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Project T: The Promise of PrEP

Note: This is a draft of a story I wrote in 2005 for the New York Times Magazine. Despite enthusiastic support from my immediate editor, the top editor deemed that it wasn’t worth running because it had a “curtain-raising aspect” and didn’t get “deeply enough into the larger issues.” Another editor at the magazine who oversaw a new section called “Idea Lab” then decided to run a vastly condensed version, which I have posted here.  The full story never ran anywhere.

It certainly had a curtain-raising aspect: PrEP first proved its worth in a large study published in 2010, and the U.S. Food and Drug Administration approved its use in 2012. 

Given current patent fights about who did what when, I think the story has valuable information–and readers can decide whether it delved deeply enough into the larger issues. Historical details often get lost in legal battles and the related media coverage.

Shortly after Matthew Bell steps out of the San Francisco spring sunshine and into Daddy’s bar, a friend comes over to gab about the good time they had here at last night’s underwear party, a Monday tradition that encourages patrons to check their pants and shirts. The two men all but yell as the album Thriller pulses out of the sound system, a nod to the fact that a jury yesterday acquitted Michael Jackson. Barbarella silently plays on flat screen monitors that hang at either end of the bar, with sci-fi sex queen Jane Fonda writhing in an orgasm machine. At a table near the front window, two model-beautiful women, both wearing sunglasses and dressed in jeans and cowboy boots, do shots of Jägermeister and passionately kiss. The man tending bar has his arms draped around the neck of a man who is nursing a drink, and they sway a little as they chat.


Daddy’s, located in the heart of the famously gay Castro District, exudes the neighborhood’s mix of sensuality, sexuality, kitsch and raunch. Bell, 31, who suggests that we meet here, lives a few blocks away and loves his adopted environs. A native of Eau Claire, Wisconsin–“it’s a lot like California,” he deadpans—Bell also enjoys calling a city home that has made gay pride as much a part of its culture as its cable cars, and he delights in its sex-positive atmosphere. “We have good vibrations,” says Bell, who has a butch topped by a slight Mohawk and is wearing gym shorts, a polo shirt, and black sneakers with red laces. “People really are very open about it, as they should be.” Personally, Bell says he has sex with five regular “buddies” and a total of about 50 different people a year. Gay men, he says, “have removed the stigma of feeling that you’ve devalued yourself if you have had multiple sexual partners.”


But of course promiscuity also fuels the HIV/AIDS epidemic, which has exacted a horrific toll on gay communities around the world. Indeed, nearly one out of every three gay men who lives in the Castro today is infected with the AIDS virus.


Bell is not in that group. Part of the younger generation of gay men who went through puberty bombarded with safe-sex messages, Bell uses condoms religiously, shuns popular drugs like crystal methamphetamine that increase risky sexual behavior, and doesn’t frequent sex clubs. And this winter, he decided to try and help curb the spread of HIV in the community at large: He joined a novel study of a prevention approach that, if it pans out, could derail the epidemic itself.


In the same way that healthy people can take malaria and tuberculosis drugs to prevent those diseases, HIV-uninfected people may be able to thwart the AIDS virus by taking an anti-HIV drug. Bell is a participant in Project T, a study run by the San Francisco Department of Public Health that is testing this provocative concept with tenofovir, which in 2001 received approval from the Food and Drug Administration (FDA) to treat HIV infection. Called pre-exposure prophylaxis, or PrEP, the strategy takes a back seat to vaccination—a few shots, after all, often can train an immune system how to defeat a bug for decades. But tenofovir PrEP’s prospects gave Bell a unique sense of hope.


Although many powerful AIDS treatments now exist, efforts to protect the uninfected with vaccines and other medical prevention strategies have struggled mightily. “At this point, people are saying, Look, I don’t really see something working,” says Bell. “In our area, the AIDS population is almost complacent: We haven’t found something, we may not ever find something.”


