Browsing by Author "Ayles, Helen"

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    Annual risk of tuberculous infection using different methods in communities with a high prevalence of TB and HIV in Zambia and South Africa
    (Public Library of Science (PLOS), 2009-11) Shanaube, Kwame; Sisminidis, Charalambos; Ayles, Helen; Beyers, Nulda; Schaap, Ab; Lawrence, Katherine-Anne; Barker, Annie; Godfrey-Faussett, Peter
    Background: The annual risk of tuberculous infection (ARTI) is a key epidemiological indicator of the extent of transmission in a community. Several methods have been suggested to estimate the prevalence of tuberculous infection using tuberculin skin test data. This paper explores the implications of using different methods to estimate prevalence of infection and ARTI. The effect of BCG vaccination on these estimates is also investigated. Methodology/Principal Findings: Tuberculin surveys among school children in 16 communities in Zambia and 8 in South Africa (SA) were performed in 2005, as part of baseline data collection and for randomisation purposes of the ZAMSTAR study. Infection prevalence and ARTI estimates were calculated using five methods: different cut-offs with or without adjustments for sensitivity, the mirror method, and mixture analysis. A total of 49,835 children were registered for the surveys, of which 25,048 (50%) had skin tests done and 22,563 (90%) of those tested were read. Infection prevalence was higher in the combined SA than Zambian communities. The mirror method resulted in the least difference of 7.8%, whereas that estimated by the cut-off methods varied from 12.2% to 17.3%. The ARTI in the Zambian and SA communities was between 0.8% and 2.8% and 2.5% and 4.2% respectively, depending on the method used. In the SA communities, the ARTI was higher among the younger children. BCG vaccination had little effect on these estimates. Conclusions/Significance: ARTI estimates are dependent on the calculation method used. All methods agreed that there were substantial differences in infection prevalence across the communities, with higher rates in SA. Although TB notification rates have increased over the past decades, the difference in cumulative exposure between younger and older children is less dramatic and a rise in risk of infection in parallel with the estimated incidence of active tuberculosis cannot be excluded. © 2009 Shanaube et al.
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    The association of hyperglycaemia with prevalent tuberculosis : a population-based cross-sectional study
    (BioMed Central, 2016) Bailey, Sarah Lou; Ayles, Helen; Beyers, Nulda; Godfrey-Faussett, Peter; Muyoyeta, Monde; Du Toit, Elizabeth; Yudkin, John S.; Floyd, Sian
    Background: Systematic reviews suggest that the incidence of diagnosed tuberculosis is two- to- three times higher in those with diabetes mellitus than in those without. Few studies have previously reported the association between diabetes or hyperglycaemia and the prevalence of active tuberculosis and none in a population-based study with microbiologically-defined tuberculosis. Most have instead concentrated on cases of diagnosed tuberculosis that present to health facilities. We had the opportunity to measure glycaemia alongside prevalent tuberculosis. A focus on prevalent tuberculosis enables estimation of the contribution of hyperglycaemia to the population prevalence of tuberculosis. Methods: A population-based cross-sectional study was conducted among adults in 24 communities from Zambia and the Western Cape (WC) province of South Africa. Prevalent tuberculosis was defined by the presence of a respiratory sample that was culture positive for M. tuberculosis. Glycaemia was measured by random blood glucose (RBG) concentration. Association with prevalent tuberculosis was explored across the whole spectrum of glycaemia. Results: Among 27,800 Zambian and 11,367 Western Cape participants, 4,431 (15.9%) and 1,835 (16.1%) respectively had a RBG concentration ≥7.0 mmol/L, and 405 (1.5%) and 322 (2.8%) respectively had a RBG concentration ≥11. 1 mmol/L. In Zambia, the prevalence of tuberculosis was 0 · 5% (142/27,395) among individuals with RBG concentration <11.1 mmol/L and also ≥11.1 mmol/L (2/405); corresponding figures for WC were 2 · 5% (272/11,045) and 4 · 0% (13/322). There was evidence for a positive linear association between hyperglycaemia and pulmonary prevalent tuberculosis. Taking a RBG cut-off 11.1 mmol/L, a combined analysis of data from Zambian and WC communities found evidence of association between hyperglycaemia and TB (adjusted odds ratio = 2 · 15, 95% CI [1 · 17–3 · 94]). The population attributable fraction of prevalent tuberculosis to hyperglycaemia for Zambia and WC combined was 0.99% (95% CI 0 · 12%–1.85%) for hyperglycaemia with a RBG cut-off of 11.1 mmol/L. Conclusions: This study demonstrates an association between hyperglycaemia and prevalent tuberculosis in a large population-based survey in Zambia and Western Cape. However, assuming causation, this association contributes little to the prevalence of TB in these populations.
