Swiss study explores trends in interruption and re-engagement in HIV care

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CATIE News 02182025
  • Swiss researchers monitored nearly 15,000 people living with HIV for interruptions to HIV care
  • 19% had their care interrupted, and upon re-engagement, many had a weakened immune system
  • Interruptions declined over the course of the study, coinciding with more tolerable HIV drugs

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The Joint United Nations Programme on AIDS (UNAIDS) has encouraged cities, regions and countries to strive for the following goals by 2025:

  • 95% of people with HIV know their infection status
  • 95% of people with HIV are taking HIV treatment (antiretroviral therapy, ART)
  • 95% of people with HIV who are taking ART have a suppressed level of HIV in their blood

These goals are important because suppression of HIV as a result of consistently taking ART leads to better health for people with HIV. Indeed, research suggests that many ART users will have near-normal life expectancy. Another benefit is that clinical trials have found that people with HIV whose virus is suppressed thanks to ART cannot transmit HIV to their sexual partners. Thus, when used as directed, ART has both treatment and prevention effects.

The UNAIDS 2025 goals focus on large populations in a city, region or country. However, at the level of a clinic, it is also important to monitor individual patients for any issues that may occur and to provide advice and assistance if there are difficulties taking ART exactly as directed.

In Switzerland

Researchers in Switzerland created a detailed database—the Swiss HIV Cohort Study—that has been collecting health-related information from people with HIV since the mid-1990s. The database has health-related information on about 70% of people with HIV in Switzerland. It is periodically updated and analyzed and provides useful reports on different health issues faced by people with HIV. 

In its latest analysis, a team of Swiss researchers scoured the database, focusing on participants who initiated ART after January 1, 1996, and who subsequently interrupted ART. The data analysis extended to July 2020 in some cases. The researchers found records of nearly 15,000 participants who were monitored for at least 10 years. Of these participants, about 19% (2,768) interrupted their care. Of the 2,768 people who interrupted care, 1,384 re-engaged in care and the remainder did not. 

A total of 552 of the 1,384 people who eventually re-engaged in care appeared to have kept taking ART while they did not attend a study clinic. Researchers inferred that these 552 participants kept taking ART because their viral loads were very low when they eventually re-engaged in care. Being disengaged from study clinics yet having a suppressed viral load may seem counter-intuitive, but this will be explained later. The remaining participants who stopped visiting the study clinics must have also stopped taking ART, as when they returned for care their viral loads were not suppressed.

Risks arising from interrupting treatment

Among participants who interrupted ART and then re-engaged in care, their average CD4+ count fell from 374 cells/mm3 before the interruption to 250 cells/mm3 14 months later when they re-engaged in care. 

Some participants took even longer to re-engage with care—more than 60 months. The average CD4+ count of these participants when they re-engaged with care was 185 cells/mm3. Having such a low CD4+ cell count indicates a weakened immune system, which places a person at high risk for life-threatening infections. 

In contrast, people who remained in care and on ART continued to find their CD4+ cell counts increasing to an average of 600 cells/mm3.

Interruption of ART also leads to an increased risk of HIV transmission because the virus is no longer suppressed. The average viral load upon re-engaging with care was nearly 40,000 copies/mL.

Researchers found that nearly 12% of participants who interrupted ART returned to study clinics with a new AIDS-related infection. The most common AIDS-related infections that developed in the time off ART included the following:

  • pneumocystis pneumonia (PCP, PJP)
  • severe fungal infection of the throat and mouth (esophageal candidiasis)
  • Kaposi’s sarcoma (KS)
  • toxoplasmosis 

The longer that participants interrupted ART, the greater the risk of developing a life-threatening infection. For instance, among participants who interrupted ART for 14 months, there was a 7% risk of developing a life-threatening complication. The figure rose to 17% for those who interrupted ART for more than 60 months.

Over time, the risk for interrupting clinic visits and/or ART decreased and remained lower in the years 2005 to 2009 (compared to 1996 to 1999) and it did not further decrease after this time. 

