Heavily treatment-experienced people in Europe do not have a higher risk of clinical events

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Among people living with HIV, the number of heavily treatment-experienced patients has increased in recent years. However, this may not translate into a higher risk of new AIDS or non-AIDS clinical events. Most heavily treatment-experienced people maintained good virological control, despite lower CD4 counts. These are the results of a European study recently published in the Journal of Acquired Immune Deficiency Syndromes.

The study

EuroSIDA is a European cohort study of people living with HIV. It holds epidemiological, clinical, biological and therapeutic data from over 23,000 individuals.

Dr Annegret Pelchen-Matthews and colleagues from EuroSIDA estimated the prevalence of heavily treatment-experienced patients in the cohort.

They propose a new definition of this status. Individuals who met any two of the following three criteria were considered heavily treatment-experienced:

  • Resistant to at least two classes of antiretroviral drugs.
  • Have changed antiretroviral regimen at least four times.
  • Are taking an antiretroviral regimen which includes four or more drugs.

Participants were adults with data recorded at any time between 2010 and 2016.

The investigators also assessed medical outcomes of becoming a heavily treatment-experienced person. Each participant was compared with three different non-heavily treatment-experienced counterparts in the cohort. These controls were randomly selected, without matching for clinical or demographic characteristics.


Of 15,570 participants, 1617 (10.4%, CI 9.9, 10.9%) were heavily treatment-experienced by the study definition. While 503 had reached this status before 2010, the other 1114 did so during the 2010-2016 follow-up.

The prevalence of heavily treatment-experienced patients increased with time. It went from 5.8% in mid-2010 to 8.9% in mid-2016. This represents an increase of 0.50% (CI 0.34, 0.66%, P = 0.0004) per year.

Most of these individuals only had remaining treatment options in two antiretroviral classes. This result was based on participants’ actual resistance data or on modelling predictions.

In west/central Europe, 16% of study participants were heavily treatment-experienced, compared to 13% and 12% in north and south Europe, respectively. However, just 26 (1.1%) of 2279 patients in eastern Europe were heavily treatment-experienced. This result reflects poorer outcomes for HIV-positive people in that region, including low levels of antiretroviral therapy coverage and virological suppression.

Participants who became heavily treatment-experienced during follow-up were older than those who did not. They were more likely to be men who have sex with men and less likely to be injecting drug users. Other trends among them were: lower nadir CD4 counts; living with HIV for over ten years; having had an AIDS diagnosis or developed a non-AIDS condition; and as suggested above, having used more antiretrovirals from all classes for a longer period of time.

Medical outcomes

Regarding medical outcomes, results are mixed. At the time participants were first classified as heavily treatment-experienced, 19.7% had a detectable viral load (≥ 400 copies). This compared to 8.7% of their non-heavily treatment-experienced counterparts. However, virologic control became similar in both groups after six months.



A person who has previously taken treatment for a condition. Treatment-experienced people may have taken several different regimens before and may have a strain of HIV that is resistant to multiple drug classes.


The presence of one or more additional health conditions at the same time as a primary condition (such as HIV).


Relating to the heart and blood vessels.

detectable viral load

When viral load is detectable, this indicates that HIV is replicating in the body. If the person is taking HIV treatment but their viral load is detectable, the treatment is not working properly. There may still be a risk of HIV transmission to sexual partners.

CD4 cells

The primary white blood cells of the immune system, which signal to other immune system cells how and when to fight infections. HIV preferentially infects and destroys CD4 cells, which are also known as CD4+ T cells or T helper cells.

CD4 counts tell a different story. For example, 13.3% of heavily treatment-experienced patients had less than 200 CD4 cells, while this was the case for only 5.1% of the non-heavily treatment-experienced patients. Moreover, in contrast to virologic control, these differences were maintained over two years of follow-up.

The incidence of AIDS events was higher among heavily treatment-experienced individuals. However, after adjustment for age, CD4 count and pre-existing co-morbidities, being heavily treatment-experienced was not strongly associated with AIDS during follow-up.

New non-AIDS events such as cancer, cardiovascular disease and kidney disease also appeared to be more frequent in heavily treatment-experienced patients. Liver disease, for example, seemed particularly prominent (unadjusted IRR 2.74, CI 1.37, 5.49, p = 0.0044) among them. However, adjusted models showed no significant association between being heavily treatment-experienced and non-AIDS events.


Pelchen-Matthews and colleagues say that “in multivariable models, the risks of AIDS and non-AIDS events could be completely explained by ageing, CD4 counts and pre-existing comorbidities.”

The less favourable CD4 trajectories in heavily treatment-experienced participants, despite good virological responses, suggest that low CD4 counts may play a key role. They say this highlights the need for treatment strategies that support immune reconstitution.

They also recommend that HIV guidelines single out heavily treatment-experienced people as a priority group for the screening and management of non-AIDS co-morbidities such as cancer and cardiovascular disease.


Pelchen-Matthews A et al. Prevalence and Outcomes for Heavily Treatment-Experienced (HTE) Individuals Living with Human Immunodeficiency Virus in a European Cohort. Journal of Acquired Immune Deficiency Syndromes, online ahead of print, February 2021.

doi: 10.1097/QAI.0000000000002635

Full image credit: Antiretroviral drugs to treat HIV infection. Image by NIAID. Available at www.flickr.com/photos/niaid/31793869534 under Creative Commons licence CC BY 2.0.