bluuebunny/crossref_metadata_2025_split huggingface dataset:
1603. Efficacy, safety and tolerability of switching to dolutegravir/lamivudine in virologically suppressed adults living with HIV on bictegravir/emtricitabine/tenofovir alafenamide -the DYAD study
Authors: Rolle Charlotte-Paige M , Castano Jamie , Nguyen Vu , Hinestrosa Federico , DeJesus Edwin 
Published: November 2023

Abstract

Background
In TANGO, switching to dolutegravir/lamivudine (DTG/3TC) was noninferior compared to continuing a tenofovir alafenamide (TAF)-based regimen, however switching from bictegravir (BIC)/emtricitabine (F)/TAF was not evaluated. Here, we present efficacy and safety of switching to DTG/3TC compared with continuing B/F/TAF in virologically suppressed adults through 24 weeks.

Methods
DYAD (NCT04585737) is an ongoing, open-label clinical trial that randomized adults with HIV-1 RNA&lt; 50 copies/mL and no prior virologic failure (2:1) to switch to once-daily fixed-dose DTG/3TC or remain on B/F/TAF. The primary endpoint is the proportion with HIV-1 RNA ≥ 50 c/mL at Week (W) 48 (FDA snapshot algorithm, ITT-E population). A planned W24 interim analysis assessed noninferiority with a 6% margin.

Results
Overall, 222 adults (16% women; 51% aged ≥50 years; 28% Black) were randomized. At W24, 3 (2%) participants on DTG/3TC and 3 (4%) on B/F/TAF had HIV-1 RNA ≥ 50 c/mL (adjusted treatment difference -2.1%, 95% confidence interval [-9.5%, 2.5%]) meeting noninferiority criteria. Through W24, 4 on DTG/3TC and 3 on B/F/TAF met confirmed virologic withdrawal (CVW) criteria and underwent resistance testing. 2/7 had treatment-emergent resistance. One B/F/TAF CVW developed M184M/I and G140G/S at W12; at study discontinuation (DC), HIV-1 RNA&lt; 50 c/mL and the participant remained on B/F/TAF. One DTG/3TC CVW had no resistance on study genotype but underwent repeat genotypic testing outside the study (ordered by clinic provider) and had M184V at W12; at study DC, HIV-1 RNA&lt; 50 c/mL on DTG/3TC and the participant was subsequently transitioned to DTG + darunavir/cobicistat (DRV/c). One non-CVW DTG/3TC participant developed M184V and K65R at W12 (genotype inadvertently collected at first episode of unconfirmed viremia); at study DC, HIV-1 RNA&lt; 50 c/mL on DTG/3TC and the participant was subsequently transitioned to DTG+DRV/c. Drug-related adverse events (AEs) and withdrawals due to AEs occurred in 31 (21%) and 6 (4%) participants with DTG/3TC and 1 (1%) and 0 participants with B/F/TAF, respectively.

Conclusion
DYAD demonstrated noninferior efficacy of switching to DTG/3TC vs. continuing B/F/TAF at W24. Higher AE rates in the DTG/3TC arm are likely consistent with the open-label nature of this switch study.

Disclosures
Charlotte-Paige M. Rolle, MD, MPH, Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Gilead: Honoraria|Janssen: Advisor/Consultant|ViiV: Advisor/Consultant|ViiV: Grant/Research Support|ViiV: Honoraria Federico Hinestrosa, MD, AbbVie: Honoraria|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Honoraria|MSD: Honoraria|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Honoraria Edwin DeJesus, MD, Gilead Sciences, Inc: Advisor/Consultant|Theratechnology: Advisor/Consultant|Theratechnology: Honoraria
1606. Dual Trajectories of Antiretroviral Therapy Adherence and Polypharmacy in Women with HIV in the United Sate
Authors: SAEED A B U B A K E R , Ghebremichael Musie , Konkle-Parker Deborah , Weiss Deborah Jones , Collins Shelby , Adimora Adaora A , Schneider Michael F , Cohen Mardge H , Tamraz Bani , Plankey Michael , Wilson Tracey , adedimeji Adebola , Haberer Jessica , Jacobson Denise L Jacobson 
Published: November 2023

Abstract

Background
Polypharmacy using five or more medications with antiretroviral therapy (ART) may increase the risk of nonadherence to prescribed treatment. We aimed to identify the interrelationship between trajectories of adherence to ART and polypharmacy.

