bluuebunny/crossref_metadata_2025_split huggingface dataset:
1006. Contraception, Pregnancy and ART in Women of Child-Bearing Years
Authors: Hasan Hira , Richey Lauren E 
Published: January 2021

Abstract

Background
Simpler anti-retroviral (ART) regimens with less pill burden and fewer side effects can improve adherence and clinical outcomes. Warnings about dolutegravir possibly causing neural tube defects (NTD) are alarming and have the potential to limit ART options for women of child-bearing years. A recent preliminary analysis from an observational study group in Botswana prompted a warning from the US Department of Health and Human Services (DHHS), released in May 2018, about the use of dolutegravir during conception.

Methods
At a large urban HIV clinic in New Orleans, a retrospective chart review was performed on adult women up to age 40 who were seen in clinic in 2018 to assess for dolutegravir use, as well as discussion of NTD and pregnancy.

Results
132 woman in the age range were seen in 2018, the mean age was 33 years (range 19 to 40). Average age of HIV diagnosis was 26. Most were African-American (83%) and 81% had Medicaid or no insurance. Eleven percent were diagnosed with HIV due to testing during pregnancy and 17% during routine screening. Sexual exposure was the main reported risk factor for HIV (69%) and 48% had another STD. Only 61% had a documented discussion of contraception and pregnancy plans. Over their treatment at the clinic, 47 pregnancies occurred. Most of the women were on integrase regimens (65%), although 14% were on protease inhibitor regimens and 20% were on other regimens or combination regimens. Forty two percent of the women were ever on dolutegravir and 12 had NTD discussed, resulting in 3 regimen changes. The main reason it was not discussed was permanent sterilization, change to a different ART regimen prior to the warning, long-term contraception, or no sexual activity. Seven pregnancies occurred while on dolutegravir, three were prior to the warning, one after the first trimester, and one ended in abortion. None had an NTD reported.

Conclusion
Dolutegravir is very commonly used due to its tolerability and simplicity. While recent reports show the risk of NTD to be lower than previously thought, it is still elevated compared to other ART and a more open discussion of pregnancy plans, contraception, and NTD if applicable, needs to occur in women living with HIV.

Disclosures
All Authors: No reported disclosures
1009. Dolutegravir and Doravirine in Combination: When Standard Antiretroviral Regimens are Unacceptable
Authors: Denyer Rachel , Zemskova Julie , Beatty Daniel , Benator Debra A 
Published: January 2021

Abstract

Background
A drug-drug interaction study between dolutegravir and doravirine in healthy volunteers found no evidence of untoward interaction. Whilst we hypothesize that the combination would be safe and effective, there is no supportive clinical data. We aimed to assess the rationale for use of dolutegravir and doravirine in combination and clinical outcomes among persons with HIV infection (PWH) receiving care at the Washington DC VAMC.

Methods
A quality improvement initiative utilized the clinical case registry to identify all PWH receiving both dolutegravir and doravirine. We conducted chart review to examine (a) the reasons for switch from other ART to dolutegravir and doravirine, and comorbidities, HIV resistance mutations or drug interactions precluding the use of standard ART, (b) adverse events or side effects and (c) achievement of virologic suppression.

Results
A case registry search revealed 21 individuals receiving combination dolutegravir doravirine from 2018–2020 (Table 1 and Figure 1). Side effects were not noted except one patient developed mild diarrhea that improved with continuation of therapy. Four patients were hospitalized during the follow-up period for reasons unrelated to the medications. One patient who was admitted to the ICU with shock and multi-organ failure was switched on admission but died four days later and therefore was not included in the analysis of viral outcome (Table 2). One patient had cardiac arrest following missed dialysis, hyperkalemia and rectal hemorrhage from metastatic rectal cancer.
Table 1: Patient Demographics.

Figure 1: Reasons for Switching to Dolutegravir with Doravirine.

Table 2: Virologic Control Before and After Switching to Dolutegravir with Doravirine.

