CAPRISA 004

Phase IIb Trial to Assess the Safety and Effectiveness of the Vaginal Microbicide 1% Tenofovir Gel for the Prevention of HIV Infection in Women.

Conducted in South Africa this phase IIb, two-arm, double-blinded, randomised, placebo controlled trial comparing 1% Tenofovir gel with a placebo gel was an expanded safety and effectiveness trial involving 900 young women at risk of sexually transmitted HIV infection. Participants were provided with a supply of single-use, pre-filled applicators according to their randomisation. While in the study, participants were asked to apply a first dose of the assigned study gel within 12 hours prior to coitus and insert a second dose as soon as possible within 12 hours after coitus. All participants received HIV risk reduction counselling, condoms, and syndromic treatment of sexually transmitted infections, if required.

Further study details as provided by Centre for the AIDS Programme of Research in South Africa:

Primary Outcome Measures:
•Comparison of HIV incidence rates in 2 arms (tenofovir vs placebo) [ Time Frame: April 2010 ] [ Designated as safety issue: Yes ]


Secondary Outcome Measures:
•To assess the impact, if any, of tenofovir gel on the incidence rate of deep epithelial disruption [ Time Frame: April 2010 ] [ Designated as safety issue: Yes ]

•To assess the impact, if any, of tenofovir gel on viral load in women who become infected with HIV during the trial. [ Time Frame: April 2010 ] [ Designated as safety issue: Yes ]

•To assess tenofovir resistance in HIV seroconvertors in the trial [ Time Frame: April 2010 ] [ Designated as safety issue: Yes ]

•To ascertain the impact, if any, of tenofovir gel on pregnancy rates and outcomes [ Time Frame: April 2010 ] [ Designated as safety issue: Yes ]

•To assess the impact, if any, of product hold at study exit on HIV infection and tenofovir resistance [ Time Frame: April 2010 ] [ Designated as safety issue: Yes ]


Enrollment: 900
Study Start Date: May 2007
Study Completion Date: March 2010
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)

Results are anticipated in July 2010 and their outcome has a bearing on ongoing trials in Zimbabwe.

Source: http://clinicaltrials.gov

Civil society and media have shared responsibility to ensure accurate, non-stigmatising reporting on HIV

News: SAfAIDS Media Desk
16 April 2010
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PRETORIA - The fight against HIV needs to be multi-sectoral and inclusive, and the media should remain a strategic partner in interventions. This was said by Mr. Jason Wessenaar, Project Director of the Siyasi Counselling and Testing Project in response to assertions that the language used by media practitioners when talking about HIV and AIDS issues often stigmatises and has done a lot of harm to, and compromised the fight against the epidemic.

The discussion followed his presentation titled using culture to address HIV and discrimination among people living with HIV' where he spoke about the importance of being careful of the language stakeholders use, as it may further stigma; terms including HIV/AIDS as opposed to HIV and AIDS, AIDS orphans as opposed to orphans and being clear to distinguish between people living with HIV and those who have AIDS were discussed.

Mr. Wessenaar explained that in South Africa, non-stigma guidelines for use in work with media practitioners - both journalists and editors - to inform reporting on HIV and gender issues have been developed. These guidelines can also be used in the workplace, and with faith based organisations. Further, a National Stigma Framework has also been developed for use by all sectors.

Media practitioners attending the Conference asserted that in their studies, journalists are not afforded the opportunity to specialise, in HIV and gender reporting for instance. Specialisation comes through the information and training that journalists receive in workshops, trainings and conferences; so civil society organisations and activists need to take some responsibility for the information that the media takes forward and circulates.

The meeting agreed that the fight against HIV must be a collective effort which includes all relevant sectors; there should be no exclusion.

Both the non-stigma guidelines and the National Stigma Framework were developed by the Siyam'kela Stigma Project at the Centre for the Study of AIDS at the University of Pretoria.

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This article covers the recently ended Changing the River's Flow Conference held at Birchwood Hotel, Johannesburg, South Africa from the 12th to the 13th of April 2010.

Worrying rise in STIs among young people

News:14 April 2010
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HARARE, 14 April 2010 (PlusNews) - A new report by Zimbabwe's National AIDS Council (NAC), showing a dramatic rise in sexually transmitted infections (STIs) among people aged 15 to 24 in the capital, Harare, has health experts worried that the country's success in reducing HIV could be unravelling.

