Study: New Therapy Shows Promise for HIV Prevention

Jodi Jacobson

Long-awaited results were released today in the New England Journal of Medicine of a study on the effectiveness of a single daily tablet for preventing HIV transmission among those at high risk of infection.

Earlier today we published an article by Anna Forbes on the implications of the iPrEx trial for women, and an article this past summer about the findings from the CAPRISA trial.

Long-awaited results were released today in the New England Journal of Medicine of a study on the effectiveness of a single daily tablet for preventing HIV transmission among those at high risk of infection. Findings from the iPrEx trial, conducted among HIV-negative gay men, transgender women, and other men who have sex with men (MSM), showed that individuals who took the oral therapy containing two widely-used HIV medications, emtricitabine and tenofovir (FTC/TDF), experienced an average of 43.8 percent fewer HIV infections than those who received placebos.  The combined antiretroviral drug is known under its brand name as Truvada.

The trial, as summarized by Medscape and in a release from the AIDS Foundation of Chicago (AFC), included 2,499 participants, including individuals from Peru, Ecuador, Brazil, South Africa, Thailand and the United States.

Half the men were randomized into the active arm that received Truvada, which is currently approved by the US Food and Drug Administration for treatment of HIV infection, and the other half were randomized into the placebo arm and received a look-alike pill with no active ingredient. All the participants tested negative for HIV at the beginning of the trial, but reported engaging in sexual practices that put them at high risk for infection. Both groups in the study were followed up for over a year, also received HIV education, testing, and condoms. Neither the participants nor the researchers knew who was assigned to which arm (placebo or Truvada) of the study.

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Enrollment for the trial began in June 2007 and was completed in December 2009. The primary analysis of the results released today includes participants who were followed until May 1, 2010, or for an average of 14 months.

Each participant was tested for HIV at monthly trial visits and given intensive pre-and-post test counseling. Additionally, they were regularly screened for sexually transmitted infections and received condoms, making up a very robust prevention package.

Study materials note that while pill-taking measures that rely on self-reports are not objective, testing to measure levels of the PrEP drug in the blood of study participants — a more reliable measure of pill-taking — also indicated that those participants who were protected against HIV infection were likely taking the study drug more regularly.  Among a subset of study participants who received the active drug, detectable levels of the PrEP drug combination were found in the blood of 51 percent (22 of 43) of a group that remained HIV-negative, but in only 9 percent (3 of 34) of participants who became HIV infected.  Low or absent drug levels underlay all of the infections that occurred among those who received active PrEP, while those who used the drug more regularly had higher levels of protection against HIV infection.

At the end of the trial, there were 36 infections in participants who received Truvada and 64 in recipients who took the placebo. Researchers calculated that the use of Truvada reduced new HIV infections by an estimated 43.8 percent overall when compared to placebo. While there appeared to be few side effects reported by the men who were taking the Truvada tablet, researchers and advocates make clear that much more information is needed regarding long term safety of this drug.

Advocates and researchers alike expressed cautious excitement about the development.

“This discovery alters the HIV prevention landscape forever. While this level of efficacy is relatively strong, PrEP is not quite ready for prime time and work remains before this strategy is rolled out. However, we are thrilled to have a new prevention option beyond male and female condoms visible on the horizon,” said Jim Pickett, Director of Advocacy at (AFC) and Chair of IRMA – International Rectal Microbicide Advocates (IRMA).  The full IRMA statement can be found here.

According to AFC: “It is important to emphasize the factors that led to successful use of Truvada to prevent HIV in iPrEx.” Adherence was a critical, so that taking the pill regularly was one of the most important factors in reducing the risk of infection. According to AFC, men who did not take the pill regularly did not see a protective benefit.

Regular HIV testing and ongoing monitoring by a physician was also critical. For this strategy to work, each of these pieces, including a doctor’s prescription, need to be in place.

“The study team found that about half of the men in the active arm of the trial were in fact not taking their pills regularly, if at all,” said Pickett of AFC. “It is not clear why this happened, but it certainly suggests that alternate means of using ARVs to prevent HIV infection may be more acceptable for these men. The primary means of transmission among gay men and other MSM is through unprotected anal intercourse. If we develop an ARV as a gel or lubricant applied rectally – a rectal microbicide – it could be more acceptable for some individuals who don’t like taking pills.”

Many gay men and other MSM already use lubricants for anal intercourse, notes Pickett, so they wouldn’t have to modify their behavior to achieve higher levels of protection with a rectal microbicide formulated as a lubricant. Adopting a new behavior—such as taking a pill every day—can be a considerable challenge for some.

