Negative Antibody Test Research Articles

Persistent Negative Antibody Test in COVID-19 Patient: A Case Report.

Persistent Negative Antibody Test in COVID-19 Patient: A Case Report.

Immunosuppression-induced clonal T-cell lymphoproliferative disease causing severe diarrhoea mimicking coeliac disease following renal transplantation: a case report

BackgroundPost-transplant lymphoproliferative disease is a recognized complication following solid organ transplantation. This is usually a B cell disease and frequently associated with Epstein Barr virus infection, although T cell PTLD can occur. T cell PTLD is usually a monomorphic, lymphomatous disease associated with an adverse prognosis.Case reportWe report a 52 year old male pre-emptive renal transplant recipient who developed severe diarrhea with weight loss following intensification of his immunosuppression due to antibody mediated rejection 3 years after transplantation. Duodenal biopsy demonstrated monoclonal CD8+ T cell duodenitis leading to increased intraepithlieal lymphocytes and sub-total villous atrophy mimicking coeliac disease. Coeliac disease was excluded by negative anti-tissue transglutaminase antibody, HLA-DQ2 and HLA-DQ8 testing. There was no evidence of lymphoma either on biopsy or CT enterography and no FDG avid disease on PET. Symptoms did not improve with reduction of immunosuppression, but resolved fully on complete withdrawal of treatment. The transplant failed and he was established on dialysis. The diagnosis was early PTLD.ConclusionsOesophagogastroduodenoscopy with small bowel biopsies is a useful investigation for determining the cause of diarrhoea in renal transplant patients when more common causes have been excluded. This is the first report that we are aware of clonal T cell PTLD mimicking coeliac disease which only resolved after complete withdrawal of immunosuppression. As treatments for lymphoma are aggressive they are only initiated in the malignant phase and management of early stage PTLD is to minimise risk of progression by reducing immunosuppression. Any plans to retransplant will have to take into consideration the possibility that PTLD will recur.

1457-P: Clinical, Biochemical, and Genetic Profile of Patients with Young-Onset Diabetes in North India

Background: Increasing prevalence of diabetes (type 1 and type 2) and obesity along with declining age of onset of type 2 diabetes, often create a diagnostic error in subtyping patients with young onset diabetes. Correct diagnosis of type of diabetes in this age group has clinical implications for management and longterm prognosis. In this study, we aimed to profile all consecutive young onset diabetes patients with respect to their clinical, biochemical, and genetic characteristics. Material and Methods: In this prospective study, conducted at a tertiary facility, all patients with diabetes onset between 18-30 years and diabetes duration less than 5 years were included. Assessment included detailed clinical and biochemical evaluation, autoantibody testing, c-peptide and genetic screening. Results: Total 100 patients were studied, out of which 80% were males and 55% were obese. Mean age of onset and median duration of diabetes were 24.98 ± 3.27 years and 18.0 months respectively. Initial clinical presentation was weight loss and osmotic symptoms in 58%, diabetic ketoacidosis in 5% and 25% patients were incidentally diagnosed. 20.8% of clinically autoimmune diabetes patients had negative antibody testing, 35.5% of clinically nonautoimmune diabetes had positive antibody testing. Overall, evidence of autoimmunity and decreased insulin secretion were found in 45% and 45% patients respectively. Ultrasound abdomen revealed small/atrophic pancreas in 9% of patients out of which nearly half did not had history of pancreatitis. Three patients were detected as MODY (1 = HNF1A and 2 = PAX4 mutations). One patient had Wolfram like syndrome (WFS1 mutation), 30 patients had variants of unknown significance. Conclusion: Evidence of autoimmunity was seen in 45%, monogenic diabetes in 4%, obesity in 55% of the study population. Higher incidence and aggressive nature of diabetes in young individuals are probably due to contributing effect of autoimmunity accompanied by increasing prevalence of obesity. Disclosure P.K. Reddy: None. G. Jevalikar: None. A.A. Singhal: None. P. Kaur: None. A. Gupta: None. S.K. Mishra: None. J.S. Wasir: None. M.S. Kuchay: Speaker’s Bureau; Self; Abbott, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. B. Bansal: None. K. Farooqui: None. H. Kaur: None. A. Mithal: Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Johnson & Johnson, Lilly Diabetes, Novo Nordisk A/S.

Detection of IgM and IgG antibodies against SARS-CoV-2 in patients with autoimmune diseases.

