We’re told over and over again not to smoke. Thank—or blame—more than 5,000 men and women who signed up for a cohort study back in 1948 in Framingham, Massachusetts.
The Framingham Heart Study found that smoking is bad for us. That’s the benefit of a cohort study. You follow a group of people to see what helps and what doesn’t. Usually, participants have something in common, say, people with diabetes. Medical advances come from such work.
Enter HIV. Striking down young men and women in the prime of their life. And children.
Enter the HIV Outpatient Study, or HOPS, in 1993, at hospitals throughout the country. Not the first HIV cohort study in the world, but like the others, vital to health and wellbeing.
The thousands of men and women who enrolled in HOPS have helped track the astounding successes seen in the epidemic. They showed, for example, that life expectancy dramatically increased, and at the same time illness dramatically decreased, with new HIV treatments that became available in 1995–96.
Many other findings also contributed to improvements in HIV health care.
“These are observational data, which always precede the ability to do controlled trials. Because if you can observe it happening, that gives fuel to the process of constructing the randomized controlled trials [the gold standard in medical research],” said Frank J. Palella, Jr., MD, professor of medicine at Northwestern University Feinberg School of Medicine, in Chicago. “But first you have to have the observation.”
Dr. Palella is principal investigator of the Northwestern HOPS site. Other sites around the country include Denver, Philadelphia, and Tampa, Florida.
Following are more observations from an observation study leader.
“It’s interesting how our goals have changed. Back then our goal was to … keep … people … from … dying,” Dr. Palella recalls. “Now, in a world where we can routinely suppress the virus, keep the immune system healthy, and extend survival, our goal has become completely different—happily. Today we usher people into old age and help them remain healthy. We talk about lifespan, and now we talk about healthspan as well. It’s a newer word to use with HIV.”
‘Healthspan’ refers to the times in life when someone is in reasonably good health. With the research findings and resulting medical advances, many of Dr. Palella’s patients today are long-term survivors. And his younger patients are reassured that they too will live a long, healthy life by staying on treatment and in care.
I have patients who have literally been my patients for 30 plus years, many for more than 20 years. I have a big cadre of patients who are older: 50s, 60s, 70s, and beyond. I’m helping with their older age issues—their blood pressure, their diabetes. Their high cholesterol or their screening for cancer. Mobility, and frailty, and physical functioning issues that are age related.
And I have another big group of people who are young, and younger, and for whom the situation is so much better. Because they don’t have to live a long period of time—or any period of time—without getting good therapy for HIV. It’s there. It’s publicly funded. You don’t have to wait for good treatments to come along. They’re here.
They didn’t arrive overnight.
When we talk about the time in which the HOPS started, in 1993, it was the bad old days where we had no effective therapy for HIV. The focus back then was profiling how people with AIDS were doing, how long they were living, and what sort of opportunistic diseases they succumbed to, and what sort of things might palliate or even just marginally improve outcomes.
We learned that there is no such thing as treating HIV too early.
I can remember that in our in-patient hospice unit at Northwestern, which was primarily for people with cancer, over half of the patients in hospice were persons with AIDS at any given time from the late ’80s and up to the mid-’90s . And they had a worse prognosis than people with cancer.
We saw so many young people, vital people, just talented people, people who had just embarked on their adult lives, taken from them, taken from us. We lost people who were important to us personally and professionally. That was very hard.
So when the triple drug protease inhibitor-based combination therapy first became available in late ’95, early ’96, it’s clear that something dramatic happened. People … stopped … dying. People who had been losing weight and feeling awful, they’re gaining weight, gaining strength. Their T cells went up, their viral loads went down. In the words of some of my patients, “These new medications have brought me back from the edge of the grave.”’ It gave people a second life.
One of my patients was featured in the Chicago Tribune. He talked about having been so ill with opportunistic infection after opportunistic infection. Then all of a sudden—he wasn’t ill. And he felt so much better. One of his quotes was put in big, bold letters: “All of a sudden I have to think about my future again.” What a wonderful thing to have to think about again!
I’m happy to tell my patients now, especially my younger patients, “You stick with the program. Take your once-a-day pill. Come and see me every few months or even half year. Get screened for STDs. Keep your nose clean and stay away from things that are bad for you and you’re going to live longer than me.” And that’s a wonderful thing to be able to say to people, something we couldn’t say as recently as 20 years ago. Again, it’s because we are so good at getting people into therapy, suppressed on therapy, and retained in care, so that HIV does not become the principle determinant of their lifespan or their healthspan. The menu of treatment options that we have available to us now is simply extraordinary.
So our goals now are to identify people with HIV, get them promptly into care and on therapy, virally suppressed, and maintained in care. Which are the five goals of the HIV continuum of care.
It was the evidence of HIV cohort studies along with other research that brought these options today.
We take it for granted now that everyone who’s diagnosed with HIV should immediately start therapy so they can get suppressed on medication and remain in care. That in turn has informed the urgency of getting … people … tested. But so much of this initial incentivization comes from information that was evident from observational databases.
