Having a less favorable progression in the CD4 cell count, despite having good virological control, could play a key role in the development of these events

Although in recent years there has been an increase in the number of people with HIV with extensive experience in the use of antiretroviral treatments, this factor may not translate into an increased risk of experiencing new related clinical events, or not, with HIV. What's more, the majority of multitreated people maintained good virological control of HIV, despite having lower CD4 cell counts. These are the main findings of a European study recently published in the Journal of Acquired Immune Deficiency Syndromes.

The advances against HIV in the last decades have been absolutely relevant for the control of the infection and for the improvement of the quality and life expectancy of people with HIV. However, long-term use of antiretroviral therapy could limit the available drug options.


To provide further evidence on this question, a team of researchers from the EuroSIDA cohort - a prospective, multicenter, cohort study containing epidemiological, clinical, biological and therapeutic data on more than 23,000 people with HIV in Europe - conducted a study with The objective of calculating the prevalence of patients with extensive experience in antiretroviral treatments in this cohort, what possible clinical consequences it could have and proposing a new definition of this condition. For people to be considered highly experienced in antiretroviral treatment, they had to meet two of these three criteria: have resistance to at least two classes of antiretroviral drugs; have changed antiretroviral regimen, at least four times; and be taking an antiretroviral regimen with four or more drugs.

The study included 15,570 adult participants with HIV and followed them between 2010 and 2016. A total of 1,617 (10.4%; 95% confidence interval [95% CI]: 9.9-10, 9%) had extensive experience in antiretroviral therapy as defined by the study. A total of 503 participants had reached that status before 2010, while the other 1,114 did so during the 2010-2016 follow-up.

The researchers also evaluated the clinical consequences of having extensive experience in the use of HIV treatments. To do this, each multitreated participant was compared with three different control participants from the cohort without such extensive treatment experience. These controls were selected randomly, without coinciding with the clinical or demographic characteristics of the cases.

The prevalence of patients with extensive treatment experience increased over time, from 5.8% in mid-2010 to 8.9% in mid-2016, representing an increase of 0.50% (95% CI: 0 , 34-0.66%; p = 0.0004) per year. Most of these people had only two types of antiretroviral families as available treatment options. This result was based on the actual data for resistance-conferring viral mutations from the participants or on the predictions of the models.

16% of the participants from Western and Central Europe had extensive treatment experience, compared to 13% and 12% in Northern and Southern Europe, respectively. However, only 26 (1.1%) of the 2,279 Eastern European participants had extensive treatment experience, reflecting the poorer outcomes for people with HIV in that region, including low levels of antiretroviral treatment coverage and of virological suppression.


Participants who acquired multitreated patient status during the 6-year follow-up were older than those who did not, and were more likely to be gay, bisexual, and other men who have sex with men (GBHSH) and less likely to be injection drug users. Other characteristics of this group were: having a lower CD4 nadir count –that is, the lowest recorded at any time–; have been living with HIV for more than 10 years; have had an AIDS diagnosis or developed a non-AIDS disease; have used more antiretrovirals of all classes over a longer period of time.

Regarding the clinical results, these were uneven. At the time the participants were first classified as multitreated patients, 19.7% had a detectable viral load equal to or greater than 400 cells / mm3, compared with 8.7% of patients in the control group. However, after six months, both groups achieved virological control in a similar proportion.

The CD4 count, however, provided quite different evidence. Thus, for example, 13.3% of patients with extensive treatment experience had a CD4 level below 200 cells / mL compared to only 5.1% of group participants. Furthermore, unlike what happened with virological control, these differences were maintained during two years of follow-up.

The incidence of AIDS-related clinical events was higher among participants with extensive treatment experience. However, when results were adjusted for age, CD4 count, and pre-existing comorbidities, being a multi-treated patient was not closely linked to experiencing AIDS-related events during follow-up.

New non-AIDS clinical events, such as cancer, cardiovascular disease, and kidney disease, also appeared to be more frequent in patients with extensive treatment experience. The presence of liver disease in them, for example, seemed to be especially high (unadjusted incidence rate ratio [uIRR]: 2.74; 95% CI: 1.37-5.49; p = 0.0044). However, adjusting the models did not show a significant association between having extensive experience in treatment and non-AIDS events.

In conclusion, the researchers note that, in multivariate models, the risks of developing AIDS-related and non-AIDS-related events could be fully explained by aging, CD4 cell counts, and pre-existing comorbidities. The less favorable evolutions in CD4 counts in participants with extensive treatment experience - despite having a good virological response - suggest that having a low CD4 count could play a key role in the development of these events, which puts highlights the need for treatment strategies that promote immune reconstitution. The team of researchers also recommends that HIV guidelines consider people with extensive treatment experience as a priority group for screening and treating non-AIDS comorbidities such as cancer and cardiovascular disease.


Source: Aidsmap / Elaboración propia (gTt-VIH).
References: 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





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