No Time to Lose: A Life in Pursuit of Deadly Viruses (22 page)

This model is very much true in Asia and most other countries, although less, perhaps, in southern Africa, where because of the very high prevalence of HIV today, if you have sex for the first time at age eighteen there may be a 20 to 30 percent chance that your first partner is already HIV positive. In any case, in India overall prevalence has gone down through this work by the private sector working hand in hand with government action, reaching the prostitutes who are most difficult to engage with. It’s a remarkable sight to see these ex-McKinsey men and women with MBAs squatting in the slums, talking to women who are among the lowest members of society. Most of the women don’t even have a birth certificate, thus no identity. One of Avahan’s first efforts is to make sure the women have a national tax card, a form of ID that allows them to open a bank account, and know how to use their mobile phones to transfer money into that account and send it to their family, where it’s more difficult for their pimps or steady partners to lay their hands on it.

No well-written consultant’s report or scientific article can capture the complex realities of both the lives of, say, sex workers in India and of the challenges of real-life AIDS programs, where the devil is in the details. Even now, whenever I visit a country or program, I make it a point to sit down with people on the front lines of HIV prevention and treatment, and with those we work with and for: be it sex workers, truckers, orphans, women in sweatshops, construction workers, various people living with HIV, drug users, homosexual men. In 2011 I spent half a day talking to sex workers in Mumbai—there wasn’t much work for them that afternoon because India and Pakistan were playing a historic cricket match—and I asked, “What has this program done for you?” One woman responded very succinctly: “I am a person now.” Not only could she manage her own money, but she was also in an organized group, so that if a client, or a group of policemen, beat her up she could call on other women for help. She could also be much more easily reached with HIV prevention messages.

Finally, because the vast majority of patients in India go to the private sector for medical care, and there is an enormous number of unlicensed practitioners of medicine, we decided to do a small study of what that meant in terms of current treatment for sexually transmitted disease, using dummy patients. We sent patients to doctors, claiming they had various manifestations of sexually transmitted disease, to see whether the physicians actually examined them and what they prescribed. Many physicians, it turned out, didn’t even ask the men to drop their pants to look at their symptoms; and they often prescribed something completely useless. We added providing professional education to our list.

We needed a practical strategy. I recalled the work of Maurice Piot (no relation), whose work I had encountered in medical school. Working at WHO in the 1960s, Piot had analyzed the tuberculosis treatment protocol and uncovered its shortcomings. Although his results were published, his systematic process had been long ago forgotten. For our purposes, let’s say 100 people have syphilis, and the first sign of that is a genital ulcer. Now assume 80 percent of people with a genital ulcer go to see a doctor. Maybe 80 percent of doctors, in such cases, prescribe a syphilis test. Then 80 percent of the patients do the test, pick up the result, go for a follow-up visit, and receive a prescription for treatment. Of those, 80 percent receive a prescription for the correct treatment, and 80 percent of those apply the treatment correctly, and are cured. We’re already down to 32 people, and we’ve been working with some very conservative approximations. We needed to do better.

Classically, WHO would have concentrated on that final stage: writing treatment guidelines for selection of the correct antibiotic and the proper application of treatment. But there’s a whole chain of events involved, including health-seeking behavior and adequate training for medical staff, which was being completely neglected. And the outcome of that neglect on the community is high transmission of disease, and, in the case of gonnorrhea or chlamydial infection the outcome for the individual may be sterility, lifelong pain, or even death.

So when I got to Geneva I unearthed this old model and tried to apply its lessons in Africa and in Brazil. We set up research projects and developed and evaluated guidelines for detecting and treating sexually transmitted disease in resource-poor environments, doing it very systematically, just as I had in Swaziland, but now for all sexually transmitted diseases. These became official WHO policy, and you still see these posters of flow charts on the wall in primary health-care clinics around the world. So in a way, just in doing that one thing, we influenced the world and the way that millions of people are cared for. The reality is that 90 percent of STDs can be treated by a semiskilled nurse or midwife, and this frees up specialist physicians for more complex cases while ensuring the care is properly delivered. It is not particularly romantic or adventurous work, but setting up policies and norms can have huge impact on people.