Detection of IgM and IgG antibodies against SARS-CoV-2 in patients with autoimmune diseases.

Repetitive ocular vestibular evoked myogenic potentials in myasthenia gravis.

To validate the repetitive ocular vestibular evoked myogenic potentials (RoVEMP) test for diagnostic use in myasthenia gravis (MG) and to investigate its value in diagnostically challenging subgroups. The RoVEMP test was performed in 92 patients with MG, 22 healthy controls, 33 patients with a neuromuscular disease other than MG (neuromuscular controls), 4 patients with Lambert-Eaton myasthenic syndrome, and 2 patients with congenital myasthenic syndrome. Mean decrement was significantly higher in patients with MG (28.4% ± 32.2) than in healthy controls (3.2% ± 13.9; p < 0.001) or neuromuscular controls (3.8% ± 26.9; p < 0.001). With neuromuscular controls as reference, a cutoff of ≥14.3% resulted in a sensitivity of 67% and a specificity of 82%. The sensitivity of the RoVEMP test was 80% in ocular MG and 63% in generalized MG. The RoVEMP test was positive in 6 of 7 patients with seronegative MG (SNMG) with isolated ocular weakness. Of 10 patients with SNMG with negative repetitive nerve stimulation (RNS) results, 73% had an abnormal RoVEMP test. The magnitude of decrement was correlated with the time since the last intake of pyridostigmine (B = 5.40; p = 0.019). The RoVEMP test is a new neurophysiologic test that, in contrast to RNS and single-fiber EMG, is able to measure neuromuscular transmission of extraocular muscles, which are the most affected muscles in MG. Especially in diagnostically challenging patients with negative antibody tests, negative RNS results, and isolated ocular muscle weakness, the RoVEMP test has a clear added value in supporting the diagnosis of MG. This study provides Class III evidence that RoVEMP distinguishes MG from other neuromuscular diseases.

Stiff limb syndrome with lower limb myoclonus

Rationale:stiff limb syndrome (SLS) is a variant of stiff-man syndrome, primarily affecting a specific limb. Its diagnosis has always been challenging due to the lack of a specific confirmation test. We present a rare case of a patient with lower limb myoclonus and rigidity.Patient concerns:A 53-year-old male presented with a sudden onset of progressive left lower extremity myoclonus and muscle rigidity for 3 days. He rapidly showed signs of right lower limb involvement with severe joint stiffness and inability to walk.Diagnosis:The symptoms nature, physical examination, careful elimination of differential diagnosis suggested a diagnosis of stiff limb syndrome.Interventions:Intravenous infusion of gamma globulin 0.4 mg/kg coupled with baclofen and clonazepam were given after admission. He also received an injection of botulinum toxin A to relieve his muscle stiffness.Outcomes:The patients’ condition improved after the initial treatment with complete disappearance of muscle twitching. Further improvements were seen later on after the local administration of botulinum toxin A.Lessons:Stiff limb syndrome shares the same complex symptoms with many other conditions. Its diagnosis relies heavily on clinical presentations and on ruling out other conditions. However, unusual symptoms such as myoclonus can occur in few cases and together with the rarity of the condition, the prevalence of misdiagnosis is high. Therefore, being aware and recognizing the signs and symptoms is crucial for proper management. Additionally, EMG is a very important test if the present condition is suspected. However, a negative EMG result or a negative anti-glutamic acid decarboxylase antibody test should not exclude SLS diagnosis.

