TIME HIV

Researchers Find New Way to Kick Out HIV From Infected Cells

Scanning electron micrograph of HIV-1
Scanning electron micrograph of HIV-1 Getty Images

The technique addresses the problem of hidden reservoirs of HIV in the body, and could herald a new way of battling the viral infection

Once HIV invades the body, it doesn’t want to leave. Every strategy that scientists have developed or are developing so far to fight the virus – from powerful anti-HIV drugs to promising vaccines that target it – suffers from the same weakness. None can ferret out every last virus in the body, and HIV has a tendency to hide out, remaining inert for years, until it flares up again to cause disease.

None, that is, until now. Kamel Khalili, director of the Comprehensive NeuroAIDS Center at Temple University School of Medicine, and his colleagues took advantage of a new gene editing technique to splice the virus out of the cells they infected – essentially returning them to their pre-infection state. The strategy relies on detecting and binding HIV-related genetic material, and therefore represents the first anti-HIV platform that could find even the dormant virus sequestered in immune cells.

MORE: Treatment as Prevention: How the New Way to Control HIV Came to Be

Even more encouraging, they also used the system to arm healthy cells from getting infected in the first place, by building genetic blockades that bounced off HIV’s genetic material. “It’s what we call a sterilizing cure,” says Khalili.

His work was done on human cells infected with HIV in cell culture, but, he believes the results are robust enough to move into animal trials and eventually into testing the idea in human patients.

The key to the strategy is the gene editing technique known as CRISPR, a way of precisely cutting DNA at pre-specified locations. CRISPR acts as a customizable pair of molecular scissors that can be programmed to find certain sequences of DNA and then, using an enzyme, make cuts at those locations. Because HIV is a retrovirus, its genetic material comes in the form of RNA; the virus co-opts a host cell’s genetic machinery to transform that RNA into DNA, which it then inserts into the cell’s genome. HIV’s genes, which it needs to survive, then get churned out by the cell.

MORE: David Ho: The Man Who Could Beat AIDS

Khalili designed a CRISPR that recognized the beginning and end of HIV’s DNA contribution, and then watched as the enzyme snipped out HIV from the cell’s genome. “I’ve been working with HIV almost since day 1 [of the epidemic] and we have developed a number of molecules that can suppress transcription or diminish replication of the virus. But I have never seen this level or eradication,” he says. “When you remove the viral genes from the chromosomes, basically you convert the cells to their pre-infection state.”

The advantage of the system lies in the fact that CRISPR can recognize viral genes wherever they are – in infected cells that are actively dividing, and in infected cells in which the virus is dormant. Current drug-based strategies can only target cells that are actively dividing and releasing more HIV, which is why they often lead to periods of undetectable virus but then cause levels of HIV to rise again. That’s the case with the Mississippi baby, who was born HIV positive and given powerful anti-HIV drugs hours after birth and appeared to be functionally cured of HIV when the virus couldn’t be detected for nearly four years, but then returned.

MORE: Rethinking HIV: After Five Years of Debate, a New Push for Prevention

Khalili admits that more work needs to be done to validate the strategy, and ensure that it’s safe. But it’s the start, he says, of a potential strategy for eradicating the virus from infected individuals. That may involve excising the virus as well as bombarding it with anti-HIV drugs. “We can get into cells, eradicate the viral genome, and that’s it,” he says.

TIME Aids

This Is What We Lost Aboard Malaysia Airways Flight MH17

UKRAINE-RUSSIA-POLITICS-CRISIS-MALAYSIA-AUSTRALIA-AIDS-FILES
Leading AIDS researcher Joep Lange during a conference on AIDS in Paris on July 14, 2003 . Jean Ayissi—AFP/Getty Images

Late last night, a terrific HIV vaccine researcher, Wayne Koff, sent me a quick note, indicating Joep Lange perished aboard the jet senselessly shot down over Ukraine. I reeled. Joep was one of the group of “Young Turks” from Amsterdam, amazing AIDS researchers that in the 1990s led the way to our modern treatment era.

This morning’s news is still uncertain, but it seems Lange was on board along with some 100 of his Dutch compatriots, and many of the passengers shared an ultimate destination – the twentieth International AIDS Conference in Melbourne, Australia. Some probably highly premature news accounts indicate a third of those shot out of the sky were en route to the conference. One additional has been confirmed – Glenn Thomas, AIDS specialist in the World Health Organization communications office.

