The aim of this research was to implement and evaluate guidelines that will be used by treatment support counsellors in an attempt to increase client adherence to antiretroviral treatment.

The aim of this research was to implement and evaluate guidelines that will be used by treatment support counsellors in an attempt to increase client adherence to antiretroviral treatment.

Thesis (DTech (Chemistry))--Cape Peninsula University of Technology, 2016. / Bimetallic silver-platinum (Ag-Pt) nanoparticles (NPs) were synthesized via simultaneous reduction of varying mole fractions of metal precursors H2PtCl6.6H2O and AgNO3 by sodium citrate. Kinetics rates of were as follows; Ag NPs (0.079 s-1), Ag-Pt NPs 1:1 (0.082 s-1) and Pt NPs (0.006 s-1). The UV visible spectrum of Ag NPs exhibited a characteristic absorption band while Pt NPs and Ag-Pt bimetallic NPs exhibited no absorption peaks. Successful formation of both monometallic and bimetallic NPs was confirmed via transmission electron microscopy (TEM); selected area electron diffraction (SAED) and energy dispersive X-ray (EDX) analysis. TEM images depicted core-shell arrangement in the bimetallic (BM) NP ratios (1:1, 1:3 and 3:1) with an average particle size of 21 nm. The particle size trend where monometallic Ag NPs (60 nm) > Pt NPs (2.5 nm) while in the BM ratios Ag-Pt NPs 1:1 (25 nm) > Ag-Pt NPs 1:3 (20.7 nm). X-ray diffraction (XRD) patterns depicted crystallinity in all the synthesized NPs with confirmation of the face centred cubic structure formation. Transducers were fabricated by drop casting the nanoparticless on the glassy carbon electrode (GCE) and their electrochemical properties studied via cyclic voltammetry (CV). High diffusion coefficient (D) and surface coverage reported were Ag NPs (6.70 cm2 s-1, 54.49 mol cm-2 ) and Ag-Pt NPs 1:1 (0.62 cm2 s-11.85 mol cm-2). Electrochemical band gaps ranged from 1.45 to 1.70 eV while the Tauc’s model band gaps of nanoparticles were found in the range of 2.48 to 3.84 eV. These band gaps were found to be inversely proportional to particle size, which was attributed to the quantum confinement effect. Both optical and electrochemical band gap portrayed similar trend as well as an increase in the BM NP relative to monometallics. These nanoparticles band gaps are within semiconductor range for most materials. The electrochemical behaviour and surface characteristics were studied using 0.1 M PBS solution by scan rates variations for the diffusion coefficient determination of modified electrodes which ranged from 0.62 to 6.10 x 10-5 cm2 s-1. Laviron’s approach for parameters such as apparent charge transfer rate constant, ks, and charge transfer coefficient, α, for electron transfer between NPs and GCE were investigated using CV. The values of electron-transfer coefficients ranged from 0.1 to 0.7 while the charge transfer rate constant values ranged from 0.74 to 31.13 s-1.

