by Sonia Shah
Providing treatment for the subjects who did become infected in the trial was another sticking point. The VaxGen vaccine was unlikely to protect anyone from an infection, researchers knew, but it might slow the course of the disease. If they treated infected subjects with the lifesaving drugs, it might be difficult to tell if the vaccine had any such effect. Drug treatment could “make . . . it impossible to design a scientifically valid [vaccine] trial,” worried one Johns Hopkins vaccine researcher. It would also burden the vaccine trials with huge drug bills. “This is a monstrous responsibility,” sputtered another clinician. Wouldn’t it be unethical, anyway? If they did provide the drugs, then people—as yet uninfected with the virus—might sign up just to get the free treatment.57
A compromise solution was found in the design of the trial. In the U.S. arm, for every subject who received a placebo, two would receive the vaccine. They’d also get triple-drug therapy should they become infected with the virus. In Thailand, things would be different. There’d be one placebo given for every active shot. If subjects became infected, they’d get therapies, but not triple-drug therapy, just double-drug therapy. “It works,” said Lurie with disgust, “but not too good.”58
After the CDC’s placebo-controlled trials proved that short-course AZT cut HIV transmission nearly as well as the long course, pressure was stepped up on Jackson to drop the placebo group in his trial in Uganda, code-named HIVNET 012, as well. Now that researchers knew beyond a shadow of a doubt that even an affordable short course of AZT—around three weeks worth, given during pregnancy—would help, there could be no decent rationale to withhold the drug from any HIV-infected pregnant woman, CDC advisers told Jackson.
Jackson was aghast. Left with just one group of women taking nevirapine and another taking an even more abbreviated course of AZT—just a couple of pills during labor and delivery—Jackson worried that he might be left with uninterpretable results. “If they had turned out to be similar, we wouldn’t have known if neither of them worked or both of them worked,” he recalls. Such inconclusive results, while surely suggestive, would be less likely to find their way into a top-tier journal. Journal editors frown upon fuzzy results, and Jackson knew it. “At the time, I tell you, it was like, this is crazy!” he says. “If we drop this placebo, chances are we won’t be able to say anything!” He had received a very large grant to look at an interesting question and had jumped through many administrative hoops in order to get his study started. To then not be able to publish any papers would clearly have been disastrous. Plus, his earlier argument, that withholding the best methods was permissible since the women wouldn’t have gotten better care anyway, still held, he said in 2003. “They said, well, the short course is effective and everybody should just implement it. Well, here we are six years later and nobody is getting it! And we knew that! People knew afterwards that this was wishful thinking. We knew that the standard of care would still be nothing for years to come.”59
But in the end, the aborted placebo arm in Jackson’s trial didn’t disrupt the study. In September 1999, Jackson and his team published results from HIVNET 012. The nevirapine had worked even better than the ultra–short course of AZT they had administered—and was easier and cheaper. Of the placebo babies born before the placebo group was dropped 36 percent contracted HIV, as did 20 percent of the babies who got the ultra-short course of AZT. Of the nevirapine babies, only 7 percent came down with HIV.
The public response was tremendous. In Uganda the results were announced by the Ugandan minister of health; in the United States, Vice President Al Gore did the honors. “It was a big deal, one of the highlights of my career,” Jackson remembers. “It was high risk, but it was also high return. For me, it’s personally been very satisfying. . . . We struck gold with nevirapine.”60 Within a few years Jackson would single-handedly command one of the biggest medical research budgets available to any investigator in the world: nearly $30 million in federal and private grants for AIDS research.61
While Jackson basked in the glory of his results, Lallemant’s active-controlled trial was still enrolling patients. Although conceived in 1994, Lallemant’s trial didn’t commence until 1997. The Harvard researcher had spent over a year convincing skeptical NIH advisers that he didn’t need a placebo group.62
And now hundreds of thousands of babies could be saved with cheap, easy, single doses of nevirapine. Jackson had a suggestion to make it even easier, which he and his team outlined in a paper accompanying his results. Why not just give a nevirapine pill to every pregnant woman in countries where HIV ran rampant? It would be easier and cheaper than testing and counseling each one to figure out which ones had the virus. It wasn’t as if the women really wanted to know whether they had the virus or not, since antiretroviral treatment was still prohibitively expensive anyway. This way, even if the mothers dropped dead, clueless as to what killed them, their babies might survive. Critics wondered whether such universal drug dosing would suck up vital foreign exchange in poor countries while dismantling vitally important counseling and testing programs that supported Ugandan families of HIV-positive women—the people who would likely care for the women’s orphaned children—in a myriad of other ways. Jackson responded with a popular refrain, which he’d repeat in papers and interviews on the subject: “don’t make the best the enemy of the good.”63
Charity groups quickly started distributing nevirapine in their clinics in poor countries. But strangely, some of the worst-hit countries in the world remained stubbornly resistant to the drug’s wonders.