Conclusion
In an era of abundant ART options, we identified a subset of older PWH whose treatment options are defined by extensive comorbidities, viral resistance, and medication interactions or toxicities. Doravirine is attractive for this population as it can be used in renal impairment, moderate hepatic impairment, is unaffected by timing of meals, and (unlike rilpivirine) has no interaction with proton pump inhibitors. Dolutegravir is included in NRTI-sparing regimens that HHS guidelines suggest should be considered in older PWH, especially with CKD. We found that dolutegravir with doravirine is well tolerated, and achieves virologic suppression in the majority of PWH, indicating this combination is useful when other ART options cannot be used.

Disclosures
All Authors: No reported disclosures
1011. Efficacy and Safety of Doravirine in Treatment-Naïve Adults ≥50 Years Old With HIV-1
Authors: Mills Anthony , Martin Elizabeth A , Liu Chih-Chin , Drolet Martine , Sklar Peter 
Published: January 2021

Abstract

Background
Nearly 50% of people living with HIV in the US are ≥50 years old. Older people are more likely to have late-stage HIV infection at diagnosis, greater risk for cardiovascular disease and certain cancers, and concurrent medications for common age-related conditions. Doravirine (DOR) is a next-generation NNRTI with activity against first-generation NNRTI-associated mutations, a neutral impact on lipids, and few drug-drug interactions with commonly used medications.

Methods
We compared Week 96 results from DOR Phase 2 and Phase 3 trials (P007, P018, and P021) in treatment-naïve adults ≥50 vs &lt; 50 years old. 855 participants received DOR 100mg +2 NRTIs in P007 & P018 or fixed combination DOR/3TC/TDF in P021; 383 participants received ritonavir-boosted darunavir (DRV) +2 NRTIs in P018; and 472 received efavirenz (EFV) 600mg +FTC/TDF in P007 or fixed combination EFV/FTC/TDF in P021. Participants who took ≥1 dose of study drug were included; the Observed Failure approach was used for missing efficacy data. All analyses were done by descriptive statistics.

Results
Of 1710 participants, 187 (11%) were 50-70 (median 54) years old at study entry. Baseline characteristics and treatment outcomes are summarized below for participants &lt; 50 vs ≥50 years old. The older cohort had more women, more participants with AIDS, and lower median CD4+ T-cell counts than the younger cohort, whereas baseline HIV-1 RNA was similar between age cohorts. Hypertension and use of analgesics were more common in older participants. In each treatment group, the older cohort had a higher proportion of participants with HIV-1 RNA&lt; 50 copies/mL at week 96 and fewer discontinuations due to lack of efficacy than the younger cohort. Mean change in CD4+ T-cell count was similar between age cohorts in the DOR and DRV groups and was lower for older participants in the EFV group. Rates of drug-related AEs and serious drug-related AEs were similar between age cohorts across all treatment groups. Discontinuations due to drug-related AEs were similar between age cohorts in the DOR group and were slightly higher for older participants in the DRV and EFV groups.

Conclusion
DOR is a beneficial option for adults ≥50 years old, given its similar efficacy and favorable safety profile compared to younger adults.
Doravirine Phase 2 and Phase 3 Trials in Treatment-Naïve Adults

Disclosures
Anthony Mills, MD, Gilead (Grant/Research Support, Advisor or Review Panel member)Janssen Pharmaceutica (Grant/Research Support, Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Shionogi (Grant/Research Support)ViiV Healthcare (Grant/Research Support, Advisor or Review Panel member) Elizabeth A. Martin, DO, MPH, MBA, Merck & Co., Inc. (Employee) Chih-Chin Liu, PhD, Merck & Co., Inc. (Employee) Martine Drolet, BPharm, LPH, MBA, Merck & Co., Inc. (Employee) Peter Sklar, MD, MPH, Merck & Co., Inc. (Employee)
1018. Health Technology Assessment of New Long-Acting, Directly-Observed HIV Treatments in Canada: Impact of Real-World Adherence to Daily Oral Therapy on Treatment, Transmission and Cost-Effectiveness
Authors: Arthurs Erin , Parker Ben , Jacob Ian , Becker Debbie , Lee Amy , Hayward Olivia , Chounta Vasiliki , Anderson Sarah-Jane , Van de Velde Nicolas 
Published: January 2021

Abstract

Background
Current antiretroviral therapy (ART) has dramatically improved outcomes for people living with HIV (PLWHIV), however adherence to daily oral dosing remains a challenge for some. New, long-acting (LA) ARTs which are directly administered by physicians eliminate the need to adhere to daily oral dosing and may improve clinical outcomes. The study objective was to evaluate costs and QALYs associated with improved adherence achieved via a novel, directly-observed therapy (DOT) of a monthly LA injectable ART, compared to standard of care (SoC), daily oral therapy.

