Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2009.

Highly-active antiretroviral therapy (HAART) has improved the prognosis of HIV-infected individuals. Unfortunately it has also been associated with impaired functional capacity and development of metabolic perturbations which increases health risk. This study tested the hypothesis that a combined cardiorespiratory and resistance exercise training (CARET) intervention may result in significant health benefits in HIV-infected individuals receiving HAART. Thirty-seven HIV-infected men and women, predominantly of lower socioeconomic status (SES), were recruited and randomly assigned to: 1) a group of moderate-intensity CARET for three months or 2) a control group receiving no exercise intervention for three months. At baseline and following the intervention, physical characteristics (body weight, body mass index, waist circumference, and blood pressure), physical fitness variables (estimated VO2max and one repetition maximum for upper and lower body), metabolic variables (fasting glucose and serum lipids), immune functioning (CD4+ T Cell count, CD4/CD8 ratio, and HIV RNA viral load), and quality of life (SF-36 Health Survey) were measured. Exercise participants evidenced increases in estimated VO2max (21%, p < 0.01), upper body strength (15%, p < 0.05), and lower body strength (22%, p < 0.05), while showing reductions in waist circumference (-2%, p < 0.05), and fasting glucose (-16%, p < 0.05). While the control group showed a significant decrease in CD4+ T cell count (-16%, p < 0.05) from baseline, the exercise group maintained a more stable count following training (-3%, p = 0.39). Finally, the exercise participants showed self-reported improvements in physical (11%, p < 0.03) and mental (10%, p < 0.02) quality of life. In conclusion, our study demonstrated that a three-month supervised and moderate intensity CARET program performed three times a week, can result in significant improvements in physical characteristics, physical fitness, metabolic variables, and physical and mental quality of life. Furthermore, the same intervention resulted in more favorable immunological responses following training in HIV-infected individuals of lower SES. Key words: Highly active antiretroviral therapy, HIV, combined aerobic and resistance exercise training, cardiorespiratory fitness, muscular strength, and immune functioning.

Thesis (M.Sc.)--Memorial University of Newfoundland, 2005. / Includes bibliographical references.

<p>In the era of AIDS, food and nutrition are becoming more of a priority for many households and communities. This is more so now that treatment is available for people infected with HIV and AIDS. Food and nutrition are fundamentally intertwined with HIV transmission and the impacts of AIDS. Evidence of the ways in which food insecurity and malnutrition may interfere with the effectiveness of antiretroviral therapy is well documented. Aim: The purpose of the study was to inform improvements in food security interventions for PLWHA through an investigation of existing food security interventions in the Khomas Region, Namibia.</p>

<p>Background: HIV/AIDS affects the health of millions of people world wide. According to the Joint United Nations Program on HIV/AIDS [UNAIDS], the number of people living with HIV globally has risen from 26 million in 2001 to 33.2 million in 2007. It is estimated that 2.5 million people were newly infected with HIV in 2007. The introduction of anti-retroviral therapy [ART] has brought hope to millions of people living with HIV and AIDS. More recently, the increased availability of treatment in many countries including Namibia has dramatically improved survival rates and lowered the incidence of opportunistic infections among HIV patients. Adherence to antiretroviral therapy (ART) is a fundamental attribute of excellent clinical HIV care and a key aspect in determining the effectiveness of treatment. Strict adherence to ART is vital to maintain low viral load and to prevent the development of drug resistant virus. Poor adherence is one of the key obstacles to successful ART for HIV positive patients. Literature has shown that there are various factors that hinder adherence to ART such as patient, service, community, family, socio-economic and work-related factors. Aim: This study aimed to describe the experiences of patients in the ART programme at Katutura State Hospital, Communicable Disease Clinic (CDC), in the Khomas region of Namibia and to explore factors that contribute to poor adherence.</p>

<p>The study utilized a qualitative case study design to explore the problem of poor access to ART in Benue State. PLWHAs, policy makers, program managers and health workers were involved in an effort to describe the factors influencing access to ART in the State. Semi structured interviews, exit interviews and focus group discussions were used. To analyse the findings, categorization was done into facilitators and barriers to access, in addition to the ways respondents believe these barriers can be overcome. Other sub-themes were also identified and sorted. Themes were linked to direct quotes from the respondents. Additional literature review was done to review available information on the themes identified. Facilitators of access included free cost and increased number of sites / beneficial effects of ART / disclosure, membership in a support group and having a treatment partner. Barriers included stigma and discrimination / hunger, poverty, transportation and opportunity costs / hospital factors / non-disclosure / inaccurate knowledge and perceptions about HIV and ART / certain religious beliefs and advice / coverage, capping of services and fear of non-availability of ART. In addition to stigma, patients bypass closer ART access points to further away hospitals because of business opportunities / financial assistance / perceived better standard of care and hope that a cure, when found, will be more accessible to patients in bigger hospitals.</p>