Methods
We included women with HIV (aged &gt;18 years) enrolled in the Women's Interagency HIV Study in the United States from 2014-2019. We used group-based trajectory modeling (GBTM) to identify trajectories of adherence to ART and polypharmacy and dual GBTM to identify the interrelationship between adherence and polypharmacy.

Results
Overall, 1538 were eligible (median age of 49 years). GBTM revealed five latent trajectories of adherence with 42% of women grouped in the consistently moderate trajectory. GBTM identified four polypharmacy trajectories with 45% categorized in the consistently low group.

Conclusion
The joint model did not reveal any interrelationship between ART adherence and polypharmacy trajectories. Future research should consider examining the interrelationship between both variables using objective measures of adherence.

Disclosures
Jessica Haberer, MD, MS, Merck: Advisor/Consultant
1612. Correlates of Sustained Viral Suppression among HIV-Positive Adults Receiving Antiretroviral Therapy from Six Secondary Health Facilities in Northern Nigeria.
Authors: TSIGA-AHMED F A T I M A H I , Musa Muhammad S , Sulaiman Abdulwahab K , Jalo Rabiu I , Bako Abdulaziz T , Sulaiman Sahabi K 
Published: November 2023

Abstract

Background
Sustained viral suppression in HIV is essential to minimize drug resistance, reduce secondary transmission and improve health outcomes necessary to achieve the UNAIDS 95-95-95 strategy. There is dearth of information on viral suppression among adults in Nigeria. Identifying correlates of sustained viral suppression will inform treatment guidelines especially for people at risk and provide recommendations to policy makers.

Methods
We collected sociodemographic and HIV-related data from a cross-section of 730 HIV-positive adults receiving antiretroviral therapy from six secondary health facilities in northern Nigeria, between October 2021 and February 2022. Sustained viral suppression was defined according to the Nigerian National Guideline for HIV Prevention, Treatment and Care as a viral load below the detection threshold of less than 20 copies of HIV RNA/ml. Proportion of participants with sustained viral suppression was estimated and a multivariable analysis used to identify independent correlates of sustained viral suppression.

Results
The sustained viral suppression rate among HIV-positive adults on ART was 35.7% [95% CI: 32.2, 39.5]. Being married [AOR 2.01; 95% CI: 1.34, 3.03] and having secondary education [AOR 0.43; 95% CI: 0.26, 0.74] were significantly associated with sustained viral suppression. Respondents on treatment for 5-10 years [AOR 1.76; 95% CI: 1.17, 2.64] and those taking two or more pills [AOR 5.67; 95% CI: 3.74, 8.62] were more likely to have sustained viral suppression. Previous treatment for opportunistic infection [AOR 0.24; 95% CI: 0.15, 0.41] significantly decreased the likelihood of sustained viral suppression.

Conclusion
Sustained viral suppression rates among HIV-positive adults on ART in the six facilities were suboptimal. While being married, taking two or more ART pills and being on treatment for 5-10 years increased the likelihood of having a suppressed viral load, being educated up to secondary level and previous treatment for opportunistic infection decreased the odds of having sustained viral suppression. There is a need to improve viral load monitoring and direct viral suppression interventions towards at risk population.

