Browsing by Author "Bock, Peter"
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- ItemAttrition 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.
- ItemBetter 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, PeterBackground: 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.
- ItemDevelopment 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.
- ItemDifferences 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, KatharinaBackground: 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.
- ItemEffect 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, SarahBACKGROUND: 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.)
- ItemThe 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.
- ItemHIV-1 RNA testing of pooled dried blood spots is feasible to diagnose acute HIV infection in resource limited settings(Medpharm Publications, 2018) Dowling, Wentzel; Veldsman, Kirsten; Katusiime, Mary Grace; Maritz, Jean; Bock, Peter; Meehan, Sue-Ann; Schalkwyk, Marije Van; Cotton, Mark F.; Preiser, Wolfgang; Van Zyl, Gert U.Objectives: Rapid human immunodeficiency virus (HIV) antibody tests, routinely used for diagnosis in adults and older children in resource-limited settings (RLS), do not detect early HIV infections prior to seroconversion or when antibody levels are still low. Nucleic acid amplification to detect HIV-1 RNA is the most sensitive method for acute HIV infection diagnosis, but is costly. We therefore investigated HIV- 1 RNA testing of pooled dried blood spots (DBS) to diagnose acute HIV infection. Design: Laboratory-based investigation. Methods: DBS were collected from HIV-1 Voluntary Counselling and Testing (HVCT) clients who tested negative on the Advanced QualityTM HIV antibody rapid test. DBS samples from five participants were pooled and tested on the COBAS AmpliPrep/COBAS TaqMan HIV-1 (CAP/CTM) Test v2. Individual DBS were tested when pools tested positive (> 200 RNA copies/ml). Acute infection was confirmed by HIV viral load testing, two fourth-generation HIV serological assays, and Geenius™ HIV 1/2 Assay for antibody band identification. Results: Of 482 participants who were tested, one (0.2%) had acute HIV infection: Fourth generation serology was low-level positive, the plasma HIV viral load was 15 929 HIV-1 RNA copies/ml, gp160 and gp41 antibody bands were positive and the p31 band was negative, indicating a Fiebig Stage 5 infection. Conclusions: Pooled DBS HIV-1 RNA testing is efficient compared to individual testing for acute HIV infection diagnosis. Early identification of participants with acute HIV infection facilitates immediate initiation of antiretroviral therapy to improve immune recovery and prevent transmission to others.
- ItemHouseholds, 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, LindseyIntroduction: 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.
- ItemHow 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, JanetBackground: 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.
- ItemHPTN 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 TeamAbstract 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.
- ItemThe impact of the HPTN 071 (PopART) intervention on mortality and AIDS related morbidity amongst HIV positive adults in South Africa(Stellenbosch : Stellenbosch University, 2018-03) Bock, Peter; Beyers, Nulda; Fidler, Sarah; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Paediatrics and Child Health.ENGLISH ABSTRACT: In 2015 WHO recommended antiretroviral treatment (ART) for all HIV-positive individuals regardless of CD4 count and set a target for Universal Access to ART, that >80% of HIV-positive individuals should be on ART. The HPTN 071 (PopART) trial, a community randomized trial in 21 communities in South Africa and Zambia, aims to to determine the impact of two community-level combination prevention packages on population-level HIV incidence. HPTN 071 (PopART) has implemented household-based HIV point of care testing (POCT) and provided ART regardless of CD4 count at department of health clinics (DOH) in the trial communities from January 2014. This was ahead of recent changes to WHO and South African ART guidelines, which now provide ART regardless of CD4 count. The primary outcome of HIV incidence was evaluated in a randomly selected research cohort, the Population Cohort (PC), which aims to recruit 44,500 HIV-positive and negative participants aged 18 to 45, approximately 2000 from each of the 21 communities. The aim of this PhD dissertation was to evaluate the outcomes of clinical activities key to effective provision of HIV treatment services in high burden settings. PhD objectives were to evaluate: i) the accuracy of household HIV POCT and the impact of routine initiation of ART at baseline CD4 counts > 500cells/mL on ii) attrition during early ART, iii) TB incidence during early ART, iv) the incidence of renal dysfunction during early ART and iv) adherence to ART. These objectives were addressed through the completion of