The overall purpose of this dissertation was to examine evidence of spillover effects of HIV care and treatment service scale up in sub-Saharan Africa in the past decade. Particularly the focus was to quantify any effect HIV treatment initiation by a person living with HIV (PLHIV) may confer health benefits to the HIV negative population by increasing utilization of non-HIV services or reduce mortality risk. This dissertation had three primary aims. The first aim was to conduct a systematic review of the effect of increasing ART uptake in high HIV prevalence communities on use of non-HIV health services, including maternal, child, in/out-patient, non-HIV laboratory, and TB diagnosis and treatment services. Overall positive effects were found on the majority of health service indicators examined for non-HIV laboratory service utilization and Tuberculosis diagnosis and treatment services. We found negative associations on the majority of indicators examined for child health services. The existing evidence did not point to clear tendencies for maternal health services and outpatient and inpatient services. Restricting the sample to studies with stronger study designs for causal inference, the positive effect on non-HIV laboratory services and the negative impact on child health services held but evidence was mixed for TB diagnosis and treatment services, maternal health services and outpatient and inpatient services. The second aim of this dissertation was to conduct regression discontinuity quasi-experiments to determine whether exposure to health benefits from ART utilization by a person living with HIV (PLHIV) in a household affects uptake of TB, hypertension (HTN) and diabetes mellitus (DM) treatment by other household members with these conditions. The study was conducted in the comprehensive population cohort followed by the Africa Health Research Institute (AHRI) in Kwazulu-Natal (KZN), South Africa. We linked PLHIV engaged in HIV care to their cohabitating household members aged ≥15 years using a unique identifier for homesteads. Household ART utilization significantly increased treatment for diabetes (RR 1.90: 95% CI 1.07-3.40) but not for TB (RR 1.12: 95% CI 0.71-2.03) or hypertension (RR 1.31: 95% CI 0.97-1.77). The third aim of this dissertation was to use the same regression discontinuity design and KZN cohort data as in aim 2 to determine whether exposure to health benefits from ART utilization by PLHIV in a household reduces all-cause mortality of other household members. Overall, household ART utilization did not decrease all-cause mortality (Hazard Ratio (HR) 0.95: 95% CI 0.65-1.4), however, restricting the analysis to a narrow CD4+ cell count range around the regression discontinuity threshold showed reduced all-cause mortality by 67% (HR 0.43: 95% CI 0.22-0.85) among household members of PLHIV on ART; the reduced risk was driven largely by the significant reduction noted among female household members (HR 0.21: 95% 0.08, 0.56).

Introduction APOBEC3G and other related cellular cytosine deaminase family members have potent antiviral activity. In the absence of HIV-1 Vif, APOBEC3G mutates the viral DNA during viral reverse transcription. Our knowledge of the Vif-APOBEC3G interaction in human populations infected with subtype C HIV-1 is limited. Investigation of interactions between HIV and its host is crucial as it can ultimately be exploited in vaccine and therapy design. We hypothesised that certain APOBEC3G haplotypes and/or their expression in peripheral blood mononuclear cells of seroconverters affect viral setpoint and CD4+ T cell counts. We also hypothesised that certain APOBEC3G genetic variants are associated with increased frequency of G to A hypermutations during primary HIV-1 infection and that Vif variability influences disease progression and its ability to neutralise APOBEC3G haplotypes. Methods Our South African study cohort consisted of females at high risk for HIV-1 infection and women with known recent HIV-1 infection. We used quantitative real-time PCR to measure APOBEC3G expression in HIV- and HIV+ samples during primary infection. APOBEC3G variants were identified by DNA sequencing and TaqMan Genotyping. The HIV-1env gene was sequenced to assess Env diversity and the extent of APOBEC3G induced hypermutations. Vif variability was assessed by plasma derived clonal Vif sequences (n= 10-20 per patient) and Vif function was assessed by APOBEC3G degradation assays and HIV-1 infectivity assays. Results We found no correlation between APOBEC3G expression levels and plasma viral loads (r=0.053, p=0.596) or CD4+ T cell counts (r=0.030, p=0.762) in 32 seroconverters. However, APOBEC3G expression levels were significantly higher in HIV- individuals compared to HIV+ individuals (p<0.0001) including matched pre- and post-infection samples from the same individuals (n=13, p<0.0001). Twenty five single nucleotide polymorphisms (SNPs) were identified within the APOBEC3G region. SNP 186R/R was associated with significantly higher viral loads (p=0.0097) and decreased CD4+ T cell levels (p=0.0081), indicating that 186R/R has a negative effect on HIV restriction. Overall HIV-1 env sequences contained a higher number of APOBEC3F compared to APOBEC3G-induced hypermutations and the number of APOBEC3F-induced hypermutations correlated negatively with viral load (r= -0.6, p=0.006) and positively with CD4 T cell counts (r=0.6, p=0.004). We cloned and sequenced a total of 392 subtype C Vifs, which showed an interpatient diversity of 6.2% to 19.2% at the amino acid level. Interestingly, Vif sequence comparison showed a strong preference for a Lysine or a Serine at position 36 for APOBEC3G 186R/R and APOBEC3G 186H/H individuals, respectively. Selected natural subtype C Vif alleles had greater ability to counteract wild type APOBEC3G 186H as compared to the APOBEC3G 186R variant as shown by both functional and HIV infectivity assays. Conclusions In conclusion, APOBEC3G expression in peripheral blood mononuclear cells does not correlate with viral loads or CD4+ T cell counts during primary HIV-1 subtype C infection. However, genetic variants of APOBEC3G may affect HIV-1 pathogenesis. Amino acid changes in Vif may influence its anti-APOBEC3 activity. HIV-1 subtype C Vifs may have adapted to counteract the more active wild type APOBEC3G as compared to the less active APOBEC3G 186R variant. These studies have improved our understanding of viral-host interactions in African populations and HIV-1 subtype C infections. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2014.

