• CAB member highlight: Angel Hernandez, University of Puerto Rico

    June 30, 2019 pendari Uncategorized

    University of Puerto Rico CAB member Angel Hernández is committed to ensuring that clinical research is translated to his largely rural community in ways that are not only understandable, but also culturally appropriate. A CAB member since 2010, Hernandez is concerned about an aging population in which 72% of PLWH are 45 years or older, research is often misunderstood, and services can be irregular.

    “While the PLWH in our community receive adequate health services,” he notes, “we still lack enough clinics with extended service hours; consistent availability of ART for inpatients at hospitals; availability of integrated primary care; and provision of support services. Our community also faces ageism, stigmas, and discrimination.”

    Hernandez responds with an impressive commitment to bridging those gaps. Since joining the ACTG, he has served on the AEC, SASC, CSC, and ITSG, as the CSS co-chair, and as part of the Forum for Collaborative HIV Research, as well as on several protocol development teams. He is also proud to have been part of the team that developed the Feedback to CAB Protocol Draft Feedback procedure, and has also collaborated on the development of the CSS scientific agenda priorities.

    What he has seen has instilled a number of priorities in Angel, which he and his colleagues are working to move forward. “My hopes for the ACTG and HIV research are to continue studies on new formulations with less toxicities that are easier to take,” he says. “A high priority should be the focus on aging issues, and increased efforts to include underrepresented populations in clinical trials. Of upmost importance is to conduct research on the long-term effects of HIV and ART in long-term survivors.”

    As for his personal legacy, Angel adds: “I want to be remembered as an active advocate who brought the concerns of participants in clinical trials to the table.”

  • Investigator highlight: Dr. Aadia Rana, University of Alabama-Birmingham, School of Medicine

    June 30, 2019 pendari Uncategorized

    ACTG researcher Dr. Aadia Rana is Associate Professor of Medicine at the University of Alabama-Birmingham and an Investigator with the Alabama CRS. Aadia’s ACTG career began in 2010 when she started working as a site investigator at The Miriam Hospital CRS under Dr. Karen Tashima. Concurrent with her NIH-funded research, which addressed the need to improve care for and treatment adherence among people living with HIV, Aadia focused on developing strategies to promote recruitment, retention, and adherence in populations poorly represented in research studies as a member of the ACTG Underrepresented Populations Committee (2012-2016). In 2015, she also joined the Long-Acting Therapy Working Group of the ARTS and the Hard-to-Reach Populations Working Group.

    Through these groups, Dr. Rana and Dr. Jose Castillo-Mancilla submitted a proposal in 2016 to compare the use of long-acting injectable antiretroviral therapy versus standard of care in individuals with a history of non-adherence to care and treatment. This proposal developed into A5359, Long-Acting Therapy to Improve Treatment SUccess in Daily LifE, A Phase III Study to Evaluate Long-Acting Antiretroviral Therapy in Non-adherent HIV-Infected Individuals (LATITUDE), which started enrolling participants in May 2019. LATITUDE tests a combination novel therapeutic strategy of injectable ART supported by short-term conditional economic incentives to improve outcomes in a challenging population. In 2017, Aadia Rana moved to UAB, where she co-directs the Ending HIV in Alabama Scientific Working group at the UAB Center for AIDS Research and became an Investigator with the ARTS.

  • Publications: Can Text Messaging Support Adherence for People Failing Secong-Line Therapy in Low- and Middle-Income Countries (MULTI-OCTAVE Study [A5288])

    June 30, 2019 pendari Uncategorized

    (ACTG) A5288 (MULTI-OCTAVE) is one of the first studies to look at interventions for medication adherence in lower-income and middle-income countries (LMICs) for individuals failing second line therapy. All participants in this unprecedented prospective interventional study were failing 2nd line ART, with the majority on lopinavir/ritonavir-based ART. Participants were either kept on that regimen or randomized to receiving third line ART regimens based on the results of viral genotyping on enrollment, and followed for a median of 72 weeks.

    A randomized cell phone-based adherence support intervention was conducted among most of the study participants. In the intervention, field staff would text participants to see how they were doing in terms of taking the ART and participants would text back, first daily and then tapering down to once a week. The study showed a small (but not significant) benefit of a mobile phone-based intervention for ART adherence on the primary outcome of achieving virological suppression at 48 weeks, and a small (and statistically significant) effect on the outcome of time to virological failure.

    The authors conclude that adherence behavior is challenging and that two-way text messaging might help a bit, but does not seem to be as fruitful as hoped.  Therefore, more research on this and other adherence support strategies are needed.

