Six Months In…. Highlights from the dynamic world of HIV-prevention and the Mapping Pathways project

Original content from the Mapping Pathways blog team

As the year 2012 passes its halfway mark, it is time to take stock of some of the key events this year in the field of HIV treatment and prevention as well as some of the highlights of the Mapping Pathways project.

The year opened on a slippery note with the January 2012 issue of Sexually Transmitted Diseases – Journal of the American Transmitted Diseases Association publishing data from a rectal health and behavior study whose findings “suggest some lubricant products may increase vulnerability to STIs.”

The paper fueled a tremendous amount of discussion in HIV treatment and prevention communities around the world, including the membership listserv run by IRMA (International Rectal Microbicide Advocates).

“We need to be clear – there are only associations between lube use for anal intercourse and STDs. There is no proof that lube use causes increased risk. We simply don’t know that. Because we don't know, IRMA has long been advocating for a lube safety research agenda to fill in our gaps in the science and the evidence base,” says Jim Pickett, Director of Prevention Advocacy and Gay Men’s Health at the AIDS Foundation of Chicago, chair of IRMA, and a member of the Mapping Pathways team. Click here for more info on lube safety.

In March, important new data, specifically from the FEM-PrEP, iPrEX and 

Partners PrEP trials, was revealed at the 19^th Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, Washington. All the webcasts and sessions from the conference can be viewed online here.

The FEM-PrEP trial’s independent data and safety monitoring board (DSMB) recommended that the trial be halted due to “futility” in April 2011 as the study could not answer the question of whether daily Truvada worked, or not, in terms of preventing HIV among the trial population. New information presented by investigators at CROI suggested that the lack of efficacy was related to low levels of adherence to medication.

While 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 indicated adherence to medication at almost 97%. Early results reported in Rome last July showed high levels of effectiveness in both men and women. These findings were reviewed at CROI, with no major changes to the estimated effectiveness of the drug.

At CROI, the Partners PrEP team presented analyses of plasma tenofovir levels in trial participants who became HIV-positive and a group of 1,000 participants who did not.

Two key findings were that individuals who remained HIV-negative had detectable blood levels of tenofovir at 82% of their study visits and that having detectable tenofovir in your blood at any given study visit was highly predictive of being HIV-negative at that visit.

The trial had a tenofovir arm, a Truvada arm and a placebo arm. According to the Partners PrEP team, “TDF (tenofovir) and FTC/TDF (Truvada) PrEP definitely provided 67% and 75% protection, respectively, against HIV-1 acquisition in African men and women at risk for HIV-1 infection, when provided in the context of other HIV-1 prevention services.” In short, women and men who took daily tenofovir-based PrEP had a significant reduction in HIV risk.

The results of the iPrEX trial indicated that gay/MSM participants who took Truvada daily had a 44% reduction in HIV incidence over the course of 1.2 years of follow-up compared with placebo. For individuals who did take the drug, and had detectable levels of drug in their bodies, the efficacy of Truvada as PrEP was approximately 90%.

At CROI, researchers presented new results of a case-control analysis on drug levels of the iPrEx trial participants that indicated that the blood-drug level observed with a dosing frequency of four doses per week was associated with a 95% reduction in HIV risk.

Mapping Pathways presented an oral abstract at the Microbicides 2012 (M2012) conference in Sydney in April. Pickett says the abstract and presentation were well received and generated a lot of interest in work Mapping Pathways has been doing and is planning to do in the coming year.

The importance of adherence was further highlighted at M2012. Says Jim “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.” (Read our entire interview with Jim here.)

In May, an important landmark was achieved when a panel of experts at the U.S. Food and Development Administration (FDA) recommended approval of Truvada for use in PrEP in HIV-uninfected gay men and MSM, HIV-uninfected partners in serodiscordant relationships and other individuals “at risk” of acquiring HIV through sexual activity.

The webcast can be seen here and copies of all the slide presentations are here. The final FDA decision is expected by mid September.

June saw Mapping Pathways team members disseminating findings at the International Association of Physicians in AIDS care (IAPAC) evidence summit on TasP and PrEP in London. Click here to see Jim’s slides and here to read more analyses of the meeting via aidsmap. .

