The Aurum Institute

Johannesburg, South Africa

The Aurum Institute

Johannesburg, South Africa
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Noguchi L.M.,Johns Hopkins University | Hillier S.L.,University of Washington | Hillier S.L.,University of Pittsburgh | Bunge K.,University of Washington | And 12 more authors.
The Lancet HIV | Year: 2015

Background Several observational studies have reported that HIV-1 acquisition seems to be higher in women who use depot medroxyprogesterone acetate (DMPA) than in those who do not use hormonal contraception. We aimed to assess whether two injectable progestin-only contraceptives, DMPA and norethisterone enanthate (NET-EN), confer diff erent risks of HIV-1 acquisition. Methods We included data from South African women who used injectable contraception while participating in the VOICE study, a multisite, randomised, placebo-controlled trial that investigated the safety and effi cacy of three formulations of tenofovir for prevention of HIV-1 infection in women between Sept 9, 2009, and Aug 13, 2012. Women were assessed monthly for contraceptive use and incident infection. We estimated the diff erence in incident HIV-1 infection between DMPA and NET-EN users by Cox proportional hazards regression analyses in this prospective cohort. The VOICE trial is registered with ClinicalTrials.gov, NCT00705679. Findings 3141 South African women using injectable contraception were included in the present analysis: 1788 (56 9%) solely used DMPA, 1097 (34 9%) solely used NET-EN, and 256 (8 2%) used both injectable types at diff erent times during follow-up. During 2733 7 person-years of follow-up, 207 incident HIV-1 infections occurred (incidence 7 57 per 100 person-years, 95% CI 6 61-8 68). Risk of HIV-1 acquisition was higher among DMPA users (incidence 8 62 per 100 person-years, 95% CI 7 35-10 11) than among NET-EN users (5 67 per 100 person-years, 4 35-7 38; hazard ratio 1 53, 95% CI 1 12-2 08; p=0 007). This association persisted when adjusted for potential confounding variables (adjusted hazard ratio [aHR] 1 41, 95% CI 1 06-1 89; p=0 02). Among women seropositive for herpes simplex virus type 2 (HSV-2) at enrolment, the aHR was 2 02 (95% CI 1 26-3 24) compared with 1 09 (0 78-1 52) for HSV-2-seronegative women (Pinteraction=0 07). Interpretation Although moderate associations in observational analyses should be interpreted with caution, these fi ndings suggest that NET-EN might be an alternative injectable drug with a lower HIV risk than DMPA in high HIV-1 incidence settings where NET-EN is available.


Chersich M.F.,University of Witwatersrand | Chersich M.F.,Ghent University | Urban M.,Stellenbosch University | Olivier L.,Foundation for Alcohol Related Research FARR | And 4 more authors.
Alcohol and Alcoholism | Year: 2012

Aims: Prevalence of fetal alcohol spectrum disorders (FASDs) is remarkably high in several provinces of South Africa; yet population-level knowledge of the harms of maternal drinking remains low. In two heavily affected areas, we assessed effectiveness of interventions to heighten awareness of these harms and to alter social norms about drinking in pregnancy. Methods: FASD prevalence, maternal knowledge and drinking behaviours were investigated in two Northern Cape Province towns, before and after interventions which included highlighting FASD using local media and health promotion talks at health facilities. Independently, two dysmorphologists and a neuropsychometrist examined children at 9 and 18 months. Results: Pre-intervention maternal knowledge of alcohol harms was low and FASD prevalence 8.9% (72/809). Interventions reached high coverage and knowledge levels increased substantially. FASD prevalence was 5.7% post-intervention (43/751; P=0.02); 0.73 lower odds, controlling for maternal age and ethnicity (95% confidence interval=0.58-0.90). No change was detected in more severe FASD forms, but in the whole population, median dysmorphology scores reduced from 4 [inter-quartile range (IQR)=2-7] to 3 (IQR=1-6; P=0.002). Conclusion: This, the first prevention study using FASD outcomes, suggests that universal prevention might reduce FASD by ∼30% and have population-level effects. This supports intensifying universal interventions where knowledge of harms of maternal drinking is low. These efforts need to be accompanied by alcohol-dependence treatment to lower more severe FASD forms. © The Author 2011. Published by Oxford University Press on behalf of the Medical Council on Alcohol. All rights reserved.