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    Attrition when providing antiretroviral treatment at CD4 counts >500cells/μL at three government clinics included in the HPTN 071 (PopART) trial in South Africa
    (Public Library of Science, 2018-04-19) Bock, Peter; Fatti, Geoffrey; Ford, Nathan; Jennings, Karen; Kruger, James; Gunst, Colette; Louis, Francoise; Grobbelaar, Nelis; Shanaube, Kwame; Floyd, Sian; Grimwood, Ashraf; Hayes, Richard; Ayles, Helen; Fidler, Sarah; Beyers, N. (Nulda)
    Introduction: WHO recommends antiretroviral treatment (ART) for all HIV-positive individuals. This study evaluated the association between baseline CD4 count and attrition in a cohort of HIV positive adults initiating ART at three department of health (DOH) clinics routinely providing ART at baseline CD4 counts >500cells/μL for the HPTN 071 (PopART) trial. Methods: All clients attending the DOH clinics were managed according to standard care guidelines with the exception that those starting ART outside of pertinent local guidelines signed research informed consent. DOH data on all HIV-positive adult clients recorded as having initiated ART between January 2014 and November 2015 at the three study clinics was analysed. Attrition, included clients lost to follow up or died, and was defined as ‘being three or more months late for an antiretroviral pharmacy pick-up appointment’. All clients were followed until attrition, transfer out or end May 2016. Results: A total of 2423 clients with a median baseline CD4 count of 328 cells/μL (IQR 195–468) were included of whom 631 (26.0%) experienced attrition and 140 (5.8%) were TFO. Attrition was highest during the first six months of ART (IR 38.3/100 PY; 95% CI 34.8–42.1). Higher attrition was found amongst those with baseline CD4 counts > 500 cells/μL compared to those with baseline CD4 counts of 0–500 cells/μL (aHR 1.26, 95%CI 1.05 to 1.52) This finding was confirmed on subset analyses when restricted to individuals non-pregnant at baseline and when restricted to individuals with follow up of > 12months. Conclusions:Attrition in this study was high, particularly during the first six months of treatment. Attrition was highest amongst clients starting ART at baseline CD4 counts > 500 cells/μL. Strategies to improve retention amongst ART clients, particularly those starting ART at baseline CD4 counts >500cells/μL, need strengthening. Improved monitoring of clients moving in and out of ART care and between clinics will assist in better understanding attrition and ART coverage in high burden countries.
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    Better virological outcomes among people living with human immunodeficiency virus (HIV) initiating early antiretroviral Tteatment (CD4 Counts ≥500 Cells/µL) in the HIV Prevention Trials Network 071 (PopART) trial in South Africa
    (Oxford University Press, 2020-01-16) Fatti, Geoffrey; Grimwood, Ashraf; Nachega, Jean B.; Nelson, Jenna A.; LaSorda, Kelsea; van Zyl, Gert; Grobbelaar, Nelis; Ayles, Helen; Hayes, Richard; Beyers, Nulda; Fidler, Sarah; Bock, Peter
    Background: There have been concerns about reduced adherence and human immunodeficiency virus (HIV) virological suppression (VS) among clinically well people initiating antiretroviral therapy (ART) with high pre-ART CD4 cell counts. We compared virological outcomes by pre-ART CD4 count, where universal ART initiation was provided in the HIV Prevention Trials Network 071 (PopART) trial in South Africa prior to routine national and international implementation. Methods: This prospective cohort study included adults initiating ART at facilities providing universal ART since January 2014. VS (<400 copies/mL), confirmed virological failure (VF) (2 consecutive viral loads >1000 copies/mL), and viral rebound were compared between participants in strata of baseline CD4 cell count. Results: The sample included 1901 participants. VS was ≥94% among participants with baseline CD4 count ≥500 cells/µL at all 6-month intervals to 30 months. The risk of an elevated viral load (≥400 copies/mL) was independently lower among participants with baseline CD4 count ≥500 cells/µL (3.3%) compared to those with CD4 count 200-499 cells/µL (9.2%) between months 18 and 30 (adjusted relative risk, 0.30 [95% confidence interval, .12-.74]; P = .010). The incidence rate of VF was 7.0, 2.0, and 0.5 per 100 person-years among participants with baseline CD4 count <200, 200-499, and ≥500 cells/µL, respectively (P < .0001). VF was independently lower among participants with baseline CD4 count ≥500 cells/µL (adjusted hazard ratio [aHR], 0.23; P = .045) and 3-fold higher among those with baseline CD4 count <200 cells/µL (aHR, 3.49; P < .0001). Conclusions: Despite previous concerns, participants initiating ART with CD4 counts ≥500 cells/µL had very good virological outcomes, being better than those with CD4 counts 200-499 cells/µL. Clinical trials registration: NCT01900977.
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    Cost-per-diagnosis as a metric for monitoring cost-effectiveness of HIV testing programmes in low-income settings in southern Africa : health economic and modelling analysis
    (International AIDS Society, 2019) Phillips, Andrew N.; Cambiano, Valentina; Nakagawa, Fumiyo; Bansi-Matharu, Loveleen; Wilson, David; Jani, Ilesh; Apollo, Tsitsi; Sculpher, Mark; Hallett, Timothy; Kerr, Cliff; Van Oosterhout, J.; Eaton, Jeffrey W.; Estill, Janne; Williams, Brian; Doi, Naoko; Cowan, Frances; Keiser, Olivia; Ford, Deborah; Hatzold, Karin; Barnabas, Ruanne; Ayles, Helen; Meyer-Rath, Gesine; Nelson, Lisa; Johnson, Cheryl; Baggaley, Rachel; Fakoya, Ade; Jahn, Andreas; Revill, Paul
    Introduction: As prevalence of undiagnosed HIV declines, it is unclear whether testing programmes will be cost-effective. To guide their HIV testing programmes, countries require appropriate metrics that can be measured. The cost-per-diagnosis is potentially a useful metric. Methods: We simulated a series of setting-scenarios for adult HIV epidemics and ART programmes typical of settings in southern Africa using an individual-based model and projected forward from 2018 under two policies: (i) a minimum package of “core” testing (i.e. testing in pregnant women, for diagnosis of symptoms, in sex workers, and in men coming forward for circumcision) is conducted, and (ii) core-testing as above plus additional testing beyond this (“additionaltesting”), for which we specify different rates of testing and various degrees to which those with HIV are more likely to test than those without HIV. We also considered a plausible range of unit test costs. The aim was to assess the relationship between cost-per-diagnosis and the incremental cost-effectiveness ratio (ICER) of the additional-testing policy. The discount rate used in the base case was 3% per annum (costs in 2018 U.S. dollars). Results: There was a strong graded relationship between the cost-per-diagnosis and the ICER. Overall, the ICER was below $500 per-DALY-averted (the cost-effectiveness threshold used in primary analysis) so long as the cost-per-diagnosis was below $315. This threshold cost-per-diagnosis was similar according to epidemic and programmatic features including the prevalence of undiagnosed HIV, the HIV incidence and a measure of HIV programme quality (the proportion of HIV diagnosed people having a viral load <1000 copies/mL). However, restricting to women, additional-testing did not appear cost-effective even at a cost-per-diagnosis of below $50, while restricting to men additional-testing was cost-effective up to a cost-per-diagnosis of $585. The threshold cost per diagnosis for testing in men to be cost-effective fell to $256 when the cost-effectiveness threshold was $300 instead of $500, and to $81 when considering a discount rate of 10% per annum. Conclusions: For testing programmes in low-income settings in southern African there is an extremely strong relationship between the cost-per-diagnosis and the cost-per-DALY averted, indicating that the cost-per-diagnosis can be used to monitor the cost-effectiveness of testing programmes.
