In South Africa 1 000 people die of AIDS everyday and 100 000 more people require ARVs every year. There is therefore an urgent need to provide access to ARVs andother essential medicines. The South African Constitution requires the government totake reasonable measures to ensure access to health care. The government has cited financial constraints as the major ohstacle to fulfilling this constitutional imperative. In an effort to stretch their budgetary resource other medium-income countries have used measures such as compulsory licences, voluntary licences and parallel importation. These measures, provided for in the TRIPS Agreement and the Doha Declaration, are available under South African legislation but have not been properly implemented due to a lack of political will. The proper use of compulsory licences by the South African government is vital because all twelve of the ARVs on the World Health Organisation's Essential Medicines List are protected in South Africa by our patent laws. However, in order to issue compulsory licences more easily and quickly the South African Legislature will need to pass legislation which clarifies the ambiguities contained in TRIPS and the Doha Declaration. Other methods to lower the price of medicines include the segmentation of the South African market in order to facilitate differential pricing. The State must balance its use of such measures with programmes to incentivise research and development into neglected diseases and HIV/AIDS. Such programmes will also assist the State's capacity to conduct its own research and development into new medicines, whilst bolstering its domestic pharmaceutical manufacturing capacity. The ultimate solution to South Africa's access to medicine problem is to create a pharmaceutical manufacturing industry capable of producing the most complex medicines, so as to lessen its dependence on drug manufacturers reducing their prices. The way to create a sophisticated pharmaceutical manufacturing capacity is to use the flexibilities in TRIPS and to uphold South Africa's high patent standards. The Constitutional Court's involvement is essential in order to force the State to implement its own policies so as to provide access to affordable medicines. / Thesis (LL.M.)-University of KwaZulu-Natal, Durban, 2008.

RN/AIDS has had a particularly devastating effect on sub-Saharan nations, including South Africa. Thus, a national rollout of antiretroviral drugs - capable of mitigating the effects of the epidemic - has been vigorously demanded by the South African public. Eventually bowing to public pressure, the Government began to implement the rollout of the drugs at public health facilities in early 2004. The University of KwaZulu-Natal announced in 2004 that it too would provide access to antiretroviral drugs for all students who require them. Thus, there is an urgent need for the institution to develop promotional campaigns that not only promote the service but that also deal with the fall-out from the problematic national rollout, and that address the complicated nature of antiretroviral therapy. The focus of this dissertation is on a promotional needs analysis for the antiretroviral rollout at the University. Specifically, the primary research aimed to determine the knowledge, attitudes and beliefs of the general student population on the topic of antiretrovirals, and by doing so, identify the needs of this audience that will have to be addressed by future promotional campaigns. The theoretical framework used to inform the research design and questions is that of social marketing; a relatively new approach to social change that uses principles of commercial marketing to achieve results among target audiences. The results of the research suggest that future promotional messages and campaigns directed at the general student population will need to focus on the following issues: clarifying the distinctions between different contexts of ARV use; increasing the awareness of the rollout at UKZN as a prerequisite to stimulating demand; addressing negative beliefs and misconceptions regarding ARVs; emphasising complementary practices to be used by individuals with RN/AIDS; addressing issues of stigma and discrimination and encouraging students to act as sources of support and information for other students. In the case of certain messages, segmentation - on the basis of race and campus - may result in a more effective dissemination of information to the target audiences. / Thesis (M.Soc.Sc.)-University of KwaZulu-Natal, 2005.

