South Africa is in dire need of a public umbilical cord blood stem cell bank (UCB SCB). A severe shortage of genetically compatible samples for BM transplantation precludes the majority of South Africans from receiving the relevant medical care. UCB is a viable alternative to BM but is currently disposed of post-delivery. UCB could furthermore serve as a resource of genetically compatible haematopoietic progenitor cells (HPCs) that could be used in gene therapy approaches directed towards a cure for HIV-1. Knowing whether HIV-1 affects or infects primitive HPCs is vital to determine the course of action for transplantation of UCB-derived genetically resistant HPCs. Collecting and storing UCB in a public UCB bank could thus serve as a vital resource of genetically compatible samples for BM transplantation. It was thought that the high incidence of HIV-1 in South African patients and the persistent stigma surrounding HIV-1 would be problematic for collecting sustainable numbers of UCB units and subjecting units to compulsory screening for infectious diseases. This was however, not the case. In the South African context, we are faced with unique and rich challenges relating to cultural and religious differences that are further augmented by linguistic constraints and educational insufficiencies. Nevertheless, the majority of patients within the interviewed patient cohort were supportive of the idea of establishing a public UCB SCB in SA and were willing to undergo additional HIV-1 screening. The Ultrio-Plus® assay was verified in this study for screening UCB units for HIV-1 and could be used in routine analyses of UCB units prior to banking. Conflicting results in the literature exist with regard to HIV-1’s ability to infect or affect haematopoietic progenitor cells. Results from this study revealed that HIV-1 was not only able to affect HPCs’ ability to form colonies in vitro, but was also capable of infecting CD34+ HPCs in some individuals. These results substantiate the theory that some CD34+ HPCs serve as viral reservoirs which could account for residual viraemia in patients on antiretroviral therapy. Results suggest that allogeneic transplantation of HIV-1 infected individuals with UCB-derived, genetically modified HPCs, should be pursued. / Thesis (PhD)--University of Pretoria, 2012. / Immunology / unrestricted

Uganda has registered more than a million deaths since the HIV virus was first offi¬cially reported in the country over 3 decades ago. The governments in partnership with different groups have implemented different programmes to address the epidemic. The support from different donors and reduction in prices of treatment resulted in the focus on antiretroviral therapy access to those affected. Presently only a quarter of the approximately 1 million infected by HIV in Uganda are undergoing antiretroviral therapy. The number of patients pause a challenge in monitoring of therapy given the overall resource needs for health care in the country. Furthermore the numbers on antiretroviral therapy are set to increase in addition to the stringent requirements in tracking and monitoring of each individual patient during therapy. This research aimed at developing a framework for adopting knowledge engineering in information systems for monitoring HIV/AIDS patients. An open source approach was adopted due to the resource constrained context of the study to ensure a cost effec¬tive and sustainable solution. The research was motivated by the inconclusive literature on open source dimensional models for data warehouses and data mining for monitor¬ing antiretroviral therapy. The first phase of the research involved a situational analysis of HIV in health care and different health care information systems in the country. An analysis of the strengths, weaknesses and opportunities of the health care system to adopt knowledge bases was done. It proposed a dimensional model for implementing a data warehouse focused on monitoring HIV patients. The second phase involved the development of a knowledge base inform of an open source data warehouse, its simulation and testing. The study involved interdisciplinary collaboration between different stakeholders in the research domain and adopted a participatory action research methodology. This involved identification of the most appropriate technologies to foster this collabora¬tion. Analysis was done of how stakeholders can take ownership of basic HIV health information system architecture as their expertise grow in managing the systems and make changes to reflect even better results out of system functionality. Data mining simulations was done on the data warehouse out of which two machine learning algorithms (regression and classification) were developed and tested using data from the data warehouse. The algorithms were used to predict patient viral load from CD4 count test figures and to classify cases of treatment failure with 83% accu¬racy. The research additionally presents an open source dimensional model for moni¬toring antiretroviral therapy and the status of information systems in health care. An architecture showing the integration of different knowledge engineering components in the study including the data warehouse, the data mining platform and user interac-tion is presented.