<p>Many studies have reported low cure rates for multidrug-resistant tuberculosis (MDRTB) patients and MDR-TB patients co-infected with human immunodeficiency virus (HIV). However, little is&nbsp / known about the effect of HIV infection and antiretroviral therapy on the treatment outcomes of MDR-TB in South Africa. Therefore, the objectives of the study are: to find out whether HIV infection&nbsp / and interactions between ARVs and second line anti-TB drugs have an impact on the following MDR-TB treatment outcomes: cure rate and treatment failure at Brewelskloof Hospital. MDR-TB&nbsp / patients were treated for 18-24 months. The study was designed as a case-control retrospective study comparing MDR-TB treatment outcomes between HIV positive (cases) and HIV negative&nbsp / patients (controls). Patients were included in the study only if they complied with the following criteria: sensitivity to second line anti-TB drugs, MDR-TB infection, co-infection with HIV (for some&nbsp / of them), male and female patients, completion of treatment between 1 January 2006 and 31 December 2008. Any patients that presented with extreme drug-resistant tuberculosis (XDR-TB)&nbsp / were excluded from the study. Data were retrospectively collected from each patient&rsquo / s medical records. There were a total of 336 patients of which 242 (72%) were MDR-TB patients and 94&nbsp / (27.9%) MDRTB co-infected with HIV patients. Out of the 242 MDR-TB patients, 167 (69.2%) were males and 75 (30.7%) were females. Of the 94 patients with MDR-TB co-infected with HIV, 51&nbsp / (54.2%) males and 43 (45.7%) females. Patients with multidrug-resistant tuberculosis co-infected with HIV who qualify for antiretroviral therapy were treated with stavudine, lamivudine and&nbsp / efavirenz while all MDR-TB patients were given kanamycin, ethionamide, ofloxacin, cycloserine and pyrazinamide. The cure rate of MDR-TB in HIV (+) patients and in HIV (-) patients is 34.5%&nbsp / and 30 % respectively. There is no significant difference between both artes (pvalue = 0.80). The MDR-TB cure rate in HIV (+) patients taking antiretroviral drugs and in HIV (+) patients without&nbsp / antiretroviral therapy is 35% and 33% respectively. The difference between both rates is not statistically significant. The study shows that 65 (28.0%) patients completed MDR-TB treatment but&nbsp / could not be classified as cured or failure, 29 (12.5%) patients failed, 76 (32.7%) defaulted, 18 (7.7%) were transferred out and 44 (18.9%) died. As far as treatment completed and defaulted is concerned,&nbsp / there is no significant statistical difference between HIV (+) and HIV (-) The number of patients who failed the MDR-TB treatment and who were transferred out is significantly higher in the HIV (-)&nbsp / group than in the HIV (+) group. Finally the number of MDR-TB patients who died is significantly higher in the HIV (+) group). The median (range) duration of antiretroviral therapy before starting&nbsp / anti-tuberculosis drugs is 10.5 (1-60) months. According to this study results, the MDR-TB treatment cure rate at Brewelkloof hospital is similar to the cure rate at the national level. The study also&nbsp / hows that HIV infection and antiretroviral drugs do not influence any influence on MDR-TB treatment outcomes.</p>

Human immune deficiency virus (HIV) and Acquire immune deficiency syndrome (AIDS) is a worldwide epidemic that impacts individuals physically, socially, and psychologically, and the rates of HIV/AIDS in youth are rising. Antiretroviral treatments have drastically prolonged life in individuals with HIV/AIDS; however, this type of treatment requires strict medication adherence. Many psychosocial factors impacting antiretroviral adherence have been explored, yet very little has been investigated regarding body image. This study investigated the potential impact of body dissatisfaction on antiretroviral medication adherence in adolescents with HIV. Seventy five male and female youth were administered questionnaires on the constructs of body dissatisfaction and medication adherence. Results support the hypothesis that body dissatisfaction negatively impacts medication adherence; yet, its effect in this sample was small (R2 = .06; F(1,61) =3.87, p =.05). Additionally, it was predicted that gender would moderate the nature of the relation between body dissatisfaction and medication adherence, given the disparate societal presentations of ideal body types among genders. However, within the current sample, gender did not have an effect on this relation. Furthermore, this study was interested in exploring if body dissatisfaction within a population of HIV-infected youth was best explained by specific body dissatisfaction with areas of the body associated with lipodystrophy or lipoatrophy syndromes. Due to a very small presentation of these syndromes in the final sample (n = 4), it was not surprising that body dissatisfaction was not best explained through specific dissatisfaction with these body parts. However, dissatisfaction with muscularity in general, was predictive of general body dissatisfaction regardless of gender. A discussion of these findings is included. This study is one of the first of its kind to explore the potential detrimental effects of body dissatisfaction in HIV infected youth.

