A Pill to Prevent HIV? What the New iPrEx Results Mean for Women

Anna Forbes

Proof that PrEP works – that there is, literally, a pill can help to prevent HIV -- is an extraordinary breakthrough, as was the news received last summer that an effective vaginal microbicide had been identified.  But what does a study focused on people engaging in rectal-penile sex have to do with women and their reproductive health?  There are many ways to answer that question -- some of them cause for celebration and some reasons for real concern.

“Pill May Prevent HIV” — it’s an attention-getting headline. On November 23, the announced results of a clinical trial conducted in Peru, Ecuador, Brazil, the United States, South Africa and Thailand showed that taking an antiretroviral drug (in the class of those used to treat HIV/AIDS) may help prevent an HIV-negative person from becoming infected if exposed to HIV. The study, called iPrEX (Iniciativa Prophylaxis in Spanish or the Pre-exposure Prophylaxis Initiative in English) showed that, overall, those taking the medication were 44 percent less likely to become infected than participants using the placebo pills. Researchers also reported that the study participants who took the drug strictly according to schedule and did not miss doses were 73 percent less likely to become infected. 

Pre-exposure Prophylaxis (PrEP) refers to the practice of using medicine to prevent yourself from getting a disease or condition before you are exposed (pre-exposure) to the thing that can cause it. You take malaria medication, for example, before traveling to areas where you may be bitten by mosquitoes that carry malaria. Having the medicine already in your system greatly reduces your chances of getting malaria if you are bitten. Some people who are severely allergic to cats may take an allergy medication before visiting a friend who has cats – another form of PrEP.  In this case, the iPrEx trial showed that HIV-negative people can reduce their risk of acquiring HIV by taking an antiretroviral pill every day.  Obviously, this strategy is nowhere nearly as effective as using condoms or having sex only with people who are HIV negative.  But it may be a good prevention tool for people who are at high risk of HIV because they do not or cannot use those risk reduction strategies.

Started in June 2007, the iPrEx study ended in 2009 after enrolling 2,499 HIV-negative gay men, male-to-female transgendered women, and other men who have sex with men (MSM).  It was conducted at 11 sites in six countries: two sites in Lima, Peru, one site in Iquitos, Peru, one site in Guayaquil, Ecuador, one site in Boston and one site in San Francisco in the United States, one site in Cape Town, South Africa, two sites in Rio de Janeiro and one site in Sao Paulo, Brazil and one site in Chiang Mai, Thailand. These locations were selected because the prevalence of HIV infection among the men and transgender women having sex with men there is extraordinarily high, between 10 and 28 percent. The iPrEx study was funded by the US National Institutes of Health (NIH) and the Bill and Melinda Gates Foundation.  The medication tested in the study was donated by their manufacturer, Gilead Sciences. 

Proof that PrEP works – that there is, literally, a pill can help to prevent HIV — is an extraordinary breakthrough, as was the news received last summer that an effective vaginal microbicide had been identified.  But what does a study focused on people engaging in rectal-penile sex have to do with women and their reproductive health?  There are many ways to answer that question — some of them cause for celebration and some reasons for real concern. Consider the following:

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1.  What do the iPrEx results mean for women? 

It’s great to know that PrEP may be an effective HIV prevention tool that women could use on their own, without a partner’s cooperation. Taken orally, the drug goes into the bloodstream and could help protect women who are having vaginal sex, anal sex or are exposed to HIV through other means. They may actually be of particular interest to women who have anal sex because many report that it is easier to insist on condom use during vaginal sex, where they can make the pregnancy prevention argument, than it is during anal sex.  This puts them at serious risk because, although estimates vary, unprotected receptive anal intercourse with an infected partner is probably five to twenty times more likely to transmit HIV than receptive vaginal sex.

Between 10 percent and 35 percent of heterosexual women in the US and UK acknowledge practicing receptive anal intercourse.  Among American men, 40 percent report having engaged in anal intercourse with a woman at some point in their lived. 