PubMed | University of Witwatersrand, South African National Institute for Communicable Diseases, The Aurum Institute and London School of Hygiene and Tropical Medicine
Type: Journal Article | Journal: Transactions of the Royal Society of Tropical Medicine and Hygiene | Year: 2016

Adults being investigated for TB in South Africa experience high mortality, yet causes of death (CoD) are not well defined. We determined CoD in this population using verbal autopsy (VA), and compared HIV- and TB-associated CoD using physician-certified verbal autopsy (PCVA) and InterVA-4 software.All contactable consenting caregivers of participants who died during a trial comparing Xpert MTB/RIF to smear microscopy were interviewed using the WHO VA tool. CoD were assigned using PCVA and InterVA-4. Kappa statistic (K) and concordance correlation coefficient (CCC) were calculated for comparison.Among 231 deaths, relatives of 137 deceased were interviewed. Of the 137 deceased 76 (55.4%) were males, median age 41 years (IQR 33-50). PCVA assigned 70 (51.1%) TB immediate CoD (44 [62.8%] pulmonary TB; 26 [37.1%] extra-pulmonary TB); 21 (15.3%) HIV/AIDS-related; and 46 (33.5%) other CoD. InterVA-4 assigned 48 (35.0%) TB deaths; 49 (35.7%) HIV/AIDS-related deaths; and 40 (29.1%) other CoD. Agreement between PCVA and InterVA-4 CoD was slight at individual level (K=0.20; 95% CI 0.10-0.30) and poor at population level (CCC 0.67; 95% CI 0.38-0.99).TB and HIV are leading CoD among adults being investigated for TB. PCVA and InterVA agreement at individual level was slight and poor at population level. VA methodology needs further development where TB and HIV are common.


PubMed | University of Witwatersrand, Uganda Heart Institute, Makerere University, Nakaseke Hospital and The Aurum Institute
Type: Journal Article | Journal: BMC pediatrics | Year: 2017

Children with congenital heart disease are at increased risk of malnutrition. The aim of this study was to describe the prevalence of wasting, underweight and stunting among children with congenital heart disease attending Mulago National Referral Hospital, Uganda.A cross-sectional study among 194 children aged 0-15 years was conducted between August 2013 and March 2014. Anthropometric measurements and clinical assessments were carried out on all children. Anthropometric z-scores based on WHO 2007 reference ranges were generated for each child. Weight-for-height z-scores were generated for children 0-5years, weight-for-age z-scores for children 0-10 years, and height-for-age and BMI-for-age z-scores for all children. Risk factors associated with malnutrition were determined by Poisson regression.One hundred and forty five (74.7%) children were aged 0-5 years; and 111 of 194 (57.2%) were female. Forty five of 145 (31.5%) children aged 0-5 years were wasted; 77 of 181 (42.5%) children aged 0-10 years were underweight; 88 of 194 (45.4%) children were stunted; and 53 of 194 (27.3%) children were thin (BMI for age z score<-2). Moderate to severe anaemia (RR 1.11, 95% CI: 1.01-1.22) and moderate to severe heart failure (RR 1.24, 95% CI: 1.13-1.36) were associated with wasting and underweight respectively. Stunting was associated with moderate to severe heart failure (RR 1.11, 95% CI: 1.01-1.21) while thinness was associated with moderate to severe heart failure (RR 1.12, 95% CI: 1.04-1.21) and moderate to severe anaemia (RR 1.15, 95% CI: 1.06-1.25).Malnutrition is common in children with congenital heart disease, and is associated with anaemia and heart failure. There is need to integrate strategies to identify and manage malnutrition during the care of children with congenital heart disease.


