The effect of tenofovir on renal function and immunological response in HIV-positive patients in Lesotho

Thesis (M. Tech. (Biomedical technology)) - Central University of technology, Free State, 2013INTRODUCTION: The renal effects of Tenofovir Disoproxil Fumarate (TDF) and antiretroviral treatment (ART) outcomes remain under-reported in African settings. The study sought to assess immunological outcomes and to compare renal function outcomes between patients exposed to TDF and unexposed patient group. METHODS: Phase 1 of the study was a retrospective case control analysis of serum creatinine data for 312 ART naïve adult patients exposed to TDF and 173 unexposed patients enrolled on ART between Dec 2006 and Jan 2011 at Roma Health Service Area in Lesotho. Sub-optimal renal function outcomes were serum creatinine clearance values <50 ml/min calculated using the Cockcroft-Gault equation. Phase 2 was based on re-sampling of the study population and analysis of CD4 counts of 516 adult naïve HIV-positive patients. Univariate logistic regression (p<0.1) and multivariate analyses (p<0.05) were performed using STATA® version 11 software. RESULTS: Overall, 153 (31.5%) patients had moderate baseline (30-60 ml/min) renal insufficiency. Renal function improved by +2 ml/min at 24 months. Almost 18% (n=312) of the patients on TDF were erroneously put on TDF. The use of TDF was a marginally significant factor (p=0.054) associated with CrCl<50 ml/min outcomes in univariate analysis but was insignificant (p=0.122) in multivariate analysis. Female gender (p=0.016), high blood pressure (p=0.009), ages over 60 (p=0.004), and underweight (p<0.001) were significantly associated with CrCl<50 ml/min outcomes. The proportion of patients who developed immunological failure in this study was low (6.8%, n=516). The mean CD4 count increased significantly after treatment (p<0.001). Baseline CD4 count below 50 cells/mm3 (p=0.049) and male gender (p=0.005) were significantly associated with sub-optimal immunological outcomes. CONCLUSIONS: TDF is a weak contributing factor associated with renal impairment outcomes compared to other variables such as hypertension, older age, underweight and female gender. More research on long term effects of TDF is recommended. Baseline renal function screening should be improved to minimise leakages of patients contraindicated of TDF. Although the patients’ immunological status generally improved, males and patients with low baseline CD4 counts should be monitored closely while on ART

Isoniazid preventive therapy for tuberculosis occurrence in HIV-positive patients in Lesotho

Published ThesisTuberculosis (TB) remains a main public health problem, particularly in people living with HIV (PLHIV) in sub-Saharan Africa (SSA). This persistent problem may be an indication of underlying problems in national health policies, and their implementation in SSA. The Southern African country of Lesotho, with one of the highest TB incidences in the world, is facing a catastrophic syndemic of HIV and tuberculosis (TB). The effectiveness of isoniazid preventive therapy (IPT), which has the potential to reduce the incidence of TB in PLHIV, has not been adequately evaluated since its introduction in 2011. This study evaluated the uptake of IPT, its effectiveness and the associated factors in Lesotho, with the aim of establishing the necessary policy changes required to prevent the occurrence of TB in PLHIV. To determine the effectiveness of IPT and the factors underpinning the implementation of this intervention in Lesotho, a quantitative evaluation as well as a qualitative study of the implementation of IPT was used. The study was therefore based on a triangulation of quantitative and qualitative research methods in two phases. The qualitative phase of the study identified health system challenges affecting the implementation of IPT, based on a cross-sectional qualitative analysis of interview responses of healthcare workers and stakeholders of the TB/HIV programmes, which included the Ministry of Health officials and support partners, purposively selected for their roles in IPT implementation in Lesotho. The rationale of this study phase was based on the premise that the rate of initiation of IPT and its effectiveness is largely dependent on the quality of implementation of the IPT programme. The qualitative study phase revealed that seven factors in the health system were affecting the implementation of IPT in the country, namely poorly decentralised HIV services; inefficient monitoring and evaluation systems; ineffective service delivery; interrupted supply chains; an undertrained and inadequate health workforce; insufficient health system financing; and inefficient health information systems. The implementation of IPT was therefore a complex task which needed certain sectors of the health system to change. The most important lesson from this is that key health interventions need a ‘health system approach’ for success. The quantitative phase of the study was a quasi-experimental review of HIV-positive medical records randomly selected from eight health institutions in six districts of Lesotho. This study phase selected two patient groups, one enrolled into antiretroviral therapy (ART) before (2004-2010 cohort), and the other one after the launch of IPT (2011-2016 cohort), to establish the rate of initiation of IPT and its effectiveness in preventing the occurrence of TB in the country. IPT uptake and its effectiveness were evaluated using an analytical model based on Cox’s proportional hazards regression analysis, an approach often used to determine the relative risk of contracting a disease and the associated factors. The quantitative study phase included 2 955 randomly selected records that met the inclusion criteria set for the study. Overall, 68.8% of the 2 955 patients had received IPT over a course of six years (2011-2016), which translated to a sluggish IPT uptake rate of 20.6 per 100 person-years over the six-year period. Notably, only 135 (6.6%) patients defaulted IPT, which is a small proportion. Comparatively, the 2011-2016 cohort had a significantly (p=0.000) higher rate of IPT initiation (27.0 per 100 person-years) than the 2004-2010 cohort, (15.8 per 100 person-years), implying that patients newly enrolled into ART had a higher rate of IPT initiation. Findings indicated that the most significant predictors for initiation of IPT were age group, district category and duration of ART. Furthermore, based on odds ratios (OR), patients in the sparsely populated districts (OR=1.6) and males (OR=2.1) had significantly (p<0.05) higher odds of defaulting IPT, compared to those in the densely populated districts and females, respectively. Whereas higher defaults in the sparsely populated districts were associated with long distance from hospitals and the mountainous terrain associated with these districts, higher rates of defaulting by males were most likely due to migrant work in South Africa. The TB incidence rate reduced from 2.3 per 100 person-years in 7 985 person-years in the 2004-2010 cohort, to 1.6 per 100 person-years in 4 223 person-years in the 2011- 2016 cohort, implying that the IPT intervention had considerably reduced the occurrence of TB. However, the use of IPT was not without adverse effects. By proportion, the most common side effects to IPT were skin rash (37.2%), peripheral neuropathy (25.4%) and liver toxicity (9.4%). In addition, out of 246 patients who had developed TB and were discovered during a follow-up, 15.9% of the patients developed TB after exposure to IPT. Further findings indicated that prescribing IPT within one year of ART commencement, which reduced TB incidences to only 1.3 incidences per 100 person-years, was the most effective intervention for preventing the occurrence of TB, compared to other commencement timing of IPT intervention. Other TB incidences per 100 person-years by timing of IPT were as follows – IPT before ART (1.7), IPT after ART (1.8), no IPT (2.6), and IPT 3-5 years after ART initiation (2.3). Gender, baseline WHO clinical stage, district category and time to IPT relative to ART commencement emerged as significant predictors of TB occurrence. Notably, increasing commencement time for IPT by one six-month interval increased the risk of contracting TB by between 6% and 59%, depending on the cohort, with the 2011-2016 cohort having a higher risk compared to the 2004-2010 cohort. The findings of this study indicate that the implementation of IPT in Lesotho has notable challenges. Clearly, there is a need to improve the rate of IPT initiation in the patient groups with the most sluggish rate of IPT uptake, and to improve retention of some patient groups with poor adherence to IPT. The findings of this study also indicate that delayed IPT commencement after ART initiation significantly affects the effectiveness of IPT. Furthermore, the study reveals that IPT is a complex health intervention, and its implementation therefore needs a health sector-wide or ‘health systems’ approach

