Plasma Cytokine Levels and Risk of HIV Type 1 (HIV-1) Transmission and Acquisition: A Nested Case-Control Study Among HIV-1–Serodiscordant Couples

Kahle, Erin; Bolton, Michael J.; Donnell, Deborah; Fong, Youyi; Celum, Connie; Wald, Anna; Lingappa, Jairam R.; Magaret, Amalia; Hughes, James P.; Corey, Lawrence; Baeten, Jared M.; McElrath, M. Juliana; Coetzee, David; Fife, Kenneth H.; Were, Edwin; Essex, Max; Makhema, Joseph; Katabira, Elly; Ronald, Allan; Bukusi, Elizabeth A.; Cohen, Craig R.; Kanweka, William; Kapiga, Saidi; Manongi, Rachel; Farquhar, Carey; John‐Stewart, Grace; Kiarie, James; Allen, Susan; Inambao, Mubiana; Farm, Orange; Delany‐Moretlwe, Sinead; Rees, Helen; Bruyn, Guy de; Gray, Glenda; McIntyre, James; Mugo, Nelly

doi:10.1093/infdis/jiu621

Cited by 50 publications

(47 citation statements)

References 44 publications

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“…In fact, it has been reported that BCG vaccination in South African newborns induced an increase in CCR5 ϩ and in HLA-DR/CD38 ϩ -expressing CD4 ϩ T cells (11,12), raising the question of whether BCG-induced CD4 ϩ T cell activation might increase the risk of HIV-1 acquisition in the pediatric population. Further, immune activation in the intestine or other sites of virus entry has been associated with increased HIV or SIV acquisition in humans and in nonhuman primates (59)(60)(61)(62)(63)(64). This conclusion is supported by our findings that infant macaques vaccinated with AMtb or BCG vaccines had increased CD4 ϩ CCR5 ϩ T cells in blood and in tissues that serve as presumed entry sites for SIV after oral exposure.…”

Section: Trained Immunity and Immune Activation Of Tb Vaccinessupporting

confidence: 71%

Balancing Trained Immunity with Persistent Immune Activation and the Risk of Simian Immunodeficiency Virus Infection in Infant Macaques Vaccinated with Attenuated Mycobacterium tuberculosis or Mycobacterium bovis BCG Vaccine

Jensen

Pena-Ponce

Piatak

et al. 2017

Clin Vaccine Immunol

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Our goal is to develop a pediatric combination vaccine to protect the vulnerable infant population against human immunodeficiency virus type 1 (HIV-1) and tuberculosis (TB) infections. The vaccine consists of an auxotroph Mycobacterium tuberculosis strain that coexpresses HIV antigens. Utilizing an infant rhesus macaque model, we have previously shown that this attenuated M. tuberculosis (AMtb)-simian immunodeficiency virus (SIV) vaccine is immunogenic, and although the vaccine did not prevent oral SIV infection, a subset of vaccinated animals was able to partially control virus replication. However, unexpectedly, vaccinated infants required fewer SIV exposures to become infected compared to naive controls. Considering that the current TB vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG), can induce potent innate immune responses and confer pathogen-unspecific trained immunity, we hypothesized that an imbalance between enhanced myeloid cell function and immune activation might have influenced the outcome of oral SIV challenge in AMtb-SIV-vaccinated infants. To address this question, we used archived samples from unchallenged animals from our previous AMtb-SIV vaccine studies and vaccinated additional infant macaques with BCG or AMtb only. Our results show that vaccinated infants, regardless of vaccine strain or regimen, had enhanced myeloid cell responses. However, CD4 ϩ T cells were concurrently activated, and the persistence of these activated target cells in oral and/or gastrointestinal tissues may have facilitated oral SIV infection. Immune activation was more pronounced in BCG-vaccinated infant macaques than in AMtb-vaccinated infant macaques, indicating a role for vaccine attenuation. These findings underline the importance of understanding the interplay of vaccine-induced immunity and immune activation and its effect on HIV acquisition risk and outcome in infants.

