The first and largest study specifically created to
examine the natural history of AIDS
MACS is an ongoing prospective study of the natural and treated histories of HIV-1 infection in homosexual and bisexual men conducted by sites located in: Baltimore, Chicago, Pittsburgh and Los Angeles.
The Chicago MACS Study (also referred to as the Men’s Health Study) is operated through facilities located at Northwestern University and The Ruth M. Rothstein CORE Center.
To the Chicago MACS Participants,
First, let us thank you for your continued participation in the study. Your contributions of time, effort, personal information, and biological samples have made it possible for us to increase our understanding both of HIV and the effects of treatment in favorably altering the course of infection. Your dedication has led to better and longer lives for affected persons. Our collaboration with you has resulted in over 1,500 research articles—all contributing to the fund of knowledge used in the fight against HIV.
As you know, antiretroviral treatment (ART) has had a deeply beneficial impact for those infected; significantly improving survival and reducing the negative outcomes associated with HIV infection. Still, recent research suggests that the processes of aging may occur more rapidly in ART-treated, HIV-infected persons when compared to HIV-uninfected individuals. Current research places HIV-treated individuals at higher risk for chronic heart, lung and metabolic illnesses known to be associated with aging.
For this reason, in addition to the preexisting assessments of aging in the MACS Study, we have implemented new tests assessing cardiac, respiratory, and metabolic function. Commensurate with this expansion, we have received funding from the National Institutes of Health to implement these additional tests and studies.
These additional research studies will help us, other researchers, and healthcare providers identify factors to monitor when assessing the effects of aging among HIV-infected persons. The improved understanding of aging that could result from these studies may lead to earlier detection and treatment of diseases associated with aging. Your participation is vital for the conduct of this important research. You have been extraordinarily loyal and committed to the MACS Study over the years. We hope that you will continue to do so and to help us reduce the impact of HIV infection on long-term quality of life. It is impossible for us to overstate the importance of your long participation. We and the scientific community continue to be grateful to you.
Studies of Heart Function and Rhythm
Most of you have already undergone an electrocardiogram or ECG/EKG which detects the electrical activity of your heart and produces tracings on paper of your heart rhythm. By ‘reading’ these graphs, a cardiologist can recognize the presence of various heart rhythm abnormalities including irregularities in the rate and pattern of heartbeats, damage to the muscles of the heart and its electrical conduction system, and the effects of various drugs and procedures (e.g. insertion of a pacemaker) on the heart. Because all MACS Study participants’ involvement in this longitudinal study includes years of follow up, knowledge of heart electrical (rhythm) conduction patterns may help identify factors that could result in the development of cardiac abnormalities. Likewise, comparisons between HIV-infected and uninfected individuals may help to identify factors that cause earlier (at a younger age) onset of heart disease in HIV-infected persons. As of May 10, 2017, the Chicago MACS Study and its participants had contributed 305 ECGs to this initiative. 1,563 ECGs have been performed across the four study centers nationally.
On the day the ECG was performed, you were asked to wear a small heart monitor, known as a ZIO patch, on your chest. This device records your every heartbeat for as long as you wear it, optimally for a period of up to 14 days. The longer the monitor is worn, the more likely it is to detect infrequent, but still significant, heart rhythm irregularities. After wearing the ZIO patch, the device is mailed to iRhythm Technologies where computer programs are used to scan the device for evidence of heart rhythm irregularities that are then reviewed by a cardiologist. This allows for the diagnosis of conditions such as atrial fibrillation (an irregular rhythm of the upper chambers of your heart) and other abnormal heart rhythms. Uncontrolled heart rhythm abnormalities can cause blood clots, strokes, heart failure and other complications if not treated appropriately. Fortunately, there are excellent treatments available for these irregular heart rhythms. In fact, several MACS Study participants have received treatment for conditions detected by this heart monitor. As of May 10, 2017, the Chicago MACS Study and its participants had submitted 252 heart monitors for analysis. 1,209 monitors were submitted across the four centers nationally.
Beginning in October 2017, we will be asking you to undergo an echocardiogram or “echo”. For this painless procedure, a technician spreads a water-based gel on your chest and then presses a device (transducer) firmly against your chest which produces a harmless ultrasound beam that passes through your chest to your heart. The transducer then records the sound waves that bounce back from your heart (known as ultrasound echoes) allowing for the production of computer-generated moving images of your heart that are recorded and displayed on a monitor.
