Tag Archives: Pre-exposure prophylaxis

(Scotland): Decision due on ‘game-changer’ Prep HIV drug

Medical chiefs in Scotland are due to announce whether a “game-changing” drug which can prevent HIV infection will be made available on the NHS.

(Story via BBC)

Research suggests a daily dose of a drug known as Prep can protect people at risk of contracting the virus.

HIV Scotland said it was “very hopeful” the Scottish Medicines Consortium (SMC) would approve the medication.

It means Scotland would become the first place in the UK to make it available on the NHS.

Campaigners estimate that up to 1,900 people north of the border could benefit from the drug, which has the brand name Truvada.

The anti-retroviral drug is currently licensed for use in Scotland, where it is used by people already diagnosed with HIV.

However, the SMC’s decision relates to its use on a preventative basis by people who do not have the virus.

What does Prep do?

Pre-exposure prophylaxis (or Prep for short) is a small, blue pill.

The pill works by protecting cells in the body and disabling the virus to stop it multiplying – should it enter the body.

Taking it once a day has been found to reduce the risk of HIV infection by 86%.

It is currently used in the US, Canada, Australia and France to help protect gay men at the highest risk of contracting HIV.


There is a growing demand for the treatment in Scotland, according to HIV Scotland’s chief executive George Valiotis.

He estimates that “a couple of dozen” Scots are using variants of the drug after buying generic versions online.

The Scottish government wrote to Gilead, the manufacturer of Truvada, to urge them to make an application to the SMC last year.

It followed a series of legal battles in England over whether the NHS or local authorities should pay for the medication.

The Court of Appeal eventually ruled that NHS England had the power to fund the drug,

The decision did not mean that NHS England had to fund Prep but in December it announced plans for a large scale clinical trial of the drug, expected to involve 10,000 participants over three years.


‘Why I buy Prep online’

Gordon Garioch is one of around “a couple of dozen” people in Scotland thought to be taking Prep regularly.

He told BBC Radio Scotland’s Good Morning Scotland that he was initially prescribed the drug by a private clinic but it was too expensive.

He now spends around £50 a month on a generic form of the drug he purchases from an online pharmacy.

“It gives me reassurance,” he said. “I’ve always been careful.

“My friends have always been careful but for some reason they became positive. So I take this extra reassurance for me to prevent myself becoming positive.”

Asked what the benefits of the decision would be, he replied: “To me personally, obviously it would be the cost.

“But it’s a generation thing as well, to prevent HIV for future generations for people who are not as lucky as myself who can pay for it.”


Speaking on BBC Radio 4’s Today programme, Mr Valiotis, of HIV Scotland, said: “Prep makes good sense. We know that it works. We know that it stops people from getting HIV, and we know that it’s cost-effective.

“And because it’s cost-effective, what that means is that it makes more money available in the long-term on the NHS to treat lots of other things as well.”

Asked if he thought the SMC would approve the drug, he said: “I’m feeling pretty hopeful because the cost-effectiveness is clear, as is the clinical-effectiveness.

“We know this works. I would be surprised if it’s a no but it’s too hard to guess.”

HIV Scotland believes the use of Prep has played a part in reducing the number of HIV infections in Scotland.

The latest figures from Health Protection Scotland show 285 new cases of HIV were reported in 2016, down from an annual average of 359 over the last five years.

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10 things you need to know about the pill to prevent HIV

The Magic Pill

It’s been called, simultaneously, a medicine to “end the HIV epidemic” and a “party drug:” Pre-exposure prophylaxis, or PrEP for short, refers to a daily antiviral treatment that prevents HIV.

That’s right: People who don’t have the virus can take a pill a day to save themselves from getting infected.

Haven’t heard about PrEP? You’re probably not alone. The drug-maker, Gilead, doesn’t advertise Truvada (its brand name) for prevention, and the Centres for Disease Control and Prevention only endorsed it this past May—two years after it hit the market.

Want to learn more about PrEP, (click here).

