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WHO’s Treat All guidelines, which eliminate eligibility thresholds for people living with HIV to receive antiretroviral therapy, have been implemented by most countries. However, the impact of Treat All on the process of HIV disease progression is unknown. We conducted a target trial to emulate a hypothetical RCT to evaluate the policy’s impact on HIV disease progression among people living with HIV. We included people enrolled in HIV care during 2013-2019 from the Central Africa International Epidemiology Databases to Evaluate AIDS. Multistate models inferred the transitional hazards of disease progression across the four WHO clinical stages (1: asymptomatic; 2: mild; 3: advanced; 4: severe) and death. We estimated hazard ratios (HR) between a cohort enrolling in HIV care after (n=4,607) and a cohort enrolling before (n=4,439) Treat All guideline implementation, with and without covariates adjustment. Treat All implementation was associated with decreased hazards of transition in most stage categories, with significant results from stage 1 to stage 2 (adjusted HR (aHR) 0.64, 95% CI 0.44-0.94) and from stage 1 to death (0.37, 0.17-0.81), and non-significant but low HR results from stage 2 to 3 (0.71, 0.50-1.01), from stage 2 to death (0.58, 0.18-1.80). Treat All implementation substantially reduced HIV disease progression.Main Point SummaryWe compared the HIV disease progression outcome between a pri- and post-Treat All periods, utilizing individual service delivery data from Central Africa International Epidemiology Databases to Evaluate AIDS. We concluded that Treat All implementation substantially reduced HIV disease progression.

Background Young adolescents with perinatally acquired human immunodeficiency virus (HIV) are at risk for poor care outcomes. We examined whether universal antiretroviral treatment (ART) eligibility policies (Treat All) improved rapid ART initiation after care enrollment among 10–14-year-olds in 7 sub-Saharan African countries. Methods Regression discontinuity analysis and data for 6912 patients aged 10–14-years were used to estimate changes in rapid ART initiation (within 30 days of care enrollment) after adoption of Treat All policies in 2 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 than in those adopting it in 2013: 23.4 percentage points (pp) (95% confidence interval, 13.9–32.8) versus 11.2pp (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 per year afterward. 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.

Introduction The Central Africa International epidemiology Database to Evaluate AIDS (CA‐IeDEA) is an open observational cohort study investigating impact, progression and long‐term outcomes of HIV/AIDS among people living with HIV (PLWH) in Burundi, Cameroon, Democratic Republic of Congo (DRC), Republic of Congo (ROC) and Rwanda. We describe trends in demographic, clinical and immunological characteristics as well as antiretroviral therapy (ART) use of patients aged > 15 years entering into HIV care in the participating CA‐IeDEA site. Methods Information on sociodemographic characteristics, height, weight, body mass index (BMI), CD4 cell count, WHO staging and ART status at entry into care from 2004 through 2018 were extracted from clinic records of patients aged > 15 years enrolling in HIV care at participating clinics in Burundi, Cameroon, DRC, ROC and Rwanda. We assessed trends in patient characteristics at enrolment in HIV care including ART initiation within the first 30 days after enrolment in care and calculated proportions, means and medians (interquartile ranges) for the main variables of interest. Results Among 69,176 patients in the CA‐IeDEA cohort, 39% were from Rwanda, 24% from ROC, 18% from Cameroon, 14% from Burundi and 5% from DRC. More women (66%) than men enrolled in care and subsequently initiated ART. Women were also younger than men (32 vs. 38 years, P

BackgroundThe Central Africa International epidemiology Database to Evaluate AIDS (CA-IeDEA) is a prospective study investigating impact, progression and long-term outcomes of HIV/AIDS among people living with HIV (PLWH) in Burundi, Cameroon, Democratic Republic of Congo (DRC), Republic of Congo (ROC) and Rwanda. We described trends in baseline demographic, clinical and immunological characteristics of patients aged >15 years entering into HIV care in the participating CA-IeDEA site and subsequent ART initiation.Materials and MethodsInformation on socio-demographic characteristics, height, weight, body mass index (BMI), CD4 cell count, WHO staging and ART status at entry into care from 2004 to 2018 were extracted from clinic records of patients aged >15 years enrolling in HIV care at participating clinics in Burundi, Cameroon, DRC, ROC and Rwanda. We assessed trends in patient characteristics at enrollment in HIV care and ART initiation at the participating site and calculated proportions, means and medians (interquartile ranges) for the main variables of interest.ResultsAmong 69,176 participants in the CA-IeDEA cohort, 39% % were from Rwanda,, 24% from ROC, 18% from Cameroon, 14% from Burundi and 5% from DRC. More women (66%) than men were enrolled in care and subsequently initiated ART. Women were also younger (32 years) than men (38 years) (p= ConclusionTrends from 2004-2018 in the characteristics of patients participating in the CA-IeDEA cohort highlight improvements over time at entry into care and subsequent ART in all participating sites.