    Gross R, Ritz J, Hughes MD, Salata R, Mugyenyi P, Hogg E, Wieclaw L, Godrey C, Wallis CL, Mellors JW, Mudhune VO, Badal-Faesen S, Grinsztejn B, Collier AC. Two-way mobile phone intervention compared with standard-of-care adherence support after second-line antiretroviral therapy failure: a multinational, randomized controlled trial. Lancet Digital Health 2019; 1: e26–34

  • Publications: OPTIONS Study (A5241) Asks Whether NRTIs are Essential in Salvage Regimens

    June 30, 2019 pendari Uncategorized

    When people with HIV develop resistance to antiretroviral medications, their clinicians often prescribe previously-used nucleoside reverse transcriptase inhibitors (NRTIs), along with other drugs, in the new “salvage” regimen, reasoning that the NRTIs may improve the chances of treatment response. These extra drugs may result in side effects, however, and it is not certain if they’re necessary if other active medicines are included in the salvage regimen. In the OPTIONS trial (ACTG A5241), the AIDS Clinical Trials Group asked whether NRTIs are an essential component of salvage regimens if the regimen has other active medications.

    The OPTIONS trial included more than 350 people with HIV who had received many different treatment regimens and developed resistance to a variety of medications before entering. The trial, which lasted almost 2 years, showed that clinicians do not need to add NRTIs to salvage regimens, as long as the new regimen has a cumulative activity of 2 or more active medicines from other drug classes.  Salvage regimens that did not include NRTIs gave similar rates of durable virologic suppression as those that included NRTIs. This means that clinicians and people with HIV can be confident that they don’t need to add NRTIs as long as the rest of the regimen is strong enough. Fortunately, with newer and better antiretroviral medications, most people with HIV will have treatment options that result in successful control of the virus. By avoiding NRTIs when we don’t need them, we reduce the pill burden, side effects and the expense of extra medicines.

    There were other important findings from the trial. The study found that younger people and those starting fewer new medications were less likely to achieve HIV suppression with salvage therapy. This means that we need to make extra efforts to make sure younger people and those who receive fewer new medicines are able to achieve successful control of their HIV. The study also used a questionnaire to assess participants’ quality of life scores before and during the study: participants in the trial had significant improvement in their scores, demonstrating the strong link between effective treatment and quality of life.

    The participation of hundreds of people with HIV who took part in the OPTIONS trial, many of whom had received treatment for more than a decade before they joined, has already made a difference: treatment guidelines have changed thanks to the contribution of the study participants and the staff at the many ACTG sites in the OPTIONS trial.

    Gandhi RT, Tashima KT, Smeaton LM, Vu V, Ritz J, Andrade A, Eron JJ, Hogg E, Fichtenbaum C. Long-term Outcomes in a Large Randomized Trial of HIV-1 Salvage Therapy: 96-week Results of AIDS Clinical Trials Group A5241 (OPTIONS). Journal of Infectious Diseases 2019 May 28
    (Accompanying editorial: Hoenig M, Little S. Salvage Antiretroviral Therapy: Time for “DeNUKElearization”?)

  • LATITUDE Study (A5359) Garners Widespread Media Attention

    June 30, 2019 pendari Uncategorized

    The LATITUDE (Long-Acting Therapy to Improve Treatment Success in Daily Life trial (ACTG A5359) study received extensive media attention on its recent opening. LATITUDE is evaluating long-acting ART (monthly injections of injections of rilpivirine and cabotegravir) in individuals who have difficulty adhering to daily oral ART. The study, which opened in May at several U.S. sites, garnered significant media attention in outlets including POZ, Bloomberg, Pharmafile, and many others. Read the study news release here. Congratulations to the LATITUDE team on the successful launch of this important new trial!

  • PHOENIx MDR-TB Study Prepares to Open

    June 30, 2019 pendari Uncategorized

    PHOENIx (Protecting Households On Exposure to Newly Diagnosed Index Multidrug-Resistant Tuberculosis Patients (A5300B/I2003B/) is a Phase III, open-label, multicenter trial to compare the efficacy and safety of 26 weeks of delamanid (DLM) versus 26 weeks of isoniazid (INH) for preventing confirmed or probable active TB among high-risk household contacts (HHCs) of adults (index case) with multidrug-resistant tuberculosis (MDR-TB). This ACTG/IMPAACT cross-network collaboration expects to follow 5610 participants (~2158 index cases and 3452 HHCs) for 96 weeks.