Next, I went to Zimbabwe to take a look at another high-risk setting for sexually transmitted disease, in so-called high-density urban areas. In 1993 Zimbabwe had the highest HIV prevalence in the world, with nearly 30 percent of pregnant women being HIV positive. In colonial times, every township was built around an administrative center, with a school, a health center, and a beer hall. The beer hall was owned by the municipality and was a main source of income for the town. Just by talking to people it became obvious that the beer halls were the center for sex. They had two sections, serving Western or traditional beer. Traditional beer was served in plastic buckets, with various sizes measured in gallons. Several people shared a bucket, and when they got drunk enough they went off and had sex, some of it paid for.

My idea was that it just wasn’t good enough to wait for people to appear at the health center with incredible abdominal pain, in the case of women, or huge ulcers on their penis, if men. We should go to the beer halls. Doctors don’t usually do that. But I wanted to see condoms promoted in and around the beer halls—posters in the toilets, baskets of free condoms, and various types of entertainment trying to focus on prevention behaviors—just as we had done in the eighties in Antwerp and elsewhere to reach gay men in the bars. Today this seems like a very obvious idea, but traditionally in public health we expected people to come to health services instead of taking the services to the people.

Then I went to Thailand, where AIDS was beginning to ravage groups of sex workers, and their spouses and children as well as their clients. My purpose was to advise the government about whether to authorize a phase 1 HIV vaccine trial by Genentech, which was looking at a candidate vaccine. (For the cognoscenti, this was based on an antigen to the gp-120 component of the HIV envelope.) There was not much evidence available from animal models to inform the decision of whether to move into wide-scale human studies or which candidate vaccine to select. Thailand already had an active and high-quality biomedical research community, and the vaccine work was led by Professor Natth Bhamarapravati, a dengue specialist from Mahidol University, and young researchers from the Thai Red Cross, such as the infectious disease physician Prahpan Phanuphak and anthropologist Werasit Sittitrai. The need was certainly there, as Thailand then had Asia’s most serious AIDS epidemic, with 4 percent of twenty-one-year-old army recruits being HIV positive in 1994. We agreed that there should be no substandard for research in Asia, that WHO would have to review all proposed study protocols before the Thai committee in charge would make a decision, and that the country should not engage in HIV vaccine trials without a strong involvement of the affected communities and a good communication plan. Following the visit, I brought a number of researchers together in Geneva to think about it, and the consensus, though not unanimous, was that we should move to early trials in humans—provided there were guidelines for safety and ethics. It turned out that this particular vaccine candidate did not protect against HIV infection, but when used in combination with another antigen, it may offer some protection, as found in another trial in Thailand in 2009. These results still require solid confirmation but, in any case, the immunization schedule is so complex, requiring multiple injections, that it is impractical for large-scale use. What matters at this stage is understanding whether protective immunity is feasible or not as a concept.

Vaccine trials are tricky: among other things, it is unethical to expose people to risk, so you have to set up a placebo group and a “vaccinated” group, and educate
both
about HIV prevention, knowing that someone, sadly, will take a risk sometime. What you’re seeking to measure is the possible number of infections that could be avoided: an odd and difficult concept to quantify. Making global recommendations was the sort of work that only a multilateral agency could do, as it is in principle not bound by the interests of a particular nation or industry: convene the best people in the world; lock them up in a room with food, water, and an agenda; and have them come up with a consensus of recommendations, independent of personal interest. (This implies careful selection of the participants, obviously, and a clear understanding of possible conflicts of interest.)