6
South Africa: Drug Trials and
AIDS Denialism
Most Americans’ lives are so intertwined with the ministrations of Western medicines from childbirth to daily aspirin that belief in its healing prowess is nearly an article of faith. But this isn’t so in most of the rest of the world. About 80 percent of people living in developing countries—together comprising 64 percent of the total world population—rely on traditional healers, not Western biomedicine, according to University of California pharmacologist Mannfred Hollinger.1 And in parts of the world where Western medicine’s foothold is flimsy at best, shoddy clinical trials can fuel a corrosive mistrust that undermines allopathic medicine more generally, with potentially devastating results.
Nowhere has this phenomenon been more apparent than in South Africa, where periodic controversies over flimsy subject protections in clinical trials ignited a volatile mix of racial resentments and mistrust accumulated over nearly fifty years of apartheid.
Between 1948 and 1994 the white minority in South Africa, descendants of Dutch, German, and French immigrants, doled out rights and privileges according to a schizoid system of racial apartness, “apartheid” in Afrikaans, the Dutch-like language they originated.2 When AIDS first emerged in the mid-1980s white conservatives in the country rejoiced openly. “If AIDS stops black population growth,” one said, “it would be like Father Christmas.”3
Apartheid had already started a slow genocide among black Africans in the country. Between 1960 and 1983 South African police had forcibly relocated over three million nonwhite South Africans from their homes into racially segregated “townships” and “homelands,” isolating them from the rest of society. While the government devoted 97 percent of its health care budget to high-tech specialized care, culminating in a revolutionary heart transplant in Cape Town’s Groote Schur Hospital in 1967,4 blacks were suffering forty-eight times more typhoid fever than whites and their children were dying from easily preventable diseases such as measles. In the townships tens of thousands of people might share a single water spigot. Conditions such as kwashiorkor, a severe form of malnutrition, raged, but the health department failed to take even minimal control measures. Black patients died waiting for ambulances to pick them up, while those reserved for whites idled nearby; those who survived the wait sometimes perished outside empty white hospitals that refused to let them enter.5
Notwithstanding notable exceptions, the mostly w
hite South African medical establishment complied with apartheid’s strictures. Some medical researchers openly studied the supposed inferiority of blacks and new bacteria that might selectively injure or kill them. The South African Medical and Dental Council extolled the physician’s right to “decide to whom he or she wanted to render a service in non-emergency situations.” Doctors worked for the security police, witnessing whippings and other torture, and signed off on fraudulent reports that those who succumbed were victims of accidents or suicides.6
When the apartheid regime finally fell to the African National Congress (ANC) in 1994, the problem of AIDS remained off the official agenda. ANC loyalists suspected that racist Western researchers had exaggerated the problem. Back in the 1980s NIH researchers had in fact circulated grossly inflated reports of HIV infections in African countries—Robert Gallo had reported that two-thirds of schoolchildren in Uganda were infected; National Cancer Institute researcher Robert Biggar, that between a quarter and one-half of the Kenyan population hosted the virus7—based entirely on faulty assays.8 Hasty conclusions about HIV originating in Haiti had crippled that impoverished nation’s tourism industry.9
When Kenyan leader Daniel arap Moi condemned AIDS as nothing more than some “new form of hate campaign” against African economies,10 many ANC supporters agreed. “It seemed far-fetched that a disease would conveniently kill fags, prostitutes, drug users and blacks,” recalls one South African ANC loyalist. “It was a Reaganite wet dream!”11
The comforting illusion that AIDS was an overhyped nonproblem wouldn’t remain intact for long. By the mid-1990s the virus’s rampage on the continent had become all too clear. But the Western AIDS establishment once again appeared unhinged from African realities. Many now proclaimed that Africans were too backward for combination antiretroviral therapy, suggesting a vicious indifference to the plight of impoverished Africans.
