Patients with human immunodeficiency virus (HIV)/AIDS live a far different life today compared with those who were infected in the 1980s and 1990s. Antiretroviral therapy has evolved from a once poorly tolerated, heavy pill burden to the availability of many once-daily single-tablet regimens. The improvements in therapy have necessitated the need to be cognizant of comorbidities as well as drug-drug interactions. Despite the tremendous advances in therapy, newer therapies are in the pipeline and continue to emerge, making care for patients burdened by HIV perhaps easier than it has ever been.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfillment of the requirements for the degree of Master of Science in Physiotherapy. Johannesburg, 2015 / The Human Immunodeficiency Virus (HIV) has been found to cause muscle weakness, wasting and peripheral neuropathies. The specific relationship between lower limb muscle strength and lower limb function in HIV positive patients on Highly Active Antiretroviral Therapy (HAART) has not been examined. The aims of the current study were to establish lower limb muscle strength in HIV positive patients on HAART, establish lower limb muscle strength in HIV negative people, compare lower limb muscle strength between patients who are HIV positive on HAART and HIV negative people, establish lower limb function in patients who are HIV positive on HAART and to establish the relationship between lower limb muscle strength and lower limb function in patients who are HIV positive on HAART. A cross-sectional, descriptive study design was used. Dynamometry was used to measure lower limb muscle strength. The lower Extremity Functional Scale (LEFS) was used to determine lower limb function. A pilot study was done to establish the feasibility and proficiency required to perform hand held dynamometry. Intra and inter-rater reliability were also determined during the pilot phase. Intra and inter-rater reliability were high for the raters' measurement of lower limb muscle strength using a dynamometer with 'r' values of 0.97. For HIV positive patients on HAART, 19% (n=22) were in the age band 45-49years, whereas 33% (n=10) of HIV negative subjects were in age interval 25-29 years. Those over 45 years who were HIV positive on HAART constituted 57% (n=64) of the sample. The mean muscle strength obtained ranged from 9.30kg/m2 in ankle dorsiflexors to 15.80kg/m2 in hip extensors in HIV positive people on HAART for an average of 4 years while knee flexors generated 11.81 kg/m2 and knee extensors generated 15.36kg/m2 in this cohort.Jn the HIV negative matched group, the mean muscle strength ranged from 11.20 kg/m2 in ankle dorsiflexors to 17.70 kg/m2 in hip extensors while knee flexors generated 12.65kg/m2 and knee extensors generated 17.07kg/m2. The majority 78% (n=88) of HIV positive patients on HAART had no difficulty with lower limb function while 22% (n=17) had difficulty. Only 2% (n=2) of HIV positive patients on HAART had quite a bit of difficulty with lower limb functional activities after measurements using the Lower Extremity Functional scale (LEFS). A multiple linear regression showed that there was a positive correlation coefficient of r=0.71 (p-value= 0.00) between lower limb muscle strength and lower limb function. The coefficient of determination 0.50 means that 50% of the changes in lower limb function are attributable to lower limb muscle strength. Gender, employment status and mode of transport also positively affected lower limb function. A detailed regression model showed that lower limb ankle plantar flexors contributed the most to lower limb function in this cohort. This is contrary to International literature which states that hip and trunk muscles are the most active in HIV negative people during lower limb functional activities. That plantar flexors contribute the most in lower limb functional activities instead of hip and trunk muscles confirms the existence of proximal weakness in this cohort which was established by other researchers. This study highlighted that 50% of lower limb function is a result of lower limb muscle strength in HIV positive people on HAART attending an outpatient clinic in Mutare, Zimbabwe. Ankle plantar flexors instead of hip flexors were the most active muscle group in lower limb functional activities in this cohort. It therefore means exercise prescription to activate/strengthen hip flexors and other proximal muscles will improve this population's lower limb functional activities since progressive resisted aerobic exercises have been proved to strengthen muscles. / AC2016

No description available.

