ACTG Network Trial Update: HAILO A5322 - Long-term Follow-up of Older HIV-infected Adults: Addressing Aging, HIV Infection & Inflammation

The Center for Disease Control and Prevention (CDC) anticipates that by the end of 2015, at least 50% of individuals in the United States who are living with HIV/AIDS will be over the age of 50. This can be attributed to a variety of factors, but most researchers agree that it is primarily linked to the routine use of combination antiretroviral therapy (cART) – potent and tolerable treatments for HIV/AIDS. The accessibility and effectiveness of this treatment has markedly prolonged the survival and quality of life of HIV-positive individuals. Those who receive cART and maintain viral suppression are now more likely to die from traditional non-infectious illnesses that clinicians are accustomed to observing in older people. These include cardiovascular disease and non-AIDS-associated malignancies.  In recent years, the focus of most clinical care and research conducted with older cART-treated, HIV-positive individuals has changed dramatically.  In general, risk prevention, screening, and prompt treatment of non-infectious co-morbidities like heart disease, cancer, and neuro-cognitive illnesses, as well as kidney, liver, and bone disease have become more routine parts of clinical care and comprise important areas of investigative focus conducted across the ACTG Network.

“Treating those who are HIV-positive itself has actually become the ‘easier part’ of the overall primary care of the HIV aging population,” said Frank J. Palella, Jr., MD, Professor of Medicine, Division of Infectious Diseases, Northwestern University, Feinberg School of Medicine. “In the early days of treatment, it was unfortunately commonplace for us to see young, physically vigorous people becoming ill with AIDS-related complications and dying over relatively short periods of time, so it is remarkable that we are at this point in time.”

As people age (with or without HIV), deterrents to good health inevitably increase. Among the aging HIV-positive population, issues that are more common than among HIV-negative individuals of a similar age include depression, mental illness, substance abuse, poverty, a feeling of isolation, and a lack of a cohesive social support network.  Most ACTG clinicians and investigators are now more closely monitoring participants for signs of aging-associated issues that impact overall well-being. These include declines in neuro-cognitive ability, physical mobility, overall self-sufficiency, and safety at home.  For example, ACTG Protocol A5322 (HAILO) Long-Term Follow-up of Older HIV-infected Adults: Addressing Issues of Aging, HIV Infection and Inflammation, led by Dr. Palella and his colleagues, is an observational (as opposed to interventional) study that monitors participants who receive treatments as prescribed by their clinicians; they are not study-determined. As these participants were already long-time participants of ACTG Protocol A5001 (ALLRT), Longitudinal Linked Randomized Trials, they have been extremely well-characterized in terms of long-term clinical and laboratory data and thereby are very well-suited for clinical investigation.

The A5322 clinical team successfully enrolled approximately 1,000 HIV-positive participants aged 40 or older. These individuals are diverse in their cART treatment experience, their co-morbid illnesses and their overall states of health. One extremely encouraging finding of this study has been how well-controlled HIV infection has remained for the vast majority of participants - many of whom initiated cART more than 10-12 years ago. There is also an incredible amount of diversity in terms of co-morbid illnesses that are being treated simultaneously in these participants. It is important that illnesses (and their treatments) that are common among aging persons, such as hypertension, diabetes mellitus, and hyperlipidemia, are well-represented in this study. 

“A5322 represents an important resource for investigators and clinicians from within and outside of the ACTG Network,” said Daniel Kuritzkes, MD, ACTG Network Principal Investigator and Chief, Division of Infectious Diseases, Brigham and Women’s Hospital.  “The long-term and detailed clinical characterization of each participant is a major strength of this study, as is the availability of contemporaneously collected and banked biological specimens.  Taken together, these constitute an impressive set of resources ripe for scientific investigation into the pathogenesis, predictors and prevention of clinical illness among aging HIV-positive individuals receiving cART.”

Another unique feature of A5322 is that it seeks to study events, conditions, and factors associated with predicting healthy aging among HIV-positive individuals. Not only are these issues extremely timely and relevant (as validated by the CDC 50% over the age of 50 statistic) it is important from a research perspective.  A5322 researchers seek not only to describe the clinical events associated with aging among HIV-positive adults, but also to evaluate how the processes of systemic inflammation and immune activation predict and corroborate such clinical events.  Regarding each A5322 participant, there are robust resources available to investigators, both in terms of the detailed long-term historical and ongoing clinical data as well as stored blood specimens that have been collected over many years. The availability of these specimens which for many patients date back to pre-cART initiation, allow for the measurement of novel and established markers of immune activation and inflammation. Additionally, because each participant contributes multiple specimens over time, the potential exists for identifying interventions effective in reducing levels of worrisome biomarkers, and to assess whether such interventions thereby prevent clinical disease.

As those living with HIV advance in age, it is important to reflect back on times when there were not effective and lifesaving treatment options available. While the beneficial effects of cART have transformed HIV infection into a chronic but manageable condition, there are still remaining concerns especially relevant for aging HIV-positive individuals include antiretroviral tolerability, safety (particularly long-term potential adverse drug effects,) successful management of co-morbid illnesses, and ongoing access to care. Since early in the HIV/AIDS epidemic, ACTG Network clinicians and researchers have been at the forefront of identifying and addressing the most urgent and important treatment issues confronting those who are HIV-positive and their care providers. The achievement of long-term survival that the use of cART has made possible for so many of our aging HIV-infected participants has resulted in shifts in the ACTG research agenda to include the study of issues vital to these individuals.