A statement from The Global Forum on MSM & HIV (MSMGF) said that:

“These findings are promising and show that there is a potential role for PrEP to play in HIV prevention for MSM. However, with this new reality comes the fact that we, as a community of advocates, must now confront difficult questions about roll-out, cost, HIV-prevention messaging and the place PrEP takes in a broader continuum of prevention interventions.”

Today, said MSMGF, “Access to ARVs remains extremely difficult around the world. UNAIDS has estimated that only 36 percent of people living with HIV who need ARVs could access them just one year ago.”

Implementation of PrEP is highly unlikely in countries where access to ARVs is already seriously limited.  Even in places where access to ARVs is more stable, PrEP will likely be targeted to groups most at risk for HIV, including MSM. This would in turn require disclosure of same-sex behavior, which could prove difficult or even dangerous in countries where violence, stigma and discrimination against MSM persists.  

The iPrEx team has rightly noted that this is not a study of PrEP in a vacuum, but a study of PrEP when combined with a suite of other proven HIV prevention interventions – a state-of-the-art model of combination prevention, which may have been an important contributing factor underlying these encouraging results, continued the MSMGF statement.

However, the additional components of this intervention also remain out of reach for the vast majority of MSM; an estimated 90 percent of MSM globally lack access to even the most basic prevention services.  To achieve true combination prevention, we must not only significantly expand access to ARVs, but also promote much greater access to condoms, lubricant and other basic sexual health services.

Another challenge of concern according to MSMGF and others is the question of  adherence, especially outside a study context.  Although study participants learned about PrEP and the importance of adherence as part of the trial protocol, researchers reported that only about half of study participants took the medication consistently.  Compounding the problem of adherence is the challenge of developing communication strategies about an intervention that is just 44 percent effective – and only when taken in combination with a full complement of prevention services.  

Dr. Ian McGowan, one of the principal investigators of the Microbicide Trials Network and Scientific Vice Chair of IRMA agreed.

“The data from the iPrEx study are encouraging but the less than ideal adherence rate to oral PrEP clearly show that we need additional prevention approaches such as rectal microbicides that could be used by men and women at risk of HIV infection through unprotected receptive anal intercourse,” he said.

The world’s third rectal microbicide trial is currently underway with sites in Pittsburgh, Pennsylvania; Boston, Massachusetts; and Birmingham, Alabama. Scientists are testing the rectal safety and acceptability of tenofovir gel, a microbicide developed for vaginal use that has shown promise for preventing HIV through vaginal intercourse. Depending on the outcome of this new study, tenofovir gel could be further evaluated to determine if it can reduce the risk of HIV among both men and women who engage in receptive anal intercourse.

According to IRMA’s Pickett, this new Phase I rectal microbicide study, known as MTN-007, aims to determine if rectal use of tenofovir gel is safe, and in particular, does not cause cells in the rectum to become more vulnerable to HIV. Investigators will also ask trial participants questions regarding the gel’s desirability. The trial is planning to recruit a total of 60 men and women.

While the rectal microbicide field has gained significant momentum, more focus and resources are needed. In 2010, U.S. $7.2 million is being spent globally on rectal microbicide research. IRMA has calculated that annual investments must increase by 40% from 2011 – 2014, to U.S. $10 million/year and must increase further to U.S. $44 million (a six-fold increase) in the years 2015 – 2020. These targets need to be met to ensure a minimum of candidate products are moving through the research pipeline into late stage testing for effectiveness.

As noted in Medscape, the iPrEX is the second major study this year demonstrating the efficacy of PrEP. In July, South African researchers in what is known as the CAPRISA 004 trial published an article in Science Express reporting how a vaginal gel containing tenofovir lowered the risk of HIV infection in sexually active women by 39 percent.

As these highly promising advances in both science and technological are being made, researchers and advocates both underscore again and again there is no silver bullet.

“PrEP is best conceived as a back-up [to more direct HIV prevention strategies],” said Robert Grant, MD, lead study author of an article published online today in the New England Journal of Medicine that reports the study findings.

Other PrEP trials are ongoing. Results from studies among heterosexuals in Africa and injection drug users in Thailand are expected next year.

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.”

Roundups Sexual Health

This Year in Sex: It’s Time to Take Action

Martha Kempner

We have the tools to work against sexually transmitted infections, harmful "conversion therapy" for LGBTQ teens, and sexual assault on college campuses. Now, we just have to use them.

This Year in Sex takes a look back at the news and research related to sexual behavior, sexuality education, contraception, sexually transmitted infections, and other topics that captured our attention in 2015.

