TAF as Effective as TDF in Cisgender Women, With Fewer Side Effects

Another important article From TheBodyPRO
By Martha Kempner

Initial data gathered from seven separate studies found tenofovir alafenamide (TAF) is just as effective as tenofovir disoproxil fumarate (Viread, TDF), with fewer side effects to the kidneys and bones, when used in cisgender women. These results, presented this week at the Conference on Retroviruses and Opportunistic Infections (CROI 2019) in Seattle, are similar to those found in cisgender men.

TDF was approved for use in patients with HIV in 2001 and for use in those with hepatitis B in 2008. The drug was highly successful and became a staple of most HIV treatment regimens, but was known to cause kidney toxicity and loss of bone density in some patients. In 2015, the Food and Drug Administration (FDA) approved the tenofovir prodrug TAF, which can be effective in smaller quantities relative to the original.

TAF is now included in a number of commonly used antiretroviral combination pills, most notably bictegravir/emtricitabine/TAF (Biktarvy) and emtricitabine/TAF (Descovy), which are among the list of first-line drugs currently recommended in U.S. first-line HIV treatment guidelines. For the most part, research has shown that TAF is equally effective as TDF with fewer negative side effects. But, as researcher Melanie Thompson, M.D., with AIDS Research Consortium of Atlanta pointed out in her presentation, the majority of participants in these studies were men.Advertisement

Though women make up 52% of adults living with HIV worldwide, they are often underrepresented in clinical trials, and health care providers are forced to assume that women will have the same results as men. For this analysis, an all-women team of researchers looked at seven studies that included a total of 779 cisgender women. Two of the studies (representing 260 of the women) were of individuals who were treatment-naive. The other five studies (representing 519 women) were conducted among virally suppressed individuals who were switching from a TDF regimen to TAF.

The data show that the two tenofovir treatments have similar efficacy rates. At 96 weeks, the FDA snapshot showed 86% viral suppression for women on TAF and 85% for those on TDF. This is close to what research has found in men — 87% viral suppression on TAF and 85% on TDF.

The reporting of adverse effects was also similar among women taking TDF and TAF. The most common side effects for treatment-naive women on both drugs included nausea, swelling of the throat and nasal passages, headache, upper respiratory infection, diarrhea, joint swelling and pain, dizziness, and back pain. Again, this was similar to the common side effects found in men on both medications.

The differences between the two drugs were most evident when it came to kidney toxicity. The analysis looked at two biomarkers that could indicate kidney injury and found that both were lower in women taking TAF than in those on TDF. Moreover, no women on TAF developed proximal renal tubular dysfunction, which is known to happen on TDF. The researchers referred to the lower adverse renal effects as a “highly treatment significant difference” between the two drugs.

The researchers also looked at adverse effects related to bone density. Women who started treatment with TAF had less bone mineral density decline than those who started on TDF. And, women who switched from TDF to TAF had improvements in bone mineral density. These were similar to the results found in men.

The analysis of the pooled data suggests that women have similar experiences with tenofovir to those of men. The researchers conclude that starting therapy with TAF or switching to TAF has significant safety advantages for women, while offering the same amount of viral suppression as treatment with TDF. Melanie Thompson ended her presentation by saying that “the other finding from this analysis is that it is both feasible and awesome to work with an all-female research team.”

Martha Kempner is a freelance writer, consultant, and sexual health expert.

The Road Ahead for HIV Cure Research

Today, with better understanding of the complex task at hand, cure researchers are investigating multiple avenues and taking the long view.  This article comes from Benjamin Ryan and was first presented online in Poz.com on January 7, 2019

Cure research and the potential for a cure is still front and centre in many of our lives and this article talks about the road ahead and some of the setbacks that have been suffered along the way.


HIV cure researchers received some disappointing news at the July 2018 International AIDS Conference in Amsterdam. Two studies in particular offered a sobering lesson on how extraordinarily complex developing a safe and effective cure for the virus will likely be.

As conference attendees learned, researchers behind a randomized trial of an HIV cure method, the largest such study to date, recently found that their efforts failed to reduce viral DNA in human participants. The trial, called RIVER, tested the “kick and kill” strategy that seeks to roust latently infected immune cells from their slumber and then kill them off. Standard HIV medications—antiretrovirals, or ARVs—work only against cells that harbor actively replicating virus. These resting infected cells are a chief component of what is known as the viral reservoir, and it’s the stubborn persistence of this reservoir that frustrates cure efforts.

In a second study presented at the conference, an antibody treatment that had shown promise in monkeys failed to prompt what is known as posttreatment control of the virus after HIV-positive humans interrupted their ARV therapy.

As scientists in this field recalibrate their expectations, the use of the term “cure” as a goal for their research is declining. Instead, investigators may seek to induce posttreatment control of HIV, or viral remission, in which a particular therapy would not eradicate the virus from the body but rather suppress HIV over an extended period without the need for long-term ARV treatment.

Nevertheless, the overall field is generally still referred to as HIV cure research.

Taking the pulse of her fellow HIV cure researchers, Sharon R. Lewin, MD, PhD, director of The Peter Doherty Institute for Infection and Immunity at the University of Melbourne in Australia, says, “If anything, there was probably more optimism four years ago because we had tried fewer things. We now know that curing HIV is definitely not an easy task.”

Looking on the bright side, Lewin points to other promising recent cure studies conducted in primates, noting, “We definitely have been able to cure a few monkeys. That’s exciting.”

But as the antibody study presented at the Amsterdam conference indicated, disappointing outcomes among humans might follow success in primate research.

“The preclinical studies have universally shown more favorable outcomes than human studies,” says Jintanat Ananworanich, MD, PhD, who in her capacity as the associate director for therapeutics research at the U.S. Military HIV Research Program directs research in the HIV cure field. “Although no strategies have resulted in remission in clinical trials thus far, tremendous knowledge on HIV persistence and immune responses has been generated. This is important to informing future trials.”

Concerns about recent setbacks notwithstanding, Lewin remains optimistic about the future of HIV cure research. “Science can also take dramatic turns with significant discoveries too,” she says. “So you never know what may change the field dramatically.”

Lewin is the lead author of a literature review recently published in The Lancet HIV, “Barriers and Strategies to Achieve a Cure for HIV,” in which she and her three coauthors offer a comprehensive summary of the impressive number of avenues researchers are pursuing in their quest for a cure, or something close to it. Below, POZ looks at the main takeaways from their paper. We also explore a few HIV cure studies published more recently.

***

Lewin and her colleagues note that the only person ever cured of HIV remains Timothy Ray Brown. As a component of his treatment for leukemia, Brown received stem cell transplants a decade ago from a donor with a genetic mutation that confers natural resistance to the virus—the surface of the donor’s immune cells lacked the CCR5 coreceptor to which most HIV attaches in order to infect the cells. As far as researchers can tell, Brown benefited from a sterilizing cure. There is no evidence in his body of any virus with the capacity to replicate, and his viral load has never rebounded. (Today, Brown actually takes Truvada [tenofovir disoproxil fumarate/emtricitabine] as pre-exposure prophylaxis [PrEP] to ensure he does not contract HIV again.)

Otherwise, in the realm of posttreatment control of HIV, quite a few people with the virus have been able to suppress their viral load for long stretches, sometimes for years, after interrupting standard ARV treatment. A recently published paper found that those who began ARVs very soon after contracting the virus are more likely to achieve such a prolonged state of viral remission after eventually going off their meds. It is likely that beginning on ARVs so promptly after infection keeps the viral reservoir relatively small, thus reducing the likelihood of latently infected cells springing to life at any given moment following a treatment interruption.

One of the most famous cases of such posttreatment control is that of the African child who was treated for HIV for less than a year after birth and, by the time the child’s case was reported in 2017, had spent over eight years in a state of viral remission. In 2015, news surfaced that an 18-year-old French individual had spent 12 years off ARVs and still controlled the virus. Then, of course, there was the 2013 case of “the Mississippi Child”—met with great fanfare—who spent a couple of years off ARVs during her very young life but ultimately, and disappointingly, experienced a viral rebound at 4 years old.

According to Lewin, scientists’ increasingly enriched comprehension of the posttreatment-control phenomenon has actually made designing HIV cure studies more difficult. Now researchers must take into account that some study participants might achieve control of their virus, even if for a short time, without the benefit of an investigative cure therapy, thus making it more challenging to prove that a cure treatment was the cause of viral remission or a delayed viral rebound after the interruption of ARV treatment.

***

Not only do latently infected immune cells evade ARV treatment, but also for every million such cells, perhaps only 60 harbor virus that can actually replicate; the rest contain defective virus. So finding those resting cells capable of waking up and repopulating the body with new virus in the absence of ARV treatment can be akin to finding a needle in a haystack. The immune system itself wastes considerable energy going after cells infected with dud copies of the virus.