STIs heighten vulnerability to HIV infection, and this age group is one of the hardest hit. According to the NAC report, more than 24,000 people were treated for STIs in 2009, compared to 8,500 cases recorded in 2008; over 60 percent of the cases were women.

During this time almost 900,000 male condoms and over 155,000 female condoms were distributed in Harare. Itai Rusike, executive director of the Community Working Group on Health (CWGH), a network of civic groups that promote health awareness, blamed the rise in STIs on a too narrow focus on HIV and AIDS treatment.

"In the last two to four years we have concentrated our focus on access to treatment, especially access to ARVs (antiretrovirals), at the expense of preventive services," he told IRIN/PlusNews.

"Right now the bulk of our AIDS levy money [a 3 percent tax on income] is going towards procurement of ARVs, to the detriment of health education awareness campaigns, especially for the young adults who are supposed to be our hope for the future."

Zimbabwe's adult HIV prevalence has been on a downward trend, dropping from 14.1 percent in 2008 to 13.7 percent in 2009.

Young people neglected

In 2009 the CWGH conducted an assessment of young people's needs for sexual reproductive health and HIV and AIDS interventions, which indicated that sex work, intergenerational relationships, early marriage, early sexual debut and unplanned pregnancy were among the challenges they faced.

In its recently published 2009 annual report the CWGH noted that young people had limited access to reproductive health information and services. "If we do not invest in preventive services, all the gains we have scored so far in HIV prevalence rate will be eroded," Rusike warned.

''If we do not invest in preventive services, all the gains we have scored so far in HIV prevalence rate will be eroded''
"Youth-led peer education activities need to be well co-ordinated and supported with financial resources, education materials, mentoring and capacity building, in order for them to be sustainable," he pointed out.

Orirando Manwere, a National AIDS Council (NAC) information officer, agreed that the rise in STI infections was an urgent call to action. "There is a need to carry out a study on why this is the trend, but generally this could be attributed to early sexual debut among the youth, unprotected sex, abuse by older men - particularly among the women and girls."

Manwere said Zimbabwe's current policy on sex education did not allow HIV and AIDS organizations to go into schools and teach young people about issues like condom use, but discussions between non-governmental organisations and government were ongoing. "It is clear that the youth are indeed sexually active and need to be empowered on sexual and reproductive health issues."

Political disruptions

AIDS activist Martha Tholanah attributed the STI increase to the violence that occurred in the aftermath of the March 2008 election.

"Youths were used to target other youths - we had reported cases of a sexual violence, which I do not think were followed up adequately, as many actors were very fearful of the repercussions if they dealt with these issues."

Many organizations, especially those working with young people, are still struggling to get on their feet after the economic and political disruptions of 2008 and beyond.

"I do not think many organisations working on sexual and reproductive health have regained the impetus they had before political and economic disruptions," Tholanah commented. "I believe we will still see more negative health effects resulting from that era."

Online at: http://www.plusnews.org/report.aspx?ReportID=88810

THE IMPACT OF MEDIA ON ADOLESCENTS' SEXUAL BEHAVIOUR

The effects of media consumption on young people's attitudes and behaviour
regarding sex should be of increasing interest to policy makers and program planners.

One concern is the extent to which frequent consumption of media with high levels of sexual content and low levels of portrayal of responsible sexual conduct is a causal influence on young people's subsequent sexual behaviour, including the responsible use of protection from pregnancy and disease.

Three basic areas for concern:
(1) What sexual content do youth pay attention to, and how they interpret what
they see and hear;
(2) Effect of media content on adolescents’ sexual beliefs and behaviour; and
(3) How the mass media can be used to promote responsible sexual behavior among
youth

The effects, if any, of growing up in an environment saturated by media that focuses on sexual behavior.
Frequent consumption of media with high levels of sexual content and low levels of portrayal of responsible sexual conduct is a causal influence on young people's subsequent sexual behaviour and young people's understanding of the dynamics and risks of sexual intercourse and its consequences are improved via their use of media. The content of various forms of media affects young people's attitudes and behaviour with regard to sexual intercourse.

Young people are heavy consumers of sexually-oriented media including TV, broadcast and satellite channels, videos, movies, magazines, and, more recently, the Internet. Content analysis has also demonstrated that broadcast satellite television contains a high, growing and increasingly explicit dose of sexual messages, and that a low proportion of such messages display or model either restraint or contraceptive use.

