Browsing by Author "Boulle, Andrew"

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    A comparison of linkage to HIV care after provider-initiated HIV testing and counselling (PITC) versus voluntary HIV counselling and testing (VCT) for patients with sexually transmitted infections in Cape Town, South Africa
    (2014-08-18) Leon, Natalie; Mathews, Catherine; Lewin, Simon; Osler, Meg; Boulle, Andrew; Lombard, Carl
    Abstract Background We examined linkage to care for patients with sexually transmitted infection who were diagnosed HIV-positive via the provider-initiated HIV testing and counselling (PITC) approach, as compared to the voluntary counselling and testing (VCT) approach, as little is known about the impact of expanded testing strategies on linkage to care. Methods In a controlled trial on PITC (Cape Town, 2007), we compared HIV follow-up care for a nested cohort of 930 HIV-positive patients. We cross-referenced HIV testing and laboratory records to determine access to CD4 and viral load testing as primary outcomes. Secondary outcomes were HIV immune status and time taken to be linked to HIV care. Logistic regression was performed to analyse the difference between arms. Results There was no difference in the main outcomes of patients with a record of CD4 testing (69.9% in the intervention, 65.2% in control sites, OR 0.82 (CI: 0.44-1.51; p = 0.526) and viral load testing (14.9% intervention versus 10.9% control arm; OR 0.69 (CI: 0.42-1.12; p = 0.131). In the intervention arm, ART-eligible patients (based on low CD4 test result), accessed viral load testing approximately 2.5 months sooner than those in the control arm (214 days vs. 288 days, HR: 0.417, 95% CI: 0.221-0.784; p = 0.007). Conclusion The PITC intervention did not improve linkage to CD4 testing, but shortened the time to viral load testing for ART-eligible patients. Major gaps found in follow-up care across both arms, indicate the need for more effective linkage-to-HIV care strategies. Trial registration Current Controlled Trials ISRCTN93692532
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    A multi-component theory-based behaviour change intervention to increase HIV self–testing uptake and linkage to HIV prevention, care and treatment among hard to reach adults in Northern Tanzania
    (2021) Njau, Bernard Joseph; Mathews, Catherine; Boulle, Andrew
    To achieve the WHO targets of 95–95–95 by 2030, whereby 95% of all people living with HIV (PLHIV) know their status, 95 % of all people with an HIV diagnosis receive sustained antiretroviral therapy (ART), and 95 % of all people receiving ART achieve viral suppression, it is imperative to introduce novel community–based testing approaches such as HIV self-testing (HIVST). HIV self–testing has been shown to empower non– testers in both developed and underdeveloped countries, to be aware of their HIV status. However, no studies on the uptake of HIVST have been conducted on hard to reach populations in Northern Tanzania. The hard to reach populations for this thesis were female bar workers (FBWs) and mountain climbing porters (MCPS) in Northern Tanzania, who exhibit high-risk behaviours for HIV infection and low rates of HIV testing and / or repeat testing. It is important to find ways to increase the uptake of HIV testing in these populations and HIVST is proposed as a means of improving HIV testing coverage in hard-to-reach populations in the context of a long-standing HIV testing program. Existing implementation science literature suggests that behaviour change interventions (BCIs) guided by behaviour change theories and using planning and evaluation frameworks (i.e. PRECEDE-PROCEED model) can be effective in increasing HIV-related behaviour change. However, the current evidence on the effectiveness of HIV-related BCI is from studies conducted in high-income countries. To address the low HIV testing rates and/or repeat testing, it was important to undertake a project of research to develop and evaluate a theory-based behaviour change intervention (BCI) to increase HIVST uptake and linkage to HIV prevention, care and treatment among FBWs and MCPs in Northern Tanzania. This thesis aimed to develop and evaluate a multi-component theory-based BCI to increase HVST uptake and linkage to HIV prevention, care and treatment among female bar workers and mountain climbing porters in Northern Tanzania.
