CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

650

Bictegravir as Universal Initial Antiretroviral Therapy: A National Target Trial Emulation Study Isaac Núñez 1 , Yanink Caro-Vega 1 , Conor MacDonald 2 , Juan L. Mosqueda 3 , Alicia Piñeirúa-Menéndez 4 , Anthony Matthews 2 1 Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico, 2 Karolinska Institute, Stockholm, Sweden, 3 Hospital Regional de Alta Especialidad del Bajío, Mexico City, Mexico, 4 Consorcio de Investigación sobre VIH SIDA TB, Mexico City, Mexico Background: Bictegravir (BIC) has been shown to be non-inferior to dolutegravir (DTG) as initial antiretroviral therapy (ART) in non-inferiority randomized controlled trials (RCTs). Mexico established in 2019 a national policy to start ART with BIC to every ART naïve person with HIV (PWH). However, BIC has not been compared to efavirenz (EFV) or raltegravir (RAL) (commonly prescribed in Mexico) and no superiority trials have been performed. Methods: We used data from the national antiretroviral surveillance system in Mexico to perform three target trial (TT) emulations for initial ART among PWH starting ART from 2019 onwards: BIC vs DTG, BIC vs EFV, and BIC vs RAL. Our approach consists of specifying the protocol of an index TT (the RCT we would ideally conduct) and emulate it with observational data while adjusting for confounding to approach randomization. Baseline was the date of ART start. People with missing viral load (VL), VL <500 copies/mm 3 , and/or missing CD4 count within the last year before ART start, those started on double-dose DTG and/or reduced-dose emtricitabine, lamivudine or tenofovir disoproxil fumarate were excluded. We performed individual logistic regressions while adjusting for treatment-outcome confounders (baseline VL and CD4, age, gender, imprisonment status, state of residence, year of ART start) to estimate risk of undetectable VL (UVL) (<50 copies/mm 3 ) for each person at 3 and 12 months. We performed intention-to-treat analyses. We calculated the mean risk of UVL for each group, risk ratios (RR) and 95% percentile-based confidence intervals using 500 bootstrap resamples. Results: 26178 PWH were included: 18894 started BIC, 2530 DTG, 562 RAL, and 4192 EFV. Most PWH were cis men (85%), median age was 31 years. 57% had a baseline viral load <100k copies, and median CD4 cell count was of 213. Only 1% of PWH were in a prison. At three months, the risk of UVL was of 79.2% vs 78.4% (BIC vs DTG, RR 1.01 [0.98-1.03]), 79.7% vs 71% (BIC vs RAL, RR 1.12 [1.03-1.22]), and 79.7% vs 63.6% (BIC vs EFV, RR 1.25 [1.21-1.3]). At twelve months, the risk of UVL was of 85.9% vs 83.6% (BIC vs DTG, RR 1.02 [0.98-1.08]), 85.9% vs 79% (BIC vs RAL, RR 1.08 [1-1.23]), and 86.6% vs 83% (BIC vs EFV, RR 1.04 [1.01-1.08]). Conclusion: BIC is superior to RAL and EFV, but not DTG, as initial ART in treatment naïve PWH for reaching UVL at 3 and 12 months. These results support existing RCTs and argue in favor of this type of country-wide strategy. HIV Detectable Low-Level Viremia Suggests a Revised Threshold for Viral Suppression in Cameroon Alex Durand NKA 1 , Joseph Fokam 1 , Collins Ambe Chenwi 1 , Efakaki Gabisa Jeremiah 1 , Yagai Bouba 1 , Serge Clotaire Billong 2 , Anne-Cecile Z-K Bissek 3 , Hamsatou Hadja 3 , Carlo Federico Perno 4 , Samuel Martin Sosso 1 , Alexis Ndjolo 1 1 Centre International de Référence Chantal Biya, Yaoundé, Cameroon, 2 University of Yaoundé, Yaoundé, Cameroon, 3 Ministère de la Santé Publique du Cameroun, Yaoundé, Cameroon, 4 Bambino Gesu Children's Hospital, Rome, Italy Background: Transitioning to dolutegravir-based therapy in Cameroon has improved viral suppression (VS) rates, known as low-level viremia (LLV) <1000copies/ml. However, there is a growing number of patients experiencing VS with detectable LLV, indicating risk of virological failure. This study aimed to characterize the distribution of LLV and associated factors in the Cameroonian context. Methods: A laboratory-based study was conducted among treatment experienced patients monitored for HIV plasma viral load (PVL) from January 2020 through April 2022 at the Chantal BIYA International Reference Centre (CIRCB), Yaoundé-Cameroon. PVL was measured using the Abbott m2000RT PCR. Among patients with LLV, levels of PVL were stratified into 4 cut-points: <50, 50-200, 201-500, and 501-999 copies/ml, with p<0.05 considered statistically significant. Results: Overall, 14970 patients were enrolled: 72.5% were female; 14219 adults, 466 adolescents, 285 children. By ART-regimens, 3411 were on NNRTI-based, 505 on PI/r-based and 11054 on DTG-based ART. Median [IQR] duration on ART was 36[27-39] months. Overall VS (<1000 copies/ml) rate was 88.8% (13291/14970) (95% CI: 88.2-89.3), and stratification in this population showed 1.5% (207/13291) with 501-999 copies/ml, 3.3% (445/13291) with 200-500 copies/ml, 10.8% (1439/13291) had 50-200 copies/ml, and 84.2%