In another of the myriad ways HIV has evolved to help ensure it sustains a lifelong infection, latently infected cells have the ability to clone themselves. Perhaps more than half of the viral reservoir cells in some people living with the virus are clones.

The matter of whether HIV continues to replicate at low levels in the face of effective ARV treatment has been the source of significant controversy in the cure field. A study presented at the 2018 Conference on Retroviruses and Opportunistic Infections in Boston found no evidence of such ongoing replication in the lymph nodes, calling into question the notable contrasting findings of a 2016 paper.

***

The lack of precise tests for measuring the viral reservoir remains a considerable obstacle for HIV researchers, both in determining the challenge they face in their quest to vanquish an infection and in assessing how well they did. Currently, scientists in the field must rely on rather crude metrics, such as changes in the overall presence of viral DNA or RNA in the blood, to gauge how a particular treatment affects the size of the reservoir. (HIV carries its genetic code in RNA, which is copied to DNA during infection of a cell.) Such metrics can underestimate the population of infected cells because most virus hides in tissues, not blood.

Scientists may also try to measure success by determining whether an HIV cure treatment is associated with a delay in viral rebound after an interruption of ARV therapy and whether such a treatment is associated with a particular level of control of the virus in the absence of standard ARV therapy for the virus.

If only scientists could identify a specific biomarker, such as a particular protein, that could predict the likelihood of a delay to viral rebound or control of the virus after a treatment interruption. Then, study participants might be spared the burden of interrupting their ARVs, a common requirement in HIV cure study designs. Asking people to stop standard HIV treatment raises ethical questions and may discourage people living with the virus from entering cure trials. That said, multiple studies have indicated that treatment interruptions in cure studies are safe.

Lewin argues that such a tidy biomarker would likely attract greater investment in the field from pharmaceutical companies. (Global funding for public sector HIV cure research increased from $88 million in 2012 to $289 million in 2017, with the lion’s share coming from the National Institutes of Health.) Such for-profit companies prefer study designs boasting a level of simplicity that will help an investigational treatment pass muster with regulatory bodies like the Food and Drug Administration. They also prefer efficient investments for their research and development dollars. So their researchers favor clearly delineated, objective means of measuring success in clinical trials of experimental agents.

Case in point: The recent discovery of a biomarker that can predict whether an individual will achieve a functional cure of hepatitis B virus (HBV) gave rise to a surge of interest from the pharmaceutical industry in researching curative therapies for HBV.

Investment in Cure Research chart

Source: “Global Investment in HIV Cure Research and Development in 2017”

Investment in Cure Research chart

Source: “Global Investment in HIV Cure Research and Development in 2017”

Avenues of Research:

Stem cell transplants

Clinicians are still trying to replicate the success of Timothy Brown’s HIV cure with similar strategies. In recent years, a number of other individuals with cancer have received stem cell transplants from donors who also have the genetic mutation related to the CCR5 coreceptor that confers resistance to the virus. One of the six such individuals whose cases have been published in scientific literature experienced a viral rebound; the other five ultimately died as a result of complications following their stem cell transplant or from their underlying cancer.

In other cases of people living with HIV who received a stem cell transplant but from a donor who lacked the CCR5-related genetic mutation, the stem cell transplant did delay the time to viral rebound by 3 to 10 months after the individuals stopped ARVs.

However, the high fatality rate following transplantation highlights how impractical, not to mention unethical, this method of attempting to cure HIV is for anyone not already facing a high risk of death due to cancer.

Gene therapy

Seeking safer alternatives to cancer-treatment-based stem cell transplants, researchers are experimenting with gene-editing techniques that alter the DNA of an individual’s immune cells. In particular, the scientists will try to deactivate the gene that gives rise to the CCR5 coreceptor, thus robbing HIV of a means of latching onto immune cells. The modified cells are then grown outside the body and ultimately reinfused into the person’s body. The aim is to spawn a population of immune cells that are resistant to infection. As the field of gene editing rapidly evolves, it is hoped that new, even more cutting-edge technology will facilitate progress on the HIV cure front.

“Kick and kill”

The method of waking up latently infected cells (the “kick” part) and then finishing them off (the “kill” part) has yielded some notably disappointing results of late, including those of the RIVER study that was presented at the July conference in Amsterdam. Researchers pursuing this strategy have looked to various cancer drugs known as HDAC inhibitors as the kick element; but thus far, they have not been able to show such drugs can actually diminish reservoir cells.

Lewin remains cautiously optimistic about further research into these medications, noting that the RIVER trial used a less advanced and relatively weak kick agent. Recent, more preliminary studies that have examined other kick agents, such as so-called TLR agonists, have shown far greater promise.

On this front, Gilead Sciences is investigating a drug known as GS-9620 that has shown positive results in primate research.

Latency silencing: “block and lock”

Effectively the opposite of the kick and kill strategy, the “block and lock” method, also known as latency silencing, is based on the presumption that if rooting out and killing all the latently infected cells in the body is too challenging, keeping them in a silent state indefinitely may be a viable alternative. A recent study conducted in mice sought to inhibit a viral protein known as tat that acts as an on-off switch for viral replication in cells. The study successfully reduced the amount of HIV RNA expressed in tissue biopsies taken from the animals, and it delayed viral rebound after the interruption of ARV treatment.

Enhancing the immune system

Researchers are investigating whether vaccines can be used to prompt the body to better control the virus.

Scientists have also invested considerable energy into studying so-called broadly neutralizing antibodies, which are natural antibodies that boast the capacity to combat a wide array of HIV strains. Research has indicated that some of these antibodies are associated with a delay in viral rebound after an ARV treatment interruption. Recently, scientists have gone high-tech by synthesizing three such antibodies into one “trispecific” antibody—a kind of all-in-one triple combination therapy—that has already shown promise in its use as pre-exposure prophylaxis (PrEP) among primates.

Modulating the immune system

Scientists are seeking to manipulate proteins that redirect the traffic of immune-fighting cells. One such example is an antibody called vedolizumab that targets a protein on the surface of CD4 cells and stops these cells from moving into the gut, where HIV focuses much of its assault on the immune system. An initial study in monkeys reported two years ago provided hope for progress in this area of research, but scientists recently repeated the study and found that the antibody had a null impact on the second go-round. Preliminary results in humans also showed that vedolizumab did not affect the time to viral rebound after individuals interrupted their ARV treatment.

Looking to the future

In all likelihood, a successful HIV cure, or posttreatment control, strategy will rely upon a combination approach based on a number of the methods currently under investigation or those yet to be imagined.

“It is clear that achieving HIV remission will not be easy and that one should not expect any single intervention to help people get to remission,” says Jintanat Ananworanich. “We are taking small steps in discovery science.”

Any successful method will need to be safe, effective and—if it is to make a significant dent in the global epidemic—scalable. An HIV cure therapy that is extraordinarily expensive thanks to, for example, the highly involved and complex process required to provide personally tailored genetic editing of an individual’s immune cells, will have little to offer poorer nations—in particular those in sub-Saharan Africa—where the need is greatest.

Curative hepatitis C virus (HCV) treatment, for example, costs tens of thousands of dollars in the United States, which has led insurers to restrict coverage of the medications. The actual cost to manufacture such medications, however, is relatively low, which allows for a steep sliding scale elsewhere around the world.

The future of HIV cure science is also up against the phenomenal success of ARV treatment, which has set a high bar for any alternative means of suppressing the virus. The life expectancy of those on ARVs is approaching normal. What’s more, the risk of transmitting HIV is effectively zero for those who maintain a fully suppressed viral load.

However, such benefits don’t speak to the psychic costs of living with a highly stigmatized lifelong infection or how a cure therapy may alleviate such burdens. Then there are the extreme difficulty and expense of getting the global population on lifelong ARV treatment. Also, even well-treated HIV is associated with an increased risk of numerous health conditions, such as cardiovascular disease and cognitive decline.

Some form of HIV cure could help address these problems. However, as HIV drug development continues to progress and long-acting injectable treatments, or even very long-lasting implants, become the standard of care, emerging HIV cure treatments may cease to offer the freedom from daily medications as an advantage over standard ARV therapy. (Or perhaps by then, long-acting antibody treatments will be the norm.)

Furthermore, if someone is in a state of posttreatment control of the virus, what reassurances will there be that the virus will remain dormant indefinitely and won’t suddenly surge back and make an individual unwittingly infectious? How frequently will people benefiting from viral remission need viral load monitoring?