1267. Contribution of Acute Infection to the Community Viral Load of an HIV Care Program

BackgroundIndividuals with acute HIV infection (AHI) are a priority for public health due to higher viral loads and greater risk of transmission. Despite potential clinical and public health benefits, rapid or immediate ART can be resource-intensive, with programmatic implications. We measured the contribution of AHI to our programs community viral load (VL) to inform our expanded testing and linkage to care program.MethodsWe calculated the contribution to the community VL for 3 HIV-positive groups from January 1, 2016 to September 1, 2018; (1) AHI (p24 antigen-positive, negative or indeterminate supplemental antibody testing), (2) new diagnoses (ND), and (3) existing diagnoses (ED). Persons who were AHI or ND were ART naïve at first VL. The contribution of each group to community VL was calculated at the first and second VL assays. Group contributions were characterized as (1) percentage of the total HIV-positive population, and (2) group contribution to community VL.Results217 persons tested positive for HIV and had an initial VL, and 69 persons linked to our program had a second VL. Time intervals between first and second VL measurements were similar between groups (Kruskal–Wallis P = 0.55). Initial VL medians were significantly different by group (Kruskal–Wallis P < 0.001), partly due to the large number of ED in care and virally suppressed ( <200 copies/mL) at first VL (n = 82). AHI contributed the fewest persons to the HIV-positive population (7.8%), but contributed the most to first VL (58.6%). ART reduced VL for all groups. The median time from diagnosis to treatment for AHI was 5.5 days (IQR 4–21). Due to both natural decay and ART, AHI contributed the least to total VL load at second assay (5.6%). Using previously published data on treated and untreated VL decay, a delay in ART of 15 days would resulted in an estimated VL of 17,721 copies/mL (95% confidence interval (537- 53,576) vs. the estimated VL with ART, 131 copies/mL (95% CI 5–294), a 135-fold increase in AHI VL.ConclusionPatients with AHI are small proportion of our cohort compared with ND and ED, but account for the greatest portion of our community VL. These data quantifies the benefit of rapid initiation of ART for AHI to reduce community VL, a priority for prevention efforts. Disclosures All authors: No reported disclosures.

2335. Newborn Dried Blood Spot for Retrospective Diagnosis of Congenital Cytomegalovirus (CMV) Infection: It’s Time for Universal Screening!

BackgroundThe diagnosis of congenital cytomegalovirus (cCMV) infection requires that CMV be detected in a body fluid before 3 weeks of age. After 3 weeks, a diagnosis of cCMV infection is difficult since one cannot differentiate between prenatal, natal, and postnatal CMV acquisition. Infants who refer on the newborn hearing screen often are diagnosed with hearing loss after 3 weeks of age. Our objective was to describe the use of the newborn dried blood spot (DBS) for detection of CMV DNA in infants who are evaluated for sensorineural hearing loss (SNHL).MethodsRetrospective review of the electronic health records of infants who were referred to the Neonatal Infectious Disease (NEO-ID) Clinic at Nationwide Children’s Hospital, Columbus, OH since 2015 for evaluation of SNHL. Demographic, clinical, laboratory, and radiographic data were reviewed. With maternal informed consent, the newborn DBS was obtained from the Ohio Department of Health for detection of CMV DNA by polymerase chain reaction (PCR) testing as previously described (Boppana et al. JAMA, 2010).ResultsEighteen infants (gestational age [mean ± SD], 38 ± 4 weeks; birth weight, 3,094 ± 705 g) with SNHL were referred by Otolaryngology for evaluation of possible cCMV infection; 17 (94%) had referred on the newborn hearing screen. The 18 infants were first tested for CMV at 151 ± 124 days of age (mean ±SD; range, 21–521 days), and 3 (17%) had a positive CMV DBS. Fourteen (78%) of the 18 infants had a positive serum CMV IgG antibody while 5 (63%) of 8 infants had CMV DNA detected in urine by PCR. Of the 3 infants with a positive CMV DBS, 2 were tested for CMV DNA PCR in urine and both were positive. Of the 3 infants, 1 had a negative serum CMV IgG antibody test at 174 days of age but the urine CMV PCR test was positive. In comparison, of 54 infants with cCMV infection confirmed by a positive urine CMV PCR in the first 3 weeks of age, 37 (68%) had a positive CMV DBS.ConclusionDBS testing for CMV DNA by PCR testing identified a small minority of infants with SNHL and thus confirming congenital infection. However, the overall sensitivity of CMV DBS testing in our cohort was 68%, suggesting that some infants with SNHL due to congenital CMV infection are missed.Disclosures All authors: No reported disclosures.

Do Myelin Oligodendrocyte Glycoprotein Antibodies Represent a Distinct Syndrome?

Do Myelin Oligodendrocyte Glycoprotein Antibodies Represent a Distinct Syndrome?

