I världen är det idag 30-35 miljoner människor som lever med HIV/AIDS och i Sverige lever idag 6 500 människor med HIV. Den HIV-drabbade är inte den enda som drabbas, då även de närstående drabbas av sjukdomens påfrestningar. Syftet med litteraturstudien var att beskriva närståendes upplevelser när en familjemedlem eller någon i närkretsen lever med HIV/AIDS. Metoden var litteraturstudie, som genomfördes med Polit och Becks niostegsmodell. Artikelrsökningen genomfördes på databaserna CINAHL och PubMed. De artiklar som inkluderades i litteraturstudien gick igenom en urvalsprocess med inklusionkriterier och granskningsmallar. Det var 11 artiklar som behölls efter urvalsprocessen med sex kvalitativa, tre kvantitativa och två med blandad metod. Resultatet är uppdelat i två huvudkategorier Emotioner samt Psykisk belastning. Underkategorierna var frustration/ilska, rädsla/oro, hopp och hopplöshet, sorg/besvikelse respektive stigmatisering, ansvar/brist på stöd samt stress. Slutsats: Dessa olika upplevelser påverkar den närstående negativt på olika sätt och kan medföra ohälsa och försämrad livskvalitet hos de närstående. Ytterligare forskning behövs.

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.

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.

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.

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.

Bakgrund: HIV är ett stort globalt problem då det inte finns botande behandling eller vaccin mot sjukdomen. Tidigare var HIV känt som sjukdom relaterat till homosexualitet, men alla kan insjukna i HIV, vid oskyddade samlag, eller vid smittöverföring från mor till barn under graviditet, förlossning eller amning. 1982 upptäcktes det första HIV-fallet hos en homosexuell man i Sverige, och under 2013 beräknades 6400 människor vara HIV-positiva. Homosexualitet är tabu i de flesta länder och homosexuella män som är HIV-positiva känner sig ofta diskriminerade och stigmatiserade i vården och även från resten av samhället. Syfte: Syftet med denna litteraturstudie var att belysa hur män som identifierar sig som homosexuella och är HIV-positiva upplever att de blir bemötta i vården. Metod: Till denna litteraturstudie har nio empiriska studier med kvalitativ forskningsmetod använts och analyserats med en beskrivande analys av innehåll inspirerad av Friberg. Artikelsökningen utfördes i databaserna Cinahl, PubMED och PsycINFO. Resultat: Resultatet fann tre kategorier av upplevelser: Vi fann att männen upplevde sig stigmatiserade och diskriminerade både i vården och av sin omgivning eller objektifierade, men även att de blev bemötta med förståelse. Den senare upplevelsen noterades oftast inom den specialiserade vården. Inom vården, bland personalen, noterades bland annat brist på empati, respekt och förståelse. Andra negativa upplevelser av bemötande var avvisande, undvikande och dömande. Flera män beskrev personalens bristande kunskap om HIV, vilket skapade otrygghet. Konklusion: Denna litteraturstudies resultat visar att det finns brister i bemötande av män som är HIV-positiva och har en homosexuell läggning. Män med homosexuell läggning och HIV-diagnos önskar att bli bemötta med respekt och som människa, och det är endast möjligt när personalen har tillräcklig kunskap om HIV. Det är viktigt att personalen har ett icke-dömande synsätt på homosexualitet och HIV. Utifrån resultatet framkommer att det behövs fler studier inom detta område med fokus på hur sjuksköterskor ska kunna hjälpa och stötta patienten med bland annat att berätta om sin sjukdom för närstående. Nyckelord: HIV, Homosexualitet, Män, Litteraturstudie, Bemötande

No description available.

Background: As of 2012, Georgia ranked fifth in the United States in the number of people diagnosed with HIV/AIDS. Given the high burden of disease among men who have sex with men (MSM), the HIV Care Continuum has become an important measure for keeping persons living with HIV in care and eventually reaching an undetectable viral load. Methods: Data were extracted from the Enhance HIV/AIDS Reporting System (eHARS) using SAS version 9.3.A univariate analysis was then performed by cross tabulating variables such as linked to care, any care in 2012, retained in care and viral suppression (VS) for men who have sex with men only (MSMO) and men who have sex with men and women (MSMW), stratified by race/ethnicity and age. Results: Among 20,676 males categorized as MSM, 14,316 (69%) were MSMO and 6,360 (31%) were MSMW. Among MSMO, 77% (N=772) were linked to care and 45% were virally suppressed and among MSMW, 75% (N=219) were linked to care and 40% were virally suppressed. Black men have the lowest percentages along the HIV Care Continuum when compared to other race/ethnicities of MSMO and Hispanic/Latino MSMW have the lowest linkage to care of any race/ethnicity for both subpopulations. In both MSMO and MSMW, linkage, any care, retention, and VS increase with increasing age. Conclusion: MSM suffer are terribly affected by HIV and a substantial proportion of MSM also engage in sexual contact with women, who may not be aware of their partner’s HIV risk status. Much speculation can be drawn about what keeps both MSMO and MSMW from being linked to care or reaching an undetectable viral load. Possibilities may include greater perception of stigma, ambivalence about HIV care and increased denial affecting ART adherence for MSMW as compared to MSMO. In order to see a drop in HIV rates within this group, the outside factors that negatively influence a person’s progress along the HIV Care Continuum toward an undetectable viral load must be understood and addressed.

No description available.

This thesis project was designed to investigate the phenotypic and genotypic variability of human immunodeficiency virus type 1 (HIV-1) drug-naive clade C reverse transcriptase (RT) and its potential impact in the development of resistance against inhibitors of RT. Five treatment-naive HIV-1 Ethiopian isolates were classified as subtype C on the basis of env gene heteroduplex mobility assays (HMA) profile and phylogenetic analysis of RT sequences. In subtype C RT, a specific KVEQ motif of silent mutations (amino acid 65, 106, 138, 161) at resistance sites was present. Two Ethiopian strains were naturally resistant to non-nucleoside RT inhibitors (NNRTI), as well as to zidovudine (ZDV), based on the natural polymorphisms of G190A and K70R, respectively. The final drug concentration that selected for NNRTI primary resistance mutations in tissue culture assays was significantly higher for clade B than clade C for each of nevirapine (NW) (10 muM versus 2 or 4 muM), efavirenz (EFV) (1muM versus 0.01muM) and delaviridine (DLV) (10muM versus 1 or 4muM), respectively. In the middle of the selection period with all the NNRTIs, subtype B viruses were harboring a mixture of both wild type and mutated forms, whereas in clade C viruses, primary resistance mutations were fully generated. Thus, we have found that clade C isolates developed more rapidly resistance (8 or 9 weeks with NVP or DLV and 13 weeks with EFV) as compared with clade B controls (at least 15 weeks with NW or DLV and 30 weeks with EFV). Odd mutations were detected during selection with NNRTIs, such as S98I, and two mutations (A62V and V75E), at sites associated to multi-drug resistance against nucleoside inhibitors (NRTIs). The substitution A62V was initially observed as a drug-naive silent mutation A62A. NW and DLV mutants were broadly cross-resistants. Following in vitro selection for drug-resistance with NNRTIs (NVP, DLV and EFV) and NRTIs [lamivudine (3TC) and ZDV], RT immunodominant regions of 14 HIV-1 s