Doctoral Degrees (Epidemiology and Biostatistics)

Permanent URI for this collection

https://scholar.sun.ac.za/handle/10019.1/100763

Browse

Recent Submissions

Now showing 1 - 5 of 13
  • Thumbnail Image
    Item
    HIV continuum of care outcomes among female sex workers in Kampala Uganda
    (Stellenbosch : Stellenbosch University, 2022-12) Atuhaire, Lydia; Nyasulu, Peter; Shumba, Constance; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics.
    ENGLISH SUMMARY: Background: Female sex workers (FSWs) account for 11% of all HIV infections globally and are twenty-six times at a greater risk of acquiring HIV than their female counterparts in the general population. In Uganda, HIV prevalence among FSWs is estimated at 31% - 37%, six times higher than the HIV prevalence of 5.4% in the general population. FSWs, not only are confronted by heightened risk to HIV infection, but they are also more vulnerable to social and economic inequalities that hinder access to HIV services throughout the HIV care continuum. Moreover, the few HIV positive FSWs who eventually access HIV care, experience unique barriers that hinder their continuity on life-long Antiretroviral therapy (ART) and thus drop out of care along the various stages of HIV continuum of care. Consequently, FSWs continue to widen the gap to attaining the global HIV treatment targets of 95-95-95 by 2025 and ending the AIDS epidemic by 2030. Notably, there has been an increased focuson improving HIV care continuum. However, data are sparse regarding the service uptake across the HIV care cascade for FSWs. Absence of recent data for FSWs impedes monitoring of HIV service provision and identifying missed opportunities important in guiding program strategies, optimal for improved and equal access to HIV services among FSWs. The aim of this research project was to understand service delivery approaches along the HIV continuum of care for FSWs in a routine care setting in Kampala, Uganda. Methods: The research project used multiple approaches to respond to the objectives as described as follows: In objective one, we conducted a systematic review on the implementation of community interventions for any of the HIV care cascade stage. We conducted a systematic search of randomized controlled trials, cohort and cross-sectional studies done in sub-Saharan African countries and published from 2004 to 2020. The study outcomes were HIV testing and diagnosis, linkage to care, receipt of ART and achievement of viral suppression. The data were analysed using random effects meta-analysis, where possible and for the rest of the studies, data were synthesized using summary statistics. For objective two, we conducted a cross-sectional survey and used simple random sampling method to select 200 participants from 12 sex work hotspots in Kampala. Participants were allocated proportionally in each hotspot. Frequencies were used to describe categorical characteristics of FSWs, and a multivariable logistic regression model was used to determine the factors associated with adherence to the HIV testing guidelines. In the third objective, we performed a retrospective cross-sectional study of routine patient management data for FSWs diagnosed with HIV and enrolled in care from January 2018 to December 2020 at the government primary health care facilities in Kampala. Two outcome variables were assessed and these which included i) Lost-to-follow-up from HIV care; and ii) Virological non-suppression. We used cluster sampling methods to select initial clusters and purposively selected a cluster of six health facilities and data was collected from 275 medical records. Both univariable and multivariable logistic regression models were performed on study outcomes. Data were analysed using Stata 15.1 software (Stata Statistical Software: Release 14. College Station, TX: Stata Corp LP). Finally, the fourth objective applied a qualitative descriptive design through use of in-depth interviews among FSWs, who were accessing HIV services through differentiated service delivery models in primary health facilities and drop-in centres in Kampala. We purposively sampled 2 health facilities and 2 drop-in centres and following the principle of data saturation, 24 FSWs were interviewed. Data analysis was conducted manually using framework analysis, and we applied an inductive approach which involved systematically reviewing the code framework, reduction, and interpretation of the data. Results: From the systematic review, the results showed variations in the effectiveness of community-based