OpenUCT :: Browsing by Author "Little, Francesca"

Browsing by Author "Little, Francesca"

Now showing 1 - 20 of 43

Open Access
A GLMM analysis of data from the Sinovuyo Caring Families Program (SCFP)
(2018) Nhapi, Raymond T; Little, Francesca; Kassanjee, R
We present an analysis of the data from a longitudinal randomized control trial that assesses the impact of an intervention program aimed at improving the quality of childcare within families. The SCFP was a group-based program implemented over two separate waves conducted in Khayelitsha and Nyanga. The data were collected at baseline, post-test and at one-year follow-up via questionnaires (self-assessment) and observational video coding. Multiple imputation (using chained equations) procedures were used to impute missing information. Generalized linear Mixed Effect Models (GLMMs) were used to assess the impact of the intervention program on the responses, adjusted for possible confounding variables. These summed scores were often right skewed with zero-inflation. All the effects (fixed and random) were estimated through the method of maximum likelihood. Primarily, an intention-to-treat analysis was done after which a per-protocol analysis was also implemented with participants who attended a specified number of the group sessions. All these GLMMs were implemented in the imputation framework.
Open Access
Approaches for Handling Time-Varying Covariates in Survival Models
(2019) Nwoko, Onyekachi Esther; Little, Francesca
Survival models are used in analysing time-to-event data. This type of data is very common in medical research. The Cox proportional hazard model is commonly used in analysing time-to-event data. However, this model is based on the proportional hazard (PH) assumption. Violation of this assumption often leads to biased results and inferences. Once non-proportionality is established, there is a need to consider time-varying effects of the covariates. Several models have been developed that relax the proportionality assumption making it possible to analyse data with time-varying effects of both baseline and time-updated covariates. I present various approaches for handling time-varying covariates and time-varying effects in time-to-event models. They include the extended Cox model which handles exogenous time-dependent covariates using the counting process formulation introduced by cite{andersen1982cox}. Andersen and Gill accounts for time varying covariates by each individual having multiple observations with the total-at-risk follow up for each individual being further divided into smaller time intervals. The joint models for the longitudinal and time-to-event processes and its extensions (parametrization and multivariate joint models) were used as it handles endogenous time-varying covariates appropriately. Another is the Aalen model, an additive model which accounts for time-varying effects. However, there are situations where all the covariates of interest do not have time-varying effects. Hence, the semi-parametric additive model can be used. In conclusion, comparisons are made on the results of all the fitted models and it shows that choice of a particular model to fit is influenced by the aim and objectives of fitting the model. In 2002, an AntiRetroviral Treatment (ART) service was established in the Cape Town township of Gugulethu, South Africa. These models will be applied to an HIV/AIDS observational dataset obtained from all patients who initiated ART within the programme between September 2002 and June 2007.
Open Access
The association of depression, impulsivity and suicidal ideation with organophosphate pesticide exposure amongst South African farm workers
(2011) Kootbodien, Tahira; London, Leslie; Little, Francesca
The objectives were to evaluate the validity and reliability of four neurobehavioral instruments used in the study and to test three models hypothesised as possible causal pathways between OP exposure and depression, impulsive behaviour and suicidal ideation.
Open Access
CD8+ T-cell interleukin-7 receptor alpha expression as a potential indicator of disease status in HIV-infected children
(Public Library of Science, 2008) Sharma, Tanvi S; Hughes, Jane; Murillo, Amarylis; Riley, Joanne; Soares, Andreia; Little, Francesca; Mitchell, Charles D; Hanekom, Willem A
BACKGROUND: Initiation and modification of antiretroviral therapy in HIV-infected children depend on viral load and CD4+ T-cell count. However, these surrogates have limitations, and complementary immunological markers to assess therapeutic response are needed. Our aim was to evaluate CD8+ T-cell expression of CD127 as a marker of disease status in HIV-infected children, based on adult data suggesting its usefulness. We hypothesized that CD127 expression on CD8+ T-cells is lower in children with more advanced disease. METHODS: In a cross-sectional evaluation, we used flow cytometry to measure CD127+ expression on CD8+ T-cells in whole blood from HIV-infected children with varying disease status. This was compared with expression of CD38 on this subset, currently used in clinical practice as a marker of disease status. RESULTS: 51 HIV-infected children were enrolled. There was a strong positive correlation between CD127 expression on CD8+ T-cells and CD4+ T-cell count, and height and weight z-scores, and a strong negative correlation between CD127 expression and viral load. In contrast, we found no association between CD38 expression and these disease status markers. CONCLUSIONS: CD8+ T-cell CD127 expression is significantly higher in children with better HIV disease control, and may have a role as an immunologic indicator of disease status. Longitudinal studies are needed to determine the utility of this marker as a potential indicator of HIV disease progression.