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. (Pharmacy)) -- University of Limpopo, 2022 / Antiretroviral (ARV) management in children is considered a challenging process, and patients receiving ARVs remain at risk of medication errors. Recently, there has also been a noticeable increase in Treatment Failure (TF) and the development of drug resistance amongst children on ART. However, ART failure amongst children seems to be an under-recognised issue, and adherence to treatment guidelines is reported to be a challenge among nurses caring for People Living with HIV (PLWHIV). Hence, the aim of this study was to explore the prescribing practices, and to determine the knowledge, understanding, and competence levels of NIMART-trained nurses’ in the management of children on Antiretroviral Therapy (ART) in Public Health Care (PHC) facilities located in a rural district of Limpopo Province. To attain the purpose of the study, the researcher in this study adopted a mixed-method, in an explanatory sequential manner. The quantitative phase adopted a descriptive cross-sectional and retrospective census of medical records to determine whether or not the children on ART were prescribed the correct ARV regimen, dose, strength, dosing frequency and received the correct quantities to last until the next appointment date. Whereas the qualitative phase embraced a total purposive sampling of the NIMART-trained professional nurses to explore their knowledge, understanding and views of ART management in children. The results highlighted that these children under study even though they were prescribed a correct ARV regimen in (n=7045; 96%) of the cases;they were only correctly dosed in (n=7797; 53%); and prescribed the correct strength (n=9539; 77%), with only (n=2748; 36.9%) having received the correct quantity of treatment to last them until the next appointment date. Most nurses even though they rated themselves very knowledgeable and competent in paediatric HIV/AIDS management. This finding was contradicting the results obtained from the medical records, as well as their responses to the given case scenario depicted some level of non-adherence to treatment guidelines as well as a lack of understanding of ARV management. From the findings of this ARV utilisation review and the implementation of the developed ART dosing and dispensing training programme. The study concludes that the nurse's prescribing practice was irrational in this cohort of children, and most prescriptions did not entirely comply with the 2014/15 HIV/AIDs treatment recommendations. Since, this cohort of children was found to be susceptible to medication related errors such as; Drug omissions in ARV regimens; Incorrect dosing & dosing frequencies; as well as incorrectly supplied quantities. From the study findings it is recommended that ARV stewardship programs should be considered in order to develop and establish a core strategy for enhancing quality improvement in the management of HIV-infected children on ART in resource-limited settings, not only to inundate viral suppression and maintain it, but also to help achieve the UNAIDS 95- 95-95 target in children under 15 year / National Research Foundation (NRF)

Thesis (MSc)--Stellenbosch University, 2014. / ENGLISH ABSTRACT: While antiretroviral therapy decreases HIV/AIDS morbidity and mortality, long-term treatment results in insulin resistance and cardiovascular diseases. A possible cause of such adverse effects may be an increase in oxidative stress resulting from protease inhibitor (PI)-induced mitochondrial dysfunction. We therefore hypothesized that PI treatment, specifically Lopinavir/Ritonavir, results in increases in myocardial reactive oxygen species (ROS), leading to downstream outcomes, i.e. elevated apoptosis. Moreover, we proposed that increased ROS levels in this instance might occur as a result of PI-mediated induction of the non-oxidative glucose pathways (NOGPs). In light of this, we also investigated the effect of PI treatment on the NOGPs by employing both in vitro and in vivo samples. For the in vitro work we employed a rat cardiomyoblast cell line, while tissues (heart, liver) were collected from two separate experimental models, i.e. a) Group A exposed to PIs via mini-osmotic pump for a period of eight weeks, and b) Group B administered PIs via a jelly-based method for 16 weeks. We found that PIs increased mitochondrial ROS levels in vitro but that this was not accompanied by a parallel rise in programmed cell death. Moreover, we found no induction of the NOGPs in response to PI exposure (for both in vitro and in vivo models here employed). However, we found that the AGE pathway was significantly down-regulated in the liver of Group A. Investigation into a proposed mechanism for this observation proved inconclusive and further studies are thus required to clarify the significance in terms of metabolic dysfunction found in the Group A model. Our study thus shows that PIs can increase ROS levels (in vitro) but that compensatory antioxidant mechanisms may prevent this in vivo. Subsequently, downstream effects were limited i.e. we did not observe NOGP induction and programmed cell death. An intriguing finding emerged, however, i.e. that PIs can elicit an impact on the AGE pathway. We propose future studies with modifications to the current rat and cell models in order to evaluate the downstream effects of PIs on the NOGPs and programmed cell death. / AFRIKAANSE OPSOMMING: Terwyl antiretrovirale terapie MIV/VIGS morbiditeit en mortaliteit verlaag, veroorsaak langtermyn behandeling insulienweerstandigheid en kardiovaskulêre siekte. 'n Moonltike oorsaak van sulke newe-effekte kan 'n toename in oksidatiewe stres veroorsaak deur die protease inhibeerder (PI)-geïnduseerde mitochondriale wanfunskionering. Ons hipotetiseer dat PI behandeling, spesifiek Lopinavir/Ritonavir, versoorsaak 'n toename in miokardiale reaktiewe suurstofspesies (ROS), wat aanleiding gee tot afstroom uitkomste, i.e. verhoogde apoptose. Verder, stel ons voor dat verhoogde ROS vlakke in hierdie geval onstaan as gevolg van PI-gemedieerde induksie van die nie-oksidatiewe glukose weë (NOGWe). In die lig hiervan het ons ook die effek van PI behandeling op die NOGWe ondersoek deur beide in vitro en in vivo monsters te gebruik. Vir die in vitro werk het ons van 'n rot kardio-mioblastsellyn gebruik gemaak, terwyl weefsels (hart, lewer) versamel is van twee afsonderlike eksperimentele modelle, i.e. a) Groep A blootgestel aan PIs via mini-osmotiese pomp vir 'n periode van agt weke, en b) Groep B PIs is toegedien via 'n jellie gebaseerde metode vir 16 weke. Ons het bevind dat die die PIs mitochondriale ROS vlakke in vitro verhoog maar dat dit nie vergesel is met 'n paralelle toename in apoptose. Verder is geen induksie van die NOGWe in reaksie op PI blootstelling waargeneem (vir beide in vitro en in vivo modelle). Hoewel ons het bevind dat die AGE weg in die lewer van Groep A beduidend afgereguleer is. Ondersoek na 'n moontlike megansime vir hierdie waarneming was onoortuigend en verdere ondersoek is nodig om die betekenis in terme van die metaboliese wanfunskionering in die Groep A model vas te stel. Ons studie toon dus aan dat PIs, ROS vlakke (in vitro) verhoog, maar dat kompensatoriese anti-oksidant meganismes in die hierdie in vivo model verhoed word. Gevolglik is die afstroom effekte beperk i.e. ons het geen NOGWe induksie en aptoptose waargeneem nie. 'n Interesante bevinding het wel uitgestaan, i.e. PIs kan 'n impak hê op die AGE weg. Ons stel dus voor dat toekomstige studies met modifikasies, tot die huidige rot- en sel-modelle gemaak word om die afstroomeffekte van PIs en apoptose te evalueer.

