Anti-retrovirals could halt Aids spread in five years

A fascinating topic and I would encourage people to participate in the web briefing (and/or call in to it by phone) on this issue that will take place this Thursday,April 1, 10-11am ET: Antiretrovirals for HIV Prevention: Panacea or Pandora's Box?, presenter: Ken Mayer, Brown University and Fenway Health. For the info on how to login to the webinar and ask questions or to call in to the global toll free numbers -- go here, where it says "webinar details":
http://www.avac.org/ht/display/ContentDetails/i/6061/pid/351

The expansion of HIV testing programmes and the advocacy of universal testing and treatment of those who test positive as a means of prevention must not violate the human rights of target populations, the Fifth IAS Conference on HIV Pathogenesis, Treatment and Prevention was told on Monday in Cape Town.

Representatives from the organisations Human Rights Watch and the AIDS and Rights Alliance of Southern Africa (ARASA) told testing advocates to ensure that testing is not coercive, that it is linked to treatment provision and treatment education, that the peer counsellors who perform testing understand confidentiality and informed consent, and that those who test positive are not subjected to ostracism within their communities.

The background to a series of seminars and discussions on the way forward for ‘treatment as prevention’ was a political disagreement among the HIV advocacy and public health communities dating from last year.

In 2008, two mathematical models appeared in HIV journals showing that universal treatment of people who test positive for HIV would reduce the epidemic in the worst-affected countries by 90 to 95% by the year 2050.

The first, by Julio Montaner’s team (Lima) at the British Columbia Centre for Excellence in HIV/AIDS, found that two-thirds of infections in the province would be averted if all patients started treatment when their CD4 cell count was around 350 cells/mm3.

The second modelling exercise (Granich) was conducted by the World Health Organization and published in The Lancet last November. This model found that achieving the somewhat utopian goal of universal HIV testing and treatment for everyone diagnosed HIV-positive would reduce HIV incidence from 2% a year to 0.1% a year within ten years and would reduce prevalence by 95% by 2050.

This report caused considerable controversy. In April 2009, a Civil Society Consultation on ART for Prevention met in Johannesburg, convened by ARASA and attended by activists from Kenya, Tanzania, Uganda, Botswana, Mauritius, South Africa and Namibia. The delegates produced a statement which declared that they had “fundamental concerns about the assumptions on which the model is based, its shortcomings from a human rights perspective and its inattention to vulnerable and marginalised groups”.

“Given the flawed and optimistic assumptions on which the model is based,” this statement continued, “the authors’ argument that the benefits of eradicating AIDS outweigh the potential violations of individual rights that this may occasion is hard to accept.”

Gus Cairns, Tuesday, July 21, 2009
http://www.aidsmap.com/en/news/C35EF8E0-2F47-4F7B-909C-6D30FB600972.asp

New research could bolster arguments for a controversial approach that could eradicate HIV transmission in South Africa within five years, said Dr Brian Williams of the South African Centre for Epidemiological Modelling and Analysis (SACEMA). 

The "test and treat" approach is based on mathematical modelling and pairs aggressive HIV testing campaigns with almost immediately putting people found to be HIV positive on treatment. In theory, this model would use early treatment to lower viral load (the amount of virus in the blood), and lower the likelihood of transmission, eventually cutting HIV prevalence rates. 

A report published in the current issue of AIDS, the Journal of the International AIDS Society, is based on a study that followed about 14,000 new mothers in Zimbabwe for about two years from 1997 to 2000 after the birth of their children.


The research showed that HIV-positive new mothers were at much greater risk of dying than their HIV-negative peers, even when the positive women had a CD4 count (which measures immune system strength) of 600 to 1,000 and was equal to or higher than that of HIV-negative women. 

Although the research was conducted before antiretrovirals were available in the public sector, the data may have answered a crucial question in the test and treat debate. 

"One of the questions around doing [the test and treat model] has been that even if you accept that there is public health benefit of testing and treating everyone, what does that do for the individual?" Williams told IRIN/PlusNews. 

"The study's authors showed that even at CD4 counts of up to 1,000, mortality among the HIV-positive women was about 50 times higher, [and] it's in the patient's interest too, to start treatment early," said Williams, who spoke in favour of test and treat at the Conference on Retroviruses and Opportunistic Infections (CROI), and the annual meeting of the American Association for the Advancement of Science, both in the Untied States. 