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    Development and validation of a prediction model for active tuberculosis case finding among HIV-negative/unknown populations
    (Nature Research (part of Springer Nature), 2019) Shih, Yun-Ju; Ayles, Helen; Lonnroth, Knut; Claassens, Mareli; Lin, Hsien-Ho
    ENGLISH ABSTRACT: A prediction model of prevalent pulmonary tuberculosis (TB) in HIV negative/unknown individuals was developed to assist systematic screening. Data from a large TB screening trial were used. A multivariable logistic regression model was developed in the South African (SA) training dataset, using TB symptoms and risk factors as predictors. The model was converted into a scoring system for risk stratification and was evaluated in separate SA and Zambian validation datasets. The number of TB cases were 355, 176, and 107 in the SA training, SA validation, and Zambian validation datasets respectively. The area under curve (AUC) of the scoring system was 0·68 (95% CI 0·64-0·72) in the SA validation set, compared to prolonged cough (0·58, 95% CI 0·54-0·62) and any TB symptoms (0·6, 95% CI 0·56–0·64). In the Zambian dataset the AUC of the scoring system was 0·66 (95% CI 0·60–0·72). In the cost-effectiveness analysis, the scoring system dominated the conventional strategies. The cost per TB case detected ranged from 429 to 1,848 USD in the SA validation set and from 171 to 10,518 USD in the Zambian dataset. The scoring system may help targeted TB case finding under budget constraints.
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    Development of parallel measures to assess HIV stigma and discrimination among people living with HIV, community members and health workers in the HPTN 071 (PopART) trial in Zambia and South Africa
    (International AIDS Society, 2019-10) Stangl, Anne L.; Lilleston, Pamela; Mathema, Hlengani; Pliakas, Triantafyllos; Krishnaratne, Shari; Sievwright, Kirsty; Bell-Mandla, Nomhle; Vermaak, Redwaan; Mainga, Tila; Steinhaus, Mara; Donnell, Deborah; Schaap, Ab; Bock, Peter; Ayles, Helen; Hayes, Richard; Hoddinott, Graeme; Bond, Virginia; Hargreaves, James R.
    Introduction: Integrating standardized measures of HIV stigma and discrimination into research studies of emerging HIV prevention approaches could enhance uptake and retention of these approaches, and care and treatment for people living with HIV (PLHIV), by informing stigma mitigation strategies. We sought to develop a succinct set of measures to capture key domains of stigma for use in research on HIV prevention technologies. Methods: From 2013 to 2015, we collected baseline data on HIV stigma from three populations (PLHIV (N = 4053), community members (N = 5782) and health workers (N = 1560)) in 21 study communities in South Africa and Zambia participating in the HPTN 071 (PopART) cluster-randomized trial. Forty questions were adapted from a harmonized set of measures developed in a consultative, global process. Informed by theory and factor analysis, we developed seven scales, with values ranging from 0 to 3, based on a 4-point agreement Likert, and calculated means to assess different aspects of stigma. Higher means reflected more stigma. We developed two measures capturing percentages of PLHIV who reported experiencing any stigma in communities or healthcare settings in the past 12 months. We validated our measures by examining reliability using Cronbach's alpha and comparing the distribution of responses across characteristics previously associated with HIV stigma. Results: Thirty-five questions ultimately contributed to seven scales and two experience measures. All scales demonstrated acceptable to very good internal consistency. Among PLHIV, a scale captured internalized stigma, and experience measures demonstrated that 22.0% of PLHIV experienced stigma in the community and 7.1% in healthcare settings. Three scales for community members assessed fear and judgement, perceived stigma in the community and perceived stigma in healthcare settings. Similarly, health worker scales assessed fear and judgement, perceived stigma in the community and perceived co-worker stigma in healthcare settings. A higher proportion of community members and health workers reported perceived stigma than the proportion of PLHIV who reported experiences of stigma. Conclusions: We developed novel, valid measures that allowed for triangulation of HIV stigma across three populations in a large-scale study. Such comparisons will illuminate how stigma influences and is influenced by programmatic changes to HIV service delivery over time.
