MSc (Microbiology) / Department of Microbiology / See the attached abstract below

Thesis (MPH.) -- University of Limpopo, 2022 / Human Immunodeficiency Virus (HIV) has affected all parts of the world, and as of 2019, more than 76 million people have been infected by HIV. South Africa has the largest population of people living with human immunodeficiency virus (HIV) in the world and the highest infected group were aged 24 to 49, and females had the highest percentage in viral load suppression for all age groups. HIV infection leads to advanced loss of CD4 T cells and the roll out of antiretroviral therapy (ART) has bring about in significant cutbacks in HIV-associated complications by recovering the CD4+ T cell count. Some patients may not be successful in attaining this result, and some may accomplish it only after a number years of treatment. The disease progression and the health conditions amongst People Living with HIV-AIDS (PLWA) has improved substantially in the past two decades. The purpose of this study was to evaluate the disease progression of the patients initiated on ART from 2017 to 2019 at the University of Limpopo Health Centre, in Limpopo province. Methodology: A descriptive retrospective investigation was carried out which followed a quantitative approach in which secondary data from medical files of 259 patients initiated on ART at University of Limpopo Health Centre was used. where outcomes of ART initiation assessed and evaluated in association with characteristics of patients. Data analysis was done using the STATA statistical software version 12 for Windows (STATA Corporation, College Station, Texas). Frequency tables were used to make comparisons between groups for continuous and categorical variables using student t-test, and chi-square test. P-value less than 0.05 at 95% confidence level were regarded as significant. Results: The research finding revealed 80.0% of the study participants were females and the mean age group of participants diagnosed HIV positive was 28.28 years with standard deviation of ±7.5. The mean of the CD4 count cells at baseline for females was 411.4 cells/μL while for males was 341.2 cells/μL (p=0.212). The mean CD4 count cells at last ART visit for females was 613.7 cells/μL while for males was 452.9 cells/μL (p<0.001). There has been significant increase of the CD4 cell count from the baseline to the last ART visit as it is noted in the increase in proportion of patients with CD4 cell count of more than 500 in all the years. The proportion of patients with baseline CD4 cell count of 200 to 350 (moderate immunodepression) were high in 2019 and 2017 at 40.6% and 40.3% respectively. Majority of the patients were transferred out to other facilities at 79.4% as most patients are students and only 2.3% mortality rate has been reported for the study period. Majority of the patients initiated on ART at University of Limpopo were in WHO stage 2 at 45.5% followed by those in stage 3 and stage 1 at 22.2% and 21.8% respectively. Patients who were 24 years or older were 1.1 times more likely to have improved CD4 cell count at the last date of ART visit as compared to younger patients but not statistically significant while males were 3.5 times more likely to have improved CD4 cell count at the last date of ART visit as compared to females which was statistically significant. Patients who were initiated on ART at WHO stage 4 were 6.67 more likely to have improved CD4 cell count at the last date of ART visit as compared to those who were initiated on ART at WHO stage 1. Conclusion: The treatment progression in the study setting was found to be convincing and acceptable which is similar to the findings reported in other studies in many other countries. The significance of CD4 cell counts monitoring for HIV patients cannot be overemphasised. This study recommends a strengthened testing and treatment programme targeted males amongst the university community, enhance provider provider relationship when patients are transferred out to other health facilities, enhance the collection of baseline and progressive data on both the CD4 cell count and viral load.

