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The role of natural killer cells in preventing HIV-1 acquisition and controlling disease progression.Naranbhai, Vivek. January 2013 (has links)
In sub-Saharan Africa, women carry a disproportionate burden of the Human
Immunodeficiency Virus Type 1 (HIV-1) pandemic. The high risk of HIV
acquisition in these women and the variability in their disease progression is
not fully understood. Natural Killer (NK) cells, which are innate immune
antiviral lymphocytes, present systemically and at mucosal surfaces, may play
a role in preventing HIV acquisition and/or altering disease progression, as
they are key early mediators of the response to viral infections and are
equipped to kill infected cells.
The purpose of this study was to evaluate the role of NK cells in HIV-1
acquisition and following acquisition, in disease progression.
The study participants were selected women who were participating in a
randomized controlled trial assessing the effectiveness of 1% Tenofovir gel in
preventing HIV-1 (CAPRISA 004 trial). The study design was a case-control
study nested within the cohorts followed up in the CAPRISA 004 trial. In this
trial, 889 sexually-active women aged 18-40 years were randomized to
receive Tenofovir or placebo gel and prospectively followed. Assessment of
HIV infection was performed monthly by rapid HIV-1 antibody tests,
supplemented by HIV-1 RNA polymerase chain reaction (PCR), p24 Western
blotting and/or ELISA. Samples obtained prior to the first positive rapid
antibody test were retrospectively tested by HIV specific PCR to identify
window period infections. The date of infection in this study was estimated as
the midpoint between the last negative and first positive antibody test, or 14
days prior to the first HIV-1 RNA-PCR positive result. Multi-parametric flow
cytometry techniques developed and validated in healthy blood donors were
used to asses the bidirectional relationship between NK cells and HIV-1. To
simulate in vivo interaction between NK cells and autologous HIV infected
cells, an in vitro infection and coculture assay was used in addition to
conventional assays of NK cell recognition of HLA-deficient cell lines. These
were supplemented with measurement of plasma cytokines by Luminex and
microbial products by ELISA. In this study, 44 cases who acquired HIV-1 were
sampled prior to infection and 39 controls who remained HIV-1 negative
despite high behavioural exposure at the timepoint when their preceding
sexual activity was highest. To understand how HIV infection affected NK
cells during early HIV-1 infection, the first sample obtained after acquisition
was studied and compared to preinfection samples from the same participant.
The case and control groups were broadly similar in the proportions using
tenofovir gel, proportions infected with HSV-2 and number of sexual partners
but tended to be marginally older than cases (27.6 vs 23.3 years). By design
control women had higher sexual activity than cases (mean 11 vs. 5.7 sex
acts per month).
The frequency of IFN-γ secreting NK cells from women who acquired HIV
infection were significantly lower than from women who remained uninfected
in response to 721 cells-an EBV transformed B cell line (background-adjusted
median 13.7% vs. 21.6%; p=0.03) and to autologous HIV infected T-cells
(background-adjusted median 0.53% vs. 2.09%; p=0.007). NK cells from HIV
acquirers displayed impaired proliferation but enhanced spontaneous
degranulation compared with non-acquirers after co-culture with HIV
uninfected or infected autologous T-cell blasts. Adjusting for age, gel arm,
HSV-2 infection status and levels of NK cell activation, IFN-γ+ NK cell
responses to autologous HIV infected cells were associated with reduced
odds of HIV acquisition (OR 0.582; 95% CI 0.35-0.98; p=0.04). In addition,
even in the absence of ex vivo stimulation, HIV acquirers had higher levels of
generalised innate immune activation measured by systemic cytokine
concentrations (TNF-α, IL2, IL-7 and IL12p40), peripheral blood platelet
concentrations (p=0.038), and non-specific ex vivo NK cell activation
(p<0.001). Generalised NK cell activation measured directly ex vivo without
stimulation was associated with acquisition. Further, if innate immune
activation was assembled as a principal component in an unsupervised
fashion but taking into account all the measures made, it was significantly
associated with HIV acquisition (OR adjusted for age, tenofovir gel use, and
HSV-2 status for PC with innate immune factor loadings 11.27; 95% CI 1.84-
69.09; p=0.009). The causes of preinfection innate immune activation could
not be established in this study but the degree of activation could not be
explained by microbial translocation as both HIV acquirers and non-acquirers
had similar levels of plasma lipopolysaccharide (LPS), soluble CD14 (sCD14)
and intestinal fatty-acid binding protein (I-FABP). Similarly, both HIV acquirers
and non-acquirers had similar NK cell and cytokine responses to Toll-like
Receptor (TLR)-2, 3 or 7/8 agonists 11. During early HIV-infection, NK cells
demonstrated significantly higher activation (p=0.03), expression of Killer-cell
immunoglobulin-like Receptors (KIR) (p=0.006) and expression of chemokine
receptor 7 (CCR7, p<0.0001) compared with prior to acquisition. Although NK
cells had reduced cytolytic potential following HIV acquisition, antiviral IFN-γ
secretion appeared to be preserved. NK cell responses were not different
between tenofovir and placebo gel recipients, but women who acquired HIV
whilst using tenofovir gel had higher gag-specific IFN-γ CD4+ T-cell
responses during early infection.