2% were retained in care with missing VL data, and 3% had disenrolled. Only 3 participants discontinued TLD. In a multivariable logistic regression model, those with age <40 years and detectable viremia at the time of TLD transition were less likely to be virally suppressed and in care at 48 weeks (Table). Furthermore, only two-thirds of those with detectable viremia at the time of transition to TLD were virally suppressed after 48 weeks. Conclusion: In the South African public sector, TLD was well tolerated with a <1% discontinuation rate. However, using an observational cohort approach with intensive outcome monitoring, only 81% of participants were virally suppressed and in care at 48 weeks. Over half of those who did not achieve the primary endpoint were lost from care or deceased. While high rates of viral suppression among those in care support widespread programmatic transition to TLD, further efforts are needed to optimize adherence and retention in care to attain programmatic goals of >95% viral suppression among those on ART.

Poster Abstracts

649

Uptake of Rapid and Early ART Initiation in Latin America and the Caribbean and Associated Factors Yanink Caro-Vega 1 , Anna K. Person 2 , Bryan E. Shepherd 2 , Rodrigo Ville 1 , Serena Koenig 3 , Carina Cesar 4 , Claudia P. Cortes 5 , Beatriz Grinsztejn 6 , Eduardo Gotuzzo 7 , Brenda E Crabtree-Ramírez 1 1 Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico, 2 Vanderbilt University, Nashville, TN, USA, 3 Harvard Medical School, Boston, MA, USA, 4 Fundación Huésped, Buenos Aires, Argentina, 5 University of Chile, Santiago, Chile, 6 Oswaldo Cruz Foundation - Fiocruz, Rio de Janeiro, Brazil, 7 Universidad Peruana Cayetano Heredia, Lima, Peru Background: In 2015, the WHO recommended initiation of ART in all persons with HIV (PWH) regardless of CD4 count. Same-day ART has proven to be feasible and effective in low- and middle-income countries and has become a standard of care in Haiti for those without TB symptoms since 2017. Nevertheless, implementation of starting ART rapidly represents a challenge in diverse settings. Thus, we evaluated the proportion of PWH with rapid and early ART initiation, associated factors and survival in our region. Methods: We included PWH ≥18 years of age, diagnosed between 2017 and 2021, and presenting for care in CCASAnet sites. We estimated the proportion of those who initiated rapid ART (≤7days; R-ART) and early ART (≤14days; E-ART) after HIV diagnosis overall and within each site. We analyzed factors associated with E-ART (age, sex at birth, education level, mode of HIV acquisition, site, calendar year, CD4 cell count) with a logistic regression (excluding Haiti where R-ART is standard of care) and the association of E-ART with overall survival with adjusted Cox models. Results: A total of 9173 PWH were included; 8507(92.7%) initiated ART, and of those 3146(37%) initiated R-ART and 4237(49%) E-ART. Overall, most of E-ART and R-ART starters were from Haiti: 2759(88%) and 3532(83%), respectively. Among those included on each site, the proportion of E-ART were: Argentina 3%, Chile 5.4%, Peru 6.8%, Mexico 25%, Brazil 34%, Honduras 44%, and Haiti 79%. Excluding Haiti, more recent year was associated with a higher probability (aOR[95%CI]) of E-ART (1.24[1.93-2.12]) in 2018 and (2.47 [2.25-2.62]) in 2021 vs 2017. Additionally, being female (1.71[1.55-1.89]), other mode of acquisition vs heterosexual mode (1.67[1.19-2.35]), upper secondary vs primary school (1.16[1.05-1.28]), and age at diagnosis (0.93[0.90-0.96]) per each 10 additional years) were associated with E-ART. Overall, E-ART was not associated with higher survival (aHR: 0.93[95%CI:0.87-1.00], p=0.052 including Haiti; aHR: 0.90(95%CI:0.77-1.05), p=0.19 excluding Haiti). Conclusion: Despite of the recommendation of ART initiation as soon as possible, Haiti is the only site in CCASAnet to initiate ART early after diagnosis of HIV in most patients. Women, younger and more educated people were more likely to initiate E-ART. Heterogeneity between health systems, policies and differential characteristics of participant sites including linkage to care strategies may contribute to these results . More research to explain these findings, is needed.

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CROI 2024 185