Symptoms in noninfectious uveitis in a pediatric cohort: Initial presentation versus recurrences

To describe the prevalence of symptoms with noninfectious uveitis (NIU) in a pediatric cohort and to assess the association between the presence of symptoms with first episode of uveitis (first-U) compared to symptoms at uveitis recurrence. The medical records of patients with NIU treated at a tertiary referral hospital from March 2008 to November 2107 were reviewed retrospectively. Symptomaticity (eye pain, eye redness, photosensitivity) was captured at initial uveitis activation and subsequent episodes. Univariate logistic regression modeling was used to identify clinical features associated with symptomatic first-U. Ordinal regression identified patient characteristics associated with symptomatic recurrence. A total of 118 cases were reviewed; of these, 92 were followed for at least 6months and had at least 1 reactivation. Juvenile idiopathic arthritis-related uveitis (JIAU) was the most common diagnosis (67/118 [57%]), followed by idiopathic uveitis (33%). In the majority, uveitis was restricted to the anterior chamber (82%). Of the 118 cases, 58 patients (49%) had symptomatic first-U, 34% JIA versus 69% non-JIA. Non-JIAU, age ≥7years, and negative antinuclear antibody (ANA) test were significantly associated with symptomatic first-U; spondyloarthritis was not. With recurrence, half had symptoms: 41% JIA versus 66% non-JIA. Of those who had symptomatic first-U, 35% were asymptomatic at recurrence. Those with JIA had 50% or less odds of symptomaticity at reactivation. Complications did not vary based on having had symptoms at first-U. Non-JIA diagnosis, older age, and ANA-negativity were associated with symptomatic first-U in our study cohort, but no patient characteristics were significantly associated with symptomatic recurrence. Clinical patterns may change during disease course, with uveitis switching from symptomatic to asymptomatic, which has implications for uveitis monitoring recommendations.

Mental health outcomes for individuals with chronic hepatitis C infection.

ObjectiveUsing data from the 2011–2015 IBM MarketScan® Commercial Claims and Encounters, we sought to assess the relationship between mental health outcomes and chronic hepatitis C infection after adjusting for important confounders. Persons with HCV antibody and RNA test results between 2011 and 2015 and continuous enrollment in fee-for-service plans were included in the analysisIntroductionHepatitis C virus (HCV) infection is a leading cause of liver disease-related morbidity and mortality in the United States and HCV incidence has been increasing. Mental illness may impact the likelihood of initial HCV infection, progress and adherence to treatment along the hepatitis C care cascade, and risk of subsequent reinfection for those cured of hepatitis C. The relationship between HCV infection and mental illness is not well understood and many studies have lacked sufficient sample size to adjust for important confounders. We sought to explore the association between chronic HCV infection and mental illness after adjusting for important confounders.MethodsWe obtained data from the 2011–2015 IBM MarketScan® Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits databases. These data consist of inpatient and outpatient service claims for persons with employer-sponsored health insurance coverage and their dependents. Persons with HCV antibody and RNA test results between 2011 and 2015 and continuous enrollment in a fee-for-service plan were included in the analysis. Chronic HCV infection was defined by a positive HCV RNA test result. Controls without chronic HCV infection had a negative HCV antibody test result and no positive HCV antibody or RNA test result in the preceding or following year. The index date was defined by the date of the earliest positive HCV RNA or negative HCV antibody test. Demographic characteristics were obtained from the MarketScan® enrollment tables. All enrollees in the study population were at least 18 years old during the year of the index date. The analysis sample was restricted to persons who were identified as receiving outpatient prescription drug claims data feeds. We estimated adjusted odds ratios (OR) for the association between mental illness (ICD-9 code 295 or 296) and HCV RNA status. Multivariate models included age (18-44, 45-64, 65+ years), sex, region, and an adjusted Charlson Comorbidity Index which excluded liver disease and hepatocellular carcinoma.ResultsWe identified 2,847 individuals with chronic HCV infection (HCV RNA+) and 57,418 controls who were HCV antibody negative. With respect to age, 83% of HCV RNA+ individuals were aged 45-64 years while only 43% of the HCV antibody negative individuals were in the same age range. Similarly, for sex, 62% and 40% of HCV RNA+ individuals and controls, respectively, were male. For unadjusted analyses, age, sex, region, comorbid conditions, and mental illness (OR= 2.25 [95% CI; 1.52 - 3.34]) were all statistically associated with HCV RNA+. For the multivariate adjusted models, these same variables remained statistically significant. For the multivariate model, individuals with a mental illness were more likely to be HCV RNA+ relative to HCV antibody negative controls. (OR= 1.95 [95% CI; 1.30 - 2.93]).ConclusionsThis study demonstrated a strong association between mental illness and HCV chronic infection after adjusting for important confounders including other comorbid conditions. A growing body of research suggests that persons with mental illness are at increased risk for contracting and transmitting HCV due to high rates of substance use and high-risk sexual behavior among infected persons as well as high rates of sexual victimization. HCV prevention efforts should be directed toward individuals with mental illness or seeking treatment for mental illness.

