CROI 2017 Abstract e-Book

Abstract eBook

Oral Abstracts

interruption (22% of all participants due to MSPN and 28% due to PN), during the 6 mos of treatment. One had peak ALT and AST > 3 X ULN and total bili > 2X ULN, but these improved and treatment restarted without a recurrence. There were 7 cases of grade 3 or 4 transaminitis and all resolved and allowed the study regimen to be continued. There were no cases of optic neuritis. As of 15 December, 2016, there has been 1 microbiological relapse. Conclusion: Current results of this greatly simplified and shortened all-oral regimen for drug resistant TB are encouraging in terms of both efficacy and safety. Prior Presentation or Publication: Yes - Data was presented at the Union conference (Liverpool, England) in October 2016 on the 15 participants that completed six months of treatment and reached the primary endpoint of six months post-treatment. This abstract provides more data as now 61 patients have been enrolled, with 34 having completed the 6 months of therapy and 20 have been followed to the primary endpoint at 6 months at treatment. Given the high rate of TB/HIV, we feel it is important to bring this information to CROI. 81LB RANDOMIZED CONTROLLED TRIAL OF PREDNISONE FOR PREVENTION OF PARADOXICAL TB-IRIS Graeme Meintjes 1 , Cari Stek 2 , Liz Blumenthal 1 , Friedrich Thienemann 1 , Charlotte Schutz 1 , Jozefien Buyze 2 , Gary Maartens 1 , Robert Wilkinson 3 , Lutgarde Lynen 2 , for the PredART Trial Team 1 Univ of Cape Town, Cape Town, South Africa, 2 Inst of Tropical Med, Antwerp, Belgium, 3 Imperial Coll, London, UK Background: Early initiation of antiretroviral therapy (ART) in patients with TB reduces mortality in those with low CD4 counts, but increases the risk of paradoxical TB-IRIS. Prednisone reduces symptoms when used to treat TB-IRIS. We determined whether prophylactic prednisone in patients at high risk for paradoxical TB-IRIS safely reduces the incidence of TB-IRIS. Methods: 1:1 randomized, double-blind, placebo-controlled trial of prednisone (40 mg/day for 2 weeks then 20 mg/day for 2 weeks) started with ART in ART-naïve adults at high risk of TB-IRIS (within 30 days of TB treatment initiation and CD4 count ≤100/μl) followed for 12 weeks. Exclusion criteria included rifampicin resistance, neurological TB, Kaposi’s sarcoma, hepatitis BsAg+ and poor clinical response to TB treatment. Primary endpoint was development of TB-IRIS, defined using the International Network for the Study of HIV- associated IRIS (INSHI) consensus case definition, adjudicated by an independent committee. Final results are presented. Results: 240 participants were enrolled: median age 36.8 (IQR=30-42.8), 60%men, median CD4 49/μl (IQR=24-86), and median HIV RNA 337,775 copies/ml (IQR=162,223- 810,812). TB was microbiologically confirmed in 175. 18 were lost to follow-up or withdrew. TB-IRIS fulfilling INSHI criteria was diagnosed in 56 in the placebo arm (46.7%) and 39 in the prednisone arm (32.5%) (p=0.02, relative risk (RR)=0.70 (95%CI=0.51-0.96)). Open label corticosteroids to treat TB-IRIS was prescribed as necessary in 34 of the placebo arm (28.3%) and 16 (13.3%) of the prednisone arm (RR=0.47 (95%CI=0.27-0.83)). 4 deaths occurred in the placebo arm (1 attributed to TB-IRIS) and 5 in the prednisone arm (p=1.0). 