Browsing by Author "Cornell, Morna"
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- ItemOpen AccessCharacteristics and outcomes of children, adolescents and young adults on antiretroviral therapy in Southern Africa, incorporating additional outcome ascertainment through linkage and tracing studies(2024) Nyakato, Patience; Cornell, Morna; Davies, Mary-AnnDespite significant progress in pediatric HIV care and treatment, children, adolescents, and young adults living with HIV (CAYHIV) continue to face challenges in achieving optimal outcomes compared to adults due to challenges like virologic non-suppression (VNS) among those in care and loss to follow-up (LTFU). Adolescents, in particular, face psychosocial and structural barriers that hinder their adherence to antiretroviral therapy (ART), leading to VNS and associated negative consequences, such as increased morbidity, drug resistance, mortality and a higher risk of HIV transmission to sexual partners and, for those who are pregnant, to their infants. LTFU is concerning as CAYHIV who are not in care are also likely not to be on ART resulting in faster disease progression, VNS, and increased morbidity and mortality. LTFU also poses a challenge to accurately measuring programme outcomes as the true outcomes of those LTFU are unknown. Accurate estimation of mortality rates among CAYHIV requires ascertaining outcomes in those LTFU and is important for the effective management of HIV care programmes. The thesis therefore aimed to describe the characteristics and outcomes of CAYHIV in Southern Africa, including additional outcomes ascertained from linkage and tracing studies among those who had been reported as LTFU at the original sites of ART initiation. The thesis consists of five papers (three published, two submitted) reporting the results from observational HIV cohorts of the International epidemiology Database to Evaluate AIDS -Southern Africa (IeDEA-SA) in six Southern African countries of Lesotho, Malawi, Mozambique, South Africa, Zambia and Zimbabwe. Chapter 1 (Introduction) lays the foundation for key issues and concepts. This is followed by the literature review (Chapter 2) which gives a comprehensive discussion on virologic outcomes among adolescents, LTFU, ascertaining outcomes among CAYHIV reported as LTFU and correction of programme-level mortality estimates for LTFU among all CAYHIV using outcomes ascertained through tracing or linkage studies. Chapters 3 and 4 examine virologic outcomes and early LTFU among younger adolescents (10-14 years, Chapter 3) and older adolescents (15-19 years, Chapter 4), with a sub-analysis among those initiating treatment during pregnancy. Chapter 3 reports increasing 75th quantile viral load values with a three-fold increase at age 14 vs age 10 years, but no specific age at which this increase is more marked, and no differences observed by sex. Chapter 4 reports a relatively low rate of virologic non suppression (15%), but a high proportion of early LTFU following ART initiation (around 30%) irrespective of pregnancy status. Chapters 5 and 6 provide results on outcomes of CAYHIV previously reported as LTFU and either traced (Chapter 5) or linked to a health information exchange (Chapter 6). We defined tracing as the physical tracking of patients reported as LTFU using text messages, phone calls and home visits while linkage was defined as the process of linking patient unique identifiers to different healthcare data platforms like pharmacy records, laboratory records, hospital admissions to identify if they have had any interaction with the healthcare system within the province outside of their original facility or ART registration. The tracing approach reveals a high proportion of unreported mortality (9%) and a low proportion of self-transfers (21%) among CAYHIV while the linkage approach reveals a low proportion of mortality (3%), and a high proportion of self transfers (47%). Chapter 7 consolidates the results in Chapters 5 and 6 alongside routinely collected data to correct mortality estimates comparing three uncorrected and three corrected methods. There is a two-fold increase in estimated mortality after incorporating deaths among successfully traced CAYHIV due to the high mortality in traced patients. In contrast, incorporating linkage data has minimal impact on mortality estimates as there were few deaths but a high number of self transfers. Tracing and linkage-informed studies both show substantial variability in mortality among retained children and those LTFU across countries and sites, respectively. The thesis concludes that virologic response among CAYHIV, particularly adolescents, has greatly improved in more recent years with improved ART regimens and is expected to continue improving with the introduction of dolutegravir based therapies. However, this can easily be jeopardized by the persistent high proportion of CAYHIV reported as LTFU across the entire continuum of HIV care. Mortality estimates can also be substantially impacted if no additional outcome ascertainment is conducted among those reported as LTFU. Tracing and linkage informed studies are, therefore, important for accurate estimation of mortality and retention estimates.