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.

BACKGROUND Estimates of incidence of switching to second-line antiretroviral therapy (ART) among children with HIV are necessary to inform the need for paediatric second-line formulations. We aimed to quantify the cumulative incidence of switching to second-line ART among children in an international cohort collaboration. METHODS In this international cohort collaboration study, we pooled individual patient-level data for children younger than 18 years who initiated ART (two or more nucleoside reverse-transcriptase inhibitors [NRTI] plus a non-NRTI [NNRTI] or boosted protease inhibitor) between 1993 and 2015 from 12 observational cohort networks in the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration. Patients who were reported to be horizontally infected with HIV and those who were enrolled in trials of treatment monitoring, switching, or interruption strategies were excluded. Switch to second-line ART was defined as change of one or more NRTI plus either change in drug class (NNRTI to protease inhibitor or vice versa) or protease inhibitor change, change from single to dual protease inhibitor, or addition of a new drug class. We used cumulative incidence curves to assess time to switching, and multivariable proportional hazards models to explore patient-level and cohort-level factors associated with switching, with death and loss to follow-up as competing risks. FINDINGS At the data cutoff of Sept 16, 2015, 182 747 children with HIV were included in the CIPHER dataset, of whom 93 351 were eligible, with 83 984 (90·0%) from sub-Saharan Africa. At ART initiation, the median patient age was 3·9 years (IQR 1·6-6·9) and 82 885 (88·8%) patients initiated NNRTI-based and 10 466 (11·2%) initiated protease inhibitor-based regimens. Median duration of follow-up after ART initiation was 26 months (IQR 9-52). 3883 (4·2%) patients switched to second-line ART after a median of 35 months (IQR 20-57) of ART. The cumulative incidence of switching at 3 years was 3·1% (95% CI 3·0-3·2), but this estimate varied widely depending on the cohort monitoring strategy, from 6·8% (6·5-7·2) in settings with routine monitoring of CD4 (CD4% or CD4 count) and viral load to 0·8% (0·6-1·0) in settings with clinical only monitoring. In multivariable analyses, patient-level factors associated with an increased likelihood of switching were male sex, older age at ART initiation, and initial NNRTI-based regimen (p

International audience; INTRODUCTION: Disclosure of HIV status to HIV-infected children and adolescents is a major care challenge. We describe current site characteristics related to disclosure of HIV status in resource-limited paediatric HIV care settings within the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium.METHODS: An online site assessment survey was conducted across the paediatric HIV care sites within six global regions of IeDEA. A standardized questionnaire was administered to the sites through the REDCap platform.RESULTS: From June 2014 to March 2015, all 180 sites of the IeDEA consortium in 31 countries completed the online survey: 57% were urban, 43% were health centres and 86% were integrated clinics (serving both adults and children). Almost all the sites (98%) reported offering disclosure counselling services. Disclosure counselling was most often provided by counsellors (87% of sites), but also by nurses (77%), physicians (74%), social workers (68%), or other clinicians (65%). It was offered to both caregivers and children in 92% of 177 sites with disclosure counselling. Disclosure resources and procedures varied across geographical regions. Most sites in each region reported performing staff members' training on disclosure (72% to 96% of sites per region), routinely collecting HIV disclosure status (50% to 91%) and involving caregivers in the disclosure process (71% to 100%). A disclosure protocol was available in 14% to 71% of sites. Among the 143 sites (79%) routinely collecting disclosure status process, the main collection method was by asking the caregiver or child (85%) about the child's knowledge of his/her HIV status. Frequency of disclosure status assessment was every three months in 63% of the sites, and 71% stored disclosure status data electronically.CONCLUSION: The majority of the sites reported offering disclosure counselling services, but educational and social support resources and capacities for data collection varied across regions. Paediatric HIV care sites worldwide still need specific staff members' training on disclosure, development and implementation of guidelines for HIV disclosure, and standardized data collection on this key issue to ensure the long-term health and wellbeing of HIV-infected youth.