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    A systematic review of qualitative evidence on factors enabling and deterring uptake of HIV self-testing in Africa
    (2019-10-15) Njau, Bernard; Covin, Christopher; Lisasi, Esther; Damian, Damian; Mushi, Declare; Boulle, Andrew; Mathews, Catherine
    Abstract Background More than 40% of adults in Sub-Saharan Africa are unaware of their HIV status. HIV self-testing (HIVST) is a novel approach with a potential to increase uptake of HIV testing and linkage to care for people who test HIV positive. We explored HIV stakeholder’s perceptions about factors that enable or deter the uptake of HIV self-testing and experiences of self-testing of adult users in Africa. Methods This systematic review of qualitative evidence included articles on qualitative studies published or made available between January 1998 to February 2018 on perspectives of key stakeholders, including HIV policymakers, HIV experts, health care providers, and adult men and women (18 years and above) about factors that enable or deter the uptake of HIV self-testing and experiences of self-testing among adult users. We searched CINAHL, MEDLINE in Pubmed, EMBASE, AJOL, PsycINFO, Social Science Citation Index (SSCI), and Web of Science for articles in English on HIVST with qualitative data from different African countries. Results In total, 258 papers were retrieved, and only nine (9) studies conducted in 5 African countries were eligible and included in this synthesis. Perceived facilitators of the uptake of HIVST were autonomy and self-empowerment, privacy, confidentiality, convenience, opportunity to test, including couples HIV testing, and ease of use. The perceived barriers included the cost of buying self-test kits, perceived unreliability of test results, low literacy, fear and anxiety of a positive test result, and potential psychological and social harms. HIV stakeholder’s concerns about HIVST included human right issues, lack of linkage to care, lack of face-to-face counseling, lack of regulatory and quality assurance systems, and quality of self-test kits. Actual HIVST users expressed preference of oral-fluid self-testing because of ease of use, and that it is less invasive and painless compared to finger-stick/whole blood-based HIV tests. Lack of clear instructions on how to use self-test kits, and existing different products of HIVST increases rates of user errors. Conclusions Overcoming factors that may deter HIV testing, and HIVST, in particular, is complex and challenging, but it has important implications for HIV stakeholders, HIVST users, and public health in general. Research is warranted to explore the actual practices related to HIVST among different populations in Africa.
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    Adherence to antiretroviral therapy in young children in Cape Town, South Africa, measured by medication return and caregiver self-report : a prospective cohort study
    (2010) Davies, Mary-Ann; Boulle, Andrew; Eley, Brian
    Excellent adherence to antiretroviral therapy (ART) is necessary if HIV-infected children are to experience the dramatically improved outcomes that this treatment affords. However, there is very limited data on adherence to antiretroviral therapy in Africa, with few studies that examine the predictive value of low technology measures of adherence in terms of viral and immune outcomes. In addition there are no long terms studies of adherence in young children in Africa.
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    Adherence to antiretroviral therapy in young children in Cape Town, South Africa, measured by medication return and caregiver self-report: a prospective cohort study
    (BioMed Central Ltd, 2008) Davies, Mary-Ann; Boulle, Andrew; Fakir, Tanzeem; Nuttall, James; Eley, Brian
    BACKGROUND:Antiretroviral therapy (ART) dramatically improves outcomes for children in Africa; however excellent adherence is required for treatment success. This study describes the utility of different measures of adherence in detecting lapses in infants and young children in Cape Town, South Africa. METHODS: In a prospective cohort of 122 HIV-infected children commenced on ART, adherence was measured monthly during the first year of treatment by medication return (MR) for both syrups and tablets/capsules. A questionnaire was administered to caregivers after 3 months of treatment to assess experience with giving medication and self-reported adherence. Viral and immune response to treatment were assessed at the end of one year and associations with measured adherence determined. RESULTS: Medication was returned for 115/122 (94%) children with median age (IQR) of 37 (16 - 61) months. Ninety-one (79%) children achieved annual average MR adherence [greater than or equal to] 90%. This was an important covariate associated with viral suppression after adjustment for disease severity (OR = 5.5 [95%CI: 0.8-35.6], p = 0.075), however was not associated with immunological response to ART. By 3 months on ART, 13 (10%) children had deceased and 11 (10%) were lost to follow-up. Questionnaires were completed by 87/98 (90%) of caregivers of those who remained in care. Sensitivity of poor reported adherence (missing [greater than or equal to] 1 dose in the previous 3 days) for MR adherence <90% was only 31.8% (95% CI: 10.7% - 53.0%). Caregivers of 33/87 (38.4%) children reported difficulties with giving medication, most commonly poor palatability (21.8%). Independent socio-demographic predictors of MR adherence [greater than or equal to] 90% were secondary education of caregivers (OR = 4.49; 95%CI: 1.10 - 18.24) and access to water and electricity (OR = 2.65; 95%CI: 0.93 - 7.55). Taking ritonavir was negatively associated with MR adherence [greater than or equal to] 90% (OR = 0.37; 95%CI: 0.13 - 1.02). CONCLUSION: Excellent adherence to ART is possible in African infants and young children and the relatively simple low technology measure of adherence by MR strongly predicts viral response. Better socio-economic status and more palatable regimens are associated with better adherence.
