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Browsing by Author "Davies, Mary-Ann"

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A comparison of death recording by health centres and civil registration in South Africans receiving antiretroviral treatment
(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 identity document (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 50 km 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.
Global temporal changes in the proportion of children with advanced disease at the start of combination antiretroviral therapy in an era of changing criteria for treatment initiation
(Wiley Open Access, 2018) Panayidou, Klea; Davies, Mary-Ann; Anderegg, Nanina; Egger, Matthias; The IeDEA; COHERE; PHACS; IMPAACT 219C Collaborations Writing Group
Introduction: The CD4 cell count and percent at initiation of combination antiretroviral therapy (cART) are measures of advanced HIV disease and thus are important indicators of programme performance for children living with HIV. In particular, World Health Organization (WHO) 2017 guidelines on advanced HIV disease noted that >80% of children aged <5 years started cART with WHO Stage 3 or 4 disease or severe immune suppression. We compared temporal trends in CD4 measures at cART start in children from low-, middle- and high-income countries, and examined the effect of WHO treatment initiation guidelines on reducing the proportion of children initiating cART with advanced disease. Methods: We included children aged <16 years from the International Epidemiology Databases to Evaluate acquired immunodeficiency syndrome (AIDS) (IeDEA) Collaboration (Caribbean, Central and South America, Asia-Pacific, and West, Central, East and Southern Africa), the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE), the North American Pediatric HIV/AIDS Cohort Study (PHACS) and International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) 219C study. Severe immunodeficiency was defined using WHO guidelines. We used generalized weighted additive mixed effect models to analyse temporal trends in CD4 measurements and piecewise regression to examine the impact of 2006 and 2010 WHO cART initiation guidelines. Results: We included 52,153 children from fourteen low-, eight lower middle-, five upper middle- and five high-income countries. From 2004 to 2013, the estimated percentage of children starting cART with severe immunodeficiency declined from 70% to 42% (low-income), 67% to 64% (lower middle-income) and 61% to 43% (upper middle-income countries). In highincome countries, severe immunodeficiency at cART initiation declined from 45% (1996) to 14% (2012). There were annual decreases in the percentage of children with severe immunodeficiency at cART initiation after the WHO guidelines revisions in 2006 (low-, lower middle- and upper middle-income countries) and 2010 (all countries). Conclusions: By 2013, less than half of children initiating cART had severe immunodeficiency worldwide. WHO treatment initiation guidelines have contributed to reducing the proportion of children and adolescents starting cART with advanced disease. However, considerable global inequity remains, in 2013, >40% of children in low- and middle-income countries started cART with severe immunodeficiency compared to <20% in high-income countries.
HIV viral load as an independent risk factor for tuberculosis in South Africa : collaborative analysis of cohort studies
(Wiley Open Access, 2017) Fenner, Lukas; Atkinson, Andrew; Boulle, Andrew; Fox, Matthew P.; Prozesky, Hans; Zurcher, Kathrin; Ballif, Marie; Furrer, Hansjakob; Zwahlen, Marcel; Davies, Mary-Ann; Egger, Matthias
Introduction: Chronic immune activation due to ongoing HIV replication may lead to impaired immune responses against opportunistic infections such as tuberculosis (TB). We studied the role of HIV replication as a risk factor for incident TB after starting antiretroviral therapy (ART). Methods: We included all HIV-positive adult patients ( 16 years) in care between 2000 and 2014 at three ART programmes in South Africa. Patients with previous TB were excluded. Missing CD4 cell counts and HIV-RNA viral loads at ART start (baseline) and during follow-up were imputed. We used parametric survival models to assess TB incidence (pulmonary and extrapulmonary) by CD4 cell and HIV-RNA levels, and estimated the rate ratios for TB by including age, sex, baseline viral loads, CD4 cell counts, and WHO clinical stage in the model. We also used Poisson general additive regression models with time-updated CD4 and HIV-RNA values, adjusting for age and sex. Results: We included 44,260 patients with a median follow-up time of 2.7 years (interquartile range [IQR] 1.0–5.0); 3,819 incident TB cases were recorded (8.6%). At baseline, the median age was 34 years (IQR 28–41); 30,675 patients (69.3%) were female. The median CD4 cell count was 156 cells/μL (IQR 79–229) and the median HIV-RNA viral load 58,000 copies/mL (IQR 6,000–240,000). Overall TB incidence was 26.2/1,000 person-years (95% confidence interval [CI] 25.3–27.0). Compared to the lowest viral load category (0–999 copies/mL), the adjusted rate ratio for TB was 1.41 (95% CI 1.15–1.75, p < 0.001) in the highest group (>10,000 copies/mL). Time-updated analyses for CD4/HIV-RNA confirmed the association of viral load with the risk for TB. Conclusions: Our results indicate that ongoing HIV replication is an important risk factor for TB, regardless of CD4 cell counts, and underline the importance of early ART start and retention on ART.