Methods
A published Markov cohort state-transition model was adapted to model the impact of treatment adherence and subsequent disease transmission. Without the need to adhere to daily dosing, the efficacy of the injectable was modelled independent of adherence whereas virologic suppression in the SoC arm was adjusted to reflect published data on adherence to daily dosing (8.12% below optimal levels observed in clinical trials).

Results
This evidence-based approach of accounting for adherence revealed an increase in lifetime costs for oral SOC of approximately $850, and QALY loss of 0.109 when compared to results without accounting for adherence. Disease transmission results yielded 3 cases averted of HIV per 1,000 patients with LA’s impact on adherence.

Conclusion
In the absence of comparative adherence estimates between a LA, injectable DOT and daily oral therapy in the real world, an evidence-based approach provides a method to address the uncertainty around the true impact on costs and QALYs of a novel mode of administration.

Disclosures
Erin Arthurs, MSc, GlaxoSmithKline (Employee) Ben Parker, MSc, HEOR Ltd. (Employee) Ian Jacob, MSc, HEOR Ltd (Employee) Debbie Becker, MSc, GSK (Consultant) Amy Lee, MSc, PhD, GSK (Consultant) Olivia Hayward, PhD, HEOR ltd. (Employee) Vasiliki Chounta, MSc, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Sarah-Jane Anderson, PhD, GlaxoSmithKline (Employee, Shareholder) Nicolas Van de Velde, PhD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee)
1020. Higher efavirenz mid-dose plasma concentration is associated with less weight gain among virologically suppressed people living with HIV
Authors: Huang Wei-chieh , Huang Sung-Hsi , Hung Chien-Ching 
Published: January 2021

Abstract

Background
Recently, an association between CYP2B6 516 G &gt; T polymorphism and weight change was observed among African people living with HIV (PLWH) who were started on efavirenz(EFV)-based antiretroviral therapy (ART). We aimed to investigate the effect of EFV mid-dose plasma concentration on weight change among Taiwanese PLWH.

Methods
The medical records of adult PLWH who were taking EFV-containing ART and had been enrolled in a EFV therapeutic drug monitoring study between Oct 2009 and May 2014 were accessed. EFV mid-dose plasma concentration (C12) was determined in the previous study and those with serial weight measurements within 48 weeks around the time of EFV C12 measurement were included in the present study. The weight change in the 48 weeks and its associations with mid-dose EFV concentrations and CYP2B6 516 G &gt; T polymorphism were examined by general estimating equations (GEE) after adjusting for age, baseline HIV viremia, baseline weight, and the companion backbone antiretroviral agents.

Results
One-hundred and fifteen predominantly male (94.8%) PLWH were included in this study (Table 1). The mean CD4 lymphocyte count was 542 cells/μL at the beginning of the observation and 94.8% achieved HIV viral suppression. Forty-four (38.3%) patients had non-wildtype CYP2B6 516 G &gt; T polymorphism. On average, the included PLWH gained 0.8 kilogram at 48 weeks and the weight change did not differ among those with wildtype and non-wildtype CYP2B6 516 G &gt; T(Figure 1). In the GEE models, CYP2B6 516 G &gt; T polymorphism was not associated with weight change (p=0.81), instead, higher EFV C12 was found to be independently associated with less weight gain (p=0.045).
Table 1. Baseline characteristics.

Figure 1. The absolute weight (A) and weight change from baseline (B) among patients with wildtype and non-wildtype CYP2B6 516G&gt;T polymorphism.