There was a time when we convened in these meetings and whispered the names of friends, colleagues, and loved ones that wouldn’t be coming this year because they died of AIDS. In our gatherings in the 1980s, grief hung like a curtain over everything, alongside anger over the way governments were responding, the lack of funding, the stigma, and so many other aspects of what it was like to live in the World of AIDS before there was treatment. We fought through the mourning to get the job done, whatever that job might be: activist protesting, scientific investigation, fundraising, even journalism. The great oratory leader of the early AIDS fight Jonathan Mann would whip us into a fever of determination to stop discrimination against people with AIDS, fight for research funding, and find a cure for the devastating disease. Jonathan, who started the first global AIDS program at WHO, was the early pandemic cheerleader, pushing everybody forward, encouraging teams of scientists to work together in ways biologists and clinicians never previously had, for any disease struggle.

The Young Turks from Amsterdam were a special breed. There were so few of them yet they accomplished a long list of spectacular breakthroughs in understanding how HIV disrupted the human immune system, smart ways to prevent transmission of the virus among drug users, careful but rapid drug discovery and testing. Joep and Jaap – two prominent Dutchmen we foreigners had trouble pronouncing. What is the world is the difference in saying Joep Lange and Jaap Goudsmit? We marveled at the pragmatism of the Dutch. To put it bluntly, they got the job done.

In 1996 the one and only joyous AIDS Conference convened in Vancouver – a meeting marked by announcement of successful combination therapy that knocked the dastardly virus down to levels undetectable in blood. There was hope for a cure, thanks in large part to the Dutch work. Some dared to speak of eradicating HIV all together.

Two years later, as hundreds of thousands of HIV-positive men and women living in wealthy countries were thriving on those treatment combinations, hope dominated the pandemic, until 1998 when Swissair Flight SR11 crashed off Nova Scotia, killing all on board. Among them, Jonathan Mann and his new wife, AIDS vaccine researcher Mary Lou Clements. Their sudden loss felt like a kick in the gut for the world AIDS community.

Here we are, sixteen years later, facing airline tragedy again. As I write this in haste we don’t have more names and the scale of the AIDS community’s loss is unclear. But the loss of one is tragedy.

Like so many of the great AIDS scientists that toiled through the years of extreme loss and urgency before there was effective treatment, Joep Lange absorbed the political dimensions of the pandemic, and gained the skills necessary to translate lab and clinical findings into high-level battles inside the United Nations and across the global stage. He became a leader, in the fullest sense of that word. Like Jonathan Mann, Joep blended science, medicine, and an activist spirit to help bring the life-sparing medicines to people in all of the world – not just rich countries.

The last time Joep and I spent time together we argued, I’m sorry to say. And I may have been completely wrong, he completely right. The saga we argued about hasn’t played out yet. Joep believed without hesitation that effective treatment, “is like a vaccine,” as he put it. The global epidemic could be stopped, he said, simply by getting every HIV+ person on the planet put on an effective regimen of treatment. Once on medicines, he insisted, the load of viruses in their blood, vaginal fluids, and semen would drop so low that they would not be contagious. And that, he said with a grin, will be the end of AIDS. I was skeptical – there were too many cases of drug resistance, non-adherence to treatment, supply chain failures to deliver vital drugs to remote or impoverished areas. I resented use of the word “vaccine” to describe universal treatment – we still desperately need an actual HIV vaccine, I insisted.

I want Joep’s optimism about eliminating AIDS through treatment to win out. I want to be wrong.

I just wish Joep was going to be around to see the great experiment play out.

A Tweeter asked me if the loss of Joep, Glenn, and other AIDS researchers and activists possibly on board MH17 would prove a major set-back in the fight against AIDS. No, I said. One of the glories of the AIDS community is that its bench is deep, its talents enormous, and its sorry history of processing grief and moving on is unparalleled. The dead, as has always been the case since this awful virus emerged in the late 1970s, will be mourned. And then energies will be mustered, to get the job done.

Until there is a cure.

Laurie Garrett is a senior fellow for Global Health at the Council on Foreign Relations. This essay also appeared on http://lauriegarrett.com/blog/.

