Master of Public Health - MPH / Adequate levels of adherence to treatment for tuberculosis (TB) and HIV at the same time poses a problem for public health in South Africa. TB/HIV co-infected patients face many potential barriers to adherence to treatment for both conditions. There is a need for more knowledge about factors influencing treatment adherence in co-infected patients on concomitant treatment. The aim of this study was to explore the barriers and facilitators to treatment adherence among people co-infected with TB/HIV living in the Alfred Nzo District, Eastern Cape, in order to identify the barriers and facilitators to adherence.

Background: Antiretroviral therapy (ART), notably lopinavir and nevirapine substantially reduces Human immune-deficiency virus (HIV) associated morbidity and mortality in HIVinfected children. Low concentrations of nevirapine and lopinavir have been linked to inferior virological outcomes; it is recommended that lopinavir and nevirapine concentrations are maintained above 1 mg/L and 3 mg/L, respectively, in order to maintain viral suppression. Adherence to both lopinavir and nevirapine ART, respectively has long known to be a crucial contributor to HIV treatment success. Lopinavir and nevirapine pharmacokinetics demonstrate considerable inter-individual variability, which may affect treatment outcomes. At least part of this variability may be explained by host genetic factors. Associations between human genetic variants and exposure to lopinavir and nevirapine are incompletely understood, and have not been studied in a South African paediatric population. Data in this thesis were from a clinical trial conducted at Rahima Moosa Mother and Child Hospital in Johannesburg to assess whether NVP can be re-used (Post-randomization Phase) among 323 children exposed to NVP for PMTCT if they are first suppressed on ritonavir-boosted lopinavir based regimen (Pre-randomization Phase). This thesis assessed the relationship between serial clinic visits lopinavir (Pre-and-Post-randomization) and nevirapine (Postrandomization) concentrations and/or percentage adherence(Pre-and-Post-randomization) and virological outcomes in children. Moreover, population pharmacokinetics models were used to characterise lopinavir and nevirapine parameters. From the final models parameters were derived and were used to assess the relationship between lopinavir and nevirapine pharmacokinetics and genetic polymorphism relevant to both drugs Methods: Cox proportional hazard regression modelling for multiple failure events was used to estimate the crude and adjusted hazard effect of lopinavir (Pre-and Post-randomization) and nevirapine(Post-randomization) concentrations and/or percent adherence(Pre-and Post-randomization) of viral load>400 copies/mL (Pre-randomization) and >50 copies/mL (Post-randomization), respectively. The population means and variances of lopinavir and nevirapine pharmacokinetic parameters at steady state were estimated using non-linear mixed-effects regression. The final models of lopinavir and nevirapine were used to derive individual clearances (CL/F), minimum concentrations (Cmin) and area under the concentration time curves (AUC). The associations between model-derived pharmacokinetic parameters and genotypes in selected genes relevant to lopinavir or nevirapine were explored. Results: In 237 children pre-randomization with viral loads and lopinavir concentrations, the crude and adjusted Cox models revealed significant associations between virologic failure (viral load>400 copies/mL) and both lopinavir plasma concentrations (<1/mg/L) and pretreatment height-for-age z-scores but not percent adherence. In 99 children postrandomization, lopinavir concentrations >1 mg/L reduced the risk of viremia (viral load >50 copies/mL) with about 40%, compared to children with LPV <1 mg/L. No association was found with percent adherence in this group. In 95 children on nevirapine post-randomization, nevirapine concentrations were not significantly associated with increased hazard of viremia (viral load >50 copies/mL). Similarly, there was no significant association with percent adherence in this group. Lopinavir and nevirapine pharmacokinetics were both separately best described with a one compartment models with absorption lag time and transit compartment absorption models, respectively. There was an age driven effect on lopinavir and nevirapine relative bioavailability, respectively. After adjusting for multiple testing, there was no significant association between lopinavir CL/F, Cmin and AUC and genetic polymorphisms in the ABCB1, CYP3A4, CYP3A5 and SLCO1B1. CYP2B6 516G→T and CYP2B6 983T→C were associated with NVP CL/F. CYP2B6 983T→C was associated with NVP Cmin and AUC. Additionally, polymorphisms in the ABCB1 and CYP3A5 were independently associated with NVP CL/F, Cmin and AUC. Conclusions: Lopinavir concentrations <1mg/L were associated with the increased hazard of viremia (viral load >400 copies/mL or >50 copies/mL). The results suggest that lopinavir plasma concentration monitoring at a routine clinic visit may be a useful tool in identifying sub-therapeutic antiretroviral concentrations in children, and this could be used as a guide to therapeutic drug monitoring in children. There was no statistically significant association between polymorphisms in the ABCB1, CYP3A4, CYP3A5 and SLCO1B1 and lopinavir pharmacokinetics. Polymorphisms in the ABCB1, CYP2B6 CYP3A4 and CYP3A5 predicted nevirapine pharmacokinetics.