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    Adjusting mortality for loss to follow-up: analysis of five ART programmes in sub-Saharan Africa
    (Public Library of Science, 2010) Brinkhof, Martin W G; Spycher, Ben D; Yiannoutsos, Constantin; Weigel, Ralf; Wood, Robin; Messou, Eugène; Boulle, Andrew; Egger, Matthias; Sterne, Jonathan A C; (IeDEA), for the International epidemiological Database to Evaluate AIDS
    BACKGROUND: Evaluation of antiretroviral treatment (ART) programmes in sub-Saharan Africa is difficult because many patients are lost to follow-up. Outcomes in these patients are generally unknown but studies tracing patients have shown mortality to be high. We adjusted programme-level mortality in the first year of antiretroviral treatment (ART) for excess mortality in patients lost to follow-up. Methods and FINDINGS: Treatment-naïve patients starting combination ART in five programmes in Côte d'Ivoire, Kenya, Malawi and South Africa were eligible. Patients whose last visit was at least nine months before the closure of the database were considered lost to follow-up. We filled missing survival times in these patients by multiple imputation, using estimates of mortality from studies that traced patients lost to follow-up. Data were analyzed using Weibull models, adjusting for age, sex, ART regimen, CD4 cell count, clinical stage and treatment programme. A total of 15,915 HIV-infected patients (median CD4 cell count 110 cells/µL, median age 35 years, 68% female) were included; 1,001 (6.3%) were known to have died and 1,285 (14.3%) were lost to follow-up in the first year of ART. Crude estimates of mortality at one year ranged from 5.7% (95% CI 4.9-6.5%) to 10.9% (9.6-12.4%) across the five programmes. Estimated mortality hazard ratios comparing patients lost to follow-up with those remaining in care ranged from 6 to 23. Adjusted estimates based on these hazard ratios ranged from 10.2% (8.9-11.6%) to 16.9% (15.0-19.1%), with relative increases in mortality ranging from 27% to 73% across programmes. CONCLUSIONS: Naïve survival analysis ignoring excess mortality in patients lost to follow-up may greatly underestimate overall mortality, and bias ART programme evaluations. Adjusted mortality estimates can be obtained based on excess mortality rates in patients lost to follow-up.
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    AIDS-associated Kaposi's sarcoma is linked to advanced disease and high mortality in a primary care HIV programme in South Africa
    (BioMed Central Ltd., 2010) Chu, Kathryn; Mahlangeni, Gcina; Swannet, Sarah; Ford, Nathan; Boulle, Andrew; Van Cutsem, Gilles
    BACKGROUND: AIDS-associated Kaposi's sarcoma is an important, life-threatening opportunistic infection among people living with HIV/AIDS in resource-limited settings. In western countries, the introduction of combination antiretroviral therapy (cART) and new chemotherapeutic agents has resulted in decreased incidence and improved prognosis of AIDS-associated Kaposi's sarcoma. In African cohorts, however, mortality remains high. In this study, we describe disease characteristics and risk factors for mortality in a public sector HIV programme in South Africa. METHODS: We analysed data from an observational cohort study of HIV-infected adults with AIDS-associated Kaposi's sarcoma, enrolled between May 2001 and January 2007 in three primary care clinics. Paper records from primary care and tertiary hospital oncology clinics were reviewed to determine the site of Kaposi's sarcoma lesions, immune reconstitution inflammatory syndrome stage, and treatment. Baseline characteristics, cART use and survival outcomes were extracted from an electronic database maintained for routine monitoring and evaluation. Cox regression was used to model associations with mortality. RESULTS: Of 6292 patients, 215 (3.4%) had AIDS-associated Kaposi's sarcoma. Lesions were most commonly oral (65%) and on the lower extremities (56%). One quarter of patients did not receive cART. The mortality and lost-to-follow-up rates were, respectively, 25 (95% CI 19-32) and eight (95% CI 5-13) per 100 person years for patients who received cART, and 70 (95% CI 42-117) and 119 (80-176) per 100 person years for patients who did not receive cART. Advanced T stage (adjusted HR, AHR = 5.3, p < 0.001), advanced S stage (AHR = 5.1, p = 0.008), and absence of chemotherapy (AHR = 2.4, p = 0.012) were associated with mortality.Patients with AIDS-associated Kaposi's sarcoma presented with advanced disease and high rates of mortality and loss to follow up. Risk factors for mortality included advanced Kaposi's sarcoma disease and lack of chemotherapy use. Contributing factors to the high mortality for patients with AIDS-associated Kaposi's sarcoma likely included late diagnosis of HIV disease, late accessibility to cART, and sub-optimal treatment of advanced Kaposi's sarcoma. CONCLUSIONS: These findings confirm the importance of early access to both cART and chemotherapy for patients with AIDS-associated Kaposi's sarcoma. Early diagnosis and improved treatment protocols in resource-poor settings are essential.