John Hargrove, co-author of the report, said the study was one of a very few that had compared the mortality rate of untreated HIV-positive adults to their HIV-negative peers and had tied this to CD4 counts - the research could never be ethically replicated in today's expanded treatment environment. 

However, there are concerns that the approach is unrealistic, given low testing uptake globally, and that putting more people on treatment earlier may lead to poor adherence and contribute to drug resistance. 

The approach is being implemented on a trial basis in high HIV prevalence areas of the United States, including the District of Columbia and New York City. The US infection rate is about 0.6 percent, according to UNAIDS. 

Williams said doing away with specific requirements like the need to verify CD4 counts would reduce costs, but estimated that it would still cost a country like South Africa at least US$2 billion a year to implement the test and treat strategy nationally. 

"Costings show that the cost of providing ARVs will be roughly balanced by the costs saved in [relation to] opportunistic infections and hospitalisations," he said. "We need a big investment initially, but in the long term we are going to be saving money. It's the only real prospect for actually stopping the epidemic." 

However, in a debate about test and treat in late 2009, Dr Francesca Conradie, deputy director of the University of Witwatersrand Clinical HIV Research Unit, argued that money was not the only issue, and that test and treat models ignored current realities, including low testing uptake. 

According to the 2008 South African National HIV Prevalence, Incidence, Behaviour and Communication Survey, only about half the people 15 years and older have been tested for HIV. 

Conradie also argued that the US had low HIV prevalence, whereas South Africa's HIV population was simply too big to meet the treatment targets cited by current test and treat models to make the approach affective - the country would have to reach more than eight times the number currently on treatment to meet the targets. 

With an HIV prevalence rate of about 18 percent and more than half a million people on treatment, South Africa runs the world's largest ARV treatment programme.
http://www.plusnews.org/Report.aspx?ReportId=88200

Thanks for this information very useful and important information. This packaged with a lot more treatment literacy would solve more problems other than just prevention of HIV. I hope more advances could be attained and that all the people that are closely following these developments, please continue circulating this information as we also do the same in the areas we are in. Success in this field will mean less money spent on the fighting new infections therefore stabilizing the incident rates of HIV. This will mean that use of resources can be maximized to the fullest. Lets embark seriously on sharing, this information by conduct more "Community Preparedness programmes" in all our locations. Paul (paulsitive at yahoo.com )

So, if a vaccine trial breaks positive by even a single endpoint, the trumpets blare from IAVI, from NIH, from UNAIDS. Yet, it is becoming clearer that antiretroviral therapy can prevent HIV transmission. We've known this for years, since MTCT and pre-exposure prophylaxis have provide proof-of-concept, and now data is coming in from models and from initial studies that the "best" prevention tool we have now may be ART.
Yet, the HIV prevention community is silent, or they complain that too much attention is focused already on treatment and ART is somehow not "real" prevention and shouldn't distract us. There was a 92% drop in infection rates in a recent study among discordant couples on ART. If we had a vaccine this effective there would be dancing in the streets.
There are communities ravaged by new infections, both in the United States and around the world, which could be sites for studies of ART as prevention as we figure out the details of its effectiveness in practice, the kinds of supportive services needed to successfully help people living with HIV/AIDS manage their meds, the plan for widespread implementation. Brian Williams and other scientists associated with WHO or CDC have overstated the case--we won't wipe out HIV in 5 years. But we could beat back HIV tremendously.
The days of the battles of treatment vs. prevention are over.
And AIDS treatment, for you economists, looks like a public good--not simply a private one, and it looks like it is cost-effective if you now assume in your own models that it can prevent HIV transmission.
ART isn't a cure and isn't a vaccine, but it can be the basis of a reinvigorated push against this epidemic, about bringing health services to those who need it, building a real comprehensive approach
to HIV and TB, dropping infection rates AND death rates all-in-one. So, what are you going to do about it? Dr. Fauci? Dr. Berkeley? Dr. Sidibe? Dr. Chan? Dr. Frieden? Dr. Goosby? Dr. Easterly? Dr. Over? Dr.
Halperin? Dr. England? Mr. Gates?
Things are NOT the same as they were yesterday--there is a powerful new prevention tool sitting right in front of you. What will you do with it?
Gregg ( gregg.gonsalves at gmail.com)

The antiretroviral drugs that revolutionized the care of people with AIDS are on the threshold of a new life as tools to prevent infection in individuals and brake the epidemic in populations as a whole.