Bell’s belief in the promise of tenofovir PrEP is shared by many AIDS doctors and researchers. “AIDS is a tough disease to transmit,” says Dr. Marcus Conant, a San Francisco clinician who runs one of the country’s largest HIV/AIDS practices and has prescribed tenofovir to select, uninfected patients. “If we could find something that just shifted the equilibrium of transmission just the least little bit, we could stop the spread of this disease.”


The enthusiasm for tenofovir PrEP is based on monkey studies, as well as the proven ability of anti-HIV drugs to prevent transmission from an infected mother to her baby. Investigators also understand how tenofovir works (it blocks a critical HIV enzyme), putting them miles ahead of AIDS vaccine researchers, who still are debating which immune responses they need to trigger. And unlike vaccines, which require years of preliminary studies before they move into real-world tests, Project T and seven other trials now underway on four continents could determine this approach’s merit in as little as two years.


But to AIDS researchers, clinicians, activists, governments, philanthropists, and even Gilead–the small Foster City, California company that makes tenofovir–PrEP has proven profoundly riddling and controversial, as it raises a host of troubling issues. Foremost among them: It’s impact on behavior. Many populations have slowed HIV’s spread by increasing condom use, decreasing sexual partners, and not sharing needles. What if taking a pill to prevent HIV infection leads people to assume they’re protected, and if this, in turn, increases the risks they take? Such “behavioral disinhibition” could wipe out any benefit tenofovir PrEP offers.


Bell, a psychology major in college, knows all about behavioral disinhibition, and as part of Project T, he receives intensive counseling sessions to lower his risks. He flatly dismisses the possibility that being part of the study might encourage people to have riskier sex, noting that Project T is a “blinded,” placebo-controlled trial, which means that participants don’t know whether they’re receiving tenofovir or a dummy pill.


But if studies prove that tenofovir PrEP works, the scales tilt. “Honestly, for a lot of other people, having sex without a condom is so illicit that it’s almost erotically charged,” says Bell. Personally, he says he’d still be afraid of contracting other sexually transmitted diseases. But if someone assured him that he was free of disease, might Bell skip the condom one night? “Yes, I would, I’m sure,” he says. “I’d just be curious.”


I don’t mean to criticize Bell: He’s smart, careful–and candid. What he’s saying, though, is that if tenofovir PrEP proves its worth, he might lower his guard. And he’s better educated and more risk-adverse than many.


The perplexing bottom line: even if tenofovir PrEP works in clinical trials, in the real world, it may fail.




Dr. Susan Buchbinder, the researcher in charge of Project T, initially had “big reservations” about tenofovir PrEP.


Buchbinder, 47, who decorates her office with cheery and bright elementary school artwork from her two daughters, has seen the darkest side of the AIDS epidemic up close. She entered medical school at the University of California, San Francisco (UCSF) the year before AIDS first surfaced and did her residency at San Francisco General Hospital at a time when few treatments could help the hordes of skeletal gay men who were bedridden with HIV-ravaged immune systems. In 1988, she joined the city’s health department, and she now directs its HIV research section, which sponsors a host of cutting-edge projects that study risk behaviors, vaccines, and the course of disease progression. If tenofovir PrEP led to behavioral inhibition, Buchbinder worried, it could wreak havoc. “It’s scary as an investigator, as a public health official, and a person who has worked with the community for many years to think about doing something that could paradoxically make the epidemic worse rather than better,” says Buchbinder.


Like many AIDS clinicians, Buchbinder specializes in arriving at pragmatic solutions to intractable problems, and when the U.S. Centers for Disease Control and Prevention (CDC) announced in 2003 that it wanted to fund tenofovir PrEP trials, she rethought her concerns. By then, she had heard several anecdotes about people trying it on their own, convincing her that scientists urgently needed to stage carefully designed studies. And she recognized the stark limits of current prevention efforts: HIV infects 10 to 20 people in San Francisco alone each week–and another 100,000 worldwide. “We need multiple strategies to help people stay uninfected,” says Buchbinder. “We need new tools.”