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    Differences in health-related quality of life between HIV-positive and HIV-negative people in Zambia and South Africa : a cross-sectional baseline survey of the HPTN 071 (PopART) trial
    (Elsevier, 2017) Thomas, Ranjeeta; Burger, Ronelle; Harper, Abigail; Kanema, Sarah; Mwenge, Lawrence; Vanqa, Nosivuyile; Bell-Mandla, Nomtha; Smith, Peter C.; Floyd, Sian; Bock, Peter; Ayles, Helen; Beyers, Nulda; Donnell, Deborah; Fidler, Sarah; Hayes, Richard; Hauck, Katharina
    Background: The life expectancy of HIV-positive individuals receiving antiretroviral therapy (ART) is approaching that of HIV-negative people. However, little is known about how these populations compare in terms of health-related quality of life (HRQoL). We aimed to compare HRQoL between HIV-positive and HIV-negative people in Zambia and South Africa. Methods: As part of the HPTN 071 (PopART) study, data from adults aged 18–44 years were gathered between Nov 28, 2013, and March 31, 2015, in large cross-sectional surveys of random samples of the general population in 21 communities in Zambia and South Africa. HRQoL data were collected with a standardised generic measure of health across five domains. We used β-distributed multivariable models to analyse differences in HRQoL scores between HIV-negative and HIV-positive individuals who were unaware of their status; aware, but not in HIV care; in HIV care, but who had not initiated ART; on ART for less than 5 years; and on ART for 5 years or more. We included controls for sociodemographic variables, herpes simplex virus type-2 status, and recreational drug use. Findings: We obtained data for 19 750 respondents in Zambia and 18 941 respondents in South Africa. Laboratoryconfirmed HIV status was available for 19 330 respondents in Zambia and 18 004 respondents in South Africa; 4128 (21%) of these 19 330 respondents in Zambia and 4012 (22%) of 18 004 respondents in South Africa had laboratory-confirmed HIV. We obtained complete HRQoL information for 19 637 respondents in Zambia and 18 429 respondents in South Africa. HRQoL scores did not differ significantly between individuals who had initiated ART more than 5 years previously and HIV-negative individuals, neither in Zambia (change in mean score –0·002, 95% CI –0·01 to 0·001; p=0·219) nor in South Africa (0·000, –0·002 to 0·003; p=0·939). However, scores did differ between HIV-positive individuals who had initiated ART less than 5 years previously and HIV-negative individuals in Zambia (–0·006, 95% CI –0·008 to –0·003; p<0·0001). A large proportion of people with clinically confirmed HIV were unaware of being HIV-positive (1768 [43%] of 4128 people in Zambia and 2026 [50%] of 4012 people in South Africa) and reported good HRQoL, with no significant differences from that of HIV-negative people (change in mean HRQoL score –0·001, 95% CI –0·003 to 0·001, p=0·216; and 0·001, –0·001 to 0·001, p=0·997, respectively). In South Africa, HRQoL scores were lower in HIV-positive individuals who were aware of their status but not enrolled in HIV care (change in mean HRQoL –0·004, 95% CI –0·01 to –0·001; p=0·010) and those in HIV care but not on ART (–0·008, –0·01 to –0·004; p=0·001) than in HIV-negative people, but the magnitudes of difference were small. Interpretation: ART is successful in helping to reduce inequalities in HRQoL between HIV-positive and HIV-negative individuals in this general population sample. These findings highlight the importance of improving awareness of HIV status and expanding ART to prevent losses in HRQoL that occur with untreated HIV progression. The gains in HRQoL after individuals initiate ART could be substantial when scaled up to the population level.
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    Effect of Universal Testing and Treatment on HIV Incidence — HPTN 071 (PopART)
    (Massachusetts Medical Society, 2019-07) Hayes, Richard J.; Donnell, Deborah; Floyd, Sian; Mandla, Nomtha; Bwalya, Justin; Sabapathy, Kalpana; Yang, Blia; Phiri, Mwelwa; Schaap, Ab; Eshleman, Susan H.; Piwowar-Manning, Estelle; Kosloff, Barry; James, Anelet; Skalland, Timothy; Wilson, Ethan; Emel, Lynda; Macleod, David; Dunbar, Rory; Simwinga, Musonda; Makola, Nozizwe; Bond, Virginia; Moore, Ayana; Griffith, Sam; Sista, Nirupama Deshmane; Vermund, Sten H.; El-Sadr, Wafaa; Burns, David N.; Hargreaves, James R.; Hauck, Katharina; Fraser, Christophe; Shanaube, Kwame; Bock, Peter; Beyers, Nulda; Ayles, Helen; Fidler, Sarah
    BACKGROUND: A universal testing and treatment strategy is a potential approach to reduce the incidence of human immunodeficiency virus (HIV) infection, yet previous trial results are inconsistent. METHODS: In the HPTN 071 (PopART) community-randomized trial conducted from 2013 through 2018, we randomly assigned 21 communities in Zambia and South Africa (total population, approximately 1 million) to group A (combination prevention intervention with universal antiretroviral therapy [ART]), group B (the prevention intervention with ART provided according to local guidelines [universal since 2016]), or group C (standard care). The prevention intervention included home-based HIV testing delivered by community workers, who also supported linkage to HIV care and ART adherence. The primary outcome, HIV incidence between months 12 and 36, was measured in a population cohort of approximately 2000 randomly sampled adults (18 to 44 years of age) per community. Viral suppression (<400 copies of HIV RNA per milliliter) was assessed in all HIV-positive participants at 24 months. RESULTS: The population cohort included 48,301 participants. Baseline HIV prevalence was 21% or 22% in each group. Between months 12 and 36, a total of 553 new HIV infections were observed during 39,702 person-years (1.4 per 100 person-years; women, 1.7; men, 0.8). The adjusted rate ratio for group A as compared with group C was 0.93 (95% confidence interval [CI], 0.74 to 1.18; P=0.51) and for group B as compared with group C was 0.70 (95% CI, 0.55 to 0.88; P=0.006). The percentage of HIV-positive participants with viral suppression at 24 months was 71.9% in group A, 67.5% in group B, and 60.2% in group C. The estimated percentage of HIV-positive adults in the community who were receiving ART at 36 months was 81% in group A and 80% in group B. CONCLUSIONS: A combination prevention intervention with ART provided according to local guidelines resulted in a 30% lower incidence of HIV infection than standard care. The lack of effect with universal ART was unanticipated and not consistent with the data on viral suppression. In this trial setting, universal testing and treatment reduced the population-level incidence of HIV infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 071 [PopArt] ClinicalTrials.gov number, NCT01900977. opens in new tab.)