In light of the FDA panel’s approval of Truvada for PrEP in May, Mapping Pathways U.S. partners, AIDS United and AIDS Foundation of Chicago, presented a webinar June 19 focusing on PrEP. Key U.S.-focused findings of the Mapping Pathways online survey and stakeholder interviews were presented at the webinar helping illuminate diverse perspectives of advocates, clinicians, policy makers and people living with HIV.

In a few weeks, Mapping Pathways team members will be presenting data collected in 2011 from India, South Africa and the U.S. at the International AIDS Conference (AIDS 2012) in Washington D.C. The data presented will include findings related to community stakeholder perspective on ARV-based prevention – “grassroots” and “grasstops” – as well as an extensive literature review conducted by RAND, a Mapping Pathways partner.

Please click here to see the complete list of Mapping Pathways activities at AIDS 2012. And join us! All posters and presentations from AIDS 2012 will be made available on the blog, and archived 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.]

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 at CROI 2012 Report an Increase of ARV Drug Resistance in the U.S.

via Aidsmeds.com, by Tim Horn

New surveillance data from the U.S. Centers for Disease Control and Prevention (CDC) suggest that about two in 10 individuals infected with HIV in recent years involved strains of the virus harboring mutations conferring at least partial resistance to one ore more available antiretroviral (ARV). The report was presented Wednesday, March 7, at the 19th Conference on Retroviruses and Opportunistic Infections in Seattle.

The U.S. Variant, Atypical, and Resistant HIV Surveillance (VARHS) system, in which HIV specimens from newly diagnosed individuals are tested for drug-resistance mutations, was established by the CDC to provide the clearest picture to date of the scope and type of resistance in the United States.

The analysis reported at CROI included a total of 10,338 resistance profiles from eight U.S. regions; this consisted of 2,339 profiles from individuals with recent infections (confirmed using a specialized antibody test or a negative HIV test results within six months before diagnosis) and 7,999 profiles from individuals with confirmed long-standing HIV infection (individuals diagnosed with AIDS within six months of testing positive for the virus). Regions represented in the analysis were Seattle, Los Angeles, Chicago, Colorado, Michigan, Louisiana, New York and South Carolina.

The system uses standard genotypic resistance testing, which identifies specific viral mutations associated with drug resistance. Because neither the recently infected individuals nor the subjects with established infection included in the analysis had yet started treatment, the presence of any HIV drug resistance mutations in their blood would indicate that the resistant virus was transmitted to them at the time of their infection.
Overall, 15.2 percent of all samples included in the analysis had evidence of at least one transmitted drug resistance mutation.

Among the recently infected individuals, 19.1 percent had evidence of at least partial resistance to at least one drug in a particular ARV class, compared with 14.7 percent of the individuals with long-standing HIV infection. This difference was found to be statistically significant, meaning it was too great to have occurred by chance.

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 Compare Differences in Progession to AIDS Between Races

via POZ Treatment News, by Tim Horn

Some sobering news from the Women’s Interagency HIV Study (WIHS): Black women living with HIV are more likely to progress to AIDS and twice as likely to die of its complications compared with white women living with HIV, according to new results from the cohort presented Tuesday, March 6, at the 19th Conference on Retroviruses and Opportunistic Infections in Seattle. Though black women were significantly less likely to adherence to antiretroviral (ARV) therapy in the analysis, their risk of AIDS-related deaths were still significantly higher after accounting for this.

Eighty percent of HIV infections globally occur in women and people of African descent, but the majority of studies on antiretroviral (ARV) therapy have been conducted in men of European descent, Kerry Murphy, MD, of Albert Einstein College of Medicine in New York and her WIHS colleagues explained in their introduction comments.

Though previous data from the WIHS—one of the largest and longest cohort studies following women living with HIV in the United States—pointed to better survival among white women in the United States, the finding was not statistically significant, at least not when the results were published in 2005. The study has been under way since 1993, with sites in Brooklyn, the Bronx, Chicago, Los Angeles, Northern California and Washington, DC.

With additional follow-up data now available, the WIHS researchers again revisited potential associations between race, AIDS-related deaths, non-AIDS related deaths and the new AIDS-related illnesses in the cohort.

Included in the analysis reported by Murphy and her colleagues at CROI were 1,471 women living with HIV on continuous ARV therapy.