Buchbinder notes that the advent in 1995 of powerful AIDS drug cocktails—called highly active antiretroviral treatment, or HAART—also has a downside: It might have fueled HIV’s spread because infected people live longer and some uninfected people have less fear of the disease. “Do I for a moment think that we shouldn’t have pursued HAART or that we shouldn’t continue to pursue it aggressively?” she asks. “Absolutely not. It’s been a critical, major breakthrough. In the same way, we have to pursue all reasonable avenues for prevention, but we have to communicate very clearly with the people who will use these tools what their strengths and what their limitations are.”


Besides behavioral disinhibition, tenofovir PrEP could cause harm by increasing resistance to the drug. HIV most easily outwits drugs when they are used alone as monotherapies, rather than in combination. If people taking tenofovir as a prophylaxis become infected, resistant mutants might quickly crop up and then spread to others, which, in time, could seriously limit the value of tenofovir as a cocktail component.


Researchers have concerns, too, about the drug itself. While HIV-infected people tolerate many toxicities caused by drugs that stave off AIDS, few side effects are worth the bargain for an uninfected person. Tenofovir arguably causes fewer serious problems than any of the other 20 HIV drugs that have FDA approval, but it can in rare instances cause kidney or bone problems that may harm perfectly healthy trial volunteers like Matthew Bell.


Project T, a 2-year study that enrolled its first volunteer in February, focuses on safety, and Buchbinder and her team are going to great lengths to assess drug toxicities (even doing bone scans) and drug resistance in anyone who becomes infected. But what separates Project T and a sister study in Atlanta from all other HIV prevention trials is the intensity with which they are measuring the relationship between taking daily pills and behavioral disinhibition. Matthew Bell and the other 199 gay and bisexual men who join the study all will receive risk-reduction counseling, free condoms, and health care services, but half will wait 9-months before taking pills so that the researchers can discretely assess whether people change behavior because of pre-conceived notions about the benefits of PrEP.


A novel computer program will help gauge risk-taking by periodically interviewing trial participants about their sex lives, drug use, and mental health. Studies have shown that people will be more forthcoming to a computer than to a human about these intimate details, says Dr. Albert Liu, the soft-spoken, clinical director of the study. “There’s what we call ‘social desirability,’” he explains. “Participants may want to say things that will please the counselor or the interviewer. If they were engaging in a lot of high risk behavior they may be less likely to disclose that.” The computer, on the other hand, shows no reaction when a man reveals that he had 10 sexual partners in the last three months, did crystal meth and ecstasy, and did not use a condom on six occasions when he had receptive anal sex with a man he knew was HIV positive.


Project T and the Atlanta study together will cost $4 million and involve 400 men. Both are funded by the CDC, which also is bankrolling an $8 million tenofovir PrEP study in 1200 sexually active adults in Botswana, and yet another $7 million trial that involves 1600 injecting drug users in Thailand. The Bill and Melinda Gates Foundation has given Family Health International $15.5 million to test the concept in 400 sex workers in Ghana and 500 heterosexual men with multiple partners in Malawi. And in October, a study expected to be financed by the U.S. National Institutes of Health likely will start in 1400 gay men in Peru. Tenofovir itself retails for about $13.50 a pill in the United States (brand name Viread), but, in each of the studies, Gilead is donating both the drug and placebo pills, which have an identical look and taste.


Researchers are acutely aware of the potential for these trials to attract sharp criticisms. “Everyone’s worried that they’re going to step on a political bomb,” says Kim Page-Shafer, an epidemiologist at UCSF who had to abandon a tenofovir PrEP study in Cambodia. Page-Shafer’s study ground to a halt after sex workers there —spurred by activists from Europe and Australia—staged protests, contending that the studies exploited particularly vulnerable participants. (Most of the complaints revolved around the longterm medical care offered to participants, the informed consent process, the quality of counseling, and other issues that had little to do with tenofovir PrEP itself.) Related protests forced a trial in Cameroon to end early, too.