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    The effect of universal testing and treatment on HIV stigma in 21 communities in Zambia and South Africa
    (Wolters Kluwer Health, 2020-11) Stangl, Anne L.; Pliakas, Triantafyllos; Maingad, Tila; Steinhaus, Mara; Mubekapi-Musadaidzwae, Constance; Viljoen, Lario; Dunbare, Rory; Schaapd, Ab; Floyd, Sian; Mandla, Nomtha; Bond, Virginia; Hoddinott, Graeme; Fidler, Sarah; Hayes, Richard; Ayles, Helen; Bock, Peter; Donnell, Deborah; Hargreaves, James R.
    Objectives: To assess the impact of a combination HIV prevention intervention including universal testing and treatment (UTT) on HIV stigma among people living with HIV, and among community members and health workers not living with HIV. Design: This HIV stigma study was nested in the HPTN 071 (PopART) trial, a three-arm cluster randomised trial conducted between 2013 and 2018 in 21 urban/peri-urban communities (12 in Zambia and nine in South Africa). Methods: Using an adjusted two-stage cluster-level analysis, controlling for baseline imbalances, we compared multiple domains of stigma between the trial arms at 36 months. Different domains of stigma were measured among three cohorts recruited across all study communities: 4178 randomly sampled adults aged 18–44 who were living with HIV, and 3487 randomly sampled adults and 1224 health workers who did not self-report living with HIV. Results: Prevalence of any stigma reported by people living with HIV at 36 months was 20.2% in arm A, 26.1% in arm B, and 19.1% in arm C (adjusted prevalence ratio, A vs. C 1.01 95% CI 0.49–2.08, B vs. C 1.34 95% CI 0.65–2.75). There were no significant differences between arms in any other measures of stigma across all three cohorts. All measures of stigma reduced over time (0.2–4.1% reduction between rounds) with most reductions statistically significant. Conclusion: We found little evidence that UTT either increased or decreased HIV stigma measured among people living with HIV, or among community members or health workers not living with HIV. Stigma reduced over time, but slowly.
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    High prevalence of Tuberculosis and insufficient case detection in two communities in the Western Cape, South Africa
    (PLoS ONE, 2013-04) Claassens, Mareli; Van Schalkwyk, Cari; De Haan, Leonie; Floyd, Sian; Dunbar, Rory; Van Helden, Paul; Godfrey-Faussett, Peter; Ayles, Helen; Borgdorff, Martien; Enarson, Donald; Beyers, Nulda
    Background: In South Africa the estimated incidence of all forms of tuberculosis (TB) for 2008 was 960/100000. It was reported that all South Africans lived in districts with Directly Observed Therapy, Short-course. However, the 2011 WHO report indicated South Africa as the only country in the world where the TB incidence is still rising. Aims: To report the results of a TB prevalence survey and to determine the speed of TB case detection in the study communities. Methods: In 2005 a TB prevalence survey was done to inform the sample size calculation for the ZAMSTAR (Zambia South Africa TB and AIDS Reduction) trial. It was a cluster survey with clustering by enumeration area; all households were visited within enumeration areas and informed consent obtained from eligible adults. A questionnaire was completed and a sputum sample collected from each adult. Samples were inoculated on both liquid mycobacterium growth indicator tube (MGIT) and Lo¨ wenstein-Jensen media. A follow-up HIV prevalence survey was done in 2007. Results: In Community A, the adjusted prevalence of culture positive TB was 32/1000 (95%CI 25–41/1000) and of smear positive TB 8/1000 (95%CI 5–13/1000). In Community B, the adjusted prevalence of culture positive TB was 24/1000 (95%CI17–32/1000) and of smear positive TB 9/1000 (95%CI 6–15/1000). In Community A the patient diagnostic rate was 0.38/person-year while in community B it was 0.30/person-year. In both communities the adjusted HIV prevalence was 25% (19–30%). Discussion: In both communities a higher TB prevalence than national estimates and a low patient diagnostic rate was calculated, suggesting that cases are not detected at a sufficient rate to interrupt transmission. These findings may contribute to the rising TB incidence in South Africa. The TB epidemic should therefore be addressed rapidly and effectively, especially in the presence of the concurrently high HIV prevalence.