Thesis (Ph.D. (Public Health)) -- University of Limpopo, 2022 / There has a significant rise in the number of HIV-infected adolescents who were missed as children and are diagnosed with perinatally acquired HIV as teenagers. In 2013, perinatally acquired HIV was estimated at around 10 000 infections globally, a figure which ballooned to38 000 by 2017. Adolescents living with perinatal HIV experience emotional upheaval as a result of their positive HIV diagnosis, which is exacerbated by real or perceived negative effects on their relationships, career, and family aspirations. They face the same challenges as other adolescents, along with the added complexity of personal decisions relating to their sexual conduct having a direct impact on the global cause to eradicate HIV/AIDS. An extensive body of literature indicates a need for emotional and psychosocial support as existing management focuses mainly on the physical aspects of infection and treatment. Aim of the study The aim of the study was to explore the challenges faced by adolescents living with perinatal HIV infection and to evaluate the designed user-friendly support programme in response to formative findings of the research in selected clinics and community health centres in the Vhembe District of the Limpopo Province in South Africa. Methodology A mixed-methods sequential exploratory design was employed to fulfil the purpose of the study. Data was collected in two phases. In qualitative phase- a total of 21 participants were interviewed using a semi-structured interview guide. The sample was purposefully selected from adolescents living with HIV/AIDS. In quantitative phase a total of 213 people participated in data collection using a questionnaire. Thematic approach was used to analyse qualitative data using Tesch’s eight steps of qualitative data analysis. Quantitative data was analysed using SPSS version 25. Descriptive statistics was used to explain and summarize data. Fischer’s test was done to establish significance of association between alcohol used, condom use and between age and gender. The results The results revealed that adolescents with perinatally acquired HIV face more challenges. They had psychosocial, emotional and economic challenges more than their peers. The current HIV/AIDS management and care has not yet recognised the specific needs these adolescents have related to their care. They have been incorporated into the general adulthood HIV/AIDS making their transition from childhood adolescence difficult. Suggestions for a mentor, and ARV modification were made and a need for a support programme emerged as one of the major themes

The study sought to identify factors motivating young people aged 14-25 years to use voluntary counseling and testing (VCT) for HIV in Malawi by interviewing 145 young people. The study identified barriers affecting and strategies promoting young people's access to VCT. The research results indicate that young people go for VCT mainly to know their HIV status. The availability of VCT services, and the provision of VCT services by peers motivate young people to access VCT. Some young people do not access VCT services due to fears of being found HIV+ve and because of the poor attitudes of the health service providers. Providing more information about VCT, involving young people as VCT providers, using youth friendly health service providers, providing VCT in a separate room for young people and through mobile services will increase young people's access to VCT services in Malawi. / Health Studies / M.A. (Public Health)

Submitted in fulfillment of the requirements for the Degree of Master of Technology: Biotechnology, Department of Biotechnology and Food Technology, Faculty of Applied Sciences, Durban University of Technology, South Africa,2009. / Nearly half of all individuals living with HIV worldwide at present are woman and the best current strategy to prevent sexually transmitted HIV is antiretrovirals (ARVs). Microbicides are ARV’s which directly target viral entry and avert infection at mucosal surfaces. However, most promising ARV entry inhibitors are biologicals which are costly to manufacture and deliver to resource-poor areas. Microbicides formulated as simple gels, which are currently not commonly used in ARV therapy, show immense potential for use in prevention and treatment of multidrug-resistant viral infections in developing countries. Among the most potent HIV entry inhibitory molecules are lectins, which target the high mannose N-linked glycans which are displayed on the surface of HIV envelope glycoproteins. Of the microbicides, the red algal protein griffithsin (GRFT) has potent anti-HIV inhibitory activity and is active by targeting the terminal mannose residues