Studies are underway testing whether periodic use of the drugs, either as pills or as vaginal or rectal gels, can prevent transmission of HIV in high-risk sexual encounters. At the same time, it's becoming clear that the incidence of HIV infection declines over time in places where most infected people know their status and are on treatment -- and thus are less likely to pass the virus to others.

Description of these effects at a big AIDS conference here is likely to spur a further swing of the treatment pendulum toward early and widespread treatment of HIV infection.

"Arguably the greatest progress in the AIDS epidemic has been in the development of highly effective drugs," said John W. Mellors, an AIDS researcher at the University of Pittsburgh and chairman of the 17th Retrovirus Conference. "This is now being applied not only to help infected individuals but as a public health approach to the whole epidemic."
By David Brown
Washington Post Staff Writer
Saturday, February 20, 2010
Since the advent of "combination antiretroviral therapy" (ART) in 1996, patients and physicians have debated how aggressively the drugs should be used.

Recognition of ART's dramatic life-extending effect was followed by the appearance of unexpected side effects, including increased risk of diabetes and heart disease and changes in many patients' appearance. As a consequence, researchers over the last 15 years have conducted dozens of studies seeking to learn how long an infected person could safely put off starting the drugs, or whether an infected person could stop taking them periodically without harm.

It's now clear that interrupting treatment is not a good idea and that starting it early in the course of infection may have real benefits, even though it means a lifetime of daily pill-taking. The new studies discussed here are likely to only increase the use of the drugs, which now number more than 30.

Antiretroviral drugs are already being given to babies born to infected mothers immediately after birth and during breast-feeding to greatly reduce the chance of infection.

"We know prevention works in babies. It shouldn't be any different in adults," Mellors said.

Several studies are underway testing "pre-exposure prophylaxis" with the drugs in people at high risk for acquiring HIV, including commercial sex workers. Some results may be available late this year.

There are already indirect hints that AIDS medicines can be prevention tools just like condoms and abstinence. Specifically, when an infected person is on a successful ART regimen, the amount of the virus in the bloodstream falls to such a low level that the chance of infecting someone else is almost nil.

In a study presented Friday, Deborah Donnell of the Fred Hutchinson Cancer Research Center in Seattle described this effect in "discordant couples" -- a couple in which only one partner is infected -- in seven African countries. When a person's HIV infection got to the stage at which ART was started, the chance that the partner would become infected fell by 92 percent.

This suggests that, at least in discordant couples, ART should be started much earlier than guidelines in African countries recommend. A similar argument could be made for all HIV-infected people in those high-prevalence countries.

Such a strategy would require a huge step-up in treatment.

The World Health Organization recommends that infected people start ART when their CD4-cell count -- a gauge of the immune system's health -- falls below 350. Now, only 30 percent of HIV-infected people in that range are getting the drugs.

Antiretroviral drugs are also breathing life into the quest for a vaginal "microbicide" that a woman could apply, in private and without her partner's knowledge, to prevent HIV infection. Numerous substances have been tried and none has worked. Researchers here described experiments in which rhesus monkeys were protected from infection with a microbicide containing maraviroc, an HIV "entry inhibitor." Taken in pill form, the drug also is concentrated in rectal tissues, suggesting it may be useful to prevent infection through anal intercourse.

One of the researchers, John Moore of Weil Cornell Medical College in New York , said his team is now working on a maraviroc-containing vaginal ring, which would release the protective drug over a period of weeks.

A potentially dramatic effect of widespread ART use was described by Julio Montaner, director of the British Columbia Center for Excellence in HIV/AIDS, which oversees treatment of virtually all HIV-infected people in that Canadian province.

In the years immediately after 1996, when the province made a big push to get HIV-infected people on antiretroviral drugs, the number of new infections fell by one-half -- probably because there were fewer people with high "viral loads" of HIV available to infect others. There was a second decline after 2004, when it became clear that starting ART earlier and not stopping it was the best strategy. Since 2007, there has been a 50 percent drop in new infections among injection drug users, who are the group with by far the highest risk of acquiring the virus.