Major advances in highly active antiretroviral therapies (ARVs) have extended the lives of people living with HIV, but there still remains an increased risk of death by cardiovascular diseases (CVD). HIV proteins and ARVs have been shown to contribute to cardiovascular dysfunction with effects on the different cell types that comprise the arterial wall. In particular, HIV-1 transactivating factor, Tat, is a cationic polypeptide that binds to endothelial cells, inducing a range of responses that have been shown to contribute to vascular dysfunction. It is well established that hemodynamics also play an important role in endothelial cell mediated atherosclerotic development where upon exposure to low or oscillatory shear stress, such as that found at branches and bifurcations, endothelial cells contribute to proteolytic vascular remodeling, by upregulating cathepsins, potent elastases and collagenases. The results of this work demonstrate that upregulation of cathepsins in vivo and in vitro is caused by a synergism between pro-atherogenic shear stress and HIV-1 proteins, elucidates pathways that are activated by HIV-1 Tat and pro-atherogenic shear stress - leading to cathepsin-mediated ECM degradation, and identifies cathepsins as novel biomarkers to monitor the adherence of patients on efavirenz- and tenofovir-containing antiretroviral regimens.

Non-nucleoside reverse transcriptase inhibitor (NNRTI) is one of the key components of antiretroviral drug regimen against human immunodeficiency virus type-1 (HIV-1) replication. However, the low genetic barriers to drug-resistance or cross-resistance, side effects, as well as the unaffordable cost of NNRTIs compromise their clinical usage. Therefore, to develop novel NNRTIs with potent antiviral activity against HIV-1 becomes a major concern in the treatment and prevention of HIV/AIDS. (+)-Calanolide A, which is a natural product initially extracted from the tropical rainforest tree Calophyllum lanigerum, was identified as an attractive NNRTI against HIV-1 despite virus strains containing drug-resistant K103N/Y181C mutations. In this study, a chemical library was constructed based on the three chiral carbon centers of (+)-Calanolide A. After screening the activity against HIVNL4-3 wild-type and several NNRTI-resistant pseudoviruses, a small molecule 10-chloromethyl-11- demethyl-12-oxo-calanolide A (F18) was identified as novel NNRTI with promising anti-HIV efficacy. Further studies were performed to investigate the antiviral breadth, drug resistance profile and underlying mechanism of the action of F18. F18 consistently displayed a potent activity against primary HIV-1 isolates including various subtypes of M group, CRF01_AE, and laboratory-adapted drug-resistant viruses in PBMC based assay. Moreover, F18 displayed distinct profiles against 17 NNRTI-resistant pseudoviruses, with an excellent potency especially against one of the most prevalent strains with the Y181C mutation (EC50=1.0nM) in cell line based assay, which was in stark contrast from the extensively used NNRTIs nevirapine and efavirenz. F18-resistant viruses were induced by in vitro serial passages, and mutation L100I was appeared to be the dominant contributor to F18-resistance, further suggesting a binding motif different from nevirapine and efavirenz. The efficacy of F18 was non-antagonistic when used in combination with other antiretrovirals against both wild-type and drug-resistant viruses in infected PBMCs. Interestingly, F18 displayed a highly synergistic antiviral effect with nevirapine against nevirapine-resistant virus (Y181C). Furthermore, in silico docking analysis suggested that F18 may bind to the HIV-1 reverse transcriptase in a way different to other NNRTIs. For the potential as an anti-HIV-1 microbicide, F18 also showed the stable and rapid release, as well as the sustained antiviral activity against HIV-1 wild-type virus in a formulation temperature-sensitive acidic gel. In summary, this study presents F18 as a new potential drug for clinical use and also underlies new mechanism-based design for future NNRTI. / published_or_final_version / Microbiology / Doctoral / Doctor of Philosophy