New options for prevention and treatment
Liz Barr

ATAC (AIDS Treatment Activists Coalition) is a national coalition of AIDS activists—many of whom are living with HIV/AIDS. ATAC works to end the AIDS epidemic by advancing research on HIV.

Members of ATAC’s Drug Development Committee (DDC) met in Philadelphia in May 2019 with representatives from the Janssen pharmaceutical company to discuss the firm’s HIV research program and drug pipeline. Janssen is active in the areas of HIV vaccine research and creating antiretroviral treatments, including long-acting formulations. Here are some highlights of our conversation.

Long-acting formulations of antiretroviral treatments

In an effort to provide more options for HIV treatment, improve adherence, and simplify regimens, Janssen is working with the HIV-focused drug company ViiV Healthcare to develop a long-acting regimen that may require only monthly or even less frequent dosing. At our meeting, we talked about preliminary market research Janssen has conducted concerning providers’ and patients’ attitudes to various forms of long-acting drugs, such as injections and/or implants, and found that long-acting options certainly have appeal. While not there yet with options in late-stage development, long-acting therapies that could be self-administered are attractive, and regardless, less frequent dosing could improve medication adherence over time. Not having to keep medications in the home could also alleviate anxiety around HIV-related stigma (less risk of someone seeing your pills in the bathroom).

ATAC members stressed that—as with contraceptive methods—the more options and choices available to the user, the better. While many people will prefer sticking with daily pills, many others may prefer using a long-acting method of treatment—and among those folks, some may prefer an implant to an injection and vice versa.

It will be important for Janssen and ViiV to maintain robust community and provider engagement as they continue to develop and market long-acting regimens. DDC members also stressed that price and ease of access will be key components of usability and user-friendliness of these new formulations. The ongoing research into long-acting treatments will reveal much about what works and what doesn’t in providing these new options—and it will be crucial that Janssen and ViiV clearly communicate the lessons that are learned.

HIV preventive vaccine research

The goal of Janssen’s HIV vaccine program is development of a broadly acting, multi-clade vaccine for HIV-1 prevention. Janssen’s vaccine program uses what’s called a “mosaic vaccine”—meaning that the actual vaccine is made up of snippets from multiple clades of HIV-1 joined to a modified, non-replicating cold virus (adenovirus). Varying clades of HIV-1 are found in different geographic regions, so addressing multiple clades with a vaccine should help make it more universally effective.

Our discussions focused on the APPROACH, TRAVERSE, and Imbokodo trials. APPROACH and TRAVERSE were phase 1 and 2a studies intended to determine which vaccine formulation and regimen will move to a phase 2b, proof-of-concept study. In APPROACH, HIV-negative adults in the U.S., Rwanda, Uganda, South Africa, and Thailand were randomized to different mosaic-based vaccine regimens. That study identified one vaccine regimen that appeared to maintain an antibody response one year after the last vaccination. (Full results from APPROACH were presented at AIDS 2018). The TRAVERSE study compared a vaccine with a tetravalent mosaic vector (combining four adenovectors expressing HIV mosaic proteins) to one with a trivalent mosaic vector (combining three) in HIV-negative people in the U.S. and Rwanda. Early data from TRAVERSE (which were presented at the 2018 Research for Prevention Conference in Madrid) showed that not only was the tetravalent vaccine well tolerated, but it also appeared to enhance volunteers’ immune responses more than the trivalent vaccine (go to bit.ly/MosaicStudyResults).

Based on the results from APPROACH and TRAVERSE, Janssen identified a vaccine candidate for the Imbokodo study (HVTN 705/HPX2008), which enrolled around 2,600 cisgender women in Southern Africa. During our meeting, ATAC members asked a number of questions about safety monitoring, plans for reservoir sampling from participants who acquire HIV, how endpoints were determined, and what happens to women who acquire HIV during the Imbokodo study (Answer: they are immediately linked to care). Janssen reiterated that all participants in their vaccine trials receive standard of care prevention methods and education.

We concluded our discussion of Janssen’s vaccine research with Mosaico (HVTN 706/HPX3002), a phase 3 efficacy study for cisgender men, transgender individuals who have sex with cisgender men or transgender individuals, or transgender individuals who are at increased risk, which was planned to start before the end of 2019 and is now underway. ATAC raised questions about the study’s design—for example, how is “high risk” defined, is a placebo arm necessary, and how will the study be implemented?

ATAC also reminded Janssen that outreach and engagement will be crucial if they want this product to have an impact for those who need it most, particularly black and Latinx people. In light of rising HIV incidence in older individuals, ATAC suggested Janssen reconsider the current upper age limit of 60 for this study. Janssen acknowledged this point, which could potentially be addressed in future studies. ATAC members stressed the importance of developing an HIV preventive vaccine for all populations, including cisgender women, and also urged Janssen to include women in sufficient numbers in trials so as to perform sex-disaggregated analyses. The Imbokodo study is evaluating the mosaic vaccine in this population.

ATAC members asked Janssen to remain in conversation with our group and other community stakeholders as Janssen conducts the Mosaico study and finalizes its plans for licensure.

New trials being considered for HIV treatment

We concluded our meeting talking through other potential trials under consideration at Janssen. The bulk of this discussion was bound by nondisclosure agreements, however, we can report the company is considering a trial of re-engagement strategies that would benefit people who’ve had previous issues with adherence. Janssen is also considering the issue of weight gain, particularly for people taking integrase inhibitors. ATAC members provided input on key populations to include in studies of weight gain, and on the importance of distinguishing between integrase inhibitor-related weight gain and non-integrase inhibitor-related weight gain.

There were 13 ATAC members in attendance at this meeting as well as one from the EATG. For more information about the AIDS Treatment Activists Coalition, go to AIDStreatmentactivists.org.

Liz Barr is a member of ATAC and former member of the AIDS Clinical Trials Group (ACTG) Community Scientific Subcommittee.