PF-06881893 (Nivestym™), a Filgrastim Biosimilar, Versus US-Licensed Filgrastim Reference Product (US-Neupogen®): Pharmacokinetics, Pharmacodynamics, Immunogenicity, and Safety of Single or Multiple Subcutaneous Doses in Healthy Volunteers.

BackgroundThree comparative clinical studies assessed the pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity and safety of PF-06881893 (filgrastim-aafi; Nivestym™), a filgrastim biosimilar, versus US-licensed reference product (filgrastim; US-Neupogen®) in healthy volunteers (HVs).MethodsTwo separate open-label, crossover-design PK/PD studies were conducted: a single-dose study (n = 24) and a multiple-dose study (n = 60). In each study, HVs were randomized to Nivestym followed by US-Neupogen, or vice versa. Study drug (5 μg/kg) was administered subcutaneously as a single injection or as five consecutive daily injections. Primary PK and PD endpoints were area under the filgrastim serum concentration–time curve, maximum observed concentration, area under the effect curve (AUEC) for absolute neutrophil count (ANC), maximum observed ANC, AUEC for cluster of differentiation (CD)-34+ count, and maximum observed CD34+ count. In an open-label, parallel-design, non-inferiority, comparative immunogenicity study, HVs were randomized (n = 128/treatment) to Nivestym or US-Neupogen. The primary endpoint was the proportion of subjects with a negative baseline antidrug antibody (ADA) test result and one or more confirmed post-dose positive ADA result.ResultsOverall demographics were as follows: female (n = 162/340); White (n = 274/340), Black (n = 58/340), and other (n = 8/340); age (18–65 years); and weight (50.8–96.5 kg). All primary PK and PD endpoints met the pre-specified criteria for PK and PD equivalence. The primary endpoint in the comparative immunogenicity study met pre-specified criteria for non-inferiority.ConclusionsNivestym demonstrated PK and PD equivalence in single and multiple subcutaneous-dose settings and non-inferiority for immunogenicity to US-Neupogen, with a comparable safety profile, supporting the demonstration of biosimilarity.Trial registrationClinicalTrials.gov C1121002 (NCT02766647); C1121003 (NCT02766634); C1121012 (NCT02923791).Electronic supplementary materialThe online version of this article (10.1007/s40259-019-00343-8) contains supplementary material, which is available to authorized users.

Test4HepC: Promoting Hepatitis C Testing to Baby Boomers Using Social Media.

Individuals born between 1945 and 1965 ("baby boomers") account for an estimated three quarters of all hepatitis C (HCV) infections in the United States. This article describes the evaluation of Test4HepC, a program that uses social media and a website to promote HCV testing to baby boomers in Los Angeles County, California. The first 16 months of Test4HepC were evaluated using an online survey (n = 302), qualitative interviews (n = 20), website and social media analytics, and records of free testing offered though the program. Test4HepC.org had 6,919 visitors; 48 individuals used the free testing offered. Within 1 month of visiting the website, 24.5% (74) of survey participants tested for HCV, 67.6% (50) received a negative HCV antibody test result, 2.7% (2) received a positive HCV antibody test result, and 25.7% (19) had not received their results as of taking the survey. Most of those not tested (60.5%) reported intention to test. In multivariable analysis, male sex and high perceived usefulness of the program website were associated with HCV testing. Qualitative interviews suggested that Test4HepC increased baby boomers' HCV risk perception and encouraged testing. Social media is a promising strategy for promoting HCV testing to baby boomers. Expanding Test4HepC to other areas and prioritizing the highest risk baby boomers could enable many people with HCV to benefit from new treatments.

BHIVA/BASHH guidelines on the use of HIV pre-exposure prophylaxis (PrEP) 2018.

We aim to provide evidence-based guidance on best clinical practice in the provision, monitoring and support of pre-exposure prophylaxis (PrEP) for the prevention of HIV acquisition. The guidelines include: (i) Guidance on risk assessment prior to PrEP; (ii) Baseline assessment; (iii) Dosing schedules; (iv) Monitoring; (v) Supporting adherence; (vi) Buying generic PrEP; and (vii) Cost-effectiveness. The guidelines are aimed at clinical professionals directly involved in, and responsible for, HIV prevention, and at community advocates and organisations responsible for supporting HIV prevention strategies in those at risk of HIV acquisition. A detailed review of the evidence base is included in Section 4. Sections 5 to 7 are intended to offer practical guidance in risk assessment, starting PrEP, ongoing management while on PrEP and stopping PrEP.