Disclosures
All Authors: No reported disclosures
1613. Frailty is Associated with Intestinal Barrier Dysfunction in Aging People Living with HIV
Authors: xu xiaolei , Yan Jiangyu , Lu Yanqiu , Yang Mengru , ouyang jing , Chen yaokai 
Published: November 2023

Abstract

Background
Recent evidence indicates that frailty is prevalent in PLWH compared to those without HIV, especially in the elderly population. However, the underlying mechanisms fundamental to this phenomenon reman unclear. Gut damage and increased microbial translocation are hallmarks of HIV infection, and are known to promote and perpetuate the chronic systemic inflammation seen in PLWTH. Meanwhile, it has been observed that chronic inflammation also contributes to the frailty. Herein, we investigate the association between frailty and intestinal barrier dysfunction in PLWH.

Methods
This cross-sectional study was designed to assimilate and analyze clinical data and results of blood samples in PLWH. According to frailty phenotype assessment, participants were stratified into three groups comprising a frailty, a pre-frailty, and a non-frailty group. We subsequently measured the levels of biomarkers of gut damage, microbial translocation, and levels of inflammatory cytokines to assess the relationship between these biomarkers and frailty.

Results
One hundred and fifty one PLWH over 50 years of age were involved in this study, and were stratified into three groups: 73 patients in the non-frailty group, 61 patients in the pre-frailty group, and 17 patients in the frailty group. Their incidence of anxiety, depression, and stress was calculated to be higher in the frailty group than other two groups (p&lt; 0.05). The concentration of gut damage biomarkers in serum, i.e., levels of regenerating islet-derived protein-3α (REG-3α) and intestinal fatty acid-binding protein (I-FABP), showed significant positive correlations with frailty, and was observed to be highest in the frailty group. On the contrary, no significant association was observed between the hematological biomarkers of microbial translocation with frailty. Additionally, IL-6, IP-10, and TNF-α concentrations in plasma were found to positively correlate with frailty in aging PLWH (i.e., these biomarkers had the highest concentrations in the frailty group).

Conclusion
Our study revealed that the inflammation induced by gut damage may contribute to frailty in elder PLWH.

Disclosures
All Authors: No reported disclosures
1614. Efficacy and Safety of Adjusted Renal Dosing of Tenofovir DF Versus Abacavir Switching in HIV Patients with Decreased Glomerular Filtration Rate After Receiving Tenofovir DF-Based Regimen
Authors: Yamasmith Eakkawit , Sirijatuphat Rujipas , Ratanasuwan Winai , Werarak Peerawong 
Published: November 2023

Abstract

Background
A switch from tenofovir disoproxil fumarate (TDF) to abacavir (ABC)-based therapy is one of treatment options for HIV-infected patients with decreased glomerular filtration rate (eGFR) after receiving a TDF-based regimen. However, ABC may not be available in some hospitals in Thailand. TDF dose reduction showed a significant improvement of eGFR without virological failure. This study aimed to compare the efficacy and safety of TDF dose reduction versus ABC switching for the treatment of patients with decreased eGFR after receiving TDF.

Methods
This open-label, randomized, non-inferiority study was conducted at Siriraj Hospital, Thailand, during March 2019 to May 2021. Eligible participants were HIV-suppressed patients aged ≤18 years with decreased eGFR (eGFR 30-60 mL/min by Cockcroft-Gault equation) after receiving TDF-based therapy. Patients were randomized (1:1 by block of four) to a TDF dose-adjusted regimen or an ABC-based regimen. The primary outcome of study was the change in eGFR at 24 weeks after regimen modification. The non-inferiority margin was -12 mL/min. Other outcomes were the virological efficacy and safety at 24 weeks after regimen modification.

