Sexual behaviour of heterosexual men and women receiving antiretroviral pre-exposure prophylaxis for HIV prevention: a longitudinal analysis

The Lancet Infectious Diseases, Early Online Publication, 17 October 2013

doi:10.1016/S1473-3099(13)70226-3 Cite or Link Using DOI

This article can be found in the following collections: Infectious Diseases (HIV/AIDS)

Copyright © 2013 Elsevier Ltd All rights reserved.

Original Text

Kenneth K Mugwanya MBChB a b, Deborah Donnell PhD c d, Prof Connie Celum MD a d e, Katherine K Thomas MS d, Patrick Ndase MBChB d, Nelly Mugo MBChB d f g, Prof Elly Katabira MBChB h, Kenneth Ngure PhD d g i, Dr Jared M Baeten MD a d e, for the Partners PrEP Study Team†

Summary

Background

Scarce data are available to assess sexual behaviour of individuals using antiretroviral pre-exposure prophylaxis for HIV prevention. Increased sexual risk taking by individuals using effective HIV prevention strategies, like pre-exposure prophylaxis, could offset the benefits of HIV prevention. We studied whether the use of pre-exposure prophylaxis in HIV-uninfected men and women in HIV-serodiscordant couples was associated with increased sexual risk behaviour.

Methods

We undertook a longitudinal analysis of data from the Partners PrEP Study, a double-blind, randomised, placebo-controlled trial of daily oral pre-exposure prophylaxis among HIV-uninfected partners of heterosexual HIV-serodiscordant couples (n=3163, ≥18 years of age). Efficacy for HIV prevention was publicly reported in July 2011, and participants continued monthly follow-up thereafter. We used regression analyses to compare the frequency of sex—unprotected by a condom—during the 12 months after compared with the 12 months before July 2011, to assess whether knowledge of pre-exposure prophylaxis efficacy for HIV prevention caused increased sexual risk behaviour.

Results

We analysed 56 132 person-months from 3024 HIV-uninfected individuals (64% male). The average frequency of unprotected sex with the HIV-infected study partner was 59 per 100 person-months before unmasking versus 53 after unmasking; we recorded no immediate change (p=0·66) or change over time (p=0·25) after July, 2011. We identified a significant increase in unprotected sex with outside partners after July, 2011, but the effect was small (average of 6·8 unprotected sex acts per year vs 6·2 acts in a predicted counterfactual scenario had patients remained masked, p=0·04). Compared with before July, 2011, we noted no significant increase in incident sexually transmitted infections or pregnancy after July, 2011.

Interpretation

Pre-exposure prophylaxis, provided as part of a comprehensive prevention package, might not result in substantial changes in risk-taking sexual behaviour by heterosexual couples.

Funding

The Bill & Melinda Gates Foundation and the US National Institute of Mental Health.

Source

New Medical Device Extremely Effective at Preventing HIV in Women

Provided by Science Daily

Previous studies have demonstrated that antiviral drugs can prevent HIV infection, but existing methods for delivering the drug fall short. Pills must be taken daily and require high doses; vaginal gels that must be applied prior to each sex act are inconvenient, yielding poor usage rates. The new ring is easily inserted and stays in place for 30 days. (Credit: Northwestern University)

Sep. 27, 2013 — It's often said that the HIV/AIDS epidemic has a woman's face. The proportion of women infected with HIV has been on the rise for a decade; in sub-Saharan Africa, women constitute 60 percent of people living with disease. While preventative drugs exist, they have often proven ineffective, especially in light of financial and cultural barriers in developing nations.

A new intravaginal ring filled with an anti-retroviral drug could help. Developed with support from the National Institute of Allergy and Infectious Diseases by Northwestern University visiting associate professor Patrick Kiser, the ring is easy to use, long lasting, and recently has demonstrated a 100 percent success rate protecting primates from the simian immunodeficiency virus (SHIV). The device will soon undergo its first test in humans.

"After 10 years of work, we have created an intravaginal ring that can prevent against multiple HIV exposures over an extended period of time, with consistent prevention levels throughout the menstrual cycle," said Kiser, an expert in intravaginal drug delivery who joined Northwestern from the University of Utah, where the research was conducted.

Kiser is a new faculty member in Northwestern's McCormick School of Engineering's Department of Biomedical Engineering and visiting associate professor of obstetrics and gynecology in the Feinberg School of Medicine.

The research was published September 16 in the Proceedings of the National Academy of Sciences (PNAS).

Previous studies have demonstrated that antiviral drugs can prevent HIV infection, but existing methods for delivering the drug fall short. Pills must be taken daily and require high doses; vaginal gels that must be applied prior to each sex act are inconvenient, yielding poor usage rates.

