<p>The Human Immune Virus (HIV) and Acquired Immuno Deficiency Syndrome (AIDS) isa pandemic that has worsened the plight of vulnerable communities and environments in Africa. It is estimated that 40,3 million adults and children are living with HIV and AIDS and 3.1 million adults and children died in 2004 in the world. Southern Africa is the most affected region with a very high HIV/AIDS prevalence rate. The primary objective of the proposed study was to examine livelihoods and coping strategies of HIV/AIDS-affected households of Zaka District in Zimbabwe. Attention was given to institutional frameworks for HIV/AIDS interventions as district and village level. A second objective of the study is whether interventions are appropriately aligned and responsive to household livelihoods and coping</p>

There are currently more than 33 million people worldwide who are infected with HIV-1 despite development of novel treatments and knowledge of prevention strategies. Within the Pumwani area of Nairobi, Kenya there is a group of commercial sex workers who are highly exposed to HIV-1. A small subset of these women have been classified as resistant to HIV-1 infection as they remain HIV un-infected despite as many as 60 unprotected sexual exposures to HIV each year. A better understanding of such a natural model of HIV resistance would be invaluable to inform the development of a protective HIV vaccine or microbicide. Globally, heterosexual transmission of HIV across mucosal surfaces is responsible for the bulk of new infections and thus it is important to examine both the macro and the micro environments of the vaginal mucosa in efforts to determine what enhances and what thwarts HIV-infection. Previous studies have shown elevated levels of RANTES, a natural ligand for the dominant HIV co-receptor CCR5, in cervicovaginal secretions of HIV-resistant women. Additionally, a novel HIV-inhibitor, Trappin-2 was previously shown to be elevated in cervicovaginal secretions of HIV-resistant women. To test the hypothesis that RANTES and Trappin-2 in cervicovaginal fluid are important mediators of HIV resistance we will: 1) measure RANTES in a much larger group of women from the Pumwani cohort, and 2) measure Trappin-2 levels in samples taken at different time points, and 3) correlate Trappin-2 levels in cervicovaginal fluid with biological confounding variables, and 4) investigate whether SDF-1 plays a role in HIV-disease progression in HIV-positive women.

APOBEC3 proteins, in particular APOBEC3G/F, are important innate host factors that contribute to protection from HIV-1 infection by inducing high levels of guanine to adenine nucleotide substitutions (termed hypermutation) during HIV-1 viral replication. These nucleotide substitutions occur at different rates and locations across the HIV-1 genome and are thought to be particularly more frequent in the pol region. The virus has evolved ways to counteract these host factors by inducing degradation of APOBEC3G/F proteins through protein interactions with HIV-1 Vif. The aim of this thesis is to characterize and investigate the role of APOBEC3G/F-mediated hypermutation in the HIV-1 genome. We identified a subset of women from the Pumwani Commercial Sex Worker (CSW) cohort with significantly higher rates of hypermutated proviruses in pol. This degree of hypermutation correlated to less severe HIV disease progression as measured by CD4+ T cell count. This was in agreement with previous studies that evidence of APOBEC-mediated hypermutation correlate with reduced disease progression, confirming APOBEC3G/F proteins role in HIV-1 disease. Furthermore, we investigated the in vitro and ex vivo interaction between HIV-1 Vif and APOBEC3G from subjects infected with hypermutated and non-hypermutated proviruses. In vitro studies indicated that HIV-1 Vif protein expression in subjects with hypermutated proviruses were quite divergent and levels of APOBEC3G also differed between subjects. Ex vivo studies in subjects with hypermutated proviruses indicated that endogenous APOBEC3G expression was greater than in subjects with hypermutated proviruses. Both studies suggest that host and viral factors such as APOBEC3G and HIV-1 Vif are playing an influential role in HIV-1 pathogenesis. Further investigations into these interactions may lead to novel strategies into the development of therapeutic drugs for the fight against HIV-1.