Globally, ~17 million women and ~2.1 million children are living with HIV. Sub-Saharan Africa accounts for 70% of HIV-infected (HIV+) persons. Mother-To-Child Transmission of HIV (MTCT) during pregnancy, delivery and breastfeeding, is the main route of HIV infection in children. The World Health Organisation recommends lifelong antiretroviral therapy (ART) for all HIV+ pregnant and breastfeeding mothers to prevent MTCT, and breastfeeding for ≥24 months for optimal child health in resource limited settings (Option B+ strategy). Initiation of ART in HIV+ adults is associated with a 2-6% decrease in areal bone mineral density (aBMD) regardless of ART regimen, but data are limited in pregnant and lactating women. Tenofovir, a preferred first-line drug in Option B+ ART regimen, is associated with 1-2% greater decreases in aBMD. Pregnancy and lactation are associated with physiological changes in maternal bone mineral density, but most evidence shows that this is recovered after cessation of breastfeeding. The hypothesis of this thesis is that ART may accentuate the normal process of bone mobilisation during pregnancy and lactation, leading to bone loss that is not recovered in the mother and/or compromised infant growth and bone mineral accretion. The primary objective of this research was to investigate if HIV+ women experience greater reductions in bone mineral compared to HIV-uninfected (HIV-) counterparts. Two groups of pregnant women, 95 HIV+ on ART (Tenofovir-Lamivudine-Efavirenz, previously ART naïve) and 96 HIV- were followed prospectively in Kampala, Uganda. Data were collected at 36 wks gestation (PG36), 2 (PP2) and 14 wks postpartum (PP14). Dual-energy x-ray absorptiometry was used to measure bone phenotype (aBMD, bone mineral content (BMC), bone area (BA), and size-adjusted BMC (SA-BMC, adjusted for height or length, weight and BA) of the whole body (WB) and lumbar spine (LS) in mother-baby pairs, and total hip (TH) in mothers. The primary outcome was the difference between groups in % change (± SE) in maternal LS aBMD between PP2 and PP14. Secondary outcomes included changes in maternal markers of bone formation (P1NP and BAP) and resorption (CTX), serum 25-hydroxy vitamin D (25(OH)D), parathyroid hormone (PTH), plasma and urine concentrations of creatinine (Cr), calcium (Ca), phosphate (PO4) and magnesium (Mg), urine mineral:creatinine ratios, TmCa/GFR and TMP/GFR, respectively), breastmilk mineral composition (Ca, P, Na, K and Na/K ratio); and infant growth Z-scores and bone mineral. Statistical models were adjusted for potential confounders. Median maternal age was 24.5 (IQR 21.1, 26.9) yrs. Mean gestation was 40.9±1.8 wks and not significantly different between groups. All women were breastfeeding at PP2 and PP14. More HIV+ women reported exclusive breastfeeding (PP2: 82.9% v 58.7%, p=0.0008; PP14: 86.7% v 66.2%, p=0.002). Body weight was 4-5% lower in HIV+ women. By PP14, mean duration of ART was 29.3±5.1 wks, adherence was > 95%, and the median CD4 count was 403 (IQR 290-528) cells/mm3. Maternal aBMD decreased between PP2 and PP14 at all skeletal sites in both groups as expected in lactation. Reductions in LS aBMD were not significantly different between groups (-1.8±0.4% vs -2.5±0.4%, p=0.3). However, HIV+ women had a significantly greater reduction in TH aBMD which persisted