Forms of media are changing constantly, so that media "diets" may be changing in
unknown, and as yet, uncharted ways. Developmentally, young people gain more
control over their media use as they mature. Individuals may selectively use and
change their use of media, in ways not clearly understood. Age, gender,
race/ethnicity and social class may influence what media individuals have access
to and choose to pay attention to. There are also suggestions that self-definition as a member of a particular clique or crowd may influence young people's choice of media. No one form of media use predominates in adolescence.

For the purposes of this article, "media" are taken to mean information and images
delivered via: printed matter, such as newspapers, magazines, and comic books;
radio, both music and talk; TV, broadcast, satellite and video, including music
videos; movies, tapes and compact discs and the games and information accessible
through computers on the Internet and World Wide Web. Program content and
advertising are both included. Unlimited access to the Internet and to the wide
range of services available on the World Wide Web is of growing interest. The
number of individuals who have ready access to computers is growing daily.

Mass media are to a great extent fueled by commercial enterprises which have as
their goals influencing individuals' purchasing decisions. While messages may
be targeted to one or another group of individuals, there is limited or no
control over who actually listens to or understands or acts upon the information
or images disseminated.

There is therefore a need for policy makers and programme planners to recognise the role played by the mass media in modelling the sexual orientation and behaviour of adolescents.

Microbicides, vaccines may need to repel HIV contact at mucosa

http://www.aidsmap.com/en/news/5B7B6E24-E8DE-4E40-86A9-3BB6E18F043C.asp
April 9, 2010
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Found in today’s AIDSmap news. Informs ecology between HIV and mucosa; also enlightens an increasingly prevalent topic in AIDS pathology studies, the phenomena – and implications – of chronic inflammation within GI tract:

Keith Alcorn, Friday, April 09, 2010

HIV can damage the walls of cells in the mucous membranes in the genital tract and the intestines, permitting the virus to pass across these barriers and infect vulnerable cells below, even when the tissue is undamaged, Canadian researchers report this week in the journal PLoS Pathogens.

The findings suggest that microbicides and vaccines may have the greatest chance of success if they can limit or prevent completely contacts between HIV's gp120 surface protein and cells in the mucous membranes of the genital tract and the intestines.

The events taking place when HIV comes into contact with mucous membranes and the immune reactions that occur within the mucosa are a critical area of research for scientists hoping to develop new methods of preventing HIV infection. All sexual transmission of HIV occurs through mucous membranes.

In their research the group from McMaster University, Ontario, with colleagues from the University of Toronto and Laval University found that in the test tube HIV’s envelope protein gp120 stimulated production of inflammatory cytokines in mucous membrane cells which made the membrane more permeable.

The authors say that this mechanism could allow HIV to enter cells below the mucous membrane surface even when it is undamaged, and may also explain why bacteria `translocate` across the intestinal wall in people with HIV more frequently than in uninfected people.

This translocation of bacteria is responsible for immune activation in people with HIV, in the view of some researchers, and may drive not only HIV disease progression but also the development of serious conditions such as atherosclerosis which are promoted by the inflammatory state that exists in people with highly activated immune systems.

Previously researchers into HIV transmission had thought that transmission was most likely to occur either when the mucous membrane was damaged (for example through trauma or ulceration) or when many activated immune cells were present (such as during a sexually transmitted infection like gonorrhoea).

But the McMaster University group found that HIV can weaken the integrity of surface cells, even when they are undamaged.

"What it does is that it makes the electrical barrier resistance of epithelial cells decrease. By doing that, the virus can cross the barrier," said lead researcher Charu Kaushic, associate professor in the Centre for Gene Therapeutics at McMaster University.

Scientists have been faced with the question of how HIV actually gets underneath epithelial cells to infect other cells that are susceptible to HIV. "It's not the cells on top," Kaushic said. "It is the immune cells underneath that have all the receptors that HIV likes to latch on to and that allow the virus to replicate and establish infection. But it has to cross the epithelial barrier first!"

The McMaster researchers grew purified primary epithelial cells in the laboratory from small pieces of tissues that were removed from women's uterus during hysterectomies, with their consent. Then, they began to study how HIV actually interacts with these cells. The electrical resistance in these cultures is used to monitor how well the epithelial cell cultures are growing and functioning.

Aisha Nazli, a researcher in Kaushic's laboratory, noticed every time she put HIV on epithelial cells their resistance went down significantly. Repeated tests confirmed this.

Kaushic said the surface protein of the virus causes the epithelial barrier to break. "The surface protein signals to the inside of the epithelial cells by binding to it", she said. "The epithelial cells start making inflammatory proteins which cause these cells to go on their self-destructive pathway."