- ItemOpen AccessA comparison of death recording by health centres and civil registration in South Africans receiving antiretroviral treatment(Journal of the International AIDS Society, 2015-12-16) Johnson, Leigh F; Dorrington, Rob E; Laubscher, Ria; Hoffmann, Christopher J; Wood, Robin; Fox, Matthew P; Cornell, Morna; Schomaker, Michael; Prozesky, Hans; Tanser, Frank; Davies, Mary-Ann; Boulle, AndrewIntroduction: There is uncertainty regarding the completeness of death recording by civil registration and by health centres in South Africa. This paper aims to compare death recording by the two systems, in cohorts of South African patients receiving antiretroviral treatment (ART). Methods: Completeness of death recording was estimated using a capture-recapture approach. Six ART programmes linked their patient record systems to the vital registration system using civil ID numbers, and provided data comparing the outcomes recorded in patient files and in the vital registration. Patients were excluded if they had missing/invalid IDs or had transferred to other ART programmes. Results: After exclusions, 91 548 patient records were included. Of deaths recorded in patients files after 2003, 94.0% (95% CI: 93.3-94.6%) were recorded by civil registration, with completeness being significantly higher in urban areas, older adults and females. Of deaths recorded by civil registration after 2003, only 35.0% (95% CI: 34.2-35.8%) were recorded in patient files, with this proportion dropping from 60% in 2004-2005 to 30% in 2010 and subsequent years. Recording of deaths in patient files was significantly higher in children and in locations within 50km of the health centre. When the information from the two systems was combined, an estimated 96.2% of all deaths were recorded (93.5% in children and 96.2% in adults). Conclusions: South Africa’s civil registration system has achieved a high level of completeness in the recording of mortality. However, the fraction of deaths recorded by health centres is low and information from patient records is insufficient by itself to evaluate levels and predictors of ART patient mortality. Previously-documented improvements in ART mortality over time may be biased if based only on data from patient records.
- ItemOpen AccessDeterminants of voluntary or coerced sexual debut among Black African female adolescents in Soweto, South Africa: Findings from The Birth to Twenty Plus cohort study(2018) Nyemba, Dorothy Chiwoniso; Ramjith, Jordache; Cornell, Morna; Mabaso, MusawenkosiEarly sexual debut whether voluntary or coerced increases exposure to high risk sex which leads to unplanned pregnancy, sexually transmitted infections including HIV and reproductive heal th problems during adolescence. This study aim s to examine the risk factors for age of sexual debut, either voluntary or coerced among Black African female adolescents from the Birth to Twenty cohort study in Soweto, South Africa . Part A is the study protocol which outlines the rationale for conducting this study , study aim, research methodology, analysis plan and ethical considerations. Part B forms the literature review which gives a summary of the existing literature and provides context for the dissertation. The objectives of the literature review were to identify published literature on determinants of either voluntary or coerced sexual debut in adolescents and identify gaps for further research. Part C is the manuscript presenting the results and discussion on the implications of key findings. The results showed that there are many Black African female adolescents who are engaging in early sexual debut and there is prevalenc e of coerced sexual debut among adolescents of similar age. Socio-economic status and maternal education were found to be significantly associated with coerced sexual debut. There is a need for interventions to delay sexual debut among young female adolescents from low socio-economic backgrounds and lower maternal education.
