Robert Deiss

A Single Dose of Benzathine Penicillin G Is as Effective as Multiple Doses of Benzathine Penicillin G for the Treatment of HIV-Infected Persons With Early Syphilis

BACKGROUND Treatment guidelines recommend the use of a single dose of benzathine penicillin G (BPG) for treating early syphilis in human immunodeficiency virus (HIV)-infected persons. However, data supporting this recommendation are limited. We examined the efficacy of single-dose BPG in the US Military HIV Natural History Study. METHODS Subjects were included if they met serologic criteria for syphilis (ie, a positive nontreponemal test [NTr] confirmed by treponemal testing). Response to treatment was assessed at 13 months and was defined by a ≥4-fold decline in NTr titer. Multivariate Cox proportional hazard regression models were utilized to examine factors associated with treatment response. RESULTS Three hundred fifty subjects (99% male) contributed 478 cases. Three hundred ninety-three cases were treated exclusively with BPG (141 with 1 dose of BPG). Treatment response was the same among those receiving 1 or >1 dose of BPG (92%). In a multivariate analysis, older age (hazard ratio [HR], 0.82 per 10-year increase; 95% confidence interval [CI], .73-.93) was associated with delayed response to treatment. Higher pretreatment titers (reference NTr titer <1:64; HR, 1.94 [95% CI, 1.58-2.39]) and CD4 counts (HR, 1.07 for every 100-cell increase [95% CI, 1.01-1.12]) were associated with a faster response to treatment. Response was not affected by the number of BPG doses received (reference, 1 dose of BPG; HR, 1.11 [95% CI, .89-1.4]). CONCLUSIONS In this cohort, additional BPG doses did not affect treatment response. Our data support the current recommendations for the use of a single dose of BPG to treat HIV-infected persons with early syphilis.

Vaccine-associated reduction in symptom severity among patients with influenza A/H3N2 disease.

BACKGROUND The moderate level of protection conferred by influenza vaccines is well-known, but the vaccines ability to attenuate symptom severity among vaccinated individuals (i.e., vaccine failures) has not been established. METHODS We enrolled otherwise healthy adults who presented with influenza-like illness (ILI) at five US military hospitals between 2009 and 2014. Influenza was diagnosed and subtyped by PCR. Individual and composite severity scores were compared between those who had vs. had not received the seasonal influenza vaccine >14 days prior to enrollment. RESULTS A total of 155 cases of influenza (A/H1N1, n=69; A/H3N2, n=66; A/untyped, n=3; B, n=17) were identified, of whom 111 (72%; A/H1N1, n=44; A/H3N2, n=52; A/untyped, n=3; B, n=12) had been vaccinated. Women were significantly less likely to be vaccinated than men (49% vs. 89%; p<0.01). In multivariate analysis, vaccinated individuals were significantly less likely to report a fever >101°F (OR 0.24; 95% CI [0.10, 0.62]) and more likely to report myalgias (OR 3.31; 95% CI [1.22, 8.97]) than vaccinated individuals. Among patients with A/H3N2 infection, upper respiratory and total symptom severity scores were significantly lower for vaccinated patients during the first 2 days of illness, and differences in total symptom severity persisted over 7 days (p<0.05 for all comparisons). Differences across additional symptom categories (lower respiratory and systemic) were also observed throughout 7 days of illness in bivariate analyses. Differences in symptom severity were not observed between vaccinated and unvaccinated participants with A/H1N1 infection. CONCLUSIONS Among patients with A/H3N2 infection, receipt of seasonal influenza vaccine was associated with reduced symptom severity. Patient-centered discussion about the benefits of influenza vaccination should be expanded to include the possibility that the vaccine could attenuate symptoms.