By studying these echo images of your heart, the cardiologist can learn important information about the flow and pressure of blood through the arteries of your heart; the structure, size and shape of your heart; the capacity of your heart to pump blood; the functioning of the valves controlling blood flow within and from your heart to major arteries; and the location and extent of any tissue damage to your heart. This test, combined with the ECG and ZIO patch, can provide a very detailed picture of the overall function of your heart and the nature of any abnormalities that may predict future heart-related health problems. By comparing the results of the echocardiograms in HIV-uninfected and infected men, we may be able to identify risk factors for heart disease that occur in association with HIV infection. Results and interpretation of your echocardiogram will be sent to you along with a copy of the physician’s report which you can share with your doctor. The echocardiogram, if done as a screening test outside the study, usually costs about $1,500.
Studies of Lung Function
Since April 1, 2017 (and through September 30, 2017), we have been asking you to participate in studies of lung function called spirometry and carbon monoxide diffusing capacity (DLCO for short). Spirometry is the most common lung function test. This test requires you to blow as hard as possible into a mouthpiece connected by a tube to a machine called a spirometer. The spirometer measures how much air you inhale and exhale, and how quickly you can move the air out of your lungs. The instrument generates graphs and measurements of the volume and speed of these air movements. The test is repeated after you inhale medicine that relaxes the muscles in your airways (bronchodilator). Carbon monoxide diffusing capacity indicates how well your lungs transfer inhaled oxygen into your blood. This test requires one additional tube of blood to be drawn on the same day as the PFT testing. The results of these tests are interpreted by a pulmonologist (lung doctor) in order to identify abnormalities in lung functioning that may have been caused by smoking; prior infection(s); impairments in lung airflow such as asthma, chronic bronchitis or emphysema; chronic exposure to pollutants in the air; or the impact of allergens, such as pollens. The lungs have a tremendous reserve capacity, so early changes in lung health and function may be occurring even though the person is unaware of any problem. Again, by comparing the results of lung function tests between HIV-uninfected and infected men, we may identify factors specific to HIV-infected persons that may lead to premature reductions in lung function and capacity. As with the other tests, we will provide you with the results along with a report which you may share with your doctor.
Sleep apnea is a common disorder that causes pauses (or stops) in breathing lasting anywhere from a few seconds to minutes while you are asleep. Sleep apnea can affect one’s quality of life and health because of daytime sleepiness and fatigue. Apnea can also induce changes in one’s metabolism, nervous system, and cardiovascular system. For reasons that are unclear, sleep apnea and other sleep disturbances are prevalent among HIV infected persons. This may be due to effects of the virus on the immune system or the effects of antiretroviral medications on metabolism. The MACS Study is currently in the planning stages for conducting an overnight home sleep study to evaluate sleep quality and severity of sleep apnea in HIV-infected as compared to uninfected men. The study will also look to see if sleep apnea is linked to cardiovascular and metabolic diseases in both HIV infected and uninfected men. This study is scheduled to begin on March 1, 2018.
Tests of Premature Loss of Fitness
History of the MACS
In the fall of 1983, a group of investigators met at the National Institutes of Health (NIH ) to design a prospective epidemiological study of the newly recognized immunodeficiency syndrome in men who had sex with men (MSM) in Los Angeles, San Francisco, and New York. Upon completion of designing the protocol, recruitment of MSM began in April of 1984 into the investigation which was named The Multicenter AIDS Cohort Study or MACS. The first wave of participant recruitment was completed by March 31, 1985. Since then three more periods of enrollment have been opened; the first in 1987 to increase the participation of African-American (AA) MSM in the study and the second in 2001 to again increase participation by AA and Hispanic MSM. In 2011, the last enrollment period was initiated focusing on men with recent HIV infections to replace recent losses caused by death and dropouts. As of March 2017, 7355 men have volunteered and participated in the MACS with 2235 of them still active; 38% are non-white and half of all participants are older than 58 years of age. In Chicago, 1683 men have enrolled into the study.
The initial recruitment in 1984-85 was carried out before we had a laboratory test to determine who was a risk of developing AIDS. HIV had been suggested as the cause of the immunodeficiency in 1983 by investigators at the Pasteur Institute in Paris but this was not confirmed until the spring of 1984 by investigators in San Francisco and the NIH. However, a blood test to determine who was infected did not become available until the spring of 1985. When the original group of MSM who had joined the MACS underwent testing, it was discovered that approximately 40 percent of the cohort was infected.
This allowed the MACS to address two important issues. First, we could determine the behaviors, clinical findings and laboratory results which were associated with progression from HIV infection to AIDS. Secondly, among the uninfected men, the behaviors that led to HIV infection and the early signs and symptoms of this viral infection could be elucidated. To date, 767 uninfected men at entry into the MACS acquired HIV infection during the study, 342 of these men developed AIDS, and 84.2% of these men have died.
Early in the course of the study it became apparent that dementia was a major problem for men who developed advanced HIV infection and AIDS. MACS investigators organized a working group of neurologists to investigate this problem. The most important early finding was that severe central nervous system (brain and spinal cord) problems were seen only in persons with AIDS and that there was no reason for HIV infected men without AIDS to be restricted in their work. This finding became the basis of World Health Organization recommendation which was widely accepted advising that persons with HIV infection need not be restricted in their activities.