- ItemOpen AccessDoes engaging with an interactive adherence intervention improve time in therapeutic range compared to receiving an education intervention alone, among patients anticoagulated with warfarin in Cape Town, South Africa?(2024) Pillay, Chriselda; Cornell, MornaBackground: Warfarin is the mainstay of oral anticoagulation in South Africa. There is wide variability between individual dose requirements. Regular International Normalised Ratio (INR) monitoring to guide dosing is required. Maintaining INR in therapeutic range is important for efficacy and safety. Time in Therapeutic Range (TTR) ≥65% is associated with better outcomes. The WarPATH study included an adherence intervention comprising patient education sessions and weekly interactive text messages with clinician contact details. We hypothesised that engaging with the interactive component of the intervention would improve TTR. Objectives: To identify predictors of higher TTR, to compare retention in INR monitoring between those who did and did not engage with the interactive component of the adherence intervention and to describe the content of those interactions. Methods: This analysis is nested in the WarPATH study, and we included South African WarPATH participants with sufficient INR results to calculate TTR (by Rosendaal method) in weeks 2-12 following warfarin initiation. We constructed a multivariable linear regression model to identify associations with higher TTR. We constructed a logistic regression model of associations with retention in INR monitoring in months four to seven following warfarin initiation (≥3 INR results, or documented warfarin stop by clinician between four and seven months if <3 INRs) Results: We included 61 participants, 51% men, median age 50 years (Inter-quartile range (IQR) 43-61). Median TTR was 40% (IQR 28-64%), only 14 (23%) achieved TTR≥65%. In a multivariable linear regression model, male sex (p= 0.04) and older age (p=0.02) were associated with higher TTR; adjusted for mobile phone ownership, anticoagulation indication and engagement with the interactive component of the adherence intervention. In 47% of telephonic interactions, participants requested assistance with systems challenges to anticoagulation care. Although TTR was not associated with engagement, in a multivariable logistic regression model (n=57), participants who engaged with the interactive component of the intervention were more likely to be retained in INR monitoring (Adjusted Odds Ratio 4.8, 95% Confidence Interval 1.32-21.1, p=0.02), adjusted for sex, age, anticoagulation indication, mobile phone ownership. Conclusion: Anticoagulation control in this cohort was poor. Participants who engaged with the interactive intervention were more likely to be retained in INR monitoring. Interaction content revealed multiple health system barriers to good anticoagulation control on warfarin. This adherence intervention is simple and scaling for public sector implementation should be explored alongside access to alternative oral anticoagulants requiring no laboratory monitoring or individualised dosing
- ItemOpen AccessEarly Antiretroviral Therapy reduces the incidence of otorrhea in a randomized study of early and deferred antiretroviral therapy: Evidence from the Children with HIV Early Antiretroviral Therapy (CHER) Study(BioMed Central Ltd, 2011) Hainline, Clotilde; Taliep, Reghana; Sorour, Gill; Nachman, Sharon; Rabie, Helena; Dobbels, Els; van Rensburg, Anita; Cornell, Morna; Violari, Avy; Madhi, Shabir; Cotton, MarkBACKGROUND: Although otorrhea occurs commonly in HIV-infected infants, there are few data. We compared the incidence of otorrhea in infants receiving early vs deferred ART in the Children with HIV Early Antiretroviral (CHER) trial. Infants aged 6 to 12 weeks of age with confirmed HIV infection and a CD4 percentage greater than or equal to 25% were randomized to early or deferred ART at two sites in South Africa. Medical records from one study site were reviewed for otorrhea.FINDINGS:Data were reviewed from the start of the trial in July 2005 until 20 June 2007, when the Data Safety Monitoring Board recommended that randomization to the deferred arm should stop and that all infants in this arm be reviewed for commencing antiretroviral therapy. Infants entered the study at a median of 7.4 weeks of age. Eleven of 38 (29%) on deferred therapy and 7 of 75 (9%) in the early-therapy group developed otorrhea (risk ratio 3.1, 95% confidence interval (CI) 1.31-7.36; p = 0.01). CONCLUSIONS: Early initiation of antiretroviral therapy is associated with significantly less otorrhea than when a deferred strategy is followed.TRIAL REGISTRATION:NCT00102960. ClinicalTrials.Gov
- ItemOpen AccessEstimating the impact of antiretroviral treatment on adult mortality trends in South Africa: A mathematical modelling study(2017) Johnson, Leigh F; May, Margaret T; Cornell, Morna; Boulle, Andrew; Egger, Matthias; Davies, Mary-AnnSubstantial reductions in adult mortality have been observed in South Africa since the mid-2000s, but there has been no formal evaluation of how much of this decline is attributable to the scale-up of antiretroviral treatment (ART), as previous models have not been calibrated to vital registration data. We developed a deterministic mathematical model to simulate the mortality trends that would have been expected in the absence of ART, and with earlier introduction of ART.