interventions along the various stages of HIV care cascade. The level of effectiveness was more pronounced in HIV testing and ART use; with average effectiveness observed in HIV diagnosis, than it is for linkage to care and viral load suppression. In addition, the interventions tended to be more impactful if they were provided in a combination of various strategies unique for each HIV care cascade stage. Among the sample of two hundred study participants from the adherence to HIV testing guidelines study, 88% of the study participants reported their HIV testing status; of these, 56% adhered to the HIV testing guidelines, having tested three or more times in the 12 months preceding the survey. Attaining a secondary education was associated with adherence to HIV testing guidelines [odds ratio (OR) 1.86, 95% confidence interval (CI) 1.01 – 3.44; P = 0.047]. Testing for sexually transmitted infection in the preceding 3 months (OR: 2.13, 95% CI: 0.95 – 4.74, P = 0.065) and accessing HIV testing at a drop-in centre (OR: 5.90, 95% CI: 0.71 – 49.1; P = 0.101) were associated with higher odds of adherence to the HIV testing guidelines, although the association was not significant. Results from the study on retention and non-viral suppression showed retention of 85.1% (n = 234) at six months, corresponding to LTFU of 14.9% (n = 41) within the same period. Retention decreased with duration of being in care to 73.5% (n = 202) at 24 months, translating to LTFU of 26.5% (n = 73). Viral load testing coverage was 62% (n = 132) and of these, 90.9% (n = 120) were virally suppressed. Factors associated with LTFU at <0.2 significance level in univariable logistic regression model were age, marital status, education level, having treatment supporter, having a telephone contact, WHO stage at baseline, and having been diagnosed with TB during the study period. In multivariable logistic regression model, age (OR: 0.56, 95% CI: 0.031 - 1.00, p = 0.049), marital status (OR: 0.46, 95% CI: 0.23 - 0.89, p = 0.021), having telephone contact (OR: 0.22, 95% CI: 0.07 - 0.70, p = 0.010) and WHO stage at baseline (OR: 0.11, 95% CI: 0.01 - 0.97, p = 0.046), were significantly associated with LTFU at 0.05 significance level after adjusting for other factors. Factors associated with viral load suppression in univariable logistic regression models included age, having telephone contact, lost to follow up, and reason for lost-to-follow-up at <0.2 level of significancy. Age at enrolment remained statistically significant in multivariable logistic regression model (OR: 0.09, 95% CI: 0.01 – 0.82 P = 0.033) at 0.05 level of significance. Findings from the qualitative phase of the research study showed that HIV services provided through community based Differentiated Service Delivery (DSD) models were perceived to be of low quality, with a non-comprehensive package of HIV services for FSWs which did not match FSWs’ needs, preferences, and health risks. In addition, services were provided irregularly with compromised privacy and being provided by health workers who were perceived to have less than adequate specialised skills. Further, the process of deciding on how and what services should be provided through community DSD models targeting FSWs, the latter were not part of the process. Consequently, FSWs preferred facility-based models even though community DSD models were considered to be as a more convenient and a less costly option for access to HIV services and were thought to be a good complementary option if the quality of services provided in the community would be improved. Conclusion: Evidence brought forward in this research project shows that the effect of community-based interventions varies across the various stages of HIV care cascade. Therefore, it is critical to consistently monitor, review, and evaluate strategies under implementation to identify and realign those that have long term impact in improving HIV services access along the care continuum for FSWs. In addition, the suboptimal retention and viral load testing coverage underscores the need to improve the quality of services provided under differentiated care models, by ensuring that services are tailored to FSWs individual preferences, needs, and contexts.
  • Thumbnail Image
    Item
    Optimisation and benchmarking of analytical approaches to estimation of population level HIV incidence from survey data
    (Stellenbosch : Stellenbosch University, 2022-04) Mhlanga, Laurette; Welte, Alex; Grebe, Eduard; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics.
