San Francisco's HIV pre-exposure prophylaxis demonstration project is now open and health officials discussed the program at a recent community forum.
Pre-exposure prophylaxis, better known as PrEP, refers to use of antiretroviral drugs prior to HIV exposure to prevent the virus from taking hold in the body. Most PrEP research has looked at a combination of oral tenofovir plus emtricitabine, the drugs in Truvada. The U.S. Food and Drug Administration approved Truvada for PrEP on July 16.
"PrEP isn't for everyone, but we're giving [people] options to keep themselves safe," said Dr. Susan Buchbinder, director of Bridge HIV (formerly the SFDPH HIV Research Section) at the September 19 forum. "We don't know if it's 100 percent effective, but it's a tool that people can use if it's right for them."
While HIV incidence rates are declining in San Francisco, there are still about 400 new cases per year, indicating that the prevention tools people have been using are not fully effective, according to Buchbinder.
Controlled trials have shown that Truvada PrEP can dramatically lower the risk of HIV infection in different population groups, but effectiveness depends taking the drugs consistently.
The iPrEx trial, which enrolled nearly 2,500 gay and bisexual men and a small number of transgender women in six countries (including San Francisco and Boston in the U.S.), found that daily Truvada reduced the risk of HIV by 42 percent overall, rising to 92 percent for participants who had drug levels in their blood indicating good adherence.
The Partners PrEP study, which looked at heterosexual serodiscordant couples in Kenya and Uganda, found that the drugs in Truvada reduced the likelihood of infection by 75 percent, while the TDF2, also looking at heterosexual men and women in Africa, showed a 62 percent risk reduction.
"PrEP is not a home run and not everyone was protected," Buchbinder summarized. "If you were to take it perfectly every day, would it always work? We don't know the answer."
While most HIV advocacy groups lauded the approval of Truvada for PrEP, skeptics have expressed doubts about whether healthy HIV-negative people will consistently take a daily pill, and raised concerns about drug resistance, side effects, and an increase in unprotected sex.
The real world
Now that Truvada PrEP has demonstrated its effectiveness in controlled clinical studies, the question is whether it will also work in the real world, without the intensive support and monitoring available in a clinical trial setting.
To answer some of these questions, the National Institute of Allergy and Infectious Diseases is partnering with local health departments to set up PrEP demonstration projects like the one launched September 21.
The first out of the gate, San Francisco's demo project aims to enroll 300 HIV-negative men who have sex with men and transgender women at City Clinic, while a sister project in Miami will enroll 200 participants.
The goals of the demonstration project include determining the level of community interest in PrEP, evaluating how well people adhere to a daily prevention regimen, and assessing whether sexual practices change, according to City Clinic medical director Stephanie Cohen.
"So far everything we know [about PrEP] is from clinical studies in which people didn't know whether they were taking PrEP or placebo," Cohen said. "There's still a lot to learn [including] how do we get PrEP out there safely and can we provide PrEP in the busy environment of City Clinic?"
Eligible participants are gay and bisexual men and transgender women who are sexually active and at risk of HIV infection. They must have a confirmed HIV-negative screening test, normal kidney function and no serious medical conditions, and must not be taking any other experimental drugs or vaccines.
Demo project participants will receive Truvada PrEP for up to 48 weeks (the duration of NIAID funding) along with a prevention package that includes risk reduction counseling and free condoms. They will receive HIV RNA tests every three months to detect early infection. They will also get regular STD tests, adherence counseling, and monitoring of side effects including changes in kidney function.
"[PrEP] studies included mostly young, healthy people, but we see people who are older and at higher risk of kidney disease and bone loss," said Harry Lampiris, chief of infectious disease at SF Veterans Administration Medical Center, who prescribes Truvada PrEP in his clinical practice. "Being more predisposed to bone or kidney [problems] doesn't mean you can't take PrEP, it just means you need to take more precautions."
Two men currently using Truvada PrEP described their experiences at the forum.
A man who identified himself only by his first name, Michael, is an iPrEx participant who has been taking PrEP for four years. He said that over this period he has only missed about a dozen pills. At age 56, he has not had any kidney or bone problems. His side effects include nausea – "mild but pretty much every day" – and "significant flatulence." Although Truvada's gastrointestinal side effects generally dissipate after several weeks, he said the problem has been chronic for him.
Derek Brocklehurst, an HIV clinic nurse, started PrEP in October 2011, having asked his doctor to prescribe it prior to approval. "I have been 100 percent adherent – it's in my backpack every day," he said, adding, "I haven't really noticed any side effects." Having had several exposures to HIV through unprotected sex, using PrEP "eased my mind," he said, and reduced anxiety about becoming infected.
Cost and access issues around PrEP are still being worked out. The demo project has funding to provide the drug and associated care and monitoring free for one year. Healthy San Francisco is now considering whether to add Truvada PrEP to its formulary, according to Cohen.
Brocklehurst said his insurance company, Anthem Blue Cross, covers PrEP and Truvada manufacturer Gilead Sciences offers co-pay assistance, so he pays nothing out of pocket. Michael said he does not know whether Kaiser Permanente will cover the drug, and he may not be able to afford to stay on PrEP after his study ends in December.
Daily Truvada may turn out not to be the optimal PrEP regimen. Albert Liu, director of HIV prevention intervention studies at Bridge HIV, described two trials looking at other types of PrEP that are now enrolling participants.
The NEXT-PrEP trial (HPTN 069), will compare the safety and tolerability of four PrEP regimens for high-risk men who have sex with men. Participants will be randomly assigned to take combinations of tenofovir, emtricitabine, maraviroc (Selzentry), or placebo; everyone will receive at least one active drug.
Study MTN-017 will look at a new formulation of a tenofovir-containing rectal gel, similar to the vaginal gel shown to reduce HIV infection risk in the CAPRISA 004 trial. Participants will be assigned to use daily oral Truvada PrEP, daily tenofovir gel, or tenofovir gel applied before and after receptive anal sex.
"We're trying to give people as many options as possible," said Buchbinder. "For some, a monthly injection is the best option, for some using [an antiretroviral] lube during sex is a great option, some would rather take a daily pill."
Cohen ended the forum noting that demo project researchers "really don't know what kind of demand we're going to get." An informal poll of the audience revealed that about half thought the study would have participants breaking down the doors, while the other half thought the DPH would have to work to convince people to try PrEP.
"It's really an individual decision for a person whether PrEP is something that makes sense in their life," Cohen concluded. "PrEP is a personal choice and we want to support people if they decide to start, if they want to stop, or if due to life changes they want to start again."
The San Francisco AIDS Foundation has collaborated with Bridge HIV, City Clinic, NIAID, Project Inform, and other organizations to develop a new website, www.PrEPfacts.org, to provide information about PrEP and the SF demo project. To check eligibility for the program, call (415) 487-5537 or visit City Clinic.