3. Electronic Theses and Dissertations (ETDs) - All submissions
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Item Predictors of weight loss in HIV-infected women on antiretroviral therapy in Rwanda.(2014-03-28) Kimenyi, Jean PaulBackground: Highly Active Antiretroviral Treatment (HAART) has reduced the frequency of weight loss/wasting associated with HIV infection. However, weight loss remains a problem, even in the HAART era. Objectives: This study was carried out to assess weight change in a cohort of HIV-infected women on HAART in Rwanda, from 2005 to 2008, and to identify factors that predict weight loss in this cohort. Methods: Data from a cohort of 449 HIV-positive women on HAART enrolled in the Rwanda Women’s Inter-association Study and Assessment (RWISA), starting in May 2005, and followed at six monthly intervals until December 2008, were analysed. The outcome assessed in this study was change in weight, measured in kilograms at 6, 12 and 24 months after HAART initiation. Nutritional status was recorded and laboratory measurements (weight, height and CD4 cell count) were taken prior and after HAART initiation. All covariates were time dependent, except for the history of weight loss which was recorded at baseline only. Generalized Estimating Equation (GEE) using the linear link (Gaussian [normal]), exchangeable covariance structure and robust standard error was used to assess the factors associated with changes in weight (weight loss or weight gain) and to control for potential confounders. Results: Prior to HAART initiation, the mean weight of the study participants was 53.1 kg (SD 9.5). The mean BMI was 21.3 kg/m2 (SD 3.6) and the mean CD4 cell count was 222.9 cells/μL (SD 120.6) [47.6% had CD4 cell counts <200 cells/μL, 52.2% had CD4 cell counts ≥200 cells/μL]. Overall, the participants gained weight from baseline to 12 months after HAART initiation. The mean weight change was 1.9 kg (SD 7.8) (p<0.001) 6 months after HAART initiation, 2.9 kg (SD 5.9) (p <0.001) 12 months after HAART initiation, and 2.4 kg (SD 6.5) (p <0.001) 24 months after HAART initiation. Six months after HAART initiation, 48.3% of participants had gained weight, and 21.0% had lost weight. Twelve months after HAART initiation, 56.9% had gained weight, and 18.3% had lost weight, Twenty-four months after HAART initiation, 56.6% had gained weight, and 22.6% had lost weight. Participants with CD4 cell counts ≤ 200 cells/μL at baseline gained more weight than those with CD4 cell counts > 200 cells/μL at 6, 12 and 24 months after HAART initiation. Participants who were underweight (BMI <18.5 kg/m2) at baseline gained more weight than other participants three months after HAART initiation. Time-dependent diarrhoea for more than two weeks and a CD4 cell count of 200 - 350 cells/μL were significantly associated with weight loss (p≤ 0.05). Others factors, such as time-dependent education level (completion of secondary school), marital status (married legally and status other than married legally or widowed), and increases in CD4 cell counts, were associated with weight gain (p≤ 0.05). Conclusion: Although the majority of participants gained weight during the first 12 months of being on HAART, a significant proportion of participants lost weight while on HAART. The findings on the predictors of weight change in HIV-positive women on HAART can be used to promote weight gain in women who start HAART. Clinicians who take care of HIV-infected patients on HAART should pay attention to those who lose weight, and those who present with diarrhoea or with CD4 cell counts of <350 cells/μL at follow-up visits, since these factors are associated with weight loss in the HAART era.Item Adherence to highly active antiretroviral treatment and loss to follow-up of pregnent women at the Themba Lethu Clinicu(2011-06-10) Nagar, ShashikalaINTRODUCTION Although much focus has been placed towards rapid scale-up of antiretroviral treatment programmes and interventions for the prevention of mother-to-child transmission of human immunodeficiency virus (HIV), very little is known about adherence to highly active antiretroviral therapy (HAART) and loss to follow-up of pregnant women in antiretroviral treatment programmes in the developing world. In this retrospective cohort analysis, we described the baseline characteristics of adult women who were pregnant at the time of HAART initiation (pregnant at start) as well as women who became pregnant during follow-up after starting HAART (pregnant after) and women who never had a pregnancy (not pregnant) during the study period. We evaluated the association of pregnancy status with adherence and loss to follow-up in these three groups of women. MATERIALS AND METHODS Themba Lethu Clinic is an urban public-sector antiretroviral rollout facility in Johannesburg, South Africa. A retrospective analysis was conducted of all adult women initiating HAART at this clinic between January 2005 and December 2007. Clinical data from these patients was analysed for differences in rates of loss to follow-up, and measured adherence rates based on CD4 