Evidence for PrEP efficacy grows, but implementation presents challenges

Pre-exposure prophylaxis (PrEP) was a major topic at the 2015 National HIV Prevention Conference (NHPC) last week in Atlanta. A growing body of evidence continues to confirm that Truvada PrEP is highly effective at preventing HIV infection if taken regularly, both in clinical trials and in real-world clinical use. Yet uptake has been uneven, and researchers and front-line health workers are learning about barriers to PrEP implementation and scale-up for diverse population groups.

"The argument is over about PrEP," US National Institute of Allergy and Infectious Diseases (NIAID) director Anthony Fauci said during his opening lecture. "If you take the drug, it works, not only in a clinical trial but in the field."

That message appears to finally be getting out to people at risk for HIV and their providers.

"We're now reaching a tipping point where clinicians are hearing that their colleagues are prescribing PrEP and maybe they could too," said Dawn Smith of the US Centers for Disease Control and Prevention (CDC).

A plenary lecture by NIAID Division of AIDS director Carl Dieffenbach and dozens of abstract presentations were devoted to different aspects of PrEP, ranging from knowledge and attitudes of users and providers, to implementation of PrEP in various settings.

"PrEP works, but only if you take it," Dieffenbach emphasised, underlining the importance of offering PrEP as part of a comprehensive prevention package that is attractive to the people most at risk for HIV.

New PrEP methods are "not on the horizon, but just over the horizon," Dieffenbach continued, potentially including broadly neutralising antibodies, microbicides in rings or other sustained-release delivery systems and long acting injectable agents. "We may one day have PrEP that can be administered once a year," he predicted.

Some of the most promising findings on Truvada (tenofovir/emtricitabine) PrEP in real-world use have come from cities with large populations of gay men, progressive political attitudes and generous public health funding.

But as New York City assistant health commissioner Demetre Daskalakis stressed, PrEP is "not just a big old gay good time," and access needs to expand "beyond our gay choir."

San Francisco experience

Several presenters touted the success of San Francisco in preventing and treating HIV. The city was a study site for the pivotal iPrEx trial and one of the first PrEP demonstration projects. By some estimates a quarter to a third of at-risk gay and bisexual men in San Francisco are on PrEP. Newly diagnosed HIV infections fell by about 40% between 2006 and 2014, though it is probably too soon for PrEP to have made a substantial contribution to the latest numbers.

Steve Gibson presented findings from the San Francisco's AIDS Foundation's Magnet, a sexual health clinic serving gay men in the Castro neighbourhood. The Magnet PrEP programme launched in November 2014. Care is provided mainly by nurses and a benefits navigator helps clients find ways to pay for Truvada. After a medical evaluation that includes HIV, sexually transmitted infection (STI) and basic lab tests, eligible participants receive a prescription the same day.

A client survey in November 2014 found that 91% had heard of PrEP, 60% were interested in it and 19% had already used it. During a one-year period, 695 people were screened for the PrEP programme and 90% enrolled.

All but two participants were non-transgender men, with a mean age of 34 years (range 18 to 71). More than two-thirds (69%) were white and 24% were another race; 24% identified as Hispanic. Participants reported an average of 19 sexual partners a year. About 20% were diagnosed with STIs at enrolment. Most (91%) wanted PrEP because they have condomless sex and 12% had an HIV-positive partner.

No new HIV infections were seen among the approximately 600 PrEP users over about one year of follow-up. Adherence remained high over time – 95% at month 1 on PrEP and 94% at month 7 reported they missed fewer than three doses during the past week. Among the 582 men surveyed at month 1, 13% reported less condom use, 15% reported more and 59% reported no change. Among the 124 men who responded at month 7, 15% said they used condoms less, 37% said they did so more and 48% reported no change.

"PrEP is easy, safe, effective and needed," Gibson and colleagues concluded, adding that administration can be done by nurses and volunteers.