In the United States, especially with the current conservative political climate, critics inevitably will emerge who charge that PrEP encourages bad behavior. When I ask Buchbinder about this, she tells the story of a colleague who similarly was challenged at a public forum about AIDS vaccines. “She said, ‘If behavior change were easy, I’d be thin,’” remembers Buchbinder. “Instead of pointing fingers at other people, we all have to look within ourselves and think about how difficult it is to change behavior. It’s very difficult to stop smoking. It’s very difficult to stop drinking. Those are things you can stop and not go back to. It’s much more difficult in some ways to change behaviors that are a normal part of living like eating or having sex. You’re not eliminating a behavior. You have to figure out how to integrate it into your life in a healthy way.”


While tenofovir PrEP for the promiscuous surely will furl some eyebrows, Buchbinder points out that it may help couples in which only one partner is infected, sex workers who have been forced into the business, or injecting drug users going through a treatment program. What’s more, people might only use PrEP briefly. “It may be that people are at risk for a defined period of time in their lives,” she says.


And Buchbinder again and again stresses that tenofovir PrEP is not meant to be a solution in and of itself. “We’re talking about using strategies in addition to, not instead of,” she says.




The California National Primate Research Center at the University of California, Davis houses 5000 monkeys that have helped reveal tenofovir PrEP’s great promise. Veterinarian Koen Van Rompay, a Belgian native who does research at the primate center, has published more than a dozen studies of the approach, and he’s a strong proponent of the human trials. “I have little doubt that it will work, because it has been so effective in the monkey system,” says Van Rompay.


Van Rompay first had success with pre-exposure prophylaxis in 1991 with a different anti-HIV drug, but the experiment only involved two monkeys and received little attention. In a landmark 1995 study, a group led by Che-Chung Tsai at the University of Washington Regional Primate Research Center wowed the field with a study of tenofovir PrEP in 25 monkeys, demonstrating that the animals warded of SIV—a simian cousin of HIV—if they received the drug anywhere from two days before to one day after the researchers attempted to infect them.


Van Rompay’s own tenofovir studies have demonstrated several novel features of the drug. It has an excellent “toxicity profile.” Because the body does not clear the drug for a relatively long time, one pill might be able to prevent infection for two days. Tenofovir somehow boosts immune responses against the virus. Animals that are intentionally infected and then quickly receive the drug fare much better than infected, untreated monkeys. And even when the virus develops mutations that make it resistant to the drug, tenofovir still helps slow progression of disease. “I haven’t seen any drug that has such an impressive track record in every aspect,” says Van Rompay. (Although a recent CDC monkey study sobered the field when it found that tenofovir failed to protect animals after the fifth time researchers attempted to infect them rectally, Van Rompay and the CDC researchers themselves suspect that they did not use high enough levels of the drug.)


Monkey tenofovir studies have raised a still more startling possibility: PrEP may work as a “pharmacovaccination.” A vaccine teaches the immune system by confronting it with a crippled version of a bug. When tenofovir aborts an infection, it cripples the AIDS virus. As the monkey experiments have shown, if researchers attempt to infect animals with SIV after they have been off the drug for more than a year, their immune systems often beat the infection; in the animals that do become infected, they much more readily handle the virus. Van Rompay and many other researchers shy away from discussing this because they worry that it will raise false hopes and give uninfected people yet another reason to wrongly think that tenofovir offers protection. Yet studying people who receive PrEP, he says, “may allow us to identify which immune responses would really be important to mimic with regard to HIV vaccines.” In other words, it may lead the AIDS vaccine field to its Holy Grail.