five studies. Four of the five studies presented were embedded within the HPTN 071 (PopART) trial. The fifth study, evaluating ART adherence, was a systematic review and meta-analysis. The study presented in chapter 3, evaluated the accuracy of household-based HIV POCT between January 2014 and August 2016 across all 21 PopART sites in both South Africa and Zambia, through a series of cross-sectional analyses. This study showed initial low HIV POCT sensitivity in South Africa (45-54%). HIV POCT sensitivity in Zambia, which implemented more extensive quality assurance (QA) and quality control (QC) and used different HIV POCT kits, during the same time period, was significantly better (95.8%). HIV POCT sensitivity in South Africa improved over time to rates comparable to the Zambian sites when implementing rigorous HIV POCT QA/QC. The studies presented in chapters 4 to 6 analysed data on a cohort of adults (≥18years of age) initiating ART regardless CD4 count at three department of health (DOH) clinics in the Western Cape, South Africa; between January 2014 and November 2015. Cohort follow-up was completed at the end of May 2016. The cohort studies evaluated the impact of routine initiation of ART at baseline CD4 counts >500 cells/μL on i) attrition ii) TB incidence and ii) incidence of renal dysfunction during early ART. A total of 2423 adults with a median baseline CD4 count of 328 (IQR 195-468) cells/μL were included in the clinic cohort. Attrition included individuals no longer retained in ART care due to loss to follow up or death (chapter 4). A total of 636 (26.2%) adults in the cohort experienced attrition during the follow-up period. Attrition was higher amongst individuals with baseline CD4 counts >500 cells/μL compared to individuals with baseline CD4 counts 0-500 cells/μL (aHR 1.28, 95%CI 1.07 -1.55). This finding raised concerns about the potential for increased attrition from ART care when providing ART regardless of CD4 count. The overall TB incidence in the cohort was 4.4 cases/100PY (chapter 5). TB incidence was lower amongst individuals with baseline CD4 counts >500 cells/μL compared to those with baseline CD4 counts 0-500 cells/ μL (aHR=0.27; 95% CI 0.12 to 0.62). There were no incident TB cases in the first three months of ART amongst individuals with baseline CD4 counts > 500 cells/ μL. These findings were promising, highly suggestive that routine provision of ART at baseline CD4 counts >500 cells/μL will lead to a significant reduction in TB amongst individuals starting ART. The prevalence of baseline moderate or severe renal dysfunction (Estimated Glomerular Filtration Rate (EGFR) < 60ml/min) in the cohort was low (1.9%) (chapter 6), as was the rate of incident moderate or severe renal dysfunction after initiation of ART (1.9cases/100PY). The study showed no significant association between baseline CD4 count and incident moderate or severe renal dysfunction occurring after initiation of ART. Analysis restricted to individuals with normal baseline renal function, showed no cases of incident moderate or severe renal dysfunction amongst individuals with baseline CD4 counts >500cells/ μL. This is also a promising finding that needs to be confirmed by completion of further studies. The fifth study (chapter 7), was a systematic review and meta-analysis of studies published between 2004 and 2015, which evaluated the association between baseline CD4 count and ART adherence. This systematic review showed lower ART adherence amongst individuals starting ART at higher baseline CD4 counts categories (pooled OR 0.90; 95%CI 0.84-0.96). Baseline CD4 count categories used in the included studies varied. The most commonly used comparison was between individuals initiating ART at CD4 counts > 200 cells/μL and at CD4 counts 0-200 cells/μL. In the two included studies that reported on individuals with baseline CD4 counts > 500 cells/μL, there was no difference in ART adherence between individuals with baseline CD4 counts > 500 cells/μL and those with baseline CD4 counts 0-500 cells/μL. Overall the studies presented for this PhD dissertation demonstrated both benefits and challenges when conducting household-based HIV POCT and routinely initiating ART in HIV-positive individuals at baseline CD4 counts >500cells/μL. The studies presented in chapters 5 and 6 suggest potential reduction in incidence of TB and renal dysfunction with routine provision of ART at baseline CD4 counts >500cell/μL; providing a strong motivation for striving to attain universal access to ART in high burden settings. At the same time, the reported low HIV POCT sensitivity and the need for rigorous QA/QC when implementing household-based HIV POCT was concerning. As were the study findings showing higher attrition and poorer ART adherence when initiating ART at higher CD4 counts. Strategies to improve HIV POCT sensitivity, retention in ART care and ART adherence, in these contexts, should therefore be a priority for programme implementers in high-burden settings.
