3. Electronic Theses and Dissertations (ETDs) - All submissions

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Subject: search.filters.subject.antiretroviral treatment

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    Adherence to highly active antiretroviral treatment and loss to follow-up of pregnent women at the Themba Lethu Clinicu
    (2011-06-10) Nagar, Shashikala
    INTRODUCTION 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.
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    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 Lorraine
    Background: 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.
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