    Twenty-seven potential participating sites from 12 countries (Botswana, Brazil, Haiti, India, Kenya, Peru, Philippines, South Africa, Tanzania, Thailand, Uganda, Zimbabwe) are eligible to apply to participate in PHOENIx. Each participating site will have a run-in phase, where the site will demonstrate its capacity to identify adults with MDR-TB (index cases), access their HHs, screen HHCs, and enroll and follow eligible HHCs. While the study opening has been delayed for a number of requested protocol changes, we now anticipate two sites (Botswana: Gabarone/12701 and Brazil: Chagas/12101) opening for enrollment this month, with others to follow.

    Congratulations to the PHOENIx’s team persistence and resilience as the study prepares to get underway! PHOENIx is critical to define the best way to prevent TB in contacts of those with MDR-TB and will have profound implications for preventative TB care worldwide.

  • Mentoring Comes Full Circle: ACTG Mentee Becomes the Mentor

    June 18, 2015 pendari Uncategorized

    Meet Timothy Wilkin, MD

    Timothy Wilkin, MD, MPH, is an Associate Professor of Medicine in the Division of Infectious Diseases at the Weill Cornell Medical College and also serves as the Cornell-Chelsea Clinical Research Site Leader and Chair of the ACTG Co-Infections and Malignancy Working Group. Dr. Wilkin has been with the ACTG Network since 2003 and credits his decision to focus on HIV/AIDS research to Michael Para, MD, Professor of Infectious Disease at The Ohio State University who inspired him during his medical school training.

    “Dr. Para had a tremendous impact on my decision to focus my career on HIV/AIDS. During my first year of medical school he invited one of his patients with HIV, who was also an activist, to speak to my class,” said Wilkin. “She opened my eyes to the rampant stigma that HIV-infected individuals encountered and she impressed me with all that she did to enlighten her community while living with advanced AIDS. That was the starting point for me.”

    During his clinical years in medical school, Dr. Wilkin was a witness to the dramatic change in the way people living with HIV were cared for as HIV protease inhibitors and combination therapy entered clinical practice.  He feels fortunate to have worked with Dr. Para and his patients to see firsthand how those therapies helped to change their lives.  At the same time, Tim also had a major impact on some of his mentors as well.

    “While in medical school, Tim was one of those great students who have an idea, the motivation to carry it out and the work ethic to see it to completion. When the fourth year student curriculum was changing in Tim’s senior year, he asked to develop a month long elective on the long term care of the HIV-infected patient who spoke to his class.  He organized the course, set-up the daily activities, the readings and the evaluation,” said Dr. Para. “I actually still use much of the course material he generated for that month long course. I think that shows just how passionate he was with regard to HIV/AIDS care and research, even during medical school.”

    Dr. Wilkin has participated in nine ACTG protocol teams (including eight as Protocol Chair or Vice-Chair) during his tenure with the ACTG Network.  He led the development of AMC052/ACTG A5246, a clinical trial that established the safety and immunogenicity of the quadrivalent HPV vaccine in HIV-infected men.  Currently, he is the Study Chair of two ongoing clinical trials: A5298 and A5282.  A5298 is a phase III trial of the quadrivalent HPV vaccine in HIV-infected men and women.  This study is the first randomized efficacy study of the HPV vaccine in HIV-infected adults and will be the first to examine the efficacy of the vaccine in a highly HPV-exposed population.   

    Dr. Wilkin developed A5282 alongside his collaborator, Cindy Firnhaber, MD, Associate Professor, Department of Internal Medicine, Director Clinical HIV Research Unit University of Witwatersrand.  Together, they were able to secure support from a NIAID/PEPFAR collaboration to help cover expensive infrastructure costs.  Cervical cancer prevention is a new area of research for many of the participating A5282 sites.  

    “Dr. Firnhaber has had an amazing impact on the care of women with HIV in South Africa,” said Wilkin. “She has led efforts to implement cervical cancer screening services for tens of thousands of HIV-infected women.  She has a wonderful team with whom I am fortunate to collaborate.”  

    Dr. Wilkin was also last year’s recipient of the Wofsy Award given to investigators who are active in the care of HIV-positive women and for researching questions important to women living with HIV.

    “It was a complete shock; I had no idea that I won the award until they announced my name,” said Wilkin.  “It is a tremendous honor and I am very proud to be included with the list of previous awardees.”

    Tim also believes that being on an ACTG protocol team or ACTG scientific committee places him in the company of highly experienced clinical researchers and world-class scientists who are shaping the way care is provided for people living with HIV.  The established investigators he has worked with over the years have taught him a great deal about how to conduct successful, high-quality clinical trials.

    To make his journey from medical student to ACTG Principle Investigator come full circle, Dr. Wilkin has recently begun mentoring younger investigators and he hopes to share all of his years of experience with them. 

