A Seattle Times reporter and photojournalist traveled to South Africa to show you how Seattle scientists are working with residents of the country’s poorest townships. The goal: an HIV vaccine.

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CAPE TOWN, South Africa — Andile Madondile set out from his home in Cape Town’s biggest township to give a presentation to his neighbors on HIV.

He had only a few yards to cross — from the two-room shack he shares with his wife and three kids, past the “spaza” shop where he buys cigarettes for 13 cents apiece, to a slightly bigger shack that serves as a home, tavern, video arcade and meeting room — but he also had worlds to bridge.

Advanced education is as rare in this part of Khayelitsha as indoor plumbing (Madondile himself relies on a streetside water tap and toilet stall a five-minute walk from his home), yet his talk was unabashedly scientific. To describe how HIV drugs work, he projected slides with terms like “reverse transcriptase enzyme” onto battered pink wallboard.

Then, the 38-year-old educator with South Africa’s largest HIV activist group, the Treatment Action Campaign, ventured into new territory: a clinical trial that needs 1,500 women across southern and east Africa.

“Antibody mediated prevention study.” Madondile enunciated the words in English, before resuming his talk in Xhosa. “This is an idea of giving people antibodies to see if it can protect them from getting HIV.”

In South Africa, the global epicenter of HIV/AIDS, with roughly 6.5 million people infected, Madondile encouraged his neighbors to sign up — even as he anticipated their concerns. “Number one,” he said, “developed countries wanting to make us guinea pigs.”

It’s that deep-seated fear that Seattle scientists and their South African partners must confront as they work together in an international network of clinics headquartered at the Fred Hutchinson Cancer Research Center on two major HIV trials in Africa.

“It’s like the big secret of Fred Hutchinson,” said Jim Maynard, director of communications and community engagement for the HIV Vaccine Trials Network, known as HVTN. Most people think about cancer when they think about the famed Seattle institution. But since 2000, when the National Institutes of Health formed the network, Fred Hutch has been leading a quest to develop an HIV vaccine — a possible end goal of the antibody study.

What that means, Maynard said, is, “If a vaccine gets approved, it will come out of Seattle.” And HIV wouldn’t just be treated, it could be virtually wiped out, like polio.

It’s a big “if.” The past 16 years have seen repeated failure, including the worst-case scenario: One test vaccine appeared to cause a higher incidence of HIV.

The picture changed, however, with a promising trial in Thailand. The network led by Fred Hutch is now trying to build on that breakthrough by conducting trials in the part of the world most devastated by HIV; in South Africa, the virus has spread to nearly a fifth of 15- to 49-year-olds.

The quest for a vaccine

From the series:

But scientific research in Africa carries challenges. An important one: overcoming skepticism, mistrust and cultural barriers that arise when a powerful and rich Western institution comes to the developing world and asks people to put foreign substances into their bodies.

To do that, Fred Hutch can’t “parachute in and say, ‘Hi, we need 4,000 people,’ ” Maynard said.

Instead, it must build relationships, put itself into the hands of African educators and recruiters such as Madondile — some of the “real heroes” of vaccine research, according to Maynard — who fan out across often impoverished and sometimes dangerous neighborhoods to give out information, allay fears and invite participation.

Around the time Madondile was giving his presentation in Khayelitsha (pronounced Kye-yuh-LEETCH-uh), on South Africa’s west coast, community educators 900 miles to the northeast were weaving their way along Soweto’s dirt roads, preparing for a gathering that would juxtapose traditional healers with Western science, sex education with religiosity.

The network needs every tool it can get because its undertaking this year is enormous.

First, along with another research network based in North Carolina, it is launching the antibody study, also known as AMP. That study tests a novel concept: infusing antibodies — proteins in the body that recognize and fight foreign substances like viruses — directly through an IV drip instead of using a vaccine to stimulate them.

The study is taking take place in Botswana, Kenya, Malawi, Mozambique, Tanzania and Zimbabwe, in addition to South Africa. A parallel study is going on in North and South America.

In November, the Seattle-based network is expected to start a traditional vaccine trial exclusively in South Africa. The first large trial in seven years, and one of only a handful ever, is seeking 5,400 participants.

For all the studies combined, nearly 10,000 people are needed.