Results
30 patients were enrolled (15 patients in the TDF dose-adjusted regimen group and 15 patients in the ABC-based regimen group). The distribution of age, sex, CD4 count, serum creatinine, eGFR and duration of TDF treatment were similar between both groups. The mean change of eGFR (SD) at 24 weeks after regimen modification were +1.87 (7.90) mL/min in the TDF dose-adjusted regimen group and +15.64 (6.53) mL/min in the ABC-based regimen group (P&lt; 0.001). The difference of mean change of eGFR between both groups at 24 weeks was -13.77 mL/min (95% CI; -20.18 to -7.36 mL/min) (P&lt; 0.001). The sustained viral suppression was observed in both groups. Two patients in the TDF dose-adjusted regimen group developed progressive kidney impairment and one of them developed Fanconi syndrome.
Baseline Characteristics
Outcomes

Conclusion
The TDF dose-adjusted regimen demonstrated the efficacy in improving eGFR but this regimen did not prove non-inferiority over the ABC-based regimen. The progression of kidney dysfunction should be cautioned in patients who received the adjusted renal dosing of TDF.

Disclosures
Eakkawit Yamasmith, Police General Hospital: Advisor/Consultant
1615. Efficacy of Long-Acting Cabotegravir and Rilpivirine in a Diverse Group of Patients in a Real-World Setting
Authors: Yared Nicholas F , Gudipati Smitha , Payne Shannon , Alvi Rija B R , Cherian John , Lodivico John Di , Markowitz Norman , Brar Indira 
Published: November 2023

Abstract

Background
Cabotegravir (CAB) + rilpivirine (RPV) is the first recommended complete long-acting (LA) regimen for maintenance of HIV-1 virologic suppression. The efficacy and safety of switching to CAB + RPV LA (CAR) has been shown in clinical trials. CAR injections offer less frequent dosing and address issues of adherence and disclosure related to daily oral cART. We describe the clinical characteristics and outcomes of switching a diverse group of people with HIV (PWH) to CAR in a real-world setting.

Methods
A retrospective cohort study was performed to assess virologic efficacy of intramuscular CAR given every 4 or 8 weeks among adult PWH receiving care at Henry Ford Health ID Clinic by an interdisciplinary team of physicians, nurses, social workers, and a pharmacist. Efficacy was defined as HIV-1 RNA &lt; 20 copies/mL at 3 months. Demographics, clinical characteristics, and outcomes were extracted from the electronic medical record.

Results
We included the first 51 patients to receive CAR. Median age was 46 years (IQR 34 -59). Black individuals were 75%, cisgender males 84%, and transgender females 3.9% of participants. PWH were diagnosed a median of 12 years ago (IQR 11-17). At time of switch, 90% had HIV viral load (VL) &lt; 20 copies/ml, and 9.8% of patients were viremic with &lt; 75 copies/ml. Mean Cd4+ cell count was 871 cells/µL (IQR 632-1603). Prior to switch, 80% had received ≥ 2 cART regimens, 75% had INSTI exposure, and 45% had NNRTI exposure. Among 38 patients with HIV-1 genotypes available prior to switch, 4 had either baseline NNRTI or INSTI mutations (Table 2). For patients with VL data at 3 months, 37 of 38 (98%) had an undetectable VL. Virologic failure occurred in 1 PWH with BMI 35 who had a Y188L RT mutation in a 2009 genotype which did not include RPV (2011 approval), with subsequent emergence of pan-NNRTI and INSTI resistance.

Conclusion
A high degree of virologic suppression at 3 months was achieved among an older, diverse cohort of PWH cared for by an interdisciplinary team. Unrecognized baseline HIV resistance to NNRTI contributed to one virologic failure. It is important to assure that genotypic susceptibility interpretations are current and to carefully assess for eligibility before switching to CAR.

Disclosures
John Di Lodivico, PharmD, Midwest AIDS Training & Education Center: Honoraria|ViiV Healthcare: Advisor/Consultant|Wayne State University: Honoraria Indira Brar, MD, Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Gilead: Honoraria|Janssen: Grant/Research Support|Janssen: Honoraria|ViiV: Advisor/Consultant|ViiV: Grant/Research Support|ViiV: Honoraria
1617. Assessment of Bloodstream Infections in Patients with Intrapartum Fever
Authors: Kamel Barbara , Doan Thien-Ly , Luchana Vidal , Oppenheim Michael , Donaghy Henry 
Published: November 2023

Abstract

Background
The American College of Obstetricians and Gynecologists (ACOG) offers guidance on the management of intraamniotic infections, where the diagnosis of chorioamnionitis can be made based on clinical criteria (e.g., maternal leukocytosis, purulent cervical drainage, or fetal tachycardia), positive amniotic fluid analysis (gram stain, glucose level, cultures), or placental pathology. No recommendations for blood cultures are made. The study purpose is to evaluate the utility of blood cultures in the management of intrapartum fever and to analyze the microbiological data.