HIV-1 integrase (IN) enzyme employs several viral and cellular proteins for nuclear translocation and crucial integration of viral cDNA. Successful identification of new viral/cellular interactions may shed light for better understanding of HIV-1 replication. 293T cells were transiently transfected with pYEF-1-TAP-IN and cell lysate were subjected to Tandem Affinity Purification system to pull down putative IN-interacting cellular partners. A number of distinct bands from the Coomassie-stained gel were excised followed by in-gel digestion and mass spectrometry. Putative cellular partners of HIV-1 IN were heat shock protein 60 (HSP60), β-tubulin, γ-actin, ATP synthase alpha subunit and histone H1.2 were identified by mass spectrometry. Additionally, SF3A3 (splicing factor 3A3), another previously reported factor, was successfully co-immunoprecipitated with IN. The C-terminal portion of IN was found to be the region of interaction with SF3A3. Overall, this study has provided better understanding of IN dynamics enriching existing knowledge of HIV-1 IN biology.

Objective: Serpins are serine protease inhibitors that are involved in a wide variety of biological functions in nature. They are known to regulate inflammation processes as well as provide host defense against microorganisms. Recent evidence has associated many types of mucosal serpins with a protective phenotype against HIV infection in women. Our hypothesis is that serpins with known antiviral activity against HIV-1 are correlated with protection in a group of HIV exposed seronegative individuals (HIV-resistant) from the Pumwani sex worker cohort. Study design: Cervico-vaginal lavage (CVL) fluid was collected from 66 HIV-positive, 82 HIV-negative and 84 HIV-resistant sex workers from the cohort. Clinical and epidemiological information was recorded at the time of sample collection. CVL protein levels were determined by BCA assay and serpin (A1 and A3) concentrations by a commercially available ELISA kit. Mucosal serpin concentrations were compared against clinical and epidemiological factors as well as sexual practices. Results: Serpin A1 was significantly higher in the HIV-resistant group compared to the HIV-negative controls (Anova: p=0.0470*). Total concentration of serpin A3 did not reach statistical significance between groups. Serpins did not correlate with age, sexual practices, contraceptive use or number of pregnancies. Serpins were differentially abundant during different stages of the menstrual cycle whereas serpin A1 was elevated during the proliferation phase but not in secretory phase (p=0.0275*). Conclusion: Serpin A1 was correlated with HIV-protection in this group of HESN women. This work will contribute to a more complete understanding of mechanisms of resistance and susceptibility to HIV infection.

Introduktion: HIV är en kronisk sjukdom vilken i Sverige uppskattas att 6 400 människor lever med. Psykosociala symtom som rädsla och oro har visat sig vanliga hos människor med HIV. Behandlingen för HIV är kostsam och har många biverkningar vilket leder till att den drabbade har ett livslångt behov av omvårdnad. Comfort theory assesment (CTA) är ett holistiskt förhållningssätt som hjälper sjuksköterskan att identifiera de omvårdnadsinterventioner som patienter är i behov av. Syfte: Litteraturstudiens syfte var var att belysa rädsla och dess ursprung hos människor som lever med en HIVinfektion. Metod: En litteraturstudie har genomförts med hjälp av Polit och Becks (2012) niostegmetod. Databaserna PubMed och Cinahl har använts liksom frisökningar för att finna de 11 artiklar som utgör resultatet av litteraturstudien. Artiklarna har genomgått en urvalsprocess och granskats. Resultat: Två huvudkategorier har identifierats och redovisats: ‘rädsla kopplad till det privata och personliga’ och ‘rädsla kopplad till samhället’ vilka redovisas med tillhörande underkategorier. Slutsats: Människor som lever med HIVinfektion upplever rädsla av olika ursprung. Rädsla upplevs i det egna hemmet såväl som i samhället. En medvetenhet hos sjuksköterskan om rädsla hos människor med HIVinfektion ger större möjlighet att ge individuell omvårdnad. För att hjälpa sjuksköterskan identifiera rädsla och ge god omvårdnad kan CTA som förhållningssätt användas.

