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Tuesday, December 7, 2010

Turnaround seen in AIDS fight

By Liz Highleyman -

David Jensen leaves a note for his boyfriend, who died 20 years ago, but whose name was only recently inscribed into the Circle of Friends at the National AIDS Memorial Grove in Golden Gate Park. As part of its World AIDS Day commemorations this year, the AIDS Grove held its first nighttime event Tuesday, November 30. Photo: Rick Gerharter
David Jensen leaves a note for his boyfriend,
who died 20 years ago, but whose name was
only recently inscribed into the Circle of Friends
 at the National AIDS Memorial Grove in Golden
Gate Park. As part of its World AIDS Day
commemorations this year, the AIDS Grove
held its first nighttime event Tuesday, Nov 30.
Despite the lack of major treatment breakthroughs, 2010 is shaping up to be a pivotal year in the history of the AIDS epidemic.

Two key trials have recently provided the first evidence that biomedical prevention methods can help reduce new infections, the latest UNAIDS figures suggest that HIV incidence and death have finally started to decline, and a growing number of experts are even starting to talk about the prospect of a cure.

To mark the 23rd commemoration of World AIDS Day on December 1, UNAIDS released its latest global epidemiology report, revealing that new HIV infections have fallen by nearly 20 percent over the past decade, while the number of AIDS-related deaths have dropped by a similar percentage during the past five years.

Looking at data from 182 countries, the authors estimated that some 2.6 million people were newly infected in 2009, compared with 3.1 million in 1999. More than 50 countries saw their infection rates stabilize or decrease.

Four African countries with especially large local epidemics - Ethiopia, South Africa, Zambia, and Zimbabwe - saw drops of more than 25 percent. But Eastern Europe and Central Asia, where the AIDS epidemic is largely fueled by injection drug use, did not fare as well.

Looking at mortality, the number of AIDS-related deaths worldwide decreased by about one-fifth, from 2.1 million in 2004 to 1.8 million in 2009.

The total number of people living with HIV/AIDS increased slightly in the past year - from 32.8 million to 33.3 million - but this is actually good news, reflecting the fact that more HIV positive people are living longer thanks to effective antiretroviral therapy.

Not all news is good news, however. While the number of people receiving anti-HIV drugs rose by about 30 percent during the past year alone, reaching just over 5 million, experts estimate that twice that number are still not getting the treatment they need.

UNAIDS estimated that nearly $16 billion was devoted to HIV/AIDS in 2009, but this fell about $10 billion short of the amount required for 2010.

U.S. and global treatment activists warn that this shortfall is likely to worsen, as wealthy countries cut back on their funding commitments in the wake of the ongoing worldwide financial crisis.

"W e can say with confidence and conviction that we have broken the trajectory of the AIDS pandemic," said UNAIDS Executive Director Michel Sidibe, but the "gains are fragile" and could be reversed without sustained effort.
Prevention promise

Even with improved access to treatment, for every individual who starts antiretroviral therapy, two additional people become newly infected, according to the UNAIDS report.

With growing evidence that we cannot "treat our way out of this epidemic," as philanthropist Bill Gates put it this summer at the International AIDS Conference in Vienna, public health experts are increasingly turning their attention to improved prevention.

The past three decades of biomedical prevention research have produced little but frustration. Countless HIV vaccine candidates have failed at early stages of testing, Merck’s V520 vaccine was actually associated with an apparent increase in the risk of infection in the STEP trial, and a combination vaccine trial in Thailand announced with much fanfare in 2009 did not live up to the hype.

But this year prevention research finally turned a corner.

At the Vienna AIDS Conference, Salim Abdool Karim reported results from the CAPRISA 004 trial, which tested a vaginal microbicide gel containing 1 percent tenofovir (the same drug in Gilead Sciences’ Viread).

South African women who applied the gel before and after sex had a 39 percent lower risk of HIV infection than women who used an inactive placebo gel, reaching 54 percent for those who used it as directed most often.

Notwithstanding the modest protective effect, these results were widely hailed as a major breakthrough.

"We are giving hope to women," said Sidibe. "For the first time we have seen results for a woman initiated and controlled HIV prevention option...If confirmed, a microbicide will be a powerful option for the prevention revolution and help us break the trajectory of the AIDS epidemic."

A similar wave of enthusiasm greeted last week’s news that pre-exposure prophylaxis, or PrEP, using the oral form of tenofovir plus emtricitabine (the drugs in the Truvada combination pill) could also lower the likelihood of HIV infection.