- ItemPatient-reported barriers to adherence to antiretroviral therapy : a systematic review and meta-analysis(Public Library of Science, 2016) Shubber, Zara; Mills, Edward J.; Nachega, Jean B.; Vreeman, Rachel; Freitas, Marcelo; Bock, Peter; Nsanzimana, Sabin; Penazzato, Martina; Appolo, Tsitsi; Doherty, Meg; Ford, NathanENGLISH SUMMARY : Background: Maintaining high levels of adherence to antiretroviral therapy (ART) is a challenge across settings and populations. Understanding the relative importance of different barriers to adherence will help inform the targeting of different interventions and future research priorities. Methods and Findings: We searched MEDLINE via PubMed, Embase, Web of Science, and PsychINFO from 01 January 1997 to 31 March 2016 for studies reporting barriers to adherence to ART. We calculated pooled proportions of reported barriers to adherence per age group (adults, adolescents, and children). We included data from 125 studies that provided information about adherence barriers for 17,061 adults, 1,099 children, and 856 adolescents. We assessed differences according to geographical location and level of economic development. The most frequently reported individual barriers included forgetting (adults 41.4%, 95% CI 37.3%–45.4%; adolescents 63.1%, 95% CI 46.3%–80.0%; children/caregivers 29.2%, 95% CI 20.1%–38.4%), being away from home (adults 30.4%, 95% CI 25.5%–35.2%; adolescents 40.7%, 95% CI 25.7%–55.6%; children/caregivers 18.5%, 95% CI 10.3%–26.8%), and a change to daily routine (adults 28.0%, 95% CI 20.9%–35.0%; adolescents 32.4%, 95% CI 0%–75.0%; children/caregivers 26.3%, 95% CI 15.3%–37.4%). Depression was reported as a barrier to adherence by more than 15% of patients across all age categories (adults 15.5%, 95% CI 12.8%–18.3%; adolescents 25.7%, 95% CI 17.7%–33.6%; children 15.1%, 95% CI 3.9%–26.3%), while alcohol/substance misuse was commonly reported by adults (12.9%, 95% CI 9.7%–16.1%) and adolescents (28.8%, 95% CI 11.8%–45.8%). Secrecy/stigma was a commonly cited barrier to adherence, reported by more than 10% of adults and children across all regions (adults 13.6%, 95% CI 11.9%–15.3%; children/caregivers 22.3%, 95% CI 10.2%–34.5%). Among adults, feeling sick (15.9%, 95% CI 13.0%–18.8%) was a more commonly cited barrier to adherence than feeling well (9.3%, 95% CI 7.2%–11.4%). Health service–related barriers, including distance to clinic (adults 17.5%, 95% CI 13.0%–21.9%) and stock outs (adults 16.1%, 95% CI 11.7%–20.4%), were also frequently reported. Limitations of this review relate to the fact that included studies differed in approaches to assessing adherence barriers and included variable durations of follow up. Studies that report self-reported adherence will likely underestimate the frequency of non-adherence. For children, barriers were mainly reported by caregivers, which may not correspond to the most important barriers faced by children. Conclusions: Patients on ART face multiple barriers to adherence, and no single intervention will be sufficient to ensure that high levels of adherence to treatment and virological suppression are sustained. For maximum efficacy, health providers should consider a more triaged approach that first identifies patients at risk of poor adherence and then seeks to establish the support that is needed to overcome the most important barriers to adherence.