Indiana University-Purdue University Indianapolis (IUPUI) / Background: The current treatment for HIV/AIDS is called highly active antiretroviral therapy (HAART) and is a combination of anti-HIV reverse transcriptase inhibitors and protease inhibitors. HAART is capable of suppressing HIV replication and subsequently improving the patients’ survival. However, the issues associated with use of HARRT such as the high cost, severe side-effects, and drug resistance have called for development of alternative anti-HIV therapeutic strategies. In this study, we screened several traditional Chinese medicinal herbal extracts for their anti-HIV activities and determined their anti-HIV mechanisms. Methods: Nine traditional Chinese medicinal (TCM) herbal plants and their respective parts derived from Hainan Island, China were extracted using a series of organic solvents, vacuum dried, and dissolved in dimethyl sulfoxide. Initial anti-HIV activity and cytotoxicity of these extracts were evaluated in HIV-infected human CD4+ T lymphocytes Jurkat. Extracts of higher anti-HIV activities and lower cytotoxicity were selected from the initial screening, and further examined for their effects on HIV-1 entry, post-entry, reverse transcriptase, gene transcription and expression using combined virology, cell biology and biochemistry techniques. Results: Four extracts derived from two different herbal plants completely blocked HIV-1 replication and showed little cytotoxicity at a concentration of 10 g/ml. None of these four extracts had any inhibitory effects on HIV-1 long terminal repeat promoter. Two of them exhibited direct inhibitory activity against HIV-1 reverse transcriptase (RT). All four extracts showed significant blocking of HIV-1 entry into target cells. Conclusions: These results demonstrated that four TCM extracts were capable of preventing HIV-1 infection and replication by blocking viral entry and/or directly inhibiting the RT activity. These results suggest the possibility of developing these extracts as potential anti-HIV therapeutic agents.

No description available.

Despite significant medical advances in HIV treatment, people living with HIV and substance use (PLWH-SU) remain left behind. Compared to people living with HIV (PLWH) without comorbid substance use, PLWH-SU are less likely to engage in medical care and to achieve viral suppression. As a result, PLWH-SU have more frequent preventable hospitalizations, higher rates of viral transmission, and greater morbidity and mortality. Although there is extensive research that explores ways to enhance PLWH-SU’s engagement in HIV care by improving patient-provider interactions, most have focused on the patient, and none have been effective. Grounded in the sociological theory of habitus, this dissertation attended to the medical provider in the patient-provider dyad and aimed to better understand how medical providers’ perceptions and dispositions towards PLWH-SU are formed, and how these perceptions and dispositions are displayed in the ways medical providers interact with and take care of PLWH-SU. Before engaging with habitus, I first conducted a systematic review on how the theory has been used to study medical providers’ clinical practices. Results of the review show that while existing literature has been limited and unclear in its usage of habitus, these studies are informative, and they demonstrate that habitus can be a suitable theoretical foundation for expanding present approaches to research on medical providers’ clinical interactions with PLWH-SU. Following the systematic review, I developed my conceptual framework of medical providers’ treatment habitus (i.e., medical providers’ dispositions towards caring for PLWH-SU) and estimated a typology of treatment habitus using survey data from 258 medical providers in Miami, Florida, Atlanta, Georgia, and the District of Columbia. My analyses show that among this sample of medical providers, there are four types of treatment habitus towards caring for PLWH-SU, and treatment habitus is associated with multi-level factors (e.g., providers’ race, study site, receipt of substance use disorder training). To further explore how medical providers came to develop and how they understand their own treatment habitus, I conducted conversational interviews with 36 medical providers who had completed the abovementioned survey. These interviews revealed medical providers exhibit a spectrum of treatment habitus that is distinguishable by their intentions (person-centered vs. provider-centered) and their methods (informative vs. directive). The interviews also revealed that there are discrepancies in how medical providers spoke about PLWH-SU and how they described their practices towards caring for PLWH-SU. Specifically, although most providers used negative terms to refer to PLWH-SU, the stigmatizing language was almost never accompanied by recollections of stigmatizing behaviors during clinical interactions with PLWH-SU. Taken together, this dissertation expanded on current knowledge about not only how medical providers act when caring for PLWH-SU, but also why they act the ways they do. Findings from this study contribute to an understudied area of HIV and substance use research and provide insights for the development of novel provider-based interventions that can improve the health of this vulnerable and marginalized population.