Going forward, however, you’ll be hearing a lot more. On Friday, the World Health Organization backed the antiviral, recommending all HIV-negative men who have sex with men consider taking it as part of a strategy to reduce the global incidence of the disease. But there’s a lot more to the story. Here’s what you need to know:

1) Public health officials aren’t recommending this pill for “all gay men,” despite what the headlines say

The pill is “for people who do not have HIV but who are at substantial risk of getting it,” according to CDC guidance. “At substantial risk” means you regularly have unprotected sex with partners of unknown HIV status. This can include men who have sex with men, heterosexual men and women, injection drug users, sex workers, and people in couples with an HIV-positive partner. In other words, not simply “all gay men.”

The latest headlines about Truvada were so misleading that the WHO had to issue a clarification noting that they support PrEP “as an additional choice”—again, not for all men who have sex with men.

“We know from surveillance that condom use is not as high as is necessary to control the epidemic”

2) Truvada is not a condom replacement

Public-health officials are not endorsing Truvada as an alternative to other forms of protection. “We are suggesting that for people who are already not using condoms, we have another option to help protect them from HIV infection,” says the CDC’s Dawn Smith, biomedical interventions implementation officer. “It’s part of being practical and realistic.” So the hope is that those who get prescriptions are folks who just aren’t using anything to protect themselves. “We know from our surveillance systems that condom use is not as high as is necessary to control the epidemic,” Smith added.

3) We don’t yet know exactly how the drug will be used in real life

Still, this public-health message hasn’t stopped some activists and AIDS campaigners from worrying aloud that the pill will undermine traditional advocacy messages about condoms—especially at a time when HIV infections are on the rise among gay men. And the truth is, we don’t yet know what kind of impact PrEP will have on people’s behaviour.

To find out, there are now “demonstration trials” being run around the world. These will look at how Truvada works outside of clinical trials, the impact of non-daily use of the drug, and whether the antiviral encourages more risky sexual behaviour or leads to an increase in other sexually-transmitted infections.

4) We do know Truvada only works effectively when taken every day

A three-year clinical trial of PrEP in HIV-negative men who have sex with men found that users got much more protection when they took the drug every day. Participants who took the drug less than half the time had a 50 percent reduction in HIV acquisition; daily users cut their risk by more than 90 percent. These results have been supported by other studies in a range of populations—from injection-drug users to heterosexual men and women. The trouble is, most people don’t take their medications as their doctors prescribe.

Drug-resistant strains of HIV have emerged when people with acute, undetected infection were given Truvada

5) Truvada can cause drug-resistant HIV infection

Drug-resistant strains of HIV have emerged when people with acute, undetected infection were given PrEP. This means they were positive when they started the medicine, but levels of the virus in their blood were hardly detectable because their infections were so new. They hadn’t made enough antibodies to show up in a test and so they were prescribed the drug anyway.

There’s some question about how serious this risk is for individuals and public health. For now, doctors are asked to confirm the HIV status of patients and to do follow-up and re-testing throughout treatment.

When asked how much of a concern drug resistance is, Smith of the CDC said, “We don’t know yet. That’s one of the things we’ll learn as the first few demonstration projects begin telling us.”

6) Besides that, it’s pretty safe

Though Truvada for the prevention of HIV was only licensed by the Food and Drug Administration in 2012, it was first authorized in 2004 to treat HIV positive patients. That’s right: the same drug used for these two purposes. Since it has been on the market as a treatment for over a decade—with very minimal side effects and harms—doctors are pretty confident in its safety profile for preventative use. There seem to be few side-effects with Truvada for prevention, the most common one being nausea.

People have been slinging the term ‘Truvada whore’ around, and the head of the aids healthcare foundation called the pill a ‘party drug’

7) “Truvada whores” are a thing

Because of the questions about whether PrEP will cause people to have risky sex and ditch condoms, there’s some related stigma in the gay community. People have even been slinging the term “Truvada whore” around, and the head of the AIDS Healthcare Foundation called Truvada a “party drug.” In response, one PrEP activist created a #TruvadaWhore t-shirt campaign to reclaim the word.

Many have pointed out that this divide parallels the early days of the birth control pill and suggestions that the medication would encourage promiscuity.

8) Uptake has been slow—but that’s not the full story

According to data from the drug maker Gilead, by March 2013 there were approximately 1,774 people in the US taking the drug. But it’s important to put this number in context. First of all, these findings were not published and peer-reviewed; they were presented at a scientific conference last year. When studied, we’ll have a better picture of the PrEP landscape and it may look quite different.  Secondly, Truvada has only been on the US market for prevention since 2012, a year after these numbers were gathered. It often takes decades for innovations to penetrate a market, especially in the conservative field of medicine.

