HIV/AIDS treatment is costly. Lesotho as a resource–limited country depends mostly on donor funding for HIV/AIDS treatment and care. Knowledge of how much was spent on treatment of HIV/AIDS was lacking. This leads to overstocking of some ART medicines resulting in expiry. Sufficient funds need to be secured for the treatment programme. The main objective of the study is to assess the cost of antiretroviral medication treatments, by specifically assessing the cost of antiretroviral regimens, antiretroviral side effects, and the cost of medicines used for prophylaxis and treatment of opportunistic infections as well as the cost of monitoring laboratory tests and dietary supplements. The study engaged both public and private ART clinics in the Maseru District in Lesotho. The study population consisted of 1 424 patients and study period was between 12 and 56 months from January 2004 to August 2008. Retrospective observational method was used. The cost for HIV/AIDS treatment comprised the cost of antiretroviral medicines and those used for their side effects, opportunistic infections (OI) prophylaxis and treatment, dietary supplements as well as monitoring laboratory tests. Prescribed daily dose (PDD) was used to calculate the cost of all the medicines used. To determine significant differences in average costs for various regimens d– values were used, while a cost/prevalence index was used to determine whether the cost was worth spending on the population or not. Cost–effectiveness ratio was also utilized in order to assess whether the cost born was worth the benefit. The main findings revealed that regimens 1a (stavudine/lamivudine/nevirapine) and 1c (zidovudine/lamivudine/nevirapine) were the least expensive (cost/prevalence index of 0.6 and 0.7 respectively). Regimens containing efavirenz were found to be more expensive than those containing nevirapine (cost/prevalence index of 1.2 and 1.7 respectively). When using d–values, there was a significant difference between the cost of regimens 1a and 1b, 1a and 1d, 1c and 1d and the information could be used for regimen switching decisions. Increase in CD4 cell count was more in stavudine–based regimens than in zidovudine–based regimens, which cost less per treatment. Cost effectiveness ratio was lower in 1a with R9.42/1cell/mm3 of CD4 cell count increase, and the highest was 1d with R31.77/1cell/mm3 of CD4 cell count increase. Therefore it was concluded that stavudine–based regimens are less costly as they have the lowest cost– effectiveness ratio in the Lesotho clinic environment. / Thesis (M.Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2011.

HIV/AIDS treatment is costly. Lesotho as a resource–limited country depends mostly on donor funding for HIV/AIDS treatment and care. Knowledge of how much was spent on treatment of HIV/AIDS was lacking. This leads to overstocking of some ART medicines resulting in expiry. Sufficient funds need to be secured for the treatment programme. The main objective of the study is to assess the cost of antiretroviral medication treatments, by specifically assessing the cost of antiretroviral regimens, antiretroviral side effects, and the cost of medicines used for prophylaxis and treatment of opportunistic infections as well as the cost of monitoring laboratory tests and dietary supplements. The study engaged both public and private ART clinics in the Maseru District in Lesotho. The study population consisted of 1 424 patients and study period was between 12 and 56 months from January 2004 to August 2008. Retrospective observational method was used. The cost for HIV/AIDS treatment comprised the cost of antiretroviral medicines and those used for their side effects, opportunistic infections (OI) prophylaxis and treatment, dietary supplements as well as monitoring laboratory tests. Prescribed daily dose (PDD) was used to calculate the cost of all the medicines used. To determine significant differences in average costs for various regimens d– values were used, while a cost/prevalence index was used to determine whether the cost was worth spending on the population or not. Cost–effectiveness ratio was also utilized in order to assess whether the cost born was worth the benefit. The main findings revealed that regimens 1a (stavudine/lamivudine/nevirapine) and 1c (zidovudine/lamivudine/nevirapine) were the least expensive (cost/prevalence index of 0.6 and 0.7 respectively). Regimens containing efavirenz were found to be more expensive than those containing nevirapine (cost/prevalence index of 1.2 and 1.7 respectively). When using d–values, there was a significant difference between the cost of regimens 1a and 1b, 1a and 1d, 1c and 1d and the information could be used for regimen switching decisions. Increase in CD4 cell count was more in stavudine–based regimens than in zidovudine–based regimens, which cost less per treatment. Cost effectiveness ratio was lower in 1a with R9.42/1cell/mm3 of CD4 cell count increase, and the highest was 1d with R31.77/1cell/mm3 of CD4 cell count increase. Therefore it was concluded that stavudine–based regimens are less costly as they have the lowest cost– effectiveness ratio in the Lesotho clinic environment. / Thesis (M.Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2011.