after adjustment for body size (-3.7±0.3% vs -2.7±0.3%, p=0.04). Median serum 25(OH)D was 67.4 nmol/L (IQR 54.8, 83.7) at PG36 and 57.6 nmol/L (48.7, 70.1) at PP14 with no significant difference between groups. Changes in 25(OH)D and PTH from PG36 to PP14 were not significantly different between groups (25(OH)D: -13.9±4.1% vs -11.1±3.1%; PTH: +60.0±6.4% vs +57.6±6.4%; both p > 0.05). However, HIV+ women had 33-35% greater plasma PTH concentrations at both PG36 and PP14. Bone formation and resorption markers increased in both groups between PG36 and PP14. HIV+ women had greater increases (CTX: +74.6±5.9% vs +56.2±5.9%; P1NP: +100.3±5.0% vs +72.6±5.0%; BAP: +67.2±3.6% vs +57.1±3.6%, all p < 0.05). They also had a greater decrease in plasma Ca (-6.6±0.5% vs-3.8±0.5%, p≤0.0001) and greater increase in plasma phosphate (+14.4±2.0% vs +7.7±2.0%, p=0.02). Changes in plasma Cr and Mg, TmP/GFR and urine mineral:creatinine ratios were not significantly different between the groups. However, at both PG36 and PP14, HIV+ had significantly lower mean plasma Ca (PG36: -1.0±0.5%; PP14: -4.1±0.6%) and TmP/GFR (PG36: -11.4±3.1%; PP14: -7.2±3.0%) but higher PTH (PG36: +33.0±7.0%; PP14: +35.3±7.6%) compared to HIV- women (all p < 0.05). Mean breastmilk Ca decreased between PP2 and PP14, and the changes were not different between the groups (-19.9±3.0% vs -24.2±3.1%, p=0.3). There were no significant changes in breastmilk phosphorus (P) in both groups, but HIV+ women had significantly higher concentrations (PP2: +9.7±3.8%, p=0.01; PP14:+9.6±3.5 %, p=0.007). Breastmilk P was significantly correlated with maternal plasma [CTX] in a separate ANCOVA model (β = +0.13±0.04% per 1% increase in CTX, p=0.0003). Mean breastmilk Na, K concentrations and Na/K decreased between PP2 and PP14 in both groups. However, HIV+ women had a smaller decrease in breastmilk Na (-44.3±8.9% vs -72.6±9.0%, p=0.03). They also had a trend towards smaller reduction in Na/K ratio (-22.2±9.3% vs -46.6.6±9.5%, p=0.07). Babies born to HIV+ mothers (HIV-exposed infants, HEI) had significantly lower gains in weight +53.0±1.4% vs +57.5±1.4%, p=0.02) compared to HIV-unexposed infants (HUI), and also lower weight-for-age (-0.47±0.16, p=0.003) and length-for-age (-0.53±0.18, p=0.005) Z-scores at PP14. HEI had a slower gain in WB BMC (+51.2±1.9% vs +57.3±1.9%, p=0.02), but the difference was not significant after adjustment for body size (-6.0±3.5% vs -7.6±3.8%, p=0.2); showing that the bone mineral accretion was appropriate for achieved infant size. In contrast, HEI had a greater increase in LS BMC (+29.5±1.7% vs +24.4±1.7%, p=0.03), a difference which remained after size-adjustment (+9.4±5.8% vs +4.3±6.2%, p=0.02). This is the first study to compare changes in maternal aBMD and bone metabolism between HIV+ mothers on Option B+ ART and HIV- counterparts. The results show a greater reduction in TH aBMD in Ugandan HIV+ women on Option-B+ ART compared to HIV- in the first three months of lactation, consistent with their greater increases in bone turnover markers, lower TmP/GFR and plasma phosphate, and higher breastmilk phosphorus concentration. Also, HEI have slower growth and whole body bone mineral accretion compared to HUI. It is important to determine if these changes are temporary or have long-term consequences for the bone health of the mother and child.