on high mannose oligosaccharides. It has a total of 6 carbohydrate binding sites per homodimer, which likely accounts for its unparalleled potency. The antiviral potency of GRFT, coupled with its lack of cellular toxicity and exceptional environmental stability make it an ideal active ingredient of a topical HIV microbicide. v Scytovirin (SVN) is an equally potent anti-HIV protein, isolated from aqueous extracts of the cyanbacterium, Scytonema varium. Low, nanomolar concentrations of SVN have been reported to inactivate laboratory strains and primary isolates of HIV- 1. The inhibition of HIV by SVN involves interactions between the protein and HIV-1 envelope glycoproteins gp120, gp160 and gp41. Current recombinant production methods for GRFT and SVN molecules are unfortunately hampered by inadequate production capacities. This project therefore aimed to determine if these molecules can be produced in plant cell culture systems. The transgenic tobacco cell culture system was evaluated to determine if it can be an alternative, cost effective production system for these molecules. Results of the study show that the microbicide genes can be cloned into plant transformation vectors, used to successfully transform SR1 tobacco cell lines and adequately produce 3.38ng and 10.5ng of GRFT and SVN protein respectively, per gram of SR1 tobacco callus fresh weight. The promising results attained in this study form the basis for further work in optimising plant cell based production systems for producing valuable anti-HIV microbicides, a possible means to curbing the elevated HIV infection rates worldwide. / CSIR

Thesis (DMed)--Stellenbosch University, 2015 / ENGLISH ABSTRACT: Introduction The increasing intake of traditional medicines among HIV/AIDS patients in sub-Saharan Africa needs urgent consideration by clinicians and other healthcare providers since the safety of such medications are unknown. The pharmacokinetic parameters - Absorption, Distribution, Metabolism and Elimination (ADME) play important role in the safety evaluation of drugs, thus implicating drug metabolizing enzymes and transporters as critical indicators for herb-drug interactions. The objective of this study was to evaluate the risk potential of seven herbal medicines commonly consumed by HIV/AIDS patients for drug interactions applying in vitro models. In this study, inhibition and induction effects of the herbal medicines on cytochrome P450s (CYPs) 1A2, 2C9, 2C19, 2D6 and 3A4 as well as P-glycoprotein (P-gp) were investigated. Methods Herbal medicines – Lessertia frutescens, Hypoxis hemerocallidea, Kalanchoe integra and Taraxacum officinale were sourced from Medico Herbs, South Africa were identified by experts from Compton Herbarium, South African National Biodiversity Institute, Cape Town. Moringa oleifera, Echinacea purpurea and Kalanchoe crenata were obtained from the repository of the National Centre for Natural Product Research (NCNPR), University of Mississippi, USA. Reversible inhibitory effect of aqueous and methanol herbal extracts were evaluated in recombinant CYPs applying the fluorescent metabolites at specified excitation/emission wavelengths; CYP1A2 (3-cyano-7-hydroxycoumarin (CHC); 405/460 nm), CYP2C9, CYP2C19 and CYP3A4 (7-hydroxy-4-(trifluoromethyl)-coumarin (HFC); 405/535 nm) and CYP2D6 (7-hydroxy-4-(aminomethyl)-coumarin (HAMC); 390/460 nm). Comparative studies in human liver microsomes (HLM) and recombinant CYPs were conducted to investigate the inhibitory effect of methanol herbal extracts and fractions on 6β testosterone hydroxylation activity. Time dependent inhibitory (TDI) effect of the herbal extracts were evaluated applying the IC50 shift fold, normalized ratio and the NADPH-, time- and concentration-dependent approaches. Influence of herbal extracts on metabolic clearance of testosterone was assessed in both HLM and human hepatocytes. The effects of each herbal extract on expression of CYP1A2, CYP3A4 and MDR1 genes were evaluated in activated human pregnane X receptor (PXR) co-transfected HepG2 cells. Finally, the inhibitory effect of herbal extracts on P-gp was assessed using the calcein-acetoxymethyl ester (calcein-AM) uptake and the digoxin radiolabelled substrates in MDCKII-MDRI cells. Results The aqueous extracts of Moringa oleifera, Kalanchoe integra, Kalanchoe crenata, Echinacea purpurea and Lessertia frutescens demonstrated high risk of in vivo inhibition on CYPs 3A4 and 1A2 with Cmax/Ki >1.0. Methanol extracts of these herbal medicines also indicated potential risk of reversible drug interaction. The methanol extracts of M. oleifera, K. crenata and L. frutescens showed strong TDI effect on CYP3A4 with IC50 shift fold >1.5 and normalised ratio <0.7. Moringa oleifera intermediately