This trend is strong support for the new paradigm of aggressively seeking out infected people and offering them ART. It may be expensive upfront but, Montaner said, "the effect of preventing one infection is so great that it becomes potentially cost-averting."

Patients with HIV who are sexually active can dramatically reduce the risk of transmitting the disease to their uninfected partners by taking antiretroviral therapy (ART), researchers stated here at the 17th Congress on Retroviruses and Opportunistic Infections (CROI).
The risk of infection between sexual partners decreased from 2.23% among those who did not receive ART to 0.39% in those couples in which the infected partner was treated with ART -- a reduction of 92%.
The drop-off in serum and genital viral loads that accompanies treatment has long been suspected -- and hoped -- to counteract transmissibility, said Deborah Donnell, PhD, Fred Hutchinson Cancer Research Center, Seattle, Washington, during an oral presentation on February 19.
For the study, researchers analysed data from the Partners in Prevention HSV/HIV Transmission Study, a randomised clinical trial of acyclovir to reduce HIV transmission among 3,408 heterosexual HIV serodiscordant couples from 7 African countries.
In the study, only 1 partner was confirmed to have HIV. The trial failed its primary endpoint of reducing HIV transmission by randomising the HIV-infected partners to acyclovir. However, Dr. Donnell and colleagues wanted to scrutinise the data to determine if being on ART during the trial had any effect on transmission.
None of the HIV-infected partners in the trial met their nations' guidelines for initiation of ART at baseline, but 10% started on therapy during the course of the trial, about half due to CD4-positive T-cell counts falling below 200 cells/mm3.
All uninfected partners were tested for HIV every 3 months and the couples received free condoms and intensive counselling. Nevertheless, 103 initially uninfected partners contracted HIV with the same genetic sequence as their infected partner, suggesting in-couple transmission.
"The implications for me are that there is both huge treatment benefit for people initiating antiretroviral therapy when their CD4 counts drop below 200 and also tremendous benefits to their partners," said Dr. Donnell.

Only 1 case of transmission possibly occurred after a patient had gone on ART. The partner appeared to have contracted the virus sometime in the 3-month period between tests, but the first positive test came 18 days after initiation of ART.
In patients who had >200 CD4-positive cells/mm3, the transmission rate was a fairly consistent 2%. Half of the linked transmissions occurred when CD4 counts remained >350 cells/mm3. However, the highest transmission rates occurred at the lowest CD4 counts, so the risk reduction with treatment was greatest for this group as well. The rate of 8.9% per year for those <200 CD4-positive cells/mm3 dropped to 0% with ART.
By Ed Susman
http://www.pslgroup.com/news/content.nsf/medicalnews/852576140048867C852...

The notion of treatment as prevention got a significant boost this week at CROI, where the results of a new study were presented by Deborah Donnell, MD, of the Fred Hutchinson Cancer Research Centre in Seattle. Dr. Donnell detailed exciting evidence that ART can prevent HIV acquisition, at least in the context of heterosexual, HIV discordant couples. 
In a multinational prospective study, researchers followed of a large cohort of couples in south and east Africa and looked at the role of ART in reducing transmission risks. The study tested the uninfected partner at the beginning of the study and at 3 month intervals, while providing free condoms and intensive prevention counseling to the couples. The infected partners were placed on ART when their CD4 counts dropped below 250.  Thirty-one percent of the infected female partners and 28 percent of the infected male partners reported unprotected sex.
The study was able to confirm whether HIV transmission occurred within the partnership through special testing.  There were 151 HIV transmission events, 108 of which were linked to partnerships.  Only one transmission event was found within a partnership where the infected person was on ART, while 102 HIV infections occurred within partnerships with no ART.  There was a 92 percent reduced risk of infection for the discordant partnerships where the partner was on ART. 
HIV transmission occurred at all CDR levels, but transmission rates were highest when the infected partners CD4 count was under 200.  This finding emphasizes the prevention imperative to expand ART access to the 40-some percent of persons in developing countries with CD4 counts below 200 who do not yet have access.
Interestingly, there was a significant reduction in unprotected sex in the partnerships where ART was introduced, from 6.2 percent to 3.7 percent.
Dr. Donnell noted that further research and more data is needed to evaluate whether prevention benefits would persist during long-term ART use. Click here to read a Reuters story on the study.

http://sciencespeaks.wordpress.com/2010/02/20/more-evidence-that-art-is-...