Methods
This is a retrospective, descriptive study that analyzes patients with blood cultures drawn within 5 days of delivery from 1/2019 to 12/2022. Procurement contaminants were excluded from the analysis. Chart reviews were conducted on the positive cultures. Data collected included age of mother, gestational age, method of delivery, presence of fetal tachycardia, cultures sent prior to admission, maternal Group B Streptococcus (GBS) status, culture results including organism (blood, placenta cultures), and antimicrobials administered. Descriptive statistics were utilized.

Results
Of the 70,540 deliveries in the study period, there were a total of 507 patients had blood cultures drawn, of which 25 were positive. Three patients were excluded because they were deemed to be procurement contaminants (e.g., 2 patients with coagulase-negative Staphylococcus species and 1 patient with Micrococcus species). Analysis of the bloodstream infection were performed on 22 patients, thus the rate of bacteremia was 4.3% in our cohort. The mean age was 33.3 ± 4.4 years with an average gestational age at birth of 32.3 ± 6.5 weeks. Of the 22 patients, 19 (86.4%) received a cesarean section and 4 (18.2%) were positive for GBS. The most common pathogen present were E. coli (45.5%) and Prevotella bivia (13.6%). The most common antimicrobials given were ertapenem (63.6%), followed by clindamycin + gentamicin (13.6%).
Organisms Isolated from Blood Cultures
E. coli was the predominant organism isolated, followed by Prevotella. Interestingly, Candida was isolated in 1 patient where empiric ertapenem or gentamicin + clindamycin would not have been sufficient.

Conclusion
Although uncommon, bacteremia can occur in patients with intrapartum fevers. Gram-negative and anaerobes were found to be most common organisms. Bloodstream infections may require a longer duration of treatment therefore blood cultures should be considered as part of the work-up of intrapartum fever.,

Disclosures
All Authors: No reported disclosures
1620. Identification of plasma biomarkers of neurological complications in patients with congenital cytomegalovirus infection by proteome analysis
Authors: Yamaguchi Makoto , Suzuki Takako , Kidokoro Hiroyuki , Iwada Ken-ichi , Fukuda Yuto , Haruta Kazunori , Torii Yuka , Ito Yoshinori , Kawada Jun-ichi 
Published: November 2023

Abstract

Background
Congenital cytomegalovirus infection (cCMV) is the leading cause of non-hereditary sensorineural hearing loss and can cause other long-term neurodevelopmental disabilities. To consider antiviral treatment, it is important to differentiate between symptomatic and asymptomatic patients by early infancy. However, it is difficult to identify neurological complications in some cases. This study aimed to identify candidate plasma biomarkers for neurological complications of cCMV during the neonatal period using proteome analysis.

Methods
This study retrospectively enrolled five patients with asymptomatic cCMV and nine patients with symptomatic cCMV, including those with hearing loss and/or abnormal brain imaging. Plasma samples were obtained during the neonatal period. After extraction of 14 high-abundant proteins from the plasma, proteins were digested by trypsin. The peptides were analyzed by liquid chromatography–mass spectrometry using an Orbitrap Fusion mass spectrometer. Protein quantification was performed using Proteome Discoverer. Levels of differently expressed proteins were validated by enzyme-linked immunosorbent assay.

