-formulation of emtricitabine and tenofovir (Truvada) was 4.7 per 1,000 person-years compared with a rate of 5 per 1,000 patient-years among women in the placebo group (P=0.81), said Lut Van Damme, MD, PhD, senior scientist at FHI 360, in Durham, N.C.

In a press briefing here at the Conference on Retroviruses and Opportunistic infections, Van Damme said it was likely that lack of adherence resulted in the failure to show a difference between those women on the active antiretrovirals and those who received placebo.

"The women in the study seriously overestimated adherence," she said. The participants told researchers that they took their assigned medicine 95% of the time. Pill counts indicated that 85% of the pills were not returned at regular points in the trial. But tests for emtricitabine/tenofovir in the blood of patients showed that only about 40% of the women had levels of the drug that would indicate the pills had been ingested within 48 hours of the tests.

The study was stopped early when an interim analysis showed that it was unlikely to prove positive.
The so-called FEM-PrEP was a randomized, double-blinded, placebo-controlled trial of once-daily oral emtricitabine/tenofovir. The primary effectiveness endpoint was incident HIV infection during 52 weeks of follow-up.

Participants attended screening, enrollment, and follow-up visits monthly. HIV seroconverters were taken off the product and followed for an additional 52 weeks

Read the Rest.


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

Mapping Pathways 2011: The year in voices

Original content from the Mapping Pathways blog team

“We are on the verge of a significant breakthrough in the AIDS response. The vision of a world with zero new HIV infections, zero discrimination, and zero AIDS-related deaths has captured the imagination of diverse partners, stakeholders and people living with and affected by HIV. New HIV infections continue to fall and more people than ever are starting treatment. With research giving us solid evidence that antiretroviral therapy can prevent new HIV infections, it is encouraging that 6.6 million people are now receiving treatment in low- and middle-income countries: nearly half those eligible.” - Michel Sidibe, UNAIDS Executive Director, World AIDS Day report


Earlier this month, WHO and UNAIDS released a World AIDS Day report providing a snapshot of goals and progress made in 2011 toward HIV/AIDS prevention. We thought we’d provide a snapshot of the Mapping Pathways project as well – but through the voices of some of the most memorable and inspiring people we spoke with this year.

APRIL:
“It’s been like Christmas every day since July at the International AIDS Conference in Vienna when the CAPRISA study results came out… We’ve gotten over this first hurdle; we’ve proven that we can create new ways to prevent HIV through the use of ARVs taken orally or applied topically but now we have to figure out how to get that pill, or gel, or whatever into the right hands in the right place at the right time. We’re grappling with all the problems that come with success.” - Jim Pickett: ‘Success! Now what?’
   
MAY:
“There is a threat – still distant but definitely visible – that we will lose this astonishing success through complacency… We can make AIDS rare – and eliminate it entirely from rich countries – using technologies that we already have. The question is whether we have the will to do it.”  - Mark Chataway: Using antiretrovirals to prevent new infections

“There’s still so much we don’t know, and these are open questions rather than being settled questions… we can’t prove that the intervention worked, and we can’t prove that the intervention didn’t work … There are still things to be learned.”  - Julie Davids: FEM-PrEP closure update – What does ‘futility’ mean exactly?

“I think whenever the field starts to go on emotion, we get into trouble… Human behavior keeps messing up the plot.”  - Dr. Linda-Gail Bekker: Of Mice, men, and microbicide trials   

JUNE:
 “I put the word MSM on the board, and do you know what one woman participant said? She said, ‘By MSM do you mean men who have sex with men? Yes, they must die; and if not, they must be killed!’ I was so taken aback. I thought, ‘Oh my God, this is where the advocacy has to start from.’” - Brian Kanyemba: A snapshot of advocacy in Africa

“The level of efficacy seen in the HPTN052 study is stunning, and is extremely important on several fronts. First, in terms of the potential of this strategy to reduce transmission, it is clearly an effective option… Of course, there are some issues associated with this strategy as well.”  - Dr. Joe Romano: Thoughts on the microbicide pipeline and the recent HPTN 052 results

“I believe that it is a political, economic and human tragedy that the first time our country has had a national HIV/AIDS strategy is exactly at the same time that we’re being told there are no resources to put it fully into place... We are, in significant ways, being restrained from putting our best minds and hearts at the forefront of this effort. When we get to the end of the day, there are good ideas, and then there are good ideas that are fully funded.”  - Julie Davids: The economic effect of HIV/AIDS in the US

JULY:
“Sex sells. People in the commercial world use sex to sell things like cars, toothpaste, pens…almost anything! Why not use sex to sell safer sex?”  - Anne Philpott: How sexy sex can help prevent HIV transmission

