MEDICINE Didanosine-Associated Retinal Toxicity (DART) Amongst HIV-Positive Patients: a Case Series and Literature Review Paul Nderitu 1 & Paraskevi Riga 2 & Samantha Mann 2 & Christina Garnavou-Xirou 1 & Haralabos Eleftheriadis 3 Accepted: 28 October 2020 # Springer Nature Switzerland AG 2020 Abstract The aim of this study is to report on didanosine-associated retinal toxicity (DART) in four adult patients with human immuno- deficiency virus (HIV) identified incidentally during routine diabetic eye screening and review all reported cases to date. This study is a retrospective, observational, case series from two health institutions with a review of published literature. DART is often asymptomatic, and patients have good vision (mean visual acuity 6/9), but in advanced cases, severe visual field defects can occur. Fundal changes range from mild granular pigmentary mottling to patches of mid-peripheral chorioretinal atrophy. Continuous expansion of chorioretinal degenerative changes posteriorly may lead to significant macular involvement as dem- onstrated in two of our cases. Despite cessation of therapy, DART was progressive in approximately 25% of reported cases. Our cases were incidentally discovered during routine diabetic eye screening and did not report any ocular symptoms prior to referral. Given the initial asymptomatic nature of DART, we believe that the true prevalence of the disease may be higher than previously thought. It may be prudent to screen and follow-up patients with a history of DDI use. We demonstrate the utility of multimodal imaging, optical coherence tomography, electrodiagnostic testing and visual fields in evaluating the effects of DART. Keywords Didanosine . HIV . Retinal toxicity . Chorioretinal atrophy Introduction Worldwide, there are over 36.9 million people living with HIV (UN AIDS 2017) with 1.8 million people newly affected with HIV per year [1]. In 2017, it was estimated that 21.7 million HIV-positive patients were accessing antiretroviral therapy (ART), an increase of 8 million people compared to 2010 [1]. In 2014, the Joint United Nations Programme on HIV/AIDS (UNAIDS) set the ambitious target of 90-90-90, aiming for 90% of all HIV-positive patients to be diagnosed, 90% to be on sustained ART and 90% to have effective viral suppression by 2020 [2]; it is therefore clear that ART use will be widespread and sustained. Didanosine (DDI), a nucleoside reverse transcriptase inhib- itor (NTRI), was first synthesised in 1964 as an anticancer drug but gained approval for use as an antiretroviral agent for the treatment of HIV by the Federal Drug Administration (FDA) in the USA in 1991 [3]. Between 2002 and 2006, the World Health Organization (WHO) recommended DDI to be used as the second-line ART treatment for HIV-positive pa- tients [3]. However, the 2013 WHO consolidated ART guide- lines did not recommend DDI as a first- or second-line ART agent due to toxicity concerns [3]. The FDA issued updated safety alerts for DDI-induced fatal pancreatitis and lactic aci- dosis in 2002 and DDI-induced non-cirrhotic portal hyperten- sion in 2010 [3]. While in most developed countries DDI has been substituted with other antiretroviral drugs, despite the reported concerns, in 2012, at least 20 countries purchased a total of 1 to 2 million US dollars’ worth of DDI, which is 3 to 10 times the cost of the preferred second-line agent lamivudine [3]. To date since 1992, there have been numerous reported cases of didanosine-associated retinal toxicity (DART) amongst adults [4–11]. The reported clinical findings of DART range from mild mid-peripheral pigmentary stippling to extensive patches of chorioretinal atrophy which can affect the macula in advanced cases [4–11]. Patients are initially This article is part of the Topical Collection on Medicine * Paul Nderitu p.nderitu@doctors.org.uk 1 King’s College Hospital, Denmark Hill, London SE5 9RS, UK 2 Guy’s and St Thomas’ Hospital, Westminster Bridge Road, London SE1 7EH, UK 3 King’s College London Faculty of Life Sciences and Medicine, Hodgkin Building, London SE1 1UL, UK SN Comprehensive Clinical Medicine https://doi.org/10.1007/s42399-020-00625-1