<p>Background: Although clinicians encounter antimycobacterial treatment in Human mmunodeficiency (HIV)-infected children as one of the most common treatments coadministered with antiretroviral treatment (ART), quantitative data on the extent of antimycobacterial treatment among HIV-infected children at the time of commencement of ART and at different times during ART is scarce. The baseline risk factors associated with being on both ART and antimycobacterial treatments are not known and it remains to be elucidated how the different exposure factors impact on the antimycobacterial treatment-free survival of children who begin ART without antimycobacterial treatment.Objectives: To describe the prevalence of antimycobacterial treatment among children at the time of starting ART and the antimycobacterial treatment-free survival after starting ART. Design: A retrospective cohort study based on record reviews at the Harriet Shezi children&lsquo / s clinic (HSCC).Population: HIV-infected children less than fifteen years of age presumed ART na&iuml / ve started on ART at HSCC.Analysis: A descriptive analysis of the prevalence of antimycobacterial treatment at time of start of ART was done. Kaplan Meier (KM) survival curves were used to determine the antimycobacterial treatment-free survival and logistic regression was used to analyze the association between baseline factors and future antimycobacterial treatment among children who had no antimycobacterial treatment at time of start of ART. Results: The prevalence of antimycobacterial treatment at the time of starting ART was 518/1941 (26.7%, 95% confidence interval (CI): 24.7-28.7). Among children who started ART without antimycobacterial treatment, the KM cumulative probability of antiretroviral and antimycobacterial (ART/antimycobacterial) co-treatment in the first 3 months of starting ART was 4.6% (95% CI: 4.1- 5.2), in the first 12 months it was 18.1% (95% CI: 17.0-19.2) and in the first 24 months of starting ART it was 24% (95% CI: 21.9-25.1). Survival analysis suggested that children with high baseline viral load, advanced World Health Organization (WHO) stage of disease, very low normalized weight for age (waz) and very young age (less than one year) at start of ART had significantly reduced antimycobacterial treatment-free survival (log rank p &lt / 0.05) in the first two years of starting ART. In the logistic regression model, age less than one year {Odds ratio (OR): 3.7 (95% CI: 2.2-6.0 / p &lt / 0.0001)} and very low weight for age Z-score (waz &lt / -3) {OR / 2.2 (95% CI: 1.4-3.6 / p = 0.0015)} were the two critical risk factors independently associated with future antimycobacterial treatment. Conclusions: Antimycobacterial treatment is extremely common among HIV-infected children at the time of starting ART and early after starting ART and the incremental risk of being on ART/antimycobacterial co-treatment decreases with time on ART. The results emphasize the need for a heightened and careful alertness for mycobacterial events especially among children starting ART with severe malnutrition and those who start ART at age less than one year. The results further suggest that it is probably optimal to start ART in children before their nutritional status has deteriorated severely in the course of the HIV disease so that they get protection against mycobacterial events by early ART.</p>

<p>Background: Although clinicians encounter antimycobacterial treatment in Human mmunodeficiency (HIV)-infected children as one of the most common treatments coadministered with antiretroviral treatment (ART), quantitative data on the extent of antimycobacterial treatment among HIV-infected children at the time of commencement of ART and at different times during ART is scarce. The baseline risk factors associated with being on both ART and antimycobacterial treatments are not known and it remains to be elucidated how the different exposure factors impact on the antimycobacterial treatment-free survival of children who begin ART without antimycobacterial treatment.Objectives: To describe the prevalence of antimycobacterial treatment among children at the time of starting ART and the antimycobacterial treatment-free survival after starting ART. Design: A retrospective cohort study based on record reviews at the Harriet Shezi children&lsquo / s clinic (HSCC).Population: HIV-infected children less than fifteen years of age presumed ART na&iuml / ve started on ART at HSCC.Analysis: A descriptive analysis of the prevalence of antimycobacterial treatment at time of start of ART was done. Kaplan Meier (KM) survival curves were used to determine the antimycobacterial treatment-free survival and logistic regression was used to analyze the association between baseline factors