- ItemOpen AccessGender differences in presentation and early survival in an antiretroviral therapy programme in Gugulethu : South Africa, 2002-2007(2008) Cornell, Morna; Myer, LandonBy 2005, an estimated 500 000 people with HIV had initiated highly active antiretroviral therapy (HAART) in sub-Saharan Africa. However, disproportionately more women than men have accessed HAART in most developing countries including South Africa. While there has been considerable recent interest in the determinants of mortality among patients receiving HAART in developing countries, there is conflicting evidence about gender differences and survival in HAAR T programmes. This study explored whether there were gender differences in early mortality among 2 843 treatment-naive men and women entering care in a large South African HAART programme. The study was a secondary analysis of patient records covering three time periods: person-time from programme entry to the initiation ofHAART; person-time from HAART initiation to one year on treatment; and the total person-time from programme entry to one year on HAART. Cox' s proportional hazards regression ·was used to investigate crude and adjusted associations between basehne characteristics and mortality as we11 as loss-to-follow-up (LTFU). Using the Sobel test, the study explored whether the degree of disease ( according to CD4 count and WHO stage) played a mediating role in any association between gender and mortality. In all three time periods, the analysis found a strong crude associ~tiol). between male gender and mortality. Prior to HAART-initiation, there was a 31 % increase in the risk of mortality (crude Hazard Ratio (HR) 1.31, 95% CI, 0.93- 1.86; p=0. 131). In the period on HAART, this association strengthened (crude HR 1.57, 95% CI, 1.14-2.16; p=0.005). Overall, male gender increased the risk of mortality in the total cohort by 49% (crude HR, 1.49, 95% CI, 1.17-1.88 ; p=001). Adjustment for baseline characteristics, including CD4 count and WHO stage, attenuated these crude associations. After adjustment, there was no increase in risk associated with male gender in the period pre-HAART (HR 1.01, 95% CI, 0.67-1.51). On HAART, there was a 19% increase in risk (HR 1.19, 95% CI, 0.88-1.67). In the total cohort, this was slightly attenuated (HR 1.15, 95% CI, 0.93-1.50). There was evidence of mediation by degree of disease. In the preHAART period, the Sobel test found significant associations between mortality and CD4 count (p=0.044) as well as WHO stage (p=0.003). On HAART, too, CD4 count (p=0.045) and WHO stage (p< 0.001) appeared to mediate the effect of gender on death. Similarly, in the total cohort, there was evidence to support mediation by CD4 count (p=0.035) and WHO stage (p<0.001). There was a crude association between male gender and the risk of being L TFU (HR for L TFU during the total study period comparing males to females, 1.26, 95% CI, 0.89-1.78 ; p=0.194). This was strengthened by adjustment for age and monthly income (HR,1.35, 95% CI, 0.92-1.97). In this cohort, men appeared to have worse survival prospects than women due to more advanced HIV disease on programme entry. Previous studies have attributed the disproportionate access of women to HAART to gender differences in health seeking behaviour. This study argues that the prime obstacle might be the existing orientation of primary health care systems in developing countries towards the needs of women more than those of men. It suggests that women have better access to primary health services through the existing focus on maternal and child health. Women who are diagnosed and referred for HAART through these services are generally younger and healthier than men, who are diagnosed through services for tuberculosis (TB) and sexually transmitted infections (STis). This might explain why fewer men than women access HAART, and why they are diagnosed at later stages of disease progression. As a result, men may be disadvantaged in access to HAAR T in South Africa. The study suggests a number of short- and long-term solutions including : further research on obstacles to male access to HAART; changes in national policy; and the establishment of male-friendly services as an entry point for men into broader health services. Such approaches might facilitate the earlier diagnosis and treatment of men and improve their survival in HAART programmes.
- ItemOpen AccessGender differences in survival among adult patients starting antiretroviral therapy in South Africa: a multicentre cohort study(Public Library of Science, 2012) Cornell, Morna; Schomaker, Michael; Garone, Daniela Belen; Giddy, Janet; Hoffmann, Christopher J; Lessells, Richard; Maskew, Mhairi; Prozesky, Hans; Wood, Robin; Johnson, Leigh FMorna Cornell and colleagues investigate differences in mortality for HIV-positive men and women on antiretroviral therapy in South Africa.