Clearly, we can’t assume that the PrEP medications tested in iPrEx will have the same effect in women’s bodies as they did in the bodies of the male and transgender study participants.  Additional PrEP trials are already underway, including a study enrolling heterosexual men and women in Botswana and the UK, one enrolling just heterosexual women in seven African countries, and one enrolling serodiscordant couples (couples with one HIV-positive and one HIV-negative member) in Kenya and Uganda.  Studies enrolling injection drug users and adolescents of all genders are also occurring. Expected to produce results in 2011-2013, these studies will tell us more about the gender-based differences (if any) in how the drugs tested in iPrEx work. But the iPrEx results are certainly cause for optimism that PrEP may provide women with another HIV prevention tool in the near future.

2.   Who will get these PrEP medications now?

Truvada® (a combination of Tenofovir Disoproxil Fumarate or TDF and Emtricitabine) is the medication tested in the iPrEx trial.   In the short term, this drug will only be legally available to iPrEx study participants, who will be offered the option to volunteer for the follow-up “open label” study. This standard procedure recognizes the ethical responsibility to allow those who took on the burden of study participation to be the first to benefit from the study results and it allows investigators to gather more information about use of the medication..    

The unusual aspect of this process, however, is that Truvada® is already on the market and regularly prescribed to treat people living with HIV.  Typically, it takes three to five years to get a new drug into consumers’ hands after it is proven to be effective. It has to be reviewed and approved by government regulators, manufacturing of it has to be scaled up, a supply chain has to be created to get it from factory to stores, etc. Truvada® is now only approved as a treatment for HIV and will have to go through a separate regulatory approval to be marketed for HIV prevention once  at least one other study confirms its efficacy at an acceptable rate.  Nevertheless, some consumers can already access it for prevention from private health care providers. Physicians in the U.S. and some other countries can, at their discretion, prescribe drugs for purposes other those for which they have been approved (a practice usually known as “off-label” use). Thus, these drugs are already available as prevention tools to those able to pay for them privately.

The third option — and one of which women’s health advocates need to be particularly mindful – is that the “pill may prevent HIV’ headlines could escalate the informal (or black market) sale of Truvada®.  Envision the following:  On one hand we have people who read the headlines and want to take a pill to protect themselves rather than having to use condoms. But they either don’t want to go to a doctor or can’t find one willing to prescribe these drugs for HIV prevention. 

On the other hand, we have people living with HIV who are being prescribed Truvada®. How do HIV-positive individuals who are poor choose between maintaining the treatment regimen they need to stay healthy and selling their pills at a high price on the street?  This may be particularly problematic for indigent women living with HIV who are trying to make ends meet for their families. What about the woman who brings the pills home only to have her partner or someone else take them away from her to use himself for prevention or to sell on the street?  This threat of mis-appropriation is one of the major differences between PrEP and microbicides. Men are foreseeably much less likely to grab up a woman’s microbicidal gel (once we have one) because they will not see it as something that other men want or that they can use, themselves.

Informal marketing and non-prescription use of PrEP drugs may also have serious public health implications. To get these pills prescribed for prevention, consumers will have to take an HIV test before each refill to ensure that they are still HIV negative. If you use PrEP when you are already HIV-positive, you may develop drug resistant virus.  You could pass this resistant strain on to other people and having it is likely to make it harder to treat your HIV infection on an on-going basis. Experts warn that epidemiological “train wrecks” could occur if access to these drugs used for both prevention and treatment is not well controlled.

Very little drug resistant virus was detected among participants in the iPrEx study because they received HIV tests monthly and stopped using the Truvada® immediately if they tested positive.  In real world use, people obtaining Truvada® without a prescription will likely not be tested regularly.  The longer they, unknowingly, continue to take the drug after acquiring HIV, the higher the chance that they may develop drug resistant virus.

Uncontrolled access could result in a rise in the prevalence and transmission of virus that is resistant to these drugs, resulting in reduced utility of first-line treatment regimens involving Viread® (an antiretroviral drug containing TDF) and Truvada® and a subsequent rise in the death rate. Someone using black market Truvada® occasionally (rather than daily) or those who sometimes buy counterfeit versions of Truvada® that contain no active drug may be particularly susceptible to developing resistant virus if they become HIV positive, are not tested, and continue to take non-prescription PrEP drugs. At the very least, we have to anticipate that increased levels of drug resistance would increase the cost of treating HIV because more second-line treatments (those able to overcome drug resistant virus) would be required.