Background: Globally, the population of adolescents living with perinatally acquired HIV (APHs) continues to expand. In this study, we pooled data from observational pediatric HIV cohorts and cohort networks, allowing comparisons of adolescents with perinatally acquired HIV in “real-life” settings across multiple regions. We describe the geographic and temporal characteristics and mortality outcomes of APHs across multiple regions, including South America and the Caribbean, North America, Europe, sub-Saharan Africa, and South and Southeast Asia. Methods and findings: Through the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER), individual retrospective longitudinal data from 12 cohort networks were pooled. All children infected with HIV who entered care before age 10 years, were not known to have horizontally acquired HIV, and were followed up beyond age 10 years were included in this analysis conducted from May 2016 to January 2017. Our primary analysis describes patient and treatment characteristics of APHs at key time points, including first HIV-associated clinic visit, antiretroviral therapy (ART) start, age 10 years, and last visit, and compares these characteristics by geographic region, country income group (CIG), and birth period. Our secondary analysis describes mortality, transfer out, and lost to follow-up (LTFU) as outcomes at age 15 years, using competing risk analysis. Among the 38,187 APHs included, 51% were female, 79% were from sub-Saharan Africa and 65% lived in low-income countries. APHs from 51 countries were included (Europe: 14 countries and 3,054 APHs; North America: 1 country and 1,032 APHs; South America and the Caribbean: 4 countries and 903 APHs; South and Southeast Asia: 7 countries and 2,902 APHs; sub-Saharan Africa, 25 countries and 30,296 APHs). Observation started as early as 1982 in Europe and 1996 in sub-Saharan Africa, and continued until at least 2014 in all regions. The median (interquartile range [IQR]) duration of adolescent follow-up was 3.1 (1.5–5.2) years for the total cohort and 6.4 (3.6–8.0) years in Europe, 3.7 (2.0–5.4) years in North America, 2.5 (1.2–4.4) years in South and Southeast Asia, 5.0 (2.7–7.5) years in South America and the Caribbean, and 2.1 (0.9–3.8) years in sub-Saharan Africa. Median (IQR) age at first visit differed substantially by region, ranging from 0.7 (0.3–2.1) years in North America to 7.1 (5.3–8.6) years in sub-Saharan Africa. The median age at ART start varied from 0.9 (0.4–2.6) years in North America to 7.9 (6.0–9.3) years in sub-Saharan Africa. The cumulative incidence estimates (95% confidence interval [CI]) at age 15 years for mortality, transfers out, and LTFU for all APHs were 2.6% (2.4%–2.8%), 15.6% (15.1%–16.0%), and 11.3% (10.9%–11.8%), respectively. Mortality was lowest in Europe (0.8% [0.5%–1.1%]) and highest in South America and the Caribbean (4.4% [3.1%–6.1%]). However, LTFU was lowest in South America and the Caribbean (4.8% [3.4%–6.7%]) and highest in sub-Saharan Africa (13.2% [12.6%–13.7%]). Study limitations include the high LTFU rate in sub-Saharan Africa, which could have affected the comparison of mortality across regions; inclusion of data only for APHs receiving ART from some countries; and unavailability of data from high-burden countries such as Nigeria. Conclusion: To our knowledge, our study represents the largest multiregional epidemiological analysis of APHs. Despite probable under-ascertained mortality, mortality in APHs remains substantially higher in sub-Saharan Africa, South and Southeast Asia, and South America and the Caribbean than in Europe. Collaborations such as CIPHER enable us to monitor current global temporal trends in outcomes over time to inform appropriate policy responses., 0, SCOPUS: ar.j, info:eu-repo/semantics/published