Magister Public Health - MPH / Approximately 1.75 million adolescents (10-19 years old) globally were living with human immunodeficiency virus (HIV) in 2020, with the Eastern and Southern African regions the most affected by HIV. Progress has been made to increase access to antiretroviral therapy (ART) for adolescents living with HIV (ALHIV) to improve their survival. However, ALHIV still have worse treatment adherence and viral suppression compared to adults and children. This is in part because routine monitoring of HIV treatment programmes does not report for ALHIV; thus making their lack of progress in ART not visible. It is imperative to determine viral suppression and the factors that are associated with viral suppression among adolescents to assess treatment outcomes at local service levels.

Magister Public Health - MPH / HIV/AIDS remains a major public health issue that is affecting all population groups and communities in Zambia. Among the most affected groups are key populations (KPs) such as female sex workers. KPs are considered at high risk of contracting HIV but have limited access to HIV services and retention in care due to internalized stigma, discrimination, criminalization, and negative attitudes towards HIV treatment. Under the USAID Open Doors project in Zambia, KPs access comprehensive HIV prevention, care and treatment services. The test and treat strategy is implemented by the project in support of the UNAIDS 90-90-90 targets by 2020 to diagnose 90% of people living with HIV, put 90% of them on treatment, and for 90% of them to have suppressed viral load.

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.

In sub-Saharan Africa, women are disproportionately affected by HIV. Sustained adherence to lifelong antiretroviral therapy (ART) is needed to ensure their own health and prevent transmission of HIV to their partners and their children. However, non-adherence to ART remains a substantial challenge with many associated risk factors. Travel is often reported in the qualitative literature as a barrier to ART adherence among women living with HIV, but few quantitative studies have explored this association. This research aimed to describe travel in the past year among mothers living with HIV in the Long-term Adherence and Care Engagement (LACE) study, to explore factors associated with travel, and to investigate the associations between travel and i) self-reported adherence, and ii) HIV viral load. Part A of this dissertation is the study protocol that introduces the need for this research and presents how the research will be carried out. Part B is a narrative literature review. The review summarises and synthesises existing research relating to HIV treatment and travel in sub-Saharan Africa, giving context to the dissertation. Part C is the journal “ready” manuscript. This section presents an analysis of data from the LACE study, a cross-sectional survey of women living with HIV approximately four years after they had started ART during pregnancy in Gugulethu, Cape Town. At the LACE study visit, data on short-term travel patterns (stayed away from home for 3 or more nights) in the past year and self-reported adherence in the past 30 days (using a validated three-item scale) were collected through structured questionnaires, and a blood specimen was tested for HIV viral load. Poisson regression models with robust standard errors were used to explore factors associated with travel (any versus none), self-reported adherence (100% versus <100%), and viral suppression (≤50 copies/mL). Results were reported as crude risk ratios (RR) and adjusted risk ratios (aRR) with 95% confidence intervals (CI). The results showed that among 353 women enrolled in the LACE study (mean age 32.6 years, 48% employed, 38% married/cohabiting, median 44 months postpartum) 23% (n=81) reported travelling in the past year. Of the women who travelled, most went to the Eastern Cape (90%) and travelled 1-2 times during the year (93%). Women who travelled were more likely to be married/cohabiting than women who had not travelled (aRR = 1.45; 95% Cl: 0.97 - 2.16). Only 9% of women who travelled (7 of 81) reported difficulty with ART adherence due to travel. Overall, 59% of women reported 100% adherence in the past 30 days: 52% of women who had travelled in the past year versus 61% of those who had not travelled (aRR = 0.83; 95% Cl: 0.66-1.04). Only 56% of the cohort were virally suppressed: 60% and 55% of those who had and had not travelled in the past year, respectively (aRR = 1.10; 95% Cl: 0.89-1.36). Travel in the past year was not significantly associated with self-reported adherence or viral suppression in crude or adjusted analyses. These results highlight that poor adherence and viremia were very common in this cohort of women, four years after starting ART in pregnancy. Almost a quarter of women reported travel in the past year but only a v few reported difficulties with adherence related to travel and we found no association between travel in the past year, self-reported adherence in the past 30 days or viremia. Further research is needed to understand adherence patterns during periods of travel and interventions are clearly needed to support women's long-term adherence to ART.