    ENGLISH SUMMARY: Disease prevalence (the proportion of a population with a condition of interest) is conceptually and procedurally much more straightforward to estimate than disease incidence (the rate of occurrence of new cases - for example, infections). For long-lasting conditions, incidence is fundamentally more difficult to estimate than prevalence, but also more interesting, as it sheds light on current epidemiological trends such as the emerging burden on health systems and the impact of recent policy interventions. Progress towards reducing reliance on questionable assumptions in the analysis of large population based surveys (for the estimation of HIV incidence) has been slow. The work of Kassanjee et al and the work of Mahiane et al, in particular, provide rigorous ways of estimating incidence by using 1) markers of ‘recent infection’, 2) the ‘gradient’ of prevalence, and 3) ‘excess mortality’ associated with HIV infection, without the need for simplifying assumptions to the effect that any particular parameters are constant over ranges of time and/or age. To date, the use of these methods has largely ignored 1) the rich details of the age and time structure of survey data, and 2) the opportunities for combining the two methods. The primary objective of this work was to find stable approaches to applying the Mahiane and Kassanjee methods to large age/time structured population survey data sets which include HIV status, and optionally, ‘recent infection’ status. In order to evaluate proposed methods, a sophisticated simulation platform was created to simulate HIV epidemics and generate survey data sets that are structured like real population survey data, with the underlying incidence, prevalence, and mortality explicitly known. The first non-trivial step in the analysis of survey data amounts essentially to performing a smoothing procedure from which the (age/time specific) prevalence of HIV infection, the prevalence of ‘recent infection’, and the gradient of prevalence of infection can be inferred without recourse to ‘epidemiological’ assumptions. The second step involves the correct accounting for uncertainty in a context-specific weighted mean of the Mahiane and Kassanjee estimators. These two steps are approached incrementally, as there are numerous details which have not previously been systematically elucidated. The investigation culminates in a proposed generic ‘once size fits most’ algorithm based on: 1) fitting survey data to generalised linear models defined by simple link functions and high order polynomials in age and time; 2) the use of a ‘moving window’ rule for data inclusion into a separate analysis for each age/time point for which incidence is to be estimated; 3) a ‘variance optimal’ weighting scheme for the combination of the Mahiane and Kassanjee estimators (when both are applicable); 4) flexible use of a delta method expansion or bootstrapping to estimate confidence intervals and p values. We find it is relatively easy to obtain estimates with practically negligible bias, but samplesizes/ sampling-density requirements are always considerable. We also make numerous observations on survey design and the inherent challenges faced by all attempts to estimate HIV incidence using surveys of reasonable size.
  • Thumbnail Image
    Item
    The impact of missing data on estimating HIV/AIDS prevalence and incidence in demographic sentinel survey studies
    (Stellenbosch : Stellenbosch University, 2022-04) Mosha, Neema Ramadhani; Machekano, Rhoderick; Young, Taryn; Todd, Jim; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics.
    ENGLISH SUMMARY: Background: Missing data is a challenge in most research, especially with observational population data such as demographic surveys. These studies often account for survey designs and clustering when estimating disease prevalence or incidence, but do not account for missing data. In other circumstances they do not explicitly state how they dealt with missing data during analysis or inappropriately handles them in practice. There are many challenges in conceptualising the pattern of missingness, its occurrence mechanism and complexity of methods for handling the problem of missing data. Ignoring the missingness of survey data can cause biased estimates and invalid conclusions. The primary aim of this PhD was to evaluate the impact of missing data on estimating HIV/AIDS prevalence in demographic sentinel surveillance studies. Methods: A systematic review of HIV studies to identify and describe methods used to analyse studies with missing data was done. A series of simulation studies to explore the precision and efficiency of the prevalence estimates using complete case analysis (CCA), multiple imputation (MI), inverse probability weighting (IPW) and double robust estimator (DR), when data are missing at random (MAR) in survey studies was done. A descriptive statistics and a complete case analysis to determine the incidence and population prevalence estimates ignoring the missingness on four different survey rounds of Magu Health Demographic Sentinel Surveillance (HDSS) was done.The surveys were conducted between 2006 and 2016, they included adults aged 15 years and above and about 50% of the population was tested for HIV in each survey. This was followed by data exploration assessing the missingness occurrence and association between missingness and other study characteristics. Finally, application of the statistical methods used in the simulations study was performed to re-estimate the prevalence of the surveys data taking into account the missingness. Results: The systematic review found 24 eligible articles from population, demographic and cross-sectional surveys that acknowledged the presence of missing data. In these studies, complete case analysis was the standard method of choice (100%) followed by multiple imputations (46%) and Heckman’s selection models (38%). A simulation study generated a hypothetical HIV survey with 32 