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Background Many people at risk for sexually transmitted infections (STIs) utilize the emergency department (ED) for evaluation and treatment of STI-related complaints. Syphilis testing rates in the ED have historically been low. Following the implementation of a joint ED and Infectious Disease (ID) multidisciplinary quality improvement initiative designed to increase syphilis testing in this setting, we sought to evaluate the demographics and clinical outcomes for patients diagnosed with early syphilis in the ED. Methods A retrospective chart review of patients with positive syphilis test results from ED encounters at the Ohio State University Wexner Medical Center East Hospital between 1 January 2019 and 31 December 2021 was performed. Demographic and clinical information was obtained for patients diagnosed with early syphilis (primary, secondary or early latent syphilis). Results Since 2019, we have observed a significant increase early syphilis cases identified in our ED despite stable rates of testing (Figure 1). There were 55 cases of early syphilis, 3 with neurosyphilis (NS) at the time of diagnosis (Figure 2). Most cases were men (38/55; 69%), Black/African American (44/55; 80%), and symptomatic (48/55; 87%). Nine of 55 patients (16%) had HIV co-infection, 2 were new diagnoses at time of syphilis diagnosis. Most patients (44/55; 80%) completed appropriate treatment. Of the symptomatic patients, 17/45 (37%) received presumptive treatment in the ED (3 cases of NS excluded). Of those who received treatment after discharge from the ED, the median time to treatment completion was 3 days (range 0-30), with 11/24 (46%) returning to the ED for treatment. Figure 1.Figure 2. Conclusion As a result of a collaborative ED/ID STI testing initiative established at our institution, we have observed a significant increase in the number of symptomatic early syphilis cases identified in our ED between 2019 and 2021, with most patients completing treatment in a timely manner. This data show that the ED is an important and feasible setting for syphilis diagnosis and treatment when appropriate support systems are in place, including established communications with ID colleagues. Disclosures Carlos Malvestutto, MD MPH, Gilead Sciences: Advisor/Consultant|Viiv Healthcare: Advisor/Consultant Susan L. Koletar, MD, Gilead Sciences: Grant/Research Support.

BackgroundWomen are underrepresented in human immunodeficiency virus (HIV) research in the United States. To determine if women screening for HIV clinical trials enrolled at lower rates than men, we performed a retrospective, cross-trial analysis.MethodsWe conducted an analysis of screening and enrollment during 2003–2013 to 31 clinical trials at 99 AIDS Clinical Trials Group network research sites in the United States. Random-effects meta regression estimated whether sex differences in not enrolling (“screen out”) varied by various individual, trial, or site characteristics.ResultsOf 10 744 persons screened, 18.9% were women. The percentages of women and men who screened out were 27.9% and 26.5%, respectively (P = .19); this small difference did not significantly vary by race, ethnicity, or age group. Most common reasons for screening out were not meeting eligibility criteria (30–35%) and opting out (23%), and these did not differ by sex. Trial and research site characteristics associated with variable screen-out by sex included HIV research domain and type of hemoglobin eligibility criterion, but individual associations did not persist after adjustment for multiple testing.ConclusionsIn the absence of evidence of significantly higher trial screen-out for women, approaching more women to screen may increase female representation in HIV trials.

BackgroundWe characterized associations between frailty and incident cardiovascular disease (CVD), diabetes mellitus (DM), bone disease, and mortality within a cohort of aging persons with human immunodeficiency virus (PWH).MethodsParticipants underwent frailty evaluations using the Fried frailty assessment (baseline and annually). Frailty was defined as having ≥3 frailty criteria. Clinical outcomes of mortality, CVD events, DM, and bone disease events were recorded throughout the study period (baseline to most recent study or clinic visit, or date of clinical outcome, whichever came first). Poisson regression models were used to evaluate associations between baseline frailty, change in frailty score over 48 weeks, and each clinical outcome.ResultsAmong 821 men and 195 women (median age 51 years), 62 (6%) were frail at baseline. Frailty scores increased by ≥1 component among 194 participants (19%) from baseline to 48 weeks. Baseline frailty was associated with an increased risk of incident CVD and DM, with a trend toward a significant association with bone events. Among frailty components, slow gait speed was associated with incident DM and borderline associated with incident CVD. An increase in frailty from baseline to week 48 was associated with mortality but not with the other clinical outcomes.ConclusionsBaseline frailty was associated with multiple adverse health outcomes (incident CVD, DM, and bone disease), while increase in frailty score was associated with mortality among PWH engaged in care. Incorporation of frailty assessments into the care of PWH may assist in improvement of functional status and risk stratification for age-related chronic diseases.