Includes bibliographical references / Introduction: Tuberculosis (TB) notification in South Africa has increased six fold over the last two decades mainly because of the Human Immunodeficiency Virus (HIV) epidemic. Globally, it was estimated that 73% of the TB cases were co-infected with HIV with more than 25% of this global co-infection burden being in South Africa alone. In 2012, globally 1.3 million deaths occurred due to TB; moreover 0.3 million were HIV-associated TB death. In 2010 TB was the leading cause of natural deaths in the population aged 15 to 24 years accounting for 14% of the total deaths in South Africa. In 2013 the proportion of patients with TB who were co-infected with HIV was extremely high at 62%.The outcome of co-infected patients was poorer than the outcome of HIV negative TB patients. However, there is little information available on the risk factors associated with TB treatment outcomes and the influence of co-infection. Method: A cross sectional study analysed Electronic TB Register (ETR.net) data from the Metro East Geographic Service Area (GSA) of the Cape Town Metro district. The dataset included adult patients aged 15 years or more, who initiated TB treatment between 1st July 2011 and 30th June 2012. In the descriptive analysis we analysed death separately but for the regression we merged death with unfavourable treatment outcome. Relative risks were used for measures of association. Univariate and multivariate analyses were performed using a generalized linear regression model. Statistically significant variables in the univariate analysis were included in the multivariate analysis. Findings: TB case notification in Eastern GSA was 922 per 100 000 population. Of the 12672 TB patients registered, 50% were co-infected with HIV. The incidence of death in co-infected was 5% versus 3% in uninfected, treatment success 67% versus 73% and unfavourable treatment outcome 28% versus 24%. The Khayelitsha sub-district had the highest proportion of the TB burden (37%) and of co-infection (65%). Fourteen percent of patients had extra-pulmonary TB (EPTB), 66% of whom were co-infected with HIV. In the multivariate analysis HIV (RR 1.2), retreatment (RR 1.4) and sputum smear microscopy not done (RR 1.4) were significantly associated with unfavourable treatment outcome. The sub districts Eastern (RR 0.9) and Northern (RR 0.7) were less likely to develop unfavourable outcome compared to Khayelitsha. In the stratified analysis, retreatment (RR 1.3) and smear not done (RR 1.3) were significant risk factors for an unfavourable treatment outcome in co-infected patients. Amongst HIV negative patients retreatment (RR 1.6) and smear not done (RR 1.6) were significant risk factors for an unfavourable treatment outcome. Conclusions: The incidence of TB is extremely high in the Eastern GSA of Cape Town however the prevalence of co-infection varies across the sub-districts. Although treatment outcomes have been improving, co-infection, retreatment and smear microscopy not done pre-treatment were factors significantly associated with an unfavourable treatment outcome. Eastern and Northern sub-districts were significantly more likely to have favourable treatment outcomes compared to Khayelitsha, where both TB incidence and HIV co-infection were greatest.

