Moving towards a person-centred HIV care cascade: An exploration of potential biases and errors in routine data in South Africa.

In 2022, in recognition of lags in data infrastructure, the World Health Organisation (WHO) recommended the use of routinely linked individual patient data to monitor HIV programmes. The WHO also recommended a move to person-centred care to better reflect the experiences of people living with HIV. The switch from aggregated service level data to person-centred data will likely introduce some biases and errors. However, little is understood about the direction and magnitude of these biases. We investigated HIV-testing and HIV-care engagement from 2014 to 2018 in the Agincourt Health and Demographic Surveillance System (HDSS). We digitised and linked HIV patient clinic records to HDSS population data in order to estimate biases in routine clinical data. Using this linked data, we followed all individuals linked to HIV-related clinic data throughout their care pathway. We built sequences to represent these pathways. We performed sequence and cluster analyses for all individuals to categorise patterns of care engagement and identified factors associated with different engagement patterns using multinomial logistic regression. Our analyses included 4947 individuals who were linked to 5084 different patient records. We found that routine data would have inflated patient numbers by 2% due to double counting. We also found that 2% of individuals included in our analyses had received multiple HIV tests. These phenomena were driven by undocumented transfers. Further analysis of engagement patterns found a low level of stable engagement in care (<33%). Engagement fell into three distinct clusters: (i) characterised by high rates of late ART initiation, unstable engagement in care, and high mortality (53.9%), (ii) characterised by early ART initiation followed by prolonged periods of LTFU (13.7%), and (iii) characterised by early ART initiation followed by stable engagement in care (32.4%). Compared to cluster (i) older individuals were less likely to be in cluster (ii) and more likely to be in cluster (iii). Those who initiated ART prior to 2016 were more likely to be in cluster (ii) and (iii) compared to cluster (i). Those who initiated ART for PMTCT (RRR: 1.88 (95% CI: 1.45, 2.44)) or TB coinfection (RRR: 2.11 (95% CI: 1.27, 3.50)) were more likely to be in cluster (ii) when compared to those who initiated ART due to CD4 eligibility criteria. Males (RRR: 0.63 (95% CI: 0.51, 0.77)) were less likely to be in cluster (iii) compared to cluster (i) as were those who initiated ART for PMTCT (RRR: 0.77 (95% CI: 0.62, 0.97)) or under test and treat guidelines when compared to those who initiated ART due to CD4 eligibility. Only a minority of patients are consistently engaged in care while the majority cycle between engagement and disengagement. Individual level data could be useful in monitoring programmes and accurately reporting patient figures if it is of high quality, has minimal missingness and is properly linked in order to account for biases that accrue from using this kind of data.

A scoping review of media campaign strategies used to reach populations living with or at high risk for Hepatitis C in high income countries to inform future national campaigns in the United Kingdom.

BACKGROUND: With the advent of direct acting antivirals, the World Health Organisation proposed eliminating Hepatitis C as a public health threat by 2030. To achieve this, countries need to diagnose, engage in care and treat their undiagnosed populations. This will require sensitisation campaigns. However previous media campaigns have had mixed impact. We conducted a scoping review to identify and understand the impact of previous Hepatitis C media campaigns. These findings could inform the delivery of future campaigns. METHODS: We searched five electronic databases for published literature on media campaigns conducted for Hepatitis C awareness, testing, and treatment in Organisation for Economic Co-operation and Development (OECD) countries since 2010. Two independent reviewers screened citations for inclusion. Additionally, we spoke to stakeholders in the Hepatitis C field in the UK and conducted a Google search to identify any unpublished literature. A quantitative synthesis was conducted to identify targeted populations, strategies and media used, aims and impact of the campaigns. RESULTS: A title and year of publication screening of 3815 citations resulted in 113 papers that had a full abstract screen. This left 50 full-text papers, 18 were included of which 9 (50%) were from Europe. 5 (27.8%) of campaigns targeted minority ethnicities, and 9 (50%) aimed to increase testing. A Google search identified 6 grey literature sources. Most campaigns were not evaluated for impact. Discussions with stakeholders identified several barriers to successful campaigns including lack of targeted messaging, stigmatising or accusatory messaging, and short-lived or intermittent campaign strategies. CONCLUSION: Future campaigns will likely need to be multifaceted and have multiple tailored interventions. Campaigns will need to be sizeable and robust, integrated into health systems and viewed as an ongoing service rather than one-offs.