The insinuation that Africans couldn’t be trusted with antiretroviral drugs outraged South African nationalists such as shaggy-haired activist physician Costa Gazi. Gazi had spent two years in prison during apartheid, and says he feels the same way about the fight against AIDS as he did the struggle to end apartheid. “Diabetics living in rural areas get tested once a month; we don’t say let’s not treat them!” Gazi says.12
When at last in 1997 South African legislators amended the country’s Medicines Act to allow the health minister to make HIV medicines affordable by breaking patents and buying cheap generics, Western interests appeared once again committed to blocking Africans from accessing the lifesaving meds. Though the measure only applied during health emergencies or when patented medicines were unaffordable, thirty-nine major drug companies marched into court to prevent the law’s implementation. “The law is arbitrary and gives the health minister too many powers,” Mirryena Deeb of the trade group Pharmaceutical Research and Manufacturers of America (PhRMA) complained. “The minister can make a decision that a drug is too expensive and the drug companies have no right to defend themselves.” The Clinton administration promptly placed South Africa on its “watch list” of patent pirates.13
With earlier suspicions about the Western medical establishment thus reinforced, ANC officials set about finding an African solution to the problem. In 1997, Thabo Mbeki, then a prominent ANC official, believed he had found one such solution in a drug called Virodene. Virodene was cheap and, according to its University of Pretoria developers, remarkably effective against AIDS. The South African Press Association accepted the developers’ claims as they were presented to President Mandela’s cabinet. “South African researchers find a cure for AIDS for fifty rand a month,” local headlines blared.14
Within days the fact that data supporting Virodene had not undergone standard peer review and stemmed from a single trial involving twelve people emerged, and apartheid’s ruling party, the National Party, was calling for the ANC health minister to be sacked for supporting the drug. By April 1998, German researchers established that Virodene was an industrial solvent that caused severe liver damage and had no effectiveness against AIDS.15 When the mostly white media and white medical establishment lambasted Mbeki for his error, ANC supporters took it as an affront. “If they had their way, we would all die of AIDS,” the health minister muttered.16
It may not have bothered Mbeki that Virodene had been rejected by drug regulatory officials in the country, because as he would later expound, such officials along with much of the rest of South Africa’s medical establishment were still dangerously biased against Africans. The South African Medical and Dental Council had retained most of their senior staff from the years of apartheid. The council hadn’t investigated reports of medical negligence, fraud, or human rights violations committed by doctors under apartheid. According to a scathing report by Physicians for Human Rights, the “vast majority” of South African doctors accused of abusing patients during the apartheid era still practiced medicine, in some cases holding top positions in the government, universities, and other institutions.17
By the time Mbeki took the helm of the South African government in 1999, his antipathy toward the Western AIDS establishment had gone rigid. According to Mbeki, received truths from Western AIDS experts were a mix of lies and half truths. The idea, promoted by Western AIDS researchers, that HIV came from Africa was “wild and insulting,” he said. They claimed that the disease could only be tamed by expensive, Western-made antiretroviral drugs, despite what he called a “large volume of scientific literature” that deemed the drugs “a danger to health.” In fact, according to Mbeki, HIV was harmless and the condition called AIDS was simply a new name for malnutrition and other diseases of poverty. By then, about one-quarter of all pregnant women in South Africa appeared to be carrying the virus, according to annual antenatal surveys, but the government refused to pick up the tab for any antiretroviral drugs to treat the women or prevent the virus from infecting their infants.18