Overall, the findings suggest that the frequency of NK cells producing IFN-γ
specifically after co-culture with HIV-1 infected target cells was associated
with protection from HIV-1 acquisition but, generalised, non-specific activation
of NK cells and other innate immune components enhanced HIV acquisition.
Since neither microbial translocation nor TLR responsiveness were
associated with pre-existing immune activation further studies will be required
to identify the drivers of generalised innate immune activation. Methods to
dampen generalised innate immune activation and/or augment specific NK
cell antiviral responses in women at risk for HIV-1 may reduce HIV-1
acquisition.
During primary HIV-1 infection, NK cells underwent impairment of cytolytic
function but not IFN-γ secretory function; this may affect their ability to affect
disease progression. Although Tenofovir gel did not alter innate immune
responses in women with breakthrough infection, it preserved HIV-specific Tcell
immune responses, the consequences of which need further exploration.
Understanding how Tenofovir gel mediated preservation of adaptive immune
responses may lead to interventions that will reinforce protective host
responses.
In conclusion, innate immune responses by NK cells have been shown to
impact HIV acquisition; HIV-specific IFN-γ responses by NK cells were
protective while generalised NK activation was detrimental. The causes of
innate immune activation are not known but these effects were independent of
the impact of Tenofovir gel. Future prevention strategies targeting mucosal
transmission of HIV should assess their impact on NK cell responses, to avoid
general innate immune activation and enhance their ability to protect against HIV acquisition. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2013.
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HIV, sex, life, and death : a cluster analysis of the "HIV Stops With Me" campaign / Human immunodeficiency viruses, sex, life, and deathVittone, Tracy J. January 2004 (has links)
Chapter One introduces the "HIV Stops With Me" campaign, research by communication scholars on how HIV/AIDS messages are channeled, cultural influences, and the target audience of these messages in order to answer: What is the "HIV Stops With Me" campaign saying about individuals infected with HIV?Chapter Two describes the cluster analysis developed by Kenneth Burke. The steps in cluster analysis are: 1) identifying the key terms in the rhetoric, 2) charting the terms that cluster around the key terms, 3) discovering emergent patterns in the clusters, and 4) naming the motive, or situation, based on the meanings of the key terms.Chapter Three is a cluster analysis of the 2002 San Francisco "HIV Stops With Me" campaign. Key terms found in this analysis are "HIV," "sex," "life/living," and "death/dying."Chapter Four contains conclusions pertaining to the analysis of the rhetorical artifact, conclusions for cluster analysis, and future implications for academic scholarship. / Department of Communication Studies
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A health technology assessment of HIV counseling and testing technologiesHutchinson, Angela Blair 07 June 2004 (has links)
No description available.
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Contemporary Approaches to Addressing HIV Prevention Needs Among Sexual and Gender Diverse Individuals in KazakhstanLee, Yong Gun January 2022 (has links)
Renewed efforts are needed to address rapidly rising HIV incidence among sexual and gender diverse (SGD) individuals—particularly cisgender gay, bisexual, and other men (MSM) and transgender and nonbinary individuals (TSM) who have sex with men—in Kazakhstan. Intervention research is uniquely positioned to advance HIV prevention through surveying factors shaping the HIV epidemic among MSM and TSM in Kazakhstan, developing and testing the effects of an HIV prevention intervention, and assessing overall social impacts of conducting research. This research proceeded to describe strategies and lessons learned during implementation of a stepped wedge clinical trial of an intervention designed to increase the number of MSM and TSM in the HIV care continuum in Kazakhstan cities of Almaty, Shymkent, and Nur-Sultan.