reduced intrinsic clearance of testosterone in human hepatocytes (2 ≤ AUC ratio ≤ 5) when scaled up to humans. Methanol extracts of Echinacea purpurea up-regulated the expression of CYP1A2, CYP3A4 and MDR1 genes in activated PXR. Kalanchoe crenata and Echinacea purpurea indicated strong inhibition on P-gp by reducing transport of digoxin across hMDR1-MDCKII cell monolayer from basolateral to apical with IC50 values of 18.24 ± 2.52 μg/mL and 24.47 ± 4.97 μg/mL, respectively. Conclusion The herbal medicines especially M. oleifera, K. integra and E. purpurea have the potential to cause herb-drug interaction in vivo if sufficient hepatic concentration is achieved in humans. / AFRIKAANSE OPSOMMING: Inleiding Die verhoogde inname van tradisionele medisynes onder MIV/VIGS-pasiënte in sub-Sahara-Afrika verg dringend oorweging deur klinici en ander gesondheidsorgverskaffers, aangesien die veiligheid van sodanige medikasies onbekend is. Die farmakokinetiese parameters – Absorpsie, Distribusie, Metabolisme en Eliminasie (ADME) – speel ’n belangrike rol by die veiligheidsevaluering van geneesmiddels, en impliseer gevolglik geneesmiddel-metaboliserende ensieme en vervoerders as kritiese indikators vir krui-geneesmiddel-interaksies (HDI). Die oogmerk van hierdie studie is om die risikopotensiaal van sewe kruiemedisynes wat algemeen deur MIV/VIGS-pasiënte geneem word, vir geneesmiddel-interaksies te evalueer deur in vitro-modelle te gebruik. In hierdie studie is die inhiberings- en induseringsuitwerkings van die kruiemedisynes op sitochroom P450’s (verkort na CYP’s) 1A2, 2C9, 2C19, 2D6 en 3A4, sowel as P-glikoproteïen (P-gp), ondersoek. Metodes Kruiemedisynes – Lessertia frutescens, Hypoxis hemerocallidea, Kalanchoe integra en Taraxacum officinale – is van Medico Herbs, Suid-Afrika, bekom en deur kundiges van die Compton-herbarium, by die Suid-Afrikaanse Nasionale Biodiversiteitsinstituut, Kaapstad, geïdentifiseer. Moringa oleifera, Echinacea purpurea en Kalanchoe crenata is van die bewaarplek van die Nasionale Sentrum vir Natuurlike Produknavorsing (NCNPR) aan die Universiteit van Mississippi in die VSA verkry. Die omkeerbare inhiberende uitwerking van kruie-ekstrakte in water en metanol is in rekombinante CYP’s geëvalueer deur die gebruik van die fluoresserende metaboliete op gespesifiseerde opwekkings-/emissiegolflengtes; CYP1A2 (3-siaan-7-hidroksikumarien (CHC); 405/460 nm), CYP2C9, CYP2C19 en CYP3A4 (7-hidroksi-4-(trifluoormetiel)-kumarien (HFC); 405/535 nm) en CYP2D6 (7-hidroksi-4-(aminometiel)-kumarien (HAMC); 390/460 nm). Vergelykende studies van menslikelewermikrosome (HLM) en rekombinante CYP’s is uitgevoer om die inhiberende uitwerking van metanolkruie-ekstrakte en -fraksies op 6β-testosteroonhidroksileringsaktiwiteit te ondersoek. Die tydafhanklike inhiberende uitwerking (TDI) van die kruie-ekstrakte is geëvalueer deur gebruikmaking van die IC50-verskuiwingsvou-, die genormaliseerdeverhoudings- en die NADPH-, tyd- en konsentrasieafhanklike benaderings. Die invloed van kruie-ekstrakte op metaboliese testosteroonverheldering is in beide HLM en menslike hepatosiete geëvalueer. Die uitwerkings van elke kruie-ekstrak op die uitdrukking van CYP1A2-, CYP3A4- en MDR1-gene is in geaktiveerde menslike pregnaan-X-reseptor(PXR)-, ko-getransfekteerde HepG2-selle geëvalueer. Laastens is die inhiberende uitwerking van kruie-ekstrakte op P-gp geëvalueer, met gebruikmaking van die kalsien-asetoksimetiel-ester (kalsien-AM)-opname en die digoksien- radiogemerkte substrate in MDCKII-MDRI-selle. Resultate Die ekstrakte in water van M. oleifera, K. integra, K. crenata, E. purpurea en L. frutescens het ’n hoë risiko van in vivo-inhibering op CYP’s 3A4 en 1A2 met Cmaks/Ki >1.0 getoon. Ekstrakte van hierdie kruiemedisynes in metanol het verder potensiële risiko van omkeerbare geneesmiddelinteraksie getoon. Die ekstrakte van M. oleifera, K. crenata en L. frutescens in metanol het sterk TDI-uitwerking op CYP3A4 met IC50-verskuiwingsvou >1.5 en genormaliseerde verhouding <0.7 getoon. M. oleifera het intermediêre vermindering van intrinsieke testosteroonverheldering in menslike hepatosiete (2 ≤ AUC verhouding ≤ 5) tot gevolg wanneer die skaal na mense verhoog word. Ekstrakte van E. purpurea in metanol het die uitdrukking van CYP1A2-, CYP3A4- en MDR1-gene in geaktiveerde PXR opgereguleer. K. crenata en E. purpurea het sterk inhibering van P-gp getoon deur die vervoer van digoksien deur die hMDR1-MDCKII-selmonolaag van basolateraal tot apikaal met IC50-waardes van onderskeidelik 18.24 ± 2.52 μg/mL en 24.47 ± 4.97 μg/mL te verminder. Gevolgtrekking Kruiemedisynes, veral M. oleifera, K. integra en E. purpurea, het die potensiaal om HDI in vivo te veroorsaak indien voldoende hepatiese konsentrasie by mense bereik word.

