But 2010 breathed new life into HIV prevention. The CAPRISA 004 study in 889 HIV-uninfected African women was the first to show that vaginal tenofovir gel (a microbicide) used before and after sex, and given with risk-reduction counseling and condoms, could decrease HIV infections in women by 39 percent.

Months later, the iPrEx study of “pre-exposure prophylaxis” (PrEP) in 2,499 HIV-uninfected gay and bisexual men and transgender women showed that daily Truvada decreased HIV infections by 44 percent overall. All study volunteers received condoms, STD screening and treatment, and risk reduction counseling.

However, drug levels showed that those who became infected were not taking drug, while up to 95 percent of persons with high drug levels were protected against HIV. Drug resistance was not associated with taking Truvada. Side effects of treatment were generally mild and infrequent.

Incremental progress

So Truvada is no magic pill. Yet we should not be dismissive of incremental progress. We should examine the issues through the lens of science rather than fear.

• Lack of effectiveness. The true effectiveness of Truvada could be between 72 percent and 95 percent with good adherence. Still, it is not a magic pill to prevent 100 percent of infections.

Though advertising leads us to believe otherwise, the drugs we take every day for hypertension, allergies, or even cancer are only “partially effective.” The question is, how much effectiveness is enough?

The answer is a balance between risks and benefits. Drug toxicities and other risks must be outweighed by the seriousness of the disease and the other options for treatment (or prevention). When there are no effective drugs for treatment (or prevention) of a life-threatening disease, we tend to tolerate higher risk and lower effectiveness because of the serious consequences of doing nothing.

For example, a large study found that, beginning in 1985, certain combination chemotherapies for breast cancer improved the 15-year survival of women under 50 years old by 38 percent. These are expensive, toxic treatments and a 38 percent benefit is not “magic.”

Yet, imperfect as they were, these treatments saved the lives of many thousands of women. Over time, treatment has improved. Progress is incremental. But how many women might have died while waiting for a magic pill?

HIV is a lethal and, as of today, incurable infection. If we could prevent 44 percent of new global infections, the effect would be stunning. But PrEP will be adopted only by a small proportion of persons at risk, and probably should only be taken by those at highest risk. A key challenge is to understand the best use of this new tool, and its effectiveness in real world settings.

• Real world information is lacking. Clinical trials are not the “real world.” In fact, it is not until drugs are widely available after FDA approval that we learn how they work in practice instead of in studies. We simply won’t know which way “real world” effectiveness will tilt until the drug is used outside of clinical trials and data are collected systematically.

A licensed indication allows the FDA to require additional data collection and monitoring, and to mandate formal educational programs for consumers and care providers about the need for condoms, counseling, STD screening, and HIV testing for persons taking PrEP. This is not impossible, as the ad pessimistically implies, but will require new paradigms.

• Increased risk. The concern that people who believe they are protected will take more risks, and increase their chance of infection, has always been part of HIV prevention research. To date this has not occurred in studies of vaccines, PrEP, or microbicides, however “real world” data must be collected.

Drug resistance has not been associated with PrEP in the three trials completed to date, but the risk should be taken seriously. Health experts estimate that drug resistance will be highest among persons who take Truvada without knowing that they already have HIV. Thus, consumers and health providers must be educated about the need for HIV testing before using Truvada and at regular intervals thereafter.

• Condoms work. There is no doubt that more aggressive public health strategies are needed to increase condom use. But condoms only work when used, and after 30 years they have not stopped this epidemic. New tools are urgently needed to supplement condoms to prevent HIV.

• Who will pay? Cost has no bearing on FDA decisions about drug licensure. However, cost issues must be part a responsible national and international discussion about PrEP. Preventing infections can be cost-effective in certain circumstances. What we cannot afford is to sidetrack promising interventions without scientific review for fear of cost or speculation about misuse.

Magical thinking does not end epidemics, but incremental progress does. PrEP will not be the right or first-line prevention approach for everyone. Or it may be right for some periods in a person’s life, but not for others. People need options. The era of combination prevention packages has begun.

The FDA must pursue its legal mandate to review the data and make approval decisions based upon science, not speculation. Rather than react with fear, we must learn to use imperfect tools wisely.

At least until that magic pill comes along.

 


Melanie Thompson, MD, is principal investigator of the AIDS Research Consortium of Atlanta, chair of the International Antiviral Society-USA Antiretroviral Treatment Guidelines Panel, co-chair of an international panel to develop guidelines for adherence to antiretroviral therapy, a member and former chair of the National Institutes of Health Office of AIDS Research Therapeutics Working Group, and principal investigator of the Atlanta site for the CDC US safety study of PrEP.

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