    “I enjoy working with younger investigators to develop their careers in clinical research,” said Wilkin. “In addition to the joy of seeing their success, these relationships are invigorating my research efforts and are leading to exciting new collaborations.”

  • Nurse Takes Time to Listen

    March 31, 2015 pendari Uncategorized

    The dry erase board in Cheryl Keenan’s office at Brigham and Women’s Hospital in Boston is filled with lists of letters and numbers. Each combination represents an HIV research study being conducted by either industry or the AIDS Clinical Trials Group (ACTG) Network. Keenan is the site’s sole research nurse. She manages roughly 20 HIV and hepatitis C virus (HCV) clinical trials, and the dry erase board helps her keep everything straight.

    “Without research there cannot be a cure,” Keenan says.

    After working for 15 years in the intensive care unit (ICU), she made the switch four years ago to infectious diseases research. Keenan sees people living with HIV who have enrolled in one of the ACTG’s studies being conducted at the Brigham and Women’s site. She check patients’ vital signs, draws blood and ensures they are not experiencing any negative side effects from the study’s medications.  

    Paul Sax, MD, is the Clinical Research Site Leader of the ACTG’s Brigham and Women’s location.

    “Cheryl came to us with extensive experience in cardiovascular disease research, which has been invaluable for several of our ACTG studies,” says Sax. “She already had a great understanding of cardiovascular issues, and then quickly learned the HIV- and hepatitis C virus-specific treatments as well. One of the consistent things I have heard from our study subjects ever since she joined our team is how compassionate and caring she is, even in the context of research. Many of them consider her like a primary care provider, as she’s is their first and major contact with our clinic!”

    Keenan says the population of study participants she sees in Boston is diverse. Although she sees more men than women, she knows there are women living with HIV in the area and she makes an extra effort to reach out to them.

    “I have a wonderful relationship with all of my patients,” Keenan says. “I know them well and they know me well. I think they know that they can reach out to me day or night for anything. Listening, really listening to people and doing what you can based on their needs is what I love to do.”

    Keenan discusses with her study participants what other clinical trials they would like to see the ACTG develop. Cure research is the response she hears most often.

    “Cure studies do require more personal time and commitment from our patients to get these more intensive studies completed,” Keenan says. “I have a few very committed individuals willing to take on more time consuming studies because they know we cannot have results without their time and commitment. They are very important to HIV research. I have many of my patients enrolled in the ACTG’s A5322 study investigating HIV and aging. They are all eager to contribute to science in one way or another. Many of my patients are involved in research because they just want to give back. They may not have much free time, but they still participate.”

    When she is not seeing patients at the ACTG’s Brigham and Women’s site, Keenan can be found spending time with her two children and husband. She also relaxes with a walk along the shore.

    “If I have free time, you can usually find me on the beach with my yellow labs,” she says. “But don’t worry, I can still answer my email.”

  • UCLA Researcher Strives to Improve ART

    January 1, 1970 pendari Uncategorized

    Eric Daar, MD, remembers completing his infectious diseases fellowship at Cedars-Sinai Medical Center in Los Angeles
    during the height of the AIDS epidemic.

    “Cedars-Sinai Medical Center was the hub of the HIV epidemic in Los Angeles,” he says. “During that time, I witnessed how devastating this disease was to a population of people that were my peers. It was too big a problem to ignore and way too interesting not to be intrigued. HIV also represented an extraordinary opportunity to get involved in something that was new
    and for which there was an enormous amount of work to be done in order to move the field forward.”

    Daar eventually became the Chief of Infectious Diseases at Cedars-Sinai. In 2001, he accepted the position as Chief of HIV Medicine at Harbor-UCLA Medical Center. The medical center is a research site with the AIDS Clinical Trials Group (ACTG) Network. For the past 13 years, Daar has been an investigator with the ACTG, specializing in antiretroviral studies and serving a Clinical Research Site Leader. He is Chair of the Network’s Antiretroviral Strategies subcommittee and a member of the ACTG’s Scientific Agenda Steering Committee.

    “I was co-chair of A5202, which was a mammoth study that along with substudy A5224s provided invaluable information to inform the treatment decisions for first-line therapy,” he says. “This study utilized all the resources of the ACTG and pulled together people with a broad range of expertise to address multiple scientific questions.”

    The studies identified the most effective combination of anti-HIV medications for people living with HIV who had never been on treatment. The substudy assessed how the different medications affected bone mineral density and fat. Paul Sax, MD, is the Clinical Research Site Leader at the ACTG’s Brigham and Women’s Hospital site in Boston. He was co-chair of study A5202 with Daar.