The purpose of this mixed methods research study was to examine the role of adherence barriers to healthcare and the impact that such barriers have on highly active antiretroviral therapy (HAART) compliance for African Americans living with HIV/AIDS. HAART helps reduce HIV/AIDS morbidity and mortality. Of the 49% of study participants who had been out of medical care for more than 12 months, financial concerns were listed as the most common barrier (22.8%). Not having the support from family and friends (17.5%), being tired of going to doctor appointments (15.8%), health challenges (12.3%), lack of transportation (12.3%), and incarceration (12.3%) were also barriers in medical care that had a direct influence on noncompliance. The overall model of the linear regression analysis was significant, R2 = .469, adjusted R2 = .458, F(1, 49) = 43.24, p < .001. Being in medical care on a regular basis accounted for 46.9% of the total variance in attending primary care visits. The outcome of this analysis confirms the hypotheses (HA1) that attending 2 primary care visits within 6 months of being linked to care increased the rate of compliance for African Americans on HAART living with HIV/AIDS. The overall model of the linear regression analysis was significant, R2 = .469, adjusted R2 = .458, F(1, 49) = 7.206, p < .001. Being in medical care on a regular basis accounted for 46.9% of the total variance in attending primary care visits. The outcome of this analysis empasizes the importance of HAART compliance. These findings can lead to positive social changes by improving quality of life and health, which impacts gainful employment, sustains positive relationships, improves finances, and increases self-sufficiency

Adherence to ARV medicines is essential to halt HIV progression, increase CD4 counts, decrease virologic impact, and improve quality of life for the infected people. However, sustaining good adherence among adolescents and young adults (AYA) has been a challenge caused by various problems such as distance to clinic, improved CD4 count which lead to complacency in adherence, and the nature of the environment. This was a quantitative, retrospective, correlational, cross-sectional study anchored by the transtheoretical model, which was used to understand how adherence rate among the study population was impacted by the predictive factors. Secondary data was collected from patient's medical records at the Federal Medical Center, Makurdi in Benue State, Nigeria. Univariate analysis was conducted using descriptive statistics. The study sample size of 656 patients was drawn from AYA ages 15-24 years. Independent t tests showed a statistically significant difference in adherence rates between rural (94%) and urban (89%) AYA, t (424) = -3.280, .001, p -?¤ .05. There was also a statistically significant difference in adherence rates of ART for patients who lived within 50 kilometers of the hospital and those who lived more than 50 kilometers away from the hospital, t (509) = -2.37, .018, p -?¤ .05. Also, there was a statistically significant correlation between adherence rate to ART and CD4 of less than 500 cells/mm3, R = .214, NS = .003, p -?¤ .05. This study provides findings for HIV implementing partners (IPs) and relevant health professionals in Nigeria useful for designing strategies that would improve adherence rate to antiretroviral therapy among AYA in Nigeria.

Magister Public Health - MPH / In 2018, it was estimated that 33,000 adolescent girls and 4,200 adolescent boys were HIV-positive in South Africa. The Free State province reports that 89% of people living with HIV are diagnosed; 72% of those diagnosed are receiving antiretroviral therapy (ART); of which 93% have achieved viral suppression (< 1000 RNA copies/mL). Thabo Mofutsanyane District has the highest HIV prevalence in the Free State province. A retrospective, quantitative cross-sectional study was conducted to determine the predictors of viral suppression among adolescents on ART in Thabo Mofutsanyane District Municipality, Free State province, South Africa. Data for all adolescents, aged 10–19 years, receiving ART in 2019 (N = 6 300) was extracted from Tier.net electronic database into an Excel spread sheet and exported into Statistical Package for the Social Sciences – Version 26 (SPSS v 26) for analysis.