Lamivudine monotherapy as a holding regimen for HIV-positive children
(Public Library of Science, 2018-10-11) Patten, Gabriela; Bernheime, Jonathan; Fairlie, Lee; Rabie, Helena; Sawry, Shobna; Technau, Karl; Eley, Brian; Davies, Mary-Ann
Background: In resource-limited settings holding regimens, such as lamivudine monotherapy (LM), are used to manage HIV-positive children failing combination antiretroviral therapy (cART) to mitigate the risk of drug resistance developing, whilst adherence barriers are addressed or when access to second- or third-line regimens is restricted. We aimed to investigate characteristics of children placed on LM and their outcomes. Methods: We describe the characteristics of children (age <16 years at cART start) from 5 IeDEA-SA cohorts with a record of LM during their treatment history. Among those on LM for >90 days we describe their immunologic outcomes on LM and their immunologic and virologic outcomes after resuming cART. Findings: We included 228 children in our study. At LM start their median age was 12.0 years (IQR 7.3–14.6), duration on cART was 3.6 years (IQR 2.0–5.9) and median CD4 count was 605.5 cells/μL (IQR 427–901). Whilst 110 (48%) had no prior protease inhibitor (PI)-exposure, of the 69 with recorded PI-exposure, 9 (13%) patients had documented resistance to all PIs. After 6 months on LM, 70% (94/135) experienced a drop in CD4, with a predicted average CD4 decline of 46.5 cells/μL (95% CI 37.7–55.4). Whilst on LM, 46% experienced a drop in CD4 to <500 cells/μL, 18 (8%) experienced WHO stage 3 or 4 events, and 3 children died. On resumption of cART the average gain in CD4 was 15.65 cells/uL per month and 66.6% (95% CI 59.3–73.7) achieved viral suppression (viral load <1000) at 6 months after resuming cART. Interpretation: Most patients experienced immune decline on LM. Its use should be avoided in those with low CD4 counts, but restricted use may be necessary when treatment options are limited. Managing children with virologic failure will continue to be challenging until more treatment options and better adherence strategies are available.
