Early antiretroviral treatment and pre-exposure prophylaxis, or PrEP �" two elements of San Francisco's Getting to Zero initiative �" are keys to reigning in the HIV epidemic worldwide, and the city is at the forefront of showing how these can be effectively implemented, researchers reported at the recent International AIDS Society Conference in Vancouver.
The Getting to Zero Consortium aims to make San Francisco the first U.S. city to eliminate new HIV infections, HIV-related deaths, and HIV stigma using a three-prong strategy of expanded access to PrEP; rapid access to antiretroviral therapy, or ART; and retention of HIV-positive people in care.
Benefits of early treatment
In 2010 San Francisco became the first city to recommend antiretroviral therapy for everyone diagnosed with HIV regardless of CD4 T-cell count. U.S. treatment guidelines adopted this recommendation in 2013 and the World Health Organization announced last week that its forthcoming global guidelines will do the same.
As reported lasted week, researchers at the conference presented data from the START trial, which showed that starting treatment immediately after diagnosis �" rather than waiting until the CD4 count falls �" reduced illness and death by 57 percent. Another pivotal study (HPTN 052) confirmed that when HIV-positive partners in mixed-status couples started treatment immediately, the risk of transmitting the virus fell by 93 percent.
Christopher Pilcher from UCSF presented findings from a feasibility study of the RAPID program at San Francisco General Hospital, which aims to speed up the process and reduce attrition as people move through the "cascade of care" from HIV diagnosis to engagement in care to starting ART to achieving undetectable viral load.
San Francisco has a well-financed HIV care system with highly experienced providers, but "no matter how well-resourced and coordinated, sequential care does take time," Pilcher said. RAPID focuses on the "very left side of the continuum of care," consolidating initial assessment, medical evaluation, and ART prescription into a single visit.
Pilcher's team analyzed outcomes in a demonstration project of 39 newly diagnosed people who participated in the RAPID program between July 2013 and December 2014. They were compared to a historical control group of people who received standard care.
Pilcher described the RAPID participants as a "high needs" population at risk of falling through the cracks of the health care system. All were men, a majority were people of color, more than a quarter were homeless, and none had health insurance.
People are typically referred to RAPID by one of the city's public HIV testing sites, generally on the day they receive their results. They get a same-day medical appointment and a taxi voucher to get to the SFGH clinic. After a brief medical exam they receive a five-day starter pack of antiretroviral medication and are encouraged to take their first dose on the spot.
Meanwhile, program counselors help participants establish ongoing insurance coverage. Most qualify for public coverage such as Medicaid or Healthy San Francisco, Pilcher told the Bay Area Reporter.
Pilcher reported that 90 percent of eligible patients opted to start ART on the day of their first visit. On average it took about one day from the time they received their HIV test result to taking their first pill. In contrast, in the historical standard care group only about a quarter started treatment within the first week and about 60 percent did so during the first month.
RAPID participants achieved undetectable HIV viral load in a median of 56 days, versus 119 to 238 days for the standard care group. Three-quarters had viral suppression after three months on treatment (compared with 38 percent in the standard care group) and 95 percent did so after six months. Most participants were still engaged in care at the end of follow-up.
Pilcher said RAPID participants and providers both had "extremely positive" opinions about the program, and the resistance he had expected from providers reluctant to start people on treatment so soon did not materialize.
At a Board of Supervisors hearing in January, Diane Havlir, chief of SFGH's HIV/AIDS division, said the city wants to expand the RAPID program from SFGH and the San Francisco Department of Public Health clinics to all public and private providers citywide.
"Test-and-treat really means collapsing the care cascade," said Nancy Padian from UC Berkeley at the conference's closing session. "When they're in your clutches, you put them on treatment."
PrEP Demo Project
Also at the conference, Albert Liu from SF DPH presented results from a trio of PrEP demonstration projects conducted at San Francisco City Clinic, the Miami-Dade County Downtown STD Clinic, and Whitman Walker Health in Washington, D.C.
After the iPrEx trial showed that daily Truvada (tenofovir/emtricitabine) PrEP reduced the risk of HIV infection for gay and bisexual men by 44 percent overall, or 92 percent among participants with measurable blood drug levels, the PrEP Demo Project was designed to see how well PrEP works in the real world.
Together the three Demo Project sites enrolled 550 at-risk gay and bisexual men and seven transgender women. Just over half came seeking PrEP themselves, while providers referred 46 percent. They received daily Truvada on an open-label basis (not randomized) for a year.
The average age was 35 years, with one in five being under 25. Nearly half were white, a third were Latino, and 7 percent were black. Risk factors included condomless anal sex with two or more partners, sex with an HIV-positive partner, or having a sexually transmitted disease.
More than three-quarters (78 percent) were still taking PrEP at the end of the one-year study. Adherence, determined by drug levels in dried blood spots, was generally good, but there were some notable disparities.
While adherence reached 90 percent in San Francisco and 88 percent in D.C., it was only 65 percent in Miami. White participants had 91 percent adherence, compared with 77 percent for Latinos and 57 percent for blacks. Being homeless or having unstable housing also had a negative effect on adherence, bringing it down to 70 percent.
In contrast, having more condomless sex was associated with better adherence, showing that people at more risk were most likely to use PrEP consistently. Liu said that odds of achieving protective drug levels did not differ based on age, education level, or alcohol or drug use.
People who started PrEP did not have more sex partners, but they were more likely to have condomless sex as their length of time on PrEP increased. The number of participants testing positive for STDs declined during the first six months on PrEP, but then rose again to almost the starting level.
Only two people were newly infected with HIV during the study, both of whom had blood drug levels showing they took PrEP less than twice a week; studies indicate that four times a week offers adequate protection. (Liu did not say which cities the new HIV infections occurred in.)
Another PrEP study reported at the conference, ATN 110, looked at 200 young gay and bisexual men (age 18-22) in a dozen U.S. cities. (It did not include San Francisco.) It likewise found that adherence was lower among black men and higher among participants with the greatest risk of HIV infection. Adherence dropped off over time, suggesting that young people may benefit from more intensive adherence support. Four ATN 110 participants became infected with HIV during the yearlong study, all of whom had very low blood drug levels.
Speaking at an IAS press briefing, Liu recommended quarterly STD screenings while using PrEP and said strategies are needed to address racial and geographic disparities, as well as the need for stable housing.
"Our results strongly support the scale-up of PrEP," Liu said. "PrEP adherence was higher among those who reported higher risk behaviors, which likely increased the cost-effectiveness and impact of PrEP."
Addressing the issue of high STD rates among people taking PrEP, iPrEx investigator Robert Grant from the Gladstone Institutes recommended that PrEP should be integrated into comprehensive sexual health programs.
"People are ready for a conversation about STDs," Grant said. "PrEP provides an opportunity for people to be tested and treated for STDs."