different scenarios exploring data when an outcome is missing 20% and 55%. This simulation showed that when data are MAR, complete case analysis produces biased and inefficient estimates. Results showed that the three methods (MI, IPW and DR) were valid and efficient if the missingness or imputation models are correctly specified, but if either of the MI or IPW models are mis-specified, then the DR estimator can still be valid. Regarding to performance of the methods, provided that correct models are used, MI is more unbiased even when there is 55% of the data missing. However with 55% missingness all estimators are less reliable. In the complete case analysis, the overall population prevalence estimates for HIV decreased from 7.2% in 2006 to 6.6% in 2016. Cox models were used to determine HIV incidence rates and risk factor analysis by sex. The incidence rate was 5.5 per 1000 person - years in women compared to 4.6 per 1000 person-years in men. Residence, marital status, mobile individuals, and individuals with two or more partners were associated with the increase in incidence of HIV in bivariate analysis. The missingness OF HIV was as high as 60.3% (in the 2016 survey) and in all surveys(Sero 5 to 8) it was associated with age, sex, residence, and marital status. Further analysis using MI, IPW and DR assuming the outcome was MAR showed that the overall HIV prevalence was not significantly different from the complete case analysis in all four of the surveys. However, there were significant differences in the HIV estimates when stratified by the covariates. Looking at the confidence intervals width multiple imputations outperformed IPW and DR by producing more narrower estimates. Conclusion: Overall, this dissertation showed that despite the availability of methods to adjust for missing data, many surveys still ignore the missingness. The reporting among articles adjusted for missingness was below guideline standards. Understanding the mechanism of missingness enhances the proper application of advanced methods to account for the missingness. With data missing at random, IPW, MI, and DR can account for the missingness and produce unbiased and efficient estimates in HIV survey studies. Also, more simplified information and awareness are still needed to allow researchers to make informed choices, specifically on which method to apply and in which situation it works best for the estimates to be more reliable and representative.
  • Thumbnail Image
    Item
    Model-based inference on the impact of early access to antiretroviral therapy to all on HIV incidence among adolescent girls and young women in Eswatini
    (Stellenbosch : Stellenbosch University, 2021-04) Chibawara, Trust; Nyasulu, Peter; Kajungu, Dan; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics.
    ENGLISH SUMMARY: Introduction: The introduction of antiretroviral drugs has enabled people living with HIV (PLHIV) to have a much better prognosis. As such, the use of antiretroviral drugs has resulted in the decline of global HIV incidence over the last decade. Whilst this achievement is important, the role of the widespread use of antiretroviral drugs on the HIV epidemic among adolescent girls and young women is still unknown. This study aimed to evaluate the impact of Early Access for all HIV-positive Adults to Antiretroviral (EAAA) on HIV incidence among adolescent girls and young women in Eswatini. Methods: To accomplish our research objectives, this research provided elaborate mathematical concepts that are multidisciplinary in nature and included evidence based systematic review, statistics, data science and public health approaches. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines was used for the systematic review. Using Simpact, an individual-based, event-driven, stochastic simulation tool, a specially designed HIV transmission model was adopted to simulate the heterosexual transmission of HIV in Eswatini. The application of a simplified model calibration approach combined clinical, biological, and behavioural indicators from the Eswatini implementation study called “Maximizing Antiretroviral Treatment for Better Health and Zero New HIV Infection: Early Access to Antiretroviral Treatment for All (MaxART EAAA)” and Eswatini demographic summary statistics to infer the impact of EAAA on HIV incidence in adolescent girls and young women. Results: The results of the systematic review showed that globally, there was no published or unpublished research found on the impact of the use of ART by HIV positive adults on HIV incidence in adolescent girls and young women. While on the other hand, our model which aimed to evaluate the impact of EAAA on older men aged 18 years and above in Eswatini showed a 45% (95% Confidence interval (CI): 37-55) reduction on HIV incidence among the adolescent girls and young women aged 15-24-years-old as opposed to CD4 cell count threshold for ART eligibility (Standard of care). Furthermore, simulated data showed that early access to ART has a similar impact of 47% (95% CI: 33-59) reduction in HIV incidence among adolescent boys and young men of the same age group. Conclusion: This study has demonstrated the impact of EAAA as a strategy to reduce new HIV infections among adolescent girls and young women aged between 15-24-years-old in the Eswatini population. These findings reinforce the need to adopt provisions for early initiation of ART treatment among HIV infected adults as a catalyst to minimize transmission of HIV to the adolescent population. Data from this study also highlight the need for other countries in the region who are faced with similar challenges of harbouring a high HIV prevalence to adopt EAAA as it has shown to be an effective approach to reduce HIV/AIDS incidence in the population. While these benefits are applaudable, we do recognize that HIV/AIDS treatment on its on is not sufficient; therefore, behavioural changes that guard against age-disparate relationships should be reinforced.