Open Access
Comparison of growth curve models for assessing height in a South African birth cohort
(2018) Niehaus, Jacqui; Little, Francesca
Childhood malnutrition is a major concern in low- to middle- income populations. This dissertation uses longitudinal data on height measurements of babies between 0 and 4 years of age to construct growth curves, which serve as a tool for assessing the health and nutritional progress of children. We wish to characterise the way height changes over time and identify predictors of that change. Various mixed effect models were fit and compared to neural networks in terms of model fit, interpretability of parameters as well as predictive power. The best fitting mixed-effect model was the Berkey-Reed 2nd order model. The neural network compared well with this model, indicating that neural networks may serve as a useful alternative to modelling longitudinal growth data. Subsequently, logistic regression was used to explain the relationship between various pre- and post-natal risk factors for stunting, a shortfall in height relative to age. The results were compared to a random forest model. Methods for variable importance in classification problems using tree-based methods were explored. The random forest model appeared to perform similarly to the logistic regression model in terms of predictive power and variable interpretation. This dissertation contributes in investigating the possibility of using machine learning techniques to identify probable correlates of childhood malnutrition.
Open Access
Constructing growth reference curves for a cohort of South African children
(2022) Ross, Melinda; Little, Francesca
Childhood growth impacts the future welfare of an individual and ultimately the nation. The importance of childhood growth monitoring with growth curves that accurately represent the growth of the population of interest cannot be overemphasised. This dissertation sought to model the growth of a cohort of South African children and compare their growth to the World Health Organisation (WHO) 2006 Child Growth Standards. Growth reference curves were derived using parametric and semi-parametric methods within the Generalised Additive Models for Location, Scale and Shape (GAMLSS) framework. Various distributions for the growth measurements were compared as well as various curve smoothing approaches for the longitudinal profiles, including cubic splines, fractional polynomials and Berkey-Reed First and Second Order models. The preferred approach was to use the Box-Cox Power Exponential (BCPE) distribution with curve smoothing by cubic splines. Non-parametric quantile regression served as a confirmation that the chosen parametric distributions were appropriate for the data. A comparison of the derived growth references to the WHO (2006) standards revealed deviations in the patterns of growth and a greater likelihood of diagnosing a child as underweight, stunted or having micro- or macrocephaly when measured against the WHO standards. The poor socioeconomic status and associated harmful exposures of the cohort were noted as potential contributing factors. A fair comparison would require a reasonably healthy and representative sample of the South African population. These findings do however call into question the appropriateness of the WHO standards for measuring the growth of South African children and bring into focus the value of developing national growth standards.
Open Access
Correction to: Bioaerosol sampling of patients with suspected pulmonary tuberculosis: a study protocol
(2020-08-24) Patterson, Benjamin; Koch, Anastasia; Gessner, Sophia; Dinkele, Ryan; Gqada, Melitta; Bryden, Wayne; Cobelens, Frank; Little, Francesca; Warner, Digby F; Wood, Robin
An amendment to this paper has been published and can be accessed via the original article
Open Access
Delays in starting antiretroviral therapy in patients with HIV-associated tuberculosis accessing non-integrated clinical services in a South African township
(BioMed Central Ltd, 2011) Lawn, Stephen; Campbell, Lucy; Kaplan, Richard; Little, Francesca; Morrow, Carl; Wood, Robin; IeDEA-Southern Africa
BACKGROUND: Delays in the initiation of antiretroviral therapy (ART) in patients with HIV-associated tuberculosis (TB) are associated with increased mortality risk. We examined the timing of ART among patients receiving care provided by non-integrated TB and ART services in Cape Town, South Africa. METHODS: In an observational cohort study, we determined the overall time delay between starting treatment for TB and starting ART in patients treated in Gugulethu township between 2002 and 2008. For patients referred from TB clinics to the separate ART clinic, we quantified and identified risk factors associated with the two component delays between starting TB treatment, enrolment in the ART clinic and subsequent initiation of ART. RESULTS: Among 893 TB patients studied (median CD4 count, 81 cells/muL), the delay between starting TB treatment and starting ART was prolonged (median, 95 days; IQR = 49-155). Delays were shorter in more recent calendar periods and among those with lower CD4 cell counts. However, the median delay was almost three-fold longer for patients referred from separate TB clinics compared to patients whose TB was diagnosed in the ART clinic (116 days versus 41 days, respectively; P < 0.001). In the most recent calendar period, the proportions of patients with CD4 cell counts < 50 cells/muL who started ART within 4 weeks of TB diagnosis were 11.1% for patients referred from TB clinics compared to 54.6% of patients with TB diagnosed in the ART service (P < 0.001). CONCLUSIONS: Delays in starting ART were prolonged, especially for patients referred from separate TB clinics. Non-integration of TB and ART services is likely to be a substantial obstacle to timely initiation of ART.