Introduction: Currently there are approximately 1.2 million people in the United States living with HIV and it is estimated that 25.6% of HIV-positive adults suffer from depression. The purpose of this study is to examine the contribution of depression on substance use and medication adherence specifically among HIV-positive adult Georgians receiving medical care for HIV. Methods: Secondary data with a probability sample of 608 HIV-positive adults who took part in the 2009-2012 Georgia Medical Monitoring Project (MMP) were analyzed. Descriptive analysis and multivariate logistic regression models were conducted to assess relationships between depression with current cigarette smoking, injection drug use, other non-injection drug use, and medication adherence, adjusting for sociodemographic covariates (age, gender, race, and education). All analyses accounted for non-response and complex sampling design and were performed using SAS 9.2 (Cary, NC). Results: Among HIV-positive adults in Georgia, approximately 9.2% met the criteria for major depression; 15.2% of women and 6.9% of men had major depression. Heterosexual adults also had a higher percentage of major depression (11.9%) compared to adults who identified as bisexual (8.3%) or homosexual (6.1%). Major depression was also highest among young adults (17.1%) and adults with high school diploma or GED (13.0%). Major depression was associated with a greater odds of current cigarette smoking (3.04; 95% CI: 1.48, 6.23); injection drug use (5.62; 95% CI: 0.96, 32.81), and other non-injection drug use (2.17; 95% CI: 1.10, 4.25), after adjusting for sociodemographic variables. Major depression was also associated with a greater odds of ART medication non-adherence, 2.52 (95% CI: 1.20, 5.28), after adjusting for gender. Conclusion: As previously found in the general population, we found significant associations between depression and smoking and other non-injection drug use among HIV-positive adults. Major depression was also associated with a greater odds of ART medication non-adherence, which is also consistent with the literature. Because HIV-positive adults have ongoing encounters with healthcare providers, screening and treatment for depression and other co-morbid substance use is needed to reduce an additional health burden in this population.

