It is estimated that 6742 South African women are diagnosed with cervical cancer and 3681 women die from the disease every year. In 1993, The Centers for Disease Control declared cervical cancer an Acquired Immunodeficiency Syndrome defining illness. Apart from persistent human papillomavirus infection, HIV infection is the most common co-factor contributing to cervical cancer in South Africa. Studies have noted that in HIV positive women, there has been an occurrence of faster progression to more advanced stages of cervical cancer with high cases of treatment failure and recurrence. There is limited literature available regarding the prognosis of HIV positive women who suffer from cervical cancer. Women who are HIV positive and have cervical cancer have not been evaluated in detail regarding their response and adherence to cervical cancer treatment. Standard treatment protocols for this set of patients have not been defined. The aim of this study was to assess how HIV positive women who have been diagnosed with cervical cancer responded and adhered to cervical cancer therapy which includes: curative radiotherapy; curative chemotherapy; concurrent chemoradiation or palliative radiotherapy. The study also evaluated the effects of the concurrent use of antiretrovirals and cervical cancer treatment. This was done to determine whether invasive cervical cancer in women who were HIV positive could be managed using the same treatment protocols as patients who were HIV negative. A historical cohort design was employed for the study. The study was conducted at the Oncology Department of a tertiary level hospital located in the Eastern Cape Province, South Africa. The total sample consisted of 196 medical records of women diagnosed with cervical cancer between 2005 and 2008. One hundred women were HIV negative, 83 were HIV positive and the HIV status of 13 women could not be determined. The records were audited over a period of two years from the date of diagnosis. The term „complete response‟ referred to patients who had no recurrence of cervical cancer and no evidence of metastases after undergoing treatment. At one month following treatment there was a significant difference in the incidence of complete response between the HIV positive patients and the HIV negative patients (Chi2 = 16.4, d.f. = 1, p = 0.00005, Cramer‟s V = 0.31). The significant difference in response to treatment between the HIV positive patients and the HIV negative patients was maintained at six months after treatment (Chi2 = 15, d.f. = 1, p = 0.00011, Cramer‟s V = 0.34), 12 months after treatment (Chi2 = 20.5, d.f. = 1, p = 0.00001, Cramer‟s V = 0.37), 18 months after treatment (Chi2 = 9.8, d.f. = 1, p = 0.00173, Cramer‟s V = 0.28) and 24 months after treatment (Chi2 = 5.0, d.f. = 1, p = 0.02571, Cramer‟s V = 0.26). At each of these intervals, cases of treatment failure and metastases were significantly higher in the HIV positive women than in the HIV negative women. Although there was no significant difference in the incidence of adherence between the HIV negative women, the HIV positive women who were on HAART and the HIV positive women who were not on HAART, there was a significant difference in the incidence of the various reasons for non adherence between the various groups. These reasons included: missed scheduled appointments (Chi2 = 2.9, d.f. = 2, p = 0.02385, Cramer‟s V = 0.31); low blood count (Chi2 = 4.0, d.f. = 2, p = 0.01327, Cramer‟s V = 0.15); radiotherapy induced skin breakdown (Chi2 = 0.6, d.f. = 2, p = 0.04581, Cramer‟s V = 0.16) and radiotherapy induced diarrhoea (Chi2 = 6.9, d.f. = 2, p = 0.03118, Cramer‟s V = 0.19). According to the 2004 National Antiretroviral Treatment Guidelines, cervical cancer patients would fall into the WHO stage IV category of HIV disease thus all patients with confirmed diagnosis of invasive cervical cancer should be commenced on antiretrovirals as soon as the cancer diagnosis is made regardless of their CD4 count. However, in the current study, 13 percent (n= 83) of the HIV positive women were not on antiretrovirals. The study concluded that HIV positive women had a higher incidence of both treatment failure and metastases to cervical cancer treatment. Standard radiotherapy and concurrent chemoradiation cervical cancer treatment protocols should be still be used in both HIV negative patients and HIV positive patients so as not to compromise tumour control. Furthermore, in accordance with the antiretroviral treatment guidelines, all HIV positive patients with cervical cancer should receive antiretrovirals irrespective of their CD4 count.