27 were hospitalized (all-cause) in the placebo arm compared with 17 in the prednisone arm (p=0.10). Grade 3 adverse events occurred more frequently in the placebo arm (45.4% vs 29.4%, p=0.01), but grade 4 adverse events were similar by arm (8.4% vs 7.6%, p=0.81). Severe infections (AIDS-defining or invasive bacterial) occurred in 18 in the placebo arm and 11 in the prednisone arm (p=0.17). There was a trend towards fewer interruptions of ART or TB treatment in the prednisone arm (8.3% vs 15.8%, p=0.07). Conclusion: In patients at high risk of paradoxical TB-IRIS, prednisone during the first 4 weeks of ART reduced the risk of TB-IRIS by 30% and further reduced the requirement for corticosteroids to treat TB-IRIS by 53%. The intervention was well-tolerated with no excess risk of infection or malignancy. 82 AMBITION-CM: HIGH-DOSE LIPOSOMAL AMPHOTERICIN FOR HIV-RELATED CRYPTOCOCCAL MENINGITIS Joseph N. Jarvis 1 , Tshepo B. Leeme 2 , Awilly A. Chofle 3 , Gabriella Bidwell 3 , Mooketsi Molefi 4 , Katlego Tsholo 2 , Nametso Lekwape 2 , Charles Muthoga 2 , Síle Molloy 5 , Thomas S. Harrison 5 1 CDC Botswana, Gaborone, Botswana, 2 Botswana–UPenn Partnership, Gaborone, Botswana, 3 Natl Inst of Med Rsr, Mwanza, Tanzania, 4 Univ of Botswana, Gaborone, Botswana, 5 St. George’s Univ of London, London, UK Methods: HIV-infected patients admitted with a first episode of cryptococcal meningitis were randomised to one of four treatment regimens: (i) L-AmB 10 mg/kg day 1 (single dose); (ii) L-AmB 10 mg/kg day 1, L-AmB 5 mg/kg day 3 (two doses); (iii) L-AmB 10 mg/kg day 1, L-AmB 5 mg/kg days 3, and 7 (three doses); (iv) standard 14-day L-AmB 3mg/kg/d (control arm). All were given with high dose fluconazole 1200mg/d. The primary endpoint was early fungicidal activity (EFA) over the initial 2 weeks of therapy, derived from serial quantitative CSF cultures. Linear regression analysis was used to compare EFA by treatment group. Results: 80 participants were enrolled – median age 38 years, 54%male, 33% on ART, median CD4=34 cells/μL, 29% abnormal mental status at baseline. Rate of fungal clearance in all three short-course high-dose arms was non-inferior to the control arm at the predefined non-inferiority margin of 0.2 logCFU/ml/day (figure). Adjusting for baseline fungal burden, CD4 count, and mental status did not alter the strength of association. One-way ANOVA analysis comparing EFA between the three short-course treatment arms found no evidence for any significant difference. Overall mortality was 29% (23/80): 29% (6/ 21) in the control arm, 22% (4/18) in the single dose arm, 15% (3/20) in the two dose arm, and 48% (10 of 21) in the three dose arm. All treatment groups were well tolerated, with only three participants experiencing DAIDS grade 4 anemia (all in the control arm), and seven DAIDS grade 4 creatinine rises, with no participants requiring treatment interruptions. Conclusion: Single doses of 10mg/kg L-AmB were well tolerated and led to non-inferior EFA compared to 14-day courses of 3mg/kg L-AmB in HIV-associated CM. Based on these results single dose 10mg/kg L-AmB is being taken forward to a phase 3 clinical endpoint trial. Background: Cryptococcal meningitis (CM) is associated with 10-20% of deaths in HIV-programs in Africa. Current antifungal treatments are inadequate and new treatment strategies are urgently needed. Recent data suggest it may be possible to deliver highly effective induction therapy with very few large doses of liposomal amphotericin B (L-AmB). We performed a phase-II randomized controlled non-inferiority trial examining the Early Fungicidal Activity (EFA) of three alternative short-course high-dose L-AmB schedules for the treatment of HIV-associated CM in Tanzania and Botswana.

Oral Abstracts

32

CROI 2017