Infectious Disease

Taylor, B. S., L. Fornos, J. Tarbutton, J. Muñoz, J. A. Saber, D. Bullock, R. Villarreal and A. E. Nijhawan (2018). “Improving HIV Care Engagement in the South from the Patient and Provider Perspective: The Role of Stigma, Social Support, and Shared Decision-Making.” AIDS Patient Care STDS 32(9): 368-378.

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Initial linkage to medical care is a critical step in the HIV care continuum leading to improved health outcomes, reduced morbidity and mortality, and decreased HIV transmission risk. We explored differences in perspectives on engagement in HIV care between people living with HIV who attended (Arrived) their initial medical provider visit (IMV) and those who did not (Missed), and between patients and providers. The study was conducted in two large majority/minority HIV treatment centers in the United States (US) south, a geographical region disproportionately impacted by HIV. The Theory of Planned Behavior informed semi-structured interviews eliciting facilitators and barriers to engagement in care from 53 participants: 40 patients in a structured sample of 20 Missed and 20 Arrived, and 13 care providers. Using Grounded Theory to frame analysis, we found similar perspectives for all groups, including beliefs in the following: patients’ control over care engagement, a lack of knowledge regarding HIV within the community, and the impact of structural barriers to HIV care such as paperwork, transportation, housing, and substance use treatment. Differences were noted by care engagement status. Missed described HIV-related discrimination, depression, and lack of social support. Arrived worried what others think about their HIV status. Providers focused on structural barriers and process, while patients focused on relational aspects of HIV care and personal connection with clinics. Participants proposed peer navigation and increased contact from clinics as interventions to reduce missed IMV. Context-appropriate interventions informed by these perspectives are needed to address the expanding southern HIV epidemic.

Cheng, L., Q. Wang, G. Li, R. Banga, J. Ma, H. Yu, F. Yasui, Z. Zhang, G. Pantaleo, M. Perreau, S. Zurawski, G. Zurawski, Y. Levy and L. Su (2018). “TLR3 agonist and CD40-targeting vaccination induces immune responses and reduces HIV-1 reservoirs.” J Clin Invest. Aug 27. [Epub ahead of print].

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Activation of HIV-1 reservoirs and induction of anti-HIV-1 T cells are critical to control HIV-1 rebound after combined antiretroviral therapy (cART). Here we evaluated in humanized mice (hu-mice) with persistent HIV-1 infection the therapeutic effect of TLR3 agonist and a CD40-targeting HIV-1 vaccine, which consists of a string of 5 highly conserved CD4+ and CD8+ T cell epitope-rich regions of HIV-1 Gag, Nef, and Pol fused to the C-terminus of a recombinant anti-human CD40 antibody (alphaCD40.HIV5pep). We show that alphaCD40.HIV5pep vaccination coadministered with poly(I:C) adjuvant induced HIV-1-specific human CD8+ and CD4+ T cell responses in hu-mice. Interestingly, poly(I:C) treatment also reactivated HIV-1 reservoirs. When administrated in therapeutic settings in HIV-1-infected hu-mice under effective cART, alphaCD40.HIV5pep with poly(I:C) vaccination induced HIV-1-specific CD8+ T cells and reduced the level of cell-associated HIV-1 DNA (or HIV-1 reservoirs) in lymphoid tissues. Most strikingly, the vaccination significantly delayed HIV-1 rebound after cART cessation. In summary, the alphaCD40.HIV5pep with poly(I:C) vaccination approach both activates replication of HIV-1 reservoirs and enhances the anti-HIV-1 T cell response, leading to a reduced level of cell-associated HIV-1 DNA or reservoirs. Our proof-of-concept study has significant implication for the development of CD40-targeting HIV-1 vaccine to enhance anti-HIV-1 immunity and reduce HIV-1 reservoirs in patients with suppressive cART.

Flannery, B., C. Smith, R. J. Garten, M. Z. Levine, J. R. Chung, M. L. Jackson, L. A. Jackson, A. S. Monto, E. T. Martin, E. A. Belongia, H. Q. McLean, M. Gaglani, K. Murthy, R. Zimmerman, M. P. Nowalk, M. R. Griffin, H. Keipp Talbot, J. J. Treanor, D. E. Wentworth and A. M. Fry (2018). “Influence of Birth Cohort on Effectiveness of 2015-2016 Influenza Vaccine Against Medically Attended Illness Due to 2009 Pandemic Influenza A(H1N1) Virus in the United States.” J Infect Dis 218(2): 189-196.