The new ring is easily inserted and stays in place for 30 days. And because it is delivered at the site of transmission, the ring -- known as a TDF-IVR (tenofovir disoproxil fumarate intravaginal ring) -- utilizes a smaller dose than pills.

The device contains powdered tenofovir, an anti-retroviral drug that is taken orally by 3.5 million HIV-infected people worldwide, but that has not previously been studied topically. But the ring's strength stems from its unique polymer construction: its elastomer swells in the presence of fluid, delivering up to 1,000 times more of the drug than current intravaginal ring technology, such as NuvaRing, which are made of silicon and have release rates that decline over time.

The upcoming clinical trial, to be conducted in November at Albert Einstein College of Medicine in New York, will evaluate the ring in 60 women over 14 days. The trial will assess the ring's safety and measure how much of the drug is released and the properties of the ring after use.

Other drugs could potentially be integrated into the ring, such as contraceptives or antiviral drugs to prevent other sexually transmitted infections -- a feature that could increase user rates, Kiser said.

"The flexibility to engineer this system to deliver multiple drugs and change release rates is extraordinary and could have a significant impact on women's health," he said.

Story Source:

The above story is based on materials provided by Northwestern University.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

1. J. M. Smith, R. Rastogi, R. S. Teller, P. Srinivasan, P. M. M. Mesquita, U. Nagaraja, J. M. McNicholl, R. M. Hendry, C. T. Dinh, A. Martin, B. C. Herold, P. F. Kiser. Intravaginal ring eluting tenofovir disoproxil fumarate completely protects macaques from multiple vaginal simian-HIV challenges. Proceedings of the National Academy of Sciences, 2013; DOI: 10.1073/pnas.1311355110

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CDC Updates HIV Preexposure Prophylaxis Guidelines

Medscape Medical News

Troy Brown

Jun 12, 2013

The Centers for Disease Control and Prevention (CDC) has updated its recommendations on the use of preexposure prophylaxis (PrEP) in individuals at high risk of acquiring HIV to include its use in injection drug users (IDUs) as well as those with high-risk sexual behaviors, the agency announced today.

The recommendations follow the results of a clinical trial, published online June 12 in the Lancet, that showed that a daily oral dose of 300 mg of tenofovir disoproxil fumarate (TDF) is effective at reducing HIV infection acquisition among injection drug users.

On July 16, the US Food and Drug Administration approved the use of a fixed-dose combination of TDF 300 mg and emtricitabine (FTC) 200 mg (Truvada, Gilead Sciences) for the indication of PrEP against sexual transmission of HIV by men who have sex with men (MSM) and heterosexually active women and men. The recommendations were based on the results of clinical trials in MSM and heterosexually active men and women. Those trials did not evaluate the use of PrEP among IDUs.

On the basis of the trial results published today, the CDC recommends that PrEP be considered as one of several prevention options for persons at very high risk for HIV acquisition through the injection of illicit drugs.

Reported injection practices that place persons at very high risk for HIV acquisition include sharing of injection equipment, injecting 1 or more times a day, and injection of cocaine or methamphetamine.

PrEP Recommendation for Injection Drug Users

Daily TDF/FTC is the preferred PrEP regimen for IDUs for the following reasons:

• TDF/FTC contains the same dose of TDF (300 mg) that has been shown to be effective for IDUs,
• TDF/FTC demonstrated no additional toxicities when compared with TDF only in PrEP trials that studied both regimens,
• IDUs are at risk for sexual exposure to HIV for which TDF/FTC is indicated, and
• TDF/FTC is approved for PrEP to prevent sexual HIV transmission in the United States.

The use of TDF/FTC for prevention of HIV transmission in those without sexual acquisition risk is at present an off-label use. The CDC recommends providing services for IDUs that include PrEP as well as measures aimed at decreasing injection and risky sexual behaviors.

In all individuals, PrEP use:

• is contraindicated in those with positive or unknown HIV status or with an estimated creatinine clearance lower than 60 mL/minute,
• should be focused on adults at very high risk for HIV acquisition,
• should be given as part of comprehensive prevention services, and
• should be given with quarterly monitoring of HIV status, pregnancy status, adverse effects, medication adherence, and risk behaviors, as directed in previous interim guidance.

Adherence to daily PrEP is vital to decrease HIV infection risk, and achieving high adherence was challenging for many participants in PrEP clinical trials.

"Providing PrEP to IDUs at very high risk for HIV acquisition could contribute to the reduction of HIV incidence in the United States," the CDC notes in the statement. "In addition, if PrEP delivery is integrated with prevention and clinical care for the additional health concerns faced by IDUs (e.g., hepatitis B and C infection, abscesses, and overdose), substance abuse treatment and behavioral health care, and social services, PrEP will contribute additional benefits to a population with multiple life-threatening physical, mental, and social health challenges."