9) The drug is expensive

Without insurance, Truvada can cost up to $14,000 a year, according to the CDC. But for most people, it is covered in their insurance programs and there’s only a co-pay. There are also medication assistance programs across the US for the uninsured that will cover the entire cost of the medication.

10)  HIV remains a socio-economic crisis around the world

Globally, men who have sex with men, prisoners, injection-drug users, and sex workers are still the groups most affected by HIV.

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US Regulators Vote For Approval of PrEP by Large Majority

The US Food and Drug Administration (FDA) took a decisive step yesterday towards approving the use of combination pill Truvada(tenofovir/FTC) as a prevention method for HIV-negative people.

The FDA’s Antiviral Drugs Advisory Committee (ADAC) voted by a majority of 19 to 3 in favour of recommending Truvada as PrEP (pre-exposure prophylaxis) for men who have sex with men, and by 19 to 2 with one abstention for an approval for use by the HIV-negative partner in serodiscordant couples.

There was a close vote, however, when it came to recommending its use generally in individuals for people at risk of HIV infection: 12 to 8, with two abstentions, voted for a general recommendation for any person at risk of HIV.

The ADAC decision was taken after an all-day meeting on 10 May. This meeting discussed the findings of a written report and also heard submissions from a large number of community prevention and treatment advocates. Interest was such that the FDA extended the time for submissions from advocates and community members from one hour to two and had to organise a ballot for access to the hearings.

The written report had concluded that concerns about safety and HIV drug resistance were not sufficient to delay the introduction of PrEP. It also decided that concerns about poor adherence levels seen in some randomised controlled trials, and about whether PrEP would negatively influence behaviour to such a degree that people ended up at greater risk of HIV, were beyond the remit of the FDA.

“I don’t think it’s our charge to judge whether people will take the medicine,” panellist Dr Tom Giordano told the Los Angeles Times. “Our charge is to judge whether it works when taken.”

Considerations of cost are also explicitly ruled out of the FDA’s remit when it comes to approving a new drug or indication.

The FDA is not bound to follow the recommendations of its advisory committees and will make a final decision by 15 June. However it is very rare for it not to do so and the large majority in favour of its approval for gay men and in serodiscordant couples makes this unlikely.

PrEP has always excited controversy amongst HIV prevention advocates and people affected by HIV. Some organisations have opposed its introduction and the AIDS Healthcare Foundation, in particular, has mounted a provocative campaign against its approval. “If you love Vioxx you’ll love PrEP,” read one poster displayed on bus shelters near the White House, referring to the painkilling drug that was withdrawn in 2004 when it was linked to heart attacks.

The majority of HIV prevention advocates, however, has supported PrEP. Mitchell Warren of the AIDS Vaccine Advocacy Coalition (AVAC) commented: “Some funders and policy makers have been awaiting a signal from the FDA before launching demonstration projects or developing implementation plans.

“The time for waiting is over. We need to get on with the work of setting priorities and rolling out PrEP to people who can benefit the most.”
The controversy was if anything reinforced when the randomised controlled trials (RCTs) of PrEP that have reported in the last 18 months –iPrEX, Fem-PrEP, Partners PrEP and TDF2 – produced strikingly different results, with headline efficacy levels ranging from zero (in Fem-PrEP) to 83% (for men in Partners PrEP). Studies of drug levels found that these results could be explained by different levels of adherence in trial participants. PrEP was 92% efficacious in participants in iPrEx who had detectable levels of drug in their blood, and it is clear that adherence levels will crucially determine whether it protects the people who take it.

At present randomised controlled trials have only tested daily doses of PrEP, though a study in France, IPERGAY, is currently testing its efficacy in gay men when taken on a before-and-after-sex basis.
In contrast concerns about negative behaviour change and participants putting themselves at greater risk of HIV have not been supported by RCT findings, but it is recognised that these will only be answered by an open-label study in which people know for sure that they are taking the drug and not a placebo.

Such a study, called PROUD, has been suggested for the UK and is awaiting a decision on approval. In this study gay men attending genitoruinary medicine clinics in the UK who are at significant risk of HIV will be offered TruvadaPrEP plus a package of behavioural support and counselling, but will be randomised to receive the PrEP component either immediately or a year later.