Introduction. The demand for comprehensive Human Immunodeficiency Virus (HIV) and Acquired Immunodeficiency Syndrome (AIDS) services is greater than the available supply, particularly for the provision of antiretroviral therapy. The resulting bottleneck in service delivery has considerable implications for people living with HIV and for resource management. Aim. The purpose of this research was to investigate loss-to-care and associated variables of adult HIV-infected people who were eligible for antiretroviral therapy, from July 2004 to December 2007 at Sinikithemba HIV Clinic in Durban, KwaZulu-Natal. Methods. An observational descriptive and analytic cohort study design was used. Secondary data sourced from Sinikithemba were collated. All HIV-infected adults, 15 years and older when registered on the TrakCare database, who were eligible for antiretroviral therapy were included in the study. Data were extracted to describe the preparation of HIV infected adults who were eligible for antiretroviral therapy. Variables were first summarised and described before the confirmatory analytic steps were taken to measure associations at the p<0.05 significance level. Results. Of the 10 424 HIV-infected adults registered at Sinikithemba, 5470 (52%) were eligible for antiretroviral therapy from July 2004 to December 2007 and 2979 (54%) of these were lost to care prior to initiating antiretroviral therapy. Six exposure variables were significantly associated with this loss-to-care, (gender, baseline CD4 count, pre-eligibility care, antiretroviral therapy delay, preparation step and waiting time). These variables remained significantly associated with loss-to-care even after controlling for confounding with logistic regression. Discussion and Recommendations. With the rapid scale-up of antiretroviral therapy programmes, the outcome of those people living with HIV lost to care before commencing therapy have not been adequately documented. This large cohort enrolled over three-and-a-half years demonstrates that the loss-to-care prior to initiation of antiretroviral therapy is a significant problem that needs to be further investigated. Focusing retention strategies at the pre-antiretroviral therapy stage of HIV care will improve overall programme outcomes. / Thesis (M.Med.)-University of KwaZulu-Natal, Durban, 2011.

HIV-positive adolescents are an increasingly numerous and challenging population in the South African HIV/AIDS epidemic. Their access to, and retention in, ART care has become a pressing public health concern. Comprised of four journal articles, this thesis explores the practice of antiretroviral treatment (ART) among a cohort of HIV-positive adolescents (age 10-19) in South Africa's Eastern Cape. By 'practice', I mean the volatile, situated and relational 'work' that goes into young people's everyday achievement of ART - into consuming daily medication, regularly attending health appointments, and participating in HIV programmes. Through an exploration of the ways in which some HIV-positive adolescents use, appropriate, or reject ART care; this thesis contributes to a much-needed evidence-base on the needs and survival strategies of adolescent ART users. Data for this study was gathered through eight months of multi-method ethnographic fieldwork with 23 HIV-positive youth, their families, and local health workers. The findings elucidate adolescent ART as a complex (and often volatile) form of social incorporation, through which young people negotiate survival, care and moral connection in contemporary South Africa. Enrolling in ART meant being encompassed into a (often hierarchical) set of social relationships, through which adolescents sought belonging, recognition and protection, amid profound insecurity. Through ART and its associated programmes, adolescents and their families attempted to strengthen familial ties, appeal to powerful patrons, petition for care, and access basic resources. Yet these pursuits were often deeply ambivalent, as discipline, blame, and resentment often came encased in the terms of care. At the crux of each article is an attempt to understand how adolescents, often alongside their families, negotiated both the social stakes and possibilities of ART. Through these discussions, we might better be able to grasp the fragility and complexity of young people's retention in ART.