“Working with vulnerable populations like transgender individuals and men who have sex with men (MSM) was really an eye opener. These are people who often have nothing to their name (often not even a roof over their head), are disowned by society and their families and are completely discriminated and stigmatized against. Yet a number of them were keen to help spread awareness about HIV/AIDS, prevention options and vaccines so that others may benefit from the information and not get infected with HIV. This degree of humanity is truly remarkable.”  - Dr. Sonali Kochhar: PrEP in India

AUGUST:
“My sense is that many people are still very uncomfortable and not quite able to figure out why we’re talking about PrEP in the Indian context. Many senior people in the field feel the focus needs to be on TLC+.”  - Anjali Gopalan: Notes from India – concerns and challenges around PrEP

“The matchmaking started because people living with HIV don’t disclose their status to their parents. In India, when the boy is 30 or the girl is 24-25, the parents want them to get married. They start looking for partners and the person who is infected is unable to talk freely to them and say, ‘Look, I have HIV and I can’t get married.’ That’s when they come to me and ask, ‘My parents are planning to get me married to an HIV-negative person – now what do I do?’ So we say okay, we’ll look for someone for you."  - Dr. Suniti Solomon: A modern-day HIV love story

“Clearly if people abstained from sex, or had sex with partners they knew to be uninfected, or used condoms 100% of the time, we wouldn’t have the HIV epidemic. But obviously, spreading billboards all over the world has not cut it.” - Dr. Linda-Gail Bekker: Safe-sex education – too little, too much?

“Placebo controlled trials are essential for the evaluation of the safety and efficacy of new products.  The placebo control group in a clinical trial provides the means of establishing any specific safety issues with a product, as well as the effectiveness of the product at preventing HIV transmission… Once a microbicide product has been adequately shown to prevent HIV transmission, it will no longer be possible to run placebo controlled trials, and the “window” will be closed."  - Dr. Joe Romano: What happens when the ‘placebo window’ closes?

SEPTEMBER:
“It boggles me that I still have to make the case for understanding the relational and contextual nature of HIV transmission and the need to recognize that people and technologies are interactive and interdependent."  - Judith Auerbach: Addressing social drivers of HIV/AIDS

“Even among groups of experts, I have noticed people getting confused – misapplying data, conclusions, or assumptions...”  -  Lori Heise: Tricky Terminology in HIV Prevention – Microbicides and Oral PrEP

“Giving gay men more information about their health only empowers them to make informed decisions. The fear that gay men will take PrEP, forego condoms and become out of control disease spreaders, harkens to the days when men feared women would become crazed nymphomaniacs thanks to the new birth control pill.” -Alex Garner: Open letter Urges that PrEP debate should be based on ‘facts not misinformation’

OCTOBER:
“Firstly, we need to work out whether this result is true or not. But even if it is true, it’s quite possible that we need to balance the benefits of avoiding an unwanted pregnancy against the small increased risk of acquiring HIV infection.”  - Dr. Tim Farley: Hormonal contraceptives and HIV – the grey area

“It’s really critical we know what research is and is not being done, what evidence does and does not exist, so that we have a solid understanding of the implications of these technologies in various social, economic, cultural, and political contexts that exist in different countries. It’s only then that we can begin to think about investing in them and the best ways to implement them."  - Molly Morgan Jones: Mapping Pathways so far – the ‘literature review’

NOVEMBER:
“If you’re talking about early treatment, you’ll have one person saying, ‘This is a quantum leap from where we are now, and it’s operationally impossible.’ And then you’ll have another person saying, ‘Well, if you have cancer, the doctor doesn’t wait till you’re half dead to give you the treatment, and so we should have been doing this years ago.’ And both are very valid points; it’s just how do you get those two people, who are equally important in making this happen, make it happen?” - Daniella Mark: It’s a question of ‘how’ in South Africa Part 1 & Part 2

DECEMBER:
“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.” - Jim Pickett: Triumphs and Trials in 2011


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

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.]

A Defining Moment in HIV Control

via The Lancet, by Salim S Abdool Karim, Quarraisha Abdool Karim

A defining moment in the global AIDS response has been reached. The discourse is no longer about HIV prevention or HIV treatment; it is now about HIV control through the implementation of antiretrovirals as key components of combination interventions. Barely a year ago, visions of HIV control would have been considered far-fetched. The impetus for this change in mindset, which has been building since the XVIII International AIDS Conference in Vienna last year, emanates from the compelling evidence that antiretroviral drugs prevent HIV infection in the general heterosexual population, which is released this week and presented at the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Rome by the Partners PrEP1 and Botswana TDF22 trials.