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    Assessing rates and contextual predictors of 5-year mortality among HIV-infected and HIV-uninfected individuals following HIV testing in Durban, South Africa
    (2019-08-28) Bassett, Ingrid V; Xu, Ai; Giddy, Janet; Bogart, Laura M; Boulle, Andrew; Millham, Lucia; Losina, Elena; Parker, Robert A
    Abstract Background Little is known about contextual factors that predict long-term mortality following HIV testing in resource-limited settings. We evaluated the impact of contextual factors on 5-year mortality among HIV-infected and HIV-uninfected individuals in Durban, South Africa. Methods We used data from the Sizanani trial (NCT01188941) in which adults (≥18y) were enrolled prior to HIV testing at 4 outpatient sites. We ascertained vital status via the South African National Population Register. We used random survival forests to identify the most influential predictors of time to death and incorporated these into a Cox model that included age, gender, HIV status, CD4 count, healthcare usage, health facility type, mental health, and self-identified barriers to care (i.e., service delivery, financial, logistical, structural and perceived health). Results Among 4816 participants, 39% were HIV-infected. Median age was 31y and 49% were female. 380 of 2508 with survival information (15%) died during median follow-up of 5.8y. For both HIV-infected and HIV-uninfected participants, each additional barrier domain increased the HR of dying by 11% (HR 1.11, 95% CI 1.05–1.18). Every 10-point increase in mental health score decreased the HR by 7% (HR 0.93, 95% CI 0.89–0.97). The hazard ratio (HR) for death of HIV-infected versus HIV-uninfected varied by age: HR of 6.59 (95% CI: 4.79–9.06) at age 20 dropping to a HR of 1.13 (95% CI: 0.86–1.48) at age 60. Conclusions Independent of serostatus, more self-identified barrier domains and poorer mental health increased mortality risk. Additionally, the impact of HIV on mortality was most pronounced in younger persons. These factors may be used to identify high-risk individuals requiring intensive follow up, regardless of serostatus. Trial registration Clinical Trials.gov Identifier NCT01188941. Registered 26 August 2010.
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    Assessing the effectiveness of the ART programme in the Western Cape Province of South Africa through triangulation of context-appropriate population level routine monitoring and surveillance systems
    (2023) Osler, Margaret; Boulle, Andrew; Ford, Nathan
    Background After a decade of free antiretroviral therapy (ART) provision, countries continued facing challenges both in trying to meet the ever-increasing pool of eligible people needing HIV treatment, and efficiently monitoring programme effectiveness to improve patient care and service delivery. Concerns about the feasibility of further treatment expansion were being debated with trials showing benefit, but with ongoing uncertainty as to whether those benefits would be realised in resource-limited settings with fragile health systems. Key questions underpinning this thesis were how to robustly develop, implement, monitor and use routine health information systems to explore pertinent epidemiological questions, including real-world effectiveness of the ART programme, determinants of ongoing morbidity and mortality, and the impact of guideline changes. Methods The thesis includes a health systems review of the implementation of person-level information systems for HIV care, followed by a number of cohort analyses based on the public-sector health services in the Western Cape, South Africa. The study population consists of people living with HIV, who had at least one CD4 test or HIV-care visit, and who were ≥16 years of age. The cohort analyses utilized a population-wide linked dataset containing all available digital data from fixed health facilities, laboratory, pharmacy, and death registry systems. The first analysis described temporal trends in the CD4 distributions over 10 years, with longitudinal categorization of ART status of people with extremely advanced HIV disease (AHD). Two analyses used a regression discontinuity design to consider the causal impact of guideline changes, while the last two analyses explored important longer-duration determinants of morbidity and mortality in a survival analysis cohort framework, including through the use of flexible parametric survival models. Results Developing a tiered suite of interoperable information solutions enabled each health facility to independently evolve from paper to offline and then hybrid/online electronic registers when dependencies such as electricity, stable networks and resources allowed them to. The largest proportion of people with severe AHD (CD4 <50 cells/µL) came from those already on ART in more recent years, in comparison to people first presenting or not eligible for ART. Of those on ART with severe AHD, more than three-quarters had a confirmed treatment