CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

in 6/13 participants,one each for Grade 4 neutropenia (likely related to TB medication), use of a disallowed medication, or AUC12h exceeding the allowed AUC12h maximum (asymptomatic). Three stopped RAL for virologic failure (VF): 1 at wk 8 (above) who was very ill; 1 at wk 12 (non-adherence); 1 at wk 12 (VF unexplained). Conclusion: A 12 mg/kg dose twice daily of RAL chewable tablets appears to safely achieve PK targets in HIV/TB co-infected children 4 wks to <2 yrs receiving rifampin, with high rates of virologic suppression by Week 8. 847 ADEQUATE DOLUTEGRAVIR EXPOSURE DOSED BID WITH RIFAMPICIN IN CHILDREN 6 TO <18 YEARS Hylke Waalewijn 1 , Hilda Mujuru 2 , Pauline Amuge 3 , Mark Cotton 4 , Pauline Bollen 1 , Man Chan 5 , Shabinah Ali 5 , Ebrahim Variava 6 , Shafic Makumbi 7 , Angela Colbers 1 , Diana Gibb 5 , Deborah Ford 5 , David M. Burger 1 , Anna Turkova 5 , for the Odyssey Trial Team 1 Radboud University Medical Center, Nijmegen, Netherlands, 2 University of Zimbabwe, Harare, Zimbabwe, 3 Baylor College of Medicine Children's Foundation, Kampala, Uganda, 4 Stellenbosch University, Cape Town, South Africa, 5 MRC Clinical Trials Unit at UCL, London, UK, 6 University of the Witwatersrand, Johannesburg, South Africa, 7 Joint Clinical Research Centre, Mbarara, Uganda Background: Adults with HIV/TB co-infection on dolutegravir (DTG)-based antiretroviral therapy (ART) can overcome the induction effect of rifampicin (RIF) by doubling the DTG dose (50mg twice(BID) instead of once(QD) daily. We undertook a pharmacokinetic (PK) substudy nested within the ongoing ODYSSEY randomised controlled trial (#NCT02259127) to evaluate DTG PK in HIV/ TB co-infected children while receiving DTG BID+RIF and DTG QD. Methods: Children aged 6-<18 years receiving DTG BID+RIF were eligible; we aimed to include 6 children aged 6-<12 years and 6 children 12-<18 years. A 12h PK curve was constructed for children on DTG BID in the last month of RIF treatment and subsequently, a 24h PK curve on DTG QD ≥4 weeks after stopping RIF. Geometric mean ratios (GMRs) were estimated comparing DTG PK parameters between the 2 periods and individual C trough levels below EC 90 (0.32 mg/L) were summarised. All children who received DTG BID+RIF aged ≥6 years were followed for serious adverse events(SAEs), grade 3/4 clinical/laboratory adverse events(AEs) and any AEs resulting in ART modification from start of DTG BID to 30 days after return to DTG QD. Results: Of 30 eligible children, 17 were enrolled in the PK substudy; 13/17 participants undertaking PK had ≥1 evaluable PK curve. 12/13 were black African, median (range) age 12.3 (6.8-16.1) years and 31.3 (19.8-48.5) kg. 12 PK curves were evaluable for DTG BID+RIF (5 on 25mg BID and 7 on 50mg BID) and 11 for DTG QD (5 on 25mg QD and 6 on 50mg QD). GMRs (90% CI) for DTG BID+RIF versus DTG QD (reference) for C trough , AUC0-24h and C max were 1.59 (1.09-2.33), 1.20 (0.90-1.59), and 0.98 (0.79-1.21), respectively. Oral clearance of DTG with RIF was increased 1.7-fold, with 41% reduction in elimination half-life. Findings were similar in children above and below 12 years old. AUC0-24h GMRs in children ≥20kg receiving WHO 2019-recommended DTG 50mg dose was 1.00 (0.61-1.62) and 1.47 (0.99-2.19) for children on 25mg dose. One child on DTG 25mg QD without RIF had C trough

848 RISK FACTORS FOR NEW HIV INFECTIONS IN THE GENERAL POPULATION IN SUB-SAHARAN AFRICA Emma Slaymaker 1 , Kathryn A. Risher 1 , Ramadhani Abdul 2 , Milly Marston 1 , Keith Tomlin 1 , Robert Newton 3 , Anthony Ndyanabo 4 , Estelle McLean 1 , Tawanda Dadirai 5 , Daniel Kwaro 6 , Kathy Baisley 7 , Coleman Kishamawe 8 , for the ALPHA Network 1 London School of Hygiene & Tropical Medicine, London, UK, 2 Ifakara Health Institute, Dar es Salaam, Tanzania, United Republic of, 3 University of York, York, UK, 4 Rakai Health Sciences Program, Kalisizo, Uganda, 5 Biomedical Research and Training Institute, Harare, Zimbabwe, 6 Kenya Medical Research Institute, Kisumu, Kenya, 7 Africa Health Research Institute, Mtubatuba, South Africa, 8 National Institute of Medical Research, Mwanza, Tanzania, United Republic of Background: Previous work identified risk factors for new HIV infections in sub-Saharan African populations but patterns of association are not consistent across studies. Different risk factor definitions and low power may explain some inconsistencies. Statistical power has not previously been estimated in these risk factor analyses. We harmonised population-based longitudinal data from general population studies in 6 sub-Saharan African countries, partners in the Network for Analysing Longitudinal Population-based HIV/AIDS data on Africa, to assess risk factors for new HIV infections. Potential risk factors were identified from the literature and a modified version of the proximate determinants framework. Methods: Individual level data covering 2005 to the end of follow up (2012- 2016) were obtained for each study. Data were arranged for survival analysis with first HIV negative test as the start of observation and HIV seroconversion as the failure event. Indviduals were censored at death, out migration and end of follow up. 70 imputations of seroconversion date were used to overcome interval censoring. Time-varying risk factors were: residence, residential mobility, time since first sex, marital status, numbers of partners in lifetime and last year, acquisition of new partners, types and combinations of partnerships, male circumcision, condom use and age gaps between partners. Piecewise exponential regression models were fitted separately by study for men and women aged 15-24 and 25-49. Crude hazard ratios were compared between studies. We estimated the statistical power to detect each association. Study- and sex- and age-specific multivariate models were fitted and consistency of risk factors evaluated. Where warranted, the pooled effects of risk factors are estimated. Results: 99097 people contributed 351457 person years (203266 fromwomen). There were 5274 seroconversions (3711 among women). Figure 1 shows the crude hazard ratio for HIV infection by selected risk factors. Most consistent findings across studies were that new & multiple partners and being formerly married increased risk whilst being circumcised decreased risk. Condom use was protective among people who had higher risk partnerships. Conclusion: Effect size and strength of evidence varied across studies and age groups and for each risk factor. Whilst lack of statistical power explains some heterogeneity there are likely to be real differences in the importance of some risk factors between populations.

Poster Abstracts

CROI 2020 316