Number and timing of primary cleft lip and palate repair surgeries in England: whole nation study of electronic health records before and during the COVID-19 pandemic.

OBJECTIVE: To quantify differences in number and timing of first primary cleft lip and palate (CLP) repair procedures during the first year of the COVID-19 pandemic (1 April 2020 to 31 March 2021; 2020/2021) compared with the preceding year (1 April 2019 to 31 March 2020; 2019/2021). DESIGN: National observational study of administrative hospital data. SETTING: National Health Service hospitals in England. STUDY POPULATION: Children <5 years undergoing primary repair for an orofacial cleft Population Consensus and Surveys Classification of Interventions and Procedures-fourth revisions (OPCS-4) codes F031, F291). MAIN EXPOSURE: Procedure date (2020/2021 vs 2019/2020). MAIN OUTCOMES: Numbers and timing (age in months) of first primary CLP procedures. RESULTS: 1716 CLP primary repair procedures were included in the analysis. In 2020/2021, 774 CLP procedures were carried out compared with 942 in 2019/2020, a reduction of 17.8% (95% CI 9.5% to 25.4%). The reduction varied over time in 2020/2021, with no surgeries at all during the first 2 months (April and May 2020). Compared with 2019/2020, first primary lip repair procedures performed in 2020/2021 were delayed by 1.6 months on average (95% CI 0.9 to 2.2 months). Delays in primary palate repairs were smaller on average but varied across the nine geographical regions. CONCLUSION: There were significant reductions in the number and delays in timing of first primary CLP repair procedures in England during the first year of the pandemic, which may affect long-term outcomes.

Gestational age at birth, chronic conditions and school outcomes: a population-based data linkage study of children born in England.

INTRODUCTION: We aimed to generate evidence about child development measured through school attainment and provision of special educational needs (SEN) across the spectrum of gestational age, including for children born early term and >41 weeks of gestation, with and without chronic health conditions. METHODS: We used a national linked dataset of hospital and education records of children born in England between 1 September 2004 and 31 August 2005. We evaluated school attainment at Key Stage 1 (KS1; age 7) and Key Stage 2 (KS2; age 11) and any SEN by age 11. We stratified analyses by chronic health conditions up to age 2, and size-for-gestation, and calculated population attributable fractions (PAF). RESULTS: Of 306 717 children, 5.8% were born <37 weeks gestation and 7.0% had a chronic condition. The percentage of children not achieving the expected level at KS1 increased from 7.6% at 41 weeks, to 50.0% at 24 weeks of gestation. A similar pattern was seen at KS2. SEN ranged from 29.0% at 41 weeks to 82.6% at 24 weeks. Children born early term (37-38 weeks of gestation) had poorer outcomes than those born at 40 weeks; 3.2% of children with SEN were attributable to having a chronic condition compared with 2.0% attributable to preterm birth. CONCLUSIONS: Children born with early identified chronic conditions contribute more to the burden of poor school outcomes than preterm birth. Evaluation is needed of how early health characteristics can be used to improve preparation for education, before and at entry to school.

The procurement and supply chain strengthening project: improving public health supply chains for better access to HIV medicines, Uganda 2011-2016.