and future antimycobacterial treatment among children who had no antimycobacterial treatment at time of start of ART. Results: The prevalence of antimycobacterial treatment at the time of starting ART was 518/1941 (26.7%, 95% confidence interval (CI): 24.7-28.7). Among children who started ART without antimycobacterial treatment, the KM cumulative probability of antiretroviral and antimycobacterial (ART/antimycobacterial) co-treatment in the first 3 months of starting ART was 4.6% (95% CI: 4.1- 5.2), in the first 12 months it was 18.1% (95% CI: 17.0-19.2) and in the first 24 months of starting ART it was 24% (95% CI: 21.9-25.1). Survival analysis suggested that children with high baseline viral load, advanced World Health Organization (WHO) stage of disease, very low normalized weight for age (waz) and very young age (less than one year) at start of ART had significantly reduced antimycobacterial treatment-free survival (log rank p &lt / 0.05) in the first two years of starting ART. In the logistic regression model, age less than one year {Odds ratio (OR): 3.7 (95% CI: 2.2-6.0 / p &lt / 0.0001)} and very low weight for age Z-score (waz &lt / -3) {OR / 2.2 (95% CI: 1.4-3.6 / p = 0.0015)} were the two critical risk factors independently associated with future antimycobacterial treatment. Conclusions: Antimycobacterial treatment is extremely common among HIV-infected children at the time of starting ART and early after starting ART and the incremental risk of being on ART/antimycobacterial co-treatment decreases with time on ART. The results emphasize the need for a heightened and careful alertness for mycobacterial events especially among children starting ART with severe malnutrition and those who start ART at age less than one year. The results further suggest that it is probably optimal to start ART in children before their nutritional status has deteriorated severely in the course of the HIV disease so that they get protection against mycobacterial events by early ART.</p>

This research focuses on the psychosocial factors that affect adherence to highly active antiretroviral therapy (HAART) amongst HIV/AIDS patients at Kalafong Hospital. Even though the development of such regimens has helped turn HIV infection in the United States into a relatively manageable, though still serious chronic disease, compliance remains one of the major challenges in managing medication for those patients living with HIV/AIDS. This is particularly relevant given the high adherence rate (95%) required to obtain a successful long-lasting effect. In South Africa non-compliance to HAART is an under-explored phenomenon. Consequently, an understanding of factors influencing compliance is still incomplete. A qualitative study that investigates non-adherence to medication in HIV/AIDS patients was undertaken at Kalafong Hospital. This study aimed to understand patients’ psychosocial difficulties resulting in non-adherence. The study was approached in terms of the health belief model (HBM), which addresses individual characteristics pertaining to change, the transtheoretical change model (TTM) and the motivational interviewing model (MI), which address both individual and social contexts pertaining to change. The findings are designed for use by healthcare professionals as a proactive compliance enhancement tool. Participants were recruited through referrals by the medical staff to the researcher. The criteria included that participants had relapsed due to non-compliance with drug therapy. Participants that were currently experiencing difficulties with adherence were also included in the study. Males and females aged between 20 and 40 were included in the study. Fifteen participants between the ages of 20 and 40 participated in the study (13 females and two males). The data were collected by means of semi-structured interviews and follow-up unstructured questions. The interviews were audio recorded and field notes were taken. Data were analysed qualitatively. Sixteen themes emerged and were further classified into two categories: individual and social context. The themes were then compared and integrated with the literature. The study concludes that psychosocial factors such as support from family, friends and healthcare workers was found to be of utmost importance in encouraging adherence. Medication can only prolong a patient’s life if the psychosocial context in which the patient is embedded is considered in the treatment plan. / Dissertation (MA)--University of Pretoria, 2008. / Psychology / unrestricted