The CDC is collaborating with other federal agencies to prepare comprehensive US Public Health Service guidelines on PrEP use with MSM, heterosexually active men and women, and IDUs. Those guidelines are scheduled for release later this year.

The complete updated interim guidelines IDUs can be found here on the CDC Web site.

Source

Also See: Daily Pill Cuts HIV Risk in IV Drug Users

Widespread Ignorance of Medication That Prevents HIV

Fran Lowry

Jun 10, 2013

Many teens and young adults at high risk for HIV in Washington, DC, would be willing to take pre-exposure prophylaxis every day to prevent infection, if only they were aware that such a thing existed.

In a study conducted to ascertain knowledge, acceptability, and willingness to use prophylaxis in sexually active at-risk people, only 10% said they had ever heard of it.

And when they learned that medication could protect them from HIV infection, most said they would take it, if offered by their healthcare provider.

The findings were presented at the 8th International Conference on HIV Treatment and Prevention Adherence in Miami, Florida. The meeting was jointly sponsored by the International Association of Physicians in AIDS Care, the National Institute of Mental Health, and the Post Graduate Institute for Medicine.

"As our study showed, there is very limited knowledge of pre-exposure prophylaxis overall," lead investigator Amanda Castel, MD, MPH, from George Washington University in DC, told Medscape Medical News. "There is a definite and urgent need for a lot of education and social marketing if pre-exposure prophylaxis is going to be an effective HIV prevention intervention."

In the past 18 months, several studies have shown that the option is an effective method of reducing HIV incidence in a variety of populations, including men who have sex with men, heterosexuals, and serodiscordant couples, where one person is negative for HIV and the other is positive.

Some ongoing trials are focusing on adolescents and young adults, but not many are looking at whether youth are even interested in pre-exposure prophylaxis or willing to take it, Dr. Castel said.

To find out, she and her colleagues surveyed 293 patients attending a clinic for sexually transmitted infections, a community-based general clinic for gay men, and a general adolescent health clinic at Children's National Medical Center in Washington, DC.

“The prevalence of HIV in Washington is higher than anywhere in Russia.”

All participants were HIV-negative and had had sex in the previous 6 months. Participants 13 to 24 years of age accounted for 45% of the cohort and those 25 years and older accounted for 55%.

"We were able to get waivers of parental consent so that we could include participants younger than 18," Dr. Castel noted.

The participants completed their surveys using iPads. "It takes away some of the interviewer bias because we were asking sensitive questions about sexual behaviors, condom use, that kind of thing," she said.

Just 31 participants had previously heard of pre-exposure prophylaxis, 9 of whom were in the younger age group.

Significantly more people in the older group than in the younger group reported that they were more likely to use the medication if it had few or no adverse effects (78% vs 62%; P = .02).

In addition, more older than younger participants reported that they would take medication if it were offered by their healthcare provider (70.6% vs 62.4%; P = .02) and would be able to follow a provider's instructions (76.9% vs 67.7%; P = .03).

Also, significantly more of the older group would prefer to take it after sex than as a daily medication (32% vs 20%; P = .004).

Finally, 64.7% of youth reported they would consider participating in future studies.

"Overall, there is very limited knowledge about pre-exposure prophylaxis and potentially poor adherence. Those things may pose pretty distinct barriers to implementation in this population," Dr. Castel said.

She conceded that taking medication every day for a condition that you don't have is difficult and requires strong motivation and organizational skills.

"A provider might have a patient who fits the high-risk-for-HIV profile, but that person might be terrible at adherence, so may not be a good candidate for pre-exposure prophylaxis, which requires taking it on a daily basis. In that situation, perhaps another prevention intervention, like encouraging condom use, could be tried," she said.

Injections of a long-acting antiretroviral might also be particularly useful for teens and young adults, she suggested.

Medscape Medical News asked Benjamin Young, MD, vice-president and chief medical officer of the International Association of Providers of AIDS Care in Washington, DC, to comment on the study. "This is a really interesting paper because we know from a number of large studies that pre-exposure prophylaxis can work in people who are at risk and who can be adherent to medication."

The study is particularly relevant in a place like Washington, DC, which has the highest prevalence of HIV in the United States, if not the world, Dr. Young added.

"I used to work part time in Russia, and the Russian Ministry of Health used to point out that the prevalence of HIV in Washington is higher than anywhere in Russia and approaches the prevalence in certain capital cities in East Africa. The United States takes on enormous efforts and spends all this money around the world, yet here in Washington, rates are super high, especially among young gay men and young gay men of color."

"I thought it was a travesty that Barrack Obama didn't walk the 3 or 4 blocks from the White House to the convention center during the AIDS conference last summer. It wasn't that he was tied up doing important state business or was out of the country. He was in the White House at the time and the flag was flying during the conference. That was particularly poignant if not outrageous to me, and I'm a supporter," Dr. Young said.

