Retrospective Evaluation of an Observational Cohort by the Central and Eastern Europe Network Group Shows a High Frequency of Potential Drug–Drug Interactions Among HIV-Positive Patients Receiving Treatment for Coronavirus Disease 2019 (COVID-19)

Botond Lakatos; Justyna Kowalska; Sergii Antoniak; Deniz Gokengin; Josip Begovac; Anna Vassilenko; Piotr Wasilewski; Lukas Fleischhans; David Jilich; Raimonda Matulionyte; Kerstin Kase; Antonios Papadopoulus; Nino Rukhadze; Arjan Harxhi; Sam Hofman; Gordana Dragovic; Marta Vasyliev; Antonija Verhaz; Nina Yancheva; Cristiana Oprea


HIV Medicine. 2022;23(6):693-700. 

In This Article

Abstract and Introduction


Objectives: The aim of this international multicentre study was to review potential drug–drug interactions (DDIs) for real-life coadministration of combination antiretroviral therapy (cART) and coronavirus disease 2019 (COVID-19)-specific medications.

Methods: The Euroguidelines in Central and Eastern Europe Network Group initiated a retrospective, observational cohort study of HIV-positive patients diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Data were collected through a standardized questionnaire and DDIs were identified using the University of Liverpool's interaction checker.

Results: In total, 524 (94.1% of 557) patients received cART at COVID-19 onset: 117 (22.3%) were female, and the median age was 42 (interquartile range 36–50) years. Only 115 (21.9%) patients were hospitalized, of whom 34 required oxygen therapy. The most frequent nucleoside reverse transcriptase inhibitor (NRTI) backbone was tenofovir disoproxil fumarate (TDF)/tenofovir alafenamide (TAF) with lamivudine or emtricitabine (XTC) (79.3%) along with an integrase strand transfer inhibitor (INSTI) (68.5%), nonnucleoside reverse transcriptase inhibitor (NNRTI) (17.7%), protease inhibitor (PI) (13.7%) or other (2.5%). In total, 148 (28.2%) patients received COVID-19-specific treatments: corticosteroids (15.7%), favipiravir (7.1%), remdesivir (3.1%), hydroxychloroquine (2.7%), tocilizumab (0.6%) and anakinra (0.2%). In total, 62 DDI episodes were identified in 58 patients (11.8% of the total cohort and 41.9% of the COVID-19-specific treatment group). The use of boosted PIs and elvitegravir accounted for 43 DDIs (29%), whereas NNRTIs were responsible for 14 DDIs (9.5%).

Conclusions: In this analysis from the Central and Eastern European region on HIV-positive persons receiving COVID-19-specific treatment, it was found that potential DDIs were common. Although low-dose steroids are mainly used for COVID-19 treatment, comedication with boosted antiretrovirals seems to have the most frequent potential for DDIs. In addition, attention should be paid to NNRTI coadministration.


There are about 1.7 million HIV-infected people in the Central Asian and Eastern European World Health Organization (WHO) region, the only region in the world with a substantially increasing incidence. The coronavirus disease 2019 (COVID-19) pandemic may have adversely affected this population of particularly vulnerable people.[1] HIV testing opportunities have tapered globally, and limited social support and counselling have yielded less efficient linkage to care and adherence to antiretroviral medication [combination antiretroviral therapy (cART)].[2] Notably, HIV-infected people with COVID-19 may have faced double social stigmatization, in both outpatient and hospital settings, especially in this region.[3]

It is currently unclear whether patients with HIV infection are at increased risk of contracting COVID-19 or developing more severe outcomes. For patients with well-controlled HIV infection with CD4 counts > 200 cells/μL, COVID-19 episodes will probably not pose a higher risk of unfavourable outcomes.[4] Providing optimal, in-hospital care for HIV-positive patients who have acquired COVID-19 is challenging in several respects. One of the most important risks is drug–drug interaction (DDI), which may result in increased toxicity and/or reduced efficacy both for cART and for COVID-19 treatments.

The race to identify potential compounds for treatment of COVID-19 has taken off in the last year, although clinically acceptable evidence of effectiveness against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is available for only a few treatment strategies.[5] Current international COVID-19 treatment guidelines widely recommend treatment strategies that are stratified by the clinical status of the patient.[6,7] Supportive care is of utmost importance throughout the treatment course. In general, administration of the antiviral remdesivir and anticoagulants is recommended for moderate/severe or hospitalized patients. Other recommended strategies include corticosteroid use in patients with oxygen supplementation, as well as other immunomodulatory agents (tocilizumab and baricitinib) for COVID-19-associated cytokine release syndrome.[6,7]

As a result, several medications may be given as routine treatment, mainly for moderately/severely or critically ill patients with COVID-19 who have treated HIV infection. Inaccurately assessed DDIs may result in serious consequences. In this analysis, we aimed to mirror a real-life scenario for potential cART and COVID-19 treatment DDIs.