The researchers say that providing viral load and exposure time are sufficient, HIV can probably disrupt any mucosal barrier in the body, although infection may not necessarily occur every time.

"This is a significant step forward in defining where prevention strategies, such as microbicides and vaccine, need to focus. Instead of trying to stop HIV from infecting the target cells underneath the epithelium, we need to think about ways to stop the virus from attaching to epithelial cells themselves," said Charu Kaushic.

Reference

Nazli A et al. Exposure to HIV-1 directly impairs mucosal epithelial barrier integrity allowing microbial translocation. PLoS Pathogens 6 (4): e1000852, 2010.

Mass Media & African Renaissance

The African Renaissance is a concept that Africa, African people and African nations can overcome the challenges that they are currently confronting and achieve cultural, scientific, economic and social renewal. Popularised by Thabo Mbeki the former President of South Africa, the concept was first articulated in the 1990s and resonates with hope for a new and refreshed Africa.

What if any, is the role of the Mass Media in the African Renaissance?
The type of information that is produced by the mass media has a significant influence on the way that Africa and Africans can address particular socio-economic, development or environmental issues. Africa’s colonial background which resulted in the concentration of black people in small regions in the country with little access to resources, limited investment in development resulted in the excessive exploitation of natural resources for the benefit of the coloniser. Mass media coverage of such issues must reflect these imbalances for purposes of reconstruction and development in Africa.

The achievement of the African Renaissance requires that Africans develop a comprehensive information creation and dissemination system for all countries on the continent at both the national and sub-national levels. The information should reflect African development ethos, African development values, African development concepts and the fundamental aspect of Ubuntu. Mass media coverage needs to address the origins, the direction and path through which development issues should be addressed. The ability to develop such a system requires commitment from all African countries to work together and to allocate sufficient financial and institutional resources.
URTNA
URTNA is a professional body with more than 48 active member organizations committed to the development of all aspects of broadcasting in Africa. It encourages the exchange of indigenous programming via satellite and videocassette; strives to obtain preferential satellite tariffs to facilitate news and program exchange; represents the African point of view on legal matters such as conventions and agreements; and works with the ITU as an advisor for the PANAFTEL project.
Since 1972, a working group conducted jointly with other international organizations has been studying the contribution of communications satellites to education, culture, and development in Africa. URTNA has conducted a long-term project with governments of member organizations to evaluate rural telecommunications needs in Africa. URTNA also presents seminars, workshops, and conferences on topics such as news, educational broadcasting and television development of communications, satellite communications, and training.

URTNA is composed of the national radio and television organizations of African states that are members of the OAU. Associate members are national radio and/or television organizations from non-African countries.

The URTNA initiative was and still is a step in the right direction in terms of addressing Africa’s information needs. African countries will have to work together and possibly set aside their own national interests to ensure that poor countries spruce up investment in developing incountry Mass Media structures that can play an important role in bringing about reconstruction and development. Only through this approach will Africa be able to use the Mass Media to drive the African agenda for Africans and counter information from the north whose development agenda may not reflect the will and aspirations of the African continent. By so doing, Africans can slowly lift their standards of living to levels that may make the African Renaissance a reality.

Microbicides: What Do They Mean For Women?

What is a “microbicide”?

“Microbicide” (mī-KRO′-bĭ-sīd) just means anything that kills microbes (like bacteria and viruses). In connection with HIV prevention, a microbicide is any substance that can substantially reduce the risk of getting or transmitting sexually transmitted infections, including HIV, when it is inserted in the vagina or rectum. No proven microbicides are on the market yet. But several candidate products are in clinical trials and the search to find one that is both safe and effective is ongoing.

What will microbicides look like and how will they work?
Some of the microbicide candidates look just like over-the-counter vaginal products—the gels, foams, films, and suppositories that are already sold for birth control or to treat vaginal infections. The difference is that microbicides are designed to stop HIV, instead of treating infections or preventing pregnancy.
Scientists are also developing some new formulations that can be used without an applicator and that women will be able to leave in place for weeks. A hollow vaginal ring (similar to the NuvaRing® contraceptive device), for example, might release the microbicide slowly for up to a month and provide round-the-clock protection.

Almost all candidate microbicides being tested right now are made with antiretroviral drugs, (ARVs ). These are the same types of drugs people who are HIV-positive use for treatment. They are re-formulated in lower doses as gels, films, etc. so they can be applied as a microbicide.