BackgroundDespite the World Health Organization (WHO) regularly updating guidelines to recommend earlier initiation of antiretroviral therapy (ART) in children, timely enrollment into care and initiation of ART in sub-Saharan Africa in children lags behind that of adults. The impact of implementing increasingly less restrictive ART guidelines on ART initiation in Central Africa has not been described.Materials and methodsData are from the Central Africa International Epidemiologic Databases to Evaluate AIDS (IeDEA) pediatric cohort of 3,426 children (0-15 years) entering HIV care at 15 sites in Burundi, DRC, and Rwanda. Measures include CD4 count, WHO clinical stage, age, and weight-for-age Z score (WAZ), each at enrollment into HIV care and at ART initiation. Changes in the medians or proportions of each measure by year of enrollment and year of ART initiation were assessed to capture potential impacts of changing ART guidelines.ResultsMedian age at care enrollment decreased from 77.2 months in 2004-05 to 30.3 months in 2012-13. The median age at ART initiation (n = 2058) decreased from 83.0 months in 2004-05 to 66.9 months in 2012-13. The proportion of children ≤24 months of age at enrollment increased from 12.7% in 2004-05 to 46.7% in 2012-13, and from 9.6% in 2004-05 to 24.2% in 2012-13 for ART initiation. The median CD4 count at enrollment into care increased from 563 (IQR: 275, 901) in 2004-05 to 660 (IQR: 339, 1071) cells/μl in 2012-13, and the median CD4 count at ART initiation increased from 310 (IQR:167, 600) in 2004-05 to 589 (IQR: 315, 1113) cells/μl in 2012-13. From 2004-05 to 2012-13, median WAZ improved from -2 (IQR: -3.4, -1.1) to -1 (IQR: -2.5, -0.2) at enrollment in care and from -2 (IQR: -3.8, -1.6) to -1 (IQR: -2.6, -0.4) at ART initiation.Discussion and conclusionAlthough HIV-infected children ≤24 months of age accounted for half of all children enrolling in care in our cohort during 2012-13, they represented less than a quarter of all those who were initiated on ART during the same period. Further research is needed to identify barriers to timely diagnosis, linkage to care, and initiation of ART among children with HIV infection.

We assessed isoniazid preventive therapy (IPT) completion and predictors among HIV-infected children and adults in two HIV clinics in Kinshasa, Democratic Republic of Congo. Between 1 September 2012 and 15 June 2013, 546 children (1-15 years) and 1532 adults (>15 years) were initiated on IPT; 86.6% (408/470) of the children and 88.2% (1129/1280) of the adults with an IPT outcome completed their therapy. Patients on antiretroviral therapy at IPT initiation were more likely to complete IPT.

Background Loss to care is high among asymptomatic HIV-infected women initiated on antiretroviral therapy (ART) during pregnancy or in the postpartum period. However, whether pregnancy itself plays a role in the high loss to care rate is uncertain. We compared loss to care over seven years between pregnant and non-pregnant women at enrollment into HIV care in the Democratic Republic of Congo (DRC). Methods We conducted a retrospective analysis of all ART-naive women aged 15–45 initiating HIV care at two large clinics in Kinshasa, DRC, from 2007–2013. Pregnancy status was recorded at care enrollment. Patients were classified as having no follow-up if they did not return to care after the initial enrollment visit. Among those with at least one follow-up visit after enrollment, we classified patients as lost to care if more than 365 days had passed since their last clinic visit. We used logistic regression to model the association between pregnancy status and no follow-up, and Cox proportional hazards regression to model the association between pregnancy status and time to loss to care. Results Of 2175 women included in the analysis, 1497 (68.8%) were pregnant at enrollment. Compared to non-pregnant women, pregnant women were less likely to be over 35 years of age (19.1% vs. 31.9%, p

Objective: We aimed to describe factors associated with mortality among children receiving antiretroviral treatment (ART) at a pediatric hospital in Kinshasa, Democratic Republic of the Congo. Results: Two hundred ninety-nine children, =2 opportunistic infections before ART initiation, severe immunosuppression as defined by age-specific CD4 count or percentage criteria, hemoglobin

Pulmonary emphysema and bronchiectasis in HIV seropositive patients has been described in the presence of injection drug use, malnutrition, repeated opportunistic infections, such as Pneumocytis jirovici pneumonia and Mycobacterium tuberculosis infection, and has been linked to the presence of HIV virus in lung tissue. Given the high burden of pulmonary infections and malnutrition among people living with HIV in resource poor settings, these individuals may be at increased risk of developing pulmonary emphysema, potentially reducing the long term benefit of antiretroviral therapy (ART) if initiated late in the course of HIV infection. In this report, we describe three HIV-infected individuals (one woman and two children) presenting with extensive pulmonary cystic disease.

Sporothrix schenckii is a ubiquitous fungus, causing mostly non life-threatening localized infections of the skin and subcutaneous tissues that can be treated with oral antifungal agents. Meningeal, pulmonary and osteoarticular dissemination occur mainly in immunosuppressed patients. Pulmonary sporothricosis is rare and responds poorly to treatment. Cases of disseminated sporotrichosis have most frequently been reported in patients residing in South America and Asia, and have increasingly been reported in AIDS patients. The distribution and pathogenicity of S. schenckii in Sub-Saharan Africa is not well known. We report a case of invasive pulmonary sporothrichosis in an eleven year old HIV-infected boy in Kinshasa, Democratic Republic of the Congo, successfully treated with oral fluconazole.