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The main aim of the work presented in this thesis was to delineate the natural history and pathogenesis of HIV related heart muscle disease. Additional studies examined the influence of HIV infection on the risk and course of infective endocarditis. Two hundred and ninety-six HIV positive adults were examined by echocardiography in a four year prospective study. Abnormal cardiac function was identified in 14.8%. Dilated cardiomyopathy was present in 4.4% borderline left ventricular dysfunction in 6.4% and isolated right ventricular dysfunction in 4%. Dilated cardiomyopathy was strongly associated with reduced survival compared to those with normal hearts (median survival from diagnosis 101 days, compared to 472 days for those with structurally normal hearts). A newly developed ELISA for anti α-myosin autoantibodies revealed abnormal results in 43% of patients with HIV heart muscle disease, 19% of HIV positive patients with normal hearts and 3% of HIV negative controls. Cardiac specific autoantibodies were also more common in HIV positive patients. Autoimmunity may therefore be important in the pathogenesis of HIV related heart muscle disease. There were no significant socio-economic differences between the HIV positive patients with and without heart disease or the lifestyle matched HIV negative controls studied but mean serum selenium was 33% lower in the HIV positive individuals. Similar differences in toenail (15% lower) and myocardial (17% lower) levels and glutathione peroxidase (15% lower) were also found, but there were no specific differences between patients with and without cardiac abnormalities. Mean α- and γ- tocopherol and α- and β- carotene levels were significantly reduced in our HIV positive patient group, compared to the local HIV negative population, but similar differences existed in a socio-economically matched group of HIV negative drug users. Intravenous drug use was the most important risk factor for the development of the condition.

No description available.

Altered susceptibility to HIV-1 infection has been observed in multiple cohort studies around the world, with a small proportion of HIV-Exposed, Seronegative (HESN) individuals remaining uninfected despite repeated exposure. Previous work has shown association of three polymorphisms in interferon regulatory factor 1 (IRF1) with decreased susceptibility to HIV-1 infection and a reduced likelihood of seroconversion. Peripheral blood mononuclear cells (PBMCs) from patients with protective IRF1 haplotype exhibited significantly lower basal IRF1 expression, reduced responsiveness to IFNγ stimulation and significantly lower HIV-1 LTR transcription during the initial stages of infection. The goal of this thesis was to characterize the effect of three IRF1 polymorphisms associated with HIV-resistant phenotype on: (1) IRF1 gene transcription, alternative splicing of IRF1 mRNA and IRF1 mRNA/protein stability (2) plasma and cervical lavage (CVL) cytokine/chemokine expression and (3) HIV pathogenesis and disease progression. Furthermore since differences in hormone expression are known to regulate IRF1 function we set out to determine if differences in plasma hormone levels contribute to the natural resistance against HIV-1 infection in the Majengo HESN cohort. Polymorphisms in the IRF1 gene do not directly affect IRF1 transcription but instead act as intronic splicing regulators. PBMCs from individuals with protective IRF1 haplotype were associated with increased inclusion of exons 7/8 and decreased protein stability when compared to cells from individuals with nonprotective haplotype. Individuals with protective IRF1 haplotype also exhibited significantly higher plasma IL15, IFNγ and IL6 expression and significantly higher CVL IL15, IFNγ, IL2 and sIL2Rα expression (with univariate analysis only) compared to those with nonprotective IRF1 haplotype. Additionally, individuals with protective IRF1 haplotype expressed significantly lower levels of plasma prolactin when compared to individuals with nonprotective haplotype. IRF1 polymorphisms were found to not be associated with HIV disease progression, suggesting that the protective effect of IRF1 polymorphisms is limited to the early stages, prior to establishment of HIV-1 infection. Furthermore, independent of IRF1 genotypes, significantly lower plasma prolactin, estrogen, progesterone and cortisol levels were observed in HESN women suggesting that hormonal regulation may be one of the main factors regulating natural resistance to HIV-1 infection in the Majengo HESN cohort.