In the international iPrEx trial - which enrolled nearly 2,500 participants worldwide, including 140 in San Francisco - gay and bisexual men who took Truvada every day had a 44 percent lower risk of infection than men who took a placebo pill, or 73 percent lower for those with the best adherence.

"Today marks a major step forward in our quest to combat HIV among MSM and other populations," Kevin Robert Frost, the CEO of the American Foundation for AIDS Research, said in response to the findings. Jim Pickett of the AIDS Foundation of Chicago and International Rectal Microbicide Advocates concurred, "This discovery alters the HIV prevention landscape forever."

Cost and controversy

Researchers, public health officials, and community advocates alike lauded the CAPRISA and iPrEx findings, but not everyone joined the celebration.

Misgivings about PrEP, in particular, echo some of the concerns arising from the announcement this past spring that San Francisco General Hospital and other facilities run by the city’s Department of Public Health would now offer antiretroviral therapy to everyone diagnosed with HIV, regardless of CD4 T-cell count.

Current U.S. guidelines call for starting antiretroviral therapy when CD4 cells fall into the 350 to 500 range, but half the expert panel setting the standard favored treatment even above this level.

The San Francisco decision was influenced by a growing body of evidence suggesting that early treatment can help prevent persistent inflammation and other damaging effects of HIV infection that occur well before CD4 counts fall into the danger zone for opportunistic infections.

"We should perhaps think of AIDS as acquired inflammatory disease syndrome," said SFGH researcher Steven Deeks. "The old paradigm was that drugs are toxic so we should wait as long as possible. The new paradigm is that while today’s drugs are not totally benign, they are less toxic than the virus."

As an added benefit, early treatment can reduce "community viral load," and mathematical models and some real-world evidence suggest that a "test-and-treat" approach has the potential to lower the overall rate of HIV transmission. One World Health Organization model even showed that universal regular testing and treatment of everyone infected could essentially halt the epidemic within 50 years.

But starting therapy sooner carries the risk of unknown long-term side effects, and some advocates fear HIV positive people could be pressured to start treatment before they need it for their own health, in order to serve public health goals.

In the case of PrEP, some skeptics worry that susceptible individuals will come to regard drugs as a substitute for condom use and other behavioral risk-reduction measures, even though the protective effect in iPrEX was modest and participants also received state-of-the-art prevention support including frequent testing, counseling, and free condoms.

Amid the PrEP enthusiasm, a new survey conducted by the Global Forum on MSM and HIV found that a majority of men who have sex with men worldwide have trouble accessing basic prevention services such as HIV testing, counseling, and affordable condoms and lubricant.

"With the excitement surrounding the promise of pre-exposure prophylaxis, it can be easy to forget that we already have a rich selection of prevention measures that we know work right now," said researcher Patrick Hebert. "[These] findings reinforce the fact that we can’t even get condoms and lube to more than half of MSM around the world."

Both early treatment and PrEP raise issues of cost and access. How can we justify giving expensive antiretroviral drugs to HIV positive people who are still healthy - not to mention people who are not even infected - when so many people with HIV worldwide cannot access or afford the treatment they need to prevent disease progression in accordance with current guidelines?

And what about the role of the pharmaceutical industry?

"It is as though a decision has been made to redirect the country’s public health response to AIDS from proven behavioral interventions, like condoms and prevention education, to the use of antiretroviral medications," wrote POZ magazine founder Sean Strub in response to San Francisco’s early treatment announcement. "Public health officials’ focus on treatment as prevention and the pharmaceutical industry’s incentive to expand markets are now in dangerously perfect alignment."

Enter eradication

The realization that treatment alone cannot end the epidemic, coupled with the recognition that persistent HIV can cause problems even in people taking antiretroviral therapy, has led to increased discussion about the possibility of actually curing HIV.

Speaking at the Vienna AIDS Conference, Sharon Lewin from Monash University in Melbourne, Australia, suggested that a cure is more scientifically feasible than ever before.

Researchers from governments, academia, and the pharmaceutical industry are exploring a variety of approaches, including drugs that can flush latent HIV out of resting cells and gene therapy to make stem cells - and the T-cells they produce - resistant to viral entry.

It is generally agreed that the prospect of complete eradication of HIV from the body, including resting CD4 cells and "reservoir" sites like the brain and gut, is not yet within sight.

But a growing number of experts think that a "functional cure" - that is, disabling the virus or strengthening the immune system enough to hold off disease progression when people stop antiretroviral therapy - is a goal that may be achievable in the foreseeable future.

"We should not and cannot continue to accept that HIV is a chronic illness that commits patients to lifelong treatment," said Lewin, who insists that finding a cure for HIV "is a human rights issue."


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