cell count response and virologic suppression. Regression models were performed to determine independent predictors of adherence and loss to follow-up and compared between the three groups. Survival analysis, in the form of Kaplan-Meier plots and log-rank tests, was used to compare the time to becoming lost to follow up. RESULTS Between 1 January 2005 and 31 December 2007, 5129 women initiated HAART at Themba Lethu Clinic, Johannesburg, South Africa. Of these women, 521 (10.0%) were pregnant at the time of HAART initiation (pregnant at start) and 291 (5.6%) became pregnant during follow-up (pregnant after). Women who were pregnant at start (16.6%) of HAART had less-advanced HIV disease than the not pregnant women and pregnant women after HAART initiation 4608 (89.9%). Overall pregnant women were significantly younger than the not pregnant women and fewer pregnant women had a CD4 <100 cells/mm3 and a WHO stage III of HIV disease. There was no significant difference in the CD4 cell count response and virological suppression between the three groups of women based on pregnancy status at 6 months and 12 months (X2=2.1, p=0.347 and X2=4.4, p=0.111 respectively). However, women pregnant at start were more likely to become lost to follow-up (X2=15.8, P=<.0001) during follow up. In the multivariate Cox logistic regression model, independent predictors of loss to follow-up were pregnancy, baseline CD4 cell count and age at initiation. Being pregnant was significantly associated with being loss to follow-up. CONCLUSIONS Pregnancy is significantly associated with defaulting treatment and becoming lost to follow-up from HAART treatment programmes. Together with being pregnant, young age and a low CD4 at baseline are high risk factors for non adherence and loss to follow-up in this sub-group of the population. Early initiation of HAART with adequate pre-treatment counselling and ongoing adherence support could help improve adherence and retention in care for patients in treatment programmes in resource-limited settings. Interventions to trace patients immediately upon missed appointments would help to reduce the number of patients’ loss to follow-up. Moreover, integration of tuberculosis (TB), antenatal care (ANC) and HIV treatment services may maximize the effectiveness of interventions aimed at reducing the loss to follow-up rate. The initiation of HAART in pregnancy requires strengthened antenatal and HIV services that target women with advanced stage disease.Item An exploration of the experiences of clients on antiretroviral therapy and their health care providers in KwaZulu Natal(2011-04-07) Mhlongo, Euphemia MbaliThe aim of the study was to explore the practice of antiretroviral (ARV) therapy services, specifically regarding the patients’ issues and experiences, as well as the experiences of the health care providers rendering these services. Qualitative research methods were used, including a metasynthesis of qualitative research articles on human immunodeficiency virus (HIV) positive patients on ARV therapy, and phenomenological methods of inquiry. The study objectives were to conduct a metasynthesis of qualitative research on HIV-positive people on ARV therapy; to investigate the experiences of HIV-positive people who are on ARV therapy; to identify the constraints faced by HIV-positive people receiving ARV therapy; and to explore adherence to ARV therapy. The study was conducted in eThekwini district in KwaZulu Natal (KZN) province. The district was chosen considering the number of clinics rolling out ARV therapy. Three institutions initiating ARV therapy participated in the study; one urban, one semi-urban and one rural clinic, to ensure representation of each type. Participants were recruited from two initiating hospitals and one Community Health Centre providing ARV therapy. The metasynthesis revealed a shared set of four themes viz.: 1. Acceptance of, and coping with, HIV positive status 2. Social support and disclosure 3. Experiences and beliefs about HIV medication and health care 4. Provider relationships and health system factors Qualitative analyses of interviews with clients indicated their experiences and concerns, and were summarized in these themes: 1. Life before and after knowing HIV status 2. Initiating and continuing ARV therapy 3. Adherence to, and side effects of, the ARV therapy treatment 4. Social support for people on ARV treatment vi 5. Positive outcomes of being on ARV treatment 6. Improving access to ARV treatment services Analyses of in-depth interviews with health care providers specified their experiences, and were categorized into three themes viz.: 1. Establishing and maintaining a good client-provider relationship 2. Facilitators of and adherence to ARV treatment 3. Barriers to access to treatmentItem Comparison of virologic outcomes in HIV-infected adolescents on Highly Active Antiretroviral Therapy in Soweto, South Africa(2011-03-23) Mabuto, TonderaiObjectives: To evaluate differences in virologic outcomes between adolescents and pre-adolescents initiated on HAART and to determine the patient baseline