  • Thumbnail Image
    Item
    Assessment of point-of-care testing for prediction of aromatase inhibitor-associated side effects in obese postmenopausal breast cancer patients screened for cardiovascular risk factors
    (Stellenbosch : Stellenbosch University, 2021-12) Milambo, Jean Paul Muambangu; Akudugu, John M.; Nyasulu, Peter S.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics.
    ENGLISH SUMMARY : Background: Aromatase inhibitors (AIs) constitute a standard of care for post- and premenopausal patients with estrogen receptor-positive breast cancer (BC). Obesity and mediators of inflammation have been identified as the most important risk and predictive factors in postmenopausal breast cancer survivors (BCS) using AIs. However, data on the feasibility of point-of-care (POC) genotyping using high sensitivity C-reactive protein (hs-CRP) and body mass index (BMI) as predictors of drug toxicity among postmenopausal BCS in African clinical settings are lacking. Aim: The study was conducted to assess the impact of AIs on hs-CRP and BMI, which are used at POC for prediction of therapy-associated side effects among obese postmenopausal breast cancer patients in Africa. Methods: One hundred and twenty-six female BC patients with cancer stages ranging from 0-III were recruited at Tygerberg Hospital (TBH) in the Western Cape Province of South Africa, between August 2014 and February 2017, for the study. A Quasi-experimental study was conducted. Patients were initially subjected to AIs and subsequently followed up at months 4, 12, and 24. Baseline clinical and biomedical assessments were conducted at commencement of study to predict hs-CRP and BMI at months 12 and 24, using a multiple imputation model. A random effects model was used to monitor the changes over the time. Statistical analyses were performed using SPSS 18.0 software (SPSS Inc., Chicago, IL, USA) and STATA version 16. Analyses were two-tailed and a p-value < 0.05 was considered statistically significant. Results: The mean age of the participants was 61 years (SD = 7.11 years; 95% CI: 60-62 years). Linear regression revealed that hs-CRP was associated with waist circumference (OR: 7.5; p= 0. 0116; 95%CI: 1.45 to 39.61) and BMI (OR: 2.15; p=0.034, 95%CI: 1.02 to 4.56). Waist circumference was associated with hypertension (OR: 3, 83; p= 0.003, 95%CI: 1.56 to 9.39), and chemotherapy was associated with waist circumference by (p= 0. 016; 95%CI: 0.11 to 0. 79). hs-CRP levels were significantly correlated with BMI and total body fat (TBF) among postmenopausal using aromatase inhibitors. Random linear effects modelling revealed stronger statistical association between BMI and homocysteine (p=0.021, 95%CI: 0.0083 to 0.1029). Weight and TBF were strongly associated after 24 months of follow-up. In addition, hs-CRP was associated with BMI (p=0.0001) and other inflammatory markers such as calcium (p=0.021, 95%CI: 0.0083 to 0.1029), phosphate (p=0.039, 95%CI: 0.0083 to 0.1029), and ferritin (p=0.002, 95%CI: 0.0199 to 0.084). Multiple imputation modelling indicated that there were statistically significant variations in TBF, weight, homocysteine, ferritin, and calcium between baseline and after 24 months of follow-up. Mathematical modeling Comparison of genotyping from HyBeacon® probe technology to Sanger sequencing showed that yielded sensitivity of 99% (95% CI: 94.55 to 99.97%), specificity of 89.44% (95% CI: 87.25 to 91.38%), PPV of 51% (95%: 43.77 to 58.26%), and NPV of 99.88% (95% CI: 99.31 to 100.00%). Based on the mathematical model, the assumptions revealed that incremental cost-effective ratio (ICER) was R7 044.55. Conclusion: This study revealed that hs-CRP and BMI are predictors of CVD-related adverse events in obese postmenopausal patients. Calcium, phosphate, homocysteine, and ferritin should also be incorporated in POCT. There were statistically significant variations in TBF, weight, hs-CRP, BMI, homocysteine, ferritin, and calcium between baseline and after 24 months of follow-up. HyBeacon® probe technology at POC for AI-associated adverse events maybe cost-effective in Africa while adjunct to standard practice. The appropriate pathways for implementation of POC testing in postmenopausal breast cancer survivors need further investigation in different clinical settings with real data for external validation.