"The bottom line is that there were no new HIV infections," Gibson said. "We've found that the combination of clinical services combined with benefits navigation is what helps ensure that people can start taking the medication the same day, often costing the client nothing."

Gibson acknowledged, however, that "PrEP in the Castro is not going to be the same as PrEP throughout San Francisco," noting that San Francisco AIDS Foundation has also opened a PrEP clinic at its South of Market location, which will serve a more diverse clientele.

San Francisco City Clinic, also located South of Market, was one site of the three-city PrEP Demo Project, after which it started an ongoing PrEP programme to meet growing demand.

Stephanie Cohen and colleagues described integration of PrEP into routine sexual health services at City Clinic, which sees approximately 11,000 clients annually, including more than 4000 HIV-negative gay and bi men. A higher proportion are non-white compared to Magnet's clientele (8% black, 29% Latino and 15% Asian). More than half of PrEP clients were uninsured and among those who had insurance 65% were on Medicaid coverage for low-income people.

The researchers said that PrEP delivery in a municipal STI clinic setting is feasible but requires dedicated staff to provide counselling and help people enrol in medication assistance programmes or other coverage.

Popular PrEP

New York City, Chicago and Seattle are other cities where PrEP has been promoted by local public health officials.

In June 2014 the governor of New York State announced a plan to end HIV/AIDS as an epidemic, and made PrEP one of the three key pillars of the effort. A majority of HIV-positive people and people at risk in the state live in New York City.

Demetre Daskalakis described Department of Health and Mental Hygiene (DOHMH) efforts to accelerate PrEP implementation, including social marketing to promote awareness in high-priority populations, creation of informational materials, lunchtime 'detailing' to train providers to deliver PrEP and maintaining a public listing of doctors and nurses willing and able to provide PrEP. DOHMH offers PrEP at no cost to people who are uninsured or underinsured at STI clinics and other sites.

Nana Mensah and colleagues looked at awareness and use of PrEP among HIV-negative gay and bi men in New York City recruited via social networking and hook-up sites or apps. They reported that PrEP awareness increased significantly, from around 30% in the Spring of 2012 to over 80% in the Autumn of 2014. PrEP use also increased significantly, from less than 2% to approximately 7%. Men who were white, older and had more than a high school education were more likely to know about and use PrEP.

A team from Chicago reported outcomes from a PrEP programme started in March 2014 at Howard Brown Health Center (HBHC), a large LGBT community health clinic. After a successful pilot programme in which the Chicago Department of Public Health's Lakeview STI Clinic referred HIV-negative gay men diagnosed with syphilis or rectal gonorrhoea and partners of HIV-positive clients to HBHC for PrEP services, the model was expanded to other DPH STI clinics.

Bryan Bautista-Gutierrez and colleagues said they significantly underestimated the amount of time a newly hired adherence counsellor would have to spend processing medication and co-pay assistance paperwork, while overestimating the time spent actually providing prevention and adherence counselling.

Washington State is not as large and does not have as high HIV prevalence as other early-adopter jurisdictions, but the state Department of Health took the lead in developing a 'PrEP DAP' drug assistance programme to help residents pay for Truvada.

PrEP DAP, launched in April 2014, uses the state's ADAP (AIDS Drug Assistance Program) infrastructure. Eligible participants are either HIV-negative people with an HIV-positive partner, or high-risk HIV-negative gay and bisexual men. A majority live in King County (which includes Seattle) and more than 80% are insured. The programme, which has no income requirements, covers the cost of Truvada only, not provider visits or lab tests.

Marie Courogen of the Washington State Department of Health reported that just over 700 participants are receiving Truvada through the programme – far more than the 200 initially planned.

To date no new HIV seroconversions have been seen among programme participants, although some early infections have been detected on initial testing of people seeking PrEP. So far the programme has managed to stay within its $2 million budget – in part because many applicants have insurance and require only co-pay assistance rather than full PrEP coverage – but it is starting to reach its limits and is looking for more sources of funding.