Adherence to combination antiretroviral therapy is important for achieving optimal HIV-related outcomes. Epidemiologic data indicate that persons with mental disorders are disproportionately affected by HIV/AIDS, which is concerning since having a mental disorder has been associated with poor adherence to medications for treatment of chronic disease states. The purpose of this study was to examine the relationship between the presence of mental disorders and adherence to combination antiretroviral therapy. Additionally, this study examined the relationship between adherence to psychotropic medications and adherence to antiretroviral therapy. Study data were collected from the Texas Medicaid Vendor Drug Program database and Texas Medicaid enrollment files. Adherence to and persistence with antiretroviral therapy, as well as adherence to psychotropic medications when applicable, were evaluated over a 12-month period in 1,321 patients starting a new combination antiretroviral regimen. The presence of a mental disorder was defined based on prescription claims for psychotropic medications. Proportion of days covered was used to calculate adherence, while persistence was defined as the number of days persistent with all antiretrovirals in the index regimen. Logistic regression was used to evaluate the relationship between psychotropic medication use and adherence to antiretroviral therapy (90% cut-off), as well as the relationship between adherence to psychotropic medications (80% cut-off) and adherence to antiretroviral therapy. The relationship between antiretroviral persistence and psychotropic medication use was evaluated using multiple linear regression. Factorial ANOVA was used to evaluate the interactions between race/ethnicity, gender, and psychotropic medication use in their effects on adherence to and persistence with antiretroviral therapy. No significant relationship was found between the presence of a mental disorder and adherence to or persistence with combination antiretroviral therapy in this study. However, the limitations of using psychotropic medication use as a proxy for mental disorders may have affected the results. Adherence to psychotropic medications overall (n = 501; OR = 3.37, 95% CI: 1.86 – 6.10; p < 0.001) and specifically to antidepressants (n = 443; OR = 4.23, 95% CI: 2.31 – 7.75; p < 0.001) was significantly associated with adherence to antiretroviral therapy, indicating a possible relationship between effective treatment for mental disorders and combination antiretroviral therapy adherence. While additional research is needed to clarify this relationship, these data support the need for an integrated approach to treatment of mental disorders and HIV/AIDS. / text

Successful antiretroviral (ARV) treatment is associated with suppression of HIV viral load and the reduction of clinical disease progression. Despite marked improvements in ARV medication, side effects from long-term treatment, such as loss of muscle mass do occur. The mechanism by which ARVs affect muscle mass is unclear, however, published in vitro data suggests a negative effect on myoblast fusion during differentiation. The objective of this study was therefore to determine the effect of ARVs on processes required for successful myogenesis; these included proliferation, migration during wound repair, and differentiation. C2C12 mouse skeletal myoblasts and human primary culture skeletal (HSk) myoblasts were incubated with Zidovudine (nucleoside reverse transcriptase inhibitor-NRTI), Tenofovir (nucleotide reverse transcriptase inhibitor-NtRTI) or Ritonavir (protease inhibitor-PI) at a concentration range of 0.01 μM to 10 μM. Proliferation was determined using crystal violet and migration was analyzed using a 2D wound healing assay. The commitment of myoblasts into the myogenic lineage was assessed via the expression of the transcription factor Pax7. Differentiation was measured by assessing the fusion index of multinucleated myotubes. C2C12 myoblast proliferation was observed to increase significantly in response to Tenofovir (1 μM and 10 μM). In HSk cells however, proliferation was observed to decrease significantly in response to Tenofovir (1 μM). Zidovudine had no consistent effect on C2C12 proliferation at any dose tested, but caused a decrease in HSk myoblast proliferation (0.01 μM and 0.1 μM); however this was statistically non-significant. A small dose-dependent increase in C2C12 and HSk cell number, although not significant, was seen in response to Ritonavir. Wound closure results revealed both dose-dependent and time-dependent effects of Tenofovir and Zidovudine on human myoblast migration, with significant decreases in the rate of wound closure (4-7 hours) noted at 0.1 μM and 0.01 μM doses respectively. Zidovudine had no significant effect on migration while Ritonavir (0.01 μM) was observed to significantly increase percentage wound closure of human myoblasts, suggesting an increased ability to migrate during wound repair. Differentiation results indicated a decrease in myoblast fusion in response to all three ARVs. However only Ritonavir was shown to negatively affect myosin heavy chain expression. Further research into the exact mechanism of decreased fusion is required. To our knowledge, this study is the first to suggest that selected ARVs may significantly influence myoblast regeneration capabilities by modulating myoblast proliferation, migration, differentiation and fusion, and thereby decrease their myogenic capability. Extended human myoblast studies on differentiation could confirm this hypothesis. / Thesis (M.Sc.)-University of KwaZulu-Natal, Westville, 2013.

Sub-Saharan Africa is the region in the world most severely affected by HIV, and Tanzania is among the most severely affected countries in the region. The introduction of antiretroviral treatment has offered hope to people living with HIV/AIDS, improving their quality of life significantly. Still, there are individuals living with HIV who either lack access to ART, or choose not to make use of the available treatments. The purpose of this thesis is to identify underlying factors perceived as barriers for HIV- positive individuals to initiate and maintain Antiretroviral treatment in Babati District, Tanzania. Twenty semi-structured interviews were carried out between the 15th of February and 6th of March 2016. The interviews were conducted with ART-patients, health workers and members of the community. An analysis was made within a theoretical framework based upon Goffman's notion of stigma and the Initial Behavioral Model by Andersen. The following obstacles to access to ART were indicated by the findings: HIV/AIDS related stigma issues, discrimination, economic barriers, ignorance due to lack of education, counseling on HIV treatment, and beliefs that HIV can be cured by traditional healers.