This dissertation has been motivated by the prolonged deficiency of access to advanced regimens of Antiretroviral drugs(ARVs) and efficient health services by people living with HIV/AIDS (PLWHA) in Zambia, a least developed Member of the World Trade Organisation (WTO). Zambia‘s reality of dire provision of health services particularly essential medicines persists despite the urgent need for sustainable access to ARV drugs in poor African countries worst affected by HIV/AIDS, having been accentuated in the international declaration on Trade Related Aspects on Intellectual Property Rights (TRIPS) and Public Health. Furthermore, under international human rights law of treaties, access to medicines including ARV drugs, has been recognised as a core component of the right to health and or life which needs to be progressively realised by governments, even in the advent of globalisation of domestic health services including provision of medicines. Whilst the Zambian government has highlighted lack of funds as the foremost impediment to efficient supply of health services particularly essential medicines. Conversely the WTO has pronounced lack of legal adoption of a plethora of flexibilities envisaged in its relevant international agreements by most poor Members, as the foremost impediment to fostering efficient public health service delivery including access to ARV drugs and therapy for PLWHA. Thus to assist in ascertaining whether the issue of deficient access to ARV drugs as a health service is as a result of legal unpreparedness in poor countries specifically Zambia; or whether it is due to provisions in the WTO trade agreements that foster globalisation of health services through liberalised trade in services and pharmaceutical patent protection of essential drugs. This dissertation will analyse the WTO‘s multilateral trade agreements and their legal impact on access to ARV drugs as a health service and a human right to health in Zambia. The foregoing analysis will be conducted through a desk review of literature on the subject, making use of paper and electronic sources. / Thesis (LL.M.)-University of KwaZulu-Natal, Durban, 2012.

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.

The relationships between post-traumatic growth (PTG), benefit finding, happiness, pessimism and antiretroviral (ART) medication adherence were examined among 10 people living with HIV or AIDS who attended HIV support groups, and were currently prescribed ART medications. Analyses indicated that none of these psychosocial factors were significantly correlated with ART adherence, that the relationships continued to be non-significant after pessimism was partialled out of the analysis, and that participants who reported achieving optimal ART adherence did not significantly differ from participants who reported taking less than optimal ART adherence in regards to PTG, benefit finding, subjective happiness, or pessimism. The results suggest that interventions designed to change these psychosocial factors may not be effective means of improving ART adherence. / Department of Psychological Science

The management of HIV-associated tuberculosis (TB) is complicated by the pharmacokinetic interactions between rifampicin (RMP) and co-administered protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors. Rifabutin (RBT) is an alternative rifamycin, preferred in patients requiring PIs. Recent studies suggest the current recommended dose of RBT in combination with boosted lopinavir (LPV/r) is suboptimal and there are insufficient pharmacokinetic data evaluating the interaction between RBT coadministered with efavirenz (EFV) and nevirapine (NVP). Pharmacogenomic studies have shown that RMP concentrations are lower in patients from sub-Saharan Africa with polymorphisms of the SLCO1B1gene but there is currently no data on the pharmacogenetic determinants of RBT exposure. The pharmacokinetics of RBT were evaluated at two different doses in HIV co-infected patients before and after the introduction of LPV/r, EFV and NVPbased antiretroviral therapy (ART). After six weeks of standard TB therapy, RBT 300 mg daily was started for four weeks. Thereafter patients were randomized to receive either RBT 150 mg daily or RBT 150 mg three times a week (TPW) with LPV/r, RBT 300mg or 450mg with NVP or RBT- 450mg or 600mg with efavirenz. After four weeks on the first RBT dose, patients switched to the alternate dose and continued until the end of TB treatment. Serial RBT and 25-O-desacetylrifabutin (dRBT) concentrations were measured during a dose interval before patients switched RBT doses. The median AUC0-24 and Cmax, of RBT in patients taking 150mg RBT TPW was significantly reduced when compared to the other treatment arms. 86% of patients whilst on this intermittent RBT arm had an AUC0-24 < 4.5 μg.h/mL, level that has been associated with acquired rifamycin resistance. Rifabutin exposure was maintained within the range of AUCs that have been shown to prevent acquired rifamycin resistance (ARR) with 150mg daily dosing in combination with LPV/r. In addition, the combination of RBT with NVP 300mg resulted in significantly increased exposure of RBT, with significantly higher exposure observed with 600mg RBT. However, the combination of RBT 450mg with EFV resulted in RBT exposure lower than 300mg RBT given alone in the same patients, whereas RBT 600mg plus NVP results in bioavailability of RBT equivalent to 300mg given alone. Rifabutin was well tolerated at all doses. Only three grade 4 laboratory toxicities, elevated transaminases, neutropenia, and uveitis, possibly related to RBT were reported in patients taking NVP. SLCO1B1 rs4149032 C>T polymorphism occurs frequently in African patients in Durban and may be associated with low RBT bioavailability. These findings support recommendations for the higher dose of RBT in combination with LPV and EFV but not with NVP. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2012.