“Sometimes I wake up in a sweat and think, ‘Oh my God, how are we ever going to accomplish this?’ ” Dr. Glenda Gray said in her Cape Town office. Gray is the government-appointed president of the South African Medical Research Council and one of the few principal investigators of HVTN outside Seattle.

Although Fred Hutch has built a state-of-the-art lab in Cape Town to streamline some of the work, the logistics are complicated, including using rural clinics never before involved in research.

“And we only have one shot,” Gray added, referring to $130 million going into the vaccine trial, not to be raised again any time soon. The antibody studies will cost an additional $144 million.

And yet, she and her colleagues express excitement at this opportune moment in HIV research. Gray calls it a “golden age.”

Advances in prevention and treatment are in sight, many of them sure to be discussed at the 21st International AIDS Conference, beginning Monday in the South African city of Durban.

In carrying out much of its work in South Africa, the Hutch-led network picked a place that in an astonishingly short time has transformed its approach to HIV. It happened in a country of cultural and socioeconomic contrasts, still grappling with its history of apartheid, a bitter legacy that shaped attitudes toward white doctors and their medicine.

“Like being in a war”

Madondile was diagnosed with HIV in 2004. Twenty-six at the time, he was weak, thin from a loss of appetite, and suffering from diarrhea, shingles and headaches.

“I thought I was going to die.”

In fact, he tried to hang himself, and was  saved only after his young daughter found him and alerted others.

HIV drugs known as antiretrovirals were available, but Madondile didn’t want them. “They are very dangerous, that’s what people said.”

That view came from the top. Then-President Thabo Mbeki, who succeeded Nelson Mandela in 1999, had come under the sway of a group of self-proclaimed “AIDS dissidents” who questioned the link between HIV and AIDS and considered antiretrovirals the toxic products of money-hungry pharmaceutical companies from the West.

While the government dragged its feet, hundreds of thousands died.

“It was like being in a war,” said Mark Heywood, co-founder of the Treatment Action Campaign.

“There were traffic jams in the cemetery and people would be crying at the wrong grave,” said Gail Johnson, founder of Nkosi’s Haven, a Johannesburg home for HIV-positive mothers, their children and AIDS orphans.

Activists, schooled in protest activism by the anti-apartheid movement, demanded the government distribute antiretrovirals.

They faced harsh criticism from some of the country’s new black leaders.

“What’s this white man’s agenda?” they asked of Heywood.

Gray remembers that as a white pediatrician in Johannesburg’s Soweto township, she was called a “killer of black women” because she gave them antiretrovirals to prevent transmission of HIV in childbirth.

“It was a scary time,” she said, for those perceived as “anti-state.”

They persevered and, aided by court rulings and Indian-made generics, got the government to roll out an antiretroviral program.

Some feared it would never catch on. In 2005, South African journalist and anthropologist Jonny Steinberg started researching a book that focused on a young, rural man’s agonized reluctance to test for HIV.

“Sizwe’s Test” fell in line with a common view of Africans as distrustful of white-led health campaigns and research.

South Africa had its own painful history that fostered distrust. In Truth and Reconciliation Commission hearings held after Mandela came to power, former government officials testified about research into biological agents, including a vaccine for sterilizing blacks.

As Steinberg wrote in a revisionist paper, antiretrovirals did catch on. What he had failed to see earlier, he admitted, was that South Africans were quietly taking note of the drugs’ remarkable effect.

Madondile turned to antiretrovirals as a last resort, when his immune system was nearly nonexistent and a pilgrimage to a Malawian sangoma, or traditional healer, proved futile.

“It took me about four months to get better,” he said — so much better that he married his HIV-negative girlfriend. They already had one child together and now have two more, all free of infection.

Madondile speaks of himself as a “changed man,” and he’s not just referring to his health.

“I used to take alcohol and beat my partner,” he said. No more. He went back to school, enrolling in an online program to become a pharmacist’s assistant. Now a supporter of the radical  Economic Freedom Fighters, he’s running to become a local ward councilor.

Wearing sunglasses and a black leather jacket on a recent day in the Khayelitsha office of the Treatment Action Campaign, Madondile showed no outward signs of having HIV.

Yet, he said, “I’m living with HIV openly.” In a country where an HIV-positive activist was once stoned to death for advocating that people be open about their status, that’s revolutionary.