Principal Investigator of the proposed study, Dr Sheena McCormack of the UK Medical Research Council (MRC), told Aidsmap: “It is unusual for the MRC to talk publicly about a trial before it receives approval, but in the case of PrEP it is so important that the trial involves and is supported by its target community.”

Original article by Gus Cairns at Nam

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Giving preventive drug to men at high risk for HIV would be cost-effective, study shows

A once-a-day pill to help prevent HIV infection could significantly reduce the spread of AIDS, but only makes economic sense if used in select, high-risk groups, Stanford University researchers conclude in a new study.

The researchers looked at the cost-effectiveness of the combination drug tenofovir-emtricitabine, which was found in a landmark 2010 trial to reduce an individual’s risk of HIV infection by 44 percent when taken daily. Patients who were particularly faithful about taking the drug reduced their risk to an even greater extent — by 73 percent.

The results generated so much interest that the Stanford researchers decided to see if it would be cost-effective to prescribe the pill daily in large populations, a prevention technique known as pre-exposure prophylaxis, or PrEP. They created an economic model focused on men who have sex with other men, or MSM, as they account for more than half of the estimated 56,000 new infections annually in the United States, according to the Centers for Disease Control and Prevention.

“Promoting PrEP to all men who have sex with men could be prohibitively expensive,” said Jessie Juusola, a PhD candidate in management science and engineering in the School of Engineering and first author of the study. “Adopting it for men who have sex with men at high risk of acquiring HIV, however, is an investment with good value that does not break the bank.”

For instance, using the pill in the general MSM population would cost $495 billion over 20 years, compared to $85 billion when targeted to those at particularly high risk, the researchers found. The study was published in the April 17 issue of the Annals of Internal Medicine.

Senior author Eran Bendavid, MD, assistant professor of medicine in the School of Medicine, said the results are a departure from a previous study, which found PrEP was not cost-effective when compared with other commonly accepted prevention programs. The new Stanford study differs in a few important respects, taking into consideration the decline in transmission rates over time as more individuals take the pill. The Stanford team also assumed individuals would stop taking PrEP after 20 years, not stay on the drug for life, as the previous study had assumed.

The pill combination, marketed under the brand name Truvada, is widely used for treating HIV infection. But it wasn’t until a landmark trial, published in the New England Journal of Medicine in November 2010, that individuals and their doctors began to seriously consider using the drug as a preventive therapy. The drug’s maker, Foster City, Calif.-based Gilead Sciences Inc., has filed a supplemental new drug application to market it for prevention purposes.

The CDC issued interim guidelines on the drug’s use in January 2011, suggesting that if practitioners prescribe it as a preventive measure, they regularly monitor patients for side effects and counsel them about adherence, condom use and other methods to reduce their risk of infection.

In developing their model, the Stanford researchers took into account the cost of the drug — about $26 a day, or almost $10,000 a year — as well as the expenses for physician visits, periodic monitoring of kidney function affected by the drug, and regular testing for HIV and sexually transmitted diseases.

“We’re talking about giving uninfected people a drug that has some toxicities, so it’s crucial to have them monitored regularly,” Bendavid said, who is also an affiliate of Stanford Health Policy, which is part of the Freeman Spogli Institute for International Studies.

Without PrEP, the researchers calculated there would be more than 490,000 new infections among the MSM population in the United States in the next 20 years. If just 20 percent of these men took the pill daily, there would be nearly 63,000 fewer infections.

However, the costs are substantial. Use of the drug by 20 percent of the MSM population would cost $98 billion over 20 years; if every man in this group took PrEP for 20 years, the costs would be a staggering $495 billion.

Given these figures, the researchers looked at the option of giving PrEP only to men who are at high risk — those who have five or more sexual partners in a year. If just 20 percent of these high-risk individuals took the drug, 41,000 new infections would be prevented over 20 years at a cost of about $16.6 billion.

At less than $50,000 per quality-adjusted life year gained (a measure of how long people live and their quality of life), that strategy represents relatively good value, according to Juusola.

“However, even though it provides good value, it is still very expensive,” she said. “In the current health-care climate, PrEP’s costs may become prohibitive, especially given the other competing priorities for HIV resources, such as providing treatment for infected individuals.”