Clinical Utility of Rheumatoid Factor and Anti-Cyclic Citrullinated Peptide Antibody in the Diagnosis and Evaluation of Disease Activity in Patients of Rheumatoid Arthritis

Background: Rheumatoid arthritis (RA), a chronic systemic inflammatory disease affects around 0.75% of adult Indian population and is characterized by multiple deformities. Diagnosis of RA is primarily based on clinical manifestations and serological evidence, with rheumatoid factor (RF) being the serological marker tested the most. The diagnostic specificity of RF in RA is poor as it is found in other rheumatic and non-rheumatic diseases. Anticyclic citrullinated peptide antibodies (Anti-CCP) are a better diagnostic and prognostic marker for RA, in contrast to RF, because of their early presence and high specificity. Methods: The present study was conducted in the Department of Microbiology and Department of Rheumatology Government Medical College and Hospital Srinagar from January 2017 to December 2017 where in a total of 300 patients with clinical features suggestive of RA were included. Anti-CCP antibody, RF, and C-Reactive Protein (CRP) levels were estimated in all these patients. Results: On the basis of clinical evaluation and serological evidence, 216 (72%) patients were diagnosed as cases of RA and 84 (28%) were classified as having other non-rheumatoid disorder Females represented majority of the patients. Anti-CCP antibody, RF and CRP reactivity were significantly more in RA patients. The sensitivity and specificity of anti-CCP antibody and RF were found to be 60.65% & 96.43% and 49.07% & 76.19% respectively. Conclusions: Anti-CCP antibodies are a highly specific marker for RA in our patient population making it a good modality in patients with early disease, in whom a timely diagnosis is most needed. The low sensitivity of the test indicates that a negative anti-CCP antibody test does not exclude disease, but its high specificity means that a positive result markedly increases the probability that the patient will have RA. Thus, anti-CCP testing is a must in patients suspected of having RA to aid in early diagnosis.

Acquisition of tenofovir-susceptible, emtricitabine-resistant HIV despite high adherence to daily pre-exposure prophylaxis: a case report

Pre-exposure prophylaxis (PrEP) with emtricitabine and tenofovir disoproxil fumarate is highly protective against HIV infection. We report a case of tenofovir-susceptible, emtricitabine-resistant HIV acquisition despite high adherence to daily PrEP. Adherence to PrEP was assessed by measuring concentrations of emtricitabine and tenofovir disoproxil fumarate or their metabolites in plasma, dried blood spots, and hair. After seroconversion, genotypic and phenotypic resistance of the acquired virus was determined by standard clinical tests and by single-genome sequencing of proviral genomes. HIV partner services identified the likely transmission partner. A 21-year-old Latino man tested positive for HIV infection 13 months after PrEP initiation. He had a negative HIV antibody test, but detectable HIV RNA with 559 copies per mL. He reported good adherence to daily PrEP. He was linked to care and immediately started antiretroviral therapy, at which point his RNA was 1544 copies per mL and his HIV antibody test was positive. The HIV genotype revealed Met184Val, Leu74Val, Leu100Ile, and Lys103Asn mutations in reverse transcriptase, and the phenotype showed susceptibility to tenofovir disoproxil fumarate and resistance to emtricitabine. Segmental hair analysis of tenofovir disoproxil fumarate concentrations measured in 1 cm segments of hair from the scalp indicated consistently high adherence to PrEP in each of the 6 months before HIV diagnosis (0·0672-0·0889 ng/mg). Concentrations of tenofovir diphosphate (1012 fmol per punch) and emtricitabine triphosphate (0·266 fmol per punch) in a dried blood spot indicated high adherence over the preceding 6 weeks. Concentrations of emtricitabine (870·5 ng/mL) and tenofovir disoproxil fumarate (188·2 ng/mL) measured in plasma 3 months before HIV seroconversion confirmed adherence in the days preceding that visit. The likely transmission partner was not engaged in HIV primary care and had a similar viral genotype. Acquisition of HIV virus that is susceptible to tenofovir disoproxil fumarate, but resistant to emtricitabine can occur despite high adherence to PrEP. Quarterly screening for HIV and sexually transmitted diseases facilitates early diagnosis in people on PrEP; when combined with prompt linkage to care and partner services this can prevent onward transmission of HIV. US National Institutes of Health.

