Impact of Therapeutic Drug Monitoring of Antiretroviral Drugs in Routine Clinical Management of People Living With HIV: A Narrative Review

Abstract

Purpose:The treatment of human immunodeficiency virus (HIV) infection has evolved significantly since the advent of highly active antiretroviral therapy. As a result, a response rate of 90-95 % now represents a realistically achievable target. Given this background, it is difficult to imagine the additional benefits that therapeutic drug monitoring (TDM) could provide in the management of HIV infection.Methods: This article is not intended to provide a systematic literature review on TDM of antiretroviral agents; rather, the authors aim to discuss the potential added value of TDM in the optimal management of people living with HIV (PLWH) in selected real-life clinical scenarios based on data collected over 10 years by their TDM service.Results: Some clinical situations, in which the selection of the optimal antiretroviral therapy is challenging, have been identified. These include poorly compliant patients, sub-optimal antiretroviral therapies (in terms of both efficacy and toxicity), polypharmacy with a high risk of drug-drug interactions (DDIs), and different patient populations, such as pregnant women. Conclusions:The transformation of HIV infection from a near universally fatal illness to a lifelong chronic disease has resulted in an HIV population that is growing and aging, placing new and increasing demands on public programs and health services. Increasingly, the management of comorbidities, polypharmacy, and DDIs and their impact on antiretroviral therapy will have to be undertaken. These clinical settings represent some of the new frontiers for the use of TDM with the goal of achieving optimal prescription and outcome for PLWH.

A Link Between Methylglyoxal and Heart Failure During HIV-1 Infection

“…The human immune cell reconstitution in mice was assessed by flow cytometry using fluorescence conjugated primary antibodies to the human antigens CD45, CD3, CD19, CD4, CD8, and CD14 from BD Pharmingen (San Diego, CA, USA). Antibodies for immunohistochemistry were obtained from AbCam Inc., Cambridge MA [anti-VAP-1, rabbit polyclonal, Cat # Ab187202; anti-TAGLN (SM22α), goat polyclonal, Cat # Ab10135]; Hycult Biotech, Wayne PA (mouse monoclonal, MG-H1, Cat # HM5017) and Santa Cruz Biotechnology Inc., Santa Cruz, CA [Glo-I [FL-184]], rabbit polyclonal, Cat # SC-67351; the non-selective inflammation-induced protein VAP-1 [E-19], goat polyclonal, Cat # sc-13741; and actin ( 1 – 19 ), goat polyclonal Cat # SC-1616). Secondary antibodies were obtained from Invitrogen Life Technologies (chicken anti-rabbit IgG coupled to Alexa Fluor 488, Cat # A21441; chicken-anti-mouse IgG coupled to Alexa Fluor 488, Cat # A21200; donkey anti-goat IgG coupled to Alexa 594 Cat # A11058); Santa Cruz Biotechnology, Inc. (Donkey anti-rabbit IgG-HRP, Cat # sc-2305 Donkey anti goat IgG-HRP Cat # sc-2304).…”

“…Modern antiretroviral drug therapies (ART) have profoundly reduced morbidities and mortality in human immunodeficiency virus type one (HIV-1) infected individuals ( 1 , 2 ). However, by contemporary estimates more than 40% of persons living with HIV-1 infection (PLWH) on long-term combination ART therapies are developing early-onset heart failure (HF) ( 3 – 7 ).…”

Transient increase in plasma HIV RNA after COVID-19 vaccination with mRNA-1272

“…Potential drug-drug interactions were screened and ruled out. Adherence to ART was indirectly confirmed by therapeutic drug monitoring, showing tenofovir trough concentrations (21 ng/L) within the expected range for TAF (10-25 ng/mL) on a leftover blood sample obtained on the same day viremia was assessed [Cattaneo et al, 2020]. Fourteen days after the increase (and the second vaccine dose), a new bloodwork was obtained and VL was suppressed again.…”

Buprenorphine–cannabis interaction in patients undergoing opioid maintenance therapy

“…Furthermore, the various antiviral medications used to treat HCV or HIV infection have been described to both inhibit and induce CYP enzymes, most notably CYP3A4. As a consequence, suboptimal levels of concurrent psychotropic medication have been found with a higher incidence in HIV/HCV-positive cohorts than in negative cohorts [18]. Wittchen and colleagues identified concomitant cannabis use in 30-46% in small and large OMT centers, respectively [2].…”

“…Elevated buprenorphine levels were only found in patients with HCV infection plus moderate-to-severe liver impairment [20,21]. Another risk factor is antiviral therapy with drugs known to cause interactions via the CYP isozymes [18,22]. The CYP3A4dependent metabolism of buprenorphine may be subject to interactions with both therapeutic and illicit drugs.…”