CROI 2024 Abstract eBook

Abstract eBook

Oral Abstracts

211

Efficacy, Safety, and PK of BIC/FTC/TAF in Adults With HIV and Tuberculosis on Rifampicin at Week 24 Anushka Naidoo 1 , Kogieleum Naidoo 1 , Marothi P. Letsoalo 1 , Hylke Waalewijn 2 , Gillian Dorse 1 , Rubeshan Perumal 1 , Mahomed-Yunus S. Moosa 3 , Emmanuella C. Osuala 1 , Resha Boodhram 1 , Dennis Israelski 4 , Paolo Denti 2 , James F. Rooney 4 , Kelly Dooley 5 , for The INSIGHT Trial Team 1 Centre for the AIDS Programme of Research in South Africa, Durban, South Africa, 2 University of Cape Town, Cape Town, South Africa, 3 University of KwaZulu-Natal, Durban, South Africa, 4 Gilead Sciences, Inc, Foster City, CA, USA, 5 Vanderbilt University, Nashville, TN, USA Background: Integrase strand transfer inhibitors, bictegravir (BIC) and dolutegravir (DTG), are currently recommended for the treatment of HIV. However, the efficacy, safety, and pharmacokinetics (PK) of BIC in people with HIV (PWH) and tuberculosis (TB) taking rifampicin-based therapy has not been evaluated. Methods: INSIGHT (NCT04734652) is an open-label, non-comparative, phase-2b randomised controlled trial in ART-naïve or non-naïve adults with HIV (CD4+ >50 cells/μL) and TB, taking a rifampicin-based TB regimen (for ≤ 8 weeks). Participants were randomised 2:1 to the BIC arm [bictegravir/ emtricitabine (FTC)/tenofovir alafenamide (TAF)] or a standard of care DTG arm [tenofovir, lamivudine, dolutegravir (TLD)], with BIC/FTC/TAF or DTG dosed twice daily, until 2 weeks post-TB treatment and once daily thereafter, until 48 weeks. Participants underwent regular clinical and safety visits, including HIV viral load measurements at baseline and weeks 4, 8, 12, 24, 40 and 48. Semi-intensive PK sampling was performed during TB treatment and post-TB treatment. Non-compartmental PK analyses for BIC were conducted in R using the PKNCA package (version 10.2). We report preliminary endpoint results for the proportion of participants with plasma HIV-1-RNA <50 copies/mL at week 24). Results: We enrolled 122 participants: 80 in the BIC and 42 in the DTG arm. Overall, 43 (35%) were female, with median (IQR) baseline viral load (copies/ mL) and CD4+ (cells/μL) of 75649 (22784-391299) and 172 (108-352) (BIC arm) and 73735 (21242-544830) and 139 (97-237) (DTG arm). Geometric mean (CV%) trough concentrations for twice daily BIC during TB treatment (75 PK-profiles) and once daily BIC after TB treatment (22 PK-profiles) were 0.397 (73.4%) mg/L and 2.29 (45.1%) mg/L. Serious adverse events were common in this population with advanced HIV and TB, but none of the 15 were related to study treatment. Median CD4+ (cells/ μL) at week 24 was 257 (197-485) (BIC arm) and 231 (170 311) (DTG arm). HIV-1-RNA at week 24 was <50 copies/mL in 71/73 (97%) and 36/37 (97%) of participants in the BIC and DTG arms, respectively, in the per- protocol analysis (Figure 1), [71/75 (95%) in BIC arm (two early withdrawals) and 36/38 (95%) in DTG arm (one death) in FDA snapshot analysis] Conclusion: Data from INSIGHT suggest that twice daily bictegravir/ emtricitabine/tenofovir-alafenamide is effective in PWH with TB taking rifampicin-based treatment. Safety, PK, and virologic response data support the use of this regimen in PWH and TB.

vaccines were experienced by 33%, 45% and 36% of 2-CpG, 3-CpG and 3- alum participants, respectively, mostly Gr 1 and 2. Vaccination site pain, fatigue, headache, malaise and myalgia were most frequent. Conclusion: In this study of PWH with prior vaccine non-response, both 2 and 3 doses of HepB-CpG achieved superior SPR compared to 3 doses of HepB-alum. No unexpected safety issues were observed. Efficacy, Safety, and Immunogenicity of H56:IC31 Vaccine for Prevention of Recurrent TB Alvaro Borges 1 , Marisa Russel 2 , Dereck Tait 2 , Elana van Brakel 2 , Andrea Cabibbe 3 , Daniela Cirillo 3 , Elisa Nemes 4 , Thomas Scriba 4 , Gavin Churchyard 5 , Rodney Dawson 6 , Isa Sabi 7 , Andreas H. Diacon 8 , Rasmus Mortensen 1 , Mark Hatherill 4 , for POR TB consortium 1 Statens Serum Institut, Copenhagen, Denmark, 2 International AIDS Vaccine Initiative, Cape Town, South Africa, 3 IRCCS Ospedale San Raffaele, Milano, Italy, 4 South African Tuberculosis Vaccine Initiative, Cape Town, South Africa, 5 The Aurum Institute, Johannesburg, South Africa, 6 University of Cape Town, Cape Town, South Africa, 7 Mbeya Medical Research Center, Mbeya, United Republic of Tanzania, 8 TASK Applied Science, Cape Town, South Africa Background: Persons with tuberculosis (TB) who are deemed cured on completion of treatment remain at higher risk of recurrent disease. The TB vaccine candidate H56:IC31 has been shown to be safe and immunogenic in phase 1/2 studies, including in treated TB patients. Whether H56:IC31 can reduce the risk of recurrent TB is unknown. Methods: In a multicenter, double-blind, randomized, placebo-controlled, event-driven trial in South Africa and Tanzania, we enrolled participants aged 18-60 years, without HIV, who were sputum smear-negative upon completion of treatment for drug-sensitive pulmonary TB. Participants were randomly assigned (1:1) to receive two doses of H56:IC31 or placebo (56 days apart) and followed up for 1 year. The primary endpoint was recurrence of culture confirmed pulmonary TB. Vaccine efficacy (VE) estimates with 95% confidence interval (95%CI) were derived from Cox proportional hazard models. Secondary endpoints included TB relapse or reinfection as differentiated by whole genome sequencing of paired sputum samples, safety, and immunogenicity. Results: 831 participants (mean age 34.7 years; 27.6% female; 66.1% black African; 76% from South Africa) were enrolled; 415 received H56:IC31 and 416 placebo. In the primary analysis, recurrent TB was observed in 23 (12 relapse; 8 reinfection; 3 indeterminate) of 400 participants (5.8%) in the H56:IC31 group; and 14 (6 relapse; 7 reinfection; 1 indeterminate) of 406 participants (3.4%) in the placebo group. VE for recurrence was -73.8% (95%CI:-246.9 to 9.8%; P=0.10). VE for relapse was -116.1% (-522.2 to 16.3%; P=0.11) and for reinfection VE was -21.1% (-245.3 to 56.5%; P=0.71). Participants in the H56:IC31 group reported more mild- to-moderate local injection reactions than in the placebo group. No H56:IC31-related serious adverse events were observed. Participants receiving H56:IC31 mounted robust H56-specific CD4+ T cell responses and H56- specific humoral (serum IgG) responses. Conclusion: This is the first reported trial with a prevention of recurrent TB design. Vaccination with H56:IC31 upon treatment completion for pulmonary tuberculosis did not reduce the risk of recurrent tuberculosis. H56:IC31 was well-tolerated and immunogenic, but may have increased the risk of relapse by endogenous strains.

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Oral Abstracts

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CROI 2024