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. 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)]. Notably, HIV-infected people with COVID-19 may have faced double social stigmatization, in both outpatient and hospital settings, especially in this region.
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. 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. 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.
HIV Medicine. 2022;23(6):693-700. © 2022 Blackwell Publishing