These pressing questions, along with HIV’s extraordinary complexity, likely make for a long and winding scientific road ahead. But thanks to the increasing funds backing such research and a growing army of top-tier scientists doggedly pursuing a cure, the future will hopefully prove bright with new developments.

Still, this field isn’t simply concerned with a binary outcome of finding the holy grail of a cure or otherwise failing to do so. Success will likely prove incremental, with scientists eventually discovering new means of further mitigating HIV’s long-term harms, further transforming a once surely fatal infection into an increasingly innocuous presence in the body and around the world.

 

Study suggests many gay and bisexual men are skeptical, but attitudes are on the rise about U=U

First published on January 11, 2018, The City University of New York

Dr. Jonathon Rendina, an Assistant Professor at Hunter College and Director of Quantitative Methods at Hunter’s Center for HIV Educational Studies & Training, and Dr. Jeffrey Parsons, Distinguished Professor at Hunter and Director of CHEST, have published a new paper in the Journal of the International AIDS Society focused on gay and bisexual men’s perceptions of the HIV treatment-as-prevention message, “Undetectable = Untransmittable.” Numerous well-controlled trials have recently demonstrated that there is effectively no risk of HIV transmission during sex with a partner who has a sustained, undetectable viral load. This notion, that HIV treatment can lead to HIV prevention, has been captured with the #UequalsU slogan popularized by Bruce Richman and the Prevention Access Campaign, of which he is Executive Director, and has gained growing popularity and endorsements, including the U.S. Centers for Disease Control and Prevention (CDC). The Hunter CHEST study sought to examine how accurate gay and bisexual men perceive this message to be by surveying more than 12,000 men across the United States in the summer of 2017.

In addition to promoting HIV knowledge, one goal of the message is to help reduce HIV stigma. Mr. Richman noted, “This study underscores the great need for further targeted educational and dissemination strategies and provides data that will be immensely valuable as we work with our partners to scale up campaigns to prevent new transmissions and reduce HIV stigma.” Among HIV-positive men, reporting a detectable viral load was associated with believing the message was less accurate. Dr. Rendina added, “What we may be seeing is that some guys who aren’t able to maintain a sustained undetectable viral load either have lower levels of knowledge potentially due to being less well-retained in care or that they may feel left out of the message and concerned it will lead to additional stigma placed on them.” He continued, “There is great promise for the message to reduce HIV stigma, but at the same we need to make sure we don’t end up marginalizing or stigmatizing those who struggle with keeping their viral loads undetectable.”

Among men with and without HIV, believing the message was more accurate was associated with having had condomless anal sex with a partner of a different HIV status. Dr. Parsons noted, “This suggests that men who understand the scientific evidence, now endorsed by the CDC, that Undetectable = Untransmittable feel more comfortable having condomless sex when a positive partner is virally suppressed. Because they know that treatment-as prevention is effective—as with other forms of biomedical prevention, like PrEP, it’s giving men more options regarding their sexual health that emphasize autonomy and sexual pleasure. The message of ‘use a condom every time’ is now outdated and limiting.” Strategies such as regular viral load monitoring, efforts to maintain medication adherence, routine screening for sexually transmitted infections, better access to PrEP, and promoting communication about biomedical prevention with sexual partners can be helpful in conjunction with treatment-as- to continue curbing the HIV epidemic and averting new epidemics among other .

Finally! The Sexy Gay PrEP Video We’ve Been Waiting For.

This article and the links to the videos first appeared in June on Poz.com  and was written by Mark King.  As we move closer to the PrEPIT WA trail launching here in Perth it is a great time to look at these videos because they share some important information. Even though they are from the US the basics are the same and the messages just as relevant.

And so, without a dime of governmental or pharmaceutical funding, Chris used an assignment for his master’s degree in cinema to create “The PrEP Project,” a four-part video series that speaks honestly — and quite explicitly — to gay men about their sex lives and why more of them should be using PrEP.

The result is the sexiest (and maybe funniest) video series on the topic anyone has produced to date. It’s exactly what PrEP advocates have been waiting for, because it isn’t beholden to stiff health department guidelines or even political correctness.

Stop everything and watch it right this minute, as long as your boss doesn’t mind some bare ass and explicit sex talk. Each episode is only five minutes.

Did I mention the series features leatherman sexpert Eric Paul Leue, as well as a gay porn star and a muscle boy also known as a drag performer? You’ve got to give points to Chris for pure resourcefulness. Better yet, aside from the eye candy, the series is adorably engaging.

The first classic prevention message that Chris refused to promote in the video was “use a condom every time.” The vast majority of people, gay or straight, do not use condoms consistently. “The rate of consistent condom use among gay men has been estimated to be as low as 17%,” Chris says, “and PrEP is the answer to that. But we still conflate condom use with morality, which just isn’t helpful.” Instead, the film speaks to the sex lives of gay men as they actually are.

The initial backlash against PrEP as an alternative to condoms — the “Truvada Whore“ argument — doesn’t bother Chris. He knows where it comes from. ”Condoms became an emotional topic,“ he says, after a generation of mortality that provided no other options. ”Now that there is an alternative, people have a hard time letting that message go.”

Rest assured, “The PrEP Project” outlines the risk of other sexually transmitted infections that can occur without condoms. It just refuses to draw a false equivalency between the consequences of HIV and those of other STI’s.

When the first video in the series launched on Facebook, it got more than 40,000 views in the first day. That is, until Facebook pulled it down for violating their irksome, often vague community standards. “That really pissed me off,” Chris admits. “I should have expected it because it is somewhat graphic sex, but I believe the people who pulled it didn’t like the message. It wasn’t about the sex. I got a lot of hate mail.”

Lucky for you, the entire series is included in this post. Enjoy!

Mark

 

https://www.poz.com/blog/finally-sexy-gay-prep-video-waiting

Beyond Positive Workshop Series

Beyond Positive is a workshop series for HIV Positive Gay and Homosexually Active Men.

Topics include Sex, Intimacy and Relationships, Stigma & Discrimination, Disclosure & Empowerment, Treatments as Prevention, Living Well and more.

Facilitated by Mark Reid, the Positive Peer Educator. The workshops will run weekly on a Tuesday evening from 6:30pm from November 14th to December 12th.

  • Tuesday November 14th
  • Tuesday November 21st
  • Tuesday November 28th
  • Tuesday December 5th
  • Tuesday December 12th

Evaluation and Debrief on Tuesday December 12th followed by dinner at 7.30pm. If have any special dietary requirements please let Mark know when you RSVP.

If you’re interested in this event, please contact:
Mark Reid on 9482 0000 or email mreid@waaids.com by Tuesday October 31st 2017 to secure a place.

Not linked in with the WA AIDS Council? Not to worry. If you haven’t connected with the WA AIDS Council previously and would like to register for this event, please contact Alli at apaterson@waaids.com or on 9482 0000, who will explain how you can get involved.

When Is There Zero Risk of Transmitting HIV?

 More leading health experts and organizations endorse “Undetectable = Untransmittable.” This is a great article that raises some important points to consider! Reprinted from The Advocate.

Over the past year, hundreds have joined the growing list of health experts and organizations around the world to endorse the Undetectable Equals Untransmittable Consensus Statement. The U=U Consensus states that a person living with HIV who has an undetectable viral load through treatment cannot transmit the virus to a sexual partner.

Issued by the Prevention Access Campaign, U=U is based upon the findings of two major scientific studies on transmission risk: HPTN 052 and PARTNER, and a smaller study called “Opposites Attract.” In all of the studies, there were no transmissions of HIV (between serodiscordant, or mixed-status, couples) when the partner living with HIV was undetectable. Over 58,000 sex acts were counted in one of the studies with not a single transmission.

Global HIV and AIDS resource NAM AIDSMap is the latest to endorse the consensus. “The scientific evidence is clear,” says Matthew Hodson, NAM’s executive director. “Someone who has undetectable levels of virus in their blood does not pose an infection risk to their sexual partners.”

Many experts are now using the terminology “zero chance” in regards to the risk of transmission when a person’s viral load is vundetectable. For those living with HIV, this is vital and life-changing information that can not only influence one’s physical health, but have an enormous impact on mental and emotional health as well. U=U will help end the HIV epidemic and may even aid in eliminating stigma.

“The fear of catching HIV from a sexual partner fuels HIV stigma,” Hodson explains. “Which is why it’s so important that the ‘undetectable equals untransmittable’ message is heard and understood. Those of us with diagnosed HIV have had to live with the idea that our bodies are dangerous. This has had a profound emotional impact on many people.”