With the worldwide increase in numbers of individuals infected with the human-immune deficiency virus (HIV) and acquired immune deficiency syndrome (AIDS), the need for more information became essential. The devastating influences and fatal outcome of this disease is inevitable. These individuals are confronted with mortality and various disabling conditions. One of these disabling conditions is the possible development of a hearing loss. Loss of hearing sensitivity related to HIV/AIDS is only one of numerous effects the virus may have on humans and their quality of life. Therefore increased awareness of HIV/AIDS and the influences of this disease is inevitable for the modern audiologist. The precise nature and the extent of the influence that HIV/AIDS and antiretroviral therapy (ART) has on the hearing ability of a person are unknown to date. Even though a relationship between hearing loss, HIV/AIDS and the administration of relevant medication is expected, no clear explanation is available to provide the public or clinicians with the necessary information on assessments, interventions and aural rehabilitation techniques. Without being able to identify the specific cause, symptoms and place of lesion of the hearing loss, it will be difficult to ensure appropriate monitoring and treatment. Information regarding the influences of HIV/AIDS and ART on hearing sensitivity had to be established to ensure appropriate intervention and rehabilitation options. The first part of this research project reviews the evidence available regarding the possible influences of HIV/AIDS on hearing. Throughout the research a cross-sectional design with quantitative and qualitative approaches were followed comprising of a structured interview, basic and specialized audiometric battery to obtain the necessary case history, as well as results for these different audiological tests that were conducted. The specialised tests included immittance measurements, distortion-product otoacoustic emission (DPOAE) and auditory brainstem response (ABR). The results of this study were discussed in terms of the three sub aims in accordance with the different audiological tests that were conducted. The results indicated that those participants with ART exposure had a significantly higher incidence of hearing loss. The pure tone averages were mainly found within normal limits but decreased with the progression of the final stages of HIV/AIDS. The high and low frequencies of the audiogram were often affected with loss of hearing sensitivity suggesting the presence of a high and low frequency slope. The final three stages of HIV/AIDS had a significantly higher incidence of bilateral hearing loss. ART exposure were associated with more severe degrees of hearing loss. The DPOAE and ABR indicated that cochlear and retro-cochlear damage existed often among these participants. Only 20% participants had abnormal tympanograms suggestive of conductive pathology. The results revealed that the type of pathology varied across the stages of HIV/AIDS. The conclusions and implications of this study are discussed. Recommendations incorporate the development of HIV/AIDS awareness campaigns that includes audiological information on the possible influences, where to refer or where to seek assistance; issues regarding the improvement of the modern audiologists’ knowledge in terms of the management of the audiological needs of individuals with HIV/AIDS and the application of these results in the industrial setting to utilize when they consider granting compensation claims. / Dissertation (MCommunication Pathology)--University of Pretoria, 2008. / Speech-Language Pathology and Audiology / unrestricted

The HIV/AIDS epidemic and the COVID-19 pandemic have ruined many people's lives. Antiretroviral therapy (ART) has controlled the HIV/AIDS epidemic and COVID-19 vaccine is expected to ease confusion caused by the pandemic. However, the supply of health-resource falls far short of the demand in resource-constrained countries; thus, decision-making about resource allocation should be discussed. Botswana, as a resource-constrained country with a high prevalence of HIV, needs to construct its own framework for ART allocation. We propose an equitable framework for ART and COVID-19 vaccine allocation in Botswana based upon the egalitarian principle, which provides each individual has an equal chance of receiving them. We use a spatial mathematical model of treatment accessibility with an equity objective function, and sequential quadratic programming is used to address the nonlinear programming model. Considering Botswana's current health infrastructure, our strategy brings the most equal health outcomes. However, the disparity of accessibility still exists between rural and urban areas even from our equitable strategy. We present proposals that can increase the accessibility of rural areas using sensitivity analysis. Our work can be applied to different contexts, especially in sub-Saharan Africa.