BACKGROUND: With countries moving towards reaching the UNAIDS 90-90-90 goal to achieve HIV epidemic control, there are going to be an unprecedented number of persons who will need to be tested, treated, and regularly monitored for viral suppression. However, most of the countries with the greatest burden of HIV/AIDS experience regular stock outages which could be detrimental to reaching these targets. ART and other commodities such as HIV test kits and laboratory supplies need to be readily and consistently available to achieve these targets. The main objective was to improve access to HIV/AIDS related commodities and strengthening institutional capacity for the management of HIV/AIDS logistics services through the MAUL procurement and supply chain strengthening project (PSSP) that rolled out four interventions on mentorship and support supervision, stock level monitoring, spatial visualization of stock indicators using GIS, and using WhatsApp to submit order reports as photo images. METHODS: Medical Access Uganda Limited, a private-not-for-profit supply chain management company in Uganda, implemented these interventions as part of a procurement and supply chain strengthening project (PSSP). These interventions were evaluated using performance monitoring indicators from 2011-2016. We tested for the significance in the change in scores of performance monitoring indicators using the test for difference in proportions. Health facilities were scored on 6 categories and accredited as bronze, silver or gold based on their total scores. Kaplan-Meier estimates were computed for time to silver, and gold ranking and univariate and multivariate Cox proportional hazards models were computed for time to gold ranking. RESULTS: We observed a significant reduction in reported stock-outs from 46 to 4% (p < 0.001) in the analysis period. Accurate stock card inventory rose from 79 to 91% (p < 0.001); adequate stock levels rose from 54 to 71% (p = 0.002) and stock reporting rates from 91 to 100% (p < 0.001). The stock order fill rate improved from a high of 93% to 97% (p = 0.375). Patient load (medium vs low adjusted hazard ratio (aHR): 2.19, p = 0.026; high vs low aHR: 2.97, p = 0.034) and number of support supervision visits (6-10 aHR: 3.33, p = 0.024; > 10 aHR: 5.78, p = 0.003) were associated with better stock management ranking scores. CONCLUSIONS: Improvements in supply chain management in countries committed to achieving the 90-90-90 goals are crucial to achieving HIV epidemic control. Health system strengthening and mentorship investments in Uganda were feasible and are essential for sustainable disease control efforts.

Reductions in hospital care among clinically vulnerable children aged 0-4 years during the COVID-19 pandemic.

OBJECTIVE: To quantify reductions in hospital care for clinically vulnerable children during the COVID-19 pandemic. DESIGN: Birth cohort. SETTING: National Health Service hospitals in England. STUDY POPULATION: All children aged <5 years with a birth recorded in hospital administrative data (January 2010-March 2021). MAIN EXPOSURE: Clinical vulnerability defined by a chronic health condition, preterm birth (<37 weeks' gestation) or low birth weight (<2500 g). MAIN OUTCOMES: Reductions in care defined by predicted hospital contact rates for 2020, estimated from 2015 to 2019, minus observed rates per 1000 child years during the first year of the pandemic (March 2020-2021). RESULTS: Of 3 813 465 children, 17.7% (one in six) were clinically vulnerable (9.5% born preterm or low birth weight, 10.3% had a chronic condition). Reductions in hospital care during the pandemic were much higher for clinically vulnerable children than peers: respectively, outpatient attendances (314 vs 73 per 1000 child years), planned admissions (55 vs 10) and unplanned admissions (105 vs 79). Clinically vulnerable children accounted for 50.1% of the reduction in outpatient attendances, 55.0% in planned admissions and 32.8% in unplanned hospital admissions. During the pandemic, weekly rates of planned care returned to prepandemic levels for infants with chronic conditions but not older children. Reductions in care differed by ethnic group and level of deprivation. Virtual outpatient attendances increased from 3.2% to 24.8% during the pandemic. CONCLUSION: One in six clinically vulnerable children accounted for one-third to one half of the reduction in hospital care during the pandemic.

Changes in adolescents' planned hospital care during the COVID-19 pandemic: analysis of linked administrative data.

OBJECTIVE: To describe changes in planned hospital care during the pandemic for vulnerable adolescents receiving children's social care (CSC) services or special educational needs (SEN) support, relative to their peers. DESIGN: Observational cohort in the Education and Child Health Insights from Linked Data database (linked de-identified administrative health, education and social care records of all children in England). STUDY POPULATION: All secondary school pupils in years 7-11 in academic year 2019/2020 (N=3 030 235). MAIN EXPOSURE: Receiving SEN support or CSC services. MAIN OUTCOMES: Changes in outpatient attendances and planned hospital admissions during the first 9 months of the pandemic (23 March-31 December 2020), estimated by comparing predicted with observed numbers and rates per 1000 child-years. RESULTS: A fifth of pupils (20.5%) received some form of statutory support: 14.2% received SEN support only, 3.6% received CSC services only and 2.7% received both. Decreases in planned hospital care were greater for these vulnerable adolescents than their peers: -290 vs -225 per 1000 child-years for outpatient attendances and -36 vs -16 per 1000 child-years for planned admissions. Overall, 21% of adolescents who were vulnerable disproportionately bore 25% of the decrease in outpatient attendances and 37% of the decrease in planned hospital admissions. Vulnerable adolescents were less likely than their peers to have face-to-face outpatient care. CONCLUSION: These findings indicate that socially vulnerable groups of children have high health needs, which may need to be prioritised to ensure equitable provision, including for catch-up of planned care postpandemic.