Van Rompay’s work had “an enormous impact” on Dr. Bob Grant, who has his hands in most every human trial of the concept. A pulmonary specialist who treats HIV-infected patients, Grant also runs an HIV lab at UCSF’s Gladstone Institute of Virology and Immunology. His team of researchers work at the school’s nascent Mission Bay campus, and their sparkling new lab is playing a central role in the Project T  and Atlanta trials, and also is spearheading the study now being launched in Peru. But ask Grant about the strategy’s prospects, and he ardently remains in what scientists call equipoise, which is a yin/yangy state of optimism/pessimism. “We do not know whether this is going to be a success or not,” says Grant, 45, another graduate of UCSF medical school. “Its application could be very broad, very narrow, or it could be a complete loser.”


Grant’s lab will hunt for evidence of drug resistance, sequencing the genes of every HIV that they isolate from people in the studies and looking for specific mutations that make tenofovir less effective. His team also will assess how PrEP alters the immune system.


Grant shares the concerns about behavioral disinhibition, but he raises the intriguing possibility that tenofovir PrEP might lead to behavioral inhibition. “It could be that these trials will show an astonishing, unprecedented decrease in risk behavior because people will finally face up to the fact that either they change their behavior or they have to take a pill every day,” says Grant.  “That’s fine with me. If there’s no risk, there’s no risk. Our job is done.”


I ask Grant what he thinks of uninfected people who are taking tenofovir outside of clinical trials. “It’s a big mistake,” he says. “I don’t think we know whether it works. I don’t think we know that it’s safe.” But, true to form, he then flips the idea on its head. “It does indicate that there’s willingness to do it if it is safe and effective.”




In February 2002, Microsoft chairman Bill Gates gave the keynote lecture at a large AIDS conference held in Seattle. After his talk, he took questions from the audience.


“If I’m having sex with my HIV-positive boyfriend, wouldn’t it make sense to take a drug for HIV like you’d take an antimalarial?” asked Dr. Mike Youle, who directs HIV clinical research and sees patients at Royal Free Hospital in London.


The question seemed to take Gates by surprise, as it likely did many in the audience who had yet to hear of PrEP. “Wouldn’t it be simpler to use condoms?” he replied.


What Gates had no way of knowing is that Youle is an uninfected gay man, and the question was far from hypothetical for him. “I have used tenofovir to protect myself,” Youle tells me over the phone. “I’m not the only HIV doctor in the world who has done that.” Youle says he used condoms when he took the drug, and he’s only done it intermittently, which some researchers have called discontinuous, or “disco,” dosing. He of course knows that PrEP is unproven and that the tenofovir may harm him, but says he has had condoms break, and he knew he was going out for fun. “When you go out for drinks, you leave the car keys at home,” he explains.


A survey done by the CDC at gay pride day events in four cities found that 7% of the people interviewed said they had tried PrEP with tenofovir or other anti-HIV drugs. But several pro-PrEP physicians I spoke with, including Youle, are reluctant to prescribe anti-HIV drugs to uninfected patients because of the unknowns. Dr. Marcus Conant is the exception.


Doctors are allowed to prescribe marketed drugs for any purpose, and Conant says he has a half-dozen, carefully chosen patients now doing tenofovir PrEP. “With my patients, it’s not even ethical for me to wait for the science,” says the avuncular Conant, who was prominently featured in the 1987 bestseller And the Band Played On and has testified before Congress about the epidemic. “The pill is available. I know the side effects. I can identify those patients who I know are at extremely high risk. Should I wait for the scientific evidence to prove that it doesn’t work before I give it to someone where it may work?”


On top of running a busy clinic, Conant set up a foundation to do AIDS education and research, and I meet with him at its headquarters, a grey two-story Victorian rowhouse located around the block from Daddy’s bar. Conant, 69, is a dermatologist by training who did an Air Force stint after medical school and has lived in the Castro since 1968. One of the first doctors in the world to treat AIDS, he unabashedly marches to his own beat.