Seattle has also pioneered the concept of a pharmacist-run PrEP service in a community pharmacy setting. Pharmacists with the One-Step PrEP service – established in March 2015 – provide blood testing, counselling and PrEP during a single visit.

"If sustainable, PrEP in pharmacies would provide an additional option for accessing this mode of HIV prevention for high-risk individuals who do not have a primary care provider or whose PCP is not experienced with this type of treatment," Elyse Tung and colleagues concluded.

Engaging communities of colour

Across the bay but a world away from San Francisco, people at risk for HIV in Oakland are more likely to be African American and to have lower incomes and less education, on average. As in San Francisco, however, a majority of people newly diagnosed with HIV are men who have sex with men (MSM) – over 70% in 2010 to 2012.

Ifeoma Udoh of Pangea presented findings from Oakland's CRUSH Project (Connecting Resources for Urban Sexual Health), a demonstration project integrating routine sexual health services – including STI screening, PrEP and post-exposure prophylaxis (PEP) – into an existing HIV primary care clinic. The project targets gay and bisexual men and transgender people age 18 to 29, with a focus on people of colour.

The CRUSH Project, started in February 2014, is located at the East Bay AIDS Center (EBAC), operated by the large non-profit Sutter Health system. The project's supportive services are modelled after EBAC's Downtown Youth Clinic, which includes outreach to at-risk youth, linkage to and retention in care, adherence support and prevention services.

"The population is very different and the makeup of the epidemic is very different" in Oakland compared to San Francisco, according to Udoh. The epidemic is "highly focused on communities of colour," and there is no publicly supported STI clinic in all of Alameda County.

Between February 2014 and November 2015 CRUSH enrolled 281 participants. At the time of the analysis 177 were currently enrolled, 66 had completed follow-up, 21 were lost to follow-up after 12 months and 17 discontinued before 12 months. Referrals primarily came from clinic staff, outside providers, community organisations or other project participants. PrEP uptake was driven by social networks, with staff outreach efforts being less successful.

Among the enrolled participants, 252 chose to start PrEP and they stayed on it for an average of about 10 months. PrEP users were mostly men (about 95%), with a small number of women or transgender participants; the average age was 25 years. About 80% were people of colour, mostly Hispanic/Latino, black or mixed race/ethnicity. About 60% were uninsured but qualified for Medicaid or Covered California (Affordable Care Act) coverage.

Participants seeking PrEP needed both sexual health and primary care services. About 70% already had STIs at enrolment – before starting PrEP. About a quarter of people seeking PrEP were found to need PEP due to a recent high-risk sexual exposure.

"The PEP to PrEP to PEP to PrEP continuum cannot be overemphasized – many went back and forth," Udoh said.

No CRUSH participants have seroconverted while on PrEP, Udoh said, although some were identified as being already HIV-positive when they came in for pre-PrEP testing.

Udoh's team concluded that it was important to include a benefits counsellor to help people access insurance. A related CRUSH Project analysis found that patient navigators and retention co-ordinators also play an important role, helping young clients navigate through the medical system, calling or texting reminders about upcoming appointments and encouraging adherence.

In response to an audience question, Udoh said that the lack of women accessing PrEP is an important issue, and the CRUSH Project will be starting an arm for women.

Turning to another city where the HIV epidemic is concentrated among people of colour, Helena Kwakwa discussed engagement of at-risk individuals and communities in PrEP services in Philadelphia.

The Philadelphia Department of Public Health operates eight federally funded health facilities in city neighbourhoods, each of which has an HIV clinic and provides a broad array of primary health services including routine HIV testing.

The Strawberry Mansion Health Center was one of the first sites in the nationwide Sustainable Health Center Implementation PrEP Pilot (SHIPP) – a three-year programme evaluating the scale-up of PrEP delivery at community health centres – and now all eight are participating. SHIPP targets MSM, people who inject drugs and at-risk heterosexual women and men. Health centre clinicians and community-based organisations that offer HIV testing are asked to refer people who test negative but are at high risk to the PrEP programme and HIV providers are asked to refer partners of their HIV-positive patients.