3. How might PrEP work in the real world?

As women’s health advocates, there are things we can do to try to ensure that the iPrEx results lead to good outcomes for women that are not eclipsed by unintended consequences. Among other things, we must:

Insist that policy makers look at real world issues, not just clinical trial results:

The CDC is preparing a PrEP implementation plan that will include public education, guidance for physicians and health care providers regarding PrEP use, and implementation research.  Advocates need to insist that the implementation research agenda include examination of the impact of informal marketing and drug sharing on the well-being of people living with HIV and on public health generally.  If evaluators focus solely on the experience of people with legal access to PrEP drugs, they may miss effects such as treatment non-adherence due to drug misappropriation, increases in drug resistant virus levels due to sporadic use of illegally obtained and/or counterfeit PrEP drugs, and other consequences indicative of informal marketing and drug sharing practices.

Call for resistance monitoring systems:

Once approved for use in the U.S., PrEP is only likely to be prescribed to high-risk people who are demonstrably unable to use other HIV prevention methods consistently.  Nevertheless, we need to put systems in place now to do baseline assessments of population-level drug resistance and then monitor the level periodically so that any effect PrEP has on the prevalence of drug resistant virus can be tracked. Research has shown that, in places where anti-retroviral drugs are widely used, between 5 and 15 percent of new HIV infections transmit drug-resistant virus from one person to another. We will need an effective evidence base to determine whether or not use of PrEP—formal or informal/”off-label”—is increasing the prevalence of HIV that is resistant to PrEP drugs. 

Demand stakeholder involvement in setting the PrEP research agenda and roll-out:

As mentioned above, trials showing how PrEP works in women’s bodies are likely to produce results in the next few years. Additional data are needed to show whether gender-based differences occur in terms of overall effectiveness and the incidence and severity of side effects during long term use. Additional trials will also be needed to determine how use of PrEP drugs affects pregnancy or breastfeeding.  Advocacy will be required to get those trials on the research agenda sooner rather than later.

Implementation research is also needed to understand the barriers that keep people from accessing HIV testing and how they can be overcome.  Women who need PrEP because they have no other prevention alternative when their partners don’t use condoms will be unable to get it if they feel unable or unwilling to get HIV testing.

Most of all, community stakeholders need to play key roles in planning and delivering highly targeted community education about PrEP.  This is essential to ensuring that women and men in high risk communities understand about how PrEP works and why it is not a replacement for condoms. People will need to hear clearly, from those they perceive as credible, that they endanger their own health—and the community’s health—if they use PrEP without a prescription or buy it on the street.

No matter how well PrEP works to prevent HIV in tightly controlled clinical trials environments, significant stumbling blocks exist to its effective use in the real world. Unfortunately, these “real world” challenges are often set aside as issues that can be addressed once roll-out of an intervention to the target population has been achieved. Funders and policymakers often see work to address them prior to introduction as optional and aspirational, rather than as an investment that is essential to the intervention’s success.

We can’t let PrEP go the route of condoms and circumcision—becoming an HIV prevention tool primarily benefitting men. As we celebrate evidence of its potential effectiveness, we must also pay close attention to what next steps are needed to put this new HIV prevention tool into the hands of the women who need it most.

Commentary Abortion

Utah Anti-Choice Law Forces Women to Pay for a Procedure That Risks Their Health

Maggie Jo Poertner Buchanan

Many anti-choice policies flout established medical standards, disrupt a woman's ability to seek and act on counsel from her trusted health-care provider, and make accessing abortion care more expensive. But one bill recently signed into law in Utah, SB 234, managed to encapsulate a number of troubling harms.

In the more than four decades since the U.S. Supreme Court recognized a woman’s constitutional right to end a pregnancy, states have enacted well over 1,000 abortion restrictions. Anti-choice forces are gaining ground: More than one-fourth of those restrictions were passed in the last five years. Last year alone, 17 states enacted 57 new laws limiting reproductive choice.