Conclusion
Our findings support that increased EFV exposure may have a negative effect on weight gain.

Disclosures
Chien-Ching Hung, MD,PHD, Abbvie (Advisor or Review Panel member, Speaker’s Bureau)Bristol-Myers Squibb (Speaker’s Bureau)Gilead Sciences (Advisor or Review Panel member, Speaker’s Bureau)Janssen (Grant/Research Support, Advisor or Review Panel member)Merck (Grant/Research Support)ViiV (Grant/Research Support, Advisor or Review Panel member, Speaker’s Bureau)
78. Outcomes and adherence to institutional empiric therapy guidelines for the treatment of cystitis in ambulatory male veterans
Authors: Pham Selena N , Ashong Chester , Rodriguez-Barradas Maria C , Hunter Andrew 
Published: January 2021

Abstract

Background
Guidelines provide primary literature demonstrating efficacy and safety of cystitis treatment in female patients, but not males. Increased antimicrobial resistance of urinary tract infection (UTI) pathogens to first line antibiotics are well-documented. In 2017, a change in institutional guidelines was made to recommend nitrofurantoin (NF) or cefpodoxime (CPD) as first line antibiotics for cystitis in males. This study aims to evaluate the efficacy of NF and CPD as first line treatment options in males with cystitis.

Methods
Single-center, retrospective chart review of male patients prescribed NF or CPD for treatment of cystitis in the outpatient setting from August 2017 to August 2018. Patients with asymptomatic bacteriuria, prostatitis or systemic signs and symptoms of UTI were excluded. Primary outcome was treatment failure, defined as requiring new emergency department (ED) or patient aligned care team (PACT) visit within 30 days after initiation of antibiotic for unresolved symptoms. Safety outcomes were based on documented adverse effects (AE) associated with antibiotic use. Chi-square was the primary statistical test for analyzing primary outcomes and other nominal variables.

Results
A total of 450 charts were reviewed with 150 patients meeting inclusion criteria (NF n = 75, CPD n = 75). Baseline characteristics were equally distributed between the two groups although the CPD group had higher serum creatinine compared to the NF group (p = 0.05). Nine patients (12%) in the NF group versus 13 patients (17.3%) in the CPD group returned to ED or PACT within 30 days (p=0.36). Inappropriate dosing was seen in 13 patients (17.3%) in the NF group vs. 2 patients (2.7%) in the CPD group (p = 0.005) and 44 patients (58.7%) in the NF group vs. 37 patients (49.3%) in the CPD group who received an inappropriate duration of treatment (p = 0.25). None of the patients reported AE associated with antibiotic use.

Conclusion
Treatment success rate of NF and CPD (88% and 82.7%, respectively) suggests that these agents might be effective first line antibiotics for cystitis in males. High rate of inappropriate long duration of treatment indicates the need for staff education and prospective audit and feedback for outpatient stewardship interventions.

Disclosures
All Authors: No reported disclosures
1044. The Incidence and Severity of Drug interactions Before and After Switching Antiretroviral Therapy to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Treatment Experienced Patients
Authors: Schafer Jason J , Pandit Neha S , Cha Agnes , Huesgen Emily , Badowski Melissa E , Sherman Elizabeth , Cocohoba Jennifer , Shimada Ayako , Keith Scott 
Published: January 2021

Abstract

Background
Switching antiretroviral therapy (ART) in virally suppressed people with HIV (PWH) can simplify treatment, improve tolerability, and limit long-term toxicity. It can also influence the presence of drug interactions (DIs) in a positive or negative manner among patients receiving concomitant medications (CMs). The extent to which switching ART to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) influences DIs in treatment-experienced PWH is unclear. The purpose of this study was to assess changes in the incidence and severity of DIs after switching to BIC/FTC/TAF.

Methods
This was a multicenter retrospective cohort study of PWH on ART and at least one prescription CM who switched to BIC/FTC/TAF between 3/2018 and 6/2019. Using the University of Liverpool’s HIV drug interaction checker, two DI analyses were performed for each patient. The first assessed patients’ pre-switch ART regimen with their CM list. The second assessed the same CM list with BIC/FTC/TAF. Each ART-CM combination was given a numerical score of 0 (no or potential weak interaction), 1 (potential interaction), or 2 (contraindicated interaction). Total DI scores for each patient, both before and after switching to BIC/FTC/TAF, were then calculated. A paired t-test analyzed changes in DI scores following ART switches and a linear regression model examined factors contributing to DI score reductions.