variables associated with virologic suppression. Design: Retrospective cohort study using routinely collected clinic and outcome data. Setting: Public sector HIV paediatric facility at Harriet Shezi Children’s Clinic (Chris Hani Baragwanath Hospital) Soweto, South Africa. Patients: HIV infected pre-adolescents (5 to < 11 years) and adolescents (11 to <18 years) initiating HAART between 1 April 2004 and 31 December 2008. Main outcomes and measures: Primary: virologic suppression (HIV viral load ≤ 400 copies/ml) and viral rebound (single HIV viral load ≥ 400 copies/ml after initial suppression) at 24, 48, 72 and 96 week follow up intervals. Secondary: determination of baseline variables associated with virologic suppression. Survival analysis was performed using the Kaplan Meier method and modelling was based on Cox proportional hazards. Results: Both groups exhibited similar incidence rates of virologic suppression by the 24th week from HAART initiation. Adolescents had a slightly lower incidence rate of early virologic suppression in comparison to pre-adolescents (197/100 person years vs. 203/100 person years). However, the observed difference was not statistically significant at 5% significance level (IRR: 0.97, 95%CI: 0.81 - 1.15). In a sub-group of children who had not virologically suppressed by the 24th week (168 days) of follow up, adolescents were 42% less likely to achieve virologic suppression after this time point than pre-adolescents ([IRR: 0.58, 95%CI: 0.35, 0.93). In the sub-group of all female participants, lower hazards of virologic suppression by the 24th week (aHR 0.76, 95%CI 0.59-0.99) and 96th week (aHR 0.70, 0.55-0.90) of follow up were observed among female adolescents when compared with female pre-adolescents. Additionally, clinically advanced disease was observed as a risk factor for non-virologic suppression by the 96th week of follow up among participants of all ages (aHR 0.75, 95%CI 0.64 -0.87). After 60 weeks from the initial virologic suppression, adolescents were twice more likely to experience rebound after this point than pre-adolescents (IRR: 2.33, 95%CI: 1.00 - 5.13). Conclusion: Given the potential for resistant strains of the HIV virus and the public health threat this presents, health care teams face complicated dilemmas regarding initiation of HAART to adolescents, particularly female adolescent patients who are likely to be non-adherent. Findings from the study advocate for intensified adherence and treatment support for all adolescents initiated on HAART to achieve virologic suppression within the first 6 months of treatment, a time after which they have been shown to exhibit inferior virologic suppression rates. Once virologic suppression has been attained, adolescents require prolonged treatment support to maintain long term virologic suppression at levels observed among pre-adolescents. We recommend further research into the comparison of virologic outcomes between pre-adolescents and adolescents on HAART, through prospective study designs. Qualitative study designs are also important to bridge the knowledge gaps on the barriers to HAART encountered by female adolescents.Item The impact of in-utero highly active antiretroviral therapy (HAART) exposure on infant outcomes(2011-02-24) Van der Merwe, Karin JoanBackground To investigate whether in-utero exposure to highly active antiretroviral treatment (HAART) is associated with low birth weight and/or preterm birth in a population of South African women with advanced HIV infection. Methods A retrospective observational study was performed on women with CD4 cell counts ≤250 cells/mm3 attending antenatal antiretroviral clinics at two clinics in Johannesburg between October 2004 and March 2007. Low birth weight (<2.5kg) and preterm birth rates (<37 weeks) were compared in those exposed versus unexposed to HAART during pregnancy. Effects of different HAART regimen and duration (<28 weeks or ≥ 28 weeks) were assessed. Results Among HAART-unexposed infants 27% (60/224) were low birth weight (LBW) compared to 23% (90/388) of early HAART-exposed and 19% (76/407) of late HAART-exposed infants (P=0.05). In the early HAART group, older maternal age was associated with LBW and higher CD4 cell count protective against LBW (AOR 1.06, 95% CI 1.00- 1.12 and AOR 0.58, 95% CI 0.46-0.73, P<0.001, respectively). HAART-exposed infants had an increased risk of preterm birth vii (<37 weeks) (15% [138/946] versus 5% [7/147], p=0.001), with early (<28 weeks) nevirapine and efavirenz having the strongest associations with preterm birth (AOR 5.4, 95%CI 2.1-13.7, P<0.001 and AOR 5.6, 95%CI 2.1-15.2, P=0.001, respectively). Conclusion Among infants born to women with CD4 cell counts <250 cells/mm3, HAART exposure was associated with preterm birth, but not with low birth weight. More advanced immunosuppression was a significant risk factor for both LBW and preterm birth, highlighting the importance of earlier HAART initiation in pregnant women, both to optimize maternal health and to improve infant outcomesItem Risk management in HIV/AIDS: ethical and economic issues concerning