Background: Inaccurate HIV risk perception by men who have sex with men (MSM) is a barrier to HIV prevention. Providing information about objective HIV risk could improve preexposure prophylaxis (PrEP) uptake. Methods: PrEP Accessibility Research & Evaluation 2 (PrEPARE2) was a randomized controlled trial of MSM to determine if an objective risk score affects future PrEP uptake. Participants completed a baseline survey to assess demographics, risk behaviors and HIV selfperceived risk (SPR). The survey generated a calculated HIV risk score (CalcR), estimating HIV risk based on reported condomless anal intercourse and sexually transmitted infections, and was provided to individuals in the intervention arm. Participants were contacted 8 weeks later to determine if they initiated PrEP. Results: Of 171 participants (median age 32; 37% Hispanic or Non-Hispanic Black; median 5 sexual partners in past 6 months), 81% had heard of PrEP, and 57% thought they were good PrEP candidates. SPR had poor agreement with CalcR (kappa=0.176) with 38% underestimating their HIV risk. At week 8, only 14 of 135 participants had initiated PrEP with no difference between arms (CalcR 11%, control 10%, p>0.99). The most common reason for not starting PrEP was low HIV risk perception. There was a relative decrease in SPR over time (p=0.06) but no difference between arms (p=0.29). Conclusion: Providing an objective HIV risk score alone did not increase PrEP uptake. HIV testing performed at testing sites may be a crucial time to correct misperceptions about risk and initiate same-day PrEP given enthusiasm for PrEP on testing day to facilitate greater uptake.

APS is the association of antiphospholipid antibodies (aPL) with thromboses and/or recurrent pregnancy loss (RPL). Among patients with SLE, one-third have aPL and 10–15% have a manifestation of secondary APS. Animal studies suggested that complement activation plays an important role in the pathogenesis of thrombosis and pregnancy loss in APS. We performed a cross-sectional study on complement proteins and genes in 525 patients with aPL. Among them, 237 experienced thromboses and 293 had SLE; 111 had both SLE and thromboses, and 106 had neither SLE nor thrombosis. Complement protein levels were determined by radial immunodiffusion for C4, C3 and factor H; and by functional ELISA for mannan binding lectin (MBL). Total C4, C4A and C4B gene copy numbers (GCN) were measured by TaqMan-based realtime PCR. Two to six copies of C4 genes are frequently present in a diploid genome, and each copy may code for an acidic C4A or a basic C4B protein. We observed significantly (a) higher protein levels of total C4, C4A, C4B, C3, and anticardiolipin (ACLA) IgG, (b) increased frequencies of lupus anticoagulant and males, and (c) decreased levels of complement factor H, MBL and ACLA-IgM among patients with thrombosis than those without thrombosis ( N = 288). We also observed significantly lower GCNs of total C4 and C4A among aPL-positive patients with both SLE and thrombosis than others. By contrast, aPL-positive subjects with SLE had significantly reduced protein levels of C3, total C4, C4A, C4B and ACLA-IgG, and higher frequency of females than those without SLE. Patients with thrombosis but without SLE ( N = 126), and patients with SLE but without thrombosis ( N = 182) had the greatest differences in mean protein levels of C3 ( p = 2.6 × 10 −6 ), C4 ( p = 2.2 × 10 −9 ) and ACLA-IgG ( p = 1.2 × 10 −5 ). RPL occurred in 23.7% of female patients and thrombotic SLE patients had the highest frequency of RPL (41.0%; p = 3.8 × 10 −10 ). Compared with non-RPL females, RPL had significantly higher frequency of thrombosis and elevated C4 protein levels. Female patients with homozygous C4A deficiency all experienced RPL ( p = 0.0001) but the opposite was true for patients with homozygous C4B deficiency ( p = 0.017). These results provide new insights and biomarkers for diagnosis and management of APS and SLE.

These findings suggest breastfeeding promotion should target women early and include sensitive, effective ways to promote breastfeeding among women who have not previously successfully breastfed. Breastfeeding history should be elicited, and plans to pump should be supported prenatally.

ObjectiveSystemic lupus erythematosus (SLE) features high frequency of cardiovascular disease (CVD) and fluctuating complement levels. The clinical trial Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) aimed to evaluate whether atorvastatin treatment reduced the progression of atherosclerosis in 221 patients with childhood-onset SLE (cSLE), using carotid intima media thickness (CIMT) as surrogates. We leveraged APPLE biorepository and trial data to investigate the relationship between complement and CVD in cSLE.MethodsGene copy numbers (GCNs) for total C4, C4A and C4B were measured by TaqMan-based real-time PCR and Southern blotting, and analysed with laboratory and clinical parameters through Student’s t-test and χ2 analyses. Effects of total C4, C4A and C4B GCNs on the response to placebo or atorvastatin treatment and progression of CIMT were examined by regression analyses.ResultsAt baseline, C4 protein levels strongly correlated with GCNs of total C4 (p=1.8×10−6). Each copy of C4 gene increased mean serum C4 by 3.28 mg/dL. Compared with those without hypertension (N=142), individuals with hypertension demonstrated significantly elevated serum levels for C4 and C3 at baseline and serially (C4: P=5.0×10−25; C3: P=5.84×10−20). Individuals with ≥2 C4B genes had 2.5 times the odds of having hypertension (p=0.016) and higher diastolic blood pressure (p=0.015) compared with those with C4B deficiency. At the study end, subjects with ≥2 C4B and atorvastatin treatment had significantly slower increase in CIMT compared with those treated with placebo (p=0.018).ConclusionscSLE with hypertension had elevated serum levels of C4 and C3 and higher GCN of C4B; cSLE with ≥2 C4B genes would benefit from statins therapy to prevent atherosclerosis.

