CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

Results: Overall, 102 patients initiated RR-TB treatment containing DLM within a median of 1.6 months (IQR 0.8-3.2) after treatment initiation; 62 (61%) were male, 91 (89%) were >19 years, 79 (77%) were HIV-positive, and 40% and 35% had multi-drug resistant tuberculosis (MDR-TB) and MDR-TB with second-line resistance, respectively. The median baseline CD4-count was 141 cells/mm 3 (n=70, IQR 61-252) and 94% of the HIV-positive patients were on ART at DLM initiation. Patients received DLM due to intolerance to drugs in the standard RR-TB regimen (n=57, 56%), limited therapeutic options (n=38, 37%), or treatment failure (n=7, 7%). Patients’ interim treatment outcomes are summarized in Table 1. Among the 30/102 patients with a positive culture at DLM initiation (22/30 HIV-positive), 25 (83%) converted to negative by month 6 (19/25 HIV-positive). Time to culture conversion 6-months after delamanid initiation did not significantly differ based on HIV-status (P>0.05). Conclusion: Early treatment outcomes among patients on DLM-containing regimens in a programmatic, primary care setting with high HIV prevalence were promising, regardless of HIV-status. As DLM has fewer drug-drug interactions with antiretroviral agents than the other novel TB drug bedaquiline, it may be an important therapeutic option for HIV/RR-TB co-infected individuals.

in both arms. Every patient in this study was cured from TB but uveitis which is associated to rifabutin developed in two patients who received RFB 300mg TIW. Conclusion: Our study suggests that RFB 150mg QD and 300mg TIW could result in adequate exposure in Thai patients who concurrently use LPV/r. Moreover, this study shows that LPV/r 400/100 mg BID can give adequate lopinavir levels in HIV and TB co-infected patients who were treated with RFB both 150 mg QD and 300 mg TIW.

Poster Abstracts

782 WIRELESSLY OBSERVED THERAPY VS DIRECTLY OBSERVED THERAPY FOR TB MEDICATION ADHERENCE Sara H. Browne 1 , Charles A. Peloquin 2 , Amanda J. Tucker 1 , Kathleen Moser 3 , Julie Low 4 , Anya Umlauf 5 , Florin Vaida 1 , Constance A. Benson 1 1 University of California San Diego, La Jolla, CA, USA, 2 University of Florida, Gainesville, FL, USA, 3 Health and Human Services Agency, San Diego, CA, USA, 4 Orange County Health Care Agency, Santa Ana, CA, USA, 5 University of California San Diego, San Diego, CA, USA Background: Directly Observed Therapy (DOT) is universally recommended to ensure Mycobacterium Tuberculosis Complex (TB) treatment adherence. DOT is resource intensive, intrusive and expensive, limiting implementation in high burden areas. Mobile technologies to confirmmedication adherence have emerged recently. However, technology validation and comparison to the existing DOT Gold Standard is lacking. FDA approved Wirelessly Observed Therapy (WOT) is the first digital technology to detect medication ingestion and provide a stand-alone system to track TB medication adherence. WOT consists of an edible ingestion sensor (IS), external wearable patch and paired mobile device, it time-and-date stamps ingestions; recordings are uploaded to a secure Internet server, for remote viewing. We have previously ‘digitized’ fixed-dose Isoniazid/Rifampin (IS-INH/RIF) by co-encapsulation with IS (see doi:10.1002/ cpt.760) and have validated WOT ingestion detection accuracy using IS-INH/RIF as 98.4% (CI 97.5-99%). We now report findings from a randomized controlled trial performed in highly funded US DOT programs comparing the proficiency of WOT and DOT to confirm TB medication adherence. Methods: Sixty-one subjects with active MTB in the continuation phase of treatment were randomized 2:1 to receive WOT using IS-INH/RIF or standard of care DOT (5 days per week). In the WOT arm, if ingestions were not remotely confirmed, the subject was contacted within 24-48 hrs. The number of doses taken confirmed by DOT versus WOT were collected, length of observation varied according to treatment prescribed. The percentage of prescribed doses that were confirmed by DOT or WOT was calculated separately for each arm, using 7 and 5 days a week comparisons. Wilcoxon rank sum test was used to compare arms.

781 PHARMACOKINETICS OF RIFABUTIN 150 MG QD VS 300 MG TIWWITH LPV/R IN HIV/TB PATIENTS Chris Fujitnirun 1 , Weerawat Manosuthi 2 , Sivaporn Gatechompol 3 , Phornchai Pingsusaen 3 , Narukjaporn Thammajaruk 3 , Angela Colbers 4 , Rob Aarnoutse 4 , Kiat Ruxrungtham 1 , David M. Burger 4 , Anchalee Avihingsanon 3 , Opass Putcharoen 1 1 Chulalongkorn University, Bangkok, Thailand, 2 Bamrasnaradura Infectious Diseases Institute, Bangkok, Thailand, 3 HIV–NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand, 4 Radboud University, Nijmegen, Netherlands Background: Rifabutin(RFB) based anti TB is an alternative when boosted protease inhibitors (PIs) are in need. RFB 150mg QD, 150mg three times a week (TIW) or 300mg TIW are recommended in different guidelines. However, the TIW dose of 150mg RFB was suggested to be sub-therapeutic . The objective of this study was to compare pharmacokinetics of RFB 150mg QD, vs 300mg TIW in combination with lopinavir/ritonavir (LPV/r) 400/100mg based cART in HIV/TB co-infected Thai patients. Methods: This was a randomized, open-label, 2- arm, intensive pharmacokinetic study, as well as a 24 week efficacy study, conducted in Thai HIV and TB co-infected patients. RFB pharmacokinetics were evaluated before and between week 2 to week 8 after coadministration of LPV/r. We used a an LC-MS/MS method to determine RFB and 25-O-desacetyl RFB (desmetRFB) at Radbound university and and HPLC method to determine LPV/r concentrations Results: A total of 21 patients were enrolled in the study. 10 patients were randomized to RFB 150mg QD and 11 patients received RFB 300mg TIW. AUC of RFB 150mg QD combined with LPV/r is moderately higher than RFB alone ( 41.9%). and AUC over 48 hours in patients with RFB 300 mg TIW combined with LPV/r is 23% higher than RFB alone. Geometric mean Cmax (CV) of RFB 150mg QD +LPV/r and 300mg QD alone were similar 0.65 mg/L versus 0.66mg/L, whereas the Cmax after RFB 300mg TIW+ LPV/r was 24% higher.Exposure to desmetRFB was 1060% and 837% higher for 150mgRFB QD+LPV/r and 300mgRFB TIW+LPV/r. Overall RFB and desmetRFB exposure were 14% and 22% lower for the 300mgRFB TIW group compared to the 150mgRFB QD group. Pharmacokinetic parameters of LPV/r are in therapeutic level and were similar

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