Thesis (MPA (Public Management and Planning))--University of Stellenbosch, 2010. / ENGLISH ABSTRACT: The accessibility of anti-retroviral drugs to patients and families affected by HIV and AIDS, and the affordability of these drugs, have been challenges to the Du Noon community in the Cape Peninsula. The aim of the study was to assess the effectiveness of primary health care services in addressing HIV/AIDS in the light of these challenges. The focus was on patients registered on the ARV programme and who were receiving treatment at Du Noon Clinic. Interviews were conducted with 15 groups of 10 patients each using a patient questionnaire. During these interviews qualitative and quantitative data were gathered and secondary data was used for quantitative analysis. The results that the data analysis yielded are in keeping with the hypothesis that the HIV/AIDS programme is effective in meeting the needs of the HIV/AIDS patients of Du Noon. After content analysis of qualitative data, two themes related to patient satisfaction emerged: positive and negative feelings that were categorised as satisfied and not satisfied with the service. Most often noted was the feeling of satisfaction with the services rendered at the clinic and that the staff were helpful. The staff rendering the service were also satisfied with the kind of service offered to the patients, but were dissatisfied with the allocation of resources. An increase in enrolment figures of patients was noted in the statistical analysis for the period 2004-2008 with 1,018 patients registered. The statistics illustrate the linear tendency in the enrolment of patients, which indicated the accessibility and affordability of the service. / AFRIKAANSE OPSOMMING: Geredelike toegang tot en die bekostigbaarheid van anti-retrivorale middels (ARM’s) vir pasiënte en families wat deur MIV en VIGS aangetas is, is ‘n uitdaging vir die Du Noon-gemeenskap in die Kaapse Skiereiland. Die doel van die studie was om die doeltreffendheid van primêre gesondheidsorgdienste te bepaal wanneer MIV/VIGS aangespreek word. Die fokus is op geregistreerde pasiënte wat die ARM-program volg en behandeling by die Du Noon Kliniek ontvang. Met behulp van ‘n pasiëntevraelys was onderhoude met 15 groepe van 10 pasiënte elk gevoer. Tydens hierdie onderhoude is kwalitatiewe data versamel en vir kwantitatiewe analise was sekondêre data aangewend. Die resultate wat uit die data analise verkry was, strook met die hipotese dat die MIV/VIGS-program doeltreffend is om die behoeftes van die pasiënte en die gemeenskap van Du Noon aan te spreek. Nadat ‘n inhoudsanalise van die kwalitatiewe data onderneem was, het twee temas rakende positiewe en negatiewe gevoelens – gekategoriseer as tevrede en nie tevrede nie – ten opsigte van die gelewerde diens na vore getree. Veral die gevoel van tevredenheid teenoor die diens gelewer by die kliniek en die personeel as behulpsaam, is opgemerk. Die personeel wat die diens lewer, was ook tevrede met die diens wat aan die pasiënte gelewer word, maar was ontevrede oor die toekenning van hulpbronne. By die statistiese analise is ‘n toename in die inskrywingsgetalle deur pasiënte waargeneem. Toename in inskrywingsgetalle deur pasiënte is gemerk in statistiese analise van 2004 - 2008, met 1,018 pasiënte geregistreer. Die statistiek het die lineêre tendens toegelig ten aansien van die inskrywing van pasiënte wat die toeganklikheid en bekostigbaarheid van die diens uitbeeld.