Compared with white women in the cohort, black women were twice as likely to die of an AIDS-related complication. This finding was statistically significant and accounted for other known predictors of AIDS death, including high depression scores, high pre-treatment viral loads, low pre-treatment CD4 cell counts, hepatitis C coinfection and a history of illicit drug use.

Read the Rest.


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

NYT: PrEP Trial Results are Re-examined

via The New York Times, by Donald G. McNeil Jr.

The failure of a daily pill to protect healthy African women against AIDS may not have been the pill’s fault but the women’s reluctance to take it, scientists at an important AIDS conference in Seattle were told this week.

Last April, a promising trial of “pre-exposure prophylaxis” — giving small protective doses of antiretroviral drugs to uninfected people — was stopped early because women were getting infected anyway. It was a discouraging setback.

But scientists at this week’s Conference on Retroviruses and Opportunistic Infections who analyzed blood samples taken from the women reported that only a quarter of those who got infected had any of the drug, Truvada, in their blood. That suggested they had not taken their pills.

Papers presented at the four-day conference offered findings both optimistic and scary. There were hints at a possible way to flush the virus out of its hiding places in cells, and at ways to let some patients safely take “vacations” from triple therapy.

It is not known why so few African women took their Truvada, but there is still an enormous stigma about AIDS in Africa, and a bottle of AIDS drugs in the home implies that someone there is sick, said Mitchell Warren, executive director of AVAC, a prevention advocacy group. Mr. Warren pointed out that Truvada had protected women in a different study that enrolled established couples in which only one partner was infected.

In a different study, researchers from the University of North Carolina at Chapel Hill showed that they had used a cancer drug, vorinostat, to purge the virus hiding in the CD4 cells of six men who were already doing well on triple-therapy cocktails.

Although the cocktails can make the virus vanish from the blood, it hides in different types of cells, ready to roar back if the patient stops taking the cocktails.

Rooting some out with vorinostat “may not be the magic bullet,” said Dr. David Margolis, the study’s lead researcher, “but it suggests we can build a path that may lead to a cure.”

Another small trial, at the Wistar Institute in Philadelphia, gave patients synthetic interferon — a virus-blocker normally made by the human body — while they took “holidays” of up to six months from triple therapy. Nine of the 20 patients did not see their viruses rebound to dangerous levels. That result will not change clinical practice right away, said Dr. Luis J. Montaner, who led the study, but suggested an alternative to lifelong triple therapy, which can be debilitating.

Read the Rest.


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

Major Budget Cuts Hinder HIV/AIDS Treatment

via Nature News, by Erika Check Hayden

Preventing the spread of HIV used to mean testing people for infection and encouraging them to practise safe sex. Increasingly, it also means prescribing drugs, as studies show that giving infected people or their uninfected partners antiretroviral drugs as soon as an infection is diagnosed can help to check the spread of AIDS.

Yet at this week’s annual Conference on Retro­viruses and Opportunistic Infections in Seattle, Washington, there was growing concern that financial austerity in the United States and elsewhere is eating away at the funding needed for a worldwide prevention effort.

Many scientists and advocates agree that there is now an “awesome possibility to prevent the spread of HIV”, says Sharonann Lynch, HIV policy adviser for Médecins Sans Frontières (MSF, also known as Doctors Without Borders) in New York. “If we decrease the money invested in treatment now, we are squandering the best opportunity we’re going to have to get ahead of the wave of new infections.”

Last month, US President Barack Obama’s 2013 budget request proposed a 10.8% cut to direct international aid for HIV programmes under the President’s Emergency Plan for AIDS Relief (PEPFAR) which, together with previous cuts, would slice more than US$1 billion from the fund’s 2010 level. And last November, the Global Fund to Fight AIDS, Tuberculosis and Malaria said that it would not hand out any more funds for scaling up AIDS treatments until 2014 because of tightening budgets in donor countries.

The shortfalls come as a slew of results presented this week reinforce a growing consensus about the power of early treatment for HIV infections. The latest data are part of a trend that accelerated last May, when HPTN 052, a clinical trial run by the multinational HIV Prevention Trials Network, showed that giving antiretroviral drugs to people who are HIV-positive can stop them from passing the virus to their uninfected partners. In light of such results, the World Health Organization is expected to issue new guidelines for managing HIV in couples soon.

Read the Rest.

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