Open Access
Detection and down-weighting of outliers in non-normal data: theory and application
(2014-08-15) Chatora,Tinashe Daniel; Gumedze, Freedom; Little, Francesca; Haines, Linda
Open Access
Determinants and consequences of the pharmacokinetics of rifampicin, isoniazid, pyrazinamide and ethambutol in a cohort of tuberculosis patients
(2004) McIlleron, Helen; Folb, Peter I; Little, Francesca; Smith, Pete
A prospectlve pharmacokinetic study was conducted amongst a cohort of 142 patients with tuberculosis (TB) susceptible to rifampicin and isoniazid at Brewelsleloof Hospital, Worcester, in the Western Cape.
Open Access
Does helminth treatment reduce the risk of active tuberculosis in a cohort of children from high tuberculosis risk population who have been vaccinated with BCG at birth?
(2009) Workman, Lesley; Ehrlich, Rodney; Little, Francesca; Hatherill, Mark
[Background] Research in adults and older children has shown an association between Mycobacterium tuberculosis and helminth infection, with those infected with helminths at greater risk of tuberculosis. This association is believed to be on the basis that chronic helminth infection can result in a functional impairment of the immune response that is necessary to clear or control infection by Mycobacterium tuberculosis (Elias et al. 2001; Rook et al. 2006; Fincham 2001). It is thus possible that the introduction of regular deworming programmes in a vulnerable population of children under the age of five years could assist their immune systems to ward off tuberculosis infection and reduce the risk of tuberculosis disease in such a population. A randomised controlled trial to compare two methods of administering bacille Camlette-Guerin (BCG) vaccination to newborns from a high tuberculosis risk population provided an opportunity to test this hypothesis in a sub-study. [Objective] The objective of this study is to determine if young children in a high-risk tuberculosis population who have been vaccinated with BCG at birth and have been treated for helminth infection are at lower risk of tuberculosis disease than children who have been vaccinated with BCG at birth but not treated for helminth infection. [Method] A case control study nested within a cohort recruited for a separate randomised control trial to compare two methods of administering BCG vaccination was carried out. Children who presented to their local clinic or hospital with symptoms of tuberculosis or a history of exposure to tuberculosis were admitted to a case verification (CV) ward for investigation of tuberculosis. Investigation of tuberculosis included a detailed history, including past helminth treatment, physical examination, tuberculin skin test, chest radiograph, gastric washing and induced sputum for culture of tuberculosis and clinical examination. A diagnostic algorithm was developed by specialist physicians and biostatisticians to classify the children into one of five tuberculosis categories. A total of 510 children (median age 18.13 months) were included in the primary analysis of this case control study. Those defined as cases were the 328 classified as "definite or probable TB" and 182, classified as "not TB", comprised the control group. Those classified as "possible TB" or "unlikely TB" were excluded. A secondary analysis was performed that included the 337 children who had been classified as "unlikely TB" with the controls resulting in a total of 847 children (median age 18.37 months). The 328 children classified as "definite or probable TB" were defined as cases and the 519 classified as "unlikely or not TB" comprised the control group. Univariate analysis was used to explore a possible relationship between tuberculosis and helminth treatment using all the variables in the sub-study (n=510 primary analysis; n=847 secondary analysis). For both the primary and secondary analysis a multivariate logistic regression model was built using a reduced sample that had a complete set of data for all the variables: primary analysis (n=435); secondary analysis (n=724). This final model was then fitted on a more complete sample as the final variables selected had fewer missing