How effective would a microbicide be?

Male and female condoms are by far the most effective tools for preventing HIV infection when used consistently and correctly. But they often are not. Mathematical modelling has shown that, if a woman uses a 50% effective microbicide at least 50% of the times she has sex, her risk of HIV would be lower overall than if her partner uses a condom only once in a while (for example if he uses it only two out of every ten times they have sex).

The effectiveness of a method is shaped by:
(1) how effective the prevention tool is and
(2) how often people use it.

Less effective methods used regularly protect better than more effective methods used occasionally.
Microbicides will likely be much less effective than condoms (perhaps in the 40% - 60% range) on a “per sex act” basis. But people who do not use condoms every time—especially women whose partners often refuse condoms—could benefit from a microbicide that they could apply, themselves, every time they have sex.
Prevention tools are just one part of what is needed for women to protect themselves from HIV. More work must also be done on the structural issues that make it hard for women to insist on condoms in the first place—like not having the economic opportunities and social autonomy to make their own choices about sex.

When and how will microbicides be available?

When: Developing new drugs is a complicated process. It often takes more than a decade to find one that is both safe and effective. At each step along the way, potential products are dropped because they fail to meet the necessary standards. Only about one out of 100 original candidates make it to the final stages of testing.

The trial results of a candidate microbicide called tenofovir will be announced in 2010. If the trial shows that tenofovir gel is effective, it will likely take another larger trial to confirm the product is effective. The current trial is a phase IIB, and regulators may require a phase III trial to confirm the results. Even after a successful phase III trial, it could take two to three years for the product to be reviewed and licensed in countries where it would be first introduced. Several candidates are already in the testing pipeline but have not yet progressed to full-scale effectiveness trials.

How:

How a microbicide is made available will depend partly on whether it is ARV-based or non-ARV-based. ARV-based microbicides are likely to be more potent against HIV and may be longer-lasting. But they also might cause more side effects, including a particular problem called drug resistance , if they are accidentally used by someone who is HIV-positive already. For this reason, women will have to see a health care provider and get an HIV test before receiving these products. They will only be available by prescription.

Non-ARV-based microbicides may be less effective against HIV than ARV-based products. And they may have to be used closer to the time of sex (likely within a few hours) because they may be harder to put into time-released devices like vaginal rings. But it is likely that non-ARV-based microbicides could be available over-the-counter in shops, without a prescription. Each type of product has advantages and disadvantages.

What could microbicides mean for women?

The possibility of a microbicide offers real hope to women who want to have their own HIV prevention tools, as well as to both women and men who have anal sex and want additional methods of protection.

Many women participating in microbicide trials have said that they would probably tell a male partner if they were using something for HIV prevention—even if the method is not as obvious to him as condoms. But, unlike condoms, microbicide use wouldn’t require a partner’s active cooperation. Talking about microbicides could be a one time conversation and does not have to happen right before sex. After that, the woman could use them on her own without need to “negotiate” or interrupt sexual spontaneity every time.

Here are some other questions women have raised about microbicides:

 “If my man knows I am using microbicides to prevent HIV, will he still use condoms?” His refusal to use one could raise her risk, even if she has a microbicide. On the other hand, women in some microbicide trials report that using a lubricating gel along with condoms makes sex more pleasurable for both partners. Some say this actually makes negotiation for condom use easier for them (that is they can say to their partners “I will use the gel if you use the condom”).

 “What will people say about me if they find out I’m using a microbicide?” Even if she is at high HIV risk, a woman may choose not to use a microbicide if she fears that doing so will make people will think she is promiscuous. So messages to promote them must steer around this kind of stigma.

 “How much will it cost and where will I get it?” In many countries, it will be essential for governments and development agencies to purchase microbicides in bulk and distribute them through public health agencies and social marketers at little or no cost. No matter how well it works, a microbicide that costs much more than a male condom will not be within reach of all women who need it.

What are the advocacy issues?

Collectively, we need to advocate for stronger support for the research and development of both ARV-based and non-ARV-based microbicides. We also need much more data on some important questions, such as how these products will affect pregnancy, breast-feeding, and the lives of women already living with HIV. Most importantly, we need to start addressing the cost and access issues now while research is still underway. Those who will eventually use microbicides must be involved in setting research priorities and helping to find answers to these questions. After all, microbicides are all about putting HIV prevention into women’s hands.