Lower birth weight-for-age and length-for-age z-scores in infants with in-utero HIV and ART exposure : a prospective study in Cape Town, South Africa
(BMC (part of Springer Nature), 2021-05-04) Nyemba, Dorothy C.; Kalk, Emma; Madlala, Hlengiwe P.; Malaba, Thokozile R.; Slogrove, Amy L.; Davies, Mary-Ann; Boulle, Andrew; Myer, Landon; Powis, Kathleen M
Background: Successful scale-up of antiretroviral therapy (ART) during pregnancy has minimized infant HIV acquisition, and over 1 million infants are born HIV-exposed but uninfected (HEU), with an increasing proportion also exposed in utero to maternal ART. While benefits of ART in pregnancy outweigh risks, some studies have reported associations between in utero ART exposure and impaired fetal growth, highlighting the need to identify the safest ART regimens for use in pregnancy. Methods: We compared birth anthropometrics of infants who were HEU with those HIV-unexposed (HU) in Cape Town, South Africa. Pregnant women had gestational age assessed by ultrasound at enrolment. Women living with HIV were on ART (predominately tenofovir-emtricitabine-efavirenz) either prior to conception or initiated during pregnancy. Birth weights and lengths were converted to weight-for-age (WAZ) and length-for-age (LAZ) z-scores using Intergrowth-21st software. Linear regression was used to compare mean z-scores adjusting for maternal and pregnancy characteristics. Results: Among 888 infants, 49% (n = 431) were HEU and 51% (n = 457) HU. Of 431 HEU infants, 62% (n = 268) were exposed to HIV and antiretrovirals (ARVs) from conception and 38% (n = 163) were exposed to ARVs during gestation but after conception (median fetal ARV exposure of 21 weeks [IQR; 17–26]). In univariable analysis, infants who were HEU had lower mean WAZ compared with HU [β = − 0.15 (95% Confidence Interval (CI): − 0.28, − 0.020)]. After adjustment for maternal age, gravidity, alcohol use, marital and employment status the effect remained [adjusted β − 0.14 (95%CI: − 0.28, − 0.01]. Similar differences were noted for mean LAZ in univariable [β − 0.20 (95%CI: − 0.42, − 0.01] but not multivariable analyses [adjusted β − 0.18 (95%CI: − 0.41, + 0.04] after adjusting for the same variables. Mean WAZ and LAZ did not vary by in utero ARV exposure duration among infants who were HEU. Conclusion: In a cohort with high prevalence of ART exposure in pregnancy, infants who were HEU had lower birth WAZ compared with those HU. Studies designed to identify the mechanisms and clinical significance of these disparities, and to establish the safest ART for use in pregnancy are urgently needed.
Monitoring the South African National Antiretroviral Treatment Programme, 2003-2007 : the IeDEA Southern Africa collaboration
(Health and Medical Publishing Group (HMPG), 2009-09) Cornell, Morne; 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, Andrew
Objectives. 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 characterise patients accessing these services; and to describe changes in services and patients from 2003 to 2007. Design and setting. Multi-cohort study of 11 ART programmes in Gauteng, Western Cape, Free State and KwaZulu-Natal. Subjects. 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 age (interquartile range) was 35.0 years (29.8-41.4) and 42.5 months (14.7-82.5), respectively. Of adults, 68% were female. The median CD4 cell count was 102 cells/μl (44-164) and was lower among males than females (86, 34-150 v. 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 increased enrolment over time. Late diagnosis and ART initiation, especially of men and children, need attention. Investment in sentinel sites will ensure good individual-level data while freeing most sites to continue with simplified reporting.
Outcomes of the South African national antiretroviral treatment programme for children : the IeDEA southern Africa collaboration
(Health and Medical Publishing Group (HMPG), 2009-10) Davies, Mary-Ann; Keiser, Olivia; Technau, Karl; Eley, Brian; Rabie, Helena; Van Cutsem, Gilles; Giddy, Janet; Wood, Robin; Boulle, Andrew; Egger, Matthias; Moultrie, Harry
Objectives. To assess paediatric antiretroviral treatment (ART) outcomes and their associations from a collaborative cohort representing 20% of the South African national treatment programme. Design and setting. Multi-cohort study of 7 public sector paediatric ART programmes in Gauteng, Western Cape and. KwaZulu-Natal provinces. Subjects. ART-naïve children (?16 years) who commenced treatment with ≥3 antiretroviral drugs before March 2008. Outcome measures. Time to death or loss to follow-up were assessed using the Kaplan-Meier method. Associations between baseline characteristics and mortality were assessed with Cox proportional hazards models stratified by site. Immune status, virological suppression and growth were described in relation to duration of ART. Results. The median (interquartile range) age of 6 078 children with 9 368 child-years of follow-up was 43 (15 - 83) months, with 29% being <18 months. Most were severely ill at ART initiation. More than 75% of children were appropriately monitored at 6-monthly intervals with viral load suppression (<400 copies/ml) being 80% or above throughout 36 months of treatment. Mortality and retention in care at 3 years were 7.7% (95% confidence interval 7.0 - 8.6%) and 81.4% (80.1-82.6%), respectively. Together with young age, all markers of disease severity (low weight-for-age z-score, high viral load, severe immune suppression, stage 3/4 disease and anaemia) were independently associated with mortality. Conclusions. Dramatic clinical benefit for children accessing the national ART programme is demonstrated. Higher mortality in infants and those with advanced disease highlights the need for early diagnosis of HIV infection and commencement of ART.
