Alberta clinic explores long-term survival among HIV-positive people

• Calgary researchers studied factors that may contribute to long-term survival with HIV.
• Adherence to medication and clinic attendance were associated with longer lives.
• Researchers also identified specialized HIV care as a possible factor in survival.

Most people diagnosed with HIV infection prior to 1996 in Canada and other high-income countries had greatly reduced life expectancy. However, in that year, potent combination anti-HIV therapy (ART) became increasingly available and was able to reverse most of the damage done to the immune systems of many people. In the current era, the effects of ART are so profound that researchers expect that the vast majority of young adults who become HIV positive today and who begin ART shortly thereafter will have near-normal life expectancy. This rosy forecast also depends on a number of related factors, such as the following:

• a person’s ability to take ART every day exactly as prescribed
• maintaining regular doctor appointments
• having blood drawn on a regular basis for laboratory analysis
• screening for and, if necessary, care and treatment of serious issues such as: mental health issues; problematic alcohol or other substance use and/or addictions; chronic infections such as hepatitis B or C virus

Most studies of long-term survivors of HIV infection have usually examined factors related to genes, immunology or virology. Researchers at the Southern Alberta Clinic in Calgary have taken a different approach to their recent analysis of long-term survivors. They scoured medical records of people who had been diagnosed with HIV from the late 1980s to 1996 and who were in continuous care in January 2016 (the end of their study period). Compared to people with HIV who had died or moved out of the region, the researchers found that long-term survivors who were alive and in care for more than 20 years tended to have been diagnosed with HIV as young adults, attended regular clinic and laboratory visits, and had taken ART longer.

Additional findings from the Alberta study reported later in this CATIE News bulletin are interesting because the researchers calculated the amount of medicine taken by participants, in kilograms, over the course of more than 20 years. Since HIV-positive patients will be taking ART for the rest of their lives, perhaps this finding has implications for the development of future HIV treatment regimens. A final important result from the study is that researchers calculated the cost of HIV care and treatment over time. This is important for clinics, policy planners, health authorities and ministries of health when planning budgets.

Study details

Researchers analysed the medical records at the Southern Alberta Clinic (SAC), focusing on people diagnosed with HIV in the region prior to 1996. People who were diagnosed elsewhere and who later moved to southern Alberta were excluded. Out of nearly 3,300 HIV-positive patients who ever used the SAC, there was a total of 876 patients who were diagnosed locally prior to 1996. Here is their status to January 2016, the end of the study:

• 50% (434 people) died
• 30% (265 people) moved and/or stopped coming to the clinic
• 8% (73 people) went in and out of care
• 12% (104 people) were continuously in care for at least 20 years

Researchers checked the timeliness of prescription refills (previous studies have found this to be linked to good adherence to ART) and the frequency of clinic visits as well as missed clinic appointments (previous studies have also linked multiple missed clinic visits to poor adherence and poor health outcomes).

A note about deaths

Researchers did not provide the precise cause of death for all deceased people. However, a majority of deaths (close to 90%) occurred in people diagnosed between 1982 and 1995—prior to the introduction of ART. One can safely assume that many of these deaths were related to complications arising from severe life-threatening infections, unremitting weight loss and cancers that are the hallmark of severe HIV-related immune deficiency—AIDS.

Focus on survivors continuously in care

As of January 2016, the average profile of the 104 long-term survivors was as follows:

• age – 57 years; 15% were older than age 65
• 11 females, 93 males
• CD4+ count – almost 600 cells/mm³
• AIDS diagnosis – nearly 30% had been diagnosed with AIDS at some point over the past two decades
• viral load less than 50 copies/mL – 97%
• length of time between HIV diagnosis and access to healthcare – two months

ART—years and weight of medicine

All 104 long-term survivors had been taking ART for more than 20 years, with various regimens. On average, they had been taking their current regimen for the past six years. This is likely a reflection of the tolerability of modern ART.

According to the researchers, over the course of the study, “on average, each individual patient consumed 8.62 kg (almost 19 pounds) of ART,” distributed as follows:

• nucleoside analogues (nukes) – 4 kg (almost 9 lbs)
• non-nucleoside analogues (non-nukes) – 2 kg (more than 5 lbs)
• protease inhibitors – 2 kg (almost 5 lbs)

The researchers did not take into account the class of ART called integrase inhibitors. These were first introduced about 10 years ago and came into wider use about six years ago.