The study emanates from the need to identify the biopsychosocial factors that influence patients’ adherence to antiretroviral therapy (ART) within the South African context The specific goal of the study was to explore these in order to make recommendations to enhance service delivery. Applied research was conducted, with its primary task being to stimulate thought and action concerning the challenges faced by patients who are on ART. In order to gather comprehensive data, the researcher engaged in a combination of the qualitative and quantitative approaches. For the qualitative case study the researcher made use of semi-structured interviews, utilizing the non-probability sampling method, aiming to understand and interpret the meaning that the multidisciplinary team accorded to matters of antiretroviral treatment. For the quantitative part of the study the probability random sampling method was made use of for the quantitative descriptive survey. Questionnaires were employed to collect data from 201 patients already on antiretroviral medication. The conclusions, which were drawn from the research findings, identified challenges to adherence to ART: the study confirmed that since the advent of combination antiretroviral therapy (HAART), HIV/AIDS has been transformed into a manageable and chronic condition, and has undoubtedly extended and improved the quality of life for people living with HIV/AIDS. However, it also confirmed that ART, is a complex intervention, which is accompanied by severe biopsychosocial implications, requiring near-perfect adherence in order to prevent the development of resistance. The impact that the various psychosocial needs of millions of HIV/AIDS people living on ART will have on current social structures and services, will tax the available professional social services, particularly the social work profession. The social correlation of HIV/AIDS and poverty is endorsed by the findings, confirming that the high level of unemployment, coupled with families who are headed by women and who receive little support, lead to almost total dependency on social security. The findings further indicate a specific relationship between socio-economic circumstances and the ability to adhere to ART. Empowering HIV/AIDS patients, to be able to adhere to ART, is therefore indicated, as is the further need for a regulator of HIV/AIDS support services, in order to protect and promote high standards of service delivery, especially counselling. / Thesis (DPhil)--University of Pretoria, 2007. / Social Work and Criminology / DPhil / unrestricted

Background: Due to its continuous exposure to food antigens and microbes, the gastrointestinal tract (GIT) is in a constant state of low level immune activation and contains an abundance of activated CCR5+CD4+ T lymphocytes, the primary target HIV-1. As a result, the GIT is a site of intense viral replication and severe CD4+ T cell depletion, a process that begins during primary HIV-1 infection and continues at a reduced rate during chronic infection in association with increased production of pro-inflammatory cytokines, a breakdown in the epithelial barrier, microbial translocation, systemic immune activation and the continued recruitment and infection of new target cells. AntiRetroviral Therapy (ART) is only partially effective in reversing these pathogenic changes. Despite the importance of the GIT in HIV-1 pathogenesis, and as a reservoir of persistent virus during ART, little is known about the diversity of HIV-1 in the GIT, or how different tissues in the GIT respond to ART. Objectives: Primary objectives of this thesis were to: 1) characterize the diversity of HIV-1 RNA variants in different parts of the GIT; 2) determine whether there is compartmentalized evolution of HIV-1 RNA variants in the GIT and whether these variants are likely to have different biological properties; 3) investigate the impact of ART on immune restoration in the GIT. Methods: A prospective study of the duodenum, jejunum, ileum and colon of African AIDS patients with chronic diarrhea and/or weight loss, sampled before and during 6 months of ART. RNA extracted from gut biopsies was reverse transcribed and PCR amplified. Env and gag PCR fragments were cloned, sequenced and subjected to extensive phylogenetic analysis; pol PCR fragments were analyzed for drug resistance. CD4+, CD8+ and CD38+CD8+ T cells levels in biopsies collected at baseline (duodenum, jejunum, ileum and colon) and after 3 (duodenum) and 6 (duodenum and colon) months of ART were quantified by flow cytometry and immunohistochemistry, plasma and tissue VL by the Nuclisens assay. Results: Viral diversity varied in different regions of the GIT with env HIV-1 RNA variants being significantly more diverse than gag variants. Gag HIV-1 RNA variants were widely dispersed among all tissue compartments. Some env variants formed tight monophyletic clusters of closely related viral quasispecies, especially in the colon, a finding that is suggestive of compartmentalized viral replication and adaptive evolution. CD4+ T cell and VL levels were significantly lower, while CD8+ including activated CD38+CD8+ T cell levels were higher in the duodenum and jejunum versus the colon. After 6 months of ART, a significant but incomplete recovery of CD4+ T cells was observed in the colon but not in the duodenum. Failed restoration of CD4+ T cells in the duodenum was associated with non-specific enteritis and CD8+ T cell activation. Conclusions: These results advance our understanding of the GIT as a host-pathogen interface by providing new insights into the diversity, evolution and dissemination of HIV-1 variants in the GIT. Strategies aimed at decreasing immune activation, especially in the small intestine, may be highly beneficial in enhancing the therapeutic efficacy of ART. / Thesis (PhD)--University of Pretoria, 2014. / lk2014 / Immunology / PhD / Unrestricted