In desperation, physicians like Gazi had taken to smuggling in bags of nevirapine pills from the United States to provide to their pregnant HIV-positive patients. Mining companies such as Anglo-American, realizing that they could lose nearly one-fifth of their miners to the disease, offered to provide antiretroviral combination therapy to their employees. But the overwhelming majority of AIDS sufferers in the country went untreated, and the virus continued its passage from mother to child unimpeded. By 2003, South Africa was home to the greatest number of HIV infected people on earth. Most had never swallowed a single antiretroviral pill, a decade after the approval of AZT and years after combination antiretroviral therapy had transformed the disease in the West.19
These demographics did not go unnoticed by drugmakers and CROs casting about for new test subjects to service the $5 billion AIDS-drug market, one projected to mushroom to nearly $15 billion by 2007.20 CROs flocked to the country to conduct trials on untreated South Africans, and cash-starved medical facilities welcomed them with open arms. At institutions like the University of Stellenbosch drug companies would soon be proposing over sixty new trials every year.21
Industry researchers struggled to discern the effect of their new drugs in Western patients who already had dozens of other meds coursing through their veins. “You want relatively clean patients, with no other disease states and no other treatment,” explained Simon Yaxley of MDS Pharma, a company that recruits experimental subjects in Eastern Europe, South Africa, Latin America, and China for multinational drug companies. “Then you can say relatively clearly that whatever happens to that patient is from the drug.” For testing new AIDS drugs, he said, “South Africa is a great country. . . . There are a lot of individuals [with AIDS] who are not treated.”22 Indeed, echoed a PhRMA spokesperson, “treament-naive patients”—those who have never been exposed to any drug treatments—are “a very important group.”23
For former Genentech marketing executive Richard Hollis experimental access to South Africa’s med-deprived masses would prove crucial. A squat, richly suited man with closely croppe
d hair, Hollis had left Genentech to “create a new Eden on earth,” by selling miracle cures through his new start-up drug company, Hollis-Eden.24 In 1994, Hollis had acquired rights to a steroidal hormone that he hoped might help prevent the onset of AIDS in HIV-infected people. The trouble was that his scientists could only measure the drug’s effects in HIV-infected people if they weren’t already taking antiretroviral drugs. Powerful antiretroviral therapy would mask the weak effects of the humble steroid as an espresso would a cup of chamomile tea.
The drug, Immunitin, could nevertheless be worthwhile, Hollis said. “If we’re correct in our approach, we could potentially help more than 1 billion people,” he proclaimed. After all, “you can’t go to third-world countries with $10,000 therapies,” he said. “You have to produce drugs that are inexpensive to manufacture and easy to administer.”25
In 1998, the CRO Quintiles helped the company arrange a short, three-month trial of Immunitin on forty untreated HIV-positive patients in South Africa. According to the disgruntled local press, “the firm want[ed] to avoid the expense of satisfying US regulators until SA guinea pigs have proved that the investment is worthwhile.”26 (Six months later the company did start a trial of the drug in American patients but there the FDA insisted that the company only enroll patients whose antiretroviral drugs had stopped working.27)
When the results of the 1998 trial turned out to be inconclusive, investors started getting snappish about the company’s ability to get a drug on the market. “They may have the greatest thing since chopped liver, but no one is biting,” one wrote in 2000. “Investors aren’t quite sure what is going on, if anything is going on.”28 The company quickly slapped defamation suits on one of its critical stockholders29 and launched a longer, more rigorous trial of Immunitin. This time, they’d test Immunitin in much sicker untreated AIDS patients.30 Twenty-five South Africans dying of AIDS—their CD4 cell counts numbered less than fifty, well below the two-hundred-count level considered dangerous—were duly enrolled. None were given antiretroviral drugs. Half were given Immunitin in the hope that it would protect them from opportunistic infections. The other half were given a placebo. Hollis-Eden tracked their deterioration for over a year. Eight months into the study, Richard Hollis donned an African-style tunic to have his picture snapped with Nelson Mandela.31