interruption (>3 months) and/or viraemia within the previous year. The biggest benefits (based on24-month survival) when increasing eligibility thresholds for ART were seen during earlier guideline changes which expanded access at lower CD4 count thresholds (from CD4 <200/µL to CD4 <350/µL); however, at a patient level, benefits from ART were seen at all three eligibility threshold changes (200, 350 and 500 cells/µl). Deferring treatment for people ineligible lead to, on average, >2 years delay prior to starting ART, increasing risk of AHD and death. The greatest increases in ART initiations and decreases in mortality happened between guideline changes, reflecting large increases in ART access prior to formal expansion of access through guideline changes. As the ART programme has matured, men living with HIV continue to have poorer access to ART, a greater risk of TB, are more likely to interrupt treatment and have inferior clinical outcomes compared to woman, especially between diagnosis and the first five years on ART. Women, however, carried the larger absolute mortality burden, due to the greater numbers living with HIV. Almost two-thirds of the ART cohort interrupted treatment for >4 months at least once, increasing their risk of death by 27%, compared to people who had never interrupted ART. Each additional interruption was associated with further increases in mortality. Conclusions Pragmatic interoperable offline/hybrid/online health information systems can be successfully implemented at scale in lower resource settings to improve patient care, provide information on interventions and inform policy and resource allocation. Programmatic ART outcomes did improve during expansion of ART eligibility including into the time-period of the treat-all policy when CD4 count criteria were removed. More people accessed ART over time, independent of guideline changes, improving population HIV outcomes. The guidelines changes were nonetheless shown to be effective at an individual level. The number of people with AHD has not decreased however due to ART experienced patients returning to care after interruptions with considerable immune deterioration. Recommendations focused on improving systems for retention, re-engagement, and AHD and are most likely applicable to similar public-sector settings in Southern Africa.
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    Association between food intake and obesity in pregnant women living with and without HIV in Cape Town, South Africa: a prospective cohort study
    (2021-08-04) Madlala, Hlengiwe P.; Steyn, Nelia P.; Kalk, Emma; Davies, Mary-Anne; Nyemba, Dorothy; Malaba, Thokozile R.; Mehta, Ushma; Petro, Gregory; Boulle, Andrew; Myer, Landon
    Background Although global nutrition/dietary transition resulting from industrialisation and urbanisation has been identified as a major contributor to widespread trends of obesity, there is limited data in pregnant women, including those living with HIV in South Africa. We examined food-based dietary intake in pregnant women with and without HIV at first antenatal care (ANC) visit, and associations with maternal overweight/obesity and gestational weight gain (GWG). Methods In an urban South African community, consecutive women living with (n = 479) and without (n = 510) HIV were enrolled and prospectively followed to delivery. Interviewer-administered non-quantitative food frequency questionnaire was used to assess dietary intake (starch, protein, dairy, fruits, vegetables, legumes, oils/fats) at enrolment. Associations with maternal body mass index (BMI) and GWG were examined using logistic regression models. Results Among women (median age 29 years, IQR 25–34), the prevalence of obesity (BMI ≥ 30 kg/m2) at first ANC was 43% and that of excessive GWG (per IOM guidelines) was 37% overall; HIV prevalence was 48%. In women without HIV, consumption of potato (any preparation) (aOR 1.98, 95% CI 1.02–3.84) and pumpkin/butternut (aOR 2.13, 95% CI 1.29–3.49) for 1–3 days a week increased the odds of overweight/obesity compared to not consuming any; milk in tea/coffee (aOR 6.04, 95% CI 1.37–26.50) increased the odds of excessive GWG. Consumption of eggs (any) (aOR 0.52, 95% CI 0.32–0.86) for 1–3 days a week reduced the odds of overweight/obesity while peanut and nuts consumption for 4–7 days a week reduced the odds (aOR 0.34, 95% CI 0.14–0.80) of excessive GWG. In women with HIV, consumption of milk/yoghurt/maas to drink/on cereals (aOR 0.35, 95% CI 0.18–0.68), tomato (raw/cooked) (aOR 0.50, 95% CI 0.30–0.84), green beans (aOR 0.41, 95% CI 0.20–0.86), mixed vegetables (aOR 0.49, 95% CI 0.29–0.84) and legumes e.g. baked beans, lentils (aOR 0.50, 95% CI 0.28–0.86) for 4–7 days a week reduced the odds of overweight/obesity; tomato (raw/cooked) (aOR 0.48, 95% CI 0.24–0.96) and mixed vegetables (aOR 0.38, 95% CI 0.18–0.78) also reduced the odds of excessive GWG. Conclusions Diet modification may promote healthy weight in pregnant women living with and without HIV.