Cost of care

The cost of care—including ART, clinic visits, lab tests, hospitalization—over the 20-year course of the study came to about $32 million (CDN). Most of this figure (84%) was driven by the cost of ART. A lesser cost arose from clinic visits and lab tests (totaling 13%) and hospitalizations accounted for 3% of total costs. On average, the cost of care for each patient was about $309,000 over the 20 years of the study, or about $15,418 per patient per year.

Reasons for survival

The researchers outlined three main factors they think contributed to the long-term survival of these patients:

Commitment and dedication

The researchers remarked upon the “consistency of patients in attending regular clinic visits two to four times a year for over 20 years and undergoing routine lab tests at each visit.” They noted that an additional factor that should be underscored is that these patients had shown “adherence to numerous daily medications over long periods of time with timely refilling of prescriptions when needed.”

An experienced clinic and the doctor-patient relationship

Another factor advanced by the researchers was that patients were able to access “a dedicated and specialized HIV care centre that can provide high-quality HIV services to patients living with HIV.” The experience of doctors, nurses and pharmacists should not be overlooked. Other studies have found that HIV-positive patients who are looked after by healthcare providers who treat more than 50 patients with HIV per year tend to have better health. Furthermore, the researchers stated that “regular follow-up over long periods of time between patients and physicians contributes to more positive interactions and results.”

A dedicated response from the ministry of health

The health services needed by HIV-positive people at the SAC are provided without charge. The researchers stated that although the cost of care per patient that they calculated was high and similar to that found in one U.S. study, “the financial support provided for care allowed these individuals to be productive in both direct and indirect ways that contribute to the well-being of the population, making ART and other HIV care cost-effective.”

Note that it is possible that several other unmeasured factors could have had an impact on the long-term survival of participants. The researchers made the following statement:

“We did not investigate health-related or lifestyle changes that long-term survivors made to contribute to better health and better health choices or mental health status, socioeconomic or education levels that may have contributed to their longevity; nor did we investigate formal or informal supports these individuals may have had that also contributed to beneficial outcomes.”

Medication consumption—how might regimens change?

The average amount of ART taken by patients over the course of the study was large when measured by weight. This is a testament to the fortitude and adherence of the patients and to the life-prolonging effects of ART.

In the early days of ART, regimens were complex; they involved taking many pills two to three times daily (in one case, every eight hours), with food and water requirements. Many early regimens came with several unpleasant and, in some cases, distressing side effects.

Most people starting ART today can choose from regimens that can be taken once daily and generally do not have food or water requirements. As well, advances in treatment and research suggest the possibility that simpler and safer regimens are in store. Here are two that have been approved in Canada in 2018 and will hopefully be on the formularies (list of medicines) subsidized by ministries of health in 2019:

• Biktarvy – a combination of three drugs in one pill: bictegravir + TAF + FTC, taken once daily. Clinical trials have found that Biktarvy is generally well tolerated and effective. TAF (tenofovir alafenamide) is a safer form of the older and widely used drug tenofovir DF.
• Juluca – a combination of two drugs in one pill: dolutegravir + rilpivirine. Taken once daily, Juluca is meant as maintenance therapy for people whose current and more complex regimen has made their viral load undetectable. Juluca must be taken with a meal.

Here are some additional simplified regimens in development:

• long-acting injectable formulations of cabotegravir + rilpivirine; meant for maintenance HIV treatment, taken once monthly
• a combination of two drugs—dolutegravir + 3TC—in one pill; meant for HIV treatment taken once daily with no food or water requirements
• MK-8591 – a nucleoside analogue with long-acting properties; this compound is still in early stage development and will be combined with another, as yet unknown, drug in the future

Back to the southern Alberta study

As mentioned earlier, as of January 2016 a total of 104 participants who had been diagnosed with HIV prior to 1996 survived. An update from the research team (Harmut Krentz, PhD, written communication) stated that as of January 2018, 95 out of 104 (91%) participants were alive.

Resources

B.C. researchers explore life expectancy among HIV-positive people – CATIE News

Swiss researchers investigate drug use and its impact on health and survival – CATIE News

Italian and U.S. researchers look to the future and explore aging-related issues – CATIE News

Canadian study finds increased risk of death among HIV-positive Indigenous people – CATIE News

Exploring factors linked to longer survival among ART users – TreatmentUpdate 200

Issues unrelated to HIV are affecting survival – TreatmentUpdate 228

—Sean R. Hosein

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