Hepatitis B Vaccine Responsiveness and Clinical Outcomes in HIV Controllers

Background Hepatitis B virus (HBV) vaccine responsiveness is associated with reduced risk of AIDS or death in HIV-infected individuals. Although HIV controllers (HIC) typically have favorable immunologic and clinical characteristics compared to non-controllers, vaccine responsiveness has not been studied. Methods and Findings In the U.S. Military HIV Natural History Study, HBV vaccine response was defined as antibody to hepatitis B surface antigen (anti-HBs) ≥10 IU/L after last vaccination. For determination of vaccine responsiveness, HIC (n = 44) and treatment-naïve non-controllers (n = 476) were not on highly active antiretroviral therapy (HAART) when vaccinated while treated non-controllers (n = 284) received all HBV vaccine doses during viral load (VL)-suppressive HAART. Progression to AIDS or death was also compared for all HIC (n = 143) and non-controllers (n = 1566) with documented anti-HBs regardless of the timing of HBV vaccination. Positive vaccine responses were more common in HIC (65.9%) compared to HAART-naïve non-controllers (36.6%; P<0.001), but similar to non-controllers on HAART (59.9%; P = 0.549). Factors associated with vaccine response for HIC compared to HAART-naïve non-controllers include HIC status (OR 2.65, 95% CI 1.23–5.89; P = 0.014), CD4 count at last vaccination (OR 1.28, 1.15–1.45 for every 100 cells/uL; P<0.001), and number of vaccine doses administered (OR 0.56, 0.35–0.88; P = 0.011). When HIC were compared to non-controllers on HAART, only CD4 count at last vaccination was significant (OR 1.23, 1.1–1.38 for every 100 cells/uL; P<0.001). The rate of AIDS or death per 100 person/years for HIC compared to non-controllers was 0.14 (95% CI 0–0.76) versus 0.98 (95% CI 0.74–1.28) for vaccine responders and 0 (95% CI 0–2.22) versus 4.11 (95% CI 3.38–4.96) for non-responders, respectively. Conclusions HIC have improved HBV vaccine responsiveness compared to treatment-naïve non-controllers, but similar to those on VL-suppressive HAART. Progression to AIDS or death can be predicted by HBV vaccine responder status for non-controllers, however these events are rarely observed in HIC.

Seroprevalence and seroincidence of herpes simplex virus (2006-2010), Syphilis (2006-2010), and vaccine-preventable human papillomavirus subtypes (2000-2010) among US military personnel

Background Sexually transmitted infections have historically been burdensome in military populations. We describe the seroprevalence and seroincidence of vaccine-preventable human papillomavirus (VP-HPV) subtypes in a sample of 200 servicemen, along with the seroprevalence and seroincidence of herpes simplex virus (HSV-1/2) and syphilis in a sample of 200 men and 200 women. Methods Sera from 200 men, along with associated demographic data, were obtained and tested for HPV serotypes at service entry and 10 years later. Similarly, 200 active-duty men and 200 active-duty women were tested for HSV-1/2 at entry to service and 4 years later. Results The baseline prevalence of VP-HPV subtypes was 14.5%, and cumulative seroincidence of new infection was 34% over a 10-year period (n = 68). Of these, 63% (n = 43) represented HPV-6, HPV-11, or both; 18% of new infections were either HPV-16 or HPV-18, and 19% (n = 13) were a mixture of all 4 strains. At entry to military service, 33.5% of men were seropositive for HSV-1 and 1.5% were positive for HSV-2; seroincidence was 3.4 and 1.1 per 100 person-years, respectively. Among women, 39% were seropositive for HSV-1 and 4.0% for HSV-2; seroincidence was 5.5 and 3.3 per 100 person-years, respectively. There were 2 prevalent and 3 incident cases of syphilis. Conclusions Sexually transmitted infections in military populations are highly prevalent, incident, and epidemiologically distinct. Our data show the rates of HPV and HSV-1/2 acquisition that are higher than those seen in the general public, again highlighting the need for continued preventive efforts. Consideration of universal HPV vaccination among men is warranted.

The Association between Sexually Transmitted Infections, Length of Service and Other Demographic Factors in the U.S. Military.