Not every HIV-positive person changed as much as Madondile. But all across South Africa, the near-dead came back to life. HIV — and ARVs, as antiretrovirals are known in even the remotest villages — became normalized.

Witness a scene at Khayelitsha’s Zola Business High School. As a Treatment Action Campaign educator talked and handed out flavored condoms in the front of the classroom one afternoon, teens lined up to test for HIV in the back. Most would get their results right away, in class, surrounded by their peers.

South Africa’s President Jacob Zuma has serious problems, chief among them corruption allegations and economic instability. But his government is now a leader when it comes to HIV. In a May speech to Parliament, Health Minister Aaron Motsoaledi, a doctor, trumpeted the “world’s biggest” testing and antiretroviral program and announced new initiatives, including the distribution of prophylactic ARVs among sex workers.

His enthusiasm carries over into research. In an interview, he called the antibody and vaccine trials “very significant.” In less than a decade, the country’s treatment program brought life expectancy, which had dropped to 53, back up to over 60. He is aiming for 70.

Like many advocating a vaccine, Motsoaledi holds out hope of an “AIDS-free generation.” South Africa is nowhere close.

Young women — in many cases, tired of hearing about AIDS, careless or bullied when it comes to condoms and preyed upon by sugar daddies, also known as “blessers” — are particularly vulnerable. A few years ago, a government survey found that more than 17 percent of women ages 20 to 24 had HIV, while the infection rate for men in that age group was 5 percent. Among 15- to 19-year-olds, girls were eight times more likely to be infected than boys.

“We need a game changer,” Motsoaledi said.

Still, he said, “I am anxious that this time around we get it right.” There’s been so much disappointment, from the vaccine and other past HIV trials, that the public has grown weary of hearing about them, according to the health minister.

And there’s a chance the new trials will come up short again, acknowledged Dr. Linda-Gail Bekker, deputy director of HVTN-affiliated Desmond Tutu HIV Centre in Cape Town. Results won’t be known for about five years.

Yet scientists have no choice but to carry on. Thirty years into the AIDS crisis, she said, it still constitutes an emergency.

“They think there’s hope”

One late May morning, Puleng Nkase was feeling stressed. A star recruiter for trials run out of an HVTN-affiliated clinic in Soweto’s massive Chris Hani Baragwanath Hospital, she was expecting a woman interested in volunteering for the antibody study to show up for screening.

If the woman passed the criteria, including HIV-negative status, she would become only the second person in all of Africa to sit for an antibody infusion. The first had done so the week before, getting her drip in a giant easy chair and a room freshly painted sky blue, to help participants feel at ease as they undergo the 30- to 60-minute procedure 10 times over two years.

But on this morning, the woman who promised to come, didn’t. So Nkase, a 41-year-old Soweto resident, hit the phone and found someone else. She has been recruiting for the antibody study for several months, accumulating around 100 names of possible participants.

Many won’t show up or won’t pass the screening. To get the 100 people her clinic is supposed to deliver, Nkase figured she needed another 100 names.

A couple hours later, she stood in Freedom Park, one of Soweto’s poorest neighborhoods, underneath a marquee bearing the initials of her clinic, PHRU, short for Perinatal HIV Research Unit. (Co-founded by Glenda Gray to research ways of preventing HIV transmission in childbirth, it kept its name even as its focus expanded.)

“Does anyone know what a vaccine is?” Nkase asked, speaking in Zulu. A couple dozen young people, drawn from a computer-skills class at the site, sat before her.

“It’s an injection,” said one woman. Another mentioned vaccines given to children.

Nkase could work with that. She ticked off well-known children’s vaccines — polio, measles — and offered prizes to the speakers in the audience: flavored condoms. Giggles ensued.

Nkase proceeded to explain how researchers would soon be testing an HIV vaccine. “To be a participant is voluntary,” she stressed. “No one is forced. You have a right to stop at any time.”

She leavened the mood with an ice breaker: Holding up a plastic penis, she asked for volunteers to demonstrate how to put on a condom. More laughter. More prizes of condoms, both male and female.

Then Nkase brought up the antibody study.

“I’m ready to sign up whoever wants,” she said.

The young people went quiet. None stepped forward.