Investigating clinic transfers among HIV patients considered lost to follow-up to improve understanding of the HIV care cascade: Findings from a cohort study in rural north-eastern South Africa.

Investigating clinical transfers of HIV patients is important for accurate estimates of retention and informing interventions to support patients. We investigate transfers for adults reported as lost to follow-up (LTFU) from eight HIV care facilities in the Agincourt health and demographic surveillance system (HDSS), South Africa. Using linked clinic and HDSS records, outcomes of adults more than 90 days late for their last scheduled clinic visit were determined through clinic and routine tracing record reviews, HDSS data, and supplementary tracing. Factors associated with transferring to another clinic were determined through Cox regression models. Transfers were graphically and geospatially visualised. Transfers were more common for women, patients living further from the clinic, and patients with higher baseline CD4 cell counts. Transfers to clinics within the HDSS were more likely to be undocumented and were significantly more likely for women pregnant at ART initiation. Transfers outside the HDSS clustered around economic hubs. Patients transferring to health facilities within the HDSS may be shopping for better care, whereas those who transfer out of the HDSS may be migrating for work. Treatment programmes should facilitate transfer processes for patients, ensure continuity of care among those migrating, and improve tracking of undocumented transfers.

Patterns of engagement in HIV care during pregnancy and breastfeeding: findings from a cohort study in North-Eastern South Africa.

BACKGROUND: Eliminating mother-to-child transmission of HIV (MTCT) in sub-Saharan Africa is hindered by limited understanding of HIV-testing and HIV-care engagement among pregnant and breastfeeding women. METHODS: We investigated HIV-testing and HIV-care engagement during pregnancy and breastfeeding from 2014 to 2018 in the Agincourt Health and Demographic Surveillance System (HDSS). We linked HIV patient clinic records to HDSS pregnancy data. We modelled time to a first recorded HIV-diagnosis following conception, and time to antiretroviral therapy (ART) initiation following diagnosis using Kaplan-Meier methods. We performed sequence and cluster analyses for all pregnancies linked to HIV-related clinic data to categorise MTCT risk period engagement patterns and identified factors associated with different engagement patterns using logistic regression. We determined factors associated with ART resumption for women who were lost to follow-up (LTFU) using Cox regression. RESULTS: Since 2014, 15% of 10,735 pregnancies were recorded as occurring to previously (51%) or newly (49%) HIV-diagnosed women. New diagnoses increased until 2016 and then declined. We identified four MTCT risk period engagement patterns (i) early ART/stable care (51.9%), (ii) early ART/unstable care (34.1%), (iii) late ART initiators (7.6%), and (iv) postnatal seroconversion/early, stable ART (6.4%). Year of delivery, mother's age, marital status, and baseline CD4 were associated with these patterns. A new pregnancy increased the likelihood of treatment resumption following LTFU. CONCLUSION: Almost half of all pregnant women did not have optimal ART coverage during the MTCT risk period. Programmes need to focus on improving retention, and leveraging new pregnancies to re-engage HIV-positive women on ART.

'If the results are negative, they motivate us'. Experiences of early infant diagnosis of HIV and engagement in Option B.