The failure on the part of President Obama to attend the AIDS conference highlights the problems that lead to such a high HIV prevalence in the nation's capital, he added.

"State-level programs work on prevention, but Washington, DC, because it doesn't have a state government but a somewhat dysfunctional city government and doesn't have adequate representation in congress, is forgotten," he said. "The AIDS epidemic is probably just one symptom of this. The study by Dr. Castel's team speaks to this problem. That is why it is important."

Dr. Young said he agrees that much more awareness about pre-exposure prophylaxis is needed.

"The amazing thing is that 90% of at-risk people didn't even know that it exists. It's probably the same nationwide; I don't think this is unique to Washington. But the study shows that people would use pre-exposure prophylaxis if they knew about it and could get it," he noted.

Dr. Castel reports no relevant financial relationships. Dr. Young is an employee of the International Association of Providers of AIDS Care and reports financial relationships with Bristol-Myers Squibb, GlaxoSmithKline, Merck & Co, ViiV Healthcare.

8th International Conference on HIV Treatment and Prevention Adherence. Presented June 3, 2013.

Source

Ending Mother-to-Child HIV Transmission

Huffington Post

Deborah Dugan CEO, (RED)

Posted: 06/10/2013 10:02 am

Imagine a world where no mother living with HIV will have to transmit the virus to her baby while giving birth. Just 10 years ago, this would have been considered an impossible goal. But, thankfully, with the incredible advances in HIV/AIDS treatment, prevention of mother-to-child transmission is real today and is helping the world take giant steps towards achieving an AIDS Free Generation. But still, 900 babies are born every day with HIV.

(RED) and the Global Fund envision a world in which no baby is born with HIV, and every mother has the opportunity to help her child thrive. To achieve this, ending mother-to-child transmission has become a cornerstone of (RED)'s commitment to the fight. But there is so much more to do before we get to our target, and we need the world to rally around making this a reality.

As a mother of three and CEO of (RED), the focus on safeguarding mothers and their babies from HIV couldn't hit closer to home. Our mission is to bring people and companies into the fight, to generate heat around the crisis and, through the Global Fund, enable some of the world's best-known companies to fund HIV/AIDS programs on the ground in Africa. Thanks to the incredible support of our partners (including Apple, Starbucks, Coca Cola and Belvedere), I am thrilled to announce that we have expanded our number of recipient countries to include Tanzania and Kenya - two countries with a high HIV/AIDS prevalence in which Global Fund programs funded by (RED) can make a real impact.

But real impact requires action. And money. Starting today, a new partnership with Johnson & Johnson means every time someone 'Likes', 'Tweets' or 'Pins' a (RED) infographic, Johnson & Johnson will donate $1 to the Global Fund, up to $100,000. Every cent from that donation will help ensure that HIV+ mothers in Africa have the tools they need to deliver healthy babies.

We are at a crucial point in the fight against HIV/AIDS. By acting now, and by acting collectively, our chances of helping deliver an AIDS Free Generation are infinitely greater.

This blog post was produced by The Huffington Post and (RED) as part of a series to support the CHOOSE (RED), SAVE LIVES campaign this June. To see other posts in the series and to see content from "The Big Push" (the initiative by the Global Fund, the recipient of (RED) monies, to fight AIDS, Tuberculosis and Malaria), click here. For more information about how you can join the fight against AIDS, please go to www.joinred.com/CHOOSERED.

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IL Lottery Launches Nation's Only HIV/AIDS Awareness and Prevention Instant Game -- 'Spread the Word'

PRESS RELEASE June 5, 2013, 1:00 p.m. ET

Since 2008 game has raised over $4.7 million 

CHICAGO, June 5, 2013 /PRNewswire/ -- This week the Illinois Lottery, in partnership with the Illinois Department of Public Health and a host of Illinois-based HIV/AIDS advocates, launched Spread the Word -- a lottery game where 100 percent of net proceeds are used for HIV/AIDS education, prevention and support programs that serve Illinoisans living with HIV/AIDS. The Illinois Lottery is the only lottery in the nation with a game whose profits are used exclusively to fund HIV/AIDS prevention and treatment programs.

(Logo: http://photos.prnewswire.com/prnh/20130528/CG21596LOGO)

Since 2008, the Illinois Lottery has contributed over $4.7 million to the fight against HIV/AIDS, through previous iterations of this game. The Lottery expects to raise an additional $1 million from the new game for HIV/AIDS prevention and treatment efforts.