    “Dr. Eric Daar combines all of the optimal characteristics of a successful clinical researcher – he is scientifically curious, understands what makes a good research question, meticulous about details and extremely supportive of other members of the research team,” says Sax. “In addition, he has an uncanny ability to resolve areas of disagreement that may arise between individuals working on the same project, all with the goal of moving the project forward!”

    In Los Angeles, Daar says his HIV clinic treats predominately Hispanic and African American men who have sex with men (MSM) and Hispanic and African American women who have sex with men. Judith Currier, MD, MSc, is the ACTG’s Vice Chair and the Principal Investigator of the University of California Los Angeles AIDS Prevention and Treatment Clinical Trials Unit (CTU). Daar’s site is part of this CTU.

    “I consider it a privilege to be able to work with Eric Daar both in the UCLA CTU and within the leadership of the ACTG,” says Currier. “He is an accomplished investigator, a skilled leader and a wonderful friend. He has the ability to see the big picture, but at the same time he has the attention to detail that is essential for research at every step along the way. He is beloved and respected by everyone in the LA community for his commitment to clinical service and education.”

    In addition to conducting research and caring for patients, Daar also works with his site’s Community Advisory Board (CAB). Each ACTG site has a CAB made up of people affected and infected by HIV. CAB members provide researchers with feedback about studies and assist with community outreach.

    “I am very involved with our CAB and meet with them on a monthly basis,” says Daar. “They are invaluable in defining what are the highest priority questions for the community as well as providing insight into study design to optimize enrollment and strategies to enhance patient participation in specific studies.”

    Reflecting on his career investigating HIV, Daar is impressed with the strides research has made thus far.

    “Going from a time where the research focus was on optimizing therapy to defining how to minimize long-term toxicity and now characterizing and strategizing how to manage some of these conditions is exciting,” he says. “We are now focused on research opportunities to manage unique conditions such as persistent neurocognitive deficits in people with suppressed viral loads and developing studies to address retention in care as well as the possibility of a cure. It is hard not to be excited with a field where there is a constant evolution of what are the highest priority scientific questions.”

  • Volunteer Gives Input on Studies

    January 1, 1970 pendari Uncategorized

    Lionel Hillard is marking five years volunteering with the AIDS Clinical Trials Group (ACTG) Network’s Trinity Health and Wellness Center site in Dallas, Texas.

    “I wanted to help find a cure for HIV and other sexually transmitted diseases,” Hillard says.

    He is a member of his site’s Community Advisory Board or CAB. Each of the ACTG’s 60 sites has a CAB made up of members from the local area who are affected or infected by HIV. The CAB holds regularly meetings in which the site’s investigators may come and solicit their input about future studies. CAB members also host events open to the community to educate people about HIV and enrolling trials within the ACTG.

    “What I like best about being a part of the ACTG is the ability to give guidance to those who are not on the front line about new medications and side effects,” Hillard says. “I also like that we are ensuring the trials being done are in the best interest of the people the study is trying to help.”

    Hillard was chosen by his site in Dallas to represent them at the Network-wide Community Advisory Board level. This group is called the Global Community Advisory Board or GCAB. Each site is represented and each representative serves a two-year term. Issues discussed within the GCAB include support of community outreach, education and participation in research. Through being a member of this committee, Hillard has been able to meet likeminded individuals from around the world who share his passion for research. Salim Bakari Ngazi is the GCAB representative from the ACTG’s Moi University Clinical Research Center in Eldoret, Kenya.

    “Lionel is a very understanding, generous person who has a passion for the community,” says Ngazi. “He is always ready to help, share and learn with other GCAB members who are old or new. I was with him when he spearheaded the GCAB subcommittee to train new CAB members. Lionel deserves a pat on the back for a job well done.”

    In addition to serving on his local site’s CAB and the Network-wide GCAB, Hillard is a member of the ACTG’s Outreach, Recruitment and Retention (OR&R) subcommittee. This group supports study teams by creating flyers to attract participants into clinical trials. OR&R also encourages honoring study participants each Dec. 2, which is the anniversary of the first person enrolling into an ACTG study back in 1986. OR&R developed a guide for sites to host an appreciation event for or write letters of gratitude to study participants.

    Hillard’s time with the ACTG has introduced him to the science surrounding HIV. Learning about the current treatments and their side effects has influenced the direction he would like to see future studies take.

    “We should research the long term effects of these anti-HIV medications on the body, especially since people are living longer now,” Hillard says. “I also think we should investigate different dosages of drugs versus a one size fits all approach.”

    When he is not volunteering with the ACTG, Hillard enjoys reading, shooting pool, photography, tennis and listening to R&B.