Conant, who counsels these half dozen men how to reduce their risks, doesn’t think behavioral disinhibition is a factor with them—they decided to throw caution to the wind long ago. But what if PrEP becomes widely used? “If AIDS wasn’t there, the bathhouses would start up again, people would go back to having multiple sexual partners, people would stop using condoms—they hate them—and all that tells me is that people really like to have sex,” says Conant. “And the reason they stopped having sex was not because George Bush doesn’t like sex. They stopped having sex because they were afraid they were going to die. Anything that people can use to rationalize that they’re not going to die from having sex, yes, they will go back to risky behavior. Should we not try to keep them from catching AIDS because we know that they will be human beings?” Conant stops and laughs. “My view is let’s eliminate this disease and let people be as sexual as they want to be without running the risk of dying.”


One night in the Castro, I have dinner with an HIV-uninfected man who for the past 2 years has received tenofovir prescriptions from Conant. I agree not to identify this patient beyond saying that he’s a middle-age professional, as he fears being punished by the insurance company that provides healthcare to both him and the man he calls his “husband,” who has full-blown AIDS. He first learned that people were doing tenofovir PrEP in a gay newsletter, but when he approached his regular physician, the doctor refused to provide it and reacted as though he were suicidal. He told his doctor that “if I wanted to kill myself, I wouldn’t be looking for this.”


The patient takes tenofovir every day, and a recent blood test of kidney function has shown potentially abnormalities, but neither Conant nor his patient is convinced that it’s related to the drug. No other potentially related side effects have surfaced. Every three months, the man checks his blood for HIV, which he calls his “testing cycle.”


Listening to the patient describe his sex life it occurs to me that he has something in common with the amateur racecar drivers who risk their lives—and the well-being of others on the track—in exchange for a thrill. As the patient explains, he simply does not like using condoms. In addition to his husband, he estimates he has an average of 5 to 10 partners each week. “It’s not like there’s a shortage of people wanting to have sex,” he says, stressing that he tells partners where he is in his testing cycle. We have a window table, and he points to the men strolling on the sidewalk outside. “You can just sort of watch them go by. It’s like hungry, not hungry, hungry, not hungry.” He also meets hungry men over the internet and at sex clubs.


The patient well understands the risks of unprotected sex, and he knows all about the potential side effects of tenofovir, which he recognizes may not work. “Better to take it than to not,” he says. And he sees AIDS up close at home. “It’s really a miserable disease,” he says. “I really don’t want to get this. I don’t want to get this, bad.” Given his sexual habits, he expects that he eventually will become infected, and he hopes that tenofovir will delay that inevitability. “No one gets out of here alive,” he shrugs. “If I get infected at 70, alright! Doing great!”


What does his husband think of his lifestyle? “He thinks I should be wrapped up in Styrofoam. ‘Never do this. Are you crazy?’ ”


I later ask Conant why he thinks patients like this man take so many risks, and rather than re-iterating how difficult it is for people to change their behavior, he notes that humans do all sorts of irrational things. “Why do we have people who weigh more than 250 pounds in this country?” asks Conant. “And why do we have people who still smoke cigarettes? Or ride motorcycles without helmets? Or drive 80 miles per hour with a kid in the back looking for the cops?”





One of the most unusual aspects to tenofovir PrEP has to do with Gilead, the company that makes the drug. Even if clinical studies show that it’s safe and effective, the company does not plan to seek a “label change” from the FDA, which would allow Gilead to market the drug for both treatment and prevention of HIV infection. “There is no desire, no belief, no march toward promoting the drug or being in a position to promote the drug for prophylaxis,” says Dr. Howard Jaffe, who meets with me at the modest Gilead headquarters in a standard-issue business park just south of San Francisco.


Jaffe, a physician who heads the company’s newly formed foundation, explains that Gilead doesn’t want to market tenofovir PrEP for legal reasons. “There would be significant liability that the company is just not in a position to completely understand or embrace,” says Jaffe. It’s the same equation that leads many drug companies to avoid the vaccine business: When healthy people suffer harm and blame it on a preventive medicine, sympathetic juries often require little evidence that the product actually caused the injury.


