CROI 2020 Abstract eBook

Abstract eBook

Oral Abstracts

(Table). Within the subset with available data (N=1518), PWH with immune dysregulation (CD4:CD8<0.8) had lower (-120ml, p<0.01) and faster decline (-6ml per year faster, pinteraction=0.02) of FEV1 compared to HIV-. PWH with CD4 nadir<200 also had lower (-159ml, p<0.01) and faster decline (-6ml/year faster, pinteraction=0.02) of FEV1 compared to HIV- adjusted for current CD4 and covariates. Conclusion: Among these participants with heavy tobacco exposure, lung function was significantly lower among PWH compared to HIV- and declined more rapidly in PWH than HIV- in those age <50. Low CD4 nadir (independent of current CD4) and immune dysregulation had a significant impact on lung function decline, irrespective of age. This finding suggests that HIV may manifest with impaired lung function in earlier ages. It also addresses the importance of achieving immune regulation in order to preserve lung function among PWH.

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BIC/FTC/TAF POSTEXPOSURE PROPHYLAXIS PROTECTS MACAQUES AGAINST RECTAL SHIV INFECTION Elena Bekerman 1 , Stephanie W. Cox 1 , Scott McCallister 1 , Tomas Cihlar 1 , Christian Callebaut 1 1 Gilead Sciences, Inc, Foster City, CA, USA Background: Current guidelines recommend 4 weeks of daily ARVs for post-exposure prophylaxis (PEP) after an HIV exposure, though the optimal duration of PEP is not known. An effective short-course regimen could simplify HIV prevention after an exposure, or provide an option for event-driven post-exposure prophylaxis (PrEP) as a simplified alternative to long-term daily regimen. Here, we evaluated PrEP/PEP regimens with Emtricitabine(FTC)/ Tenofovir Alafenamide(TAF) combined with different doses of Bictegravir(BIC) in a non-human primate model of SHIV exposure. Methods: A pharmacokinetic study was conducted in rhesus macaques with varying amounts of BIC + FTC/TAF (200/25 mg) to select BIC dose. Two efficacy studies were performed with 6 to 8 repeat low dose SHIV162P3 rectal challenges 2 weeks apart to minimize residual drug exposure. Two oral doses of ARVs were administered at different times relative to virus exposure. In Study 1, BIC/FTC/TAF (25/200/25mg) or FTC/TAF (200/25mg) was given at -2h/+24h (n=6), +24/+48h (n=6), or +48h/+72h (n=6 or 5). Follow-up Study 2 tested 100mg BIC in combination with FTC/TAF, (100/200/25mg) given at +6h/+30h, +12/+36h, +24h/+48h, +48h/+72h or FTC/TAF (200/25mg) at +6h/+30h or +12/+36h (n=6 each). A Kaplan-Meier survival analysis was conducted and a log-rank test was used to compare time to infection relative to placebo controls. Results: After 8 virus challenges in Study 1, BIC/FTC/TAF (25/200/25mg) protected 6/6 animals in the -2h/+24h group, 1/6 animals in the +24/+48h group and 0/6 animals in the +48/+72h group (Table 1). FTC/TAF alone protected 5/6 animals in the -2h/+24h group, 1/6 in the +24/+48h group and 0/5 in the +48/+72h group. After 6 virus challenges in Study 2, BIC/FTC/TAF (100/200/25mg) protected 5/6 animals in the +6h/+30h group, 6/6 animals in the +12/+36h, 4/6 animals in the +24h/+48h, and 3/6 animals in the +48h/+72h group (Table 1). In contrast, FTC/TAF (200/25mg) protected 3/6 animals in the +6h/+30h group and 4/6 animals in the +12/+36h group. Conclusion: Two doses of FTC/TAF + BIC (100mg) initiated up to 24h after rectal virus exposure were protective in a SHIV/macaque model. FTC/TAF + BIC (25mg) provided similar protection to FTC/TAF alone and were only efficacious when used as -2/+24h regimen. These results provide support to further study FTC/TAF + BIC (100mg) as a simplified event-driven PEP regimen.

Oral Abstracts

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AZITHROMYCIN FOR TREATMENT OF HIV-RELATED CHRONIC LUNG DISEASE IN AFRICAN CHILDREN Rashida A. Ferrand 1 , Grace McHugh 2 , Andrea M. Rehman 1 , Hilda Mujuru 3 , Mark Nicol 4 , Sarah Rowland-Jones 5 , Trond Flaegstad 6 , Tore Gurtteberg 6 , Victoria Simms 1 , Elizabeth L. Corbett 1 , Helen A. Weiss 1 , Edith D. Majonga 2 , Katharina Kranzer 1 , Jon O. Odland 6 , for the BREATHE Trial Group 1 London School of Hygiene & Tropical Medicine, London, UK, 2 Biomedical Research and Training Institute, Harare, Zimbabwe, 3 University of Zimbabwe, Harare, Zimbabwe, 4 University of Cape Town, Cape Town, South Africa, 5 University of Oxford, Oxford, UK, 6 Arctic University of Norway, Tromso, Norway Background: HIV-related chronic lung disease (HCLD) in children and adolescents is associated with substantial morbidity, despite antiretroviral therapy (ART). HCLD may be a consequence of repeated respiratory tract infections and/or dysregulated immune activation. Macrolides have anti-inflammatory and antimicrobial properties, and we hypothesized that azithromycin (AZM) would improve lung function and morbidity through preventing respiratory tract infections and controlling systemic inflammation. Methods: We conducted a randomized double-blinded, placebo-controlled trial among children aged 6-19 years on ART with HCLD (defined as FEV1 Z-score<-1) in Malawi and Zimbabwe. Once-weekly AZM (with weight-based dosing) or placebo was administered for 48 weeks. Primary outcome was mean difference in FEV1 Z-score. Secondary outcomes were mortality, hospitalisations and acute respiratory exacerbations (ARE). Outcomes were adjusted for age, sex, trial site and HIV viral load (VL) at baseline, using robust standards errors for multiple event data. Results: A total of 347 children were recruited (49% female, median age 15.3 years) of whom 44% had a VL>1000copies/ml and 74%were on first-line ART; 90%were taking cotrimoxazole prophylaxis and the median CD4 count was 571cells/µl. Previous treatment for tuberculosis was reported by 28% and chronic cough by 9%, and 44% had an abnormally high respiratory rate. We randomized 174 to AZM and 173 to placebo. At the end of 48 weeks of treatment, the mean difference between arms in FEV1 Z-score was 0.06 (95% CI 0.10, 0.21; p=0.48). There was a significant difference in incidence of ARE, adjusted incidence rate ratio 0.50 (95% CI 0.25, 1.00; p=0.05) (Figure 1). The rate ratio for hospitalizations was 0.24 (0.06-1.07, p=0.061) comparing AZM to placebo. Mortality was 0/100pyrs in the AZM vs 1.95/100pyrs in the placebo arm. Conclusion: This is the first ever trial of an intervention to address HCLD in children. While once-weekly AZM had no effect on pulmonary function, it reduced mortality, hospitalizations and incidence of AREs. AZM is an effective intervention in reducing morbidity associated with HCLD in children and adolescents.

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CROI 2020