Viral Loads Within 6 Weeks After Diagnosis of HIV Infection in Early and Later Stages: Observational Study Using National Surveillance Data.

BackgroundEarly (including acute) HIV infection is associated with viral loads higher than those in later stages.ObjectiveThis study aimed to examine the association between acute infection and viral loads near the time of diagnosis using data reported to the US National HIV Surveillance System.MethodsWe analyzed data on infections diagnosed in 2012-2016 and reported through December 2017. Diagnosis and staging were based on the 2014 US surveillance case definition for HIV infection. We divided early HIV-1 infection (stage 0) into two subcategories. Subcategory 0α: a negative or indeterminate HIV-1 antibody test was ≤60 days after the first confirmed positive HIV-1 test or a negative or indeterminate antibody test or qualitative HIV-1 nucleic acid test (NAT) was ≤180 days before the first positive test, the latter being a NAT or detectable viral load. Subcategory 0β: a negative or indeterminate antibody or qualitative NAT was ≤180 days before the first positive test, the latter being an HIV antibody or antigen/antibody test. We compared median earliest viral loads for each stage and subcategory in each of the first 6 weeks after diagnosis using only the earliest viral load for each individual.ResultsOf 203,392 infections, 56.69% (115,297/203,392) were reported with a quantified earliest viral load within 6 weeks after diagnosis and criteria sufficient to determine the stage at diagnosis. Among 5081 infections at stage 0, the median earliest viral load fell from 694,000 copies/mL in week 1 to 125,022 in week 2 and 43,473 by week 6. Among 30,910 infections in stage 1, the median earliest viral load ranged 15,412-17,495. Among 42,784 infections in stage 2, the median viral load declined from 44,973 in week 1 to 38,497 in week 6. Among 36,522 infections in stage 3 (AIDS), the median viral load dropped from 205,862 in week 1 to 119,000 in week 6. The median earliest viral load in stage 0 subcategory 0α fell from 1,344,590 copies/mL in week 1 to 362,467 in week 2 and 47,320 in week 6, while that in subcategory 0β was 70,114 copies/mL in week 1 and then 32,033 to 44,067 in weeks 2-6. The median viral load in subcategory 0α was higher than that in subcategory 0β in each of the first 6 weeks after diagnosis (P<.001).ConclusionsIn the 1st week after diagnosis, viral loads in early infections are generally several times higher than those in later stages at diagnosis. By the 3rd week, however, most are lower than those in stage 3. High viral loads in early infection are much more common in subcategory 0α than in subcategory 0β, consistent with 0α comprising mostly acute infections and 0β comprising mostly postacute early infections. These findings may inform the prioritization of interventions for prevention.

A Rare Case of Plasmablastic Lymphoma with Gastric Involvement

Plasmablastic lymphoma (PBL) is a relatively rare, but highly aggressive lymphoma commonly found in the setting of HIV disease.PBL is defined by the World Health Organization as a “diffuse proliferation of large neoplastic cells most of which resemble B-cell immunoblasts, but in which all tumor cells have a plasma cell immunophenotype.”Here we present a unique case of Ann Arbor Stage IV PBL with extranodal gastric involvement diagnosed in an immunocompetent male. An 80-year-old Hispanic male presented to the emergency department with nausea and epigastric pain for four days duration. The patient also endorsed progressive dysphagia to solids and liquids over the past several weeks prior to presentation. Significant findings on physical exam included a pale, well-nourished male with mild epigastric tenderness on light palpation. CT scan revealed diffuse thickening of the gastric wall with a 7.4cm x 6.5cm intraluminal infiltrating mass with luminal narrowing. An EGD was subsequently performed for better visualization and biopsy (Figure 1). Histopathologic studies ultimately identified the mass as malignant plasmablastic lymphoma with aberrant cytokeratin expression. HIV testing was negative but EBV IgG antibody testing was abnormally high. Immunophenotype analysis revealed that CD-138 was strongly positive, CD-20 was negative, CD-45 was weakly positive, and Ki-67 expression was greater than 90% (Figure 2). The patient was started on CHOP chemotherapy regimen.2659_A Figure 1. Large, 5cm, semi-circumferential, easily friable and fungating mass as observed from GE junction during EGD2659_B Figure 2. Histology and Immunophenotype Analysis. (A) High-power magnification showing atypical plasma cells. (B) CD-20 negative. (C) CD-138 positive. (D) Ki-67 Index > 90%.Recent meta-analysis has shown that the median age of diagnosis for HIV-negative PBL is 55 years. Although the pathogenesis of PBL remains incompletely understood, the association with EBV infection and the virus' role in prevention of apoptosis of B cells is well documented.EBV positivity and CD45 expression represent good prognostic indicators for this patient; on the other hand, Ann Arbor Stage IV classification and Ki-67 expression > 80% are typically associated with poor outcome. After the oral mucosa, the GI tract is the most common site of involvement for HIV-negative PBL cases. This case represents a rare phenotypic variant in which the BCL-6 transcription factor is positive, suggesting that perhaps this case is a hybrid of diffuse large B-cell lymphoma (DLBCL) and PBL. Despite the recent advances in the treatment for PBL, prognosis remains poor with the median overall survival of nine months and a 2-year overall survival rate of 10% for HIV-negative PBL.