In this randomized pilot clinical trial, dolutegravir plus lamivudine was noninferior to continuation of standard 3-drug maintenance antiretroviral therapy. There was no emergence of drug resistance in the participant who experienced virologic failure while receiving dolutegravir plus lamivudine. Clinical Trials Registration {"type":"clinical-trial","attrs":{"text":"NCT02263326","term_id":"NCT02263326"}}NCT02263326

Background Although statins, angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) are generally well tolerated, the impact of these therapies individually or in combination on the change in neurocognitive function in persons with human immunodeficiency virus infection is unknown. Methods The study included participants in the AIDS Clinical Trials Group Longitudinal Linked Randomized Trials cohort participants not receiving a statin or ACEI/ARB within 30 days of first neurologic assessment (baseline), with assessments by NPZ-3 (z score of averaged Trailmaking A and B tests and digit symbol test [DST]) from ≥2 measurements. Marginal structural models estimated the causal effect of statin or ACEI/ARB initiation on neurocognitive function; initial constant slope was assumed during the first year of treatment and a second constant slope thereafter. Results Of 3949 eligible participants, 16% started therapy with a statin, 11% with an ACEI/ARB, and 5% with both. Statin therapy had no significant effect on the composite NPZ-3 (primary outcome), Trailmaking B test, or DST. A small, nonsignificant positive effect on the Trailmaking A test was seen during year 1 (estimate, 0.088; 95% confidence interval, -.010 to .187; P = .08) and a small but significant negative effect (-0.033; -.058 to -.009; P = .007) in each subsequent year. ACEI/ARB therapy had a significant negative effect on the DST (-0.117; 95% confidence interval, -.217 to .016; P = .02) during year 1 but minimal effect in subsequent years or on other neurocognitive domains. Conclusions In summary, although modest declines in neurocognitive performance were seen in single domains with statin or ACEI/ARB therapy, we did not find consistent evidence that statins or ACEI/ARB have an effect on global neurocognitive function. Future studies should focus on long-term neurocognitive effects.

In the ASPIRE trial, antiretroviral therapy (ART) switch to dolutegravir plus lamivudine (DTG+3TC) was comparable to 3-drug ART in maintaining viral suppression by standard viral load assays. We used an ultrasensitive assay to assess whether this switch led to increased residual viremia. At entry, levels of residual viremia did not differ significantly between arms (DTG+3TC vs 3-drug ART: mean, 5.0 vs 4.2 HIV-1 RNA copies/mL; P = .64). After randomization, no significant between-group differences were found at either week 24 or 48. These results show no evidence for increased viral replication on DTG+3TC and support its further investigation as a dual ART strategy.

BackgroundBroadly neutralizing monoclonal antibodies (bnMAbs) may promote clearance of HIV-1-expressing cells through antibody-dependent cell-mediated cytotoxicity. We evaluated the effect of the CD4-binding site bnMAb, VRC01, on measures of HIV-1 persistence in chronically infected individuals.MethodsA5342 was a phase 1, randomized, double-blind, placebo-controlled, parallel-arm study. Participants on effective antiretroviral therapy (ART) were randomized to receive 2 infusions of VRC01 (40 mg/kg) at entry and week 3, and 2 infusions of placebo (saline) at weeks 6 and 9; or 2 infusions of placebo at entry and week 3, and 2 infusions of VRC01 at weeks 6 and 9.ResultsInfusion of VRC01 was safe and well tolerated. The median fold-change in the cell-associated HIV-1 RNA/DNA ratio from baseline to week 6 was 1.12 and 0.83 for the VRC01 and placebo arms, respectively, with no significant difference between arms (P = .16). There were no significant differences in the proportions with residual plasma viremia ≥1 copies/mL or in phorbol 12-myristate 13-acetate/ionomycin-induced virus production from CD4+ T cells between arms (both P > .05).ConclusionsIn individuals with chronic HIV-1 infection on ART, VRC01 infusions were safe and well tolerated but did not affect plasma viremia, cellular HIV-1 RNA/DNA levels, or stimulated virus production from CD4+ T cells.ClinicalTrials.gov IdentifierNCT02411539