- ItemRetention in care and factors critical for effectively implementing antiretroviral adherence clubs in a rural district in South Africa(Wiley Open Access, 2019-09-03) Bock, Peter; Gunst, Colette; Maschilla, Leonard; Holtman, Rory; Grobbelaar, Nelis; Wademan, Dillon; Dunbar, Rory; Fatti, Geoffrey; Kruger, James; Ford, Nathan; Hoddinott, Graeme; Meehan, Sue-AnnIntroduction: Differentiated models of care that include referral of antiretroviral treatment (ART) clients to adherence clubs are an important strategy to help clinics manage increased number of clients living with HIV in resource-constrained settings. This study reported on (i) clinical outcomes among ART clients attending community-based adherence clubs and (ii) experiences of adherence clubs and perceptions of factors key to successful adherence club implementation among clients and healthcare workers. Methods: A retrospective cohort analysis of routine data and a descriptive analysis of data collected through self-administered surveys completed by clients and healthcare workers were completed. Clients starting ART at the study clinic, between January 2014 and December 2015, were included in the cohort analysis and followed up until December 2016. The survey data were collected from August to September 2017. The primary outcome for the cohort analysis was a comparison of loss to follow-up (LTFU) between clients staying in clinic care and those referred to adherence clubs. Survey data reported on client experiences of and healthcare worker perceptions of adherence club care. Results: Cohort analysis reported on 465 participants, median baseline CD4 count 374 (IQR: 234 to 532) cells/ll and median follow-up time 20.7 (IQR 14.1 to 27.7) months. Overall, 202 (43.4%) participants were referred to an adherence club. LTFU was lower in those attending an adherence club (aHR =0.25, 95% CI: 0.11 to 0.56). This finding was confirmed on analysis restricted to those eligible for adherence club referral (aHR =0.28, 95% CI: 0.12 to 0.65). Factors highlighted as associated with successful adherence club implementation included: (i) referral of stable clients to the club, (ii) an ideal club size of ≥20 members, (iii) club services led by a counsellor (iv) using churches or community halls as venues (v) effective communication between all parties, and (vi) timely delivery of prepacked medication. Conclusions: This study showed good clinical outcomes, positive patient experiences and healthcare worker perceptions of the adherence club model. Factors associated with successful adherence club implementation, highlighted in this study, can be used to guide implementers in the scale-up of adherence club services across varied high-burden settings.
- ItemStigma and HIV service access among transfeminine and gender diverse women in South Africa – a narrative analysis of longitudinal qualitative data from the HPTN 071 (PopART) trial(BMC (part of Springer Nature), 2020-12-10) De Villiers, Laing; Thomas, Angelique; Jivan, Dionne; Hoddinott, Graeme; Hargreaves, James R.; Bond, Virginia; Stangl, Anne; Bock, Peter; Reynolds, LindseyBackground: Transgender women have a disproportionately high HIV prevalence compared to cisgender women and men who have sex with men, which puts them at risk of HIV-related stigma (Baral SD et al., Lancet Infect Dis, 13;3, 2013). People whose gender identities are in tension with dominant social norms (including transgender women) often also experience gender identity-related stigma. There has been increasing attention to transgender people in HIV research and interventions. However, very little research has been done in sub-Saharan African countries. Methods: We conducted a qualitative cohort study which included eight transfeminine and/or gender diverse women (four living with HIV) in Western Cape, South Africa, for a follow-up period of 12–18 months. Using a narrative analysis approach, we set out to understand how transfeminine and gender diverse participants in the cohort anticipated, experienced and internalised HIV stigma and gender identity stigma, and how these stigmas affected HIV service access. Result: We found that participants reported anticipated, experienced, and internalised stigma relating both to their gender identity and to living with HIV. Participants reported inconsistent uptake of antiretroviral therapy (ART) services (including ART initiation and adherence) that they linked to stigma. We also found that gender diverse women and transfeminine women are challenged with other stigmatising social identities, like being a sex worker, drug user and/or a man (or assigned male sex at birth) who have sex with men (MSM). We use the terms ‘transfeminine’ and ‘gender diverse’ as terms that are inclusive of gender variant people who were all assigned male sex at birth and identify as women in some or all aspects of their lives. The persons in our study also showed gender identifications that were fluid and sometimes varied in different contexts and situations, therefore gender identity and sexual identity were often conflated for these individuals. Participants managed high levels of reported stigma by drawing on social support networks like families, friends and peers. Conclusion: Our study provides exploratory work on how stigma may affect HIV services uptake amongst gender diverse women and transfeminine women in South Africa. We recommend future studies to further explore the unique HIV risks of gender diverse individuals.
