CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

620

No Impact on the CNS After Switching to Dolutegravir/Lamivudine From a 3-Drug Regimen Linn Renborg 1 , Aylin Yilmaz 2 , Kristina Nyström 1 , Staffan Nilsson 1 , Henrik Zetterberg 1 , Magnus Gisslén 1 1 Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden, 2 University of Gothenburg, Gothenburg, Sweden Background: Dual-drug therapy with dolutegravir/lamivudine (DTG/3TC) is effective in achieving viral suppression in the blood, but its impact on HIV infection in the central nervous system (CNS) remains insufficiently explored. In this study, we aimed to investigate its effect in the CNS through assessment of cerebrospinal fluid (CSF) in individuals switching to DTG/3TC from a three-drug regimen. Methods: The Gothenburg HIV CSF Study Cohort comprises a longitudinal study investigating HIV infection in the CNS. From this cohort, we retrospectively included all adult individuals who were on suppressive antiretroviral therapy and who switched to DTG/3TC and who also had undergone lumbar punctures up to one year before and up to two years after. CSF NfL levels were measured by ELISA, HIV RNA quantitative PCR was performed using Cobas 6800. ß2-microglobulin was measured using nephelometry, IgG using immunoturbidimetry. Other analyses were performed using standard laboratory methods. Results: Lumbar punctures were performed in 20 of the 119 individuals with HIV who switched to DTG/3TC between 2017 and 2023. All were virally suppressed (< 50 HIV RNA copies/mL) in blood and CSF at the time of switch. Fifteen were on a regimen containing an integrase inhibitor at baseline. Seven participants were female. Median age at switch was 55 years. All participants remained suppressed in blood throughout the follow-up period, mean 384 days, while one patient had an asymptomatic minor increase of CSF HIV RNA to 70 copies/ml without elevation of CSF white blood cell count or NfL. When age adjusted to 50 years, mean CSF NfL levels were 528 ug/ml at baseline and 520 ug/ml at follow-up. The small difference was not significant. Neither were any significant differences observed in albumin ratio, IgG index, CSF ß2 microglobulin, CSF white blood cell count, between baseline and follow-up. Conclusions: In this study, we observed no evidence of neuronal injury, as measured by NfL, or any other marker of CNS injury or inflammation following the switch to DTG/3TC. The results will be further explored by investigating additional injury and inflammatory biomarkers in CSF, as well as NfL and other CNS injury markers in plasma, in the entire cohort who switched to DTG/3TC. Greater Cognitive Decline in Cognitively Unimpaired Older Thai PWH at Baseline Akarin Hiransuthikul 1 , Tanakorn Apornpong 2 , Stephen Kerr 1 , Chuleeporn Wongvoranet 2 , Win Min Han 3 , Hay Mar Su Lwin 2 , Napon Hiranburana 2 , Sasiwimol Ubolyam 4 , Anchalee Avihingsanon 5 , for the HIV-NAT 006 and 207 Study Teams 1 Chulalongkorn University, Bangkok, Thailand, 2 HIV Netherlands Australia Thailand Research Collaboration, Bangkok, Thailand, 3 Kirby Institute, Sydney, Australia, 4 Thai Red Cross AIDS Research Centre, Bangkok, Thailand, 5 HIV-NAT, Thai Red Cross AIDS and Infectious Disease Research Centre, Bangkok, Thailand Background: Cognitive impairment remains a crucial health issue among people with HIV (PWH). However, the course of cognitive impairment has shifted considerably since the introduction of combined antiretroviral therapy. We aimed to determine the differences in cognitive decline between PWH WITHDRAWN

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Cognitive and Sensorimotor Difficulties in Well-Controlled People With HIV Living in Uganda Leah H. Rubin 1 , Kathleen Ridgeway 2 , Rebecca E. Easter 2 , Raha M. Dastgheyb 3 , Jonathan H. Ye 2 , Eran F. Shorer 2 , Aggrey Anok 4 , Stephen Tomusange 4 , Julie Mannarino 5 , Deanna Saylor 3 , Noeline Nakasujja 6 , Gertrude Nakigozi 4 , Robert Paul 5 1 The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 2 The Johns Hopkins University, Baltimore, MD, USA, 3 The Johns Hopkins University School of Medicine, Baltimore, MD, USA, 4 Rakai Health Sciences Program, Kalisizo, Uganda, 5 University of Missouri St Louis, St Louis, MO, USA, 6 Makerere University College of Health Sciences, Kampala, Uganda Background: Individual differences in early life experiences (e.g., trauma), behaviors (e.g., substance use), the immune response of the body-brain, and HIV treatment contribute to a range of brain health complications (BHCs) in people with HIV (PWH). In sub-Saharan Africa, particularly in Rakai, Uganda, these individual factors are often less pronounced; substance use is low, and ART initiation and types are similar among this typically virally suppressed, middle-aged population. We aimed to investigate BHCs in virally suppressed, middle-aged PWH compared to people without HIV (PWoH) in Rakai, Uganda. Methods: Participants enrolled through the Rakai Community Cohort Study (338 PWH with HIV RNA <200cp/ml, 249 PWoH) were administered a Research Domain Criteria (RDoC) battery focused on cognitive, sensorimotor, and social processing systems that included: Auditory Verbal Learning Test [AVLT], Symbol Digit, Color Trails, Grooved Pegboard (GPEG), Flanker, affective Go/No-Go, Figure-8, and Facial Emotion Perception Task. Timed outcomes were log transformed and reverse scored, so higher scores reflect better performance. Demographically-adjusted norms were computed (using PWoH) for all outcomes. Multivariable logistic regressions were used to examine serostatus differences in impairment (>1 standard deviation) in RDoC outcomes. Benjamini-Hochberg Procedure was used to control the false discovery rate (FDR). Analyses controlled for sensory smptoms (tingling, burning, numbness in hands or feet) and childhood sexual abuse (Childhood Trauma Questionnaire subscale) as they differed by serostatus and related to outcomes. No other confounders were identified. Results: Participants had minimal self-reported medical comorbidities and PWH were similar to PWoH in age (43.9[20-65] vs. 43.5[28-68]yrs), sex (male, 54 vs. 46%), and education (6.1 vs. 5.8yrs). Compared to PWoH, PWH reported more sensory symptoms (29 vs. 21%, P =0.03) and greater experience of any childhood sexual abuse (27 vs. 15%, P =0.002). In adjusted analyses, PWH were more likely to be impaired than PWoH on Color Trails, Symbol Digit, GPEG, Figure-8, and AVLT recognition ( Figure 1 ). Notably, there were no differences on AVLT learning and memory. Conclusions: Cognitive and sensorimotor difficulties are significant concerns in PWH living in Rakai, Uganda with minimal confounding conditions common in Western cohorts. These difficulties merit clinical attention and further investigation to determine mechanisms and treatment options.

Poster Abstracts

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