Last year, Bruce Richman, executive director of Prevention Access Campaign, unveiled the short documentary film Undetectable = Untransmittable (produced by Linus Ignatius). Richman says, “Exaggerating the ‘danger’ we are to others is an act of violence against all of us with HIV, and makes us vulnerable to a myriad of harms and injustices. We deserve and demand accurate and meaningful information that is not only critical to our social, sexual, and reproductive health, but is essential to end the epidemic.”

International HIV Conference Reveals Exciting Progress in Global HIV Fight

Highlights from the research presented at the 9th International AIDS Society Conference on HIV Science in Paris. Thanks to the team at Poz.com for this great coverage that I think makes interesting reading.

August 22, 2017  By Benjamin Ryan

The fight to combat the global HIV epidemic is charting exciting progress on numerous fronts. This includes a rapidly increasing proportion of those living with the virus on treatment as well as falling infection and AIDS-related death rates. Additionally, there have been various promising advances in research into new antiretroviral (ARV) treatments and forms of pre-exposure prophylaxis (PrEP), not to mention vaccines and means of prompting long-term viral remission that may allow some people with the virus to stop taking daily drugs.

The more than 7,000 HIV researchers and advocates who attended the 9th International AIDS Society Conference on HIV Science (IAS 2017), which took place in Paris from July 23 to 26, learned of these and other signs of great hope for the future of the worldwide epidemic. However, they were also confronted with the finer details of the considerable challenges ahead, most notably flat or declining funding from wealthy donor nations for efforts to fight the epidemic in poorer nations.

To follow is a summary of the major findings presented at the conference. Click on the hyperlinks for greater detail about any of the studies. For a complete newsfeed of all IAS 2017 reporting, click here.

Linda-Gail Bekker, PhD, the International AIDS Society (IAS) President and International Scientific Chair of IAS 2017 in Paris, speaking at the opening sessionBenjamin Ryan

Global Treatment

major announcement from Joint United Nations Programme on HIV/AIDS (UNAIDS) kicked off the conference: An estimated half of all people living with HIV worldwide,19.5 million out of 36.7 million, are now on ARV treatment. According to a lengthy UNAIDS report on the state of the global epidemic, in 2016 an estimated 70 percent of the global HIV population had been diagnosed, 77 percent of those diagnosed were on ARVs and 82 percent of those on ARVs had a fully suppressed viral load. Since 2014, UNAIDS has pushed nations to get each of those three figures to 90 percent, otherwise known as the 90-90-90 targets.

Treatment rates have soared while new infections and AIDS-related deaths have dropped considerably in eastern and southern Africa in particular. Meanwhile, Central Asia and Eastern Europe is the only major region that has seen a worsening epidemic, with its HIV infection rate rising 60 percent and its AIDS-related death rate rising 27 percent during the 2010s.

UNAIDS

UNAIDS

Excitingly, a highly reliable survey conducted in Swaziland and presented at IAS 2017 found that in just five years the hard-hit nation had doubled the proportion of its HIV population on ARVs while cutting its new infection rate in half.

Velephi Okello of the Swaziland Ministry of Health at IAS 2017 in ParisBenjamin Ryan

Globally, people with HIV are starting ARV treatment progressively earlier. However, the median CD4 count at treatment initiation remains above 350, indicating that considerable work needs to be done to move closer to treating everyone living with the virus, as recommended by the World Health Organization (WHO).

The continued flat funding seen in recent years for the effort to fight HIV in lower-income nations threatens progress in treating HIV on a grand scale. One analysis presented at the conference projected that if funding continues only at current levels, the proportion of people with the virus on treatment and virally suppressed will stagnate accordingly.

Jessica McGillen, PhD, presents a key slide that projects the impact of U.S. funding on viral suppression rates in 18 sub-Saharan African nations.Courtesy of Benjamin Ryan

Another threat to progress fighting global HIV is WHO’s finding that HIV drug resistance is on the rise. In numerous nations recently surveyed, 10 percent of those starting HIV treatment had a strain of virus resistant to some of the most widely used ARVs.

HIV Treatment as Prevention

Yet another study has seen no transmissions within a large cohort of partners when the HIV-positive member of a mixed-HIV-status couple is on ARVs and has an undetectable viral load. Between the Opposites Attract study reported at the Paris conference and the previously reported PARTNER study, there are now data on about 35,000 condomless sex acts between such gay male partners without a single HIV transmission. The PARTNER and HPTN 052 studies have also seen no transmissions between heterosexual partners within such a context. The PARTNER study is currently in a new phase to gather more data from gay male couples.

According to scientific experts discussing these collected research findings at the Paris conference, the risk of transmitting HIV through condomless sex when an individual has an undetectable viral load is so vanishingly small that it is effectively zero.

Another study presented at the conference raised worries about how poor adherence to ARVs among youths may compromise the powerful effects of HIV treatment as prevention. An analysis of 13- to 24-year-olds receiving ARV treatment in Philadelphia found that about one in six were episodically at high risk of transmitting the virus.

PhiladelphiaIstock

Viral Remission

Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID), says he no longer talks about an effort to develop an HIV cure, per se. Instead, he prefers the goal of prompting “viral remission” or “post-treatment control” of the virus, in which an individual maintains an undetectable viral load without daily ARV treatment. Conference attendees learned that a 9-year-old South African child has been in such a state for eight years, following just 40 weeks of ARV treatment begun after the child contracted the virus at birth.

Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID), speaking at IAS 2017Benjamin Ryan

An additional presented case study described how a man who contracted HIV only days before starting Truvada (tenofovir disoproxil fumarate/emtricitabine) as PrEP and who was quickly put on a full HIV treatment regimen spent seven months off treatment before experiencing a viral rebound.

HIV Prevention, Including Vaccines

A major push in the HIV research field is to find effective so-called broadly neutralizing antibodies against the virus for use in vaccines, as PrEP or as treatment. Addressing concerns about how to mass-produce such antibodies, one team of researchers found that they could prompt their production by immunizing calves.

In an early-stage study, one HIV vaccine candidate showed promise by prompting a robust immune response in a small collection of volunteers. Pending the results of another study, this vaccine may go into an advanced global trial as soon as late 2017.

Following definitive studies showing that voluntary medical male circumcision reduces female-to-male HIV transmission by about 60 percent, there has been a massive effort to circumcise men in sub-Saharan Africa in recent years. Research over the past few years has begun to show that this endeavor has likely driven down infection rates among men. Now, a study presented at IAS 2017 indicated that women also likely benefit from the male circumcision push, with lower rates of associated HIV and herpes simplex virus type 2.

Cancer

major forum exploring how much HIV and cancer treatment researchers have to learn from and share with one another as they develop highly advanced forms of treatment preceded the conference. The two fields share the goal of overcoming the immune system’s inability to combat a malignant force, be it a tumor or HIV-infected immune cells.

HIV Drug Development

The long-acting injectable regimen of cabotegravir and Edurant (rilpivirine) given every four or eight weeks successfully suppressed HIV over a 96-week period among 90 percent of participants in a major trial.

Gilead Sciences recently applied for approval from the U.S. Food and Drug Administration (FDA) of its new combination tablet of the experimental integrase inhibitor bictegravir plus the contents of the company’s Descovy (emtricitabine/tenofovir alafenamide). The FDA granted the tablet priority review; a decision is expected by February 12, 2018. A study presented at IAS 2017 found that compared with other approved regimens, this combination had fewer side effects and was similarly effective in suppressing HIV among those starting ARVs for the first time.

Another study found that the first single-tablet regimen containing a protease inhibitor, specifically Prezista (darunavir), was highly effective in suppressing HIV. When combined with Tybost (cobicistat) and Descovy (emtricitabine/tenofovir alafenamide), Prezista led to a continued undetectable viral load among 96 percent of those who switched from a successful multi-tablet ARV regimen.

Additionally, a recent study found that among first-timers to HIV treatment, a new single-tablet combo regimen containing the investigational non-nucleoside reverse transcriptase inhibitor doravirine, Epivir (lamivudine) and Viread (tenofovir disoproxil fumarate) causes fewer central nervous system and metabolic side effects and is as effective as Atripla (efavirenz/tenofovir disoproxil fumarate/emtricitabine).

PrEP

Researchers are fast at work exploring new forms of PrEP to help address issues such as toxicity, adherence and the need for novel, female-specific forms of HIV prevention.

One study validated ongoing advanced research into a long-acting injectable form of PrEP, finding that long-acting cabotegravir given every eight weeks was well tolerated and yielded drug levels expected to afford maximum protection against HIV. Additionally, a study of a vaginal ring form of PrEP given to teenage girls in the United States found that an ARV-containing monthly ring was safe and that the participants used it well.

