HIV/Sexual Health Clinical Education Session

Transcription

1 HIV/Sexual Health Clinical Education Session About These Slide These slides may not be published, posted online, or used in commercial presentations without permission. Please contact for details. ASHM SSHC 2018 HIV/Sexual Health Clinical Education Centre

2 The New England Journal of Medicine December 2017 to October 2018 Ruthy McIver Sydney Sexual Health Centre October 31, 2018

3 Original Article Phase 3 Study of Ibalizumab for Multidrug-Resistant HIV-1 Emu B. et al. J ARVs with novel mechanisms of action needed for multidrug-resistant HIV Ibalizuma (Trogarzo): new entry inhibitor Blocks HIV entry by binding to CD4 receptor Engineered broadly neutralising monoclonal antibody (mab) First mab with FDA approval - March 2018 IV infusion every two weeks Used in combination with other ARVs Review article: Engineering multi-specific antibodies against HIV N Engl J Med, Volume 379: , Aug 16, 2018 enrolment Heavily treatmentexperienced Multidrug resistant HIV Failing current ART Viral load > 1000 Deaths & discontinuations unrelated AE = IRIS (unrelated to infusion)

4 demographics and clinical characteristics Age median (range) 53 (23-65) Male no. (%) 34 (85) Years since diagnosis median (range) 23 (2-30) VL > 100,000 copies no. (%) 7 (18) CD4 median (range) 73 (0-676) No. ARVs received median (range) 10 (3-22) resistance profile at baseline

5 study procedures results Virologic Outcome Day 14 (n=40) Wk 24 (n=40) Wk 48 (n=27) > 0.5 log 10 HIV RNA decrease, % 83* - - > 1.0 log 10 HIV RNA decrease, % > 2.0 log 10 HIV RNA decrease, % HIV RNA < 50 copies/ml HIV RNA < 200 copies/ml, % Mean HIV RNA decrease from baseline, % *primary endpoint; p<0.001 vs 3% at day 7

6 limitations Small safety and efficacy database Rare safety events Drug interactions Individually tailored background ART with variable efficacy Uncertain contribution of Ibalizumab to patient response No control group Complex population No data on long-term response Perspective Ibalizumab for Multidrug-Resistant HIV Accepting Uncertainty Sheikh V et al. FDA approved a streamlined trial design for Ibalizumab J Patients and clinicians may accept greater risks for drugs when conditions are life-threatening and there are no other options Sample size proportionate to population with MDR HIV Patients were their own controls (pre and post infusion) Safety and tolerability assessed at 24 rather than 48 weeks Post-marketing pharmacovigilance N Engl J Med, Volume 379: Aug 16, 2018

7 Image Challenge A 35 year old male presented to the emergency psychiatry service with paranoid delusions and was found to have patchy, irregular alopecia of the scalp. What is the most likely diagnosis? Secondary syphilis RPR 1:128 Hair usually regrows after treatment nej.md/ppbcdb Special Article Clinical Trial Participants Views of the Risks and Benefits of Data Sharing Mello MM et al J + Sharing participant trial data: scientific, ethical and economical - Potential obstacles: financial, technical and operational N Engl J Med 2018; 378: June 7, 2018

8 methods 10 page focus-tested questionnaire 9 principal investigators at 3 research centres facilitated access to recent trial participants

9 summary Most thought benefits outweigh risks High willingness regardless of how data used High willingness even if no personal benefit Concerns about using data for marketing and litigation thoughts Additional considerations in sexual health Generalisability Re-identifiable data vs unidentifiable data Sample bias Meaningful consent

10 Original Article Tenofovir vs Placebo to Prevent Perinatal Transmission of Hepatitis B Jourdain G et al Multicentre, double-blind RCT 17 public hospitals in Thailand HBIg at birth plus HBV vaccine at 0,1,2,4,6 months Inclusion: positive HBeAG and HBV DNA >200,000 Exclusion: HIV, HCV, renal impairment N Engl J Med 378: , March 8, 2018

11 limitations Underpowered Generalisability Median vaccination and HBIg 1.2 and 1.3 hours after birth Editorial A Shift in Thinking to Reduce Mother-to-Infant Transmission of HBV Dusheiko, G Despite WHO recommendations, only 48% of countries give HBV vaccine at birth Infant and childhood infections most common Although no addition benefit with TDF in this study, vaccine plus HBIg soon after birth is effective Third trimester treatment important if vaccinations at birth not feasible N Engl J Med 378: , March 8, 2018

12 Original Article Phase 2b controlled trial of M72/AS01 Vaccine to prevent TB Van Der Meeren O et al TB leading infectious cause of death worldwide ¼ of the world affected by latent TB Latent TB can develop into active infection 3500 randomised to receive 2 doses of vaccine or placebo Results: Significant reduction in pulmonary TB in Healthy HIV negative (mostly) BCG-vaccinated adults with latent TB

13 Editorial New Promise for Vaccines against Tuberculosis Bloom B Small numbers in this study Interesting that this is the first vaccine to work in people already infected with latent TB Still need a vaccine that works in people with and without TB N Engl J Med; 379: Oct, 2018 Original Article Persistance of Zika Virus in Body Fluids Final Report Paz-Baily G et al Condoms for at least 3 months after symptoms or exposure if conception planned N Engl J Med 379: September 2018

14 review articles HIV-Associated Cancers and Related Diseases Yarchoa and Uldrick, March 2018 DOI: /NEJMra Kidney Diseases Associated with HIV Infection Cohen, Kopp and Kimmel, Dec 2017 DOI: /NEJMra