Background Mental health (MH) conditions and pain are common among people living with HIV (PLWH). An understanding of factors associated with prescriptions for these conditions and clinical impact of the prescriptions may improve care of MH disorders in PLWH. Methods The use of mental health/pain-related medications was examined among PLWH within the AIDS Clinical Trials Group A5322 (HAILO) study. Use of medications (any use and class) was compared by sex. Multivariable logistic models estimated the association between MH medications (any/none) with (i) insurance status and race/ethnicity and (ii) baseline and incident slow gait (>1 second/m) and neurocognitive impairment (NCI) over 4 years. Results Of 1035 participants, the median age was 51. 81% were men, 30% black, and 20% Hispanic. Similar numbers of men (34%) and women (38%) were on MH medications (P = 0.19).Women were more likely to be prescribed opioids (12% vs. 5%; P < 0.001); other classes were similar. In multivariable models, MH-medicated PLWH were more likely to have Medicare (odds ratio [OR] 2.50, 95% CI 1.50–4.16, P < 0.001) or public insurance (1.85; 1.23–2.78, P = 0.003) vs. no/unknown insurance; and less likely to be Hispanic vs. white (0.48; 0.33–0.69; P < 0.001). MH-medicated PLWH had greater odds of baseline slow gait (1.80; 1.34–2.40; P < 0.001). The sex-specific ORs for NCI were qualitatively different (men: 1.70; 1.09–2.66; women: 0.96; 0.43–2.18); but this difference was not significant in the multivariable model (P interaction = 0.227). There was an increased risk of incident slow gait among MH-medicated men but not women (hazard ratio 1.74; 1.22–2.48 vs. 0.76; 0.38–1.52, P interaction = 0.038), and a trend toward increased risk of incident NCI (1.76; 0.91, 3.39, P = 0.09) for both sexes. Conclusion Our results highlight socioeconomic and ethnic differences in prescription of MH medications. The higher proportion of opiate prescriptions among women needs confirmation and should be a priority for intervention. The greater risk of baseline NCI and incident slow gait among men may be the result of differences in toxicity, drug interactions, or persistent mental health symptoms; further investigation is needed to optimize outcomes in PLWH and prescription of mental health medications. Disclosures All authors: No reported disclosures.

INTRODUCTION The prevalence of smoking is high among the human immunodeficiency virus (HIV)-infected population, yet there are few studies of tobacco dependence treatment in this population. This paper reports the safety of varenicline versus nicotine replacement therapy (NRT) and describes preliminary results about the effectiveness of varenicline versus NRT in HIV-infected smokers. METHODS Participants completed 12 weeks of telephone counseling and either varenicline or NRT. Varenicline was encouraged as the preferred intervention; NRT was used for those unable/unwilling to take varenicline. Adverse events (AEs), related to pharmacotherapy, were monitored. Biochemically confirmed abstinence at 3 months was examined. Inverse probability of treatment weighted logistic regression models was fit to compare participants on varenicline to those on NRT. RESULTS Among participants on varenicline (n = 118), the most common AEs were nausea, sleep problems, and mood disturbances. One person reported suicidal ideation; there were no cardiovascular complications. There were no differences in the varenicline AE profile between participants on combination antiretroviral therapy (ART) and those not on ART. The percentages of confirmed abstainers were 11.8% in the NRT group and 25.6% in the varenicline group. The odds of being abstinent were 2.54 times as great in the varenicline group compared with the NRT group in the propensity weighted model (95% CI 1.43-4.49). CONCLUSIONS In this preliminary study, the safety profile of varenicline among HIV-infected smokers resembles findings among smokers without HIV. In addition, varenicline may be more effective at promoting abstinence in this population. Future randomized clinical trials are warranted.

BackgroundHuman immunodeficiency virus (HIV)-infected individuals have increased risk for vascular thrombosis, potentially driven by interactions between activated leukocytes and the endothelium.MethodsMonocyte subsets (CD14+CD16−, CD14+CD16+, CD14DimCD16+) from HIV negative (HIV−) and antiretroviral therapy-treated HIV positive (HIV+) participants (N = 19 and 49) were analyzed by flow cytometry for adhesion molecule expression (lymphocyte function-associated antigen 1 [LFA-1], macrophage-1 antigen [Mac-1], CD11c/CD18, very late antigen [VLA]-4) and the fractalkine receptor (CX3CR1); these receptors recognize ligands (intercellular adhesion molecules [ICAMs], vascular cell adhesion molecule [VCAM]-1, fractalkine) on activated endothelial cells (ECs) and promote vascular migration. Plasma markers of monocyte (soluble [s]CD14, sCD163) and EC (VCAM-1, ICAM-1,2, fractalkine) activation and systemic (tumor necrosis factor receptor [TNFR-I], TNFR-II) and vascular (lipoprotein-associated phospholipase A2 [Lp-PLA2]) inflammation were measured by enzyme-linked immunosorbent assay.ResultsProportions of CD16+ monocyte subsets were increased in HIV+ participants. Among all monocyte subsets, levels of LFA-1 were increased and CX3CR1 levels were decreased in HIV+ participants (P < .01). Levels of sCD163, sCD14, fractalkine, ICAM-1, VCAM-1, TNFR-II, and Lp-PLA2 were also increased in HIV+ participants (P < .05), and levels of sCD14, TNFR-I, and TNFR-II were directly related to ICAM-1 and VCAM-1 levels in HIV+ participants. Expression of CX3CR1 on monocyte subsets was inversely related to plasma Lp-PLA2 (P < .05 for all).ConclusionsIncreased proportions of CD16+ monocytes, cells with altered adhesion molecule expression, combined with elevated levels of their ligands, may promote vascular inflammation in HIV infection.

