Gone but Not Lost: Implications for Estimating HIV Care Outcomes When Loss to Clinic Is Not Loss to Care

Background: In some time-to-event analyses, it is unclear whether loss to follow up should be treated as a censoring event or competing event. Such ambiguity is particularly common in HIV research that uses routinely collected clinical data to report the timing of key milestones along the HIV care continuum. In this setting, loss to follow up may be viewed as a censoring event, under the assumption that patients who are "lost" from a study clinic immediately enroll in care elsewhere, or a competing event, under the assumption that people "lost" are out of care all together. Methods: We illustrate an approach to address this ambiguity when estimating the 2-year risk of antiretroviral treatment initiation among 19,506 people living with HIV who enrolled in the IeDEA Central Africa cohort between 2006 and 2017, along with published estimates from tracing studies in Africa. We also assessed the finite sample properties of the proposed approach using simulation experiments. Results: The estimated 2-year risk of treatment initiation was 69% if patients were censored at loss to follow up or 59% if losses to follow up were treated as competing events. Using the proposed approach, we estimated that the 2-year risk of antiretroviral therapy initiation was 62% (95% confidence interval: 61, 62). The proposed approach had little bias and appropriate confidence interval coverage under scenarios examined in the simulation experiments. Conclusions: The proposed approach relaxes the assumptions inherent in treating loss to follow up as a censoring or competing event in clinical HIV cohort studies

Impact of universal antiretroviral treatment eligibility on rapid treatment initiation among young adolescents with HIV in sub-Saharan Africa.

BACKGROUND Young adolescents with perinatally-acquired HIV are at risk for poor care outcomes. We examined whether universal antiretroviral treatment (ART) eligibility policies (Treat All) improved rapid ART initiation following care enrollment among 10-14-year-olds in seven sub-Saharan African countries. METHODS Regression discontinuity analysis and data for 6,912 10-14-year-old patients were used to estimate changes in rapid ART initiation (within 30 days of care enrollment) following adoption of Treat All policies in two groups of countries: Uganda and Zambia (policy adopted in 2013) and Burundi, Democratic Republic of the Congo, Kenya, Malawi, and Rwanda (policy adopted in 2016). RESULTS There were immediate increases in rapid ART initiation among young adolescents after national adoption of Treat All. Increases were greater in countries adopting the policy in 2016, compared with those adopting it in 2013: 23.4 percentage points (pp) (95%CI: 13.9-32.8) vs. 11.2pp (95%CI: 2.5-19.9). However, the rate of increase in rapid ART initiation among 10-14-year-olds rose appreciably in countries with earlier treatment expansions, from 1.5pp per year before Treat All to 7.7pp afterwards. CONCLUSIONS Universal ART eligibility has increased rapid treatment initiation among young adolescents enrolling in HIV care. Further research should assess their retention in care and viral suppression under Treat All

Global temporal changes in the proportion of children with advanced disease at the start of combination antiretroviral therapy in an era of changing criteria for treatment initiation

Introduction: The CD4 cell count and percent at initiation of combination antiretroviral therapy (cART) are measures of advanced HIV disease and thus are important indicators of programme performance for children living with HIV. In particular, World Health Organization (WHO) 2017 guidelines on advanced HIV disease noted that >80% of children aged <5 years started cART with WHO Stage 3 or 4 disease or severe immune suppression. We compared temporal trends in CD4 measures at cART start in children from low-, middle- and high-income countries, and examined the effect of WHO treatment initiation guidelines on reducing the proportion of children initiating cART with advanced disease. Methods: We included children aged <16 years from the International Epidemiology Databases to Evaluate acquired immunodeficiency syndrome (AIDS) (IeDEA) Collaboration (Caribbean, Central and South America, Asia-Pacific, and West, Central, East and Southern Africa), the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE), the North American Pediatric HIV/AIDS Cohort Study (PHACS) and International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) 219C study. Severe immunodeficiency was defined using WHO guidelines. We used generalized weighted additive mixed effect models to analyse temporal trends in CD4 measurements and piecewise regression to examine the impact of 2006 and 2010 WHO cART initiation guidelines. Results: We included 52,153 children from fourteen low-, eight lower middle-, five upper middle- and five high-income countries. From 2004 to 2013, the estimated percentage of children starting cART with severe immunodeficiency declined from 70% to 42% (low-income), 67% to 64% (lower middle-income) and 61% to 43% (upper middle-income countries). In high-income countries, severe immunodeficiency at cART initiation declined from 45% (1996) to 14% (2012). There were annual decreases in the percentage of children with severe immunodeficiency at cART initiation after the WHO guidelines revisions in 2006 (low-, lower middle- and upper middle-income countries) and 2010 (all countries). Conclusions: By 2013, less than half of children initiating cART had severe immunodeficiency worldwide. WHO treatment initiation guidelines have contributed to reducing the proportion of children and adolescents starting cART with advanced disease. However, considerable global inequity remains, in 2013, >40% of children in low- and middle-income countries started cART with severe immunodeficiency compared to <20% in high-income countries