This study aimed at exploring the influence of the home environment of women that were on the prevention of mother-to-child transmission (PMTCT) programme for HIV/AIDS. A qualitative descriptive study was conducted to explore the home environment for the psycho-social support that was available for women on the PMTCT programme and the influence this had on compliance to the programme. Data collection was done using a semi-structured interview guide, with a sample size of 14 participants (n=14). The data was then coded and grouped into categories and major themes. The findings revealed that the common barriers that prevented full disclosure of an HIV positive status included stigma and discrimination, fear of social isolation and financial dependence. A major constraint that affected the women’s full utilisation of the PMTCT preventative strategies and their adherence to treatment was the poor acceptance of people living with HIV in the family and community / Health Studies / M.A. (Health Studies)

Thesis (MScMedSc (Pathology. Medical Microbiology))--University of Stellenbosch, 2006. / Acquired immunodeficiency syndrome (AIDS) was first reported in 5 homosexual men in Unite States of America in 1981 as a series of opportunistic infections which occasionally occurred in adults. Subsequently, it has been achieved that human immunodeficiency virus type 1 (HIV-1) is the cause of AIDS and this aetiological agent has spread all over the world. The virus primarily attacks CD4+ T cells and gradually leads to progressive depletion of CD4 T lymphocytes from peripheral blood and lymphoid organs. Since CD4+ T cells are vital immune cells in induction and regulation of both cell-mediated and humoral immune responses, depletion of these cells ultimately results in a profound immunodeficiency characterized by susceptibility to variety of opportunistic infection. Apoptosis have been commonly proposed as the mechanism of CD4 depletion because elevated levels of apoptosis were observed in HIV-1 infected individuals (Ameisen et al., 1991; Groux et al., 1992 & Oyaizu et al., 1993). Nevertheless, there was evidence showing that HIV-1 infected cells died not from apoptosis (Bolton et al., 2002) and another study reported that inhibition of apoptosis resulted in high viral production (Antoni et al., 1995). These controversial views indicated that the mechanism of CD4 depletion and the immuno-pathogenesis of apoptosis should be considered. As a pilot sub-study, eight HIV-1 infected subjects were enrolled to determine the methods in measuring apoptosis. Three different cell separations: (1) whole blood cells, (2) buffy coat cells and (3) isolated PBMCs were prepared to determine whether different cell preparations result in different measurements of apoptosis. In addition, FITC-labelled Annexin V, an early marker of apoptosis, and flow-cytometer based scatter methods based on characteristics of apoptotic cells were used to investigate the difference in analytical methods in determining the levels of apoptosis. Firstly, it was found that whole blood samples yielded more precise measurements in measuring apoptosis, followed by Buffy coat and then PBMC samples. Secondly, this sub-study also indicated that the scatter method as well as fluorenscent labelled Annexin V could be useful markers for apoptosis. Secondly, different surface markers of apoptosis were used to investigate apoptosis in HIV-1 infected adults. Fifty-eight HIV-1 infected adults were involved in this sub-study. They were classified into three categories based on CDC CD4 category classification (CDC, 1993). According to the data, the