She said the costs could be significantly reduced if the pill is found to be effective when used intermittently, rather than on a daily basis. Current trials are examining the effectiveness of the drug when used less often.

Other co-authors are Margaret Brandeau, PhD, the Coleman F. Fung Professor
of Engineering, and Douglas Owens, MD, MS, the Henry J. Kaiser, Jr. Professor at Stanford and senior investigator at the Veterans Affairs Palo Alto Health Care System. Owens also is director of Stanford’s Center for Health Policy/Primary Care and Outcomes Research.

The study was funded by the National Institutes of Health and the Department of Veterans Affairs.

Information about Stanford’s departments of Management Science and Engineering and of Medicine, which also supported the work, is available at http://www.stanford.edu/dept/MSandE/ and at http://medicine.stanford.edu/.

Original Article by Ruthann Richter at Standford School of Medicine

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PrEP acceptable to UK gay men, studies find

Pre-exposure prophylaxis (PrEP) would be an acceptable HIV prevention strategy for large numbers of gay, bisexual and other men who have sex with men in major UK cities, according to two studies presented to the British HIV Association (BHIVA) conference in Birmingham this week.

The conference also heard details of a small pilot PrEP study, likely to start recruiting later this year.

A cross-sectional survey of 842 HIV-negative gay and bisexual men, recruited at bars, clubs and saunas in London, suggested that half the respondents would be interested in taking PrEP.

Respondents were given information about pre-exposure prophylaxis and asked: “If PrEP were available, how likely is it that you would take a pill (oral dose) on a daily basis to prevent HIV infection?”.

Half said yes, with 16% saying they were likely to take PrEP and 34% saying they were very likely to. Men interested in PrEP were slightly more likely to be under the age of 35 (AOR adjusted odds ratio 1.58), have attended a sexual health clinic in the past year (AOR 1.59) and to have previously taken post-exposure prophylaxis (PEP) (AOR 1.96). After statistical adjustment, various measures of risky sex were no longer associated with interest in PrEP.

In this survey, 17 men (2.1% of those answering the question) said that they had previously taken antiretroviral drugs to reduce their risk of HIV infection.

Secondly, clinicians at the Manchester Centre for Sexual Health surveyed HIV-negative men attending their service who reported unprotected receptive anal intercourse. Of the 121 men who responded, 36% said they would be “very willing” to take PrEP while only 14% said they would not take the treatment. Daily dosing was perceived as a better option by four fifths of respondents – just one fifth would prefer taking a dose before sexual activity.

These data confirm and reinforce findings from a study reported in November 2011, which found that half the gay men surveyed would consider taking PrEP. Once again, daily dosing was preferred to taking a dose before sex. In the qualitative data, men commented that sex is often spontaneous and that they felt daily dosing would facilitate adherence.

However these data are all based on giving men a few key facts about PrEP and presenting it as a hypothetical option. In real-life circumstances, where men think more seriously about PrEP as an option and hear friends’ experience of taking it, actual uptake and sustainability may be very different.

While the Manchester respondents largely assured the researchers that they would take all their doses of PrEP and wouldn’t have more risky sex, real-life experience needs to be tested in research.

To this end, the Medical Research Council are seeking funding for a 5000-participant, two-year study which would randomise HIV-negative gay men who report unprotected anal intercourse to either take PrEP (Truvada) and attend motivational interviewing (intervention group) or to be put on a one-year waiting list for PrEP and to have motivational interviewing in the meantime (control group).

For the researchers, it is crucial that this is an open label but randomised study, in which participants know whether they are receiving the actual drug. This unusual research design would, they argue, tell us more about the real-world effectiveness of PrEP than a blinded study as it would take into account the possible impact of participants taking more sexual risks because they felt that PrEP afforded some protection. (Researchers call this ‘risk compensation’ or ‘behavioural disinhibition’).

Rather than test efficacy in artificial conditions, the study would therefore test effectiveness in more realistic UK conditions.

So far, however, the potential funders of this costly study have not been persuaded by this argument and it is unclear whether the study will be able to go ahead.

What will, however, start recruiting later this year is a pilot version of the same study, aiming to include 500 men who attend one of around twelve sexual health clinics.