The prospect of the work presented in this thesis has been to engineer Cre recombinase to recognize and recombine a sequence from an HIV-1 Long Terminal Repeat (LTR), characterize the recombination proficiency of the evolved recombinase in mammalian cells and explore the potential of the recombinase for a novel antiretroviral strategy.

With great appreciation, I would like to accentuate the substantial contributions of the following people who made this project possible: To Dr. CMT Fourie (my supervisor), Prof. JM van Rooyen (my co–supervisor) and Prof. AE Schutte (my co–supervisor) whose gracious advise, patient guidance, commitment and support have enabled me to plan, analyse, interpret and write this project in a scientific manner. It has been an educational experience for me, thank you. To Mr. LS Wyldbore for the language editing of this dissertation. I thank all the participants, researchers, field workers and supporting staff of the PURE study. The financial assistance of the National Research Foundation (DAAD–NRF) towards this research is hereby acknowledged. A special thanks to my parents, sister, Albert, family and friends, thank you for the never–ending love, support, patience and understanding that you gave me throughout this project. Last, but not the least, a special thank to God for giving me the opportunity, talent, determination and endurance to complete this project. / Thesis (M.Sc. (Physiology))--North-West University, Potchefstroom Campus, 2012.

With great appreciation, I would like to accentuate the substantial contributions of the following people who made this project possible: To Dr. CMT Fourie (my supervisor), Prof. JM van Rooyen (my co–supervisor) and Prof. AE Schutte (my co–supervisor) whose gracious advise, patient guidance, commitment and support have enabled me to plan, analyse, interpret and write this project in a scientific manner. It has been an educational experience for me, thank you. To Mr. LS Wyldbore for the language editing of this dissertation. I thank all the participants, researchers, field workers and supporting staff of the PURE study. The financial assistance of the National Research Foundation (DAAD–NRF) towards this research is hereby acknowledged. A special thanks to my parents, sister, Albert, family and friends, thank you for the never–ending love, support, patience and understanding that you gave me throughout this project. Last, but not the least, a special thank to God for giving me the opportunity, talent, determination and endurance to complete this project. / Thesis (M.Sc. (Physiology))--North-West University, Potchefstroom Campus, 2012.

Antiretroviral drugs are successful in controlling HIV/AIDS and reducing disease progression. Antiretroviral regimens are stopped in up to 25% of all patients during their initial treatment therapy as a result of adverse drug effects, failing treatment and nonadherence within the initial eight months of treatment (Sharma et al., 2007: 235). A pharmacovigilance surveillance system makes it possible for physicians, pharmacists and other healthcare providers to report suspected ADRs. The purpose of this system is to operate as a guide in identification of new ADRs and predisposing risk factors to known ADRs. The objective of this study was to assess the prevalence and documentation of adverse drug reactions (ADR) in the private and public antiretroviral clinics in Maseru district, with special reference to zidovudine (AZT) and tenofovir (TDF) - based regimens. The empirical investigation was divided into two phases. The first phase was a cross-sectional quantitative retrospective drug utilisation review study which focused on the occurrence of adverse drug reactions in patients taking zidovudine (AZT) and tenofovir (TDF). The second phase, a survey in a form of questionnaires for the health professionals. Drug utilisation review: The sample size of patients was 300. Of the 44 patients who experience ADRs, 72.73% (n = 32) were female and 27.27% (n = 12) were male. A greater number of patients who experienced ADRs were females with 43.18% (n = 19) presenting with skin rash, 27.27% (n = 12) with nausea/vomiting, and 2.27% (n = 1) with diarrhoea. In male patients, 2.27% (n = 1) had peripheral neuropathy, 18.18% (n = 8) skin rash, 2.27% (n = 1) Fanconi syndrome, 2.27% (n = 1) nausea/vomiting, and 2.27% (n = 1) diarrhoea. Patients whose ART regimen changed due to ADRs were five. 60% (n = 3) of the patients were females and 40% (n = 2) were males. There was an estimated increase of 0.0025 cell/mm³, 0.0026 cell/mm³, 