Few studies have explored the relationship between early infant diagnosis (EID) of HIV and mothers' engagement in care under Option B+. We conducted in-depth interviews with 20 women who initiated antiretroviral therapy (ART) under Option B+ in rural South Africa to explore the interactions between EID and maternal care engagement. Drawing on practice theory, we identified themes relating to Option B+ care engagement and EID. Women's practice of engagement with HIV care shaped their decision-making around EID. Mothers who disengaged from care during pregnancy were less inclined to utilise EID as they lacked information about its availability and benefits. For some mothers, tensions between wanting to breastfeed and perceptions that it could facilitate transmission led to repeated utilisation of EID as reassurance that the child remained negative. Some mothers used their child's negative result as a proxy for their status, subsequently disengaging from care. For some participants, an HIV diagnosis of their infant and the subsequent double burden of treatment visits for themselves and their infant, contributed to their disengagement. Women's care-seeking practices for themselves and their infants work in a symbiotic ecosystem and should be viewed interdependently to tailor interventions to improve EID uptake and Option B+ care engagement.

Outcomes After Being Lost to Follow-up Differ for Pregnant and Postpartum Women When Compared With the General HIV Treatment Population in Rural South Africa.

BACKGROUND: Undetermined attrition prohibits full understanding of the coverage and effectiveness of HIV programs. Outcomes following loss to follow-up (LTFU) among antiretroviral therapy (ART) patients may differ according to their reasons for ART initiation. SETTING: We compare the true outcomes of adult patients previously identified as LTFU by reason for ART initiation in 8 health facilities in north eastern South Africa. METHODS: Adult HIV patient records were linked to health and demographic surveillance system (HDSS) data from 2014 to 2017. Outcomes of adults categorized as LTFU (>90 days late for the last scheduled clinic visit) were determined through clinic and routine tracing record reviews, consultation of HDSS data, and supplementary tracing. We calculated the proportion of patients per outcome category and performed competing risk survival analysis to estimate the cumulative incidence of death, transfer, migration, ART interruption, and re-engagement following LTFU. RESULTS: Of 895/1017 patients LTFU with an outcome ascertained, 120 (13.4%) had died, 225 (25.1%) re-engaged, 50 (5.6%) migrated out of the HDSS, 75 (8.4%) were alive and not on treatment, and 315 (35.1%) transferred their treatment. These outcomes varied by sex and pregnancy status at ART initiation. Mortality was less likely among pregnant women, patients with higher baseline CD4, and more likely among older patients. CONCLUSIONS: Patient survival and transfers to other facilities are considerably higher than those suggested in earlier studies. Outcomes differ for women who were pregnant or postpartum when initiating ART, with this population less likely to have died and more likely to have migrated.

Misreporting of Patient Outcomes in the South African National HIV Treatment Database: Consequences for Programme Planning, Monitoring, and Evaluation.

Background: Monitoring progress toward global treatment targets using HIV programme data in sub-Saharan Africa has proved challenging. Constraints in routine data collection and reporting can lead to biased estimates of treatment outcomes. In 2010, South Africa introduced an electronic patient monitoring system for HIV patient visits, TIER.Net. We compare treatment status and outcomes recorded in TIER.Net to outcomes ascertained through detailed record review and tracing in order to assess discrepancies and biases in retention and mortality rates. Methods: The Agincourt Health and Demographic Surveillance System (HDSS) in north-eastern South Africa is served by eight public primary healthcare facilities. Since 2014, HIV patient visits are logged electronically at these clinics, with patient records individually linked to their HDSS record. These data were used to generate a list of patients >90 days late for their last scheduled clinic visit and deemed lost to follow-up (LTFU). Patient outcomes were ascertained through a review of the TIER.Net database, physical patient files, registers kept by two non-government organizations that assist with patient tracing, cross-referencing with the HDSS records and supplementary physical tracing. Descriptive statistics were used to compare patient outcomes reported in TIER.Net to their outcome ascertained in the study. Results: Of 1,074 patients that were eligible for this analysis, TIER.Net classified 533 (49.6%) as LTFU, 80 (7.4%) as deceased, and 186 (17.3%) as transferred out. TIER.Net misclassified 36% of patient outcomes, overestimating LTFU and underestimating mortality and transfers out. TIER.Net missed 40% of deaths and 43% of transfers out. Patients categorized as LTFU in TIER.Net were more likely to be misclassified than patients classified as deceased or transferred out. Discussion: Misclassification of patient outcomes in TIER.Net has consequences for programme forecasting, monitoring and evaluation. Undocumented transfers accounted for the majority of misclassification, suggesting that the transfer process between clinics should be improved for more accurate reporting of patient outcomes. Processes that lead to correct classification of patient status including patient tracing should be strengthened. Clinics could cross-check all available data sources before classifying patients as LTFU. Programme evaluators and modelers could consider using correction factors to improve estimates of outcomes from TIER.Net.