"Spread the Word is a perfect example of what a Lottery is all about," said Michael Jones, Superintendent of the Illinois Lottery. "Lotteries exist to fund important causes. In Illinois, those causes include public schools, roads and bridges, and four special areas determined by the Illinois Legislature: Veterans' programs, MS research, Breast Cancer research, and services that support people with HIV/AIDS. With the new Spread the Word game, anyone who would like to support this cause can buy a $2 Spread the Word instant ticket and have a chance to win up to $20,000 cash. If they play and lose, they know their money will go to fund vital support services for people in Illinois living with HIV/AIDS."

According to the Illinois Department of Public Health, the agency responsible for administering Spread the Word grants, Illinois ranks seventh nationwide in the diagnosis of HIV infections, and fifth in the estimated number of AIDS cases. In 2011, there were 1,760 new cases of HIV/AIDS diagnosed in Illinois. In Chicago, there are more than 20,000 people living with HIV/AIDS -- three times the national prevalence rate.

"Knowing your HIV status puts you in greater control. I encourage everyone to utilize the resources available -- many of which are free and confidential -- to get tested," said Illinois Department of Public Health Director Dr. LaMar Hasbrouck. "We're proud that our partnership with the Illinois Lottery through this specialty ticket will continue to provide much-needed resources for people living with HIV/AIDS in Illinois."

Spread the Word was officially unveiled at the James R. Thompson Center Wednesday, June 5 during the Chicago National HIV Testing Collaborative's "Step Up, Get Tested" campaign. More information on the month-long testing campaign is available at www.stepupgettested.com. The Spread the Word instant game is available at more than 8,100 Illinois Lottery retailers throughout the state. If you don't see Spread the Word displayed at your local retailer, please ask for it.

About Illinois Lottery: Founded in 1974, the Illinois Lottery has contributed over $17.5 billion to the state Common School Fund to assist K-12 public schools, as well as the Capital Projects Fund. Players must be at least 18 years old. More information is available at www.illinoislottery.com.

About HIV/AIDS in Illinois

For more information about HIV/AIDS in Illinois, call the Illinois AIDS/HIV & STD Hotline at 1-800-243-2437 or TTY (hearing impaired use only) 1-800-782-0423. It's free and anonymous (no names). Trained counselors can help to answer your questions and help you to find a testing site that's right for you. They are available seven days a week (9 a.m. to 9 p.m. on weekdays and 10 a.m. to 6 p.m. on weekends). To find the closest free HIV testing site by calling the department's HIV/AIDS and STD Hotline at 1-800-AID-AIDS (1-800-243-2437). IDPH's innovative Text2Survive mobile service also provides free HIV testing locations by texting IL plus ZIP code to 36363. This service is also available in Spanish by texting "CENTRO" plus ZIP code to 36363.

 
Contact:  Mike Lang 217-524-5158 
          Chanele Newton 312-368-5814 

SOURCE Illinois Lottery

/Web site: http://www.illinoislottery.com

Source

HIV Treatment as Prevention -- Across an Entire Community

Shira Berman, Salim S. Abdool Karim, MBChB, PhD

DisclosuresMay 03, 2013

Editor's Note: In 2011, the HIV Prevention Trials Network (HPTN) 052 study of serodiscordant couples demonstrated that lowering viral load through the use of antiretroviral therapy (ART) in an infected partner could lower the risk for HIV acquisition by the uninfected partner.^[1] In early 2013, using data on more than 16,000 people in the Hlabisa HIV Treatment and Care Programme in rural KwaZulu-Natal, South Africa, investigators demonstrated a real-world setting application of this principle: Individual HIV acquisition risk in KwaZulu-Natal declined significantly with increasing ART coverage in the surrounding local community.^[2]

In an interview with Medscape, Salim S. Abdool Karim, MBChB, PhD, Professor at the Centre for the AIDS Programme of Research in South Africa (CAPRISA) at the University of KwaZulu-Natal in Durban, South Africa, reviewed the findings from this study and considers what more we need to learn about treatment as prevention strategies moving forward.

Medscape: The report in Science focused on the real-world application of how increased ART coverage changes the demographics of HIV acquisition. Why was a study like this important?

Dr. Karim: When the HPTN 052 results were published, we had, for the first time, a clear idea of the very high efficacy that is possible with the use of ART to suppress viral load and lower the risk for HIV transmission to HIV-negative partners. But even before the HPTN 052 results, there was a study by Donnell and colleagues^[3] published in The Lancet that showed a very low incidence of HIV infection in serodiscordant couples in which the HIV-positive partner was receiving ART.^[4] Mathematical models have also provided some indication of the potential impact of "treatment as prevention." However, it was not known what the impact would be if this strategy were implemented in the real world.

The data from the study published in Science provide, for the first time, a compelling picture of the effects that ART scale-up within a community can have not only in terms of its treatment impact but also in terms of its prevention potential.

Why is it that they were able to show this in this particular community?