- ItemTowards 90-90 : findings after two years of the HPTN 071 (PopART) cluster-randomized trial of a universal testing-and-treatment intervention in Zambia(Public Library of Science, 2018) Floyd, Sian; Ayles, Helen; Schaap, Albertus; Shanaube, Kwame; MacLeod, David; Phiri, Mwelwa; Griffith, Sam; Bock, Peter; Beyers, Nulda; Fidler, Sarah; Hayes, RichardBackground: HPTN071(PopART) is a 3-arm community-randomised study in 21 peri-urban/urban communities in Zambia and the Western Cape of South Africa, with high HIV prevalence and high mobility especially among young adults. In Arm A communities, from November 2013 community HIV care providers (CHiPs) have delivered the “PopART” universal-test-and-treat (UTT) package in annual rounds, during which they visit all households and offer HIV testing. CHiPs refer HIV-positive (HIV+) individuals to routine HIV clinic services, where universal ART (irrespective of CD4 count) is offered, with re-visits to support linkage to care. The overall goal is to reduce population-level adult HIV incidence, through achieving high HIV testing and treatment coverage. Methods and findings: The second annual round was June 2015-October 2016. Included in analysis are all individuals aged ≥15 years who consented to participate, with extrapolation to the total population. Our three main outcomes are (1) knowledge of HIV+ status (2) ART coverage, by the end of Round 2 (R2) and compared with the start of R2, and (3) retention on ART on the day of consenting to participate in R2. We used “time-to-event” methods to estimate the median time to start ART after referral to care. CHiPs visited 45,631 households during R2, ~98% of the estimated total across the four communities, and for 94% (43,022/45,631) consent was given for all household members to be listed on the CHiPs’ electronic register; 120,272 individuals aged ≥15 years were listed, among whom 64% of men (37,265/57,901) and 86% (53,516/62,371) of women consented to participate in R2. We estimated there were 6,521 HIV+ men and 10,690 HIV+ women in the total population of visited households; and that ~80% and ~90% of HIV+ men and women respectively knew their HIV+ status by the end of R2, fairly similar across age groups but lower among those who did not participate in Round 1 (R1). Among those who knew their HIV+ status, ~80% of both men and women were on ART by the end of R2, close to 90% among men aged ≥45 and women aged ≥35 years, but lower among younger adults, those who were resident in R1 but did not participate in R1, and those who were newly resident in the area of the community in which they were living in R2. Overall ART coverage was ~65% among HIV+ men and ~75% among HIV+ women, compared with the cumulative 90–90 target of 81%. Among those who reported ever taking ART, 93% of men and 95% of women self-reported they were on ART and missed 0 pills in the last 3 days. The median time to start ART after referral to care was ~6 months in R2, similar across the age range 25–54 years, compared with ~9.5 months in R1. The two main limitations to our findings were that a comparison with control-arm communities cannot be made until the end of the study; and that to extrapolate to the total population, assumptions were required about individuals who were resident, but did not participate, in R2. Conclusions: Overall coverage against the 90–90 targets was high after two years of intervention, but was lower among men, individuals aged 18–34 years, and those who did not participate in R1. Our findings reflect the relative difficulties for CHiPs to contact men at home, compared with women, and that it is challenging to reach high levels of testing and treatment coverage in communities with substantial mobility and in-migration. The shortened time to start ART after referral to care in R2, compared with R1, was likely attributable to multiple factors including an increased focus of the CHiPs on linkage to care; increasing community acceptance and understanding of the CHiPs, and of ART and UTT, with time; increased coordination with the clinics to facilitate linkage; and clinic improvements.