Brief Report: The Amsterdam Symptom and Risk-Based Score Predicts for Acute HIV Infection in Men Who Have Sex With Men in San Diego.

Dijkstra et al recently described a risk- and symptom-based score moderately predictive for HIV seroconversion in the preceding 6-12 months in men who have sex with men (MSM) in Amsterdam. Our objective was to determine whether this "Amsterdam Score" could also predict for acute HIV infection (AHI) in MSM. This study is a case-control analysis of a prospectively enrolled cohort of MSM who voluntarily presented for HIV testing in San Diego. The study sample was composed of MSM who screened HIV antibody-negative and then either tested positive with AHI [HIV nucleic acid test (NAT)-positive] or tested HIV NAT-negative. The Amsterdam Score was calculated for each participant in the study sample. Score performance was assessed using receiver operating characteristic curves and their area under the curve (AUC). An optimal cutoff was determined using the Youden index. Seven hundred fifty-seven MSM (110 AHI and 647 HIV NAT-negative) were included in the analysis. AHI and HIV-negative cases were similar in age [median 32 years (interquartile range 26-42) vs 33 (27-45), respectively, P = 0.082]. The Amsterdam Score yielded a receiver operating characteristic curve with an AUC of 0.88 (95% confidence interval: 0.84 to 0.91). An optimal cutoff of ≥1.6 was 78.2% sensitive and 81.0% specific. The risk- and symptom-based Amsterdam Score was highly predictive (AUC of 0.88) of AHI in MSM in San Diego. The Amsterdam Score could be used to target NAT utilization in resource-poor settings among MSM who test HIV antibody-negative, although the potential cost-savings must be balanced with the risk of missing AHI diagnoses.

ACOG Committee Opinion No. 752: Prenatal and Perinatal Human Immunodeficiency Virus Testing.

Given the enormous advances in the prevention of perinatal transmission of human immunodeficiency virus (HIV), it is clear that early identification and treatment of all pregnant women with HIV is the best way to prevent neonatal infection and also improve women's health. Furthermore, new evidence suggests that early initiation of antiretroviral therapy in the course of infection is beneficial for individuals infected with HIV and reduces the rate of sexual transmission to partners who are not infected. Screening should be performed after women have been notified that HIV screening is recommended for all pregnant patients and that they will receive an HIV test as part of the routine panel of prenatal tests unless they decline (opt-out screening). Human immunodeficiency virus testing using the opt-out approach, which is currently permitted in every jurisdiction in the United States, should be a routine component of care for women during prepregnancy and as early in pregnancy as possible. Repeat HIV testing in the third trimester, preferably before 36 weeks of gestation, is recommended for pregnant women with initial negative HIV antibody tests who are known to be at high risk of acquiring HIV infection; who are receiving care in facilities that have an HIV incidence in pregnant women of at least 1 per 1,000 per year; who are incarcerated; who reside in jurisdictions with elevated HIV incidence; or who have signs and symptoms consistent with acute HIV infection (eg, fever, lymphadenopathy, skin rash, myalgias, arthralgias, headache, oral ulcers, leukopenia, thrombocytopenia, or transaminase elevation). Rapid screening during labor and delivery or during the immediate postpartum period using the opt-out approach should be done for women who were not tested earlier in pregnancy or whose HIV status is otherwise unknown. Results should be available 24 hours a day and within 1 hour. If a rapid HIV test result in labor is reactive, antiretroviral prophylaxis should be immediately initiated while waiting for supplemental test results. If the diagnosis of HIV infection is established, the woman should be linked into ongoing care with a specialist in HIV care for comanagement.