TIME Australia

After MH17 Ukraine Crash, Global AIDS Researchers Mourn Lost Colleagues

The cause of HIV/AIDS research will be set back because of experts lost in the Malaysia Airlines Ukraine disaster

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[UPDATE: 7/18/14, 11:52 AM EDT]

There was a pall over the 20th annual International AIDS Conference in Melbourne even before the crash of Flight MH17 in eastern Ukraine, which killed an estimated 100 delegates who were en route to the meeting. [Update: Later reports suggest that the number of delegates lost is much lower.]

In the past couple of years the vibrant showcase event—part serious science, part activist networking and carnivalhas been headily optimistic, as HIV treatments improved and the possibility of a cure no longer seemed so far off. “The mood is always an important part,” says Professor Mike Toole, an international communicable diseases veteran with Melbourne’s Burnet Institute who has been at the HIV/AIDS front line since the pandemic began some 30 years ago.

Toole remembers that the landmark Durban International AIDS Conference back in 2000 demonstrated to this eclectic crowd—a disparate crew of laboratory researchers, front-line health workers, activists and people living with the infection—their powerful potential. It was in Durban that the commitment to deliver then-prohibitively expensive antiretroviral drugs to the world’s poorest populations ignited, and was carried through over the next few years by organizations like The Global Fund and the U.S. President’s Emergency Fund for Aids Relief.

The past two International Aids Society (IAS) meetings, in Vienna and Washington DC, have been buoyed by signals that a breakthrough was close, and the expectation was that the momentum would continue into Melbourne. Then, barely a week ago, came a serious blow. For over a year many members of the HIV/AIDS community had been pinning their hopes for a breakthrough on the so-called Mississippi baby, an HIV-positive infant that had apparently been cured through aggressive drug treatment soon after birth. But on July 10, news came, that the child was showing symptoms that the virus had returned.

Although there are other programs that indicate that it might be possible to eliminate HIV infection from a human body, the apparent relapse of the Mississippi baby “depressed people incredibly,” says Toole.

Then came yesterday’s tragedy. For Toole and others HIV/AIDS experts the crash summoned up ghosts. “It reminds me of the Swissair flight, New York to Geneva, when Jonathan Mann died,” he says. Mann then the founding director of the World Health Organization’s global AIDS program was killed with several other researchers, including his wife Mary-Lou Clements-Mann, en route to AIDS meetings when the plane crashed in Canada, September 3, 1998. “I lost five friends on that flight.”

In Sydney, at a pre-conference gathering on July 18, about 200 delegates spent the day closely monitoring Twitter and exchanging snippets of news, desperate for updates on who would and would not be joining them in Melbourne. The word there was that a substantial number of the 100-plus delegates reported to be on the downed aircraft were part of the global network of activists and people living with AIDS.

With only a handful of names of the deceased confirmed by Friday, it’s difficult to measure the overall impact on HIV/AIDS research and advocacy. But the loss of internationally renowned Dutch researcher Joep Lange—a former president of the IAS—would be a massive blow. “It will have a big psychological effect,” says Toole. “He was one of the leaders in the field.”

Another known casualty was Glenn Thomas, a British media officer working for WHO in Geneva. Thomas was to be part of a media launch on July 20 revealing new tools to reduce harm to users of intravenous drugs. He was also recognized as a particularly effective communicator on the links between HIV/AIDS and tuberculosis, says Toole. (The risk of developing TB is up to 20 times greater in people infected with HIV, and in 2012, of the 8.6 million new cases of TB diagnosed internationally, 1.1 million were among people with HIV.)“And the other hundred [on board]—we don’t know who they are, what it means.”

The annual AIS conferences are like no other medical gathering, says Professor Rob Moodie of the University of Melbourne, a former senior WHO official and longtime Australian public health specialist. “You have this incredible mixture of scientists and clinicians, public health people, civilian organizers, human rights activists, people who have the virus … who all have some sort of sense of ownership and collective leadership.”

The energy and collaborations of these gatherings have helped drive the huge advances achieved in understanding and responses to HIV/AIDS in a relatively short time. “We learned more about HIV in the first 10 years than we did in a century with other diseases,” says Moodie. The involvement of grassroots activist groups—as well as lab researchers—has been key to that success. MH17’s toll would not only be measured in the loss of medical expertise, but of advocacy, understanding and hard-won personal experience.