Thesis (MPhil)--Stellenbosch University, 2013. / ENGLISH ABSTRACT: This study, which was conducted from 1 to 31 October 2012, was aimed at describing the main factors that influence adolescent adherence to antiretroviral treatment in three selected health facilities of Palapye Health District. During the one-month data collection period, 30 adolescents were interviewed using semi-structured interview tools. Different factors influencing adolescent adherence to antiretroviral treatment were highlighted and adherence to such treatment was measured using the method of calculating the percentage of returned pills. The mean adherence level for the entire sample was 76.96%, with common factors contributing to poor adherence among adolescents being found to be the poor processing of disclosure, stigma, the accessibility of health facilities, due distance and waiting time, the nature of social support, and feelings toward taking antiretroviral. Thus, by addressing adolescent adherence to antiretroviral treatment, adolescent-adherence counselling before and during treatment is to be shaped, insisting on the preparation of young patient caregivers for the process of disclosure; the reinforcement of positive messages during consultations; insistence on the importance of disclosing HIV status to others; the implementation of the antiretroviral dispensing outreach at health posts; and exerting effort to reduce the waiting time at health facilities prioritising young patients and adolescents. / AFRIKAANSE OPSOMMING: Hierdie studie, wat vanaf 1 tot 31 Oktober 2012 onderneem is, het ten doel gehad om die hooffaktore te beskryf wat adolessente se getrouheid met antiretrovirale behandeling in drie gekose gesondheidsfasiliteite in die Palapye-gesondheidsdistrik beïnvloed. Semigestruktureerde onderhoude is gedurende die maand lange datainsamelingstydperk met 30 adolessente gevoer. Die studie dui op verskillende faktore wat adolessente se getrouheid met antiretrovirale behandeling beïnvloed, welke getrouheid gemeet is aan die hand van die persentasie teruggestuurde pille. Die gemiddelde getrouheidsvlak vir die algehele steekproef was 76,96%. Algemene faktore wat oënskynlik tot swak behandelingsgetrouheid onder adolessente bydra, is die swak verwerking van MIV-statusonthulling, stigma, die toeganklikheid van gesondheidsfasiliteite, reisafstand en wagtyd, die aard van maatskaplike steun, en gevoelens oor die gebruik van antiretrovirale middels. Hierdie ondersoek na adolessente se getrouheid met antiretrovirale behandeling behoort adolessentberading oor behandelingsgetrouheid voor én gedurende behandeling te rig. Die klem moet in die besonder val op die voorbereiding van die versorgers van jong pasiënte om die onthullingsproses beter te hanteer; die versterking van positiewe boodskappe gedurende konsultasies; die belang van MIV-statusonthulling aan ander; die inwerkingstelling van uitreikaksies om voorskrifte vir antiretrovirale middels by sogenaamde ‘gesondheidstasies’ te resepteer, en daadwerklike pogings om die wagtyd by gesondheidsfasiliteite te verkort, met voorrang aan jong pasiënte en adolessente.

Thesis (MFamMed) -- Stellenbosch University, 2012. / ENGLISH ABSTRACT: Background Sub-Saharan Africa has been hard hit by the HIV/AIDS epidemic with an estimated 22.9 million adults infected in 2010. The advent of antiretroviral therapy (ART) has seen significant reduction in mortality from AIDS related illnesses. With the reduction of mortality and the indisputable positive results seen from the use of Anti-retroviral Treatment (ART), the demand both from people living with HIV and health care providers to phase in less toxic ARVs while maintaining simplified fixed-dose combinations has increased considerably. Botswana like most low-resource countries has adapted the WHO recommendation of daily ART as opposed to the previous twice daily HAART. No evidence from resource limited settings has been found that clearly indicates the superiority of regimens based on AZT, d4T or TDF. Aim The primary aim was to compare treatment response between two cohorts. The secondary aim was to compare any association of regimen to age or gender. Objectives To comparatively determine treatment response at 3 months based on immunological response (shown by an increase in CD4 above pre-therapy levels) and viral load response. Methods The study is a retrospective comparative cohort study. Three ART sites were selected from a total of 6 sites. A sample size of 263 was required to achieve a 90% effect power. An equal number of patient records were reviewed per site and each arm had an equal number of reviewed records. A total of 286 patient record files which fit the inclusion criteria were retrospectively analysed and data entered in Excel before being analysed using Statistica Version 10. A p <0.05 represents statistical significance whilst a 95% confidence interval was used for estimation of unknown variables. Results n=263. The overall sample was predominantly male (75.19%). An overwhelming majority (95.88%) of patients in both arms had undetectable viral loads (VL<400). A significant association was found between the regimen and viral load (p=0.0315-Pearson Chi Test). The difference in CD4 between the two arms was not statistically significant (p=0.655890-ANOVA). A positive association was found between the regimen and gender (p=0.03190-Pearson Chi Test). This was possibly owing to the high numbers of males and no statistical adjustment to gender made. No association was found in the difference in CD4 cell counts for regimen and gender (p=0.612191-Anova). Conclusion Treatment response at 3 months post initiation between once daily and twice daily HAART in Gaborone Botswana by use of virologic and immunologic response has been shown to be comparable. The use of one regimen over the other as first line as recommended by WHO and the subsequent adoption of the current first line regimen by the Botswana Ministry of Health may be justified. This study has therefore reinforced the applicability of previous findings in other settings of this recommendation. As part of the targeted audience and indeed as a partner in the care and management of HIV, the responsibility to ensure applicability of the recommendations set out for resource limited areas has been achieved through this study. However, bigger randomized trials in resource limited settings are needed to justify and accredit these findings as well as add to the evidence obtained in developed countries.