data for the observations: primary analysis (n=493); secondary analysis (n=822). [Result] A total of 35.69% of the study sample in the primary analysis had been treated for helminth infection. The proportion of children who had been treated for helminth infection was similar in the cases and controls (35.98% and 35.16% respectively). Univariate logistic regression showed no association between tuberculosis and treatment for helminth infection: [odds ratio (OR) 1.04; 95% confidence interval (CI) 0.71 - 1.51]. Multivariate analysis adjusted for the effect of nutritional status, recorded as height for age z score (haz), number of occupants sharing the same dwelling as the child, gender and birth site showed a similar result: (OR 1.03; 95% CI 0.69 " 1.53). The OR is very close to 1 with a 95% CI that includes 1, which indicates that there is not a statistically significant association between tuberculosis and helminth treatment. In the secondary analysis, a total of 38.61% of the study sample had been treated for helminth infection. In this analysis the proportion of children who had been treated for helminth infection showed a difference between the cases and controls (35.98% and 40.27% respectively). Univariate logistic regression showed a 17% relative reduction in tuberculosis odds but this was not a statistically significant result: (OR 0.83; 95% CI 0.63 " 1.11). Multivariate analysis adjusted for the effect of haz, number of children sharing the same dwelling as the child and gender, showed a similar result: (OR 0.85; 95% CI 0.63 " 1.15). [Conclusion] The primary analysis of this observational study does not support the hypothesis that helminth treatment reduces the risk of tuberculosis disease in young children in a high-risk tuberculosis population. Although the secondary analysis showed a 15% relative reduction in tuberculosis odds after adjusting for the effect of haz, number of occupants sharing the same dwelling as the child and gender, this was not a statistically significant result. [Final Conclusion] This study does not support the hypothesis that helminth treatment reduces the risk of tuberculosis disease in young children in a high-risk tuberculosis population.
Open Access
Early and late direct costs in a Southern African antiretroviral treatment programme: a retrospective cohort analysis
(Public Library of Science, 2009) Leisegang, Rory; Cleary, Susan; Hislop, Michael; Davidse, Alistair; Regensberg, Leon; Little, Francesca; Maartens, Gary
Gary Maartens and colleagues describe the direct heath care costs and identify the drivers of cost over time in an HIV managed care program in Southern Africa.
Open Access
Effect of artemether-lumefantrine policy and improved vector control on malaria burden in KwaZulu-Natal, South Africa
(Public Library of Science, 2005) Barnes, Karen I; Durrheim, David N; Little, Francesca; Jackson, Amanda; Mehta, Ushma; Allen, Elizabeth; Dlamini, Sicelo S; Tsoka, Joyce; Bredenkamp, Barry; Mthembu, D Jotham
In KwaZulu-Natal strengthening of vector control and a change in antimalarial treatment policy to use of artemether-lumefantrine has been associated with a decrease in malaria cases, admissions, and deaths.
Open Access
Effect of artemether-lumefantrine policy and improved vector control on malaria burden in KwaZulu-Natal, South Africa
(2005) Barnes, Karen I; Durrheim, David N; Little, Francesca; Jackson, Amanda; Mehta, Ushma; Allen, Elizabeth; Dlamini, Sicelo S; Tsoka, Joyce; Bredekamp, Barry; Mthembu, D Jotham; White, Nicholas J; Sharp, Brian L
Between 1995 and 2000, KwaZulu–Natal province, South Africa, experienced a marked increase in Plasmodium falciparum malaria, fuelled by pyrethroid and sulfadoxine-pyrimethamine resistance. In response, vector control was strengthened and artemether-lumefantrine (AL) was deployed in the first Ministry of Health artemisinin-based combination treatment policy in Africa. In South Africa, effective vector and parasite control had historically ensured low-intensity malaria transmission. Malaria is diagnosed definitively and treatment is provided free of charge in reasonably accessible public-sector health-care facilities.