Many of these policies flout established medical standards, disrupt a woman’s ability to seek and act on counsel from her trusted health-care provider, and make accessing abortion care more expensive. But one bill recently signed into law in Utah, SB 234, managed to encapsulate a number of troubling harms. SB 234 requires women, with only very narrow exceptions, to undergo anesthesia if they choose abortion care after the approximate midway point of pregnancy. While only a small number of patients seek such care, at least one physician has noted that the law could also apply to women seeking to induce labor—an undoubtedly unintended consequence. And the women themselves may have to pay out-of-pocket for the anesthesia, which could cost them thousands of dollars.

To be clear, anesthesia is already sometimes used during abortion care for a variety of reasons, individual to the patient. But the type of anesthesia used is often local or regional, meaning the patient remains alert because only a portion of her body is affected. However, because of how the Utah law is written, physicians will likely be required to administer general anesthesia: the type that affects both a patient’s brain and total body, rendering the woman unconscious.

General anesthesia, while generally safe for much of the population, does not come without risk of complications, including stroke, heart attack, and even death. Previously, Utah required providers to tell a woman she had the option to undergo anesthesia when ending a pregnancy. Some women may very well choose anesthesia for their own reasons. But Utah’s new mandate forces women to put their health, and even lives, in harm’s way for no stated medical benefit to them.

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Notably, the text of SB 234 also struck a requirement that a woman’s doctor inform her of these risks as she decides whether to use anesthesia. There is a perverse logic in eliminating this requirement—the patient can no longer decide if those risks would keep her from undergoing anesthesia—but it highlights how the state has placed itself between patient and provider. No longer can a woman have a meaningful, open dialogue with a provider she trusts on the pros and cons of a medical procedure; the decision has been made for both doctor and patient by the state.

Further, abortion care, for which Utah prohibits almost all private and public insurance coverage, can be difficult for many to afford. Requiring general anesthesia, which can cost hundreds to thousands of dollars when not covered by insurance, makes the door to access safe abortion care even more difficult to open, if not entirely impossible. The bill provides no guidance on how the cost of the mandated anesthesia will be covered. This new restriction, like so many others, falls hardest on low-income women and families.

To add further insult to injury, the author of SB 234 is trained as an accountant. He admitted during debate over the bill that he didn’t know what drugs, exactly, his legislation would require doctors to force on women if they choose abortion care. Instead, he said his concern was over the idea that a fetus may be able to feel pain at this point in a pregnancy—something no reputable medical organization has found to be the case.

Anti-choice politicians and advocates have a long history of political interference when it comes to a woman’s own health care decisions. For years, states like Ohio prohibited providers from following the most up-to-date, evidence-based standards for medication abortion. And despite a recent FDA opinion clarifying these best practices, some states are still pushing the outdated requirements. Other states, such as Wisconsin, force providers to show and describe a medically unnecessary ultrasound image to most women before abortion care, even over her objection. In more than a dozen states, women are forced to undergo “counseling” that necessitates two trips to a clinic in order to end a pregnancy—not only driving up the cost of care, but also insinuating that women aren’t capable of making an informed decision without the government’s interference.

Utah’s new law, however, may be the first time a state renders a doctor’s advice moot while also forcing a woman to pay significantly for something that increases risks to her health.

Roundups Sexual Health

This Week in Sex: News From the HIV Epidemic

Martha Kempner

This week in sex: Scientists report the first case of HIV transmission to a patient adhering to PrEP protocols, two studies show a new vaginal ring can help women prevent HIV, and young people still aren't getting tested for the virus.

This Week in Sex is a weekly summary of news and research related to sexual behavior, sexuality education, contraception, STIs, and more.

With the death of Nancy Reagan, the 1980s AIDS crisis is back in the national spotlight. But, of course, HIV and AIDS are still ongoing problems that affect millions of people. This week in sex, we review scientists reporting the first case of HIV transmission to a patient adhering to PrEP protocols, two studies showing a new vaginal ring can help women prevent HIV, and evidence that young people still aren’t getting tested for the virus.

First Case of HIV Transmission While on Truvada

Last week, Canadian scientists reported on what they believe to be the first HIV infection in a patient who was following a PreP (Pre-Exposure Prophylaxis) regimen.

