and Dolutegravir Combination Therapy in ART Experienced HIV-infected Patients: A Preliminary Report Alexandra Stang, Tracy Perry, Nada Fadul Department of Internal Medicine, Division of Infectious Diseases. East Carolina University/Brody School of Medicine

ABSTRACT METHODS RESULTS

Patients with HIV may require change in therapy for We conducted a chart review of HIV-infected patients, aged 18 years or older, who were A total of 87 charts were reviewed: 64 (74%) on DRV/DTG alone and 23 (26%) on DRV/DTG plus additional agents. simplification, salvage or to avoid side effects. There is seen at our clinic between August 2013 and December 2015, who were on a combination The mean age was 49.3 (range 18-79); 29 (33.3%) were female; and 77 (89%) were black. CAD or CAD equivalent limited data on the use of dolutegravir (DTG) and - of DRV/DTG alone or with additional active agents. We collected the following data was present in 27 (31%), CKD in 24 (28%), and chronic hepatitis B infection in 3 (3%) patients. The majority 86 or -boosted darunvair (DRV) combination therapy retrospectively: age, gender, race, most recent HIV viral load (VL) and CD4 count prior to (99%) of patients were treatment experienced; 60 (69%) had been treated with 3 or more antiretroviral drug classes; alone or with additional active agents in patients with HIV. starting DRV/DTG, and the baseline comorbidities of coronary artery disease (CAD) or 57 (66%) were experienced, including 6 (6.9%) with baseline integrase resistance. Baseline HIV viral load The objectives of this study were to describe the current CAD equivalent, chronic kidney disease (CKD), and chronic hepatitis B. Provider notes was >200 copies/mL in 41 (47%); and CD4 count was <200 in 29 (33%) patients. Reason for switch was reported as use and indications of DTG/DRV combination and to were examined for the rationale for selecting DRV/DTG as treatment and subsequently salvage in 42 patients (48%) simplification in 33 patients (38%), renal impairment in 11 patients (13%), and other in evaluate its effectiveness on viral load suppression (VLS). classified as either salvage (provider documentation of nonadherence or uncontrolled HIV 6 patients (7%). Baseline demographic and virologic characteristics and reasons for switching did not differ between We conducted a retrospective chart review of HIV-infected VL), simplification (reduction in pill burden in a patient with controlled HIV), renal the group of patients on DRV/DTG dual therapy versus those on DRV/DTG plus additional active antiretroviral patients, 18 years or older who were seen at our clinic insufficiency, or other. Data regarding the patient’s prior treatment history and any agents, with the exception of more patients with comorbid CAD in the former group and more patients with integrase between August 2013 to December 2015, who were on genotypic resistance were also extracted. In patients with resistance- inhibitor RAMs in the latter. DRV/DTG combination alone or with additional active associated mutations (RAMs), dolutegravir was dosed twice a day. agents. VLS was achieved or maintained in 40 of 46 patients (87%) who presented for follow up at 6-8 weeks, 25 of 28 HIV VL was collected retrospectively and/or prospectively for one year at time intervals (89%) at 3-4 months, and 35 of 41 (85%) at 5-6 months, and 55 of 61 (90%) at 7-12 months after starting therapy. We collected demographic, clinical and laboratory typical for follow up visits at our clinic: Between 6-8 weeks, 3-4 months, 5-6 months, and VLS did not differ between the group of patients treated with DRV/DTG alone versus DRV/DTG plus additional information. VLS was achieved or maintained in 40 of 46 7-12 months after initiation of DRV/DTG. Viral load suppression (VLS) was defined as HIV active agents. patients (87%) who presented for follow up at 6-8 weeks, VL <200 copies/mL. Reasons for the discontinuation of DRV/DTG were also noted. 25 of 28 (89%) at 3-4 months, and 35/41 (85%) at 5-6 Six patients were later switched off of DRV/DTG to another combination, of whom only two required switch due to months, and 55/61 (90%) at 7-12 months after starting Data was analyzed with descriptive statistics, Mann-Whitney U Test, and Fisher’s Exact intolerance (rash in 1 and large pill size in 1). therapy. Our preliminary results suggest that DRV/DTG tests. combination is a viable switch option in HIV patients with the majority of patients achieving or maintaining VLS at 1 year of follow up and only 2 patients required a regimen change due to intolerance.

INTRODUCTION

Interest in NRTI-sparing regimens developed in light of associated long term toxicities associated with some NRTIs and the need to develop salvage regimens for heavily treatment-experienced patients with multiple drug resistance mutations in which NRTIs may have reduced potency.

Raltegravir (RAL) has been investigated previously in combination with DRV. The ANRS 139 TRIO study of treatment-experienced patients with multidrug-resistant HIV found a high percentage of viruses who initiated RAL, DRV, and achieved a durable virologic response, regardless of whether these patients received an optimized background regimen1. The NEAT-001/ANRS 143 trial found the NRTI-sparing dual regimen of RAL plus DRV was noninferior to the 3 drug combination of fumarate (TDF), (FTC) and DRV as first-line therapy in treatment-naive patients; however, the RAL/DRV CONCLUSIONS group was associated with higher rates of treatment failure in patients with high pretreatment HIV RNA or low CD4 Our preliminary results suggest that the combination of boosted darunavir and dolutegravir is a viable switch option counts, and emergence of resistance mutations was in HIV patients, with the majority of patients in this small, single-center, real-world cohort achieving or maintaining higher2. VLS at 1 year of follow up and only 2 patients requiring a regimen change due to intolerance. Although conclusions are limited by the nature of the study design and sample size, DRV/DTG therapy appears to be an effective option Recent studies have also examined the use of the newer for salvage therapy, particularly in heavily-treatment experienced patients. integrase inhibitor DTG as part of dual therapy with either a PI or NNRTI. Patients who switched from standard antiretroviral therapy to a two-drug regimen of DTG plus maintained an undetectable viral load for 48 REFERENCES weeks in the SWORD-1 and SWORD-2 trials3. As such, there is limited but growing data to support the efficacy of 1. Yazdanpanah Y, Fagard C, Descamps D, et al. High rate of virologic suppression with plus etravirine and darunavir/ritonavir among NRTI-sparing, dual therapy with DTG. We aim to provide a treatment-experienced patients infected with multidrug-resistant HIV: results of the ANRS 139 TRIO trial, Clin Infect Dis 2009; 49: 1441–49. description of our real-world experience with DRV/DTG to 2. Raffi F, Babiker AG, Richert L et al. Ritonavir-boosted darunavir combined with raltegravir or tenofovir–emtricitabine in antiretroviral-naive adults add to that knowledge. infected with HIV-1: 96 week results from the NEAT001/ANRS143 randomized non-inferiority trial. Lancet 2014; 384: 1942–51. 3. Llibre JM, Hung CC, Brinson C, et al. Phase III SWORD 1&2: switch to DTG+RPV maintains virologic suppression through 48 wks. In: Program and abstracts of the 2017 Conference on Retroviruses and Opportunistic Infections; February 13-16, 2017; Seattle. Abstract 44LB.