The circumstances are unique in that population. The first and very important issue to understand is that ART was simply not available for many years in that community. It was official government policy not to provide ART during South Africa's "denialist" era. Eventually, when the government did decide to provide antiretrovirals, it took them quite a while to establish health systems capabilities to initiate therapy. So, in this community, the researchers were dealing with a huge backlog of patients who needed treatment.

In essence, then, this Hlabisa community was experiencing a rapidly advancing HIV epidemic associated with a very high mortality rate because of the absence of treatment. With the increasing prevalence and the concomitant large number of infected individuals in this community, it was also experiencing a very high HIV incidence rate within the population.

In this kind of situation, introducing ART and providing it to scale puts a spotlight on the substantial impact it can have on such areas as the huge improvement in life expectancy. The HIV epidemic wiped out almost 10 years of life expectancy; with the introduction of ART, we're now regaining those lost years of survival. So what we're seeing in this community in Hlabisa in northern KwaZulu-Natal is a return in life expectancy to the pre-HIV era. That's a very substantial impact. If you add 10 years of life expectancy in that community of nearly 100,000 people, you've got a million new years of peoples' lives. These are potentially productive life-years gained to be able to contribute toward society. It's just amazing when you think about that scale of impact.

But it was not only that those who were treated who benefited -- those who were HIV-negative also benefited from HIV-infected people getting treatment. In communities in which the rollout of ART was highest, we saw a substantial impact on HIV transmission and declines in HIV incidence.

This demonstrates the real-world impact of treatment as prevention -- where HIV-positive people are getting the intervention, but HIV-negative people are benefiting from the intervention.

To me, it highlights how we've come full circle. On the basis of data from the Rakai Project Study Group,^[5] we thought that if someone doesn't have a detectable viral load, they would probably not transmit HIV. The Rakai study provided the initial discovery of the central role of viral load in HIV transmission when its data showed that transmission among couples was dependent on viral load. The next step in the sequence was the observation of the effects of ART in cohorts.^[3] In this secondary analysis of serodiscordant couples, the data provided observational evidence of the potential impact of ART on HIV transmission. Then came the HPTN 052 randomized controlled trial in discordant couples that showed convincingly that treatment of HIV-infected partners is highly efficacious.^[1] Now we've gone to the final step, where we have evidence of an impact in the real world.

On a note of caution, these data do not mean that the effect observed in Hlabisa will be necessarily present in every community. Owing to the unique circumstances in that community, where they were deprived of ART for such a long period and the epidemic was able to progress to such an advanced stage, when ART was introduced and scaled up, you could see a substantial impact. But it has shown us that with real-world implementation, treatment both to improve the HIV-infected patient's health and as prevention for the partners of HIV-infected patients is of benefit.

Medscape: On that point about the applicability of these findings to other communities, the investigators showed this tremendous impact in communities that had coverage rates of 30%-40%. That's a fairly low coverage rate, but obviously, in this community, that was a huge step forward.

Dr. Karim: Absolutely. When coverage goes from 0% to 30%, a big difference can be observed. But when there is a slow incremental growth of coverage, it is much less likely to lead to this kind of impact.

But there's another factor that is affecting outcomes: We're identifying key populations and treating them at the earliest stages. In other words, the 30%-40% that are being treating in that community are the important 30%-40% -- the ones with the low CD4 counts and the highest viral loads. So they're not just lowering each individual's viral load, but also lowering the overall mean community-level viral load. That's probably one of the mechanisms leading to the impact that was observed.

It is not clear whether such dramatic and large benefits would be readily observed in other communities where ART scale-up has been more incremental. Observing a large effect within this specific community was feasible due to its unique circumstances.

Medscape: Moving forward, having measured such a dramatic impact in this community, is it reasonable to think that we might see continued benefit if coverage is higher but increases at a slower, incremental rate?

Dr. Karim: These kinds of interventions can reach a point where substantial increases in coverage may be required for smaller additional benefits. So although the initial intervention had a very substantial effect at relatively low coverage rates, to improve on that and to get a marginal increase above the currently observed effect may require substantially higher coverage rates.

One way to assess the potential impact of increased coverage is to model the different coverage levels and the impact on the community base on the Hlabisa data -- to essentially ask such questions as, "If you achieved 80% coverage, what would that do?"

Three community-based randomized controlled trials being conducted by the National Institutes of Health, USAID, and the Centers for Disease Control and Prevention with the President's Emergency Plan for AIDS Relief (PEPFAR) funding^[6] are asking a more direct question: If we can scale up ART from the current coverage rate, which is around 30%, and achieve 60% or 80% coverage, what is the magnitude of the impact on survival and on HIV transmission to HIV-negative people?

These 3 studies will help us determine how incremental increases in treatment coverage through active scale-up strategies may or may not continue to show a prevention benefit.