level of apoptotic CD4+ T cells measured by the scatter method was high in CD4 category 1, decreased in category 2 and finally increased again in category 3. This tendency was in parallel with CD95 (Fas) expression on CD4+ T cells. The curve formed a “V” shape according to the three CD4 categories. Together with the gradually increased plasma viral load, these data reflect an activated immune response at early stage of infection and under controlled viraemia. This possibly represents the immune response trying to eliminate infected cells as a means of survival. The high level of apoptosis in category 3 could indicate a disordered immune system accounting for the rapid loss of CD4+ T cells and progression to AIDS. A novel finding of this study was the presence of two CD4+ populations in 10 HIV-1 infected subjects, which were CD4dim and CD4bright. These 10 subjects had relatively high CD4 count and low viral replication. Statistical analysis showed they had significantly higher levels of apoptosis in CD4 and CD8 T lymphocytes, measured by the scatter method, than those subjects presenting single CD4 population. In addition, when comparing the two CD4 subpopulations, it was found that CD4dim cells had significant higher level of apoptosis and CD95 expression than the CD4bright cells. Finally, the virological and immunological effects of antiretroviral therapy (ART) were investigated in two cohorts of HIV-1 infected children. Fourteen HIV-1 infected children were involved in investigation of 12-month long-term effect, while another five children were involved in a short-term 1-month follow-up study. In addition, a different assay of detecting apoptosis: terminal deoxynucleotidyltransferase deoxyuridine triphosphates nick end labeling (TUNEL) was conducted to measure the level of apoptotic PBMCs. According to the findings from 12-month and 1-month sub-studies, it appeared that ART could be effective in suppression of viral replication at an early stage. However, the immunological effect, such as CD4 reconstitution, could only be seen as a long-term effect, since immune recovery would take a long time. In addition, different regimens containing protease inhibitors (PIs) might be more effective in inhibiting apoptosis than non-nucleoside reverse transcriptase inhibitors (NNRTIs).

Thesis (MScMedSc)--Stellenbosch University, 2013. / The diversity of HIV-1 sequences derived from patients in Bushbuckridge, Mpumalanga, was investigated. The gag p24, pol p10 and p66/p51, pol p31 and env gp41 gene fragments from 51 patients were amplified and sequenced. Quality control on the sequences was carried out using the LANL QC online tool. HIV-1 subtype was assigned using the LANL QC (RIP), REGA and jpHMM online tools. Subtype for the pol gene fragment was further designated using the SCUEAL online tool. Most of the sequences, that is 89%, belonged to HIV-1 subtype C. LANL QC (RIP), REGA, jpHMM also detected recombinants in 11% of the sequences. One of the isolates could only have the env gp41 gene fragment amplified and sequenced, which was determined to be HIV-1 subtype B. Phylogenetic analysis using the Neighbor-Joining and Maximum Likelihood methods from MEGA v 5 showed that, except for the env gp41 designated as a subtype B, all sequences in the study clustered with HIV-1 subtype C. Significantly, phylogenetic analysis showed that not only are the Bushbuckridge, Mpumalanga sequences related to HIV-1 subtype C sequences from southern Africa, India, Ethiopia and Brazil, but it is possible there has been multiple introductions of HIV-1 in the province. SDRMs were observed in two samples.