As well as allowing the researchers to have a dry run of the main trial and identify teething problems with its strategy, it should also provide valuable information on the number of men who actually follow through on a clinician’s offer of PrEP. Data on the characteristics of men who seek PrEP, drop-out rates and risk compensation will also be collected.

The researchers intend to take some of these data back to the main study’s potential funders, in order to support a revised application.

Acceptability of taking HIV treatment for prevention purposes

As well as asking people hypothetical questions about PrEP, researchers have also been asking people waiting for an HIV test result hypothetical questions about treatment as prevention.

Individuals from high-risk groups attending the Jefferiss Wing at St Mary’s Hospital for HIV testing were given an explanatory paragraph about treatment, infectiousness and safer sex. They were then asked: “If you were diagnosed with HIV would you consider taking treatment to reduce the risk of passing on infection (even if you did not need to take treatment for your own health)?”.

Four out of five respondents said ‘yes’. Encouragingly, gay men who reported unprotected anal intercourse in the past three months were more likely than others to be interested in the idea. Less encouragingly, people who had had a sexually transmitted infection or who had previously taken PEP were slightly less likely to say that they would take treatment for prevention.

The researchers suggested that the latter factor may be associated with PEP users’ experience of side-effects. It contrasts with the findings of the London PrEP attitudes study described above which found people who had previously taken PEP more likely to be interested in PrEP.

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A Tale of Two Trials: How Adherence is Everything in PrEP

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

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

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

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

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

The Partners PrEP study

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

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

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

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

The FEM-PrEP study

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

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

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

Resistance

In FEM-PrEP, there were five cases of drug-resistant virus (all with the single M184V FTC resistance mutation), four in the Truvada arm and one on placebo. Two of the four cases in women assigned Truvada were clearly cases of transmission of virus that was already drug-resistant and not caused by women partially adherent to PrEP becoming infected, while the other two are still under investigation.

There were two cases of drug-resistant virus in Partners PrEP but in both cases these turned out to be people who were enrolled while suffering from acute HIV infection: there were no cases of drug-resistant virus amongst 74 infections post-randomisation.

One observation common to both studies was that the only side-effect that was measurably different between drug and placebo was nausea and vomiting. In Partners PrEP Truvada was associated with a modest increase in gastro-intestinal symptoms in the first month and in FEM-PrEP the rates were also significantly higher. Whether this is enough to deter participants from continuing their pills who are not strongly motivated needs further research.

Why were there differences in adherence?

Jared Baeten and Lut van Damme, principal investigators respectively of Partners PrEP and FEM-PrEP, were asked why they thought adherence was so much lower in FEM-PrEP than in Partners PrEP.

Baeten commented that they were very different populations. The men and women in Partners PrEP had to define themselves as being in a stable relationship – stable enough to last for at least the two-year length of the trial. Partners would have encouraged their spouse to take their pills, and a qualitative study has already confirmed that many participants saw PrEP as an opportunity to preserve their relationship despite the strain imposed by different HIV status.

He was asked why PrEP would be used in a couple where it would be more logical for the HIV-positive partner to be on treatment. He said one use of PrEP within couples might be to bridge the gap in time between the positive partner’s diagnosis and their starting treatment and becoming virally undetectable.

Van Damme said that the women in FEM-PrEP were much younger and had high levels of sexually transmitted infections (STIs). Initial qualitative surveys had shown that many did not believe themselves to be at high risk of HIV, despite high incidence in their community. There was also a high pregnancy rate in the study despite reported high levels of oral contraceptive use, showing that low adherence to medications was not restricted to Truvada. There was no evidence that participants were sharing their pills with others and, contrary to what the data initially suggested, the pregnancy rate was no higher in women taking PrEP, ruling out theories that interactions between the PrEP drugs and the menstrual cycle may have made women more vulnerable to HIV.

“What we have learned from this trial is that risk perception and understanding one’s own risk are important motivators for people to use biomedical prevention methods,” she concluded.

Dr Sharon Hillier of the Microbicides Trial Network, commenting on the PrEP trials at the conference, commented: “PrEP is very, very effective if you use it very, very well.”

References

Baeten J et al. ARV PrEP for HIV-1 prevention among heterosexual men and women. 19th Conference on Retroviruses and Opportunistic Infections, Seattle, abstract 29, 2012. The abstract is available on the official conference website.