“There is a black cloud on this conference,” says Toole. “I don’t think there is anything that can retrieve that.”

Still, Toole was confident that delegates would be driven to achieve as much as they could in memory of their colleagues. He welcomed the move by the City of Melbourne on July 18 to cancel fireworks that had been scheduled to kick off the conference, but was disappointed that that’s night fixture in the Australian Football League competition—to which AIDS2014 delegates had been given tickets as part of the cultural program—did not pause for a minute of silence.

TIME Infectious Disease

WHO Says All Men Who Have Sex With Men Should Take Antiretroviral Drugs

A nurse takes blood for a free HIV test, during an HIV/AIDS awareness rally on World AIDS Day in San Salvador
A nurse takes blood for a free HIV test during an HIV/AIDS awareness rally on World AIDS Day in San Salvador on December 1, 2011. Luis Galdamez—Reuters

Warns of 'exploding epidemics' of HIV among gay men

The World Health Organization has suggested for the first time that all men who have sex with men should take antiretroviral medicine, warning that HIV infection rates among gay men are exploding around the world.

In guidelines published Friday, it said that it “strongly recommends men who have sex with men consider taking antiretroviral medicines as an additional method of preventing HIV infection.” Similar guidelines were issued by the U.S. in May.

Gottfried Hirnschall, the head of WHO’s HIV department, says that infection rates among homosexual men are increasing again 33 years after the epidemic hit, partially because the infection doesn’t hold as much fear to a younger generation with access to drugs that enable users to live with AIDS.

“We are seeing exploding epidemics,” Hirnschall told reporters in Geneva.

Although HIV infection rates did drop by a third between 2001 and 2012, Hirnschall characterized progress as “uneven.”

[AFP]

TIME Aids

Girl ‘Cured’ of HIV Has Relapsed

Dr. Hannah Gay, a pediatric HIV specialist at the University of Mississippi on March 3, 2013.
Dr. Hannah Gay, a pediatric HIV specialist at the University of Mississippi on March 3, 2013. Jay Ferchaud—University of Mississippi Medical Center/AP

"Certainly, this is a disappointing turn of events"

A 4-year-old girl believed to have been cured of HIV showed detectable levels of the virus, federal officials said Thursday in a blow to anti-HIV efforts.

The Mississippi girl had been off of antiretroviral therapy for more than two years, and doctors believed that she could serve as a model for eradicating HIV in babies born with the virus.

But on Thursday, the National Institute of Allergy and Infectious Diseases said that researchers had found detectable HIV levels in the girl this month.

“Certainly, this is a disappointing turn of events for this young child, the medical staff involved in the child’s care and the HIV/AIDS research community,” Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said in a statement.

The girl was born with HIV, and doctors administered anti-AIDS therapy nearly immediately after her birth and continued with the treatment for months. After the girl and her mother missed several treatment appointments, doctors found that the girl was still HIV-free — leading them to believe that the early treatment may have successfully eliminated the virus. Still, experts say they knew a relapse was a possibility.

Since HIV was detected in the girl this month, doctors have resumed treatment. But despite her relapse, researchers say her case still provides a valuable understanding of early HIV treatment.

“The case of the Mississippi child indicates that early antiretroviral treatment in this HIV-infected infant did not completely eliminate the reservoir of HIV-infected cells that was established upon infection but may have considerably limited its development and averted the need for antiretroviral medication over a considerable period,” Fauci said in a statement. “Now we must direct our attention to understanding why that is and determining whether the period of sustained remission in the absence of therapy can be prolonged even further.”

TIME Research

AIDS Research Team in Iowa Loses $1.38M Grant

Dong-Pyou Han
Former Iowa State University researcher Dong-Pyou Han leaves the federal courthouse in Des Moines, Iowa, Jul1 1, 2014. Charlie Neibergall—AP

(DES MOINES, Iowa) — An AIDS research team at Iowa State University will not get the final $1.38 million payment of a National Institutes of Health five-year grant after a team member admitted last year to faking research results, the NIH said Tuesday.

One of the members of the research team, Dong-Pyou Han, has pleaded not guilty in federal court to four counts of making false statements in research reports. He is free on bond awaiting trial scheduled for Sept. 2.