Liability is but one risk that tenofovir PrEP presents to Gilead. Tenofovir has ample sales that the new studies could threaten: testing it as a monotherapy might, for example, reveal side effects that are masked when the drug is used in combination. If tenofovir PrEP does increase the spread of drug resistant HIV strains, that, too, could dent the drug’s value. And Gilead already has taken a public relations drubbing because of the tenofovir PrEP trials. At the international AIDS conference in July 2004,  ACT UP Paris and the Asian Pacific Network of Sex Workers jointly issued a hyperbolic press release that claimed Gilead “organizes the infection of sex workers.” The activists also trashed the company’s exhibition booth at the Bangkok meeting, splattering it with fake blood.


Although Jaffe says Gilead is “delighted” that the studies are underway, besides supplying pills, it provides little else. This is in stark contrast to the way most drug makers behave when their products are in multi-site clinical trials.  Typically, companies devote millions of dollars to such studies and have their own scientists coordinate the various sites so that they can “pool” data to arrive at more convincing results. With tenofovir PrEP, the researchers themselves informally have formed an alliance to attempt to do just that, but it’s a challenging task. When I suggest to Jaffe that Gilead has a standoffish position toward these studies, he bristles. “I’ve had equal number of people telling me we should be more involved and others telling me we should be less involved,” says Jaffe.


Gilead now offers the drug at cost (82 cents per pill) to poor countries, and will do the same if tenofovir PrEP works. “There’s no going back,” says Jaffe. The company also has not sought patents in Africa or in India, China or Thailand, leaving generic manufacturers in those locales free to make it.


But without the FDA’s endorsement of tenofovir PrEP, it could be that insurance companies in wealthy countries will not reimburse its off-label use. Poor countries may also find that donors and their own governments are reluctant to buy the drug for prevention, too.


Jaffe acknowledges that tenofovir PrEP might boost Gilead’s bottom line, and he says the company has modeled what would happen if it proves to be over 80 percent effective. “We imagine that demand would go very, very high,” Jaffe says. Beyond the treatment market? I ask. “Oh, absolutely,” he says.




One evening in June, five gay men on Project T’s community advisory board, or CAB, meet with the researchers running to discuss how it fits in with the other trials underway. The tricky question of what will happen if tenofovir PrEP works surfaces repeatedly. Buchbinder urges everyone to avoid even using the word “works.” Instead, she advises, talk about whether tenofovir PrEP reduces infection. “The question that we might end up asking is do we care if it only drives it down a little bit?” asks Buchbinder. “Is this something you would actually promote as a strategy to prevent infections?”  How much reduction is good enough? 70%? 50%? 30%? And if it becomes a standard of care, all future prevention trials, including vaccine studies, ethically will have to use it in the placebo arm, making it that much more difficult to discern whether those interventions work.


The CAB members, veteran AIDS activists and community organizers, all speak science fluently, and have a sophisticated discussion with Buchbinder, Grant and Liu about drug resistance, quality control, and the fact that none of the current studies evaluate whether disco dosing works, which may be less toxic—and more popular—than daily PrEP. They also talk about drugs now being developed that might work better than tenofovir. And then the groups muses over the “home run” scenario: Clear, indisputable evidence that tenofovir PrEP—even accounting for behavioral disinhibition—is safe and effective. “If we get a positive result from any prevention study,” Buchbinder says, “we’ll have a big party first.”


In a best case scenario, mathematical models show that if tenofovir PrEP worked 90% of the time and was used by 90% of people at high-risk of becoming infected, a big party would be called for: It could cut new infections by more than 80% in a few years time.


Relying on a pill to thwart HIV infections of course will always take a back seat to a good vaccine. Still, the history of AIDS treatment says that staying alive is about new drugs being developed just as the old ones are reaching their limits, jumping from riverstone to riverstone. For millions of people, staying uninfected is about getting from riverstone to riverstone, too. Tenofovir PrEP might just be a riverstone on the way to that dreamed of vaccine.