- ItemUnderstanding low sensitivity of community-based HIV rapid testing : experiences from the HPTN 071 (PopART) trial in Zambia and South Africa(Wiley Open Access, 2017-08-27) Bock, Peter; Phiri, Comfort; Piwowar-Manning, Estelle; Kosloff, Barry; Mandla, Nomtha; Young, Alicia; James, Anelet; Schaap, A. b.; Scheepers, Michelle; Donnell, Deborah; Griffith, Sam; El-Sadr, Wafaa; Shanaube, Kwame; Beyers, Nulda; Hayes, Richard; Fidler, Sarah; Ayles, HelenIntroduction: Population-wide HIV testing services (HTS) must be delivered in order to achieve universal antiretroviral treatment (ART) coverage. To accurately deliver HTS at such scale, non-facility-based HIV point-of-care testing (HIV-POCT) is necessary but requires rigorous quality assurance (QA). This study assessed the performance of community-wide HTS in Zambia and South Africa (SA) as part of the HPTN 071 (PopART) study and explores the impact of quality improvement interventions on HTS performance. Methods: Between 2014 and 2016, HIV-POCT was undertaken within households both as part of the randomly selected HPTN 071 research cohort (Population Cohort [PC]) and as part of the intervention provided by community HIV-care providers. HIVPOCT followed national algorithms in both countries. Consenting PC participants provided a venous blood sample in addition to being offered HIV-POCT. We compared results obtained in the PC using a laboratory-based gold standard (GS) testing algorithm and HIV-POCT. Comprehensive QA mechanisms were put in place to support the community-wide testing. Participants who were identified as having a false negative or false positive HIV rapid test were revisited and offered retesting. Results: We initially observed poor sensitivity (45–54%, 95% confidence interval [CI] 31–69) of HIV-POCT in the PC in SA compared to sensitivity in Zambia for the same time period of 95.8% (95% CI 93–98). In both countries, specificity of HIVPOCT was >98%. With enhanced QA interventions and adoption of the same HIV-POCT algorithm, sensitivity in SA improved to a similar level as in Zambia. Conclusions: This is one of the first reports of HIV-POCT performance during wide-scale delivery of HTS compared to a GS laboratory algorithm. HIV-POCT in a real-world setting had a lower sensitivity than anticipated. Appropriate choice of HIVPOCT algorithms, intensive training and supervision, and robust QA mechanisms are necessary to optimize HIV-POCT test performance when testing is delivered at a community level. HIV-POCT in clients who did not disclose that they were on ART may have contributed to false negative HIV-POCT results and should be the topic of future research.
- ItemUnderstanding the time needed to link to care and start ART in seven HPTN 071 (PopART) study communities in Zambia and South Africa(Springer, 2019) Seeley, Janet; Bond, Virginia; Yang, Blia; Floyd, Sian; MacLeod, David; Viljoen, Lario; Phiri, Mwelwa; Simuyaba, Melvin; Hoddinott, Graeme; Shanaube, Kwame; Bwalya, Chiti; De Villiers, Laing; Jennings, Karen; Mwanza, Margaret; Schaap, Ab; Dunbar, Rory; Sabapathy, Kalpana; Ayles, Helen; Bock, Peter; Hayes, Richard; Fidler, SarahTo achieve UNAIDS 90:90:90 targets at population-level, knowledge of HIV status must be followed by timely linkage to care, initiation and maintenance of antiretroviral therapy (ART) for all people living with HIV (PLHIV). Interpreting quantitative patterns using qualitative data, we investigate time taken to link to care and initiate ART amongst individuals aware of their HIV-status in high HIV-prevalence urban communities in the HPTN 071 (PopART) study, a community-randomised trial of a combination HIV prevention package, including universal testing and treatment, in 21 communities in Zambia and South Africa. Data are drawn from the seven intervention communities where immediate ART irrespective if CD4 count was offered from the trial-start in 2014. Median time from HIV-diagnosis to ART initiation reduced after 2 years of delivering the intervention from 10 to 6 months in both countries but varied by gender and community of residence. Social and health system realities impact decisions made by PLHIV about ART initiation.