Twelve-year mortality in adults initiating antiretroviral therapy in South Africa
(Wiley Open Access, 2018) Cornell, Morna; Johnson, Leigh F.; Wood, Robin; Tanser, Frank; Fox, Matthew P.; Prozesky, Hans; Schomaker, Michael; Egger, Matthias; Davies, Mary-Ann; Boulle, Andrew
Introduction: South Africa has the largest number of individuals living with HIV and the largest antiretroviral therapy (ART) programme worldwide. In September 2016, ART eligibility was extended to all 7.1 million HIV-positive South Africans. To ensure that further expansion of services does not compromise quality of care, long-term outcomes must be monitored. Few studies have reported long-term mortality in resource-constrained settings, where mortality ascertainment is challenging. Combining site records with data linked to the national vital registration system, sites in the International Epidemiology Databases to Evaluate AIDS Southern Africa collaboration can identify >95% of deaths in patients with civil identification numbers (IDs). This study used linked data to explore long-term mortality and viral suppression among adults starting ART in South Africa. Methods: The study was a cohort analysis of routine data on adults with IDs starting ART 2004–2015 in five large ART cohorts. Mortality was estimated overall and by gender using the Kaplan-Meier estimator and Cox’s proportional hazards regression. Standardized mortality ratios (SMRs) were calculated by dividing observed numbers of deaths by numbers expected if patients had been HIV-negative. Viral suppression in patients with viral loads (VLs) in their last year of followup was the secondary outcome. Results: Among 72,812 adults followed for 350,376 person years (pyrs), the crude mortality rate was 3.08 (95% CI 3.02– 3.14)/100 pyrs. Patients were predominantly female (67%) and the percentage of men initiating ART did not increase. Cumulative mortality 12 years after ART initiation was 23.9% (33.4% male and 19.4% female). Mortality peaked in patients enrolling in 2007–2009 and was higher in men than women at all durations. Observed mortality rates were higher than HIVnegative mortality, decreasing with duration. By 48 months, observed mortality was close to that in the HIV-negative population, and SMRs were similar for all baseline CD4 strata. Three-quarters of patients had VLs in their last year, and 86% of these were virally suppressed. Conclusions: The South African ART programme has shown a remarkable ability to initiate and manage patients successfully over 12 years, despite rapid expansion. With further scale-up, testing and initiating men on ART must be a national priority.
When to start antiretroviral therapy in children aged 2-5 years : a collaborative causal modelling analysis of cohort studies from Southern Africa
(PLoS, 2013-11-19) Schomaker, Michael; Egger, Matthias; Ndirangu, James; Moultrie, Harri; Technau, Karl; Cox, Vivian; Giddy, Janet; Phiri, Sam; Chimbetete, Cleophas; Wood, Robin; Gsponer, Thomas; Moore, Carolyn Bolton; Rabie, Helena; Eley, Brian; Muhe, Lulu; Penazzato, Martina; Essajee, Shaffiq; Keiser, Olivia; Davies, Mary-Ann
Background There is limited evidence on the optimal timing of antiretroviral therapy (ART) initiation in children 2–5 y of age. We conducted a causal modelling analysis using the International Epidemiologic Databases to Evaluate AIDS–Southern Africa (IeDEA-SA) collaborative dataset to determine the difference in mortality when starting ART in children aged 2–5 y immediately (irrespective of CD4 criteria), as recommended in the World Health Organization (WHO) 2013 guidelines, compared to deferring to lower CD4 thresholds, for example, the WHO 2010 recommended threshold of CD4 count <750 cells/mm3 or CD4 percentage (CD4%) <25%. Methods and Findings ART-naïve children enrolling in HIV care at IeDEA-SA sites who were between 24 and 59 mo of age at first visit and with ≥1 visit prior to ART initiation and ≥1 follow-up visit were included. We estimated mortality for ART initiation at different CD4 thresholds for up to 3 y using g-computation, adjusting for measured time-dependent confounding of CD4 percent, CD4 count, and weight-for-age z-score. Confidence