Challenges with tracing patients on antiretroviral therapy who are late for clinic appointments in rural South Africa and recommendations for future practice.

Background: It is common practice for HIV programmes to routinely trace patients who are late for a scheduled clinic visit to ensure continued care engagement. In South Africa, patients who are late for a scheduled visit are identified from clinic registers, and called by telephone up to three times by designated clinic staff, with home visits conducted for those who are unreachable by phone. It is important to understand outcomes among late patients in order to have accurate mortality data, identify defaulters to attempt to re-engage them into care, and have accurate estimates of patients still in care for planning purposes.Objective: We conducted a study to assess whether tracing of HIV patients in clinics in rural north-eastern South Africa was implemented in line with national policies.Methods: Thirty-three person-day of observations took place during multiple visits to eight facilities between October 2017 and January 2018 during which clinic tracing processes were captured. The facility level implementation processes were compared to the intended tracing process and gaps and challenges were identified.Results: Challenges to implementing effective tracing procedures fell into three broad categories: i) facility-level barriers, ii) issues relating to data, documentation and record-keeping, and iii) challenges relating to the roles and responsibilities of the different actors in the tracing cascade.We recommend improving linkages between clinics, improving record-keeping systems, and regular training of community health workers involved in tracing activities. Improved links between clinics would reduce the chance of patients being lost between clinics. Record-keeping systems could be improved through motivating health workers to take ownership of their data and training them on the importance of complete data. Finally, training of community health workers may improve sustained motivation, and improve their ability to respond appropriately to their clients' needs.Conclusions: Substantial investment in data infrastructure and healthcare staff training is needed to improve routine tracing.

Outcomes of patients lost to follow-up after antiretroviral therapy initiation in rural north-eastern South Africa.

OBJECTIVE: The vital status of patients lost to follow-up often remains unknown in antiretroviral therapy (ART) programmes in sub-Saharan Africa because medical records are no longer updated once the patient disengages from care. Thus, we aimed to assess the outcomes of patients lost to follow-up after ART initiation in north-eastern South Africa. METHODS: Using data from a rural area in north-eastern South Africa, we estimated the cumulative incidence of patient outcomes (i) after treatment initiation using clinical records, and (ii) after loss to follow-up (LTFU) using data from clients that have been individually linked to Agincourt Health and Demographic Surveillance System (AHDSS) database. Aside from LTFU, we considered mortality, re-engagement and migration out of the study site. Cox proportional hazards regression was used to identify covariates of these patient outcomes. RESULTS: Between April 2014 and July 2017, 3700 patients initiated ART and contributed a total of 6818 person-years of follow-up time. Three years after ART initiation, clinical record-based estimates of LTFU, mortality and documented transfers were 41.0% (95% CI: 38.5-43.4%), 1.9% (95% CI 1.0-3.2%) and 0.1% (95% CI 0.0-0.9%), respectively. Among those who were LTFU, the cumulative incidence of re-engagement, out-migration and mortality at 3 years were 38.1% (95% CI 33.1-43.0%), 49.4% (95% CI 43.1-55.3%) and 4.7% (95% CI 3.5-6.2%), respectively. Pregnant or breastfeeding women, foreigners and those who initiated ART most recently were at an increased risk of LTFU. CONCLUSION: LTFU among patients starting ART in north-eastern South Africa is relatively high and has increased in recent years as more asymptomatic patients have initiated treatment. Even though this tendency is of concern in light of the prevention of onwards transmission, we also found that re-engagement in care is common and mortality among persons LTFU relatively low.

