CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

6.04[3.4-10.6]. With GS-9620 and SAHA singly, 5[63%] and 4[50%] participants exhibited reactivation, respectively. With dual stimulation, reactivation was detected in 5 participants. Median msRUPM fold change to DMSO was 1.5[0.97 2.34] for PPI, 1.53[0.78-1.93] for GS-9620, 0.76[0-1.52] for SAHA, and 1.22[0.76 1.56] for GS-9620 plus SAHA. One participant, durably suppressed since infancy, had no reactivation, and one participant displayed inhibition of ms-transcripts under all conditions. PPI stimulation was associated with upregulation of CD69, CD25, and HLA-DR whereas only CD69 was upregulated in SAHA conditions. Secreted IL-6 was higher after GS-9620 stimulation compared to DMSO. Histone acetylation effects were seen in 5 participants after SAHA treatment. Conclusion: These findings suggest that pediatric reservoirs can be reactivated with innate immune enhancers, such as TLR7 agonist and HDACi, with implications for use as therapeutics to purge HIV-1 reservoirs. Predictive Markers for Sustained Viral Suppression on Dual bNAbs During ART Interruption in Children Jaspreet Banga 1 , Bryan S. Nelson 2 , Gbolahan Ajibola 3 , Terence Mohammed 3 , Nyaladzi Maphorisa 3 , Oganne Batlang 3 , Maureen Sakoi-Mosetlhi 3 , Molly Pretorius Holme 2 , Kathleen M. Powis 4 , Shahin Lockman 5 , Michael D. Hughes 2 , Joseph M. Makhema 3 , Daniel R. Kuritzkes 5 , Mathias Lichterfeld 6 , Roger Shapiro 2 1 Beth Israel Deaconess Medical Center, Boston, MA, USA, 2 Harvard TH Chan School of Public Health, Boston, MA, USA, 3 Botswana Harvard AIDS Institute Partnership, Gabarone, Botswana, 4 Massachusetts General Hospital, Boston, MA, USA, 5 Brigham and Women's Hospital, Boston, MA, USA, 6 Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA Background: Phenotyping to identify susceptibility to broadly neutralizing antibodies (bNAbs) is costly and logistically challenging, and simple clinical markers to predict bNAb treatment success for children are needed. The combination of a negative qualitative HIV DNA and negative enzyme immunosorbent assay (EIA) at study entry was previously reported to correlate with success in the Tatelo Study in Botswana. We now report findings for additional biomarker combinations, at entry to and during the bNAb-only step of the study. Methods: Twenty-five children received up to 24 weeks of bNAb-only treatment (VRC01LS+10-1074) following ART interruption. HIV qualitative DNA and HIV RNA were performed every 1-2 weeks and EIA every 4-8 weeks. Using Fisher's exact test we compared the proportion of infants who remained virally suppressed to < 400 copies/mL (successes) to those with detectable virus by assay type. Results: During the bNAb-only step of Tatelo there were a median of 8 qualitative HIV DNA measurements, 12 HIV-1 RNA "target detection" measurements, and 4 EIA measurements per participant available for analysis. At bNAb-only step entry, 13/25 (52%) had negative qualitative DNA and 17/25 (68%) had negative EIA, and 10/25 (40%) were negative for both. Nine of the 13 (69%) with negative qualitative DNA succeeded compared with 2/12 (17%) with positive or indeterminate qualitative DNA (p=0.02). Nine of the 17 (53%) with negative EIA succeeded compared with 2/8 (25%) with positive EIA (p=0.23). Combining biomarkers, 8/10 (80%) who were negative/negative at bNAb-only entry succeeded, compared with 3/15 (20%) with any other pattern (p=0.005); all 8 successes (and no failures) were also negative/negative at study entry (the bNAb+ART overlap step), as previously reported. HIV-1 RNA "target detection" was below the assay limit in all but one participant at the start of the bNAb only step. In the visit immediately prior to any viral rebound, target detection occurred in only 1/14 (7%) participants (Figure 1). No marker or combination of markers reliably changed in the 3 visits prior to rebound. Conclusion: Negative qualitative DNA, and especially negative/negative DNA and EIA, at start of bNAb-only treatment predicted maintenance of viral suppression among children on dual bNAbs. HIV-1 RNA target detection below the assay limit did not prove to be a predictive biomarker, and no biomarker combination was clinically useful in the visits preceding failure.

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High Proportion of False-Positive HIV Results With Point-of-Care Birth Testing in Botswana Gbolahan Ajibola 1 , Nyaladzi Maphorisa 1 , Aischa Niesar 2 , Terence Mohammed 1 , Maureen Sakoi-Mosetlhi 1 , Oganne Batlang 1 , Sikhulile Moyo 1 , Molly Pretorius Holme 3 , Kathleen M. Powis 4 , Shahin Lockman 2 , Joseph M. Makhema 1 , Mathias Lichterfeld 5 , Roger Shapiro 3 1 Botswana Harvard AIDS Institute Partnership, Gabarone, Botswana, 2 Brigham and Women's Hospital, Boston, MA, USA, 3 Harvard TH Chan School of Public Health, Boston, MA, USA, 4 Massachusetts General Hospital, Boston, MA, USA, 5 Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA Background: As countries in Sub-Saharan Africa move toward rollout of point of-care testing (POCT), risk for false positive testing and pathways to make accurate HIV diagnoses need to be understood. Methods: The Moso Study identified newborns at high risk of HIV acquisition at 35 delivery facilities in Botswana. High-risk status was defined primarily (but not exclusively) as limited maternal ART duration in pregnancy. HIV testing was performed using the Cepheid Xpert® HIV-1 qualitative POCT platform, with Roche CAP/CTM HIV-1 qualitative confirmation for those testing positive. Further testing with HIV-1 RNA quantification and droplet digital polymerase chain reaction (ddPCR) was conducted for discordant results. Subsequent 6-week HIV test results for infants with negative birth POCT were abstracted from national electronic laboratory/medical records. Results: From July 2022–August 2023, using 6 Xpert® machines housed in close proximity to the 35 delivery sites, 1479 high-risk newborns were tested for HIV with POCT at a median of 21 hours of life (range 0, 158 hours). Thirty-one newborns (2%) had initial positive results, but only 11 (39%) were confirmed positive by Roche CAP/CTM testing, for an overall vertical transmission rate of 0.7% in high-risk neonates. The 20 (1.4%) false positives were further evaluated by HIV-1 RNA testing (all undetectable < 40 copies/mL); ddPCR testing was performed on 18 (90%) false positive samples with no target detected in any. Follow-up testing of false positives to date has remained negative. Of the 20 initial false positive samples, 18 (90%) were tested on just 1 of the 6 Xpert® machines; this machine was removed from service and is under evaluation, without an identifiable cause for the false positive results (operator error deemed unlikely). Excluding all 453 samples tested on this machine yields a false positivity rate of 0.2% (2/1026), or 15% (2/13) of all positive results. The median cycle threshold (CT) value for false positive results on the Xpert® platform was 39.2 (range 34.5, 43.9) compared with a median of 32.9 (range 24.2, 41.0) for true positives, indicating some overlap between groups (Figure 1). Conclusion: The Xpert® POCT platform offers affordable and easily implementable birth testing for HIV, but false positive testing may occur. High CT values provide an initial indication of a possible false positive result, but all positive testing must be confirmed by either HIV-1 RNA testing, HIV-1 DNA testing, or both.

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Poster Abstracts

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