Why did interruptions in care and treatment occur?

Note that the rate of disengagement from ART was relatively high at the start of the study, but then fell and remained stable over the course of the study. Over time, options for ART became simpler (once-daily dosing) and much better tolerated than what would have been available in the 1990s. This means that adherence became easier and there were fewer side effects, which could likely account for the decline in ART cessation. 

Studies in other countries have found that certain factors—such as socio-economic challenges, lack of perceived benefit of ART, difficulties in coping with an HIV diagnosis, ART side effects—play a role in disengagement from care. The researchers argue that it is unlikely that these factors played a role in the Swiss study. What’s more, the researchers (who are experienced physicians) inferred that some interruptions in care occurred in the Swiss clinics possibly for the following reasons:

  • participants temporarily left the country – people who temporarily left were able to obtain HIV care while residents outside of Switzerland. Some of the participants who interrupted care in Switzerland were born in sub-Saharan Africa, which might explain why some people who stopped attending Swiss clinics were able to stay on ART.
  • substance use-related issues – about 38% of participants who interrupted ART engaged in substance use. It is possible that some people in this population did not receive the support necessary to help them adhere to ART.

Interviews would be helpful

A major drawback of this study (and of many studies on adherence) is that researchers were unable to interview participants about their reasons for withdrawing from care and/or ART. Such studies are expensive and time consuming. What’s more, there is fierce competition for research funds and there are many urgent medical issues that also require studies. Additionally, scientific funding agencies tend to not prioritize large studies that interview people. 

However, the Swiss researchers have done an analysis of a large database and found that disengagement from HIV care and treatment does occur. The study results therefore provide a rationale for monitoring clinic databases and sending an alert to clinic staff when participants have been out of care for a certain period (this may vary from patient to patient and could be four to six months). The researchers stated that based on other studies, clinic staff could then intervene with “telephone calls, letters sent by mail or email, and home visits by specialized outreach teams.” The researchers also stated that studies in the U.S. have found that the following interventions can help some patients re-engage with care:

  • patient navigators
  • appointment assistance and alerts
  • psychosocial support
  • finding a community member to accompany patients to appointments

The Swiss research underscores that there are sub-populations of people who interrupt care and/or ART. Future studies that include interviews with people who disengage from care and treatment are vital if regions and countries are to maintain and exceed UNAIDS goals.

In Canada

Researchers in Canada probed pharmacy databases to analyze anonymized information on the prescription refill habits of nearly 19,000 people with HIV. Over a period of 10 years (2010 to 2020), they found that nearly 45% of participants had less-than-ideal adherence to ART. They based this conclusion on the timing of prescription refills and noting the number of days when participants did not have any pills, counting those days as periods when people would not be adherent. In general, people who were non-adherent in the Canadian study were struggling with a number of co-existing health conditions and/or tended to be younger. 

In the United States

In one U.S. study, researchers analysed anonymized data from more than 200,000 people with HIV, focusing on the period of July 2017 to September 2018. Participants were from every state. The researchers also reviewed pharmacy refill records and found that more than 60% of participants had less than 90% adherence. These participants did not appear to be filling their prescriptions on time and went for periods without HIV treatment. 

In another U.S. study, researchers explored adherence and the risk of HIV becoming partially or wholly resistant to treatment. They found that rates of resistance to treatment varied between 20% and 54%, depending on the state. What’s more, the researchers found that states with the highest levels of HIV drug resistance tended to have people with HIV who as a group had poor rates of adherence to treatment.

Bear in mind

The studies from Switzerland, Canada and the U.S. suggest that adherence is an issue for some, perhaps many, people with HIV. Long-acting regimens, such as Cabenuva (injectable cabotegravir + rilpivirine), that are ultimately injected once every two months are one potential solution for some patients. However, even with Cabenuva, clinic and laboratory visits are required. Clinics need additional funding to engage in studies of adherence and ways to support patients so that the impressive survival benefits of ART can be maintained.

—Sean R. Hosein

Resource

2025 AIDS Targets – UNAIDS 

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