the restriction of HAART access only to adherent patients(2011-02-15) Chawana, RichardSouth Africa, like many other developing nations, is faced with the challenge of mobilising resources to fight the HIV/AIDS pandemic. There is a huge budget gap between the ideal and actual funding provided to achieve universal access to highly active antiretroviral therapy (HAART), which leads to the inevitable rationing of HAART. Although healthcare spending has been increasing in South Africa, new demands are being placed on the HAART roll out programmes. This is particularly due to the emergence of HIV drug resistance (HIVDR). Because non-adherence to HAART is strongly linked to drug resistance, this is a major threat to any successful HAART programme. In the face of restricted resources, this research report looks at some of the ethical and economic implications of non-adherence to HAART. I suggest that there is merit in considering that HAART be restricted only to adherent patients.Item A rural-urban comparison of patient characteristics and HIV treatment outcomes in South Africa(2011-02-14) Ekrikpo, Udeme EkpenyongBackground: Few studies have compared the sociodemographic characteristics and treatment outcomes of HIV/AIDS patients in rural and urban South Africa. Aim: This study compared the baseline socio-demographic characteristics and treatment outcomes (time to mortality, immunologic and virologic response) of HAART-naïve patients in urban and rural South Africa. Methodology: A secondary analysis of data obtained from the Themba Lethu Clinic, Helen Joseph Hospital, Johannesburg (urban site) and the ACTS clinic, Mpumalanga (rural site) from January 2005 to December 2008 was used to make comparison of baseline socio-demographic and clinical characteristics of patients in both cohorts. The survival experience and predictors of mortality was performed using Kaplan – Meier survival analysis and Cox proportional hazards models while effects on immunologic and virologic responses to HAART were modeled using logistic regression. Results: At initiation of HAART, the rural cohort had similar CD4 count and body mass index, but lower haemoglobin levels, compared to the urban cohort. The median follow up time for both cohorts was 566 days with the urban cohort having a mortality rate of 5.6/100 person-years compared to the 4.8/100 person-years of the rural cohort. CD4 count, BMI and WHO stage were predictors of mortality in both cohorts. Logistic regression models for virologic and immunologic response did not show any difference by site in the multivariate models. Conclusion: Though there are differences in the baseline sociodemographic and clinical characteristics of rural and urban patients starting HAART for the first time, achievement of immunologic and virologic response at 6 months of therapy were similar in both cohorts. Continued public health enlightenment campaigns and nutritional support programs should be undertaken to ensure patients present early and benefit from treatment.Item The burden of metabolic diseases amongst HIV positive patients on HAART attending the Johannesburg Hospital(2010-10-15) Julius, Henry PatrickBackground: The increase use of highly active antiretroviral therapy (HAART) among patients with HIV infection and AIDS has led to increasing reports of metabolic abnormalities such as diabetes mellitus, hypertension, dyslipidaemia and obesity. Therefore, it is important to explore the burden of these diseases among HIV infected patients. Objectives: To determine the burden of metabolic diseases (hypertension, diabetes, obesity and dyslipidaemia) in patients attending HIV clinic at the Charlotte Maxeke Johannesburg Academic Hospital (JHBH). Methodology: It was a cross-sectional study. The study population included patients attending JHBH HIV clinic and on HAART for more than one year. A sample size of 304 patients, including 237 females and 67 males partook in this study. Anthropometric measurements were taken from patients and blood samples of these patients were sent to laboratory for lipograms, HbA1c, random glucose, CD4 lymphocytes counts as well as HIV viral load testing. The data was analysed with standard statistical software Epi-info version 6.0. Both descriptive and analytical statistics was used. Results: The prevalence of metabolic syndrome according to the IDF was 20.4 %; obesity (BMI 30 kg/m2) was 16.8% and patients that were overweight (BMI > 25 kg/m2 and BMI < 29.9 kg/m2) was 28.6%; hypercholesterolemia (TC 5.0 mmol/l) = 35.5%; HDL< 1.29 mmol\L in females was 58% and HDL <1.04 mmol/l in males was 36%; elevated triglycerides 1.7 mmol/l was 30% and only 16% was classified as being hypertensive (BP 140/90 mmHg and / or on Hypertensive medication). The majority of the patients (86.2%) had a CD4 lymphocyte count 200 X 106 cells/l and 84% of patients had less than detectable limits for viral loads (VL< 40 copies / μl), which has been reported as optimum levels for metabolic diseases in HAART recipients. Conclusion: These results clearly indicate that there is a growing burden of metabolic diseases among HIV