PubMed | University of Amsterdam, University of Witwatersrand, The Aurum Institute and KNCV Tuberculosis Foundation
Type: | Journal: BMC infectious diseases | Year: 2016

Intensified case finding (ICF) and earlier antiretroviral therapy (ART) initiation are strategies to reduce burden of HIV-associated tuberculosis (TB). We describe incidence of and associated factors for TB among HIV-positive individuals with CD4 counts>350 cells/l in South Africa.Prospective cohort study of individuals recruited for a TB vaccine trial. Eligible individuals without prevalent TB were followed up at 6 and 12months after enrolment. Cox proportional hazards regression was used to determine factors associated with risk of incident TB.Six hundred thirty-four individuals were included in the analysis [80.9% female, 57.9% on ART, median CD4 count 562 cells/l (IQR 466-694 cells/l)]. TB incidence was 2.7 per 100 person-years (pyrs) (95% CI 1.6-4.4 per 100 pyrs) and did not differ significantly between those on ART and those not on ART [HR 0.65 (95% CI 0.24-1.81)]. Low body mass index (BMI <18.5kg/m(2)) was associated with incident TB [HR 3.87 (95% CI 1.09-13.73)]. Half of the cases occurred in the first 6months of follow up and may have been prevalent or incubating cases at enrolment.TB incidence was high and associated with low BMI. Intensified case finding for TB should be strengthened for all HIV positive individuals regardless of their CD4 count or ART status.


Johnston V.,London School of Hygiene and Tropical Medicine | Fielding K.,London School of Hygiene and Tropical Medicine | Charalambous S.,The Aurum Institute | Mampho M.,The Aurum Institute | And 5 more authors.
PLoS ONE | Year: 2012

Background: As antiretroviral treatment (ART) programmes in resource-limited settings mature, more patients are experiencing virological failure. Without resistance testing, deciding who should switch to second-line ART can be difficult. The consequences for second-line outcomes are unclear. In a workplace- and community-based multi-site programme, with 6-monthly virological monitoring, we describe outcomes and predictors of viral suppression on second-line, protease inhibitor-based ART. Methods: We used prospectively collected clinic data from patients commencing first-line ART between 1/1/03 and 31/12/08 to construct a study cohort of patients switched to second-line ART in the presence of a viral load (VL) ≥400 copies/ml. Predictors of VL<400 copies/ml within 15 months of switch were assessed using modified Poisson regression to estimate risk ratios. Results: 205 workplace patients (91.7% male; median age 43 yrs) and 212 community patients (38.7% male; median age 36 yrs) switched regimens. At switch compared to community patients, workplace patients had a longer duration of viraemia, higher VL, lower CD4 count, and higher reported non-adherence on first-line ART. Non-adherence was the reported reason for switching in a higher proportion of workplace patients. Following switch, 48.3% (workplace) and 72.0% (community) achieved VL<400, with non-adherence (17.9% vs. 1.4%) and virological rebound (35.6% vs. 13.2% with available measures) reported more commonly in the workplace programme. In adjusted analysis of the workplace programme, lower switch VL and younger age were associated with VL<400. In the community programme, shorter duration of viraemia, higher CD4 count and transfers into programme on ART were associated with VL<400. Conclusion: High levels of viral suppression on second-line ART can be, but are not always, achieved in multi-site treatment programmes with both individual- and programme-level factors influencing outcomes. Strategies to support both healthcare workers and patients during this switch period need to be evaluated; sub-optimal adherence, particularly in the workplace programme must be addressed. © 2012 Johnston et al.


Velen K.,The Aurum Institute | Lewis J.J.,The Aurum Institute | Lewis J.J.,London School of Hygiene and Tropical Medicine | Charalambous S.,The Aurum Institute | And 5 more authors.
PLoS ONE | Year: 2013