intervals were constructed using bootstrapping. The median (first; third quartile) age at first visit of 2,934 children (51% male) included in the analysis was 3.3 y (2.6; 4.1), with a median (first; third quartile) CD4 count of 592 cells/mm3 (356; 895) and median (first; third quartile) CD4% of 16% (10%; 23%). The estimated cumulative mortality after 3 y for ART initiation at different CD4 thresholds ranged from 3.4% (95% CI: 2.1–6.5) (no ART) to 2.1% (95% CI: 1.3%–3.5%) (ART irrespective of CD4 value). Estimated mortality was overall higher when initiating ART at lower CD4 values or not at all. There was no mortality difference between starting ART immediately, irrespective of CD4 value, and ART initiation at the WHO 2010 recommended threshold of CD4 count <750 cells/mm3 or CD4% <25%, with mortality estimates of 2.1% (95% CI: 1.3%–3.5%) and 2.2% (95% CI: 1.4%–3.5%) after 3 y, respectively. The analysis was limited by loss to follow-up and the unavailability of WHO staging data. Conclusions The results indicate no mortality difference for up to 3 y between ART initiation irrespective of CD4 value and ART initiation at a threshold of CD4 count <750 cells/mm3 or CD4% <25%, but there are overall higher point estimates for mortality when ART is initiated at lower CD4 values.
Where do HIV-infected adolescents go after transfer? – Tracking transition/transfer of HIV-infected adolescents using linkage of cohort data to a health information system platform
(Wiley Open Access, 2017) Davies, Mary-Ann; Tsondai, Priscilla; Tiffin, Nicki; Eley, Brian; Rabie, Helena; Euvrard, Jonathan; Orrell, Catherine; Prozesky, Hans; Wood, Robin; Cogill, Dolphina; Haas, Andreas D.; Sohn, Annette H.; Boulle, Andrew
Introduction: To evaluate long-term outcomes in HIV-infected adolescents, it is important to identify ways of tracking outcomes after transfer to a different health facility. The Department of Health (DoH) in the Western Cape Province (WCP) of South Africa uses a single unique identifier for all patients across the health service platform. We examined adolescent outcomes after transfer by linking data from four International epidemiology Databases to Evaluate AIDS Southern Africa (IeDEA-SA) cohorts in the WCP with DoH data. Methods: We included adolescents on antiretroviral therapy who transferred out of their original cohort from 10 to 19 years of age between 2004 and 2014. The DoH conducted the linkage separately for each cohort and linked anonymized data were then combined. The primary outcome was successful transfer defined as having a patient record at a facility other than the original facility after the transfer date. Secondary outcomes included the proportion of patients retained, with HIV-RNA <400 copies/ml and CD4 > 500 cells/μl at 1, 2 and 3 years post-transfer. Results: Of 460 adolescents transferred out (53% female), 72% transferred at 10–14 years old, and 79% transferred out of tertiary facilities. Overall, 81% of patients transferred successfully at a median (interquartile range) of 56 (27–134) days following transfer date; 95% reached the transfer site <18 months after transfer out. Among those transferring successfully, the proportion retained decreased from 1 to 3 years post-transfer (90–84%). There was no significant difference between transfer and 1–3 years post-transfer in the proportion of retained adolescents with HIV-RNA <400 copies/ml and CD4 > 500 cells/μl except for HIV-RNA <400 copies/ml at 3 years (86% vs. 75%; p = 0.007). The proportion virologically suppressed and with CD4 > 500 cells/μl was significantly lower at 1 and 2 years post-transfer in those transferring at 15–19 vs. 10–14 years of age. Using laboratory data alone over-estimated time to successful transfer. Conclusions: Linking cohort data to health information system data allowed efficient assessment of post-transfer outcomes. Although >80% of adolescents transferred successfully with nearly 85% of them retained for 3 years post-transfer, the decline in the proportion virologically suppressed and poorer outcomes in older adolescents are concerns.

Browsing by Author "Davies, Mary-Ann"

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