The impact of the HPTN 071 (PopART) intervention on mortality and AIDS related morbidity amongst HIV positive adults in South Africa
| dc.contributor.advisor | Beyers, Nulda | en_ZA |
| dc.contributor.advisor | Fidler, Sarah | en_ZA |
| dc.contributor.author | Bock, Peter | en_ZA |
| dc.contributor.other | Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Paediatrics and Child Health. | en_ZA |
| dc.date.accessioned | 2018-02-27T12:18:35Z | |
| dc.date.accessioned | 2018-04-09T11:48:25Z | |
| dc.date.available | 2018-12-31T03:00:08Z | |
| dc.date.issued | 2018-03 | |
| dc.description | Thesis (PhD)--Stellenbosch University, 2018. | en_ZA |
| dc.description.abstract | 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. | en_ZA |
| dc.description.abstract | AFRIKAANSE OPSOMMING: Die Wêreldgesondheidsorganisasie (WGO) het in 2015 antiretrovirale behandeling (ART) aanbeveel vir alle MIV-positiewe individue, ongeag hulle CD4-telling. Wat universele toegang tot ART betref, het die WGO die mikpunt gestel dat ten minste 80% van MIV-positiewe individue op ART behoort te wees. Die doel van die HPTN 071 (PopART) proef, ’n verewekansigde proef in 21 gemeenskappe in Suid-Afrika en Zambië, is om te bepaal hoe twee kombinasievoorkomingspakkette op gemeenskapsvlak MIV-insidensie op bevolkingsvlak beïnvloed. HPTN 071 (PopART) het sedert Januarie 2014 tuisgebaseerde MIV-sorgpunttoetsing (“POCT”) van stapel gestuur en, ongeag CD4-telling, ART by staatsklinieke in die proefgemeenskappe voorsien. Dít was vóór die onlangse veranderinge aan WGO- en Suid-Afrikaanse riglyne oor ART, wat nou vir ART-behandeling ongeag CD4-telling voorsiening maak. Die hoofuitkoms van MIV-insidensie is beoordeel in ’n ewekansig-gekose navorsingskohort, die populasiekohort (“PC”), wat beoog om uiteindelik 44 500 MIV-positiewe en -negatiewe deelnemers tussen die ouderdom van 18 en 45 – sowat 2 000 uit elk van die 21 gemeenskappe – te werf. Die doel van hierdie PhD-proefskrif was om die uitkomste te bepaal van kliniese aktiwiteite wat die kern uitmaak van die doeltreffende voorsiening van MIV-behandelingsdienste in omgewings met ’n hoë siektelas. Die doelwitte van die PhD-studie was om te evalueer i) hoe akkuraat tuisgebaseerde MIV POCT is en watter impak die roetineaanvang van ART by individue met CD4-basislyntellings bo 500 selle/μL het op ii) attrisie in die vroeë fases van ARV-behandeling, iii) TB-insidensie in die vroeë fases van ARV-behandeling, iv) die insidensie van nierdisfunksie in die vroeë fases van ARV-behandeling, en v) ARV-getrouheid. In die strewe na hierdie doelwitte is vyf studies uitgevoer. Vier van die vyf studies is binne die HPTN 071 (PopART) proef uitgevoer. Die vyfde studie, wat ARV-getrouheid beoordeel, was ’n stelselmatige oorsig en metaontleding. Die studie wat in hoofstuk 3 beskryf word, het ’n aantal deursneeontledings gebruik om die akkuraatheid van tuisgebaseerde MIV POCT tussen Januarie 2014 en Augustus 2016 by ál 21 PopART-terreine in Suid-Afrika sowel as Zambië te beoordeel. Hierdie studie het op aanvanklik lae MIV POCT-sensitiwiteit in Suid-Afrika gedui (45-54%). MIV POCT-sensitiwiteit in Zambië, wat meer omvattende gehalteversekering en -beheer toegepas en ander MIV POCT-toestelle gebruik het, was beduidend beter vir dieselfde tydperk (95,8%). MIV POCT-sensitiwiteit in Suid-Afrika het mettertyd verbeter tot soortgelyke syfers as in Zambië deur die toepassing van streng gehalteversekering en -beheer. Die studies wat in hoofstuk 4 tot 6 gemeld word, het die data ontleed van ’n kohort volwassenes (18 jaar of ouer) wat tussen Januarie 2014 en November 2015 by drie staatsklinieke in die Wes-Kaap, Suid-Afrika, met ART begin het. Kohortnasorg is teen die einde van Mei 2016 voltooi. Die kohortstudies het bepaal watter impak die roetineaanvang van ART by individue met CD4-basislyntellings bo 500 selle/μL het op i) attrisie, ii) TB-insidensie, en iii) die insidensie van nierdisfunksie in die vroeë fases van ARV-behandeling. Altesaam 2 423 volwassenes met ’n gemiddelde CD4-basislyntelling van 328 (IQR 195-468) selle/μL is by die kliniekkohort ingesluit. Attrisie het individue ingesluit wat verlore was vir ARV-sorg weens hetsy verlies uit die nasorgstelsel of sterfte (hoofstuk 4). ’n Totaal van 636 (26,2%) volwassenes in die kohort het in die loop van die nasorgtydperk attrisie ervaar. Attrisie was hoër onder