Various studies addressed the ongoing question of how starting PrEP affects sexual risk taking and rates of sexually transmitted infections (STI) among men who have sex with men (MSM). An analysisof British MSM on Truvada for HIV prevention found that they tended to fold PrEP into their set of personal HIV risk-reduction rules, sometimes easing those rules when taking PrEP. Self-reporting indicated that the men did not tend to simply abandon condoms wholesale. Meanwhile, a long-term study of MSM in the United States found that those who started PrEP tended to proceed to report higher rates of condomless sex with casual partners, in particular with HIV-positive partners.

At London’s 56 Dean Street, the city’s main sexual health clinic catering to MSM, gonorrhea diagnoses fell 24 percent between 2015 and 2016 while HIV rates dropped 42 percent. This occurred as use of PrEP soared among men using the clinic’s services and as the clinic, instigated impressive new policies to encourage HIV and STI testing and to treat individuals for both types of infections as soon after diagnosis as possible.

The 56 Dean Street clinic in LondonBenjamin Ryan

PrEP use in the United States continues to increase, reaching the current estimate of 136,000 users. However, the rate of increase in those starting PrEP seen in each progressive quarter has slowed (in other words, about the same number of people are beginning PrEP each quarter). Troublingly, PrEP use is apparently still largely relegated to white MSM age 25 and older, raising concerns that those at the very highest risk for the virus, young Black MSM in particular, will for the most part fail to benefit from the highly effective HIV prevention method that has now been on the market for five years.

new analysis found that the non-daily dosing protocol for PrEP, known as on-demand PrEP, studied in the French and Canadian IPERGAY trial of high-risk MSM worked well even when the men had sex infrequently. There have been concerns that the high level of protection seen among men in the study, who were instructed to take Truvada only in the couple of days surrounding sex, was likely a by-product of the fact that the men tended to have sex so frequently that they often wound up maintaining a relatively steady level of Truvada in their bloodstream—rather than the result of the particulars of the dosing protocol.

separate study of Dutch MSM examined the reasons why they preferred on-demand versus daily PrEP, as well as their reasons for switching between the protocols or stopping them altogether. An expectation of better adhering to one protocol over another was found to be a major deciding factor. Additionally, a national survey of U.S. MSM found that concerns about the cost of PrEP and associated side effects are major barriers to men using Truvada for prevention.

Long-Acting Injectable HIV Treatment Moves Closer to Reality

Interesting reading from TheBody.com about long-acting injectable HIV treatment.

Long-acting injectable treatment takes another step closer to becoming a real-world option for people living with HIV. The latest 96-week data from the LATTE-2 study, which is investigating long-acting injectable maintenance therapy for people with HIV, were presented at the 2017 International Conference on HIV Science, in Paris.

While viral suppression rates were very high, another notable finding was how much participants appreciated not having to take pills every day — another sign that long-acting treatment could translate well to the real world and become the future of medication adherence.

What Is Maintenance Therapy?

“Maintenance therapy” is the concept that, after people with HIV achieve and sustain an undetectable viral load through current conventional means (a treatment regimen of at least one pill once a day, containing three or four drugs) for an extended period, they can switch to a regimen containing fewer drugs (either one or two). The idea is that they can take fewer drugs, thereby being exposed to less toxicity while still maintaining an undetectable viral load.

This is not yet a standard practice in real-world settings, but it could eventually mean that, instead of taking a pill containing three or four drugs every day, you take a pill containing only two. However, the LATTE-2 study takes this idea even further and proposes that, instead of taking a pill every day, people could receive an injection of long-acting drugs lasting up to four or eight weeks.

LATTE-2 Study Background

Since the study started a couple of years ago, the results have continued to be very promising (particularly last year’s 48-week data), and the current 96-week data are equally positive.

The study began with an “induction phase,” during which all participants were put on a daily oral treatment regimen containing cabotegravir and Epzicom (Abacavir/3TC, Kivexa). After 20 weeks, those who achieved an undetectable viral load (286 participants) were then randomized to receive one of three options:

  1. A long-acting injectable regimen containing cabotegravir + Edurant (rilpivirine) every four weeks (the Q4W group).
  2. A long-acting injectable regimen containing cabotegravir + Edurant every eight weeks (the Q8W group).
  3. The previous daily oral regimen of cabotegravir and Epzicom (the control group).

LATTE-2 Study Results

After 96 weeks, 94% of those in the Q8W group maintained an undetectable viral load, compared with 87% in the Q4W group and 84% in the oral control group.

“Serious adverse events,” meaning occurrences that are considered severe or damaging (but not necessarily a reaction or side effect), occurred in 10% of the Q8W group, 10% of the Q4W group and 13% of the control group, but the researchers noted that none were related to the drug.

Severe drug-related adverse events were reported in 2% of the Q4W group, 4% of the Q4W group and 2% of the control group. The most common drug-related adverse events were cold-like symptoms, headache and diarrhea.

Injection site reactions, meaning pain or discomfort felt afterward at the part of the body where the injection took place, were common (97% in the Q8W group and 96% in the Q4W group) but were mostly mild and moderate, with less than 1% being classified as severe.

In terms of “virologic failure,” meaning the treatment wasn’t able to keep the person’s viral load undetectable, there were only two cases in the Q8W group, one in the control group and none in the Q4W group. Out of these, only one in the Q8W group was linked to drug resistance (when a person’s HIV develops resistance against a drug that the person is taking). However, none of these occurred after week 48 and up to week 96.

Freedom From Daily Pills

Perhaps more important than viral suppression data was the overwhelming satisfaction felt by study participants about not having to take pills every day.

Based on a survey, 99% of the Q8W group and 97% of the Q4W group reported being very satisfied with their current treatment, compared with 91% of the control group. When asked how satisfied they would be to continue their current treatment, 99% of both the Q8W and Q4W groups expressed the desire to continue long-acting injectable treatment, compared with only 78% of the control group.

“It’s surprising to me — patients at our site that are on the study — how much they appreciate not having to take pills. I think that’s something that I really didn’t calculate. There’s this kind of feeling of freeness from being bound to oral therapy every day,” said lead study author Joseph Eron Jr., M.D., at an IAS 2017 press conference.

For now, the injections have to be administered by health care professionals, but the drug manufacturers are looking at potential ways to make the regimen self-administered.

The injectable drug regimen will move on into phase-3 clinical trials, two of which are fully enrolled, according to Eron.

Warren Tong is the senior science editor for TheBody.com and TheBodyPRO.com.

Follow Warren on Twitter: @WarrenAtTheBody.

The Evidence for U=U: Why Negligible Risk Is Zero Risk

Republished from The Body Pro – http://www.thebodypro.com/

August 10, 2017

Over the last year, hundreds of HIV organisations have joined a new campaign to endorse the statement that HIV transmission does not occur when viral load is undetectable on ART.

And while the dramatic impact of ART on reducing HIV transmission has been known for a long time, it is new to say ART stops transmission completely.

This change is especially important given that prejudice and discrimination against HIV positive people is still widespread. So while it is easy to simply answer “no” to the question of whether someone with an undetectable viral load is still infectious, it is more complicated to explain why.

This article summarises selected key studies from 20 years of accumulating evidence that should directly challenge the prejudice and fear of HIV that is still widespread.

U=U: Undetectable = Untransmittible (or Uninfectious)

Launched in 2016, the Undetectable = Untransmittable (U=U) campaign is based on the following statement: “A person living with HIV who has undetectable viral load does not transmit HIV to their partners”.1,2

The statement has been endorsed by more than 350 HIV organisations from 34 countries, including by leading scientific and medical organisations such as the International AIDS Society (IAS), UNAIDS, and the British HIV Association (BHIVA).2

The support for the statement is also remarkable given that science is not able to prove a negative — ie that something will not happen.

Instead, people who claim that HIV is transmittable when viral load is undetectable, should be challenged to prove it.

20 Years of Accumulating Evidence

The scientific approach to understanding the world usually involves three stages.

  1. Observing something.
  2. Deciding on one or more hypotheses that might explain it.
  3. Testing any theory in a suitable experiment.

The strength of this approach is that a good study, by definition, should be repeatable. If the results are true and not by accident, other researchers should be able to repeat the study and get similar and consistent results each time.

The evidence supporting U=U includes different types of research spanning observational studies, randomised trials, systematic reviews and expert opinion (see Table 1).

Key stages in this timeline include:

  • 1998: observations that triple therapy ART reduced transmission.
  • 1998: expert opinion that risk would be reduced (including based on reviewing evidence related to the details of this protection).
  • 2000 — 2005: prospective observational studies and related research (Rakai cohort and others).
  • 2008: further expert opinion and evidence review (Swiss Statement).
  • 2011: first evidence from a randomised clinical trial (HPTN 052).
  • 2014 — 2017: further prospective observational studies (PARTNER and Opposites Attract) — the first studies to provide data about risks for gay men.
  • 2016 — 2017: further expert opinion (U=U campaign).