The Partners PrEP trial,1 involving 4758 HIV discordant couples from Kenya and Uganda, found that daily oral tenofovir disoproxil fumarate (TDF) and TDF-emtricitabine reduced HIV transmission by 62% and 73%, respectively. The Bostwana TDF2 trial,2 in 1200 heterosexual men and women from the general population, found that daily oral TDF-emtricitabine reduced HIV transmission by 63%. These findings follow close on the heels of the CAPRISA 004 trial3 of tenofovir gel, the iPrEX trial4 of oral TDF-emtricitabine in men who have sex with men, and the HPTN 052 trial5 of early antiretroviral treatment as HIV prevention. Importantly, these new findings fill a critical gap in HIV prevention with a readily available antiretroviral approach to prevent heterosexual transmission in both men and women (figure). Women benefit from a new prevention option under their control, which is particularly important for those not assured of their partner's fidelity or willingness to use a condom. The hope these studies add to HIV prevention is further bolstered by the recent step taken by the pharmaceutical company Gilead Sciences Inc to lodge TDF and emtricitabine with the UNITAID patent pool,12 thus enabling lower cost versions of the drugs to be manufactured and thereby facilitating wider access in poor countries.

 There is now no doubt that antiretroviral drugs prevent HIV infection. However, important scientific questions remain. Does the inclusion of emtricitabine in pre-exposure prophylaxis (PrEP) formulations provide sufficient additional benefit to warrant the additional costs and side-effects? Are levels of effectiveness and safety similar for daily use and use-with-sex of PrEP? Do the safety, effectiveness, cost, and acceptability profiles of oral and topical PrEP merit implementation of both formulations? Does PrEP lead to masking of HIV acquisition that is then revealed once PrEP is withdrawn? Can the new results be generalised to the type of hyper-endemic settings (HIV incidence more than 5% per annum) where the FEMPrEP trial13 was done? Since inadequate drug levels may not have been responsible for the lack of effectiveness observed in the FEMPrEP study,14 the search for an explanation for this intriguing and contrary result needs to be pursued with vigour.

There are also many practical questions about implementation: how to increase uptake of HIV testing;15 how often to monitor HIV status in people on PrEP; how to achieve high coverage in those at highest risk; how to maintain high levels of adherence; how to reduce the risk of migration away from condoms (behavioural disinhibition); and how to monitor the risk of drug resistance. While attempts are being made to obtain data to address these questions and to generate data to guide effective implementation, the development of normative guidance by WHO/UNAIDS and submissions for regulatory approvals of TDF and TDF-emtricitabine as PrEP for HIV infection are key next steps.

As antiretroviral drugs take a key role in the global effort to control the HIV epidemic, there is much to be learned from the contraceptive field where multiple technologies, approaches, formulations, and dosing options were developed to enable and maximise user choice and increase levels of uptake, coverage, and adherence and thereby improve the public health impact.

Beyond the questions of implementation, the future scientific challenge looming large for PrEP is finding a drug or class of drugs with a resistance profile that does not interfere with existing first-line and second-line AIDS treatment. Treatment of HIV-positive people for HIV prevention and PrEP and microbicides for HIV-negative people are two sides of the same coin, and cannot be viewed in isolation from each other. Although research on treatment for prevention, PrEP, and microbicides has mostly occurred in separate silos, their findings converge into a single focus in HIV prevention and necessitate guidance on how to use all three strategies synergistically for maximum benefit depending on the nature of the HIV epidemic. There is no magic bullet for the HIV epidemic. Treatment for prevention will be dependent on the extent to which couples establish their HIV status, whether the HIV-positive partner in a discordant couple adheres to therapy, and whether the HIV-negative partner maintains fidelity within the partnership. PrEP will be dependent on the extent to which people seek to establish and regularly monitor their HIV status and those on PrEP adhere to their regimen and clinical monitoring. Hyper-endemic communities, such as those in South Africa where HIV prevalence in the community is high, may require both interventions jointly and synergistically: treatment of people infected with HIV to reduce risk of transmission within the discordant couple, and PrEP to reduce the HIV-negative partner's risk of HIV acquisition from outside partners.

Therein lie the three most complex policy, implementation, fiscal, and ethical challenges generated by these new findings. First, how to scale up HIV testing, a key prerequisite in settings with stigma and discrimination. Second, how to extend antiretrovirals for both treatment and prevention when many of Africa's health systems are already struggling to cope with patients with AIDS and are not able to initiate antiretroviral therapy in everyone who currently needs it for their survival. Third, in the context of limited resources how best to ration and prioritise the limited available implementation capacity.

In this defining moment in the response to HIV, a global commitment to increased financial resources for implementation, health systems strengthening, and greater implementation efficiency is imperative. Anything less will crush the hope and promise that antiretroviral drugs can change the course of the HIV epidemic.
We were the co-Principal Investigators of the CAPRISA 004 trial of tenofovir gel. QAK is co-Principal Investigator of the HIV Prevention Trials Network, which is undertaking HPTN 052 trial of treatment for prevention. SSAK is an executive committee member of the Microbicide Trials Network, which is undertaking VOICE trial of oral and topical PrEP.