Open Access
Efficacy of sulfadoxine-pyrimethamine with and without artesunate for the treatment of uncomplicated malaria in Mozambique : a randomised controlled trial
(2008) Allen, Elizabeth; Boulle, Andrew; Little, Francesca
[Background and rationale] Malaria accounts for a large public health burden in Mozambique and a treatment policy with effective anti-malarials is a key component of their malaria control programme. Artemisinin-based combination therapies (ACTs) are now generally considered as the best treatment for uncomplicated falciparum malaria; the use of artesunate (AS) in combination with sulfadoxine-pyrimethamine (SP) is recommended by the World Health Organisation (WHO). Mozambique policy-makers recommended that an ACT be implemented and studied in 2003. Therefore this RCT was conducted to compare SP monotherapy with AS, plus SP in order to provide further evidence of available treatment options in the region. [Trial design and methods] A prospective multi-centre, open-label, parallel-group randomised clinical trial (RCT) was conducted at 4 public health facilities in Maputo Province, Mozambique during the malaria seasons of 2003 - 2004 and 2004 - 2005. Eligible patients were aged over 1 year with body weight over 10kg and uncomplicated Plasmodium falciparum malaria (parasitaemia less than 500 000 asexual parasites/ml blood with axillary temperature less than or equal to 37.5oC or a history of fever). Patients were excluded if they took other anti- malarials or folate within 7 days, had moderately severe/severe malaria, history of G6PD deficiency or allergy to study drugs, or serious underlying disease. Patients were randomly assigned to sulfadoxine-pyrimethamine (SP): a single oral 25/1.25mg per kg dose on Day 0, with a maximum of 3 tablets), or artesunate (AS) plus SP: SP as above, plus single oral doses of 4mg/kg AS on Days 0, 1 and 2 with a maximum daily dose of 4 tablets). The study aimed to compare the efficacy of SP monotherapy to SP in combination with AS as first line treatment of uncomplicated falciparum malaria. The primary objective was the comparison of the time to treatment failure (the relative hazard of treatment failure) between groups using standard WHO response to treatment definitions for low to moderate malaria transmission areas, modified to a 42 day follow up. Randomisation was computer-generated with sequential allocation concealed in opaque sealed envelopes. Treatments were open-label, however laboratory staff responsible for parasite density measurements (in order to determine the primary efficacy end point) were blinded to treatment allocation.
Open Access
Efficacy of sulphadoxine-pyrimethamine with or without artesunate for the treatment of uncomplicated Plasmodium falciparum malaria in southern Mozambique: a randomized controlled trial
(BioMed Central Ltd, 2009) Allen, Elizabeth N; Little, Francesca; Camba, Tunisio; Cassam, Yasmin; Raman, Jaishree; Boulle, Andrew; Barnes, Karen I
BACKGROUND: An artemisinin-based combination therapy, artesunate (AS) plus sulphadoxine-pyrimethamine (SP), was compared to SP monotherapy to provide evidence of further treatment options in southern Mozambique. METHODS: Between 2003 and 2005, 411 patients over one year and 10 kg with uncomplicated Plasmodium falciparum malaria were randomly allocated SP (25/1.25 mg per kg day 0) or AS/SP (as above plus 4 mg/kg artesunate days 0, 1 and 2). Allocation was concealed, but treatment was open-label except to microscopists. The primary objective was the relative risk of treatment failure, which was assessed using World Health Organization response definitions modified to a 42-day follow-up. RESULTS: Of the 411 subjects enrolled, 359 (87.3%) completed the follow up period (SP n = 175, AS/SP n = 184). A survival analysis including 408 subjects showed that the polymerase chain reaction-adjusted cure rates were 90.4% (95% confidence interval [CI] 84.9%-93.9%) and 98.0% (95% CI 94.8%-99.3%) for SP and AS/SP respectively. Multivariable analysis showed that treatment with AS/SP decreased the relative hazard of treatment failure by 80% compared to SP (hazard ratio [HR] 0.2; 95% CI 0.1-0.6) and age over seven years decreased the relative hazard of failure by 70% (HR 0.3; 95% CI 0.1-0.9), when compared to younger age. However, having a quintuple dhfr/dhps mutation increased the relative hazard of failure compared to fewer mutations (HR 3.2; 95% CI 1.3-7.5) and baseline axillary temperature increased the relative hazard of failure by 50% for each degreesC increase (HR 1.5; 95% CI 1.1-2.2). CONCLUSION: While both treatments were efficacious, AS plus SP significantly decreased the relative hazard of treatment failure compared to SP monotherapy Artesunate plus sulphadoxine-pyrimethamine, but not sulphadoxine-pyrimethamine monotherapy, met the current WHO criteria of >95% efficacy for policy implementation.TRIAL REGISTRATION:NCT00203736 and NCT00203814
Open Access
An evaluation of the quality of antenatal care and patient satisfaction in two provinces of South Africa
(2011) Besada, Donnela; Stinson, Kathryn; Coetzee, David; Little, Francesca
The aim of this study was to investigate the quality of service delivery for HIV-infected women at antenatal clinics in the Western Cape and Free State provinces, South Africa and to highlight areas for improvement. It was part of a larger one to determine the effectiveness of PMTCT programmes in 4 countries. These two provinces were selected because the researchers had access to facilities there. The population included all clinics with antenatal services in these provinces. Pregnant women attending the clinics were selected to assess care at these services. The sampling frame for the facility survey consisted of the antenatal clinics that referred patients to the delivery sites where the first component of the PEARL study, a cord blood surveillance exercise had taken place.