Each of these studies is now explained in more detail.

Early Evidence: Mother-to-Child And Ugandan Heterosexual Couples

A remarkable report in July 1998 provided some of the first clinical evidence for the impact of viral load on HIV transmission.

At the IAS conference held in Geneva, Dr Karen Beckerman reported on a small cohort of HIV positive women in San Francisco who had used triple therapy during pregnancy. Instead of the 30% mother-to-infant transmissions reported before ART, or the 10% seen with AZT monotherapy, triple therapy reduced transmissions to approaching zero.3

Although this study reported on vertical rather than sexual transmission it provided clinical results showing that an undetectable viral load stopped a much higher risk of transmission.

Then later that year, the December 1998 update to the US DHHS guidelines, included “possibly decreasing the risk of viral transmission” as an additional reason for starting ART.4

These expert guidelines noted the lack of direct evidence supporting this statement and emphasised that condoms should still be used even with undetectable viral load — but this inclusion in the 100-page document from leading US doctors this was important.

One of the next key studies provided direct evidence linking viral load with risk of HIV sexual transmission. This was a prospective observational cohort study in 415 serodifferent heterosexual couples in Rakai, Uganda, where one partner was HIV positive and the other was HIV negative. The study, by Thomas Quinn and colleagues was published in the New England Journal of Medicine in 2000.5

After median follow-up of 22 months, the risk of HIV transmission was not only clearly linked to higher viral load. No transmissions were reported among the 51 couples where the HIV positive partner had viral load below 1500 copies/mL.

Several details of the Rakai study are important. It was before ART was available and condom use was low. It found that transmissions rates were similar for men and women and that other STIs didn’t affect HIV risk. It also reported highly significant impact from circumcision — all the men who became positive during the study were uncircumcised.

These results were 17 years ago.

Expert Opinion and Evidence Review: The Swiss Statement

From 2000 to 2008, many smaller studies reported reductions in other routes of transmission, or supplemented observational data with supportive research, such as reporting the impact of ART in genital fluids.

For example, in 2005, a Spanish cohort reported on 393 heterosexual serodifferent couples where the negative partner became HIV positive during the period 1991 to 2003. The results were presented for three time periods — pre-ART (1991-1993), early-ART (1996-1998) and late-ART (1999-2003) — and reported no transmissions when the positive partner was on ART.6

Cautions for these results were that other risks reduced over time, such as condoms being more widely used and people having less sex as they grew older, but zero transmissions was still significant.

In 2008, Petro Vernazza and colleagues published the first high profile evidence review that concluded that ART stopped transmission.7

This paper, published in French but quickly translated into English, was a response to the laws in Switzerland that criminalised an HIV positive person if they had sex with a negative partner, even if condoms were being or if a couple wanted to conceive with full consent. This paper reviewed more than 25 studies and concluded that transmission didn’t occur. The estimated risk as a very rare event was less than 1 in 100,000 (0.00001%) — and therefore effectively zero.

Important considerations for the Swiss Statement included that the HIV positive person should be adherent on effective ART (not missing doses), have an undetectable viral load, and not have sexual infections that might increase viral load.

The Swiss Statement was not only widely publicised but it was also widely cricitised, generating a very high profile. As such, it set a challenge to other doctors and researchers to report any cases that disproved the statement. Given the competitive nature of academic research, it is notable that after almost ten years no cases have been published that refute the Swiss Statement.

Randomised Study: HPTN 052

Scientists grade evidence based on the design of studies to be able to prove a link between and intervention and outcome. For many questions, the best quality of evidence comes from a randomised clinical trial. The process of randomly assigning participants to two or more groups where only the intervention is different, is the best way to rule out the results having been due to chance.

Because there is always the potential for other factors to affect outcomes, randomised studies are usually credited as the gold standard for evidence.

In 2011, US researchers, led by Myron Cohen and colleagues at the HIV Prevention Treatment Network (HPTN) reported early results from the HPTN 052 study.8

HPTN 052 recruited more than 1700 serodifferent couples (mainly in southern Africa, Latin America and South-East Asia. These were almost entirely heterosexual couples, and the HIV positive partners were randomised to either start ART immediately or wait until their CD4 count dropped to 350 cells/mm3 (the then threshold in WHO guidelines for starting treatment).

All couples were supported with condoms and information on reducing the risk of HIV transmission, but it soon became clear that HIV transmissions were almost exclusively occurring in the group waiting for ART. Of the 39 transmissions, 28 were linked to HIV positive partner. Of these, 27/28 were in group waiting for ART. The single transmission in the immediate ART group occurred within weeks of starting treatment, when viral load would have still been high and certainly detectable.

This provided a very high level of evidence that ART was directly linked to protection against sexual transmission and as a result the HPTN 052 study was stopped early so that all HIV positive participants could receive immediate ART. Longer follow-up of HPTN continued for at least another four years and confirmed these early results.9

HPTN 052 produced evidence to enable HIV positive people to access ART earlier in order to protect their partners — called Treatment as Prevention (TasP). But limitations of the study meant that it could only report relative differences between the two study groups, rather than quantify any actual risk (even if the risk was theoretical).

Again, this was a heterosexual study, anal sex was rarely reported and condom use was relatively high. This meant that while ART could be proved to reduce infection, the study couldn’t estimate how low this risk became, or the likely risk for different types of sex.

Large Observational Cohorts: PARTNER Study and Opposite’s Attract

In 1999, several years before the results from HPTN 052, a group of European researchers led by Jens Lundgren from the Centre of Excellence for Health, Immunity and Infections (CHIP) launched the prospective observational PARTNER study.10,11

The PARTNER study was important for enrolling serodifferent couples where the HIV positive partner was on ART and where the couples were already not always using condoms (often for many years).

Importantly, approximately one-third of the almost 900 couples were gay men and the study included detailed questionnaires on sexual activity to estimate risk based on actual exposure. As with all studies, information about reducing HIV transmission, including free condoms, were included for all participants. All couples were then followed over time, trying to see whether transmissions occurred.

In a planned early analysis, presented at a conference in February 2014, PARTNER reported zero linked (within-partner) transmissions after more than 44,000 times when condoms hadn’t been used and viral load was undetectable (defined as less than 200 copies/mL).10

PARTNER also provided reassurance for previous theoretical concerns from viral load blips or other STIs. No transmissions were seen in the 91 couples where the positive partner reported an STI (approximately one-third of gay couples had open relationships). The final results, presented and published in July 2016, reported zero transmissions after 58,000 times without condoms.11

The PARTNER results made headlines globally, but a less well-known aspect of this study was that the ground-breaking results took nearly two years to be published. This is likely linked to the implications the results would have on HIV prevention campaigns that were based on always using a condom, even when the limitation of condom-only prevention were clear from continued high rates of HIV transmission.

Because an important outcome of the PARTNER study is to quantify the theoretical range of risk (the upper limit of the 95% confidence interval), the PARTNER 2 study continued to collect results in gay couples to provide an equal balance of evidence compared to heterosexual data.12

Finally, at the IAS conference held in Paris in 2017, results from the Opposite’s Attract study in 358 gay male couples from Australia, Thailand and Brazil, also reported zero linked transmissions after almost 17,000 when condoms were not used.13

Again, STIs were not uncommon (present in around 1,000 of these occasions) and didn’t result in HIV transmission.

Zero to Negligible: What Is in a Word

HIV transmission, even without a condom and without ART, is generally an uncommon event.

For example, the average upper range of estimated per-exposure risk ranges from 0.014 for receptive anal sex (14 in 1000) to from 0.001 for receptive or insertive vaginal sex (1 in 1000) and the lower ranges are many fold lower.14

However, during the first 2 to 4 weeks after infection, when viral load can be millions of copies/mL and people still believe they are HIV negative, risk will be higher. This led to many health campaigns pointing out that a someone who believes they are HIV negative based on their last HIV test is associated with a much higher relative risk than any HIV positive person with undetectable viral load on ART.

Nevertheless, the semantic difference between zero risk and negligible risk, even when this theoretical risk is increasingly tiny (as with the Swiss Statement), prevented some people saying that the risk was effectively zero.

The most significant change over the last year, driven by the U=U campaign, has been for leading HIV scientists to now assert that a negligible theoretical risk is effectively zero.

Reversing the Challenge to Prove if Transmission Is Possible

Under ideal circumstances, large prospective studies that were designed to find cases of transmission when viral load was undetectable have not been able to do so.

So the evidence gap in 2017 is now the lack of any proof showing that HIV transmission is possible when viral load is undetectable.