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    Associations of severe hyperlactataemia and lactic acidosis in HIV-infected patients receiving antiretroviral theraphy
    (2007) Osler, Meg; Boulle, Andrew
    Severe symptomatic hyperlactataemia and lactic acidosis (SHLA) are life-threatening events that are occurring at increasing incidence levels in South Africa. Globally, the rise in SHLA cases is closely correlated to the increased accessibility of anti retroviral (ARV) medication for human immunodeficiency virus (HIV). Although hyperlactataemia and lactic acidosis were once thought of as rare conditions, they are now being recognized as important concerns when administering antiretroviral therapy. A better understanding of the risk factors for SHLA is important in combating the morbidity and mortality associated with such an adverse event.
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    Baseline prevalence and incidence and risk factors for new-onset drug induced hearing loss in adults receiving drug-resistant tuberculosis (DR-TB) treatment in Khayelitsha, South Africa
    (2013) Njuguna, Christine Wanjiku; Cox, Helen; Boulle, Andrew
    Treatment for drug-resistant tuberculosis (DR-TB) is longer and associated with more significant side-effects than drug susceptible TB. Second line injectable therapy using kanamycin, amikacin or capreomycin is associated with irreversible hearing loss. There is a scarcity of literature regarding the frequency of hearing loss as well as associated risk factors, particularly with long term use. This study aimed to determine the incidence and risk factors for hearing loss among patients receiving second line injectable drugs.
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    C-reactive protein and procalcitonin to discriminate between tuberculosis, Pneumocystis jirovecii pneumonia, and bacterial pneumonia in HIV-infected inpatients meeting WHO criteria for seriously ill: a prospective cohort study
    (BioMed Central, 2018-08-14) Mendelson, Fiona; Griesel, Rulan; Tiffin, Nicki; Rangaka, Molebogeng; Boulle, Andrew; Mendelson, Marc; Maartens, Gary
    Background Tuberculosis, bacterial community-acquired pneumonia (CAP), and Pneumocystis jirovecii pneumonia (PJP) are the three commonest causes of hospitalisation in HIV-infected adults. Prompt diagnosis and treatment initiation are important to reduce morbidity and mortality, but are hampered by limited diagnostic resources in resource poor settings. C-reactive protein (CRP) and procalcitonin have shown diagnostic utility for respiratory tract infections, however few studies have focussed on their ability to distinguish between tuberculosis, CAP, and PJP in HIV-infected inpatients. Methods We evaluated the diagnostic accuracy of CRP and procalcitonin, compared with composite reference standards, to discriminate between the three target infections in adult HIV-infected inpatients in two district level hospitals in Cape Town, South Africa. Participants were admitted with current cough and danger signs in accordance with the WHO algorithm for tuberculosis in seriously ill HIV-infected patients. Study clinicians were blinded to CRP and procalcitonin results. Results Two hundred forty-eight participants met study case definitions: 133 with tuberculosis, 61 with CAP, 16 with PJP, and 38 with mixed infection. In the 210 particpants with single infections the differences in median CRP and procalcitonin concentrations between the three infections were statistically significant, but distributions overlapped considerably. CRP and procalcitonin concentrations were highest in the CAP group and lowest in the PJP group. CRP and procalcitonin cut-offs with sensitivities of ≥90% were found for all three target infection pairs, but corresponding specificities were low. Highest receiver operating characteristic areas under the curve for CRP and procalcitonin were for PJP versus tuberculosis and PJP versus CAP (0.68 and 0.71, and 0.74 and 0.69 respectively). Conclusions CRP and procalcitonin showed limited value in discriminating between the three target infections due to widely overlapping distributions, but diagnostic accuracy was higher for discriminating PJP from CAP or tuberculosis. Our findings show limitations for CRP and procalcitonin, particularly for discriminiation of tuberculosis form CAP, however they may have greater diagnostic utility as part of a panel of biomarkers or in clinical prediction rules.