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PrEP is a method of HIV prevention. By taking a daily pill that contains two HIV medicines, sold under the name Truvada, individuals who are HIV-negative but considered to be at high risk of contracting the virus can prevent infection. Studies have found that PrEP is very effective—the Centers for Disease Control and Prevention estimates that people who take the medication every day can reduce their risk of infection by more than 90 percent from sex and by more than 70 percent from injection drug use. One study of men taking PrEP found no infections over a two-and-a-half-year period.

PrEP is less effective when not taken regularly, but the new case of reported PrEP failure involves a 43-year-old man who said that he took his medication daily. His pharmacy records back up that assertion. The man’s partner has HIV, but is on a drug regimen and has an undetectable viral load. The man did report other sexual encounters without condoms with casual partners in the weeks leading up to his diagnosis.

Dr. David Knox, the lead author of this case study, notes that it is difficult to know if a patient really did adhere to the drug regimen, but the evidence in this case suggests that he did. He concluded, “Failure of PrEP in this case was likely due to the transmission of a PrEP-resistant, multi-class resistant strain of HIV 1.”

Experts say, however, that they never expected PrEP to be infallible. As Richard Harrigan of the British Columbia Center for Excellence in HIV/AIDS told Pink News, “I certainly don’t think that this is a situation which calls for panic …. It is an example that demonstrates that PrEP can sometimes be ineffective in the face of drug resistant virus, in the same way that treatment itself can sometimes be ineffective in the face of drug resistant virus.”

Still, some fear that the new study will add to the ongoing debate and apathy that seem to surround PrEP. While some experts see it as a must-have prevention tool, others worry that it will encourage men who have sex with men to forgo using condoms and perhaps increase their risk for other sexually transmitted infections. Still, only 30,000 people in the United States are taking the drug—an estimated one-twentieth of those who could benefit from it.

A New Vaginal Ring Could Help Women Prevent HIV Infection

Researchers have announced promising results from two studies looking at new technology that could help women prevent HIV. The dapivirine ring, named after the drug it contains, was developed by the International Partnership for Microbicides. It looks like the contraceptive ring, Nuvaring, and is similarly inserted high up into the vagina for a month at a time. Instead of releasing hormones to prevent ovulation, however, this ring releases an antiretroviral drug to prevent HIV from reproducing in healthy cells. (A ring that could prevent both pregnancy and HIV is being developed.)

The two studies of the ring are being conducted in Africa. One study recruited about 2,600 women in Malawi, South Africa, Uganda, and Zimbabwe. It found that the ring reduced HIV infection by 27 percent overall and 61 percent for women over age 25. The other study, which is still underway, involves just under 2,000 women in seven sites in South Africa and Uganda. Early results suggest that the ring reduced infection by 31 percent overall when compared to the placebo.

Both studies found that the ring provided little protection to women ages 18-to-21. Researchers are now working to determine how adherence and other biological factors may have impacted such an outcome.

Young People Not Getting Tested for HIV

A study in the February issue of Pediatrics found that HIV testing rates among young people have not increased in the last decade. The researchers looked at data from the Youth Risk Behavior Survey (YRBS), which asks current high school students about sexual behaviors in addition to questions about drugs and alcohol, violence, nutrition, and personal safety (such as using bike helmets and seat belts). Specifically, the YRBS asks students if they’ve ever been tested for HIV.

Using YRBS data collected between 2005 and 2013, the researchers estimated that 22 percent of teens who had ever had sex had been tested for HIV. The percent who had received HIV tests was higher (34 percent) among those who reported four or more lifetime partners. Overall, male teens (17 percent) were less likely than their female peers (27 percent) to have been tested.

Researchers also looked at data from the Behavioral Risk Factor Surveillance System, which asks similar questions to young adults ages 18 to 24. Among people in this age group, between the years of 2011 to 2013, an average of 33 percent had ever been tested. This review of data also found that the percentage of young women who get tested for HIV has been decreasing in recent years—from 42.4 percent in 2011 to 39.5 percent in 2013.

The authors simply conclude, “HIV testing programs do not appear to be successfully reaching high school students and young adults.” They go on to suggest, “Multipronged testing strategies, including provider education, system-level interventions in clinical settings, adolescent-friendly testing services, and sexual health education will likely be needed to increase testing and reduce the percentage of adolescents and young adults living with HIV infection.”