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

In Conversation with Daniella Mark: It's a question of “How?” in South Africa

* Original content from our Mapping Pathways blog team

We checked in with our colleague Daniella Mark from the Desmond Tutu HIV Foundation in South Africa, a Mapping Pathways partner organisation. For the past year, she has been conducting in-depth stakeholder interviews with South African policymakers, advocates, community leaders, physicians, academics, and scientists. As Daniella puts it, “All of these people are essentially gatekeepers; they have the ability to either push forward or halt a particular HIV prevention strategy or technology.”  We spoke with her about some of the trends she’s observing from her on-the-ground interviews, and her insights on HIV prevention within the South African context. This is the first part of a two-part interview.

Please briefly tell us a bit about yourself?

DM: Yes, of course. I’ve been with the Desmond Tutu HIV Foundation for six years now. My field of expertise is psychosocial research in the HIV field, which includes prevention — researching behavioural interventions or psychosocial issues around biomedical interventions (such as risk reduction counselling), as well as treatment — researching things like adherence and loss to follow-up and the psychosocial issues that impact them, like alcohol and drug abuse.

The Mapping Pathways research has been going on for almost a year now. What are some of the general trends you’re noticing for South Africa from the stakeholder interviews? 

DM: Because I’ve been doing the interviews myself, I am very close to the data. In general, what’s particular to South Africa is that while people are interested in different prevention technologies and strategies, there’s this huge concern about resources. It’s just that we have such a high incidence rate and, as of now, we have no prevention technology to effectively fight the disease apart from tools like condoms or, in some circumstances, circumcision. And we’ve been battling to make sure even these prevention strategies are effectively rolled out. So when you talk to people about something as far away from these existing prevention tools as PrEP, they can’t even imagine how we can incorporate this into our present strategy. 

So, I’m finding that capacity/resource concerns are present in each interview. People are in a state that they don’t know how we can pull this off. There’s also this ethical concern amongst researchers that we’re not effectively doing what we know works to curb the epidemic (condoms, etc), so there’s this ethical question over whether we can start revving up to bigger, more expensive prevention strategies if we’re not even giving sick people the treatment they need.

What is the general feeling about PrEP amongst the HIV advocacy community in SA right now?

DM: I’m finding that, as a whole, there is an interest in PrEP but there’s a lot of trepidation about “how”? I think people have this feeling that there are conflicting trial results, and it’s not quite clear how we put iPrEx and FEM-PrEP together, for instance. How do we understand these two conflicting results? We need to understand all this better. There’s a feeling that there’s a lot of excitement around PrEP, but it’s not particularly justified in the context of South Africa. In SA, we have a generalised epidemic, so we wouldn’t know which specific group to roll PrEP out too — we would need to give it to our entire population of 50 million people, or at least our adult population of 30 million, which is just not feasible. Whereas, in countries like the States or in India, you could find specific groups, such as gay men or men who have sex with men, to give PrEP to — which makes the question of resources and costs more manageable. So there is concern about the size of the group we would have to roll PrEP out to in South Africa, and also about the efficacy of the strategy. 

There is also concern about how we don’t have all the drugs available for treatment. It takes time to get pharma companies to give drugs to us at third-world prices, and interlinked to this concern are the questions of adherence and resistance. Tenofovir, which is one of the main drugs for use as part of antiretroviral therapy combinations such as those used in PrEP, is also first-line treatment in South Africa; what happens when an individual becomes resistant to it before they even present for first-line treatment? Second-line is far more expensive and we have no third-line options. There is a further and related concern that patients who are not symptomatic might adhere more poorly to PrEP (since they are not HIV-positive and are not experiencing HIV-related symptoms that may act as adherence motivators). As a result, they may be more likely to become resistant to the drugs, and then we’ll have difficulty providing treatment options if they were to become infected.

Other questions about “how” revolve around where would we run this programme out of? Would we open more HIV clinics with capacity to serve the general population as well as those infected? But then we run into the problem of stigma, which is a huge problem in Africa. Would people want to come to an HIV clinic for PrEP and face the stigma of going to such a clinic if they are not even infected? There were some suggestions that we could run PrEP programmes out of family-planning clinics, but then the individuals in the clinic would need upscaled training, and do we have the resources and money to provide this training effectively? 

So, right now in South Africa, the feeling about PrEP is how, how, how? People are open to it, but want more consistent data or at least to understand the inconsistencies in the data. Mostly though, the feeling is that we have to figure out these questions for ourselves — we can’t even follow the lead of the countries we normally follow such as the United States, because our situation is different since we have such a high incidence rate and generalised epidemic.

Stay tuned to the Mapping Pathways blog for the second part of Daniella’s insightful interview on the HIV-prevention mood in South Africa, and what she thinks some of the big questions and trends for 2012 will be.

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