- ItemA universal testing and treatment intervention to improve HIV control : one-year results from intervention communities in Zambia in the HPTN 071 (PopART) cluster-randomised trial(Public Library of Science, 2017) Hayes, Richard; Floyd, Sian; Schaap, Ab; Shanaube, Kwame; Bock, Peter; Sabapathy, Kalpana; Griffith, Sam; Donnell, Deborah; Piwowar-Manning, Estelle; El-Sadr, Wafaa; Beyers, Nulda; Ayles, Helen; Fidler, SarahBackground: The Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets require that, by 2020, 90% of those living with HIV know their status, 90% of known HIV-positive individuals receive sustained antiretroviral therapy (ART), and 90% of individuals on ART have durable viral suppression. The HPTN 071 (PopART) trial is measuring the impact of a universal testing and treatment intervention on population-level HIV incidence in 21 urban communities in Zambia and South Africa. We report observational data from four communities in Zambia to assess progress towards the UNAIDS targets after 1 y of the PopART intervention. Methods and findings: The PopART intervention comprises annual rounds of home-based HIV testing delivered by community HIV-care providers (CHiPs) who also support linkage to care, ART retention, and other services. Data from four communities in Zambia receiving the full intervention (including immediate ART for all individuals with HIV) were used to determine proportions of participants who knew their HIV status after the CHiP visit; proportions linking to care and initiating ART following referral; and overall proportions of HIV-infected individuals who knew their status (first 90 target) and the proportion of these on ART (second 90 target), pre- and post-intervention. We are not able to assess progress towards the third 90 target at this stage of the study. Overall, 121,130 adults (59,283 men and 61,847 women) were enumerated in 46,714 households during the first annual round (December 2013 to June 2015). Of the 45,399 (77%) men and 55,703 (90%) women consenting to the intervention, 80% of men and 85% of women knew their HIV status after the CHiP visit. Of 6,197 HIV-positive adults referred by CHiPs, 42% (95% CI: 40%–43%) initiated ART within 6 mo and 53% (95% CI: 52%–55%) within 12 mo. In the entire population, the estimated proportion of HIV-positive adults who knew their status increased from 52% to 78% for men and from 56% to 87% for women. The estimated proportion of known HIV-positive individuals on ART increased overall from 54% after the CHiP visit to 74% by the end of the round for men and from 53% to 73% for women. The estimated overall proportion of HIV-positive adults on ART, irrespective of whether they knew their status, increased from 44% to 61%, compared with the 81% target (the product of the first two 90 targets). Coverage was lower among young men and women than in older age groups. The main limitation of the study was the need for assumptions concerning knowledge of HIV status and ART coverage among adults not consenting to the intervention or HIV testing, although our conclusions were robust in sensitivity analyses. Conclusions: In this analysis, acceptance of HIV testing among those consenting to the intervention was high, although linkage to care and ART initiation took longer than expected. Knowledge of HIV-positive status increased steeply after 1 y, almost attaining the first 90 target in women and approaching it in men. The second 90 target was more challenging, with approximately three-quarters of known HIV-positive individuals on ART by the end of the annual round. Achieving higher test uptake in men and more rapid linkage to care will be key objectives during the second annual round of the intervention.