References

Source

AHF Advocacy Against Gilead’s Truvada as HIV Prevention Yields Stronger FDA Drug Warning Label

October 11, 2012 09:52 PM Eastern Daylight Time

New warning label is welcomed by AIDS advocates who were astounded by recommendation by an FDA Advisory Panel earlier this year to allow Gilead to market use of its blockbuster AIDS treatment as a form of HIV prevention in uninfected individuals without any HIV testing requirement whatsoever

AHF and other advocates strenuously opposed use of the AIDS treatment as a form of HIV prevention pill, concerned about efficacy, medication adherence issues among uninfected high-risk populations; ‘Black box warning’ label on Truvada for prevention now recommends HIV testing every three months

WASHINGTON--(BUSINESS WIRE)--AIDS Healthcare Foundation (AHF), the nation’s largest HIV/AIDS nonprofit medical provider, welcomed the news today the boxed warning label (also called the ‘black box warning’) on Gilead Sciences’ blockbuster AIDS treatment Truvada for use as a form of an HIV prevention pill appears much stronger than proposed versions of the label earlier this year. The new warning label is being welcomed by AIDS advocates from AHF and other organizations who were astounded by a recommendation by a Food and Drug Administration (FDA) Advisory Panel to allow Gilead to market use of Truvada as a form of HIV prevention in uninfected individuals, particularly when the panel—comprised of 23 physicians, scientists and members of the general public—also recommended that the FDA allow Gilead to market the drug for such use without any requirement for HIV testing whatsoever.

“From the beginning, AHF and many other advocates strenuously opposed use of this well-established AIDS treatment as a form of an HIV prevention pill, concerned about both the efficacy of the treatment as well as medication adherence issues among uninfected high-risk populations,” said Michael Weinstein, President of AIDS Healthcare Foundation. “It is difficult for many of those who are already infected with HIV to properly comply with daily drug regimens. Expecting uninfected people to remember to take a drug every day for a disease that they don’t have is an even more daunting challenge. At least now the ‘black box warning’ label on Truvada for prevention recommends HIV testing every three months. It is good to see that the FDA and Gilead have finally come to this realization. I believe it was in part because of our advocacy over the past year opposing the drug for this use that this warning label is now stronger.”

The FDA Advisory Panel took place in May in Silver Spring, MD, at FDA headquarters. Nearly 30 advocates from AHF and other groups spoke against use of the drug for HIV prevention to the panel, which nevertheless indicated it would give preliminary approval to Gilead for use as HIV prevention.

Later in the summer, at the ‘Controlling the HIV Epidemic with ARVs’Summit, held in London June 11-12, a Gilead official publicly disclosed in a plenary session in which he was participating that use of its blockbuster AIDS treatment Truvada (emtricitabine/tenofovir disoproxil fumarate) for pre-exposure prophylaxis (PrEP) to prevent possible HIV infection would have labeling indicating that a negative HIV test will be required before a prescription.

Following is what the Truvada packaging and printed drug warning inserts now state regarding use of the drug for pre-exposure prophylaxis (PrEP) for HIV prevention:

For PrEP:

"When prescribing TRUVADA for pre-exposure prophylaxis, healthcare providers must:

• prescribe TRUVADA as part of a comprehensive prevention strategy because TRUVADA is not always effective in preventing the acquisition of HIV-1 infection [See Warnings and Precautions (5.9)];
• counsel all uninfected individuals to strictly adhere to the recommended TRUVADA dosing schedule because the effectiveness of TRUVADA in reducing the risk of acquiring HIV-1 was strongly correlated with adherence as demonstrated by measurable drug levels in clinical trials [See Warnings and Precautions (5.9)];
• confirm a negative HIV-1 test immediately prior to initiating TRUVADA for a PrEP indication. If clinical symptoms consistent with acute viral infection are present and recent (<1 month) exposures are suspected, delay starting PrEP for at least one month and reconfirm HIV-1 status or use a test approved by the FDA as an aid in the diagnosis of HIV-1 infection, including acute or primary HIV-1 infection. [See Warnings and Precautions (5.9)]; and
• screen for HIV-1 infection at least once every 3 months while taking TRUVADA for PrEP."

About AIDS Healthcare Foundation

AIDS Healthcare Foundation (AHF), the largest global AIDS organization, currently provides medical care and/or services to more than 176,000 individuals in 27 countries worldwide in the US, Africa, Latin America/Caribbean, the Asia/Pacific Region and Eastern Europe. To learn more about AHF, please visit our website: www.aidshealth.org, find us on Facebook: www.facebook.com/aidshealth and follow us on Twitter: @aidshealthcare.

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FDA Panel Recommends First Drug for HIV Prevention

Truvada (emtricitabine/tenofovir disoproxil fumarate)

From Medscape Medical News

Janis C. Kelly

May 11, 2012 — The US Food and Drug Administration's (FDA's) Antiviral Drugs Advisory Committee has strongly backed approval of the first-ever drug for the prevention of sexually acquired HIV-1 infection.