The research team, led by biomedical sciences professor Michael Cho, was awarded $6.8 million to be paid over five years by the NIH, but it won’t see the last payment. The team previously received grants totaling $7.6 million.

The university has agreed to repay the government $496,000 for Han’s salary and other costs tied to his employment at ISU during the research. Han may not apply for or receive grants from the U.S. government for three years, the NIH said, but Cho’s team and other researchers at ISU can.

“NIH makes funding decisions based on scientific merit of the proposed research to eligible organizations/institutions. The researchers are eligible to apply for future NIH grant funding through their institutions just as other researchers may apply,” the agency said in an emailed statement.

University spokesman John McCarroll said the team, which consists of 10 researchers, has sufficient funding to continue its work. McCarroll said experts at federal agencies have told him it can take two to five years to recover from the negative perceptions created by a misconduct incident.

He said Cho continues to be a respected researcher and people seem to understand he was not aware of faked lab work.

“This has received national and international attention and I know he has been somewhat embarrassed by that and he doesn’t want to go through that again,” McCarroll said. Cho did not immediately respond to messages for comment.

According to the indictment filed last month in U.S. District Court in Des Moines, Han’s misconduct dates to when he worked at Case Western Reserve University in Cleveland under Cho, who was leading a team testing an experimental HIV vaccine on rabbits.

Starting in 2008, Cho’s team received initial NIH funding. Cho reported soon that his vaccine was causing rabbits to develop antibodies to HIV, which was considered a major breakthrough in HIV/AIDS vaccine research by NIH officials and the research community.

Iowa State recruited Cho in 2009, and his team — including Han — soon received a five-year grant to continue the research. The team reported progress until a group of researchers at Harvard University found in January 2013 the promising results had been achieved with rabbit blood spiked with human antibodies.

An ISU investigation pinpointed Han leading him to write in a Sept. 30, 2013, confession letter that he started the fraud in 2009 “because he wanted (results) to look better” and that he acted alone.

“I was foolish, coward, and not frank,” he wrote.

Han, 57, a native of South Korea, has been allowed by the court to live in Ohio near his family and travel to Iowa for court appearances.

TIME

AIDS Scientist Pleads Not Guilty to Faking Study

DES MOINES, Iowa — A former Iowa State University scientist pleaded not guilty Tuesday to charges alleging that he falsified research for an AIDS vaccine to secure millions of dollars in federal funding.

Dong-Pyou Han, 57, entered his not guilty pleas to four counts of making false statements during his initial court appearance in Des Moines federal court. Each count carries a maximum sentence of five years in prison and a $250,000 fine.

Han was released on bond and his trial was scheduled for Sept. 2. Han and his attorney, Joe Herrold, declined to comment after the hearing.

Han, who was born in South Korea, was guided through the proceedings by an interpreter in California who attended the hearing by phone. The only time he addressed the court was to say “yes” when asked if he understood the charges.

The hearing was initially scheduled for last week, but Han was hospitalized after getting into a traffic accident in Ohio, where he has been living since resigning from Iowa State last fall. Magistrate Judge Celeste Bremer said Han has indicated he plans to move back to Iowa, where he’ll be under the jurisdiction of federal probation officers, and she thanked him for managing to make it to the rescheduled hearing.

“I’m sorry to hear about your car accident and I’m glad you’re out of the hospital,” she said.

According to prosecutors, Han wrote a letter to university officials before he resigned last fall in which he confessed that he had spiked samples of rabbit blood with human antibodies to make an experimental HIV vaccine appear to have great promise. Han told them he started the fraud in 2009 “because he wanted (results) to look better” and that he acted alone.

“I was foolish, coward, and not frank,” he allegedly wrote.

Han’s actions raised hopes of a breakthrough in the scientific community. But the alleged misconduct was uncovered last year after scientists at Harvard University discovered the spiked samples.

According to the indictment, Han’s misconduct caused colleagues to make false statements in a federal grant application and progress reports to NIH.

The NIH paid out $5 million under that grant as of last month. Iowa State has agreed to pay back NIH nearly $500,000 for the cost of Han’s salary.

Experts say it is extremely rare for criminal charges to be brought in cases of scientific fraud, but that Han’s alleged wrongdoing was extraordinary.