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    Central nervous system disorders afrer starting antiretroviral therapy in South Africa
    (Lippincott, Williams & Wilkins, 2010) Asselman, Valerie; Thienemann, Fredrich; Pepper, Dominique J; Boulle, Andrew; Wilkinson, Robert J; Graeme Meintjes; Marais, Suzaan
    Objective: To describe the spectrum of central nervous system (CNS) disease during the first year of antiretroviral therapy (ART), and to determine the contribution of neurological immune reconstitution inflammatory syndrome (IRIS). Design: A prospective observational cohort study conducted over a 12-month period at a public sector referral hospital in South Africa. Methods: HIV seropositive patients who developed new or recurrent neurological or psychiatric symptom(s) or sign(s) within the first year of starting ART were enrolled. We used the number of patients starting ART in the referral area in the preceding year as the denominator to calculate the incidence of referral for neurological deterioration. Patients with delirium and peripheral neuropathy were excluded. Outcome at six months was recorded. Results: Seventy-five patients were enrolled. The median nadir CD4+ count was 64 cells/μL. 59% of patients were receiving antituberculosis treatment. The incidence of referral for CNS deterioration in the first year of ART was 23.3 cases (95% CI, 18.3–29.2) per 1000 patient years at risk. CNS tuberculosis (n=27, 36%), cryptococcal meningitis (n=18, 24%), intracerebral space occupying lesions (other than tuberculoma) (n=10, 13%) and psychosis (n=9, 12%) were the most frequent diagnoses. Paradoxical neurological IRIS was diagnosed in 21 patients (28%), related to tuberculosis in 16 and cryptococcosis in 5. At 6 months, 23% of patients had died and 20% were lost to follow-up. Conclusion: Opportunistic infections, notably tuberculosis and cryptococcosis, were the most frequent causes for neurological deterioration after starting ART. Neurological IRIS occurred in over a quarter of patients.
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    Child-headed households in South Africa: A statistical brief 2009
    (Children's Institute, 2009) Meintjes, Helen; Hall, Katharine; Marera, Double-Hugh; Boulle, Andrew
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    Cohort Profile: The Western Cape Pregnancy Exposure Registry (WCPER)
    (2022-06) Kalk, Emma; Heekes, Alexa; Slogrove, Amy; Phelanyane, Florence; Davies, Mary-Ann; Myer, Landon; Euvrard, Jonathan; Kroon, Max; Petro, Greg; Fieggen, Karen; Stewart, Chantal; Rhoda, Natasha; Gebhardt, Stefan; Osman, Ayesha; Anderson, Kim; Boulle, Andrew; Mehta, Ushma
    Purpose: The Western Cape Pregnancy Exposure Registry (PER) was established at two public sector healthcare sentinel sites in the Western Cape province, South Africa, to provide ongoing surveillance of drug exposures in pregnancy and associations with pregnancy outcomes. Participants: Established in 2016, all women attending their first antenatal visit at primary care obstetric facilities were enrolled and followed to pregnancy outcome regardless of the site (ie, primary, secondary, tertiary facility). Routine operational obstetric and medical data are digitised from the clinical stationery at the healthcare facilities. Data collection has been integrated into existing services and information platforms and supports routine operations. The PER is situated within the Provincial Health Data Centre, an information exchange that harmonises and consolidates all health-related electronic data in the province. Data are contributed via linkage across a unique identifier. This relationship limits the missing data in the PER, allows validation and avoids misclassification in the population-level data set. Findings to date: Approximately 5000 and 3500 pregnant women enter the data set annually at the urban and rural sites, respectively. As of August 2021, >30 000 pregnancies have been recorded and outcomes have been determined for 93%. Analysis of key obstetric and neonatal health indicators derived from the PER are consistent with the aggregate data in the District Health Information System. Future plans: This represents significant infrastructure, able to address clinical and epidemiological concerns in a low/middle-income setting.
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    A 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, Andrew
    Introduction: 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.