Technologies for trapped-ion quantum information systems

Scaling-up from prototype systems to dense arrays of ions on chip, or vast networks of ions connected by photonic channels, will require developing entirely new technologies that combine miniaturized ion trapping systems with devices to capture, transmit and detect light, while refining how ions are confined and controlled. Building a cohesive ion system from such diverse parts involves many challenges, including navigating materials incompatibilities and undesired coupling between elements. Here, we review our recent efforts to create scalable ion systems incorporating unconventional materials such as graphene and indium tin oxide, integrating devices like optical fibers and mirrors, and exploring alternative ion loading and trapping techniques.Comment: 19 pages, 18 figure

Medicinal herbs used by HIV-positive people in Lesotho

Background: The use of medicinal herbs whose efficacy and toxicities are not known by HIV-positive people in Lesotho is a threat to the effectiveness of antiretroviral treatment. This study explored some medicinal herbs used by HIV-positive people in Lesotho and the reasons for their use.Methods: This was a cross sectional study based on a questionnaire distributed to purposively-sampled HIV-positive people in Leribe and Maseru districts of Lesotho. The participants’ socio-demographic and clinical variables were summarized usingfrequency tables in Stata version 13 statistical software. Data variables for  medicinal herbs used, frequency of use, uses by the participants and in the literature, parts of plants used and the method of preparation were also explored.Results: Out of 400 questionnaires distributed to the participants, 389 were returned with data acceptable for analysis. Ages of the participants ranged from 18 to 75 years (Mean=43 + 11.6). Out of the 272 (69.9%) participants who conceded that they had used medicinal herbs at least once, 30 (7.7%) participants used medicinal herbs frequently while 242 (62.2 %) rarely used the herbs. At least 20 plant species belonging to 16 families were reportedly used by the participants. Asteraceae was the most common plant family reportedly used by the participants. Allium sativum and Dicoma anomala, reportedly used by 21.0% and 14.3%  respectively, were the most commonly used medicinal herbs in this population. In addition, boosting the immune system and treating gastrointestinal ailments, apparently cited by 32% and 28% participants respectively, were the most  commonly reported reasons for using medicinal herbs.Conclusion: A considerable proportion (69.9%) of HIV-positive people use  medicinal herbs in this population, and 7.7% use them frequently. At least 20 plant species belonging to 16 families were reportedly used by the participants. HIV counselling protocols in Lesotho should emphasize the dangers of using medicinal herbs whose safety and compatibility with antiretroviral drugs is not known. The efficacy and toxicity profiles of the medicinal plants identified in this study need to be investigated. Furthermore, the effects of these plants on antiretroviral treatment outcomes including herb-drug interactions need to be explored.Key words: Allium sativum; Anti-retroviral treatment; Dicoma anomala; Herb-drug interaction; HIV; Medicinal her