ISSN 1472-4863 hiv treatmen+ (e) HTB: 2019 vol 20 no 4 bulletin 28 March 2019: no 4 CROI 2019: second reports C O N T E N T S EDITORIAL 2 • Integrase inhibitors and neural tube defects: SUPPLEMENTS 2 more data still needed • U=U resources for UK clinics: free posters, • Double-dose levonorgestrel implant does not postcards and factsheets completely overcome interaction with efavirenz i-BASE APPEAL 2 • Efavirenz and rifampicin together reduce levels of • i-Base 2019 appeal: we need your help…. injectable contraception CONFERENCE REPORTS 3 • Bedaquiline and delamanid safe when given Conference on Retroviruses and Opportunistic together to treat drug resistant TB Infections (CROI 2019), 4–7 March, 2019 • Isoniazid preventative therapy in HIV positive • Introduction pregnant women not linked to poor outcomes • Maturation inhibitor GSK’232 reduces viral load ANTIRETROVIRALS 11 by –1.5 log at day 10 • Dear Doctor letter: Increased risk of treatment • Capsid inhibitor GS-6297 shows potential for failure and increased risk of mother-to-child 3-monthly injections transmission of HIV infection dues to lower • First phase 1 results from bNAb PGT121 in HIV exposure of elvitegravir and cobicistat during the positive people second and third trimesters of pregnancy • Dolutegravir/3TC dual ART is as effective at FUTURE MEETINGS 12 lowest viral load cut-off as triple therapy in • Conference listing 2019 GEMINI Studies PUBLICATIONS AND SERVICES • Same-day ART in San Francisco: long-term FROM i-BASE 13 follow-up from Rapid-ART clinic ORDER FORM 14 Published by HIV i-Base HIV TREATMENT BULLETIN h-tb EDITORIAL HIV TREATMENT BULLETIN This issue of HTB includes our second set of reports from HTB is published in electronic format by HIV i-Base. As with all the recent CROI 2019 conference. i-Base publications, subscriptions are free and can be ordered These include reports on pipeline compounds from three new using the form on the back page or directly online: classes – a maturation inhibitor, a capsid inhbitor and first results http://www.i-Base.info of a monocolonal antibody PGT121. or by sending an email to: [email protected] Editor: Simon Collins Two posters reported that rapid-ART access continues to Contributing Editor: Polly Clayden produce good results in San Francisco and there are additional supportive results for dolutegravir/3TC dual therapy from the Medical consultants: GEMINI study. Dr Tristan Barber, Royal Free Hospital, London. In a major review, Polly Clayden reports in depth on the current Dr Karen Beckerman, Albert Einstein College of Medicine, NY. Dr Sanjay Bhagani, Royal Free Hospital, London. data covering the possible signal of neural tube defects associated with dolutegravir. Prof. Diana Gibb, Medical Research Council, London. Dr Gareth Hardy, PhD. Other reports include pharmacokinetic and drug interaction Prof. Saye Khoo, University of Liverpool Hospital. studies including that double-dose levonorgestrel implant does Prof. Clive Loveday, ILVC, UK. not overcome an interaction with efavirenz, that efavirenz and Prof. James McIntyre, Chris Hani Baragwanath Hosp. S Africa. rifampicin together reduce levels of injectable contraception and Dr Graeme Moyle, Chelsea & Westminster Hosp, London. that bedaquiline and delamanid can be given together to treat Dr Stefan Mauss, Düsseldorf. MDR TB. Prof. Caroline Sabin, UCL Medical School, London. Dr Graham P Taylor, Imperial College, London. SUPPLEMENTS Dr Stephen Taylor, Birmingham Heartlands Hospital. * U=U resources for UK clinics: free Dr Gareth Tudor-Williams, Imperial College, London. /u-equals-u posters, postcards and factsheets U=UUNDETECTABLE Dr Edmund Wilkins, Manchester General Hospital.. viral load means HIV IS Please continue to order these free UNTRANSMITTABLE HTB is a not-for-profit community publication. It reviews the www.i-Base.info * Undetectable = Untransmittable most important medical advances related to clinical man- resources. agement of HIV including access to treatment. We compile comments to articles from consultant, author and editorial Customise U=U posters for your clinic responses. i-Base can customise U=U posters to include We encourage i-Base originated material to be reprinted for pictures of your doctors, nurses, pharmacists, peer community use but copyright remains with HIV i-Base. A credit advocates or any other staff that would like to help and link to the author, the HTB issue and the i-Base website is publicise U=U. always appreciated. Copyright for other articles remains with the credited source. We thank other organisations for this use Personalising these for your clinic is easy and might and encourage readers to visit the linked websites. be an especially nice way to support U=U. HIV i-Base receives educational grants from