Background Numerous studies have found higher rates of sexually transmitted infections (STIs) among military personnel than the general population, but the cumulative risk of acquiring STIs throughout an individual’s military career has not been described. Methods Using ICD-9 diagnosis codes, we analyzed the medical records of 100,005 individuals from all service branches, divided in equal cohorts (n = 6,667) between 1997 and 2011. As women receive frequent STI screening compared to men, these groups were analyzed separately. Incidence rates were calculated for pathogen-specific STIs along with syndromic diagnoses. Descriptive statistics were used to characterize the individuals within each accession year cohort; repeat infections were censored. Results The total sample included 29,010 females and 70,995 males. The STI incidence rates (per 100 person-years) for women and men, respectively, were as follows: chlamydia (3.5 and 0.7), gonorrhea (1.1 and 0.4), HIV (0.04 and 0.07) and syphilis (0.14 and 0.15). During the study period, 22% of women and 3.3% of men received a pathogen-specific STI diagnosis; inclusion of syndromic diagnoses increased STI prevalence to 41% and 5.5%, respectively. In multivariate analyses, factors associated with etiologic and syndromic STIs among women included African American race, younger age and fewer years of education. In the overall sample, increasing number of years of service was associated with an increased likelihood of an STI diagnosis (p<0.001 for trend). Conclusion In this survey of military personnel, we found very high rates of STI acquisition throughout military service, especially among women, demonstrating that STI-related risk is significant and ongoing throughout military service. Lower STI incidence rates among men may represent under-diagnosis and demonstrate a need for enhancing male-directed screening and diagnostic interventions.

Prevalence of Staphylococcus aureus Colonization and Risk Factors for Infection Among Military Personnel in a Shipboard Setting.

Staphylococcal skin and soft tissue infections (SSTIs), especially those due to methicillin-resistant Staphylococcus aureus (MRSA) are an important public health issue for the military. Limited data exist regarding the prevalence of S. aureus colonization in the shipboard setting. We conducted a cross-sectional, observational study to determine the point prevalence of S. aureus colonization among military personnel onboard a naval vessel. Asymptomatic active duty personnel completed a survey for risk factors associated with colonization and SSTIs. Culture specimens were obtained from the anterior nares, pharynx, groin, and perirectal regions. MRSA isolates underwent testing for antimicrobial resistance, virulence factors, and pulsed-field type. 400 individuals were enrolled, 198 (49.5%) of whom were colonized with S. aureus, with MRSA identified in 14 participants (3.5%). No significant risk factors were associated with MRSA colonization. USA800 was the most common colonizing MRSA strain in the cohort and was detected in 10 participants (71%). Two participants (14%) were colonized with USA300 MRSA. In this first report of S. aureus epidemiology in a shipboard setting, we observed high rates of S. aureus and MRSA colonization. Longitudinal studies are needed to document the incident rates of S. aureus colonization during shipboard deployment and its impact on SSTI risk.

Brief Report: Racial Comparison of D-dimer Levels in Us Male Military Personnel Before and After Hiv Infection and Viral Suppression

Background: D-dimer blood levels in persons with HIV infection are associated with risk of serious non-AIDS conditions and death. Black race has been correlated with higher D-dimer levels in several studies. We examined the effects of race and HIV on D-dimer over time and the impact of viral load suppression by longitudinally comparing changes in levels among healthy young adult male African Americans and whites before HIV seroconversion and before and after initiation of antiretroviral therapy (ART). Methods: We analyzed D-dimer levels and clinical and laboratory data of 192 participants enrolled in the US Military HIV Natural History Study, a 30-year cohort of military personnel infected with HIV. D-dimer levels were measured on stored sera from each participant at 3 time points: (1) before HIV seroconversion (Pre-SC), (2) ≥6 months after HIV seroconversion but before ART initiation (Post-SC), and (3) ≥6 months after ART with documented viral suppression (Post-ART). Levels were compared at each time point using nonparametric and logistic regression analysis. Results: Compared with whites (n = 106), African Americans (n = 86) had higher D-dimer levels post-SC (P = 0.007), but in the same individuals, pre-SC baseline and post-ART levels were similar (P = 0.40 and P = 0.99, respectively). There were no racial differences in CD4 cell counts, HIV RNA viral load, time from estimated seroconversion to ART initiation, and duration on ART. Conclusions: Observed longitudinally, racial differences in D-dimer levels were seen only during HIV viremia. Higher levels of D-dimer commonly observed in African Americans are likely due to factors in addition to race.

