Thomas O’Bryan

D-Dimer Levels before HIV Seroconversion Remain Elevated Even after Viral Suppression and Are Associated with an Increased Risk of Non-AIDS Events

The mechanism underlying the excess risk of non-AIDS diseases among HIV infected people is unclear. HIV associated inflammation/hypercoagulability likely plays a role. While antiretroviral therapy (ART) may return this process to pre-HIV levels, this has not been directly demonstrated. We analyzed data/specimens on 249 HIV+ participants from the US Military HIV Natural History Study, a prospective, multicenter observational cohort of >5600 active duty military personnel and beneficiaries living with HIV. We used stored blood specimens to measure D-dimer and Interleukin-6 (IL-6) at three time points: pre-HIV seroconversion, ≥6 months post-HIV seroconversion but prior to ART initiation, and ≥6 months post-ART with documented HIV viral suppression on two successive evaluations. We evaluated the changes in biomarker levels between time points, and the association between these biomarker changes and future non-AIDS events. During a median follow-up of 3.7 years, there were 28 incident non-AIDS diseases. At ART initiation, the median CD4 count was 361cells/mm3; median duration of documented HIV infection 392 days; median time on ART was 354 days. Adjusted mean percent increase in D-dimer levels from pre-seroconversion to post-ART was 75.1% (95% confidence interval 24.6–148.0, p = 0.002). This increase in D-dimer was associated with a significant 22% increase risk of future non-AIDS events (p = 0.03). Changes in IL-6 levels across time points were small and not associated with future non-AIDS events. In conclusion, ART initiation and HIV viral suppression does not eliminate HIV associated elevation in D-dimer levels. This residual pathology is associated with an increased risk of future non-AIDS diseases.

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.

Self-administration of intranasal influenza vaccine: Immunogenicity and volunteer acceptance

BACKGROUND In outbreak settings, mass vaccination strategies could maximize health protection of military personnel. Self-administration of live attenuated influenza vaccine (LAIV) may be a means to vaccinate large numbers of people and achieve deployment readiness while sparing the use of human resources. METHODS A phase IV, open-label, randomized controlled trial evaluating the immunogenicity and acceptance of self-administered (SA) LAIV was conducted from 2012 to 2014. SA subjects were randomized to either individual self-administration or self-administration in a group setting. Control randomized subjects received healthcare worker-administered (HCWA) LAIV. Anti-hemagglutinin (HAI) antibody concentrations were measured pre- and post-vaccination. The primary endpoint was immunogenicity non-inferiority between SA and HCWA groups. Subjects were surveyed on preferred administration method. RESULTS A total of 1077 subjects consented and were randomized (529 SA, 548 HCWA). Subject characteristics were very similar between groups, though SA subjects were younger, more likely to be white and on active duty. The per-protocol analysis included 1024 subjects (501 SA, 523 HCWA). Post-vaccination geometric mean titers by vaccine strain and by study group (HCWA vs. SA) were: A/H1N1 (45.8 vs. 48.7, respectively; p=0.43), A/H3N2 (45.5 vs. 46.4; p=0.80), B/Yamagata (17.2 vs. 17.8; p=0.55). Seroresponses to A components were high (∼67%), while seroresponses to B components were lower (∼25%). Seroresponse did not differ by administration method. Baseline preference for administration method was similar between groups, with the majority in each group expressing no preference. At follow-up, the majority (64%) of SA subjects preferred SA vaccine. CONCLUSIONS LAIV immunogenicity was similar for HCWA and SA vaccines. SA was well-tolerated and preferred to HCWA among those who performed SA.

Toxoplasma gondii seroprevalence: 30-year trend in an HIV-infected US military cohort

To determine if Toxoplasma gondii IgG antibody prevalence is declining in HIV-infected persons, we analyzed data (1984-2013) from the US Military HIV Natural History Study. We found that T. gondii seroprevalence at enrollment was associated with age and decreased significantly after 1995 (P=0.004), similar to the general US population.

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.