Open Access
Exploring the seasonality of reported treated malaria cases in Mpumalanga, South Africa
(Public Library of Science, 2013) Silal, Sheetal Prakash; Barnes, Karen I; Kok, Gerdalize; Mabuza, Aaron; Little, Francesca
South Africa, having met the World Health Organisation's pre-elimination criteria, has set a goal to achieve malaria elimination by 2018. Mpumalanga, one of three provinces where malaria transmission still occurs, has a malaria season subject to unstable transmission that is prone to sporadic outbreaks. As South Africa prepares to intensify efforts towards malaria elimination, there is a need to understand patterns in malaria transmission so that efforts may be targeted appropriately. This paper describes the seasonality of transmission by exploring the relationship between malaria cases and three potential drivers: rainfall, geography (physical location) and the source of infection (local/imported). Seasonal decomposition of the time series by Locally estimated scatterplot smoothing is applied to the case data for the geographical and source of infection sub-groups. The relationship between cases and rainfall is assessed using a cross-correlation analysis. The malaria season was found to have a short period of no/low level of reported cases and a triple peak in reported cases between September and May; the three peaks occurring in October, January and May. The seasonal pattern of locally-sourced infection mimics the triple-peak characteristic of the total series while imported infections contribute mostly to the second and third peak of the season (Christmas and Easter respectively). Geographically, Bushbuckridge municipality, which exhibits a different pattern of cases, contributed mostly to the first and second peaks in cases while Maputo province (Mozambique) experienced a similar pattern in transmission to the imported cases. Though rainfall lagged at 4 weeks was significantly correlated with malaria cases, this effect was dampened due to the growing proportion of imported cases since 2006. These findings may be useful as they enhance the understanding of the current incidence pattern and may inform mathematical models that enable one to predict the impact changes in these drivers will have on malaria transmission.
Open Access
Hitting a Moving Target: A Model for Malaria Elimination in the Presence of Population Movement
(Public Library of Science, 2015) Silal, Sheetal Prakash; Little, Francesca; Barnes, Karen Irma; White, Lisa Jane
South Africa is committed to eliminating malaria with a goal of zero local transmission by 2018. Malaria elimination strategies may be unsuccessful if they focus only on vector biology, and ignore the mobility patterns of humans, particularly where the majority of infections are imported. In the first study in Mpumalanga Province in South Africa designed for this purpose, a metapopulation model is developed to assess the impact of their proposed elimination-focused policy interventions. A stochastic, non-linear, ordinary-differential equation model is fitted to malaria data from Mpumalanga and neighbouring Maputo Province in Mozambique. Further scaling-up of vector control is predicted to lead to a minimal reduction in local infections, while mass drug administration and focal screening and treatment at the Mpumalanga-Maputo border are predicted to have only a short-lived impact. Source reduction in Maputo Province is predicted to generate large reductions in local infections through stemming imported infections. The mathematical model predicts malaria elimination to be possible only when imported infections are treated before entry or eliminated at the source suggesting that a regionally focused strategy appears needed, for achieving malaria elimination in Mpumalanga and South Africa.
Open Access
Impact of immune activation and inflammation on the susceptibility to HIV infection and disease progression in HIV serodiscordant and seroconcordant couples
(2014) Jaumdally, Shameem Zaer; Passmore, Jo-Ann; Gumbi, Pamela; Little, Francesca
The biological correlates of protection against HIV infection remain poorly characterized, hindering the development of an effective prevention strategy. Studies of individuals who resist HIV infection or progress more slowly after being infected are important for the conception of appropriate approaches for mimicking the effective responses against HIV infection or progression. The role of immune activation and chronic inflammation in the modulation of HIV acquisition risk and/or rate of HIV disease progression has been proposed as one of the most important mechanisms determining risk and pathogenesis but is not fully understood. A state of immune quiescence has been associated with protection against HIV infection and slower disease progression. To explore potential risk factors associated with HIV transmission and HIV disease progression, this dissertation investigates the relationship between clinical and biological biomarkers and resistance to HIV infection or disease progression (including viral load, CD4 counts, cellular activation, soluble inflammatory and regulatory cytokines, and HIV co-receptor expression) in stable long-term HIV seroconcordant and serodiscordant couples.