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Section: Trained Immunity and Immune Activation Of Tb Vaccinessupporting

confidence: 71%

Balancing Trained Immunity with Persistent Immune Activation and the Risk of Simian Immunodeficiency Virus Infection in Infant Macaques Vaccinated with Attenuated Mycobacterium tuberculosis or Mycobacterium bovis BCG Vaccine

Jensen

Pena-Ponce

Piatak

et al. 2017

Clin Vaccine Immunol

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“…A woman reported situation in which she obtained a restraining order but her abusive partner violated it: The restraining order didn’t do no good, because 23 said, “It’s just a piece a paper. It’s not going to stop me.” And he proved it that it was not going to stop him.…”

Section: Resultsmentioning

confidence: 99%

“…The restraining order didn’t do no good, because 23 said, “It’s just a piece a paper. It’s not going to stop me.” And he proved it that it was not going to stop him.…”

Section: Resultsmentioning

confidence: 99%

Multiple Intimate Partner Violence Experiences: Knowledge, Access, Utilization and Barriers to Utilization of Resources by Women of the African Diaspora

Sabri¹,

Huerta

Alexander³

et al. 2015

hpu

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Objective This study examined knowledge, access, utilization, and barriers to use of resources among Black women exposed to multiple types of intimate partner violence in Baltimore, Maryland and the U.S. Virgin Islands (USVI). Methods We analyzed quantitative survey data collected by 163 women recruited from primary care, prenatal or family planning clinics in Baltimore and the USVI. In addition we analyzed qualitative data from in-depth interviews with 11 women. Quantitative data were analyzed using descriptive statistics and qualitative data were analyzed using thematic analysis. Results A substantial proportion of Black women with multiple types of violence experiences lacked knowledge of, did not have access to, and did not use resources. Barriers to resource use were identified at the individual, relationship, and community levels. Conclusion There is need for programs to develop awareness, promote access and utilization of resources, and eliminate barriers to resource use among abused Black women.

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“…Blood biomarkers have also been associated with increased risk of HIV infection [25,26]. Others from our group reported that women who later became HIV-infected had higher plasma concentrations of TNF-α, IL-2, IL-7, and IL-12p70 than women who remained uninfected [25].…”

Section: Systemic Markers Of Inflammation Chemokine Gradients and Himentioning

confidence: 99%

“…We found that these and other cytokines do not correlate between blood and the genital tract, suggesting that cytokine risk factors identified in blood do not predict those in the genital tract and vice versa [9,27]. Kahle et al found that elevated plasma IP-10 and IL-10 concentrations predicted HIV seroconversion in individuals in HIV discordant relationships [26]. …”

Section: Systemic Markers Of Inflammation Chemokine Gradients and Himentioning

confidence: 99%

Genital inflammation, immune activation and risk of sexual HIV acquisition

Passmore

Jaspan

Masson

2016

Current Opinion in HIV and AIDS

127

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Purpose: Women who have genital inflammation are at increased risk of sexual HIV infection. The purpose of this review is to evaluate the mechanisms for this relationship, causes of genital inflammation and strategies to manage this condition. Recent Findings: We have recently shown in a cohort of South African women that HIV seroconversion was associated with persistently raised genital inflammatory cytokines (including MIP-1α, MIP-1β and IP-10). Elevated inflammatory cytokine concentrations may facilitate HIV infection by recruiting and activating HIV target cells and disrupting the mucosal epithelial barrier. BV and STIs, which are predominantly asymptomatic in women, cause lower genital tract inflammation and increased HIV acquisition risk. In Africa, where syndromic management of STIs and BV is standard-of-care, the substantial burden of asymptomatic infections has likely contributed to high HIV incidence rates. Summary: A genital inflammatory profile contributes to the high risk of HIV acquisition in African women. STIs and BV are poorly managed in Africa and other developing nations and as such remain major drivers of persistent genital inflammation and HIV acquisition among these women.

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Plasma Cytokine Levels and Risk of HIV Type 1 (HIV-1) Transmission and Acquisition: A Nested Case-Control Study Among HIV-1–Serodiscordant Couples

Abstract: Immune activation, as measured by levels of cytokine markers, particularly elevated levels of IL-10 and CXCL1, are associated with increased HIV-1 susceptibility and infectiousness.

Cited by 50 publications

References 44 publications

Balancing Trained Immunity with Persistent Immune Activation and the Risk of Simian Immunodeficiency Virus Infection in Infant Macaques Vaccinated with Attenuated Mycobacterium tuberculosis or Mycobacterium bovis BCG Vaccine

Balancing Trained Immunity with Persistent Immune Activation and the Risk of Simian Immunodeficiency Virus Infection in Infant Macaques Vaccinated with Attenuated Mycobacterium tuberculosis or Mycobacterium bovis BCG Vaccine

Multiple Intimate Partner Violence Experiences: Knowledge, Access, Utilization and Barriers to Utilization of Resources by Women of the African Diaspora

Genital inflammation, immune activation and risk of sexual HIV acquisition

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