Van Damme L et al. The FEM-PrEP Trial of Emtricitabine/Tenofovir Disoproxil Fumarate (Truvada) among African Women. 19th Conference on Retroviruses and Opportunistic Infections, Seattle, abstract 32LB, 2012. The abstract is available on the official conference website.

Donnell D et al. Tenofovir disoproxil fumarate drug levels indicate PrEP use is strongly correlated with HIV-1 protective effects: Kenya and Uganda. 19th Conference on Retroviruses and Opportunistic Infections, Seattle, abstract 30, 2012. The abstract is available on the official conference website.

A webcast of the session HIV prevention: PrEP, microbicides and circumcision, is available through the official conference website.

Original Article via NAM

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Questions on Tactics to Prevent HIV [PrEP]

PrEP is short for PreExposure Prophylaxis and may be part of comprehensive HIV prevention services in which HIV negative people who are at high risk, take antiretroviral medication daily to try to lower their chances of becoming infected with HIV if they are exposed to it.

To date, PrEP has been shown to be effective in men who have sex with men (MSM) and heterosexual men and women.

The effectiveness of biomedical approaches to prevent HIV infection was a key theme of the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2011), held July 17-20, 2011, in Rome.

Among the major studies presented, Robert Grant from the Gladstone Institute of the University of California at San Francisco described final data from the iPrEx trial, which showed that pre-exposure prophylaxis (PrEP) using tenofovir/emtricitabine (Truvada) reduced new HIV infections by 42% overall, and by more than 90% among people who demonstrated good adherence.

The US Centers for Disease Control and Prevention (CDC) has recommended testing patients for HIV before they begin taking the drugs and again at two- to three-month intervals. The FDA could also require drug companies to set up a registry of patients taking the drugs and ask that patients provide proof of a negative HIV test before getting their medications refilled.

Deciding who to treat with PrEP could also be a challenge. The CDC reported on 3 August that rates of new HIV infection in the United States are stable overall, but are rising in young men who have sex with men. Yet if these men aren’t using the prevention measures already available, there’s little reason to think doctors will have an easier time convincing them to take a daily pill.

The question of who should get PrEP is more difficult in many developing nations, which cannot even afford to treat everyone currently infected with HIV. PrEP would cost hundreds of dollars per patient per year in developing countries, and many thousands of dollars in rich nations.

Even with regimens costing less than £1 per day, developing nations will be forced to choose between providing more treatment for those who already need it and potentially preventing new infections. Myron Cohen, a doctor and researcher at the University of North Carolina at Chapel Hill, points out that half of young girls in some parts of sub-Saharan Africa become infected with HIV by their mid-twenties. “That’s unacceptable, so I see that as one potential population for PrEP,” says Cohen.

Although the cost-effectiveness of PrEP increases in higher-risk populations, it will be politically dicey for financially strapped countries to justify distributing drugs to those in these groups. “Even if you thought the best use of the pills would be for sex workers, it would be very difficult to take a limited supply of pills and give them to high-risk populations at the expense of people who are dying of infection,” says Cohen.

In the past year, three landmark clinical trials have shown that a daily dose of the antiretroviral medication Truvada can protect individuals from infection with H.I.V.— a significant discovery, given the failure so far of all efforts to develop a vaccine against the virus.

Now researchers in San Francisco and Miami are planning to test this prevention strategy, called pre-exposure prophylaxis, or PrEP, in a pilot study supported by the National Institutes of Health. The researchers will soon recruit up to 500 uninfected men who have sex with men, especially those considered to be at greatest risk of infection, such as younger gay men and, in particular, African-Americans.

The men will be asked to take Truvada daily, and the researchers will monitor their compliance with the regimen, their sexual behavior and their health status. Already, though, the prospect of antiretroviral drugs’ being used for prevention as well as treatment is raising complex questions for researchers and advocates.

Will healthy uninfected people consistently take an expensive and powerful drug that can cause a range of side effects? Is it fair to provide medications to H.I.V.-negative individuals when so many of those already infected do not have access? Will those receiving the drug be more likely to engage in risky sex because they believe they are protected — even if they do not always take it as prescribed?

The issues are more than academic: According to anecdotal reports, some doctors are already prescribing the medications to some H.I.V.-negative patients, said Dr. Kenneth Mayer, a chairman of the Fenway Institute, a research and advocacy center for  gay, lesbian, bisexual and transgender health in Boston, who has been involved in research into PrEP.