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    Correcting for mortality among patients lost to follow up on antiretroviral therapy in South Africa: a cohort analysis
    (Public Library of Science, 2011) Van Cutsem, Gilles; Ford, Nathan; Hildebrand, Katherine; Goemaere, Eric; Mathee, Shaheed; Abrahams, Musaed; Coetzee, David; Boulle, Andrew
    BACKGROUND: Loss to follow-up (LTF) challenges the reporting of antiretroviral treatment (ART) programmes, since it encompasses patients alive but lost to programme and deaths misclassified as LTF. We describe LTF before and after correction for mortality in a primary care ART programme with linkages to the national vital registration system. Methods and FINDINGS: We included 6411 patients enrolled on ART between March 2001 and June 2007. Patients LTF with available civil identification numbers were matched with the national vital registration system to ascertain vital status. Corrected mortality and true LTF were determined by weighting these patients to represent all patients LTF. We used Kaplan-Meier estimates and Cox regression to describe LTF, mortality among those LTF, and true LTF. Of 627 patients LTF, 85 (28.8%) had died within 3 months after their last clinic visits. Respective estimates of LTF before and after correction for mortality were 6.9% (95% confidence interval [CI] 6.2-7.6) and 4.3% (95% CI 3.5-5.3) at one year on ART, and 23.9% (95% CI 21.0-27.2) and 19.7% (95% CI 16.1-23.7) at 5 years. After correction for mortality, the hazard of LTF was reversed from decreasing to increasing with time on ART. Younger age, higher baseline CD4 count, pregnancy and increasing calendar year were associated with higher true LTF. Mortality of patients LTF at 1, 12 and 24 months after their last visits was respectively 23.1%, 30.9% and 43.8%; 78.0% of deaths occurred during the first 3 months after last visit and 45.0% in patients on ART for 0 to 3 months. CONCLUSIONS: Mortality of patients LTF was high and occurred early after last clinic visit, especially in patients recently started on ART. Correction for these misclassified deaths revealed that the risk of true LTF increased over time. Research targeting groups at higher risk of LTF (youth, pregnant women and patients with higher CD4 counts) is needed.
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    The cost, cause and place of death in patients dying with HIV/AIDS and who have access to ART
    (2005) Hellström, Lize; Boulle, Andrew
    The study aimed to explore the causes of death, the costs involved in these deaths as well as the places where these deaths occurred. As all patients had access to ART once registered with the disease management company, AfA, most patients would have received ART, once the criteria for starting treatment were met.
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    The cost-effectiveness of Antiretroviral Treatment in Khayelitsha, South Africa - a primary data analysis
    (BioMed Central Ltd, 2006) Cleary, Susan; McIntyre, Di; Boulle, Andrew
    BACKGROUND:Given the size of the HIV epidemic in South Africa and other developing countries, scaling up antiretroviral treatment (ART) represents one of the key public health challenges of the next decade. Appropriate priority setting and budgeting can be assisted by economic data on the costs and cost-effectiveness of ART. The objectives of this research were therefore to estimate HIV healthcare utilisation, the unit costs of HIV services and the cost per life year (LY) and quality adjusted life year (QALY) gained of HIV treatment interventions from a provider's perspective. METHODS: Data on service utilisation, outcomes and costs were collected in the Western Cape Province of South Africa. Utilisation of a full range of HIV healthcare services was estimated from 1,729 patients in the Khayelitsha cohort (1,146 No-ART patient-years, 2,229 ART patient-years) using a before and after study design. Full economic costs of HIV-related services were calculated and were complemented by appropriate secondary data. ART effects (deaths, therapy discontinuation and switching to second-line) were from the same 1,729 patients followed for a maximum of 4 years on ART. No-ART outcomes were estimated from a local natural history cohort. Health-related quality of life was assessed on a sub-sample of 95 patients. Markov modelling was used to calculate lifetime costs, LYs and QALYs and uncertainty was assessed through probabilistic sensitivity analysis on all utilisation and outcome variables. An alternative scenario was constructed to enhance generalizability. RESULTS: Discounted lifetime costs for No-ART and ART were US$2,743 and US$9,435 over 2 and 8 QALYs respectively. The incremental cost-effectiveness ratio through the use of ART versus No-ART was US$1,102 (95% CI 1,043-1,210) per QALY and US$984 (95% CI 913-1,078) per life year gained. In an alternative scenario where adjustments were made across cost, outcome and utilisation parameters, costs and outcomes were lower, but the ICER was similar. CONCLUSION: Decisions to scale-up ART across sub-Saharan Africa have been made in the absence of incremental lifetime cost and cost-effectiveness data which seriously limits attempts to secure funds at the global level for HIV treatment or to set priorities at the country level. This article presents baseline cost-effectiveness data from one of the longest running public healthcare antiretroviral treatment programmes in Africa that could assist in enhancing efficient resource allocation and equitable access to HIV treatment.