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    HIV treatment-as-prevention research : taking the right road at the crossroads
    (Public Library of Science, 2015) Hayes, Richard; Fidler, Sarah; Cori, Anne; Fraser, Christophe; Floyd, Sian; Ayles, Helen; Beyers, Nulda; El-Sadr, Wafaa; HPTN 071 (PopART) Study Team
    No abstract available
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    Households, fluidity, and HIV service delivery in Zambia and South Africa – an exploratory analysis of longitudinal qualitative data from the HPTN 071 (PopART) trial
    (Wiley Open Access, 2018) Hoddinott, Graeme; Myburgh, Hanlie; De Villiers, Laing; Ndubani, Rhoda; Mantantana, Jabulile; Thomas, Angelique; Mbewe, Madalitso; Ayles, Helen; Bock, Peter; Seeley, Janet; Shanaube, Kwame; Hargreaves, James; Bond, Virginia; Reynolds, Lindsey
    Introduction: Population distributions, family and household compositions, and people’s sense of belonging and social stability in southern Africa have been shaped by tumultuous, continuing large-scale historical disruptions. As a result, many people experience high levels of geographic and social fluidity, which intersect with individual and population-level migration patterns. We describe the complexities of household fluidity and HIV service access in South Africa and Zambia to explore implications for health systems and service delivery in contexts of high household fluidity. Methods: HPTN 071 (PopART) is a three-arm cluster randomized controlled trial implemented in 21 peri-urban study communities in Zambia and South Africa between 2013 and 2018. A qualitative cohort nested in the trial included 148 purposively sampled households. Data collection was informed by ethnographic and participatory research principles. The analysis process was reflexive and findings are descriptive narrative summaries of emergent ideas. Results: Households in southern Africa are extremely fluid, with people having a tenuous sense of security in their social networks. This fluidity intersects with high individual and population mobility. To characterize fluidity, we describe thematic patterns of household membership and residence. We also identify reasons people give for moving around and shifting social ties, including economic survival, fostering interpersonal relationships, participating in cultural, traditional, religious, or familial gatherings, being institutionalized, and maintaining patterns of substance use. High fluidity disrupted HIV service access for some participants. Despite these challenges, many participants were able to regularly access HIV testing services and participants living with HIV were especially resourceful in maintaining continuity of antiretroviral therapy (ART). We identify three key features of health service interactions that facilitated care continuity: disclosure to family members, understanding attitudes among health services staff including flexibility to accommodate clients’ transient pressures, and participants’ agency in ARTrelated decisions. Conclusions: Choices made to manage one’s experiential sense of household fluidity are intentional responses to livelihood and social support constraints. To enhance retention in care for people living with HIV, policy makers and service providers should focus on creating responsive, flexible health service delivery systems designed to accommodate many shifts in client circumstances.
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    How place matters for addressing the HIV epidemic : evidence from the HPTN 071 (PopART) cluster-randomised controlled trial in Zambia and South Africa
    (BMC, 2021-04-06) Bond, Virginia; Hoddinott, Graeme; Viljoen, Lario; Ngwenya, Fredrick; Simuyaba, Melvin; Chiti, Bwalya; Ndubani, Rhoda; Makola, Nozizwe; Donnell, Deborah; Schaap, Ab; Floyd, Sian; Hargreaves, James; Shanaube, Kwame; Fidler, Sarah; Bock, Peter; Ayles, Helen; Hayes, Richard; Simwinga, Musonda; Seeley, Janet
    Background: In a cluster-randomised trial (CRT) of combination HIV prevention (HPTN 071 (PopART)) in 12 Zambian communities and nine South African communities, carried out from 2012 to 2018, the intervention arm A that offered HIV treatment irrespective of CD4 count did not have a significant impact on population level HIV incidence. Intervention arm B, where HIV incidence was reduced by 30%, followed national guidelines that mid trial (2016) changed from starting HIV treatment according to a CD4 threshold of 500 to universal treatment. Using social science data on the 21 communities, we consider how place (community context) might have influenced the primary outcome result. Methods: A social science component documented longitudinally the context of trial communities. Data were collected through rapid qualitative assessment, interviews, group discussions and observations. There were a total of 1547 participants and 1127 observations. Using these data, literature and a series of qualitative analysis steps, we identified key community characteristics of relevance to HIV and triangulated these with HIV community level incidence. Results: Two interdependent social factors were relevant to communities’ capability to manage HIV: stability/ instability and responsiveness/resistance. Key components of stability were social cohesion; limited social change; a vibrant local economy; better health, education and recreational services; strong institutional presence; established middle-class residents; predictable mobility; and less poverty and crime. Key components of responsiveness were community leadership being open to change, stronger history of HIV initiatives, willingness to take up HIV services, less HIV-related stigma and a supported and enterprising youth population. There was a clear pattern of social factors across arms. Intervention arm A communities were notably more resistant and unstable. Intervention arm B communities were overall more responsive and stable. Conclusions: In the specific case of the dissonant primary outcome results from the HPTN 071 (PopART) trial, the chance allocation of less stable, less responsive communities to arm A compared to arm B may explain some of the apparently smaller impact of the intervention in arm A. Stability and responsiveness appear to be two key social factors that may be relevant to secular trends in HIV incidence. We advocate for a systematic approach, using these factors as a framework, to community context in CRTs and monitoring HIV prevention efforts.