Background Despite being at high risk for depression, patients with childhood-onset systemic lupus erythematosus (c-SLE) are infrequently and inconsistently screened for depression by their pediatric rheumatologists. We aimed to systematically increase rates of formal depression screening for c-SLE patients in an academic Pediatric Rheumatology clinic. Methods Our multi-disciplinary quality improvement (QI) team used electronic health record (EHR) documentation to retroactively calculate baseline rates of documented depression screening using the Patient Health Questionnaire-9 (PHQ-9). We then engaged key stakeholders to develop a clinical workflow for formal depression screening in the clinic. We also provided education to providers regarding mental health disorders in c-SLE, with an emphasis on prevalence, screening methods, and management of positive screens. We then used the Plan-Do-Study Act (PDSA) method of QI to systematically evaluate and adjust our process in real time. The primary outcome was the percentage of patients with c-SLE seen per month who had a documented PHQ-9 screening within the past year. Results The percentage of children with documented PHQ-9 results ranged from 0 to 4.5 % at baseline to 91.0 % within 12 months of project initiation. By the end of the project, monthly screening rates greater than 80 % has been sustained for 10 months. As a result of these efforts, twenty-seven (48.2 %) patients with at least mild depressive symptoms were identified while seven (12.5 %) with thoughts of self-harm were referred to appropriate mental health resources. Conclusions Routine formal depression screening is feasible in a busy subspecialty clinic. Using QI methods, rates of formal depression screening among children with c-SLE were increased from an average of 3.3 % per month to a sustained monthly rate of greater than 80 %. Individuals with depressive symptoms and/or thoughts of self-harm were identified and referred to appropriate mental health resources.

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BackgroundAntiphospholoipid syndrome (APS) is the association of antiphospholipid antibodies (aPL) with thromboses and/or recurrent pregnancy loss (RPL). Among patients with SLE, one-third have aPL and 10%–15% have a manifestation of secondary APS. Although mouse models suggested complement drives the pathogenesis of APS, we have little knowledge on how complement proteins and genes contribute to the pathology of human APS, and the concurrence of SLE and APS.MethodsWe performed a cross-sectional study on complement proteins and genes in 525 patients with aPL. Among them, 237 experienced thromboses and 293 had SLE; 111 had both SLE and thromboses, and 106 had neither SLE nor thrombosis. Complement protein levels were determined by radial immunodiffusion for C4, C3 and factor H; and by functional ELISA for mannan binding lectin (MBL). Total C4, C4A and C4B gene copy numbers (GCN) were measured by TaqMan-based realtime PCR.ResultsTwo to six copies of C4 genes are frequently present in a diploid genome, and each copy may code for an acidic C4A or a basic C4B protein. We observed significantly (a) higher protein levels of total C4, C4A, C4B, C3 and anticardiolipin (ACLA) IgG, (b) increased frequencies of lupus anticoagulant and males, and (c) depressed levels of complement factor H, MBL and ACLA-IgM among patients with thrombosis than those without thrombosis (n=288). We also observed significantly lower GCNs of total C4 and C4A among aPL-positive patients with both SLE and thrombosis than others. By contrast, aPL-positive subjects with SLE had significantly reduced protein levels of C3, total C4, C4A, C4B and ACLA-IgG, and higher frequency of females than those without SLE. Patients with thrombosis but without SLE (n=126), and patients with SLE but without thrombosis (n=182) had the greatest differences in mean protein levels of C3 (p=2.6×10–6), C4 (p=2.2×10–9) and ACLA-IgG (p=1.2×10–5). RPL occurred in 23.7% of female patients and thrombotic SLE patients had the highest frequency of RPL (41.0%; p=3.8×10–10). Compared with non-RPL females, RPL had significantly higher frequency of thrombosis and elevated C4 protein levels. Female patients with homozygous C4A deficiency all experienced RPL (p=0.0001) but the opposite was true for patients with homozygous C4B deficiency (p=0.017).ConclusionsThere are substantial differences for complement protein concentrations and genetic diversities among aPL-positive patients with thromboses, recurrent pregnancy loss and SLE. These results are relvant for diagnosis and management of APS and SLE.Funding Source(s):This work was supported by NIH grants 1 R01 AR050078, 1 R21070905, 1 R01 AR073311 (CYY), and RR00046 (UNC).

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