Etiology and clinical characteristics of influenza-like illness in healthy adults by hospitalization status

Abstract Background Viral respiratory infections are a common cause of hospitalization for younger, otherwise-healthy populations. In this study, we describe the epidemiology of influenza-like illness in non-elderly adults within the U.S. Military Health System (MHS) by pathogen and hospitalization status. Methods The Acute Respiratory Infection Consortium (ARIC) is a prospective cohort of patients with influenza-like illness within the MHS. Participants between 18 and 65 years of age were identified in outpatient settings between 2012 and 2017, and were excluded if pregnant, if reporting chronic cardiac, respiratory, renal, or neurologic disease, or if on long-term aspirin therapy. Demographics, nasopharyngeal swabs and symptom data were collected; swabs were tested for viral pathogens using a target-enriched multiplex PCR panel (TEM-PCRTM, Diatherix LLC). Data were analyzed to compare clinical features and risks for hospitalization. Results 397 participants met inclusion criteria. 34 participants required hospitalization; 363 were outpatients. Median length of hospitalization was 2 days. A virus was identified in 58.4% of outpatients (OP) and 55.9% of inpatients (IP); coronaviruses (63/363), enteroviruses (50/363), and influenza A (73/363) predominated in OP, whereas influenza A predominated among IP (35.3%, 12/34). There were no significant differences between OP and IP in terms of age, gender, ethnicity, or tobacco use. IP were more likely to be obese (BMI ≥30, 43.3% vs. 20.5%, P = 0.004) and less likely to have received influenza vaccination (45.5% vs. 16.9%, P > 0.001). IP with influenza did not report more severe symptoms (chills, cough, sore throat, diarrhea, myalgia, or headache) on enrollment but were more likely to have fever (temperature ≥38.0⁰ C) than OP (92.9 vs. 57.1%, P = 0.014). Conclusion Influenza A is the most frequently identified cause of hospitalization among healthy, non-elderly adults with viral respiratory infection. Although age and tobacco use may be risks for viral acquisition, they do not appear to increase the risk of hospitalization in infected patients. Non-obese BMI and influenza vaccination appear protective against hospitalization, even in a relatively healthy cohort. Disclosures L. Malone, Diatherix Laboratories: Employee, Salary; E. Grigorenko, Diatherix Laboratories: Employee, Salary; D. Stalons, Diatherix Laboratories: Employee, Salary

Calculated Globulin Adds Predictive Value to Hepatitis B Vaccine Response in HIV-infected Persons Independently of HIV Viral load and CD4 Cell Count