0.0024 cell/mm³, 0.0025 cell/mm³, and of 0.0019 cell/mm³ in CD4 cell count per day according to sex, age group, weight group, initial ART regimen, and ADRs, respectively. An estimated increase of 0.00021 g/dL, 0.00022 g/dL, 0.00018 g/dL, 0.00022 g/dL, and of 0.00020 g/dL in Hb profile per day occurred according to sex, age group, weight group, initial ART regimen, and ADRs, respectively. There was an estimated increase of 0.000062%, 0.000046%, 0.000068%, 0.000062%, and of 0.00017% in neutrophil count according to sex, age group, weight group, initial ART regimen, and ADRs per day, respectively. There was an estimated increase of 0.000044 IU/L, 0.000043 IU/L, 0.000046 IU/L, and of 0.000028 IU/L in ALT according to sex, age group, weight group, and initial ART regimen per day, respectively. An estimated decrease of 0.000013 IU/L in ALT according to ADRs per day also occurred. There was an estimated decrease of 0.00038 μmol/L, 0.00039 μmol/L, 0.00040 μmol/L, 0.00040 μmol/L, and of 0.00028 μmol/L in serum creatinine per day according to sex, age group, weight group, initial ART regimen, and ADRs, respectively. There was an estimated decline of 0.00023 mmol/L, 0.00022 mmol/L, 0.00023 mmol/L, 0.00024 mmol/L, and of 0.00015 mmol/L per day in urea according to sex, age group, weight group, initial ART regimen, and ADRs, respectively. Health professional’s questionnaire: 49 health professionals responded to the questionnaire. 100% (n= 49) of the participants showed that they did not use the yellow card scheme to report ADRs. 34.65% (n = 17) use the individual case safety reports. 57.14% (n = 28) used the structured databases to report ADRs. 85.71% (n = 42) documented in the patient bukana, and 6.12% (n = 3) used the HIV/AIDS ART card to document ADRs occurrence. 91.84% (n = 45) of the health professionals never filled the ADR reporting form in their working environment. In conclusion, adverse drug reactions occurring in a hospital or healthcare facility should be recorded and reported by the medical practitioners, nurses, pharmacists, and the pharmacy technicians. Therefore, it is important to assess the continuous evaluation of the benefits and harm of medicines which will help in achieving the ultimate goal of making safer and more effective treatment available for patients. As well as to help the health professionals to participate in the very important process of continuous surveillance of safety and efficacy of pharmaceutical products used in clinical practice. / MPham (Pharmacy Practice), North-West University, Potchefstroom Campus, 2014

Antiretroviral drugs are successful in controlling HIV/AIDS and reducing disease progression. Antiretroviral regimens are stopped in up to 25% of all patients during their initial treatment therapy as a result of adverse drug effects, failing treatment and nonadherence within the initial eight months of treatment (Sharma et al., 2007: 235). A pharmacovigilance surveillance system makes it possible for physicians, pharmacists and other healthcare providers to report suspected ADRs. The purpose of this system is to operate as a guide in identification of new ADRs and predisposing risk factors to known ADRs. The objective of this study was to assess the prevalence and documentation of adverse drug reactions (ADR) in the private and public antiretroviral clinics in Maseru district, with special reference to zidovudine (AZT) and tenofovir (TDF) - based regimens. The empirical investigation was divided into two phases. The first phase was a cross-sectional quantitative retrospective drug utilisation review study which focused on the occurrence of adverse drug reactions in patients taking zidovudine (AZT) and tenofovir (TDF). The second phase, a survey in a form of questionnaires for the health professionals. Drug utilisation review: The sample size of patients was 300. Of the 44 patients who experience ADRs, 72.73% (n = 32) were female and 27.27% (n = 12) were male. A greater number of patients who experienced ADRs were females with 43.18% (n = 19) presenting with skin rash, 27.27% (n = 12) with nausea/vomiting, and 2.27% (n = 1) with diarrhoea. In male patients, 2.27% (n = 1) had peripheral neuropathy, 18.18% (n = 8) skin rash, 2.27% (n = 1) Fanconi syndrome, 2.27% (n = 1) nausea/vomiting, and 2.27% (n = 1) diarrhoea. Patients whose ART regimen changed due to ADRs were five. 60% (n = 3) of the patients were females and 40% (n = 2) were males. There was an estimated increase of 0.0025 cell/mm³, 0.0026 cell/mm³, 0.0024 cell/mm³, 0.0025 cell/mm³, and of 0.0019 cell/mm³ in CD4 cell