This reverses the scientific challenge from proving safety to proving risk. Purely theoretical risks are no longer a good enough level of evidence to sustain stigma and discrimination and certainly not criminalisation.

Instead, there is no evidence to show that HIV transmission occurs when viral load is undetectable. People who want to assert the theory that HIV transmission might be possible, now have to provide some level of proof.

Conclusion

A comprehensive body of evidence now supports the U=U statement. This ranges from early clinical and theoretical studies, though small observational studies, randomised trials and the large prospective cohorts.

In addition, no cases of HIV transmission have been reported, over nine years since the Swiss Statement set this challenge. This includes data for gay men, for couples that have anal sex, over periods when low-level viral blips are likely and even when STIs are present.

In reality, even if the actual risk is zero, it is not healthy to think about anything in life as being risk-free. Even if at some point in the future an unlucky and rare case of transmission is reported with undetectable viral load, the U=U campaign is still right for closing the gap between zero and the real-life meaning of negligible in real terms.

Table 1: Key Selected Evidence Supporting U=U
Study Study Details Results Date Reference
San Francisco cohort Clinical results from small cohort of HIV positive women using triple ART during pregnancy. Transmission from mother to baby was reduced to approaching zero. 1998 Beckerman K et al. [3]
DHHS guidelines Expert opinion included in evidence-based guidelines. Theoretical plausibility of reducing transmission risk was used as a factor for early ART. 1998 DHHS guidelines. [4]
Ugandan cohort (Rakai) Prospective observational cohort in ~ 400 serodifferent couples. Zero transmissions when viral load was less than 1500 copies/mL. 2000 Quinn TC et al. [5]
Spanish cohort Prospective observational study in 393 heterosexual discordant couples enrolled from 1991 to 2003 where the negative partner became HIV positive. Zero transmissions in couples where the HIV positive partner was on ART with undetectable viral load. Cautions emphasised good adherence and no STIs. 2005 Castella A et al. [6]
Swiss Statement Expert opinion and evidence review of >25 smaller studies looking at impact of ART on risk factors for HIV transmission. Concluded that transmission would not occur undetectable with viral load. 2008 Vernazza P et al. [7]
HPTN 052 1763 serodifferent heterosexual couples randomised to immediate or deferred ART.Although condom use was high the impact of ART was highly significant. All infections occurred in people with detectable viral load: n=17 in the deferred ART group and one early infection in the ART group before VL was undetectable. Follow-up reported out to four years. 2011 Cohen M et al. [8, 9]
PARTNER Prospective observational European study in ~900 serodifferent couples who were not using condoms. Final results reported zero transmissions after more than 58,000 times couples had sex without condoms when viral load was undetectable <200 copies/mL. 2014 (interim presented).
2016 (final, presented and published)
Rodgers A et al. [10, 11]
Opposite’s Attract Prospective observational study in 358 serodifferent gay male couples in Australia, Thailand and Brazil. Zero transmissions when viral load was undetectable <200 copies/mL. 2017 Grulich A et al. [12]
PARTNER2 Extension of PARTNER study to collect additional follow-up in gay male couples. Study is fully recruited and still ongoing (2014-2017). Expected 2018. [13]

This article is based on a talk given to the Positive People’s Forum held in Glasgow on 1 July 2017. [15]

[Note from TheBody.com: This article was originally published by HIV i-Base on Aug. 9, 2017. We have cross-posted it with their permission.]

References

  1. Undetectable = Untransmittible
    www.preventionaccess.org
  2. U=U consensus statement: Risk of sexual transmission of HIV from a person living with HIV who has an undetectable viral load.
    www.preventionaccess.org/consensus
  3. Beckerman K et al. Control of maternal HIV-1 disease during pregnancy. Int Conf AIDS 1998 Jun 28-Jul 3; 12:41. Poster abstract 459.
    http://i-base.info/ttfa/wp-content/uploads/2012/05/Beckerman-Abs459-IAS-geneva-1998.pdf (PDF)
  4. U.S. Department of Health and Human Services (DHHS). Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. December 1998.
    https://aidsinfo.nih.gov/guidelines/archive/adult-and-adolescent-guidelines
    https://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL12011998012.pdf (PDF)
  5. Quinn TC et al. Viral load and heterosexual transmission of HIV type 1. Rakai Project Study Group. N Engl J Med 2000; 342: 921-929. Free online access.
    www.nejm.org/doi/full/10.1056/NEJM200003303421303
  6. Castilla J, del Romero J, Hernando V, Marincovich B, Garcia S, Rodriguez C. Effectiveness of highly active antiretroviral therapy in reducing heterosexual transmission of HIV. J Acquir Immune Defic Syndr. 2005;40:96-101. Free full text.
    http://journals.lww.com/jaids/Fulltext/2005/09010/Effectiveness_of_Highly_Active_Antiretroviral.16.aspx
  7. Vernazza P et al. HIV-positive individuals not suffering from any other STD and adhering to an effective antiretroviral treatment do not transmit HIV sexually. (Les personnes séropositives ne souffrant d’aucune autre MST et suivant un traitment antirétroviral efficace ne transmettent pas le VIH par voie sexuelle). Bulletin des médecins suisses 89 (5), 30 January 2008. Included with English translation.
    http://i-base.info/qa/wp-content/uploads/2008/02/Swiss-Commission-statement_May-2008_translation-EN.pdf (PDF)
  8. Cohen MS et al for the HPTN 052 Study Team. Prevention of HIV-1 infection with early antiretroviral therapy. Supplementary information. NEJM 2011; 365:493-505.
    www.nejm.org/doi/full/10.1056/NEJMoa1105243
  9. Cohen MS et al. Final results of the HPTN 052 randomized controlled trial: antiretroviral therapy prevents HIV transmission. IAS 2015, 19-22 July 2015, Vancouver. MOAC0101LB.
    http://dx.doi.org/10.7448/IAS.18.5.20482
  10. Rodger A et al. HIV transmission risk through condomless sex if HIV+ partner on suppressive ART: PARTNER Study. 21st CROI, 3-6 March 2014, Boston. Oral late breaker abstract 153LB.
    www.croiwebcasts.org/console/player/22072 (webcast)
  11. Rodger AJ et al for the PARTNER study group. Sexual activity without condoms and risk of HIV transmission in serodifferent couples when the HIV-positive partner is using suppressive antiretroviral therapy. JAMA, 2016;316(2):1-11. DOI: 10.1001/jama.2016.5148. (12 July 2016). Full free access.
    http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.5148
  12. PARTNER2 Study (2014-2017).
    www.cphiv.dk/PARTNER-2
  13. Grulich A et al. HIV treatment prevents HIV transmission in male serodiscordant couples in Australia, Thailand and Brazil. IAS 2017, Paris. Oral abstract TUAC0506LB.
    http://programme.ias2017.org/Abstract/Abstract/5469
  14. Fox J et al. Quantifying sexual exposure to HIV within an HIV-serodiscordant relationship: development of an algorithm. AIDS 2011, 25:1065-1082. DOI:10.1097/QAD.0b013e328344fe4a. Free online access.
    http://journals.lww.com/aidsonline/Abstract/2011/05150/Quantifying_sexual_exposure_to_HIV_within_an.7.aspx
  15. Collins S. Undetectable = Uninfectious. Positive Person’s Forum, 1 July 2017, Glasgow.
    http://i-base.info/slide-sets
    http://i-base.info/wp-content/uploads/2016/02/Positive-Forum-Scotland-2017-Undetectable-FINAL.pdf (PDF)

Community Pharmacy Dispensing

Dispensing rules for HIV ART medication changed on 1 July 2015. This mean you can fill your script and collect your HIV ART from a number of select community pharmacies. Unfortunately we will not just be able to waltz into a community pharmacy and have the pharmacist pull our ARTs off the shelf. The majority of community pharmacies will not keep HIV ART medicines in stock, instead they will order as and when customers require. That means you will need to have a conversation in advance with your pharmacist so your medication can be ordered ahead of time to avoid treatment interruptions.

It’s important to know this service will cost. We are lucky in Western Australia that our HIV ART medication dispensing fee at the public hospitals is paid for by the WA Department of Health. However, when you collect your medication from a community pharmacy you will have to pay either a general patient co-payment or a concessional co-payment. What does this mean? Check out the table below:

table-pharmacy
If you think community dispensing might right for you have a chat to your HIV clinician/ clinical nurse so they are aware you will be taking your script outside of the hospital. For refills, plan ahead. You can leave your script with your chosen pharmacy and use http://medadvisor.com.au/ on a smart phone or computer to keep track of your scripts, remotely refill scripts and more. I highly recommend checking it out. And if postal deliveries are something you’re interested in, chat with the pharmacist to ask about options.