Background:Tenofovir (TDF) is part of the WHO recommended first-line antiretroviral therapy (ART); however, there are limited data comparing TDF to other nucleoside reverse transcriptase inhibitors in resource-limited-settings. Using a routine workplace and community-based ART cohort in South Africa, we assessed single drug substitution, HIV RNA suppression, CD4 count increase, loss-from-care, and mortality between TDF, stavudine (d4T) 30 mg dose, and zidovudine (AZT).Methods:In a prospective cohort study we included ART naïve patients aged ≥17 years-old who initiated ART containing TDF, d4T, or AZT between 2007 and 2009. For analysis of single drug substitutions we used a competing-risks time-to-event analysis; for loss-from-care, mixed-effect Poisson modeling; for HIV RNA suppression, competing-risks logistic regression; for CD4 count slope, mixed-effects linear regression; and for mortality, proportional hazards modeling.Results:Of 6,196 patients, the initial drug was TDF for 665 (11%), d4T for 4,179 (68%), and AZT for 1,352 (22%). During the first 6 months of ART, the adjusted hazard ratio for a single drug substitution was 2.3 for d4T (95% confidence interval [CI]: 0.27, 19) and 5.2 for AZT (95% CI: 1.1, 23), compared to TDF; whereas, after 6 months, it was 10 (95% CI: 5.8, 18) and 4.4 (95% CI: 2.5, 7.8) for d4T and AZT, respectively. Virologic suppression was similar by agent; however, CD4 count rise was lowest for AZT. The adjusted hazard ratio for loss-from-care, when compared to TDF, was 1.5 (95% CI: 1.1, 1.9) for d4T and 1.2 (95% CI: 1.1, 1.4) for AZT. The adjusted hazard ratio for mortality, when compared to TDF, was 2.7 (95% CI: 2.0, 3.5) and 1.4 (95% CI: 1.3, 1.5) and for d4T and AZT, respectively.Discussion:In routine care, TDF appeared to perform better than either d4T or AZT, most notably with less drug substitution and mortality than for either other agent. © 2013 Velen et al.


Wallis R.S.,The Aurum Institute
Frontiers in Microbiology | Year: 2016

The natural history of human infection with Mycobacterium tuberculosis (Mtb) is highly variable, as is the response to treatment of active tuberculosis. There is presently no direct means to identify individuals in whom Mtb infection has been eradicated, whether by a bactericidal immune response or sterilizing antimicrobial chemotherapy. Mathematical models can assist in such circumstances by measuring or predicting events that cannot be directly observed. The 3 models discussed in this review illustrate instances in which mathematical models were used to identify individuals with innate resistance to Mtb infection, determine the etiologic mechanism of tuberculosis in patients treated with tumor necrosis factor blockers, and predict the risk of relapse in persons undergoing tuberculosis treatment. These examples illustrate the power of various types of mathematic models to increase knowledge and thereby inform interventions in the present global tuberculosis epidemic. © 2016 Wallis.


Grant
Agency: GTR | Branch: MRC | Program: | Phase: Intramural | Award Amount: 371.25K | Year: 2016

Contact tracing in a household of person with TB is a well-known method for finding other people with TB earlier. Other benefits include the opportunity for HIV testing and linking people with HIV to health care. There are problems with the approach including high costs, difficulties with finding household members and differences in the number of people with TB found. Primary health care is currently being reorganised in South Africa. The new approach includes local outreach teams that deliver home and community based health services. Household contract tracing could be combined into these new teams. Our project uses different research methods to develop, implement and evaluate a combined model of household contact tracing, potentially using the new outreach teams. In Phase I we aim to understand more about the local outreach teams, and find out ways to help implement a new combined model household contact tracing. In Phase II, the new model will be implemented in three different districts in South Africa. In Phase III we will analyse our data to see if the new combined model is practicable, and can it find other household members with TB and allow an opportunity to test people for HIV and link people with HIV to health care. We will also collect costs of the new model.


PubMed | The Aurum Institute
Type: Journal Article | Journal: HIV medicine | Year: 2016

To assess the effect of chronic hepatitis B on survival and clinical complexity among people living with HIV following antiretroviral therapy (ART) initiation.We evaluated mortality and single-drug substitutions up to 3 years from ART initiation (median follow-up 2.75 years; interquartile range 2-3 years) among patients with and without chronic hepatitis B (CHB) enrolled in a workplace HIV care programme in South Africa.Mortality was increased for CHB patients with hepatitis B virus (HBV) DNA levels > 10 000 copies/mL (adjusted hazard ratio 3.1; 95% confidence interval 1.2-8.0) compared with non-CHB patients. We did not observe a similar difference between non-CHB patients and those with CHB and HBV DNA < 10 000 copies/mL (adjusted hazard ratio 0.70; 95% confidence interval 0.2-2.3). Single-drug substitutions occurred more frequently among coinfected patients regardless of HBV DNA level.Our findings suggest that CHB may increase mortality and complicate ART management.

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