charitable trusts, For further information please contact Roy Trevelion individual donors and pharmaceutical companies. All editorial at i-Base: policies are strictly independent of funding sources. [email protected] i-Base 2019 appeal HIV i-Base, 107 The Maltings, This year we are continuing a funding appeal to help i-Base 169 Tower Bridge Road, London, SE1 3LJ. continue to provide free publications and services. T: +44 (0) 20 8616 2210. Your help has been inspiring – and we hope this support will continue during 2019. If 1000 people support us with £5 a month http://www.i-Base.info we will be on course to meet our funding shortfall. HIV i-Base is a registered charity no 1081905 All help is appreciated. and company reg no 3962064. HTB was formerly known as DrFax. http://i-base.info/i-base-appeal-we-need-your-help 2 28 March 2019 • Vol 20 No 4 www.i-Base.info PROOF FOR COMMENT ONLY PROOF FOR COMMENT ONLY HIV TREATMENT BULLETIN CROI 2019 Seattle CONFERENCE REPORTS CROI 2019: ANTIRETROVIRALS Maturation inhibitor GSK’232 reduces Conference on Retroviruses and viral load by –1.5 log at day 10 Opportunistic Infections (CROI 2019) 4–7 March, 2019 Simon Collins, HIV i-Base Results from a 10-day phase 2a dose-finding study for GSK2838232 (GSK’232) – a maturation inhibitor in development at GSK – were presented by Edwin DeJesus Introduction from Orlando Immunology Centre. This year the Conference on Retroviruses and Maturation inhibitors bind to gag protein to target a late-stage of Opportunistic Infections (CROI 2019) was held in Seattle viral lifecycle and the development of two previous compounds in from 4–7 March. this class were stopped due to limited activity due to commonly occurring polymorphisms (beviramat) and side effects (BMS- The meeting had an exciting programme with research that we 955176). will report over at least the next three issues of HTB. The new GSK compound has good in vitro potency, minimal CROI is notable for providing same-day or next-day webcasts for protein binding and broad-spectrum activity (including against most talks and comprehensive online access to abstracts and polymorphisms associated with beviramat). PDF files for posters. GSK-232 was given once-daily with cobicistat boosting. Doses http://www.croiconference.org in this two-part study were 20 mg, 50 mg, 100 mg and 200 mg - BHIVA have also organised an excellent series of CROI feedback each given with cobicistat 150 mg. The 100 mg dose was run as workshops and slides and webcasts from the London meeting the first part of this study. are also posted online. Approximate baseline characteristics of the 33 participants https://www.bhiva.org/BestofCROI2019 (largely young white men) included mean CD4 and viral load of 540 cells/mm3 and 58,000 copies/mL (range: 1300 to 363,000). This is the second set of HTB reports from the CROI. Mean viral load decline at day 10 was –1.5 log copies/mL in • Maturation inhibitor GSK’232 reduces viral load by –1.5 log at the 200 mg arm and 1.2 log copes/mL on the 50 mg and 100 day 10 mg arms, sustained for several days before returning towards • Capsid inhibitor GS-6297 shows potential for 3-monthly baseline over the following 10 days. injections Steady state was reached by day 8 and most PK parameters • First phase 1 results from bNAb PGT121 in HIV positive (AUC, Cmax and C trough) showed broadly dose-proportional people responses. • Dolutegravir/3TC dual ART is as effective at lowest viral load Resistance results at days 1 and 11 were available for 28/33 cut-off as triple therapy in GEMINI Studies participants. Two participants (one in 50 mg and one in 100 mg arms) had genotypic changes at A364A/W in gag, which • Same-day ART in San Francisco: long-term follow-up from phenotypic resistance to GSK’232 detected at day 11 in the 50 Rapid-ART clinic mg participant. • Integrase inhibitors and neural tube defects: more data still Reduced baseline sensitivity to GSK’232 in another participant in needed the 50 mg arm only produced a viral load reduction of 0.17 log • Double-dose levonorgestrel implant does not overcome copies/mL. interaction with efavirenz Tolerability was good with no pattern form mild/moderate side • Efavirenz and rifampicin together reduce levels of injectable effects or dose relationship, with no serious events and no contraception discontinuations. There were no grade 3/4 lab abnormalities or clinically significant ECG abnormalities. • Bedaquiline and delamanid safe when given together to treat drug resistant TB Reference • Isoniazid preventative therapy in HIV positive pregnant women DeJesus E et al. A phase IIa study of novel maturation inhibitor GSK2838232 in HIV patients. Conference on Retroviruses and Opportunistic Infections (CROI), not linked to poor outcomes 4-7 March 2019,