In a marathon 12-hour session, the panel recommended approval of a supplemental indication for Truvada (emtricitabine/tenofovir disoproxil fumarate) for preexposure prophylaxis (PrEP) in:

• HIV-uninfected men who have sex with men,
• HIV-uninfected partners in serodiscordant couples, and
• other individuals (such as sex workers) who are at risk of acquiring HIV through sexual activity.

The panel also urged the agency to "put some teeth into" Gilead's proposed risk evaluation and mitigation strategy (REMS) because of concerns that healthy people taking Truvada for HIV prevention will be harmed if they become infected with HIV and do not change from single-drug PrEP prophylaxis to a 3-drug combination antiretroviral treatment regimen, that continuing single-drug Truvada after HIV infection will lead to development of Truvada-resistant viral strains, and that taking the PrEP regimen increases the risk for adverse effects, particularly kidney damage.

The hearing occurred against the background of growing concern that the number of new HIV infections in the United States has remained at about 50,000 per year for the past decade. Most (75%) new HIV infections are in men. Black men have the highest incidence of new HIV overall: Incidence is 8 times higher in blacks and 3 times higher in Hispanics/Latinos than in whites.

The main driver of HIV transmission in the United States is unprotected anal sex between men who have sex with men (MSM), who represent about 2% of the population older than 13 years but account for from 56% to 61% of new HIV infections annually. The number of new HIV infections among 13- to 29-year-old MSM increased 38% from 2006 to 2009, largely because of a 48% increase among young black MSM, according to the FDA background document. Proponents of the Truvada PrEP approach hope that the daily pill will be "another tool in the toolbox" for reducing the continuing spread of HIV.

In support of the requested new indication, Gilead Science presented data from the Preexposure Prophylaxis Initiative (iPrEx) trial, which found that MSM participants who took Truvada daily had a 44% reduction in HIV incidence over the course of 1.2 years of follow-up compared with placebo. The study participants also received monthly HIV testing, free condoms, treatment for other sexually transmitted diseases, and routine counseling and were paid for participation in the study. Even with this supportive structure, nearly half of the study participants had no detectable level of Truvada when tested, suggesting that they were not taking the drug regularly.

Results of the iPrEx study were published online November 23, 2010, in the New England Journal of Medicine. Several speakers during the public comments part of the committee meeting reported that Truvada is already being seen as a "medical condom" (in the words of AIDS Healthcare Foundation's Whitney Engeran-Cordova) and might be taken intermittently or as a "party drug," leading to rapid development of Truvada-resistant HIV.

The resistance problem is one reason the FDA took the unusual step of asking that Gilead design a REMS, something that typically happens only when there are concerns about drug toxicity. The proposed REMS includes mailings to about 200,000 healthcare providers; a medication guide for uninfected individuals; voluntary training for primary care prescribers, infectious disease specialists, emergency medicine physicians, obstetrician-gynecologists, and addiction specialists on the importance of strict adherence to daily dosing and of regular monitoring of HIV serostatus; a prescriber safety brochure; an individual safety brochure; and a "TRUVADA for PrEP" wallet card for the patient. The REMS does not require participation by either physician or patient in the education program before making Truvada available.

The REMS plan also does not require a negative HIV test ("documentation of safe use condition") for a patient to receive each 30-day supply of Truvada, which sparked considerable criticism from the panel.

The possibility of "behavioral compensation" (reduced condom use by a patient who assumes protection from the pill) was dismissed by Gilead speakers but remained a concern for several panelists, who noted that condoms, used correctly, are more than 90% effective at preventing HIV infection.

Panelist and speakers also questioned whether the 44% protection seen in the clinical trial would also occur in "real-world" settings, as it requires daily use by a healthy person of a drug that costs $13,000 per year and carries some risk for adverse effects.

The committee voted 19 to 3 in favor of Truvada PrEP for HIV-uninfected MSM, 19 to 2 (1 abstention) in favor of Truvada PrEP for HIV-uninfected partners of those with HIV, and 12 to 8 (2 abstentions) in favor of Truvada PrEP for others at risk of acquiring HIV through sexual activity. The panel also favored monthly HIV testing and regular monitoring of renal function for those taking Truvada PrEP.

The panel ran out of time before full consideration of the proposed REMS, of postmarketing studies that should be required, and on whether current evidence makes the conduct of placebo-controlled trials of primary HIV prevention unethical.

The FDA is expected to make a final decision on the Truvada prophylaxis indication by June 15. It is already approved as part of combination therapy for treatment of HIV infection.

FDA Antiviral Drugs Advisory Committee Meeting. Silver Spring, Maryland. May 10, 2012.

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