individue met CD4-basislyntellings bo 500 selle/μL vergeleke met diegene met CD4-basislyntellings van 0-500 selle/μL (aHR 1,28, 95% CI 1,07-1,55). Hierdie bevinding wek kommer oor ’n moontlike toename in attrisie uit ARV-sorg wanneer ART ongeag CD4-tellings voorsien sal word. Die algehele TB-insidensie in die kohort was 4,4 gevalle/100 PJ (hoofstuk 5). TB-insidensie was laer onder individue met CD4-basislyntellings bo 500 selle/μL vergeleke met diegene met CD4-basislyntellings van 0-500 selle/μL (aHR = 0,27; 95% CI 0,12-0,62). Daar was geen voortvloeiende TB-gevalle in die eerste drie maande van ARV-behandeling onder individue met CD4-basislyntellings bo 500 selle/μL nie. Hierdie bevindinge is belowend en ’n sterk aanduiding dat die roetinevoorsiening van ART op CD4-basislyntellings bo 500 selle/μL tot ’n beduidende afname in TB sal lei onder individue wat met ARV-behandeling begin. Die prevalensie van matige of ernstige basislynnierdisfunksie (geskatte glomerulêre filtreertempo (“EGFR”) van minder as 60 ml/min) in die kohort was laag (1,9%) (hoofstuk 6), en so ook die insidensiesyfer van matige of ernstige nierdisfunksie ná die aanvang van ART (1,9 gevalle/100 PJ). Die studie dui op geen beduidende verband tussen CD4-basislyntellings en voortvloeiende matige of ernstige nierdisfunksie ná die aanvang van ARV-behandeling nie. Ontleding van slegs daardie individue met normale basislynnierfunksie bring geen gevalle van voortvloeiende matige of ernstige nierdisfunksie aan die lig onder diegene met CD4-basislyntellings bo 500 selle/μL nie. Ook dít is ’n belowende bevinding, wat met verdere studies bevestig moet word. Die vyfde studie (hoofstuk 7) was ’n stelselmatige oorsig en metaontleding van studies wat tussen 2004 en 2015 gepubliseer is en wat die verband tussen CD4-basislyntellings en ARV-getrouheid beoordeel. Hierdie stelselmatige oorsig dui op laer ARV-getrouheid onder individue wat in hoër CD4-basislyntellingkategorieë met ARV-behandeling begin (saamgevoeg OF 0,90; 95% CI 0,84-0,96). Voormelde gepubliseerde studies het van verskillende CD4-basislyntellingkategorieë gebruik gemaak. Die algemeenste vergelyking was dié tussen individue wat op CD4-tellings bo 200 selle/μL en CD4-tellings van 0-200 selle/μL met ARV-behandeling begin. In die twee gepubliseerde studies wat oor individue met CD4-basislyntellings bo 500 selle/μL verslag gedoen het, was daar geen verskil in ARV-getrouheid tussen individue met CD4-basislyntellings bo 500 selle/μL en dié met CD4-basislyntellings van 0-500 selle/μL nie. Die studies wat vir hierdie PhD-proefskrif onderneem is, bring oor die algemeen bepaalde voordele sowel as uitdagings aan die lig wat tuisgebaseerde MIV POCT en die roetine voorsiening van ART by MIV-positiewe individue met CD4-basislyntellings bo 500 selle/μL betref. Die studies in hoofstukke 5 en 6 dui op ’n moontlike afname in die insidensie van TB en nierdisfunksie met die roetine voorsiening van ART op CD4-basislyntellings bo 500 selle/μL, wat as sterk motivering dien vir die strewe na universele toegang tot ART in omgewings met ’n hoë siektelas. Terselfdertyd is die aangemelde lae MIV POCT-sensitiwiteit en die behoefte aan streng gehalteversekering en -beheer in die implementering van tuisgebaseerde MIV POCT kommerwekkend, soos ook die bevindinge wat dui op hoër attrisie en swakker ARV-getrouheid onder diegene wat op hoër CD4-tellings met ARV-behandeling begin. Strategieë om MIV POCT-sensitiwiteit, behoud in ARV-sorg sowel as ARV-getrouheid in hierdie konteks te verbeter, behoort dus ’n voorrangsaak te wees vir program implementeerders in omgewings met ’n hoë siektelas. | en_ZA |
| dc.embargo.terms | 2018-12-31 | |
| dc.format.extent | 138 pages | en_ZA |
| dc.identifier.uri | http://hdl.handle.net/10019.1/103935 | |
| dc.language.iso | en_ZA | en_ZA |
| dc.publisher | Stellenbosch : Stellenbosch University | en_ZA |
| dc.rights.holder | Stellenbosch University | en_ZA |
| dc.subject | HPTN 071 | en_ZA |
| dc.subject | PopART | en_ZA |
| dc.subject | HIV Mortality | en_ZA |
| dc.subject | AIDS related mobidity | en_ZA |
| dc.subject | HIV infections -- Complications | en_ZA |
| dc.subject | HIV-positive persons | en_ZA |
| dc.title | The impact of the HPTN 071 (PopART) intervention on mortality and AIDS related morbidity amongst HIV positive adults in South Africa | en_ZA |
| dc.type | Thesis | en_ZA |