Thus, this three-paper dissertation aimed to: (1) identify psychosocial factors associated with lifetime, past-12-month, and past-6-month HIV testing among a sample of MSM and TSM enrolled in the clinical trial; (2) describe the process of implementing remote training of facilitators for remotely delivering the HIV preventive intervention; and (3) assess social impacts of participating in the clinical trial. MSM and TSM from the study cities were recruited into the clinical trial and administered a structured behavioral survey at their primary visit and at follow-up visits every six months thereafter.
After a period of no intervention implementation (‘pre-implementation period’), the intervention was implemented sequentially every six months in the study cities. Among 304 MSM and TSM enrolled in the clinical trial during the pre-implementation period, lifetime and past-12-month HIV testing were positively associated with polydrug use and negatively with sexual transmission HIV risk, and past-6-month HIV testing was negatively associated with sexual risk. The process of developing and implementing remote training of facilitators was guided by a protocol outlining phases involving formative assessment and planning, fundamentals training, and feedback loop and technical assistance.
Out of 627 MSM and TSM who completed their primary assessment during the clinical trial, 579 (92%) returned for at least one follow-up visit; of these individuals, 88% reported at least one positive social impact, while 2% reported at least one negative social impact. Findings underscore the value of expanding access to substance use treatment for HIV prevention among MSM and TSM in Kazakhstan, the viability of remote training of facilitators for remote intervention delivery, and the feasibility of conducting HIV prevention research involving MSM and TSM with many benefits and few risks.
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The efficacy of graphic imagery in HIV/AIDS prevention campaigns : a case study of lovelife outdoor materialOjo, Olutunmise Adesola January 2009 (has links)
Thesis (M. Tech.) - Central University of Technology, Free State, 2009 / The aim of health communication campaigns and visual communication material (VCM) is to positively influence audience health behaviour and attitude. VCM has been used in this respect effectively as a vehicle to convey information about HIV/AIDS over the past three decades. It has been used to promote health knowledge and awareness in order to reduce the transmission of the virus.
The aim of this study was to determine the efficacy of graphic imagery in HIV/AIDS VCM.
To realise this aim, the researcher set the following objectives:
* To review relevant literature in order to isolate key features and process those that communicators must consider/follow when developing HIV/AIDS VCM;
* To determine the comprehension of selected outdoor HIV/AIDS messages, the graphics used in these messages, illustration preferences, and an evaluation of the self-efficacy of selected loveLife outdoor visual messages; and
* To propose a model that communicators can use as a guideline when developing
VCM.
The outcome of the review suggests a compilation of features, design guidelines and variables that may contribute to the effectiveness of VCM. The results of the empirical study indicate that suitable graphic imagery fosters message comprehension, while inappropriate imagery inhibits comprehension, and realistic and appropriate imagery is preferred to abstract and representational imagery. Familiar images can contribute towards improved comprehension of HIV/AIDS messages. These findings also gave birth to the proposed ‘O’ communication model, which is a reflection of the results of the empirical study.
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Women's vulnerability, sexual power and prevention of stigma : what do prevention campaigns tell usBue, Martine Eriksen 04 1900 (has links)
Thesis (MA)--Stellenbosch University, 2014. / ENGLISH ABSTRACT: The HIV-epidemic that is evident in South Africa today is infecting more women than men. This is
mostly due to the vulnerability that women are facing in sexual relationships, where they are not able
to negotiate the terms and conditions of their sexual engagement. Patriarchy, the culture of masculinity
and a general male dominance influence women’s dependency on their man and agency inside and
outside of the home, and contribute to the oppression of women both generally in society and sexually.
Women have by this not the control over their own bodies and are for this reason in a high-risk
position of contracting HIV. The vulnerability is further linked to the stigmatisation that women
experience if they do try to negotiate preventative measures to reduce the risk of transmission. The
fear of being stigmatised as ‘loose’ or HIV-positive by both men and women if suggesting condom
use, inhibits women to propose the necessary actions for protection. Stigmatising behaviours also
impact on a person’s fear of becoming HIV-positive and reduces the likelihood of getting tested,
disclose one’s status to sexual partners and receive treatment.