Which pharmacies are onboard?
There are 11 community pharmacies in Perth currently with the capacity to fill your HIV ART scripts, however I’m sure more will come aboard with time. They include:

  1. Amcal Max Burswood, 265 Great Eastern Highway. Ask for pharmacist:
    Tyson Wellman, Ph: 9361 8777
  2. Craven’s Pharmacy, 2/553 Hay St, Perth CBD. Ask for Ron Stuurstraat,
    Ph: 9325 4375
  3. Beaufort St 24 Hour Chemist, 647 Beaufort St, Mount Lawley. Ask for pharmacists Althea Cao & Alexis McLeod, Ph: 9328 7775
  4. Helena Estate Pharmacy, Shop 3, 1 Torquata Bvd, Helena Valley. Ask for pharmacist Julie Stuurstaart, Ph: 9250 5811
  5. Maddington Village Pharmacy, Shop 3, Maddington Village, Westfield St, Maddington. Ask for pharmacist Nathan Paull & Christian Rossi, Ph: 9459 6179

Note: PrEP is not currently TGA-licensed, nor is it available in Australia on the PBS. You will not be able to get PrEP from your community pharmacist.

6. Mckenzies Chemist
Pharmacist: Jamie Tran / Dalini Rajalingam
689 Beaufort St, Mt Lawley WA 6050
Ph: 9328 9447
Hours:  8am – 9pm seven days a week

7.  Northbridge Pharmacy
Pharmacists: Lynh Pham / Kerry Ly.
Shop 1, 154-156 Newcastle Street, WA 6000
Ph: 9328 9447
Hours:
Monday to Friday 8am – 7pm
Saturday 9am – 5pm
Sunday 9am – 3pm

8. Pharmacy 777 Applecross
Pharmacists: Clare Woodrow / Carolyn Holmes
777 Canning Hwy, WA 6153
Ph 9444 5551
7am – 11pm seven days a week

9. Pharmacy 777 Glendalough
Pharmacists: Wayne Lee / Chloe Chew
Shop 8-10, Glendalough Village Shopping Centre,
Crn Harborne St & Jon Sanders Dr, WA 6016
Ph 9444 5551
8am – 10pm seven days a week

10. Pharmacy 777 Maylands
Pharmacists: Storm Meacock / Greg Da Rui
238 Guildford Rd, Maylands, WA 6051
Ph 9271 5659
8am – 10pm seven days a week

11. Swan View Pharmacy
Pharmacist: Michael Slater
Shop 3, Swan View Shopping Centre, Gladstone & Marlboro Roads, Swan View WA 6056
Ph: 9294 2917
Hours:
Monday, Tuesday, Wednesday, Friday 8.30am – 6pm
Thursday 8.30am – 7pm
Saturday 8.00am – 5pm
Sunday 11.00am – 5pm

pharmacymap
Figure 1: Map of community pharmacies currently on board with HIV ART dispensing (Aug 2015)

Triumeq (abacavir 600mg, dolutegravir 50mg and lamivudine 300 mg)

TriumeqTriumeq a new single tablet regimen (STR), combining abacavir 600mg, dolutegravir 50mg and lamivudine 300 mg has been approved by the Therapeutic Goods Administration (TGA) in Australia. It is manufactured by ViiV Healthcare and is already available in the US (Aug 2014) and European Union (Sept 2014).

It is the first single-tablet regime that does not contain Truvada (tenofovir disoproxil fumerate/emtricitabine), making it a potential option for those who have impaired kidney function and/or bone toxicity.

Triumeq is considered suitable for ARV treatment-naïve or those without resistance to any of the three ARV agents (abacavir, dolutegravir, lamivudine). A component of Triumeq – dolutegravir, is a second generation intergrase inhibitor and is suitable for those who have resistance to first gen raltegravir and elvitegravir.

Before commencing Triumeq an abacavir hypersensitivity test is conducted, this genetic test screens for the presence of the human leukocyte antigen HLA-B*5701 allele. Presence of the HLA-B85701 allele is strongly associated with a hypersensitivity reaction to abacavir. Without genetic screening the reaction occurs in 5-8% of patients and is most common in those with a Northern European descent. Hypersensitivity to abacavir is a multi-organ syndrome, including symptoms such as rash, fever, fatigue, nausea, diarrhoea, abdominal pain and respiratory issues. Symptoms typically appear in the first 6 weeks of commencing abacavir treatment.

Triumeq can be taken with or without food and there are no restrictions regarding level of viral load or CD4 count.

Triumeq is not yet available on the Pharmaceutical Benefits Scheme (PBS). A decision is expected in Q2 2015.

References

TGA approved Triumeq
FDA Approves New Single-Tablet HIV Regimen, Triumeq
AIDSinfo drug database Abacavir / Dolutegravir / Lamivudine

Australian Treatment Cascade

At the beginning of January I wrote about New Year resolutions for our HIV management. That got me thinking about the treatment cascade. You may not have heard of it, so let me explain.

The HIV care and treatment cascade is a graph which helps us visualise the proportion of:

  • people with HIV in Australia,
  • those diagnosed,
  • linked to care,
  • retained in care,
  • receiving ART (treatment) and
  • having an undetectable viral load (UVL).

The Kirby Institute calculate of the 100% of people in Australia who are HIV-positive about 86% of people know they are living with HIV. 78% & 76% are linked and retained in care. 66% are receiving HIV treatment and 62% have an UVL.

Or as I like to describe:

72% who know they are HIV-positive are accessing HIV treatment and have an UVL’.

poz in oz figure 1

Figure 1: Estimates HIV care and treatment cascade in Australia at the end of 2013

 

So how are we doing compared to other countries?

Well at a conference in Glasgow in 2014 Raymond et al. presented an abstract on ‘Large disparities in HIV treatment cascades between eight European and high-income countries: analysis of break points.’ Or in other words, ‘How do treatment cascades from high income countries compare?’

Australia came in 1st place! We are estimated to have the highest proportion of people living with HIV on treatment with an UVL. I was surprised to find the United States at the bottom of the list, with only 25% having an UVL. This is lower than some sub-Saharan African countries where an estimated 29% of PLHIV have an UVL. Clinicians and public health officials can use these ‘cascades’ to help focus efforts and improve successes, such as increasing HIV testing or better referral pathways.

poz in oz figure 2

Figure 2: Treatment cascade in high-income countries

In Australia it looks like our 2015 HIV management resolutions are already in full swing. Now lets aim for the UNAIDS ambitious targets of 90:90:90. 90% of all people living with HIV knowing their HIV status, 90% of all people diagnosed with HIV receiving HIV treatment and 90% of all people receiving HIV treatment having an UVL.

References:

Estimated HIV care and treatment cascade in Australia (best estimate and uncertainty bounds of plausible limits) “HIV in Australia: Annual Surveillance Report 2014 Supplement”

“Australia performs best in HIV treatment cascade – 62% with undetectable viral load”

New Year Resolutions

new yearLove them or hate them, stick to them or ditch ‘em, New Year resolutions are common talk around this time of year. We promise ourselves acts of self-improvement or doing something nice for others, yet whether they last really depends on our level of motivation.

I consider managing my HIV to be a worthy resolution. Every year I promise myself to remain engaged in clinical care and adhere to my HIV medication. It might seem like a no brainer, but for me after years and years of living with HIV it really does take a back seat to what’s going on in the rest of my life.

Wherever you are on your HIV journey perhaps you can make a New Year resolution about managing your HIV in 2015?

Things you can do to get on and stay on track:

    • Start HIV treatment (if you haven’t already). Studies prove starting treatment regardless of CD4 count has significant benefit to your health, reducing viral load and onward transmission.
    • Adhere to your medication, set an alarm (if like me you get a bit forgetful)!
    • Write down scheduled hospital and GP appointments in your diary, calendar or smartphone. If you’re worried someone might look you could write these in code, i.e. Coffee with Fiona (aka Fiona Stanley Hospital).
    • Work out in advance medication refills. Nothing is worse than stressing you don’t have enough tablets to get you through to Monday!
    • Keep up with regular blood tests, typically every time you collect a new script. This is the only way of knowing the HIV medication is working correctly and you have an undetectable viral load (UVL)
    • Foster a good relationship with a HIV clinician/GP, one where you feel there is a partnership and are confident having a two-way conversation.
      Get help & support for other concerns such as financial vulnerability, mental health, substance use or unstable housing in order to help you fully engage with medical care and adhere to HIV treatment.

Perhaps if you need some help to get started you could schedule an appointment with a support officer at WAAC on 9482 0000. Good luck and let’s kick start our HIV management with a bang in 2015!!!