At the time the HIV Outpatient Study began, AIDS was the leading cause of death for men in the U.S., and more so for young men. As an infectious disease clinician,
Dr. Palella was at the right place at the right time.
But beside the incredible death rate and lack of effective treatment, there was the stigma.
It was a very interesting and peculiar space to be in, because of an illness that was fatal and had no good therapies, which had a social stigma. It was a disease that implied a lifestyle status, and had financial, insurance coverage, and job implications, and familial alienation. Embracing HIV and AIDS as a disease state and persons with HIV as a population was a very brave and extraordinary thing to do.
In those days, even the medical providers who worked in HIV were shunned by other staff members.
Today, the stigma continues.
People of color, in addition, have to deal with the misinformation born of institutional mistrust. When Dr. Palella talks about a good prognosis for their disease, they’re often surprised.
I think they hear my talk and take it to heart, but then they sometimes say, “I didn’t know that,” or “Wow, on the streets I’m hearing that that’s not always the case for everyone. Maybe for my ethnic group or my racial group, that it doesn’t work as well,” being Black, Latino, or any other group. People hear things on the street which just … aren’t … true.
Even as new findings continued to show the benefits of treatment, sometimes—but not always—there were racial differences. Some of those are due to socioeconomic differences, not the chemical compounds themselves.
Also seen were problems like adverse events and high cost.
Those problems, however, provided the impetus for newer and better medications—safer and better tolerated.
All the while, the treatment benefits continued.
We learned that there is no such thing as treating HIV too early.
We were able to show from this work that starting earlier is better. There’s not a T cell count—no CD4 cell count—above which we fail to demonstrate the benefits of therapy. This is both in terms of avoiding HIV-related illness, but also the aging-related illnesses like heart disease, kidney disease, liver disease, and cancer. Starting late will still save people’s lives and bring them back from the brink of death. But death comes over the long term, over decades, when you … start … therapy … as soon … as possible.
As a big bonus we also learned over the last six or seven years that when you get somebody on therapy and virally suppress them you make them essentially incapable of sexually transmitting HIV. That is a huge part of prevention.
Undetectable equals untransmittable. Treatment equals prevention. It’s true. The best prevention of HIV is identifying and treating people with HIV so they cannot transmit it sexually.
Undetectable equals untransmittable. Treatment equals prevention. It’s true.
We have learned this over and over and over again, and it constitutes yet another important reason to identify people with HIV as soon as possible. Use universal screening and get them on the virally suppressive therapy. Not just for their own sake but for the sake of everyone whom they come in contact with, for the sake of the entire community, and all of society.
So, today Dr. Palella is taking care of patients as they age, expecting their lives to be as good as that of anyone else their age. And taking care of younger patients as well, with the expectation that they too will live long and healthy lives. Reminding all of them that taking care of their health benefits everyone.
I hope to keep my patients impassioned to stick with the program for themselves and for people they love. So we can keep everybody together regardless of HIV status.
The HIV Outpatient Study (HOPS) recognized its first 25 years of service with an article detailing its work and findings.
“The HOPS contributed to characterizing new conditions (e.g., lipodystrophy), demonstrated reduced mortality with earlier HIV treatment, uncovered associations between select antiretroviral therapy use and cardiovascular disease, and documented remarkable shifts in morbidity from AIDS opportunistic infections to chronic non-communicable diseases,” the team reported in April.
HOPS is a cohort study, looking at outcomes in a group of people sharing a particular trait, in this case, HIV. HOPS was the first cohort group to report that HIV treatment with protease inhibitor drugs greatly reduced the risk of death and disease.
It was established by the Centers for Disease Control and Prevention (CDC) in 1993.
In 2017, its 25th year, 89% of HOPS participants had undetectable viral loads (less than 200). Nearly 11,000 participants enrolled in the study in that quarter of a century.
“Few sources of longitudinal data exist profiling people living with HIV (PLWH) spanning that period,” the HOPS group noted. “Cohort data enable investigating new exposure and disease associations and monitoring progress along the HIV care continuum. …
“During the past 25 years, HOPS participants and physicians have both witnessed and contributed to the advances and remarkable changes in the clinical epidemiology of treated HIV infection. The findings generated by clinical HIV research, including the HOPS, have informed both U.S. and international guidelines and recommendations shaping clinical practice today.”
The complete manuscript, published in April 2020, is available from the journal Open Forum Infectious Diseases (OFID) at academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofaa123/5819208. OFID is an open-access journal from the Infectious Diseases Society of America (IDSA) and the HIV Medicine Association (HIVMA).
“Mortality among the patients declined from 29.4 per 100 person-years in the first quarter of 1995 to 8.8 per 100 in the second quarter of 1997. There were reductions in mortality regardless of sex, race, age, and risk factors for transmission of HIV. The incidence of any of three major opportunistic infections (Pneumocystis carinii pneumonia, Mycobacterium avium complex disease, and cytomegalovirus retinitis) declined from 21.9 per 100 person-years in 1994 to 3.7 per 100 person-years by mid-1997.”
—Palella FJ, Jr., Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. New England Journal of Medicine 1998; 338(13): 853-60.