count per day according to sex, age group, weight group, initial ART regimen, and ADRs, respectively. An estimated increase of 0.00021 g/dL, 0.00022 g/dL, 0.00018 g/dL, 0.00022 g/dL, and of 0.00020 g/dL in Hb profile per day occurred according to sex, age group, weight group, initial ART regimen, and ADRs, respectively. There was an estimated increase of 0.000062%, 0.000046%, 0.000068%, 0.000062%, and of 0.00017% in neutrophil count according to sex, age group, weight group, initial ART regimen, and ADRs per day, respectively. There was an estimated increase of 0.000044 IU/L, 0.000043 IU/L, 0.000046 IU/L, and of 0.000028 IU/L in ALT according to sex, age group, weight group, and initial ART regimen per day, respectively. An estimated decrease of 0.000013 IU/L in ALT according to ADRs per day also occurred. There was an estimated decrease of 0.00038 μmol/L, 0.00039 μmol/L, 0.00040 μmol/L, 0.00040 μmol/L, and of 0.00028 μmol/L in serum creatinine per day according to sex, age group, weight group, initial ART regimen, and ADRs, respectively. There was an estimated decline of 0.00023 mmol/L, 0.00022 mmol/L, 0.00023 mmol/L, 0.00024 mmol/L, and of 0.00015 mmol/L per day in urea according to sex, age group, weight group, initial ART regimen, and ADRs, respectively. Health professional’s questionnaire: 49 health professionals responded to the questionnaire. 100% (n= 49) of the participants showed that they did not use the yellow card scheme to report ADRs. 34.65% (n = 17) use the individual case safety reports. 57.14% (n = 28) used the structured databases to report ADRs. 85.71% (n = 42) documented in the patient bukana, and 6.12% (n = 3) used the HIV/AIDS ART card to document ADRs occurrence. 91.84% (n = 45) of the health professionals never filled the ADR reporting form in their working environment. In conclusion, adverse drug reactions occurring in a hospital or healthcare facility should be recorded and reported by the medical practitioners, nurses, pharmacists, and the pharmacy technicians. Therefore, it is important to assess the continuous evaluation of the benefits and harm of medicines which will help in achieving the ultimate goal of making safer and more effective treatment available for patients. As well as to help the health professionals to participate in the very important process of continuous surveillance of safety and efficacy of pharmaceutical products used in clinical practice. / MPham (Pharmacy Practice), North-West University, Potchefstroom Campus, 2014

The background and problem statement focuses on antiretroviral therapy (ART) and the use of mobile technology to improve compliance within a primary health care (PHC) context in South Africa. South Africa is one of the countries, globally, with the highest HIV incidence and prevalence and ART enrolled patients visiting PHC facilities. Compliance to ART plays an integral part in effective HIV/AIDS management. HIV/AIDS management entails a complex process of patient education and pharmacological control to improve ART compliance in South Africa. Studies were done in South Africa on reminder messages as most studies focused on chronic conditions in general. A literature review explored what is known about ART and mobile technology to improve compliance. Literature confirmed that compliance through reminder messages were done worldwide and in Sub-Saharan countries. Previous research indicated that the compliance rate of the patients increased through reminder messages. Yet there is a gap in the literature regarding reminder messages combined with health education on ART compliance. The aim of the study was to determine the impact of reminder messages combined with health education on ART compliance among patients receiving ART at a PHC facility Methodology: The study followed a quantitative, experimental, intervention, randomised multi-group, pre- and post measurement design (Creswell, 2012:1, Welman et al., 2012:80). The research design is experimental because the researcher applied an intervention (reminder messages) to two experimental groups. Random sampling was applied and participants were grouped into three groups: Group A, (control group), Group B, (reminder messages only) and Group C (reminder messages combined with health education). A preand post-measurement design is followed as each participant’s pill count and return date were measured before and after the reminder messages with/without health education were given. The sample size was 202 eligible patients receiving Regime 1 and 2 ART’s (Lamuvidine, Tenofovir, Efavirenz, Nevirapine, Alluvia® and