OBJECTIF: Le statut vital des patients perdus au suivi reste souvent inconnu dans les programmes de traitement antirétroviral (ART) en Afrique subsaharienne parce que les dossiers médicaux ne sont plus mis à jour une fois que le patient se désengage des soins. Notre objectif était d'évaluer les résultats des patients dans le nord-est de l'Afrique du Sud. MÉTHODES: A l'aide de données provenant d'une zone rurale du nord-est de l'Afrique du Sud, nous avons estimé l'incidence cumulée des résultats pour les patients (i) après le début du traitement à l'aide des dossiers cliniques et (ii) après la perte au suivi (PS) à l'aide des données des patients qui ont été reliées individuellement à la base de données du système de surveillance démographique et de santé (AHDSS) d'Agincourt. Outre les PS, nous avons pris en compte la mortalité, le réengagement et la migration hors du site de l'étude. La régression des risques proportionnels de Cox a été utilisée pour identifier les covariables de ces résultats pour le patient. RÉSULTATS: Entre avril 2014 et juillet 2017, 3.700 patients ont commencé l'ART constituant un suivi total de 6.818 années-personnes. Trois ans après le début de l'ART, les estimations des PS, de la mortalité et des transferts documentés selon les registres cliniques étaient de 41,0% (IC95%: 38,5% à 43,4%), 1,9% (IC95%: 1,0% à 3,2%) et 0,1% (IC95%: 0,0% -0,9%), respectivement. Parmi ceux qui étaient PS, l'incidence cumulative de réengagement, d'émigration et de mortalité à trois ans était de 38,1% (IC95%: 33,1% à 43,0%), 49,4% (IC95%: 43,1% à 55,3%) et 4,7% (IC95%: 3,5% -6,2%), respectivement. Les femmes enceintes ou allaitantes, les étrangers et les personnes qui ont commencé l'ART le plus récemment couraient un risque accru de PS. CONCLUSION: La PS chez les patients commençant une ART dans le nord-est de l'Afrique du Sud est relativement élevée et a augmenté ces dernières années à mesure que davantage de patients asymptomatiques ont commencé le traitement. Même si cette tendance est préoccupante à la lumière de la prévention de la transmission, nous avons également constaté que le réengagement dans les soins était courant et que la mortalité parmi les PS était relativement faible.

Successes and challenges in optimizing the viral load cascade to improve antiretroviral therapy adherence and rationalize second-line switches in Swaziland.

INTRODUCTION: As antiretroviral therapy (ART) is scaled up, more patients become eligible for routine viral load (VL) monitoring, the most important tool for monitoring ART efficacy. For HIV programmes to become effective, leakages along the VL cascade need to be minimized and treatment switching needs to be optimized. However, many HIV programmes in resource-constrained settings report significant shortfalls. METHODS: From a public sector HIV programme in rural Swaziland, we evaluated the VL cascade of adults (≥18 years) on ART from the time of the first elevated VL (>1000 copies/mL) between January 2013 and June 2014 to treatment switching by December 2015. We additionally described HIV drug resistance for patients with virological failure. We used descriptive statistics and Kaplan-Meier estimates to describe the different steps along the cascade and regression models to determine factors associated with outcomes. RESULTS AND DISCUSSION: Of 828 patients with a first elevated VL, 252 (30.4%) did not receive any enhanced adherence counselling (EAC). Six hundred and ninety-six (84.1%) patients had a follow-up VL measurement, and the predictors of receiving a follow-up VL were being a second-line patient (adjusted hazard ratio (aHR): 0.72; p = 0.051), Hlathikhulu health zone (aHR: 0.79; p = 0.013) and having received two EAC sessions (aHR: 1.31; p = 0.023). Four hundred and ten patients (58.9%) achieved VL re-suppression. Predictors of re-suppression were age 50 to 64 (adjusted odds ratio (aOR): 2.02; p = 0.015) compared with age 18 to 34 years, being on second-line treatment (aOR: 3.29; p = 0.003) and two (aOR: 1.66; p = 0.045) or three (aOR: 1.86; p = 0.003) EAC sessions. Of 278 patients eligible to switch to second-line therapy, 120 (43.2%) had switched by the end of the study. Finally, of 155 successfully sequenced dried blood spots, 144 (92.9%) were from first-line patients. Of these, 133 (positive predictive value: 92.4%) had resistance patterns that necessitated treatment switching. CONCLUSIONS: Patients on ART with high VLs were more likely to re-suppress if they received EAC. Failure to re-suppress after counselling was predictive of genotypically confirmed resistance patterns requiring treatment switching. Delays in switching were significant despite the ability of the WHO algorithm to predict treatment failure. Despite significant progress in recent years, enhanced focus on quality care along the VL cascade in resource-limited settings is crucial.