Thesis (M.S.)--Ohio University, August, 2003. / Title from PDF t.p. Includes bibliographical references (leaves 93-114)

ENGLISH ABSTRACT: HIV/AIDS is the leading cause of death in Sub-Saharan Africa. According to 2001 estimates, there are 28.5 million people living with HIV in Africa, comprising more than 70% of the world’s HIV-infected population. HIV/AIDS remains one of the most important social and public health threats in Sub-Saharan Africa. UNAIDS 2006 estimates that 5.5 million people are living with HIV, and almost 1,000 AIDS deaths occur every day in South Africa. South Africa is currently one of the most severely affected countries in the world. Antiretroviral therapy (ART) is currently the only treatment available for HIV. It does not cure HIV infection, but reduces HIV related mortality and morbidity. / AFRIKAANS ABSTRACT: No abstract available

Thesis (MNutr (Interdisciplinary Health Sciences. Human Nutrition))--Stellenbosch University, 2008. / Background and objectives: An understanding of the effect of HAART on different aspects of health, including nutritional status, of HIV-infected individuals in South Africa is needed to ensure that appropriate population-specific guidelines and policies can be developed. This study aimed to investigate the impact of HAART on nutritional status, focusing on changes in anthropometric measures, and to explore the relationship between these measures and immunological and virological response to HAART. Methods: A prospective study of 30 adult females was carried out at a clinic in Cato Manor, KwaZulu-Natal. Anthropometric measurements, including weight, mid-upper arm circumference (MUAC), waist circumference, hip circumference, body mass index (BMI) and waist-to-hip ratio (WHR), were performed at baseline and 12 and 24 weeks after commencing HAART. Laboratory values, including CD4 lymphocyte count, viral load, albumin and haemoglobin as well as bioelectrical impedance analysis data, including lean body mass (LBM), fat mass (FM) and body fat percentage (BF%), were collected at baseline and after 24 weeks on HAART. Results: Overall, there was a statistically significant increase in all anthropometric measures, except WHR and LBM. The mean weight change was 3.4±5.8kg (p=0.006). Fifty percent of the subjects had a BMI above normal at baseline and mean BMI increased from 25.6±5.7kg/m2 to 27.3±5.6kg/m2 (p=0.007). Seventy percent of subjects gained weight, 18.5% had a stable weight and 11.1% lost weight. The weight gain in most subjects was attributable to a gain in FM while in subjects who lost weight, the loss consisted mainly of LBM. Some patients with stable body weight experienced changes in the relative proportions of fat and lean mass. Six patients showed evidence of disproportionate gains and losses in body circumference measurements which may be indicative of fat redistribution. Subjects with lower CD4 lymphocyte counts experienced greater increases in weight, BMI, FM and BF%. The strongest correlation was observed with FM (rs=-0.53; p=0.00). Greater increases in weight, BMI, MUAC, waist circumference, hip circumference, FM and BF% were seen in those with lower baseline haemoglobin. Baseline viral load and albumin did not correlate significantly with changes in any anthropometric variables. Change in CD4 count was only significantly associated with baseline MUAC (rs=0.40; p=0.04). Change in viral load was significantly correlated with baseline weight, LBM, FM, BF% and MUAC with the strongest correlation being with weight (rs=0.44; p=0.01). No significant association was found between anthropometric changes and changes in CD4 count and viral load between baseline and the 24-week visit. Conclusion: Overall, subjects experienced a significant increase in most anthropometric measures. There appears to be a relationship between some anthropometric and laboratory measures but this needs clarification. The findings of this study demonstrate the value of including circumference measurements and body composition techniques as part of nutritional status assessment and demonstrate the need for studies to determine the prevalence and significance of overweight and obesity in the HIV-infected population. Research is needed to determine the best methods of bringing about the most favourable anthropometric changes to enhance the health of patients on HAART.

Thesis (MPhil (Journalism))--University of Stellenbosch, 2006. / This study presents an observation, analysis and effect indication of the media portrayal of the antiretroviral drug nevirapine in Western Cape daily newspapers. The research is aimed at ascertaining the quality and consequences of science reporting on an essential, yet too often politically controversial, AIDS treatment within the South African context. This work ultimately offers suggestions as to how the media could play a more beneficial role for the South African public when reporting on nevirapine and HIV/AIDS treatment in general.