Indiana University-Purdue University Indianapolis (IUPUI) / The antiretroviral drug efavirenz remains a cornerstone for treatment-naïve HIV patients. Subsequent to the demonstration that efavirenz is a substrate of cytochrome P450 (CYP) 2B6, a number of clinical studies found that the CYP2B6*6 allele is significantly associated with higher efavirenz exposure and/or adverse reactions. However, the mechanism of reduced efavirenz metabolism by this genetic variant is not fully understood and whether this variant exhibits differential susceptibility to metabolic inhibition is also unknown. Ths use of efavirenz is further complicated by the drug interactions associated with it. Therefore, I hypothezised that 1) the CYP2B6*6 allele reduces efavirenz metabolism by altering catalytic properties of CYP2B6; 2) efavirenz alters the pharmacokinetics of co-administered drugs by inhibiting drug metabolizing enzymes. A series of studies was carried out in hepatic microsomal preparations to determine the functional consequences of the CYP2B6*6 allele and to assess inhibition potency of efavirenz on 8 CYPs. The major findings for these studies include: 1) the CYP2B6*6 allele reduces efavirenz metabolism by decreasing substrate binding and catalytic efficiency; 2) functional consequences of the CYP2B6*6 allele appear to be substrate- and cytochrome b5-dependent; 3) the CYP2B6*6 allele confers increased susceptibility to metabolic inhibition; and 4) efavirenz inhibits the activities of CYP2B6, 2C8, 2C9 and 2C19 at therapeutically relevant concentrations. In addition, I explored the hypothesis that the incorporation of in vitro mechanism by which the CYP2B6*6 allele reduced efavirenz metabolism predicts the genetic effect of this allele on efavirenz clearance after a single oral dose by modeling approach. A pharmacogenetics-based in vitro-in vivo extrapolation (IVIVE) model was developed to predict human efavirenz clearance. Taken together, results from this dissertation provide new mechanistic information on how the CYP2B6*6 allale alters substrate metabolism and drug interactions; demonstrate new mechanisms of efavirenz-mediated inhibition interactions; and demonstrate the utility of a pharmacogenetics-based predictive model that can serve as a basis for future studies with efavirenz and other CYP2B6 substrates. Overall these data provide improved understanding of genetic and non-genetic determinant of efavirenz disposition and drug interactions associated with it.

As the Human Immunodeficiency Virus (HIV) prevalence rises, uninfected Basotho face an increased risk of exposure. This necessitates strengthening of strategies that prevent exposure, and where exposure has occurred, measures that prevent infection. One such measure is Human Immunodeficiency Virus (HIV) Post-Exposure Prophylaxis (PEP). Awareness and knowledge of HIV PEP is therefore of paramount importance. The purpose of this study was to assess knowledge, attitudes and utilisation of HIV PEP among adults in Roma, Lesotho. A quantitative cross-sectional study was conducted among 96 adult outpatients at St Joseph’s Hospital. Data were collected by means of structured questionnaire and analysed using SPSS version 23.0. Results were presented using charts and tables. Awareness of HIV PEP among the respondents was found to be very low and for most respondents’ knowledge of HIV PEP was either non-existent or very poor. Utilisation was also found to be very low. Attitudes towards HIV PEP were, however, found to be favourable. More studies should be conducted throughout the country to further explore Basotho’s knowledge, attitude and use of HIV PEP. / Health Studies / M.A. (Nursing Science)

Background: South Africa has a generalised HIV epidemic which is managed through free Antiretroviral Therapy (ART). Adherence to ART has emerged as a crucial issue in HIV/AIDS therapeutics. Purpose: The aim of the study was to explore determining factors for poor and excellent adherence to ART for HIV positive patients residing in Barberton, a mining town in Mpumalanga Province. Methodology: A generic qualitative research design was undertaken. Data was collected through in-depth qualitative interviews from a purposive sample of 13 ART patients. Qualitative interpretive analysis was employed. Findings: The study found that excellent adherence to ART is significantly associated with the availability, effectiveness and comprehensiveness of HIV services, psychological support and medical advances. Side effects of ART, opportunistic infections and alcohol and drug use hinder adherence. However, longer duration on ART enhanced self-efficacy and facilitated adherence. Successful ART is dependent on taking ARVs as prescribed and executing necessary lifestyle changes. / Health Studies / M.P.H.