Results
A total of 411 patients were included in the analysis (Table 1) of which 236 (57%) had at least one DI present at baseline. On average, patients had a baseline DI score of 1.4 (SD 1.8) and experienced a 1 point reduction (95% CI -1.1,-0.8) after switching to BIC/FTC/TAF (p &lt; 0.0001). After adjusting for demographic variables as well as baseline ART and CM categories in the regression model, switching to BIC/FTC/TAF led to significant DI score reductions in patients receiving CMs for the following conditions: cardiovascular disease, neurologic and psychiatric disorders, chronic pain, inflammation, gastrointestinal and urologic conditions and conditions requiring hormonal therapy (Table 2).
Table 1. Descriptive Summary of Baseline Characteristics, n =411.

Table 2. Linear Regression for the Difference of DI scores (post – pre), n =376.

Conclusion
Switching ART to BIC/FTC/TAF can reduce the incidence of DIs among treatment-experienced PWH who are receiving CMs for a broad range of comorbid conditions.

Disclosures
Jason J. Schafer, PharmD, MPH, Gilead (Research Grant or Support)Merck (Grant/Research Support, Advisor or Review Panel member)ViiV (Advisor or Review Panel member) Elizabeth Sherman, PharmD, Gilead (Grant/Research Support) Jennifer Cocohoba, PharmD, AAHIVP, BCPS, Viiv (Grant/Research Support)
1050. Hepatitis C Infection amongst People who Inject Drugs (PWID): Injection Practices and Risk Factors
Authors: Sankar Nityasri , Murray Kim , Burris Debra D , Thakarar Kinna 
Published: January 2021

Abstract

Background
The rapidly progressing U.S. opioid epidemic has led to an increased prevalence of infections associated with injection drug use (IDU), such as Hepatitis C (HCV). Previous studies have identified a lack of screening, prevention, and treatment of HCV, which has contributed to an increase in HCV-related mortality. Transmission has been linked to unsafe injection practices. Our study aims to characterize risk factors associated with Hepatitis C (HCV) exposure amongst people who inject drugs (PWID) in Maine, a state heavily impacted by the opioid epidemic.

Methods
Data was obtained from a cross-sectional study of participants hospitalized with an IDU-associated infection at four hospitals in Maine identified as high-risk for HIV/HCV outbreaks. The Audio Computer-Assisted Self-Interview survey and medical record review were used to collect data. The components from the BIRSI 7-item score were used to assess the use of safe injection practices. HCV exposure was defined as HCV antibody positive and/or self-reported exposure. Analysis was performed using descriptive analyses and univariate regression modeling.

Results
Of the 101 participants enrolled, n=76 (75%) were identified as having exposure to HCV. Out of participants exposed to HCV, 57% reported homelessness (p=&lt; 0.01). Participants exposed to HCV were more likely to have bacteremia during hospitalization (25%, p=.02). All participants unexposed to HCV perceived low likelihood of contracting HCV due to injecting (p=.01). Seventy-one percent of people exposed to HCV reported infrequent use alcohol pads prior to injecting (p=&lt; 0.01) and 67% reported infrequent hand-washing (p=.09). Participants with a higher BIRSI-7 score had higher odds of exposure to HCV (OR=1.48, 95% CI 1.10-2.04).

Conclusion
The data obtained highlights significant relationships between HCV exposure and certain risk factors. Homelessness was found to be associated with HCV exposure, suggesting an opportunity for more targeted intervention within this subgroup of PWID. Unsafe injection practices as measured by the BIRSI-7 score were related to HCV exposure, indicating educational opportunities about safe injection practices. Overall, targeted harm reduction services could be beneficial in the screening and prevention of HCV exposure amongst PWID.

Disclosures
All Authors: No reported disclosures