Objective. We sought to compare clearance rates of plasma human immunodeficiency virus type 1 (HIV-1) RNA in men and women starting triple-nucleoside-based versus efavirenz (EFV)-based regimens. Methods. First- and second-phase decay rates of plasma HIV-1 were compared in men and women initiating a triple nucleoside reverse-transcriptase inhibitor (NRTI) regimen versus regimens that included EFV plus an NRTI. Subjects (n = 64) were randomized to receive zidovudine/lamivudine/abacavir (triple-nucleoside regimen), zidovudine/lamivudine plus EFV (3-drug EFV regimen) or zidovudine/lamivudine/abacavir plus EFV (4-drug EFV regimen). Plasma HIV-1 RNA levels were fitted to a biexponential viral-dynamics model using a nonlinear mixed-effects model. Nonparametric Wilcoxon tests compared empirical Bayes estimates of first- and second-phase viral decay rates between treatment arms and sex. Results. Median first-phase viral decay rates were significantly faster in subjects receiving the 3-drug EFV regimen (0.67/day), compared with those receiving the triple-nucleoside regimen (0.56/day; P = .02). The second-phase viral decay rate was also faster in the 3-drug EFV group than in the triple-nucleoside group (P = .09). Decay rates in the 4-drug EFV group were intermediate. Viral decay rates were not significantly different in men and women. Conclusions. Faster initial viral decay in subjects randomized to a 3-drug EFV-based regimen corresponded to the overall superior efficacy of that regimen. Viral decay rates did not differ by sex.

Descriptions of the durability and consequences of immune reconstitution in patients who start highly active antiretroviral therapy (HAART) while severely immunosuppressed are limited.Patients with previous CD4+ cell counts50 cells/mm3, all of whom had HAART-induced increases in CD4+ cell counts of100 cells/mm3 on 2 separate occasions (measured sequentially at least 4 weeks apart), were enrolled in a prospective trial and observed every 16-32 weeks. Evaluations included assessments for new opportunistic complications, virologic (human immunodeficiency virus [HIV] RNA load) and immunologic (CD4+ cell count) responses, or death.The median follow-up duration for 612 subjects was 184 weeks (range, 8-216 weeks). The rate of increase in CD4+ cell counts was approximately 5.9 cells/mm3 every 8 weeks, with the degree of increase associated with the baseline HIV RNA load (500 vs.or =500 copies/mL). Subsequent measurements of virologic suppression based on HIV RNA levels were also associated with predicted CD4+ cell responses. Thirty-three AIDS-defining illnesses were reported (1.75 events per 100 person-years of follow-up);40% (14 cases) occurred with higher than expected CD4+ cell counts.CD4+ cell count increases are related to virological control, with continuing increases seen in individuals who are immunosuppressed. Opportunistic illnesses and/or complications are infrequent but can occur at any time, even in patients who maintained an elevated CD4+ cell count.

We conducted a multicenter, prospective study of the risk factors, natural history, and outcome of fluconazole-refractory mucosal candidiasis (FRMC) in 832 persons with advanced human immunodeficiency virus (HIV) infection (median CD4 cell count, 14/mm3) during 1994-1996. FRMC was defined as mucosal candidiasis that failed to resolve despite 14 days of therapy with daily doses (> or =200 mg) of fluconazole. Thirty-six persons (4.3%) had FRMC (35, oral; 1, esophageal), for an incidence of 4.2 per 100 person-years (859.7 total years of follow-up). In a multivariate model, the use of trimethoprim-sulfamethoxazole within 6 months of enrollment (relative risk [RR], 2.39; P=.04) and the use of fluconazole daily or every other day (RR, 5.64; P=.004) were significantly associated with the development of FRMC. The median survival after the development of FRMC was 32.6 weeks. In conclusion, the annual incidence of FRMC was