STIs Are on the Rise in Every Group

This year, it seemed like every week there was a new headline about a rise in sexually transmitted infections or diseases among a specific group, in a certain geographic area, or even among the general population. When states released their 2014 STI data, we learned that Minnesota’s rates hit a record high and that the rate of gonorrhea nearly doubled in Montana between 2013 and 2014. Counties across the country reported rising rates of chlamydia, gonorrhea, and syphilis. California’s Humboldt County, for example, noted a tenfold increase in gonorrhea since 2010, and Clark County, Nevada—home of Las Vegas—reported a 50 percent increase from 2014 in the number of cases of primary and secondary syphilis.

In fact, many of the headlines this year involved syphilis—a curable disease that the United States was once close to eliminating because rates were so low has continued its resurgence. A Department of Defense report, for example, points to a 41 percent increase in the rate of this disease among men in the military. Another disturbing report showed a dramatic rise in the number of babies born with syphilis; congenital syphilis can cause miscarriage, stillbirth, severe illness in the infant, and even early infant death. This reflects both an increase in cases of the disease among women and a lack of prenatal testing that could catch and treat syphilis during pregnancy. This year, there was also an outbreak of ocular syphilis on the West Coast that led to blindness in at least one patient.

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While syphilis is on the rise in both men and women, 90 percent of cases are in men, 83 percent of which are those who have sex with men in cases where the gender of the partner is known.

Young people are also disproportionately impacted by STIs, specifically chlamydia and gonorrhea—54 percent of the cases of gonorrhea and 66 percent of cases of chlamydia reported to the CDC occurred in those younger than 25. Though if detected early and treated, those STIs can be cured, they can also cause future health problems, including infertility.

Perhaps the ultimate headline about STIs this year, however, was the one in which we learned that almost everyone has herpes. A report by the World Health Organization estimated that 3.7 billion people worldwide—or about two out of every three adults across the globe—are infected with herpes simplex virus 1.

All of this news should remind us that sexually transmitted diseases and infections are a public health crisis and we have to up a fight. We need to prevent the spread by educating young people and adults and making condoms readily available. We need to invest in testing that can help people detect STIs before they face many potential health consequences and prevent them from spreading further. And, we need, of course, to provide access to treatment and combat stigma-based fear.

We Know How to Prevent HIV (Now We Just Have to Keep Doing It)

There was a lot of good news this year when it comes to preventing HIV, much of which focused on how well pre-exposure prophylaxis (PrEP) can work. PrEP is a combination of two antiretroviral drugs—tenofovir and emtricitabine—used to treat people who have HIV. When taken daily by people who are HIV-negative, these drugs have been shown to prevent transmission of the virus. In fact, a study by Kaiser Permanente found that since the approval of PrEP in 2012, none of the patients who were using it became infected with HIV. This was actually better than the researchers expected given the findings in clinical trials.

Incorporating PrEP into a multifaceted HIV-prevention program can work, and San Francisco—once a hotbed of the national HIV and AIDS epidemic—proved that, with just 302 new HIV diagnoses in 2014. Getting those HIV-negative residents who are at high risk of contracting the virus onto PrEP is one of the strategies the city uses. In addition, the city provides rapid treatment for the newly diagnosed and continued follow-up appointments to make sure that patients stay on their treatment plan. This can not only help them stay healthy but can prevent the further spread of the virus, as people who adhere to an antiretroviral drug protocol can suppress the virus to the point that they cannot transmit it to others. In San Francisco, 82 percent of residents with HIV are in care and 72 percent are suppressed. This is significantly higher than national statistics, which show that 39 percent of those with HIV are in treatment and only 30 are taking their drug regimen regularly enough to be considered suppressed.

While it will be difficult for many places to adopt a system as expensive as the one in San Francisco, its success shows us that we have the tools we need to prevent HIV. And, in fact, diagnoses of HIV are down in the United States by 19 percent, though the success was not evenly spread: some groups, such as Latino and Black men who have sex with men, are actually seeing increases. It’s time to renew our investment in ending this epidemic for everyone.

Vaccines (Including the HPV Vaccine) Are Not Dangerous, But Skipping Them Is

The year started with a massive outbreak of the measles on the West Coast, so it’s not surprising that there was a lot of conversation about the value of inoculations and what happens when too many people in a certain area are not vaccinated. In the midst of the epidemic and the debate, some schools asked unvaccinated children to stay home, and some states tried to close loopholes that make it easy for parents to opt of required vaccines because of “personal beliefs.”

Unfortunately, many of these personal beliefs are based on false reports and misinformation suggesting that certain vaccines cause autism. A study of anti-vaccine websites found that this misinformation is abundant on the Internet. Of 480 sites dedicated to the anti-vaccine movement, about 65 percent claimed that vaccines are dangerous, about 62 percent claimed vaccines cause autism, and roughly 40 percent claimed vaccines caused “brain injury.” Many of these facts lacked citations, but some were based on misinterpretation of legitimate research.