This thesis examines cultural and socio-economic issues that contribute to gender inequality in South
Africa, and can generate stigma towards women on the basis of HIV and AIDS. This is done by using
radical feminism as the theoretical framework for contextualising how women are situated in the
South African society, in terms of general and sexual agency. Through the method of content analysis
and the findings from the theoretical framework, the thesis further analyses how the three HIVprevention
campaigns loveLife, Brothers for Life and TAC manage to address the issues related to
stigma based on HIV/AIDS, which are directed towards women. Race, class and gender are all factors that influence the likelihood of becoming HIV-infected and of
becoming stigmatised. Women’s low social status situates women in a position where they are more
probable to be the object of stigmatisation since they already are considered lower in rank. If the
women also are of colour, poor and low educated the chances of becoming stigmatised on the basis of
HIV and AIDS are even more likely, the same is the chances of becoming HIV-infected. This
indicates that poor, uneducated black women are the group that is most vulnerable towards
stigmatisation as well as towards HIV-transmission.
Socio-economic and cultural factors have a strong influence on the gender inequality in sexual
relationships found in South Africa, which cause HIV to spread and can generate stigmatising
behaviours. Stigmatisation on the basis of HIV/AIDS is therefore important to address in order to
reduce the number of new HIV-infections. The three campaigns analysed for this thesis did neither directly address stigma on a general level nor directed towards women. The campaigns are therefore
considered to be missing an important feature of HIV-prevention in South Africa. / AFRIKAANSE OPSOMMING: Die huidige Suid-Afrikaanse Vigsepidemie infekteer meer vroue as mans. Dit is die geval weens die
kwesbaarheid wat vroue ervaar in seksuele verhoudings, waar vroue nie die mag het om die
omstandighede van hul seksuele interaksies te onderhandel nie. Patriargie, die kultuur van manlikheid
en ‘n algemene manlike dominansie beïnvloed vroue se mag en dra by tot die onderdrukking van
vroue, beide in die samelewing in die algemeen en in seksuele verhoudings. Om hierdie rede het vroue
nie beheer oor hul eie liggame nie en daarom ervaar hulle ‘n hoë risiko om MIV op te doen.
Hierdie kwesbaarheid word ook verbind aan die stigmatisering wat vroue ervaar wanneer hulle
probeer om voorkomende aksie te neem ten einde die risiko van Vigsoordrag te verminder. Die vrees
om deur mans en ander vroue gestigmatiseer te word as iemand met ‘losse sedes’, of as iemand wat
MIV-positief is wanneer hulle kondoomgebruik voorstel, weerhou vroue daarvan om die nodige
voorkomende aksie vir selfbeskerming te neem. Stigmatiserende gedrag het ook ‘n impak op ‘n mens
se vrees om MIV-positief te word en verminder die waarskynliheid dat jy jouself vir die virus sal laat
toets, dat iemand hul status aan seksuele maats sal verklaar, of behandeling sal ontvang. Diegene wat
reeds MIV onder lede het is bang om hul status te verklaar weens die gepaardgaande stigma.
Hierdie tesis ondersoek kulturele en sosio-ekonomiese kwessies wat bydra tot geslagsongelykheid in
Suid-Afrika, en wat stigma kan veroorsaak teenoor vroue met betrekking tot MIV and Vigs. Die studie
analiseer dan of Vigsveldtogte hierdie stigma kan aanspreek. Dit word gedoen deur radikale
feminisme toe te pas as ‘n teoretiese raamwerk om vroue se plek in die Suid-Afrikaanse samelewing te
kontekstualiseer, beide in terme van algemene en seksuele mag. Die metode van inhoudsanalise word
toegepas om drie Vigsvoorkomingsveldtogte (loveLife, Brothers for Life en TAC) te analiseer en vas
te stel of en hoe hulle kwessies wat betrekking het op stigma teenoor vroue aanspreek. Sosio-ekonomiese en kulturele faktore het ‘n sterk invloed op die geslagsongelykeid in seksuele
verhoudings in Suid-Afrika; dit lei daartoe dat MIV versprei word en kan stigmatiserende gedrag
vererger. Om hierdie rede is dit belangrik dat MIV/Vigsvoorkomingsveldtogte stigmatisering
aanspreek ten einde gedrag te wysig en om die getal nuwe Vigsbesmettings te laat daal. Die drie
veldtogte wat in hierdie tesis geanaliseer is het beide nagelaat om stigma direk aan te spreek op ‘n
algemene vlak, en was ook nie direk gerig op vroue nie. Die veldtogte kan daarom beskou word as
ontoereikend deurdat hulle belangrike komponente van MIV-voorkomig in Suid-Afrika misgekyk het.
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