At WHO I could set agendas, and one of my private obsessions in HIV research was vaginal microbicides. These are creams and ovules that women could put in the vagina (they already existed as very imperfect contraceptives). I felt strongly that to stop the heterosexual spread of HIV, we needed to find an effective prevention technique that women could control because they might not be able to insist that their partners use a condom. Microbicides had shown some indications that they could be effective to some degree in protecting against gonorrhea, and in 1988 I had received a grant from AmFar, the American Foundation for AIDS Research, founded by Elizabeth Taylor and Mathilde Krim, to begin looking at whether any spermicides could be effective against HIV. We had done a baseline study in Kinshasa and in Antwerp to evaluate spermicide use among prostitutes: Do they prefer ovules or vaginal tablets? Which product of spermicide do they prefer? Is frequent use associated with side effects? This was, I believe, the first study of microbicides for HIV prevention. It gave rise to a larger study of actual effectiveness by Joan Kreiss in Nairobi that found that use of a sponge containing nonoxynol-9, a spermicide, actually
increased
the risk of HIV acquisition in women, because it caused vaginal irritation and abrasions.

Still, I hadn’t given up on microbicides, so when I got to GPA I convened a meeting of experts on the subject. We initiated a study with another product, which was another failure. This is how science advances—it isn’t blind, but it falters and zigzags. It was not until 2010, after several studies had failed, that a vaginal microbicide gel containing tenofovir, an antiretroviral drug, was shown by the remarkable science couple Quarraisha and Salim Abdool Karim in South Africa to be about 40 percent effective if used once before and once after sexual intercourse. This proof of concept, indicating that the right microbicide could prevent HIV in women, at last opened the door for intense work to refine and intensify the gel to attain more complete protection.

Through my interest in a vaginal microbicide for the prevention of HIV, I met a genius of drug development, Paul Janssen, the founder of Janssen Pharmaceutics in Belgium. He had discovered more than 80 new medicines that made it to market—more than anybody else in the world. He was not only a master chemist and pharmacologist, but also a very erudite Renaissance man, who had thought about the big problems of history and society, and had a flair for opportunities. For example, his was the first Western pharmaceutical company to start a joint venture in China, in Xian, as early as 1985. Paul became an unfailing friend; we were each other’s sounding board, and we had incredibly stimulating discussions about drug and microbicide development and how to bring medicines to the people in developing countries. His passion was to discover a simple and inexpensive treatment for HIV infection, if possible a cure, for use in poor countries. I could not always follow his drawings of chemical structures of potentially new molecules, and often had to look up what we had discussed in my pharmacology textbooks (this is before there was Google).

At my request, Paul invested in various pharmacological preparations of a vaginal microbicide. “Dr. Paul,” as he was affectionately called by all his employees, died in 2003 in Rome when attending a meeting of the Pontifical Academy of Sciences to celebrate its 400th anniversary. A former student of mine, Dr. Paul Stoffels is now realizing Dr. Paul’s dream by bringing new potent antiretroviral drugs—some of which we discussed at our meetings back in the 1990s—to market through Janssen of Johnson & Johnson. That is how long it can take to bring a new medicine on the market. Stoffels too is an exceptional entrepreneur. He founded the pharmaceutical start-up Tibotec, which my lab in Antwerp closely collaborated with early on. Tibotec developed not only new antiretrovirals, but also a much needed drug against tuberculosis. It was the first TB drug developed in over three decades, because the pharmaceutical industry basically had not invested in such research despite the increasing development of resistance.

In 1994 nearly every AIDS patient died. This was true all over the world, but in the worst affected populations in Africa, the suffering of patients was inhuman and people died much faster. They had no access even to painkillers or drugs to treat their opportunistic infections. As the Global Programme on Aids we could simply not continue to focus only on prevention: we had to provide solace to patients with AIDS and ensure that the treatment of opportunistic infections would become affordable. Janssen Pharmaceutics was the first pharmaceutical company willing to help. It offered millions of doses of ketoconazole for use in Africa.