“I think that’s going to increase, but it’s very incremental,” said Dr. Mayer, who believes PrEP is an important new weapon in the H.I.V. prevention arsenal. “People have a lot of questions.”

AIDS advocates have generally expressed optimism that the strategy, if applied carefully, could help reduce the approximately 50,000 new H.I.V. infections that occur annually in the United States. But one major provider of services to people with H.I.V., the AIDS Healthcare Foundation in Los Angeles, has initiated a media and ad campaign raising serious concerns.

The foundation’s president, Michael Weinstein, noted that participants in the first round of PrEP research were counseled extensively that not following the protocol could reduce any protective effect, and yet many still failed to take their pills as prescribed. Adherence to the regimen is likely to be even worse under real-world conditions, he said.

“We deal with tens of thousands of patients here who are positive, and a high percentage of them have adherence issues,” said Mr. Weinstein. “So the idea that young gay men who don’t have this disease are going to take this routinely is highly questionable.”

Mr. Weinstein is particularly concerned that the Food and Drug Administration could soon approve Truvada for use in H.I.V. prevention as well as treatment, which would undoubtedly lead to greater use of the drug. Gilead Sciences, the company that makes the drug, has said it is likely to file such an application with the F.D.A. early next year.

Once the F.D.A. approves a drug for any use, doctors can legally prescribe it “off-label” for other purposes. Drug companies, however, are allowed to promote their products only for indications specifically approved by the agency.

In one of the three earlier clinical trials, among men who have sex with men, PrEP reduced new infections by 44 percent over all. Among men who adhered closely to the prescribed daily regimen, however, protection against infection was greater than 90 percent.

Some researchers worry that sexually active individuals who only sporadically adhere to the PrEP regimen may not realize that they are still at risk for infection; at the same time, feeling “protected,” they may be less vigilant about practicing safe sex and getting regular H.I.V. testing.

And inconsistent use of medications among those who do not realize they are infected could encourage new drug-resistant forms of H.I.V., some experts fear.

Dr. Grant Colfax, director of H.I.V. prevention and research at the San Francisco Department of Public Health, said he hopes that the new research will yield important information about how best to use the emerging strategy.

“The question is, will people be able to maintain the regimen?” said Dr. Colfax, whose agency is a major partner in the study. “What are the risks and benefits outside of a randomized clinical trial? Will they want to take the pill, will there be changes in their risky behavior, will they come back to get H.I.V. testing on a quarterly basis?”

Dr. Howard Jaffe, chairman and president of the Gilead Foundation, acknowledged that adherence was a problem in earlier studies. But he said that participants in the upcoming research, unlike those in the trials, will all know that they are receiving the actual drug, not a placebo, and that the drug can prevent H.I.V. infection if taken as directed. That critical new information, he said, could help motivate them to stick to the prescribed regimen.

The three recent PrEP trials focused on different populations: heterosexual couples in East Africa in which one person was H.I.V.-positive and the other was not; sexually active young adults in Botswana; and men who have sex with men in the United States and five other countries. (A fourth trial, among African women, was stopped early because PrEP was not found to be working.)

The trial involving the East African couples reported that the infection rate was 73 percent lower in the group taking Truvada; among the group in Botswana, there was a 63-percent drop.

“Now that it’s been proven to be effective, the discussion is a much different discussion than when you’re enrolling people for a placebo-controlled trial,” Dr. Jaffe of the Gilead Foundation said.

Truvada combines two antiretroviral drugs, Viread and Emtriva, both also made by Gilead. Besides the upcoming study in the United States, results from additional research into the use of Truvada as H.I.V. prevention are expected over the next few years.

The drug currently costs thousands of dollars a year. A recent editorial in the medical journal Lancet Infectious Diseases raised ethical concerns about the new approach, noting that many people with H.I.V. do not have access to the lifesaving medications.

“How can these drugs be provided as prevention to those high-risk populations, while people with the disease in need of treatment continue to go without?” said the editorial.

In response, proponents of PrEP say that it would be unethical not to explore the new approach, given its potential to reduce infection rates, especially among vulnerable populations whose members have often found it difficult to consistently practice safe sex.

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