CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

time polymerase chain reaction (PCR) at antiretroviral therapy (ART) initiation, and after 12 and 84 weeks post-initiation in a case-cohort design. Associations between CMV viraemia and mortality were evaluated using multivariable models, adjusting for HIV viral load, CD4 percentage and inflammatory biomarkers. Results: CMV viraemia was associated with mortality, but the relationship differed by country and assay type. In Zimbabwe, where a more sensitive assay led to a high prevalence of detectable CMV (73%), each log rise in CMV viral load was associated with 2-fold higher mortality (adjusted hazard ratio (aHR) 2.35; 95% confidence interval (CI) 1.34, 4.12). In Uganda, where the assay sensitivity was lower, children with detectable CMV viraemia (26%) had almost 3-fold higher mortality than children without detectable CMV (aHR 2.86; 95%CI 1.02, 8.33). Conclusion: CMV viraemia at the time of ART initiation is associated with mortality in children with HIV in sub-Saharan Africa, independent of HIV viral load, immunosuppression and immune activation. Future studies should evaluate whether suppressing CMV viraemia reduces mortality in children with HIV. Sex Differences in Growth Trajectories Between Early-Treated Infants With HIV and Controls Ana Barrios-Tascon 1 , Renate Strehlau 2 , Faeezah Patel 2 , Megan Burke 2 , Stephanie Shiau 3 , Yanhan Shen 1 , Stephen M. Arpadi 1 , Elaine J. Abrams 1 , Caroline T. Tiemessen 2 , Louise Kuhn 1 , for the LEOPARD Study Team 1 Columbia University, New York, NY, USA, 2 University of the Witwatersrand, Johannesburg, South Africa, 3 Rutgers University, Piscataway, NJ, USA Background: Perinatally-acquired HIV infection is associated with increased risk of postnatal growth deficits which are only partially corrected with antiretroviral therapy (ART). Studies of sex differences in immune recovery and virologic response to ART among infants with perinatally acquired HIV (IHIV) have reported conflicting results. Here we investigate the role of sex in modifying the growth trajectories of IHIV who started ART at an early age. Methods: As part of an early ART trial conducted in Johannesburg, South Africa (2015-2018), 116 IVHIV diagnosed within 48 hours of birth initiated ART as early as possible, consisting of nevirapine (switched to lopinavir-ritonavir >= 42 weeks postmenstrual age) lamivudine, and zidovudine (switched to abacavir at 3 months). Eighty infants born to mothers living with HIV but found to be uninfected (IHEU) were enrolled as controls, receiving daily nevirapine for 6 weeks, and twice-daily zidovudine added if high risk. Both groups were followed prospectively through 48 weeks and anthropometric parameters collected. Age and sex adjusted Z-scores for weight (WAZ) and length (LAZ) were compared between IHIV and IHEU, as well as stratified by sex. Generalized linear models were used to describe growth trajectories and main and interactive effects. Results: Just under half the infants were male (48.5%), similar proportions in IHIV and IHEU. The deficits in growth through 48 weeks associated with HIV status were most marked in female infants (Figure). Mean WAZ (β= -0.51 [standard error,0.22], p=0.02) and LAZ (β= -0.50 [0.21], p=0.02) were lower in female IHIV than in female IHEU overall (Figure). In contrast, trajectories of WAZ (β= -0.21 [0.30], p=0.48) and LAZ (β= 0.03 [0.32], p=0.92) between male IHIV and male IHEU were similar. Combining the two groups, males had lower WAZ than females over the 48 week period. Males also had lower LAZ than females, with significant differences at 12 and 24 weeks (-1.84 [0.22] vs -1.34[0.12], p=0.04 and -1.53 [0.19] vs -1.01 [0.12], p=0.02). The mean WAZ and LAZ in neither group attained WHO standards by 48 weeks. Conclusion: Deficits in WAZ and LAZ in IHIV with early ART compared to IHEU were greater in girls. This pattern was observed despite boys having consistently lower anthropometric parameters than girls in both groups. Factors responsible for this sex difference are not clear, but early ART initiation and/or perinatal infection appears have a differential impact on growth according to sex.

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1 in 5 Sub-Saharan Infants Switches From Undetectable to Detectable HIV Viral Load During Follow-Up Sheila Fernández-Luis 1 , Sara Dominguez-Rodriguez 1 , Louise Kuhn 2 , Mark F. Cotton 3 , Carlo Giaquinto 4 , Paolo Rossi 5 , Anita Janse van Rensburg 3 , Avy Violari 6 , Maria Grazia Lain 7 , Elisa López-Varela 8 , Mariam Sylla 9 , Pauline Amugue 10 , Pablo Rojo 1 , Alfredo Tagarro 1 , for epiical 1 Hospital Universitario 12 de Octubre, Madrid, Spain, 2 University of California Irvine, Irvine, CA, USA, 3 Stellenbosch University, Cape Town, South Africa, 4 University of Padova, Padova, Italy, 5 Bambino Gesu Children's Hospital, Rome, Italy, 6 University of the Witwatersrand, Johannesburg, South Africa, 7 Fundação Ariel Glaser Contra o SIDA Pediátrico, Maputo, Mozambique, 8 Barcelona Institute for Global Health, Barcelona, Spain, 9 Hôpital Gabriel Touré, Bamako, Mali, 10 Baylor College of Medicine, Houston, TX, USA Background: The initiation of antiretroviral therapy (ART) early in HIV infection results in a rapid decline in viral load (VL) and a small HIV reservoir. However, children treated early face long-term challenges to maintaining viral suppression. We studied the longer-term VL dynamics of a cohort of early treated children. Methods: From May 2018 to May 2021, we enrolled infants initiating ART within 6 months of birth and within 3 months of diagnosis in six sites from 3 African countries. We represented VL status transitions with Sankey plot. Results: Of 215 infants enrolled, the median age at HIV diagnosis was 31 days [0; 48]. The median age at ART initiation was 34 days [26;73]. The most common starting ART regimen was Lamivudine + Abacavir + Lopinavir/ritonavir in 140/215 (65%), 10% switched to DTG in 2021. Median VL at ART initiation was 4.9 log 10 copies/mL [3.6;5.8]. Median follow-up duration at analysis was 34.0 months [IQR, 16.3;44.1]. Twenty-five children (11.6%) died, 51/215 (23.7%) completed 4 years of follow-up, 76/215 (35.3%) remained in care and 63/215 (29.3%) were lost to follow-up. A total of 58.0% and 51.1% of children had detectable VL at 1 year and 2 years year of follow-up, respectively. Ninety-eight of 193 infants (50.7%) achieved virologic suppression at some point during the study. Among these, the median time to suppression (ART initiation to two consecutives undetectable VLs) was 5.5 months [IQR, 2.1-15.6]. Over time, the proportion of children with undetectable VLs increased, but a median of 19.1% switched from undetectable to undetectable VLs during follow-up visits. Notably, most patients who died or were lost to follow-up had detectable VLs in previous visits. Conclusion: Undetectable VL increased across time, but oscillations between undetectable and detectable VL in the long term were frequent. This underscores the need for further investigations to assess the potential clinical implications of these fluctuations on patient outcomes and the size of the viral reservoir.

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Poster Abstracts

CROI 2024 306