- ItemOpen AccessLong-term virologic responses to responses to antiretroviral therapy among patients entering adherence clubs in Khayelitsha, Cape Town South Africa(2018) Kehoe, Kathleen; Cornell, MornaIntroduction: In 2017, approximately 36.9 million people were living with HIV and 58.1% were accessing antiretroviral therapy (ART) worldwide. In South Africa, ART coverage was 48.6% in 2015, and has since increased due to the implementation of universal Test and Treat. Given the need for lifelong care for millions of individuals, differentiated models of care for ART services are required. One such model, adherence clubs (ACs) for stable ART patients, has been successfully scaled-up in the Cape Metro Health District. In this study, we describe long-term virologic outcomes of patients who have ever entered ACs. Methods: Adult patients enrolled in ACs in Khayelitsha between January 2011 and June 2017 were eligible for inclusion. Time to, and risk factors for, an elevated viral load (first viral load >1000 copies/mL) and confirmed virologic failure (two consecutive viral loads >1000 copies/mL two to nine months apart) were estimated using the Kaplan-Meier estimator and Cox proportional hazards models. Viral load completeness was assessed at 4, 16, 28, 40 and 52 months of follow up. Results: Of 11 830 patients, 74% were female and 45% were aged 35-44 years at AC enrolment. The median time on ART at enrolment was 4.7 years (interquartile range (IQR) 2.7-7.1). An elevated viral load was observed in 517 patients (4%), 141 (27%) of whom subsequently experienced confirmed virologic failure. The median time from an elevated viral load to confirmed virologic failure was 137 days (IQR 112-168). Risk of an elevated viral load and confirmed virologic failure was higher among patients with a longer duration on ART and lower among older patients. The proportion of completed viral load tests ranged from 79% at 4 months to 75% at 52 months. Over 90% of patients with viral load assessments remained virologically suppressed (<400 copies/mL). Conclusion: This study demonstrates low rates of confirmed virologic failure among patients who entered ACs. The majority of patients remained stable despite the rapid growth of ACs, supporting the continued expansion of the model, particularly for men. Monitoring was generally consistent, but suboptimal among those who experienced an elevated viral load. Patients referred to ACs, younger patients and those with longer duration of ART should be prioritised to ensure they remain stable on lifelong ART.
- ItemOpen AccessMonitoring the South African National Antireteoviral Treatment Programme, 2003-2007: The IeDEA Southern Africa Collaboration(2009) Cornell, Morna; Technau, Karl; Fairall, Lara; Wood, Robin; Moultrie, Harry; Van Cutsem, Gilles; Giddy, Janet; Mohapi, Lerato; Eley, Brian; MacPhail, Patrick; Prozesky, Hans; Rabie, Helena; Davies, Mary-Ann; Maxwell, Nicola; Boulle, AndrewObjectives: To introduce the combined South African cohorts of the International Epidemiologic Databases to Evaluate AIDS-Southern Africa (IeDEA-SA) collaboration as reflecting the South African national antiretroviral treatment (ART) programme; to characterize patients accessing these services; and to describe changes in services and patients 2003-2007. Design & setting Multi-cohort study of 11 ART programmes in Gauteng, Western Cape, Free State and KwaZulu-Natal. Subjects ART-naïve adults and children (<16 years old) who initiated ART with ≥3 antiretroviral drugs before 2008. Results: Most sites were offering free treatment to adults and children in the public sector, ranging from 264 to 17,835 patients per site. Among 45,383 adults and 6,198 children combined, median (IQR) range was 35.0 years (29.8-41.4) and 42.5 months (14.7-82.5) respectively. Of adults, 68% were female. Median CD4 cell count was 102 cells/µL (44-164) and was lower among males than females (86, 34-150 vs 110, 50-169, p<0.001). Median CD4% among children was 12% (7-17.7). Between 2003 and 2007, enrolment increased 11-fold in adults and 3-fold in children. Median CD4 count at enrolment increased for all adults (67-111 cells/µL, p<0.001) and for those in Stage IV (39-89 cells/µL, p<0.001). Among children <5 years, baseline CD4% increased over time (11.5%-16.0%, p<0.001). Conclusions: IeDEA-SA provides a unique opportunity to report on the national ART programme. The study describes dramatically increasing enrolment. Late presentation, especially of men and children, remains a concern. Investment in sentinel sites ensures good individual-level data while freeing most sites to continue with simplified reporting.