Results
In total, 456 proteins were identified and quantified. Levels of 65 proteins were significantly higher in patients with symptomatic cCMV than in those with asymptomatic cCMV. The top two enriched categories for these proteins according to pathway enrichment analysis were “complement and coagulation cascade” and “inflammatory response.” In contrast, levels of 30 proteins were significantly higher in patients with abnormal brain imaging. Plasma levels of fms-related receptor tyrosine kinase 4 (FLT4) were significantly higher in patients with symptomatic cCMV than in those with asymptomatic cCMV. Moreover, levels of plasma peptidylprolyl isomerase A (PPIA) were significantly higher in patients with abnormal brain imaging than in those without.

Conclusion
Proteome analysis showed that the proteins related to inflammatory response pathways were upregulated in patients with symptomatic cCMV. FLT4 and PPIA can be used as novel diagnostic biomarkers for neurological complications of cCMV to enable early therapeutic intervention with antiviral agents.

Disclosures
All Authors: No reported disclosures
1622. Increase in Congenital Toxoplasmosis and Acute Toxoplasmosis Among Pregnant Women in the US during the COVID-19 pandemic
Authors: Contopoulos-Ioannidis Despina , Bonetti Valerie , Montoya Jose G 
Published: November 2023

Abstract

Background
During the COVID19 pandemic a rise in diverse opportunistic infections has been described

Methods
In this retrospective cohort study, we analyzed the trajectory of new congenital toxoplasmosis (CT) cases and cases of acute toxoplasmosis among pregnant women (AT-P) during the COVID19-pandemic (2020-2022) compared to a pre-pandemic period (2000-2019). We perused data from the Remington’s Laboratory, the National Reference Laboratory for Toxoplasmosis in the US. We calculated the yearly number of cases of CT and AT-P; the incidence rate (IR) of CT and AT-P (IR=number of cases/total number of children &lt; 12 months or pregnant women respectively tested by the Toxoplasma IgG-Dye test). We used ARIMA time-series models to compare the trajectory slopes between the two periods.

Results
In the pre-pandemic period there were 196 CT cases among 8194 tested children&lt; 12 months and 814 AT-P cases among 33,345 pregnant women. The respective numbers during the pandemic were 43 CT among 1833 tested children &lt; 12 months and 65 AT-P among 1983 pregnant women. In 2022 we had the largest number of CT cases (21 CT in 2022 vs 6 in 2019) and similarly a high number of AT-P cases (22 AT-P in 2022 vs 16 in 2019)(Fig 1). This increase occurred, despite a drop in the total number of samples tested in the Lab ≥2020, due to programmatic changes in one major Lab client (Fig 2). The yearly IR of CT increased during the pandemic, from 1.05 cases/100 tested (6/574) in 2019 to 3.71 cases/ 100 tested (21/566) in 2022. The yearly IR of AT-P also increased during the pandemic, from 1.35 cases/ 100 tested (16/1183) in 2019 to 3.79 cases/100 tested (22/580) in 2022 (Fig 3). There was a positive trajectory-slope trend in CT and AT-P during the pandemic. This occurred after a preceding negative trajectory-slope trend in AT-P in the pre-pandemic period.Figure 1:Number of Congenital Toxoplasmosis and Acute Toxoplasmosis during Pregnancy cases: 2000-2022Figure 2:Toxoplasmosis IgG Dye tests in Pregnant Women and in Children &lt;12 months of age: 2000-2022Figure 3:Incidence Rates of Congenital Toxoplasmosis (IR-CT)and Acute Toxoplasmosis During Pregnancy (IR-AT-P): 2000-2022

Conclusion
During the pandemic, there was a rising trend in CT and AT-P cases diagnosed in the National Reference Lab for toxoplasmosis in the US. In 2022 there was a peak in the CT cases. The etiology remains unclear. A possible increase- during the lockdowns-in the contact of pregnant women with cats and/or a possible limited prenatal-preventive-guidance during the pandemic due to possible disruption in prenatal care services, could have been contributing factors. These trends need further monitoring.

Disclosures
All Authors: No reported disclosures