During the period of the 1980s, the death rate among the infected MACS participants was very high. As of the fall of 2016, close to 56 percent of men who entered the MACS with HIV infection have died. The MACS investigators were among the first to demonstrated that the T-Helper cell count below 200/mm3 were associated with a high rate of pneumocystis pneumonia (PCP) and helper cell counts below 100/mm3 put individuals at risk for cytomegalovirus retinitis, atypical mycobacterial infections, and infection of the brain with the parasite Toxoplasma gondii. Giving antibiotics to prevent some of these opportunistic infections helped but the early agents available to treat the HIV infection did not prevent progression to AIDS or death.
An early observation of MACS investigators was that the progression of newly acquired HIV infections to AIDS differed from individual to individual. Determinants of this heterogeneity included age at the time of infection and host genetics. The genetic makeup of an individual determines their immune response to HIV which in turn controls the rate of viral replication. Lower levels of replication result in slower progression of untreated HIV infection. Host genetics also determines susceptibility to HIV infection. The MACS contributed to the discovery of an uncommon mutation which protects people with this mutation from the usual form of HIV which is transmitted sexually.
With the availability of effective antiretroviral therapy in late 1995, progression to AIDS and death decreased dramatically. Close to 80% of participants in the MACS taking drugs have suppressed HIV replication and the median T-helper cell count is near 600/mm3. Stopping drug treatment results in progression of HIV infection and disease. With the greatly improved survival of infected participants, the MACS has focused on the health status of men who were living longer. To accomplish this investigators have been recruited into working groups with interest in diseases of the heart, lungs, kidneys, liver and metabolic diseases such as diabetes. The behavioral working group has continued to study behaviors to determine why men fail to adhere to treatment. Recreational drugs and alcohol use have been shown to be associated with poor adherence. Drug use also is associated with a marked increase in the risk of acquiring HIV infection. The neurology working group continues to investigate brain function among aging HIV infected men and the aging working group is attempting to determine whether or not HIV infected men age more rapidly than infected men.
The long follow up and presence of both HIV infected and uninfected men provide the MACS with a unique insight into men’s health.
2014 Update on MACS Sub-studies
As MACS participants grow older, it has become important to understand the effects of HIV on the aging process. The purpose of the MACS Bone Strength Study is to understand whether older HIV-positive men have a higher risk of fracture compared to HIV-negative men of a similar age. For this, approximately 400 men from the MACS study have undergone a series of tests including DXA and CAT scans, a blood draw, and some simple clinical tests. In fact, many people in the MACS study have participated in these simple clinical tests, as the balancing assessments were recently added to the standard set of tests given to all MACS participants, and anyone between the ages of 60 and 69 has been asked to participate by doing reaching assessments and chair stands. Based on the self-reported data from those participating in the MACS and those participating in the BOSS, preliminary results show that poor balance confidence doubled the odds of falling, where balance and physical function tests did not predict falls. And while there was no significant difference in the proportion of men with HIV who fell versus those without, the HIV group had significantly higher rate of falls with fracture.
The MACS has done multiple Cardiovascular sub-studies and has just recently begun it’s third. The cardiovascular studies have been conducted to explore the relationship between HIV infection and the narrowing, blockage or hardening of the heart, also known as atherosclerosis. The second cardiovascular study run in 2009/2010, included 764 participants of the MACS, aged 40-70 years. Findings showed that a greater prevalence and extent of non-calcified plaque – more prone to rupture, therefore precipitating thrombosis and acute coronary syndromes than calcified plaque – among HIV positive men than HIV negative men. These findings suggest that men with HIV infection are at an increased risk for the development of coronary artery disease. Now, the third MACS cardiovascular sub-study has commenced with the objective of determining whether atherosclerosis increases faster in HIV positive men than in HIV negative men. 172 men of the MACS study who have participated in the two prior subclinical cardiovascular protocols are getting a series of CAT scans, some after having an injection of contrast dye, to take pictures of the blood vessels and body fat, as well as a blood test.
Many men of the MACS study have participated in the POPS sub-study, and although many participants have anticipated the mouthwash rinse with lackluster enthusiasm, the study has been doing very important work in regards to oral HPV. Due to the assistance of the MACS participants who helped with this study, the POPS was able to observe an increased risk for oral HPV for those with a reduced current CD4 cell count, and no history of a tonsillectomy. The study also observes an increased risk of oral HPV with greater numbers of recent partners for oral sex and rimming for HIV uninfected, and increased risk with greater number of lifetime partners for HIV infected. Factors such as gender, smoking habits, and age significantly decreased the clearance of infection.