Abstract Background Response rates to hepatitis B (HBV) virus vaccine are low compared with the general population. Recent data suggest baseline total IgG levels add predictive value for vaccine failure. We retrospectively analyzed the relationship of calculated globulin (CG) levels with HBV vaccine response in participants in the U.S. Military HIV Natural History Study (NHS). Methods NHS is a longitudinal observational cohort of DoD active duty and beneficiaries with HIV infection, enrolling since 1986. Inclusion criteria was: (1) no current or past HBV or hepatitis C infection (2) HBV vaccination after positive HIV date, (3) available post-vaccination follow-up serum HBV surface antibody (HBsAb) test, (4) CD4 cell count, HIV RNA viral load (VL), and protein levels within 90 days prior to the last vaccine dose. Using a standard approach, CG levels were derived by subtracting the albumin level from total protein. Variables were analyzed using univariate and multivariate logistic regression model. Results Data from 674 eligible participants were analyzed. Subjects were 87% male, 44% Caucasian, 41% African-American. At time of last vaccine dose, median values were age, 34 yrs; CD4 cells/uL, 515; nadir CD4 cells/ul, 318. 51% were receiving ART and VL was <400 copies/ml in 51%. Overall, HBV vaccine response rate was 54%. Among CG quartiles, HBV vaccine response was 70%, 60%, 40% and 44% from lowest to highest quartile respectively (P < 0.001). In the multivariate analysis, CD4 cell count, VL and CG were independently associated with vaccine response (Table). Conclusion CG levels at time of last dose independently predicted successful HBV vaccine response in HIV-infected persons. These data suggest B-cell dysfunction, characterized by higher CG levels, may be clinically significant regardless of VL and CD4 cell count. Univariate Analysis* Multivariate Analysis* Age per decade 1.21 (1.04–1.43) 0.94 (0.77–1.13) Female gender 1.44 (0.91–2.27) 1.38 (0.81–2.33) Non-white race 1.11 (0.81–1.51) 1.21 (0.83–1.76) >3 vaccine doses 1.71 (1.26–2.37) 1.09 (0.79–1.59) CD4 cell at last vaccine dose (per 100 cells) 1.22 (1.14–1.31) 1.13 (1.04–1.22) VL per log 10 0.68 (0.60–0.77) 0.77 (0.65–0.97) CG above median (3.3 g/dl) 0.39 (0.29–0.53) 0.66 (0.44–0.97) Disclosures All authors: No reported disclosures.

Self-Testing is a Feasible and Acceptable Option for Identifying Extra-genital Gonorrhea (GC) and Chlamydia (CT) infections in HIV Infected Persons

Abstract Background Compliance with guidelines recommending extra-genital testing for GC/CT in HIV-infected men who have sex with men is variable. Proposed barriers to testing, such as patient reluctance and provider discomfort, could be eliminated by self-testing. In this study, we evaluate the feasibility and acceptability of extra-genital self-testing and assess the adequacy of an oral rinse for the diagnosis of GC/CT infections. Methods HIV-infected subjects receiving care at one of three military treatment facilities participated in this study. Subjects received standardized instructions on sample collection and participated in a questionnaire designed to evaluate acceptability of this method. In addition, all subjects underwent testing by their provider. Gen Probe Aptima Combo 2 assay was used for testing the swabs and the rinse. Results A total of 148 HIV-infected subjects (median age 43 years, 40% African-Americans and 35% Caucasians) enrolled in the study. Test results are tabulated below. Of the 126 oral rinses tested, 6 (4.7%) tested positive for GC and 1 for CT (0.8%). Of the 6 rinses testing positive for GC, 2 tested negative on concomitantly collected swabs, and 1 swab testing positive for GC was negative on the rinse. Of note, 2 swabs testing positive for GC on self-collection but negative on provider swabs tested positive on the rinse. Over 95% of the subjects indicated that they understood the instructions and had collected the swabs as instructed. Most subjects (≥90%) indicated that they were comfortable collecting the swabs and oral rinses at home. Approximately15% of the subjects preferred that their providers collected the swabs. Conclusion In this study, self-collected samples yielded more positive results than provider collected samples, and the performance of oral rinses and pharyngeal swabs were similar. Our results suggest self-testing is a feasible and acceptable method for collecting extra-genital samples. Adoption of self-testing could improve compliance with the guidelines. Test Results By Anatomical Site and Collection Method Provider Self Self Provider Rectal GC 5 (3.4%) 5 (3.4%) Concordant Pharyngeal GC 8 (5.4%) 6 (4.1%) Discordant Rectal CT 4 (2.7%) 6 (4.1%) Discordant Pharyngeal CT 1 (0.7%) 2 (1.3%) Discordant Disclosures All authors: No reported disclosures.