There have been only a handful of instances over the past 30 years in which criminal charges were brought in cases of alleged scientific fraud, Ivan Oransky, who co-founded of Retraction Watch, which tracks research misconduct, recently told The Associated Press.

Oransky said charges are rarely brought because the U.S. Office of Research Integrity, which investigates misconduct, doesn’t have prosecution authority, and most cases involve smaller amounts of money. However, he said Han’s case was “particularly brazen.”

 

TIME Health Care

Complaint Alleges Discrimination Against Those With HIV/AIDS by Insurers

Two health organizations claim that four insurance companies are violating the Affordable Care Act

The National Health Law Program and the AIDS Institute filed a complaint with federal health officials Thursday asserting that four insurance companies have structured their plans in a way that discourages people living with HIV or AIDS from choosing them. If the accusations are true, those insurance companies would be violating a civil rights section of the Affordable Care Act.

The two health organizations say the insurance companies, which offer plans in Florida through the federal online exchange, require that HIV and AIDS patients pay for a percentage of their drugs instead of a flat $10 co-pay. HIV and AIDS drugs can get expensive, so asking patients to pay 40% to 50% of the wholesale cost of their drug — thousands of dollars — becomes burdensome.

The two groups also allege that the plans require high up-front costs and too many prior authorizations. Federal health officials are reviewing the complaint.

TIME movies

Taylor Kitsch: Working on The Normal Heart Was “Gutting”

The actor discusses the making of the AIDS-crisis movie

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Taylor Kitsch was at home in Austin when his manager sent him the script for The Normal Heart, the Ryan Murphy-directed adaptation of the seminal Larry Kramer play about the early days of AIDS (airing on HBO on May 25). The story traces the early days of the leading AIDS-advocacy group GMHC in the days when the disease was widely misunderstood, through the fictionalized stories of its founders.

As Kitsch recalls, his manager said that whatever he was doing at the time was less important than reading the script. Most of the other primary characters had been cast, but by the time the actor got halfway through reading it, he knew that he wanted to fight for the role of the Bruce Niles, a banker who becomes an activist despite remaining in the closet.

“It was an opportunity to tell something that’s bigger than all of us and still needs to be told,” he says.

But getting the role didn’t mean the hard part was over. As he discusses in the video above, telling the heart-wrenching story of a group of friends facing a devastating crisis proved, not surprisingly, to be a taxing experience. Kitsch says that emotions were already heightened on set, but that one particular scene involving the difficulties his character has to go through to retrieve a body from a hospital was “gutting.”

“That was something that I wasn’t hoping we would do too many takes,” he says. “You try to do this in any scene, but this one more in particular than others, of just like, you don’t need to dramatize this stuff as an actor. You just be honest to what’s in front of you and what’s going on.”

TIME Aids

CDC Recommends Anti-HIV Pill for High-Risk Groups

Truvada AIDS Anti-HIV
Bottles of antiretroviral drug Truvada are shown at Jack's Pharmacy in San Anselmo, Calif. on Nov. 23, 2010. Justin Sullivan—Getty Images

The daily medication, sold in generic form as Truvada, could transform AIDS prevention in America. If taken regularly, the drug can reduce risk of infection in high-risk populations by up to 92%, the Centers for Disease Control and Prevention says

The U.S. government has recommended that hundreds of thousands of people at risk for AIDS take a daily drug that is effective in preventing the virus.

The Centers for Disease Control and Prevention issued an official recommendation Wednesday that people at high risk of contracting AIDS take a combination of two medicines called Pre-exposure prophylaxis (PrEP), which is known to help prevent infection of HIV, the virus that causes the deadly, incurable disease.

If taken regularly, the drug can reduce risk of infection in high-risk populations by up to 92%, the CDC says.

PreP comes in a generic version called Truvada and is used widely in AIDS treatment programs in poor countries. The CDC’s recommendation could, if followed widely, increase the number of people taking the drug in the U.S. from fewer than 10,000 to half a million, the New York Times reported.

The CDC recommends the drug, in combination with condom use, to gay men who have sex without using condoms, heterosexuals who sleep with intravenous drug users or bisexuals, and anyone who has sex with someone they know to be HIV-positive, as well as anyone who shares needles or injects drugs.

HIV rates have held stubbornly flat for the past decade, and a sharp decline in condom usage has raised concerns among health officials.

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