Thesis (MScMedSc) –Stellenbosch University, 2014. / ENGLISH ABSTRACT: HIV-infection is characterized by depletion of CD4+ T-cells from the gut-associated lymphoid tissue (GALT) which causes irreparable gastrointestinal tract damage and subsequent microbial translocation of bacterial products such as lipopolysaccharide (LPS), a component of Gram-negative bacteria, into systemic circulation. HIV infection also affects the functions and relative population sizes of various immune cells, such as monocytes. Monocytes are important innate immune cells as they are often the first cells recruited to sites of infection and inflammation. They then either promote inflammatory processes; elicit adaptive immune responses, through their antigen presenting ability; aid in pathogen and debris clearance or aid in damage repair. This cross-sectional study investigated functional changes to monocytes and monocyte subsets (CD14+CD16- and CD14+CD16+) in HIV+, treatment naïve individuals and healthy uninfected controls, using whole blood assays and isolated monocytes. A number of chemokine receptors associated with function and homing, and specific gut-homing receptors, were investigated. Monocyte activation, apoptotic potential and intracellular monocyte cytokine production were also investigated. All markers were evaluated using multi-parameter flow cytometry. Monocyte responsiveness to in vitro LPS stimulation and expression of the afore-mentioned chemokine receptors to viral load, CD4+ count and CD38/8 T-cell expression was also assessed. During HIV-infection monocytes appeared primed to exit systemic circulation and migrate towards the gut, as seen through elevated CD62-L (p < 0.005) and CCR7 (p < 0.005), whereas the CD14+CD16+ subset was increased (p = 0.0461) and exhibited a higher activation status through increased CD69 expression (p < 0.005) compared to the CD14+CD16- subset. An interesting observation was the significantly increased IL-10 production by the CD14+CD16+ subset (p < 0.005). An elevated CCR5 expression in total monocytes (p < 0.005) was also seen. After LPS stimulation, the HIV+ group displayed unique and significant percentage increases in the total monocyte population. The findings of the current study suggest that monocyte functionality may be retained during HIV-infection and that CD14+CD16+ monocytes play a vital role during HIV-infection evidenced by their preferential expansion and priming for GALT migration. The production of IL-10 by this subset further highlights their importance and emphasizes the need for future studies on the role of these cells in chronic stable HIV-1 infection and whilst disease progresses. / AFRIKAANSE OPSOMMING: MIV-infeksie word gekenmerk deur die uitputting van CD4+ T-selle, veral uit die derm-verwante limfweefsel (GALT). Dit veroorsaak onherstelbare skade aan die spysverteringskanaal en die daaropvolgende mikrobiese translokasie van bakteriële produkte soos LPS, „n komponent van Gram-negatiewe bakterieë, wat gaan binne sistemiese sirkulasie. MIV-infeksie beinvloed die funksies en relatiewe bevolkingsgrootte van verskeie immuun selle, insluitend monosiete. Monosiete is belangrike ingebore immuun selle en is dikwels die eerste selle wat gewerf word na areas van infeksie en inflammasie. Monosiete kan inflammatoriese prosesse bevorder of aanpabare immuunstelsel reaksies ontlok deur middel van hul antigeen aanbiedings vermoë of help met patogeen en puin klaring en skade herstel. In hierdie deursnee-studie het ons veranderinge aan monosiete (CD14+CD16+ en CD14+CD16-) ondersoek in MIV+ behandelde naïef individue en gesonde onbesmette kontroles, deur die gebruik van hele bloed toetse en geïsoleerde monosiete. 'n Aantal chemokine reseptore, wat verband hou met homing en funksie was ondersoek in toevoeging tot spesifieke derm-homing reseptore. Monosiet aktivering, apoptese potensiaal en intrasellulêre monosiet sitokien produksie was ook ondersoek. Alle merkers is ondersoek deur multi-parameter vloeisitometrie. Die beoordeel reaksies van monosiete na in vitro LPS stimulasie en die uitdrukking van die merkers met merkers van algemene immuun aktivering en MIV-siekte patogenese was ook ondersoek. CD14+CD16+ monosiete was gedurende MIV-infeksie verhoog (p-waarde = 0.0461). Daar was 'n hoër algehele monosiet uitdrukking van verskeie chemokine merkers soos CD69 (p-waarde < 0.005) uitdrukking; CD62-L (p-waarde < 0.005), en CCR7 (p-waarde < 0.005) uitdrukking in die CD14+CD16+ subgroep. Daar was ook „n toename in IL-10 produksie, veral in die CD14+CD16+ subgroep (p-waarde < 0.005). Hoewel baie funksionele merker reaksies dieselfde was, het die MIV+ groep „n unieke en beduidende persentasie verhooging in die totale monosiet bevolking getoon. Ons algehele bevindinge dui op 'n voorkeur uitbreiding van CD14+CD16+ monosiete tydens MIV-infeksie. Die CD14+CD16+ monosiet subgroep blyk ook bevoordeel word met betrekking tot voorbereiding vir migrasie na limfknope en die GALT. Die toename in geaktiveer de CD14+CD16+ monosiete op siekte webwerwe is waarskynlik 'n groot bydraende faktor tot aanhoudende immuun aktivering wat op sy beurt virale replikasie bevorder. Hierdie resultate beklemtoon die behoefte om die rol van hierdie selle en in veral die CD14+CD16+ subgroep, in kroniese stabiele MIV-1 infeksie verder te studeer en terwyl siekte bevorder.