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    HPTN 071 (PopART) : a cluster-randomized trial of the population impact of an HIV combination prevention intervention including universal testing and treatment : mathematical model
    (PLoS, 2014-01-15) Cori, Anne; Ayles, Helen; Beyers, Nulda; Schaap, Ab; Floyd, Sian; Sabapathy, Kalpana; Eaton, Jeffrey W.; Hauck, Katharina; Smith, Peter; Griffith, Sam; Moore, Ayana; Donnell, Deborah; Vermund, Sten H.; Fidler, Sarah; Hayes, Richard; Fraser, Christophe
    Background: The HPTN 052 trial confirmed that antiretroviral therapy (ART) can nearly eliminate HIV transmission from successfully treated HIV-infected individuals within couples. Here, we present the mathematical modeling used to inform the design and monitoring of a new trial aiming to test whether widespread provision of ART is feasible and can substantially reduce population-level HIV incidence. Methods and Findings: The HPTN 071 (PopART) trial is a three-arm cluster-randomized trial of 21 large population clusters in Zambia and South Africa, starting in 2013. A combination prevention package including home-based voluntary testing and counseling, and ART for HIV positive individuals, will be delivered in arms A and B, with ART offered universally in arm A and according to national guidelines in arm B. Arm C will be the control arm. The primary endpoint is the cumulative three-year HIV incidence. We developed a mathematical model of heterosexual HIV transmission, informed by recent data on HIV-1 natural history. We focused on realistically modeling the intervention package. Parameters were calibrated to data previously collected in these communities and national surveillance data. We predict that, if targets are reached, HIV incidence over three years will drop by >60% in arm A and >25% in arm B, relative to arm C. The considerable uncertainty in the predicted reduction in incidence justifies the need for a trial. The main drivers of this uncertainty are possible community-level behavioral changes associated with the intervention, uptake of testing and treatment, as well as ART retention and adherence. Conclusions: The HPTN 071 (PopART) trial intervention could reduce HIV population-level incidence by >60% over three years. This intervention could serve as a paradigm for national or supra-national implementation. Our analysis highlights the role mathematical modeling can play in trial development and monitoring, and more widely in evaluating the impact of treatment as prevention.
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    HPTN 071 (PopART) : rationale and design of a cluster-randomised trial of the population impact of an HIV combination prevention intervention including universal testing and treatment - a study protocol for a cluster randomised trial
    (BioMed Central, 2014-02) Hayes, Richard; Ayles, Helen; Beyers, Nulda; Sabapathy, Kalpana; Floyd, Sian; Shanaube, Kwame; Bock, Peter; Griffith, Sam; Moore, Ayana; Watson-Jones, Deborah; Fraser, Christophe; Vermund, Sten H.; Fidler, Sarah; The HPTN 071 (PopART) Study Team
    Abstract Background Effective interventions to reduce HIV incidence in sub-Saharan Africa are urgently needed. Mathematical modelling and the HIV Prevention Trials Network (HPTN) 052 trial results suggest that universal HIV testing combined with immediate antiretroviral treatment (ART) should substantially reduce incidence and may eliminate HIV as a public health problem. We describe the rationale and design of a trial to evaluate this hypothesis. Methods/Design A rigorously-designed trial of universal testing and treatment (UTT) interventions is needed because: i) it is unknown whether these interventions can be delivered to scale with adequate uptake; ii) there are many uncertainties in the models such that the population-level impact of these interventions is unknown; and ii) there are potential adverse effects including sexual risk disinhibition, HIV-related stigma, over-burdening of health systems, poor adherence, toxicity, and drug resistance.In the HPTN 071 (PopART) trial, 21 communities in Zambia and South Africa (total population 1.2 m) will be randomly allocated to three arms. Arm A will receive the full PopART combination HIV prevention package including annual home-based HIV testing, promotion of medical male circumcision for HIV-negative men, and offer of immediate ART for those testing HIV-positive; Arm B will receive the full package except that ART initiation will follow current national guidelines; Arm C will receive standard of care. A Population Cohort of 2,500 adults will be randomly selected in each community and followed for 3 years to measure the primary outcome of HIV incidence. Based on model projections, the trial will be well-powered to detect predicted effects on HIV incidence and secondary outcomes. Discussion Trial results, combined with modelling and cost data, will provide short-term and long-term estimates of cost-effectiveness of UTT interventions. Importantly, the three-arm design will enable assessment of how much could be achieved by optimal delivery of current policies and the costs and benefits of extending this to UTT. Trial registration ClinicalTrials.gov NCT01900977.
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    Interpretation of serial interferon-gamma test results to measure new tuberculosis infection among household contacts in Zambia and South Africa
    (BioMed Central, 2020-10-15) Sloot, Rosa; Shanaube, Kwame; Claassens, Mareli; Telisinghe, Lily; Schaap, Ab; Godfrey-Faussett, Peter; Ayles, Helen; Floyd, Sian
    Background: A more stringent QuantiFERON-TB Gold In-Tube (QFT) conversion (from negative to positive) definition has been proposed to allow more definite detection of recent tuberculosis (TB) infection. We explored alternative conversion definitions to assist the interpretation of serial QFT results and estimate incidence of TB infection in a large cohort study. Methods: We used QFT serial results from TB household contacts aged ≥15 years, collected at baseline and during two follow-up visits (2006–2011) as part of a cohort study in 24 communities in Zambia and South Africa (SA). Conversion rates using the manufacturers’ definition (interferon-gamma (IFN-g) < 0.35 to ≥0.35, ‘def1’) were compared with stricter definitions (IFN-g < 0.2 to ≥0.7 IU/ml, ‘def2’; IFN-g < 0.2 to ≥1.05 IU/ml, ‘def3’; IFN-g < 0.2 to ≥1.4 IU/ml, ‘def4’). Poisson regression was used for analysis. Results: One thousand three hundred sixty-five individuals in Zambia and 822 in SA had QFT results available. Among HIV-negative individuals, the QFT conversion rate was 27.4 per 100 person-years (CI:22.9–32.6) using def1, 19.0 using def2 (CI:15.2–23.7), 14.7 using def3 (CI:11.5–18.8), and 12.0 using def4 (CI:9.2–15.7). Relative differences across def1-def4 were similar in Zambia and SA. Using def1, conversion was less likely if HIV positive not on antiretroviral treatment compared to HIV negative (aRR = 0.7, 95%CI = 0.4–0.9), in analysis including both countries. The same direction of associations were found using def 2–4. Conclusion: High conversion rates were found even with the strictest definition, indicating high incidence of TB infection among household contacts of TB patients in these communities. The trade-off between sensitivity and specificity using different thresholds of QFT conversion remains unknown due to the absence of a reference standard. However, we identified boundaries within which an appropriate definition might fall, and our strictest definition plausibly has high specificity.