“I would love to be involved but I’m just scared of needles,” Lindokuhle Nkonyane, a 20-year-old whose brother died of AIDS, explained afterward.

Nkase knows that’s a barrier. And there are others, she said over lunch at a steak and ribs place in Soweto’s Maponya Mall. “People are afraid of being injected with something they don’t know.”

They also worry the blood they would have to give for lab tests will never be replaced, weakening them. Some, she said, believe Americans have tasked local researchers with collecting blood to sell it.

Fred Hutch’s name is not mentioned in recruiting. Most on the receiving end would not know that Fred Hutch built a lab in Cape Town. Nor would they realize that Jim Maynard had flown to Cape Town twice in the last six months or that you can sometimes find South Africans at the Hutch in Seattle. (“Beautiful but I didn’t like the food,” said PHRU community-advisory-board member Thembeka Cynthia Maduna.)

But in an age of HIV funding in Africa from the President’s Emergency Plan for AIDS Relief and the Bill & Melinda Gates Foundation, a vague sense of U.S. involvement hangs in the background.

At the same time, Nkase reckons her job is made easier by the mass acceptance of antiretrovirals and the increased openness with which people talk about HIV. “They think there’s hope,” she said.

The next morning, she and her team were back in Freedom Park, making their way through clusters of small brick homes and shacks and speaking in Zulu, Tsonga and Sotho.

In a living room packed with two armchairs, two love seats and a flat-screen TV, Nkase told 63-year-old Zodwa Witness Mchunu about an HIV Vaccine Awareness Day event that would publicize the new HIV research. “I hope God can help us and we have a breakthrough with this vaccine,” Mchunu said.

To a young man peering over a fence, Nkase teased: “I’ve seen your face. If you don’t come tomorrow, I’ll drag you from the house.”

Two major HIV trials

Antibody mediated prevention studies (AMP)

What it’s doing: Infusing an HIV-fighting antibody through an IV drip.

Where it’s happening: One study is in South Africa, Botswana, Kenya, Malawi, Mozambique, Tanzania and Zimbabwe.

The other is in the U.S., Brazil and Peru.

Who’s involved: The trials are funded by the U.S. National Institute of Allergy and Infectious Diseases and run by the Fred Hutch-led HIV Vaccine Trials Network and the Durham, N.C.-based HIV Prevention Trials Network.

Who’s eligible: 1,500 HIV-negative women in Africa; in North and South America, 2,700 HIV-negative men and transgender people who have sex with men.

When did it start: This spring.

Pro: Unlike vaccines tested so far, the antibody resists the overwhelming majority of HIV strains around the world.

Con: Lengthy and repeated infusions are not practical.

Vaccine trial

What it’s doing: Injecting a vaccine developed after a promising trial in Thailand.

Where it’s happening: South Africa.

Who’s involved: The HIV Vaccine Trials Network, headquartered at Fred Hutch. Partners include the Bill & Melinda Gates Foundation, the National Institute of Allergy and Infectious Diseases and the South African Medical Research Council.

Who’s eligible: 5,400 HIV-negative men and women.

When does it start: November.

Pro: Practicality.

Con: This exact vaccine will likely not work in other parts of the world.

She worked the neighborhood like a politician, alternately admiring babies, a mat of drying corn kernels and an aspiring artist’s portfolio.

The following day, after the roosters had finished their early-morning wanderings, the garbage collectors had emptied bins but left mounds of litter untouched, and the honking from rush-hour minivan taxis had subsided, the event got under way on the grounds of a neighborhood nonprofit.

“Viva, vaccine, viva!” someone chanted, calling to mind old anti-apartheid rallies.

Even more, the event resembled a religious revival with ritual, hymns and sermons.

Traditional healers danced around a candle and burning incense.

“Through the use of condoms, I can conquer anything,” people sang in Zulu, waving previously distributed condoms in the air.

“Remember where we came from — from beetroot?” said the emcee, Busi Buthelezi, another member of the PHRU community advisory board. She was referring to statements by Mbeki’s health minister that beetroot, garlic and lemon — rather than antiretrovirals — could stop the progression of HIV.

“Hello! Where are we now?” Buthelezi continued. “There is a light. Remember I told you. Something exciting is coming.”

Coming Monday: More about the long road to an HIV vaccine in this two-part series