patients on HAART attending the Johannesburg hospital HIV clinic. The current study also indicates that the metabolic disturbances are more frequent in women than in men, except for hypertension.Item Impact of viral and host genetic factors on antiretroviral treatment outcome in South African HIV-1 subtype C infected AIDS patients(2010-09-20) Wallis, Carole LorraineBackground: The availability of highly active antiretroviral (ARV) treatment in the South African government sector has reduced the morbidity and mortality associated with HIV-1 infection. However, ARV drug resistance and toxicity are major obstacles to achieving and maintaining virus suppression, but there is no provision for ARV drug resistance testing in the public sector. To date, most studies of ARV drug resistance in HIV-1 reverse transcriptase (RT) and protease (PR), are based on sequence data from HIV-1 subtype B, whereas subtype C is the predominant circulating subtype in South Africa. Moreover, host genetic polymorphisms associated with ARV drug toxicity have not been investigated in South African populations. This study evaluated viral and host genetic factors associated with ARV treatment outcome in 812 ARV drug-naive South African AIDS participants enrolled on the CIPRA-SA study from Johannesburg and Cape Town. Methodology: An affordable in-house genotyping protocol (subtype C specific) was established and validated to monitor the emergence of ARV drug resistance. This assay was used to genotype all CIPRA-SA participants failing the first- and second-line ARV drug regimens. Allellic discrimination assays to identify the G1344A, A6986G, G516T and C3435T SNPs in CYP3A4, 3A5, 2B6 and MDR-1, respectively, associated with ARV metabolism and absorption were p erformed. Results: The in-house ARV drug resistance assay successfully genotyped 95% of patient samples, including non-C subtypes from 8 African sites. Treatment failure was experienced in 371 participants, mainly due to toxicity (n=134) or virological failure (n=83). Overall, CIPRA-SA participants with a lower CD4+ T-cell count at study onset were more likely to experience viral failure. Genotyping using the in-house assay revealed that 6 participants had ARV drug resistance mutations at study entry. Treatment failure of 58 participants was a result of ARV drug resistance mutations, whereas 19 had no known ARV drug resistance mutations. The most frequent mutations were M184V (67%) and K103N (50%). K65R was present (3%) and one participant harboured TAMs. Longitudinal genotypic analysis showed that NNRTI mutations accumulated at a rate of one per three months left on failing therapy. No PR mutations were detected amongst participants experiencing second-line failure. The four SNPs analysed occured in similar frequencies between a background and the CIPRA-SA cohort. Furthermore, no statistically significant association could be found between these four SNPs and viral failure and/or toxicity. Conclusion: Overall, HIV-1 subtype C-infected individuals receiving ARV therapy develop many of the known subtype B drug resistance mutations. However, the ARV drug resistance patterns in the closely monitored CIPRA-SA cohort were less complex compared to published data from the region, confirming that more frequent viral load monitoring, genotyping, and a virological failure cut-off value of 1000 RNA copies/ml ensure a better prognosis, and preserve future ARV treatment options.Item An analysis of clinical signs and symptoms which best predict the need for HAART initiation in HIV infected South African women(2010-09-15) Horumpende, Pius GeraldBackground. South Africa is currently experiencing one of the most severe AIDS epidemics in the world. The major challenge lies in prompt identification and early initiation of treatment in those eligible for HAART. Clinical staging has previously been recommended for use in settings where CD4 + count testing is not available. We conducted secondary data analysis to determine whether clinical symptoms and signs are useful in predicting the need for HAART initiation (CD4 + count < 200 cells/μL) in South Africa. Methods. Screening data from a randomized controlled trial in women who were HIV positive were analysed. All participants were interviewed using a structured questionnaire to elicit symptom history and then physical examination was done. Participants were staged using WHO criteria. Blood was drawn for CD4 + testing. The association between signs and symptoms and a CD4 + < 200 cells/μL was assessed using logistic regression. Results. Among 589 HIV infected women aged between 18 and 58 years, 90% were assessed as WHO clinical stages I/II. The median CD4 + count was 403 cells/μL (IQR: 273-586). Among women who were WHO stage I/II, 13% had CD4 + count < 200 cells/μL and required HAART. The WHO clinical staging had a low sensitivity (4%) but high specificity for detecting those that require treatment. Conclusion: In a setting where asymptomatic patients are diagnosed with HIV, clinical assessment can not replace CD4 + count testing as a method of identifying those that need treatment.