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    Patient diagnostic rate as indicator of tuberculosis case detection, South Africa
    (Centers for Disease Control and Prevention, 2016) Claassens, Mareli; Van Schalkwyk, Cari; Dunbar, Rory; Ayles, Helen; Beyers, Nulda
    ENGLISH SUMMARY : To address the uncertainty of the indirectly measured tuberculosis case detection rate, we used survey data stratified by HIV status to calculate the patient diagnostic rate, a directly measurable indicator, in 8 communities in South Africa. Rates were lower among HIV-negative than HIV-positive persons. Tuberculosis programs should focus on HIV-negative persons.
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    Prevalence of tuberculosis, HIV and respiratory symptoms in two Zambian communities: Implications for tuberculosis control in the era of HIV
    (Public Library of Science (PLOS), 2009-05) Ayles, Helen; Schaap, Albertus; Nota, Amos; Sismanidis, Charalambos; Tembwe, Ruth; De Haas, Petra; Muyoyeta, Monde; Beyers, Nulda; Godfrey-Faussett, Peter
    Background: The Stop TB Partnership target for tuberculosis is to have reduced the prevalence of tuberculosis by 50% comparing 2015 to 1990. This target is challenging as few prevalence surveys have been conducted, especially in high burden tuberculosis and HIV countries. Current tuberculosis control strategies in high HIV prevalent settings are therefore based on limited epidemiological evidence and more evidence is needed from community-based surveys to inform improved policy formulation. Methods and Findings: 8044 adults were sampled from 2 sub-districts (wards) in Lusaka province, Zambia. Questionnaires were used to screen for symptoms, respiratory samples were obtained for culture and oral secretions collected for HIV testing. 79 individuals were found to have Mycobacterium tuberculosis in their sputum, giving an adjusted overall prevalence of tuberculosis of 870/100,000 (95% CI 570-1160/100,000). The adjusted overall prevalence of HIV was 28.61% (95% CI 26.04-31.19). HIV- infection was significantly associated with prevalent tuberculosis (Adj OR 2.3, 95% CI 1.42-3.74) and the population attributable fraction of HIV for prevalent tuberculosis was 36%. Symptoms such as prolonged cough (adj OR 12.72, 95% CI 7.05-22.94) and fever (Adj OR 2.04, 95%CI 1.23-3.39), were associated with prevalent tuberculosis, but 8 (10%) individuals with prevalent tuberculosis denied having any symptoms at all and only 34 (43%) would have been classified as a TB suspect by current guidelines. Conclusions: Undiagnosed tuberculosis is a challenge for tuberculosis control and new approaches are needed if we are to reach international targets. Epidemiological studies can inform screening algorithms for both detection and prevention of active tuberculosis. © 2009 Ayles et al.
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    Risk factors associated with positive quantiFERON-TB gold in-tube and tuberculin skin tests results in Zambia and South Africa
    (Public Library of Science (PLOS), 2011-04) Shanaube, Kwame; Hargreaves, James; Fielding, Katherine; Schaap, Ab; Lawrence, Katherine-Anne; Hensen, Bernadette; Sismanidis, Charalambos; Menezes, Angela; Beyers, Nulda; Ayles, Helen; Godfrey-Faussett, Peter
    Introduction: The utility of T-cell based interferon-gamma release assays for the diagnosis of latent tuberculosis infection remains unclear in settings with a high burden of tuberculosis. Objectives: To determine risk factors associated with positive QuantiFERON-TB Gold In-Tube (QFT-GIT) and tuberculin skin test (TST) results and the level of agreement between the tests; to explore the hypotheses that positivity in QFT-GIT is more related to recent infection and less affected by HIV than the TST. Methods: Adult household contacts of tuberculosis patients were invited to participate in a cross-sectional study across 24 communities in Zambia and South Africa. HIV, QFT-GIT and TST tests were done. A questionnaire was used to assess risk factors. Results: A total of 2,220 contacts were seen. 1,803 individuals had interpretable results for both tests, 1,147 (63.6%) were QFT-GIT positive while 725 (40.2%) were TST positive. Agreement between the tests was low (kappa = 0.24). QFT-GIT and TST results were associated with increasing age (adjusted OR [aOR] for each 10 year increase for QFT-GIT 1.15; 95% CI: 1.06-1.25, and for TST aOR: 1.10; 95% CI 1.01-1.20). HIV positivity was less common among those with positive results on QFT-GIT (aOR: 0.51; 95% CI: 0.39-0.67) and TST (aOR: 0.61; 95% CI: 0.46-0.82). Smear positivity of the index case was associated with QFT-GIT (aOR: 1.25; 95% CI: 0.90-1.74) and TST (aOR: 1.39; 95% CI: 0.98-1.98) results. We found little evidence in our data to support our hypotheses. Conclusion: QFT-GIT may not be more sensitive than the TST to detect risk factors associated with tuberculous infection. We found little evidence to support the hypotheses that positivity in QFT-GIT is more related to recent infection and less affected by HIV than the TST. © 2011 Shanaube et al.