Zidovudine) at a PHC facility in the North West, South Africa (N=202). The sample size was determined with guidance of statistical services to ensure that results obtained from the study would be reliable and significant. Data collection was done in three phases. Phase one (1) consisted of collecting the biographical data and a pre-measurement of pill count and return dates for participants in Groups A, B and C. Phase two (2) consisted of sending bi-weekly messages (Group B) via WinSMS and with health education (Group C) for three (3) months. Phase three (3) consisted of post-measurement of participants’ pill count and return date for Groups A,B and C. Data collection stretched over six months (October 2013-March 2014), namely three months pre-measurement, then activation of intervention combined with another three months post-measurement. Descriptive and inferential statistical analysis was conducted through SPSS (SPSS Inc., 2013). Descriptive statistics indicated that more female patients visited the PHC facility for ART on a more regular basis. It was concluded that the experimental group proved a slight increase in compliance with regards to return date after the SMS intervention. No difference was noted in compliance to pill counts. It can also be concluded that pill counts is a complex monitoring procedure with room for error from the patients’ aspect. / MCur, North-West University, Potchefstroom Campus, 2015

Globally an estimated 33.4 million people were living with HIV/AIDS by 2008 (UNAIDS, 2009a:7). One of the main challenges facing the Republic of South Africa (RSA) today is the HIV/AIDS epidemic (NSP, 2007:17). By mid-year 2011 an estimated 5.38 million people (10.6% of the total population) were living with HIV/AIDS in the RSA (Statistics South Africa, 2011:2). Currently South Africa has the largest number of people enrolled in the Highly Active Antiretroviral Treatment programme (HAART) in the world (WHO, 2008:59). The objective of this study was to determine retrospectively the medicine treatment patterns of HAART at a district hospital in the North West Province of South Africa. The study was conducted at Thusong hospital in the Ditsobotla sub-district of the North West Province of South Africa. A non-experimental, retrospective, cross-sectional, drug utilisation research methodology was used to obtain the data. The target population included patients of all ages who visited Thusong hospital pharmacy during the data collection period, which commenced on 01 February 2012 and ended on 31 March 2012. The data of three hundred and ninety nine (N=399) adult and one hundred and sixty one (N=161) paediatric patients on HAART were used. The adult female patients accounted for almost 70% (n=276, 69.17%) and the adult male patients for only 30% (n=123, 30.83%). The male paediatric patients represented just over 60% (n=97, 60.25%), whereas the female paediatric patients comprised less than 40% (n=64, 39.75%). The majority of adult patients were unmarried (n=323, 80.95%) and this group of patients were also the youngest group (μ=36.38 ± 8.98 years) on ARV treatment. Almost 86% (85.96%, n=343) of adult patients were registered as unemployed. Ninety two (n=92, 23.06%) adult patients and fifty eight (n=58, 36.03%) paediatric patients defaulted treatment during the defined period. The investigation into the adult medicine treatment patterns revealed that more than half (52.38%, n=209) of all the adult patients were receiving regimen 1atn (EFV, TDF and 3TC), followed by 20.80% (n=83) on regimen 1a (EFV, D4T and 3TC). Most paediatric patients (n=73, 45.34%) were on regimen P1c (EFV, D4T and 3TC) and the second most (n=45, 27.95%) were on regimen P1a (D4T, 3TC and LPV/r). The average weight of adult female patients was 57.18kg (± 15.78kg) and the average adult male patient weighed 55.87kg (± 10.17kg) on initiation of HAART. The average adult male patient was initiated on HAART with a CD4 count of 130cells/mm3 (± 99.45cells/mm3), while for adult female patients it was 160cells/mm3 (± 96.52cells/mm3). The average male child was initiated with a CD4 count of 509.1cells/mm3 and the average female paediatric patient with 477.3cells/mm3. The average viral load for adult female patients on initiation of HAART was 103046copies/mm3 (± 189146copies/mm3) and for adult male patients it was 416600copies/mm3 (± 439746copies/mm3). The difference between the viral load of adult female and male patients were described as statistically (p=0.0006) and practically (d=0.713) significant. The average