The scientific truth is that vaccines are safe and have no connection to autism. If there was any doubt, yet another study was released this year confirming it. In fact, the only study that has ever found a connection was proven to be falsified by an unethical researcher who stood to make a profit.

Of course, that didn’t stop the field of Republican presidential hopefuls—which includes two medical doctors—from trying to score political points by suggesting the government may “push” “unnecessary” vaccines.

Though not mentioned by name, they may have been referring to the HPV vaccine, which has always been controversial because of its connection to sex. There seems to be a sense that because HPV is sexually transmitted, vaccinating against it is less important or will give teens permission to have sex. Numerous studies have shown this to be false. One study published this year even found that girls who have gotten the HPV vaccine take fewer sexual risks.

But the fear and misinformation continues, and it turns out doctors might not be helping matters. One study showed doctors may be discouraging the HPV vaccine by not strongly recommending it, not doing so in a timely manner (the CDC advises that vaccinations should start at age 11), and only suggesting it to young people they perceive to be at risk. This could be part of why HPV vaccination rates still lag behind those of other recommended vaccines.

We need to remember that this vaccine prevents cancer. The newest protects against nine strains of the virus and has the potential to prevent 90 percent of cervical, vulvar, vaginal, and anal cancer. And there is reason to believe it will also prevent oral cancer. That’s five cancers prevented by one series of shots.

Of course, like the others, it can only work if our children obtain it. Hopefully, it will not take another outbreak of a preventable disease like measles for us to realize how lucky we are to live in an age in which we know how to stop so many of the diseases that disabled and killed generations before us.

Government Weighs in on ‘Conversion Therapy’

This year saw many positive developments in the struggle for LGBTQ rights, one of which was a willingness of both the White House and many senators to come out against “conversion therapy” for young people. Sometimes called reparative therapy, this is the practice of trying to change a person’s sexual orientation or “cure” their homosexuality. While no legitimate medical organizations sanction such a practice, some young people are subjected to it because their parents or their religion disapprove of same-sex relationships.

Conversion therapy can include anything from Bible study to forced heterosexual dating to aversion therapy, in which patients are shown homosexual erotica and shocked every time they display arousal. Research has found not only that it does not work to change an individual’s sexual orientation, but that it can be harmful and lead to depression, shame, and suicidal thoughts.

In April, the White House released a report condemning the practice for teenagers and asking states to ban it for minors. In an accompanying letter President Obama wrote: “Tonight, somewhere in America, a young person, let’s say a young man, will struggle to fall to sleep, wrestling alone with a secret he’s held as long as he can remember. Soon, perhaps, he will decide it’s time to let that secret out. What happens next depends on him, his family, as well as his friends and his teachers and his community. But it also depends on us—on the kind of society we engender, the kind of future we build.” Two Democratic legislators echoed this sentiment when they offered a resolution asking the Senate to condemn the practice as well, and a report from the Substance Abuse and Mental Health Services Administration attempted to offer parents alternatives that can support LGBTQ young people.

This year Oregon joined those states—including New Jersey, California, and the District of Columbia—that do ban the practice. Furthermore, a challenge to New Jersey’s ban failed when the U.S. Supreme Court turned the case away.

Doing away with harmful practices is a step in the right direction for LGBTQ adolescents, but there is still much more to do in order to protect and educate all of our young people.

We All Continued Talking About Consent

The problem of sexual assault on college campuses was pervasive in the news in 2015. At the end of last year, California became the first state to pass a law mandating affirmative consent on college campuses, also known as “yes means yes.” This year, New York joined it, and other states are considering doing the same.

Affirmative consent has its critics, who say that the standard is unclear and unrealistic in real-life settings. A poll by the Kaiser Family Foundation found that most college students (83 percent) had heard of affirmative consent and many (69 percent) felt it was very or at least somewhat realistic. But when asked whether different scenarios met the standard, students showed a variety of opinions, proving that putting the standard into practice might be tricky.

Still, I believe the conversations about affirmative consent have been useful. They have given us a platform to talk more about the role of alcohol in sexual behavior and sexual assault, and what happens when one is not passed out but clearly very drunk—and therefore incapable of giving consent. We’ve made college students more clearly establish their own boundaries. And educators have been able to both reiterate and go beyond the “no means no” message to talk about what good, consensual sex might look like.

Affirmative consent is not the end-all solution to sexual assault—it won’t, for example, prevent some perpetrators intent on raping. But if we talk about it enough and start before college—California, for example, mandated affirmative consent message in high school—we might have a generation who can think critically about their own behavior and the behavior of others, a generation that is prepared for healthy sexual relationships and knows that, at the bare minimum, a sexual encounter must include consent.