Kwakwa reported that more than 90 people are now receiving PrEP through the health centres. About a third are women – higher than the proportions in other cities where PrEP programmes primarily target gay men – and 80% are people of colour, mostly African American. During follow-up 10 people discontinued PrEP, mainly due to changing circumstances. Unfortunately one person who stopped PrEP due to mild gastrointestinal symptoms seroconverted four weeks later.

Kwakwa said that while prevention services are reaching the people who are at highest risk for HIV infection, only a small number are making it all the way through the PrEP engagement cascade.

Of the 412 men and 280 women initially referred for PrEP – mostly coming from HIV testing sites at primary care or STI clinics – 234 men and 139 women indicated they were interested, but only 63 men and 22 women started Truvada. That is, just 15% of the men and 8% of the women who were referred ultimately started PrEP. People referred by clinicians, peers or partners were more likely to do so than those referred from HIV testing sites.

Kwakwa's team concluded that "timing is key," and finding ways to respond to referrals quickly and in person has improved follow-through. Given that women were about equally likely to express interest in PrEP but less likely to start, they suggested reaching out to women through family planning providers.

PrEP in the Deep South

Finally, Laura Beauchamps described a PrEP collaboration between a federally funded STI clinic and a community-based primary care clinic in Jackson, Mississippi – a community with among the highest HIV and STI rates in the US.

The Crossroads Clinic offers free STI and HIV testing to nearly 5000 people annually, of whom more than 90% are black, about half are women and 16% are MSM; approximately 12% are young (age 13 to 29) black gay and bi men, the group with the highest HIV incidence. About 2% of all clinic patients – but 12% of young gay MSM – test positive for HIV. The Open Arms Healthcare Center focuses on healthcare for the LGBT population and communities of colour.

In January 2014 the two clinics established a collaboration to implement a PrEP programme. The Crossroads Clinic screens clients for risk behaviour, performs HIV and STI testing and discusses PrEP, while Open Arms does the initial PrEP appointment, clinical evaluation, Truvada prescribing and follow-up every three months.

Beauchamps described 130 gay and bi men who discussed PrEP and expressed interest; 78% were African American. Although 76% were classified as being at high risk for HIV, only 26% perceived themselves as such. Most (86%) said they would be likely to take PrEP if it were prescribed that same day, but only half as many (43%) attended a first PrEP clinical appointment; 73 men ultimately received a prescription for Truvada.

Of the 18% who said they were not interested in a clinical appointment for PrEP, the main reason was low perceived risk. Among those who expressed initial interest but did not follow up with an appointment, more than half expressed concerns about side effects and cost, while a quarter worried about interactions between Truvada and alcohol or drugs.

Among the young black gay men who received a Truvada prescription there was again high attrition. Just over two-thirds (69%) actually started taking PrEP, 56% were retained in care at three months and only 35% were still in care at six months.

Based on this experience Beauchamps and her team recommend developing a patient navigator programme to assist with education and help overcome common barriers to scaling-up PrEP.

While there has been much discussion of the impact of PrEP on sexually transmitted infections among gay and bi men, these and other studies show that men seeking or being referred for PrEP already are not using condoms and have high STI rates.

"Rectal gonorrhoea is pretty much a slam dunk indicator that a person could benefit from PrEP," Dieffenbach said during his plenary talk. "So many people who want PrEP are already going condomless," he added. "If a patient has gonorrhoea, their provider can say, 'You could have had HIV, but PrEP is protecting you'…'Keep up the good work' has got to be part of our message."

"When you're screening for STIs every three months, you're going to see more than when people come in less often," said Dawn Smith of the CDC, suggesting that the resistance of some providers to offer PrEP is like a doctor saying, "I could give you drugs to control your diabetes, but instead I want you to lose weight."