Characteristics of HIV-infected Children at Enrollment Into Care and at Antiretroviral Therapy Initiation in Central Africa

BACKGROUND: Despite 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 METHODS: Data 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. RESULTS: Median 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 childre

Phenotypic and genotypic monitoring of Schistosoma mansoni in Tanzanian schoolchildren five years into a preventative chemotherapy national control programme

We conducted combined in vitro PZQ efficacy testing with population genetic analyses of S. mansoni collected from children from two schools in 2010, five years after the introduction of a National Control Programme. Children at one school had received four annual PZQ treatments and the other school had received two mass treatments in total. We compared genetic differentiation, indices of genetic diversity, and estimated adult worm burden from parasites collected in 2010 with samples collected in 2005 (before the control programme began) and in 2006 (six months after the first PZQ treatment). Using 2010 larval samples, we also compared the genetic similarity of those with high and low in vitro sensitivity to PZQ

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

Pulmonary cystic disease in HIV positive individuals in the Democratic Republic of Congo: three case reports

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

Models of support for disclosure of HIV status to HIV-infected children and adolescents in resource-limited settings

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

Viral Load Status Before Switching to Dolutegravir-Containing Antiretroviral Therapy and Associations With Human Immunodeficiency Virus Treatment Outcomes in Sub-Saharan Africa

Background: Dolutegravir is being rolled out globally as part of preferred antiretroviral therapy (ART) regimens, including among treatment-experienced patients. The role of viral load (VL) testing before switching patients already on ART to a dolutegravir-containing regimen is less clear in real-world settings. Methods: We included patients from the International epidemiology Databases to Evaluate AIDS consortium who switched from a nevirapine- or efavirenz-containing regimen to one with dolutegravir. We used multivariable cause-specific hazards regression to estimate the association of the most recent VL test in the 12 months before switching with subsequent outcomes. Results: We included 36 393 patients at 37 sites in 5 countries (Democratic Republic of the Congo, Kenya, Rwanda, Tanzania, Uganda) who switched to dolutegravir from July 2017 through February 2020, with a median follow-up of approximately 11 months. Compared with those who switched with a VL <200 copies/mL, patients without a recent VL test or with a preswitch VL ≥1000 copies/mL had significantly increased hazards of an incident VL ≥1000 copies/mL (adjusted hazard ratio [aHR], 2.89; 95% confidence interval [CI], 1.99-4.19 and aHR, 6.60; 95% CI, 4.36-9.99, respectively) and pulmonary tuberculosis or a World Health Organization clinical stage 4 event (aHR, 4.78; 95% CI, 2.77-8.24 and aHR, 13.97; 95% CI, 6.62-29.50, respectively). Conclusions: A VL test before switching to dolutegravir may help identify patients who need additional clinical monitoring and/or adherence support. Further surveillance of patients who switched to dolutegravir with an unknown or unsuppressed VL is needed

The epidemiology of adolescents living with perinatally acquired HIV: A cross-region global cohort analysis

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.info:eu-repo/semantics/publishedVersio

Two-year longitudinal survey reveals high genetic diversity of Schistosoma mansoni with adult worms surviving praziquantel treatment at the start of mass drug administration in Uganda

Background: A key component of schistosomiasis control is mass drug administration with praziquantel. While control interventions have been successful in several endemic regions, mass drug administration has been less effective in others. Here we focus on the impact of repeated praziquantel treatment on the population structure and genetic diversity of Schistosoma mansoni. Methods: We examined S. mansoni epidemiology, population genetics, and variation in praziquantel susceptibility in parasites isolated from children across three primary schools in a high endemicity region at the onset of the Ugandan National Control Programme. Children were sampled at 11 timepoints over two years, including one week and four weeks post-praziquantel treatment to evaluate short-term impacts on clearance and evidence of natural variation in susceptibility to praziquantel. Results: Prevalence of S. mansoni was 85% at baseline. A total of 3576 miracidia larval parasites, isolated from 203 individual children, were genotyped at seven loci. Overall, genetic diversity was high and there was low genetic differentiation, indicating high rates of parasite gene flow. Schistosome siblings were found both pre-treatment and four weeks post-treatment, demonstrating adult worms surviving treatment and natural praziquantel susceptibility variation in these populations at the beginning of mass drug administration. However, we did not find evidence for selection on these parasites. While genetic diversity decreased in the short-term (four weeks post-treatment), diversity did not decrease over the entire period despite four rounds of mass treatment. Furthermore, within-host genetic diversity was affected by host age, host sex, infection intensity and recent praziquantel treatment. Conclusions: Our findings suggest that praziquantel treatments have short-term impacts on these parasite populations but impacts were transient and no long-term reduction in genetic diversity was observed. High gene flow reduces the likelihood of local adaptation, so even though parasites surviving treatment were observed, these were likely to be diluted at the beginning of the Ugandan National Control Programme. Together, these results suggest that MDA in isolation may be insufficient to reduce schistosome populations in regions with high genetic diversity and gene flow