Challenges and successes in the implementation of option B+ to prevent mother-to-child transmission of HIV in southern Swaziland.

BACKGROUND: Universal antiretroviral therapy (ART) for all pregnant/ breastfeeding women living with Human Immunodeficiency Virus (HIV), known as Prevention of mother-to child transmission of HIV (PMTCT) Option B+ (PMTCTB+), is being scaled up in most countries in Sub-Saharan Africa. In the transition to PMTCTB+, many countries face challenges with proper implementation of the HIV care cascade. We aimed to describe the feasibility of a PMTCTB+ approach in the public health sector in Swaziland. METHODS: Lifelong ART was offered to a cohort of HIV+ pregnant women aged ≥16 years at the first antenatal care (ANC1) visit in 9 public sector facilities, between 01/2013 and 06/2014. The study enrolment period was divided into 3 phases (early: 01-06/2013, mid: 07-12/2013 and late: 01-06/2014) to account for temporal trends. Kaplan-Meier estimates and Cox proportional-hazards regression models were applied for ART initiation and attrition analyses. RESULTS: Of 665 HIV+ pregnant women, 496 (74.6%) initiated ART. ART initiation increased in later study enrolment phases (mid: aHR: 1.41; later: aHR: 2.36), and decreased at CD4 ≥ 500 (aHR: 0.69). 52.9% were retained in care at 24 months. Attrition was associated with ANC1 in the third trimester (aHR: 2.37), attending a secondary care facility (aHR: 1.98) and ART initiation during later enrolment phases (mid aHR: 1.48; late aHR: 1.67). Of 373 women eligible, 67.3% received a first VL. 223/251 (88.8%) were virologically suppressed (< 1000 copies/mL). Of 670 infants, 53.6% received an EID test, 320/359 had a test result recorded and of whom 7 (2.2%) were HIV+. CONCLUSIONS: PMTCTB+ was found to be feasible in this setting, with high rates of maternal viral suppression and low transmission to the infant. High treatment attrition, poor follow-up of mother-baby pairs and under-utilisation of VL and EID testing are important programmatic challenges.

Super Learner Analysis of Electronic Adherence Data Improves Viral Prediction and May Provide Strategies for Selective HIV RNA Monitoring.

OBJECTIVE: Regular HIV RNA testing for all HIV-positive patients on antiretroviral therapy (ART) is expensive and has low yield since most tests are undetectable. Selective testing of those at higher risk of failure may improve efficiency. We investigated whether a novel analysis of adherence data could correctly classify virological failure and potentially inform a selective testing strategy. DESIGN: Multisite prospective cohort consortium. METHODS: We evaluated longitudinal data on 1478 adult patients treated with ART and monitored using the Medication Event Monitoring System (MEMS) in 16 US cohorts contributing to the MACH14 consortium. Because the relationship between adherence and virological failure is complex and heterogeneous, we applied a machine-learning algorithm (Super Learner) to build a model for classifying failure and evaluated its performance using cross-validation. RESULTS: Application of the Super Learner algorithm to MEMS data, combined with data on CD4 T-cell counts and ART regimen, significantly improved classification of virological failure over a single MEMS adherence measure. Area under the receiver operating characteristic curve, evaluated on data not used in model fitting, was 0.78 (95% confidence interval: 0.75 to 0.80) and 0.79 (95% confidence interval: 0.76 to 0.81) for failure defined as single HIV RNA level >1000 copies per milliliter or >400 copies per milliliter, respectively. Our results suggest that 25%-31% of viral load tests could be avoided while maintaining sensitivity for failure detection at or above 95%, for a cost savings of $16-$29 per person-month. CONCLUSIONS: Our findings provide initial proof of concept for the potential use of electronic medication adherence data to reduce costs through behavior-driven HIV RNA testing.