viral load for female paediatric patients on initiation of HAART was 242207copies/mm3 (± 709133copies/mm3) and for male paediatric patients it was 329734copies/mm3 (± 674532copies/mm3). Adult patients that received HAART at more than 12 consultations revealed an average weight gain of 3.43kg (± 8.11kg) from initiation of treatment. This group also showed an average increase of 214.71cells/mm3 (± 248.24cells/mm3) in CD4 count and an average reduction in viral load of 170944copies/mm3 (± 191854.69copies/mm3) from the day they started HAART up to the last date of receiving treatment. The paediatric patients on treatment for more than 12 consultations showed an average weight gain of 6.56kg (± 3.75kg) from initiation of ARV treatmentup to the last date of receiving treatment. They also showed an average increase in CD4 count of 396.63cells/mm3 (± 594.53cells/mm3) and a very encouraging average decrease of 538369.37copies/mm3 (± 948634.46copies/mm3) in the viral load. / MPham (Pharmacy Practice), North-West University, Potchefstroom Campus, 2014

The background and problem statement focuses on antiretroviral therapy (ART) and the use of mobile technology to improve compliance within a primary health care (PHC) context in South Africa. South Africa is one of the countries, globally, with the highest HIV incidence and prevalence and ART enrolled patients visiting PHC facilities. Compliance to ART plays an integral part in effective HIV/AIDS management. HIV/AIDS management entails a complex process of patient education and pharmacological control to improve ART compliance in South Africa. Studies were done in South Africa on reminder messages as most studies focused on chronic conditions in general. A literature review explored what is known about ART and mobile technology to improve compliance. Literature confirmed that compliance through reminder messages were done worldwide and in Sub-Saharan countries. Previous research indicated that the compliance rate of the patients increased through reminder messages. Yet there is a gap in the literature regarding reminder messages combined with health education on ART compliance. The aim of the study was to determine the impact of reminder messages combined with health education on ART compliance among patients receiving ART at a PHC facility Methodology: The study followed a quantitative, experimental, intervention, randomised multi-group, pre- and post measurement design (Creswell, 2012:1, Welman et al., 2012:80). The research design is experimental because the researcher applied an intervention (reminder messages) to two experimental groups. Random sampling was applied and participants were grouped into three groups: Group A, (control group), Group B, (reminder messages only) and Group C (reminder messages combined with health education). A preand post-measurement design is followed as each participant’s pill count and return date were measured before and after the reminder messages with/without health education were given. The sample size was 202 eligible patients receiving Regime 1 and 2 ART’s (Lamuvidine, Tenofovir, Efavirenz, Nevirapine, Alluvia® and Zidovudine) at a PHC facility in the North West, South Africa (N=202). The sample size was determined with guidance of statistical services to ensure that results obtained from the study would be reliable and significant. Data collection was done in three phases. Phase one (1) consisted of collecting the biographical data and a pre-measurement of pill count and return dates for participants in Groups A, B and C. Phase two (2) consisted of sending bi-weekly messages (Group B) via WinSMS and with health education (Group C) for three (3) months. Phase three (3) consisted of post-measurement of participants’ pill count and return date for Groups A,B and C. Data collection stretched over six months (October 2013-March 2014), namely three months pre-measurement, then activation of intervention combined with another three months post-measurement. Descriptive and inferential statistical analysis was conducted through SPSS (SPSS Inc., 2013). Descriptive statistics indicated that more female patients visited the PHC facility for ART on a more regular basis. It was concluded that the experimental group proved a slight increase in compliance with regards to return date after the SMS intervention. No difference was noted in compliance to pill counts. It can also be concluded that pill counts is a complex monitoring procedure with room for error from the patients’ aspect. / MCur, North-West University, Potchefstroom Campus, 2015