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Background: The effectiveness of influenza vaccine during 2015-2016 was reduced in some age groups as compared to that in previous 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09 virus)-predominant seasons. We hypothesized that the age at first exposure to specific influenza A(H1N1) viruses could influence vaccine effectiveness (VE). Methods: We estimated the effectiveness of influenza vaccine against polymerase chain reaction-confirmed influenza A(H1N1)pdm09-associated medically attended illness from the 2010-2011 season through the 2015-2016 season, according to patient birth cohort using data from the Influenza Vaccine Effectiveness Network. Birth cohorts were defined a priori on the basis of likely immunologic priming with groups of influenza A(H1N1) viruses that circulated during 1918-2015. VE was calculated as 100 x [1 – adjusted odds ratio] from logistic regression models comparing the odds of vaccination among influenza virus-positive versus influenza test-negative patients. Results: A total of 2115 A(H1N1)pdm09 virus-positive and 14 696 influenza virus-negative patients aged >/=6 months were included. VE was 61% (95% confidence interval [CI], 56%-66%) against A(H1N1)pdm09-associated illness during the 2010-2011 through 2013-2014 seasons, compared with 47% (95% CI, 36%-56%) during 2015-2016. During 2015-2016, A(H1N1)pdm09-specific VE was 22% (95% CI, -7%-43%) among adults born during 1958-1979 versus 61% (95% CI, 54%-66%) for all other birth cohorts combined. Conclusion: Findings suggest an association between reduced VE against influenza A(H1N1)pdm09-related illness during 2015-2016 and early exposure to specific influenza A(H1N1) viruses.

Flannery, B., J. R. Chung, E. A. Belongia, H. Q. McLean, M. Gaglani, K. Murthy, R. K. Zimmerman, M. P. Nowalk, M. L. Jackson, L. A. Jackson, A. S. Monto, E. T. Martin, A. Foust, W. Sessions, L. Berman, J. R. Barnes, S. Spencer and A. M. Fry (2018). “Interim estimates of 2017-18 seasonal influenza vaccine effectiveness – United States, February 2018.” Am J Transplant 18(4): 1020-1025.

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Early and widespread influenza activity during the 2017–18 influenza season provided the opportunity to estimate interim VE against several circulating influenza viruses, including the predominant A(H3N2) virus. These interim estimates reflect ongoing challenges with the A(H3N2) vaccine component since the 2011–12 season. The interim estimate of 25% VE against A(H3N2) viruses this season indicates that vaccination provided some protection, in contrast to recently reported, nonsignificant interim estimates of 17% from Canada and 10% from Australia, and is similar to final (32%) VE estimates in the United States against A(H3N2) viruses during 2016–173.6 However, among children aged 6 months through 8 years, the interim estimates against any influenza and A(H3N2) virus infection were higher; the risk for A(H3N2) associated medically‐attended influenza illness was reduced by more than half (59%) among vaccinated children. Also, with interim VE estimates of 67% and 42% against influenza A(H1N1)pdm09 and B viruses, respectively, vaccination provided substantial protection against circulating A(H1N1)pdm09 viruses, as well as moderate protection against influenza B viruses predominantly belonging to the B/Yamagata lineage, the second influenza type B component included in quadrivalent vaccines. CDC continues to recommend influenza vaccination while influenza viruses are circulating in the community; several more weeks of influenza activity are likely. Influenza vaccination has prevented thousands of hospitalizations during previous seasons when influenza A(H3N2) viruses were predominant, including during the 2014–15 season when interim VE estimates were similar to those reported here. Appropriate use of influenza antiviral medications for treatment of severely ill persons or persons at high risk for complications from influenza who develop influenza symptoms is important, especially among older adults, who currently have the highest hospitalization rates. (Excerpt from text, p. 1021-1022; no abstract available.)

Stewart, R. J., B. Flannery, J. R. Chung, M. Gaglani, M. Reis, R. K. Zimmerman, M. P. Nowalk, L. Jackson, M. L. Jackson, A. S. Monto, E. T. Martin, E. A. Belongia, H. Q. McLean, A. M. Fry and F. P. Havers (2018). “Influenza Antiviral Prescribing for Outpatients With an Acute Respiratory Illness and at High Risk for Influenza-Associated Complications During 5 Influenza Seasons-United States, 2011-2016.” Clin Infect Dis 66(7): 1035-1041.

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Background: Influenza causes millions of illnesses annually; certain groups are at higher risk for complications. Early antiviral treatment can reduce the risk of complications and is recommended for outpatients at increased risk. We describe antiviral prescribing among high-risk outpatients for 5 influenza seasons and explore factors that may influence prescribing. Methods: We analyzed antiviral prescription and clinical data for high-risk outpatients aged >/=6 months with an acute respiratory illness (ARI) and enrolled in the US Influenza Vaccine Effectiveness Network during the 2011-2012 through 2015-2016 influenza seasons. We obtained clinical information from interviews and electronic medical records and tested all enrollees for influenza with real-time reverse-transcription polymerase chain reaction (rRT-PCR). We calculated the number of patients with ARI that must be treated to treat 1 patient with influenza. Results: Among high-risk outpatients with ARI who presented to care within 2 days of symptom onset (early), 15% (718/4861) were prescribed an antiviral medication, including 472 of 1292 (37%) of those with rRT-PCR-confirmed influenza. Forty percent of high-risk outpatients with influenza presented to care early. Earlier presentation was associated with antiviral treatment (odds ratio [OR], 4.1; 95% confidence interval [CI], 3.5-4.8), as was fever (OR, 3.2; 95% CI, 2.7-3.8), although 25% of high-risk outpatients with influenza were afebrile. Empiric treatment of 4 high-risk outpatients with ARI was needed to treat 1 patient with influenza. Conclusions: Influenza antiviral medications were infrequently prescribed for high-risk outpatients with ARI who would benefit most. Efforts to increase appropriate antiviral prescribing are needed to reduce influenza-associated complications.