HIV-associated anemia after 96 weeks on therapy: determinants across age ranges in Uganda and Zimbabwe.

Given the detrimental effects of HIV-associated anemia on morbidity, we determined factors associated with anemia after 96 weeks of antiretroviral therapy (ART) across age groups. An HIV-positive cohort (n=3,580) of children age 5-14, reproductive age adults 18-49, and older adults ≥50 from two randomized trials in Uganda and Zimbabwe were evaluated from initiation of therapy through 96 weeks. We conducted logistic and multinomial regression to evaluate common and differential determinants for anemia at 96 weeks on therapy. Prior to initiation of ART, the prevalence of anemia (age 5-11 <10.5 g/dl, 12-14 <11 g/dl, adult females <11 g/dl, adult males <12 g/dl) was 43%, which decreased to 13% at week 96 (p<0.001). Older adults had a significantly higher likelihood of anemia compared to reproductive age adults (OR 2.60, 95% CI 1.44-4.70, p=0.002). Reproductive age females had a significantly higher odds of anemia compared to men at week 96 (OR 2.56, 95% CI 1.92-3.40, p<0.001), and particularly a greater odds for microcytic anemia compared to males in the same age group (p=0.001). Other common factors associated with anemia included low body mass index (BMI) and microcytosis; greater increases in CD4 count to week 96 were protective. Thus, while ART significantly reduced the prevalence of anemia at 96 weeks, 13% of the population continued to be anemic. Specific groups, such as reproductive age females and older adults, have a greater odds of anemia and may guide clinicians to pursue further evaluation and management

EXPLORING BIOGRAPHIES: THE EDUCATIONAL JOURNEY TOWARDS BECOMING INCLUSIVE EDUCATORS OF CHILDREN WITH DISABILITIES

The current study explored the formative processes of twelve student teachers constructing role understandings in the context of their experiences and interactions with people with disabilities. In particular, it examined the participants’ changing notions of self-as-teacher and their unfolding perceptions of an inclusive educator’s role in teaching children with disabilities. The research aimed to investigate personal and professional forms of knowledge linked with the prior subjective life experiences of the student teachers and those arising from their interactions in situated learning experiences in community settings. The contextual framework of the study focused on the development of the student teachers’ unique understandings and awareness of people with disabilities through processes of biographical situated learning. The investigation examined participants’ voluntary out-ofcourse experiences with people with disabilities across three community settings for the ways in which these experiences facilitated the participants’ emerging role understandings. These settings included respite experiences in families’ homes of young children with disabilities receiving early intervention, an after-school recreational program for primary and secondary aged children and adolescents with disabilities, and an independent living centre providing post-school options and activities for adults with disabilities. ii Two groups participated in the current study, each consisted of six student teachers in the Bachelor of Education Course at the Bathurst campus of Charles Sturt University. Group One participants were in the second year compulsory inclusive education subject and Group Two participants were in the third year elective early intervention subject. The investigation examines the nature of reflexive and reflective processes of the student teachers from subjective, conflict realities in an attempt to link community experiences with real-life issues affecting inclusive educational practices. The voluntary community experiences engaged the research participants in multi-faceted interactions with people with disabilities, providing thought-provoking contexts for their reflections on observations, responses and reactions to situations, such as critical incidents. The participants engaged in reflexive and reflective processes in records made in learning journals and in semi-structured interviews conducted throughout the investigation. Results were analysed from a constructivist research paradigm to investigate their emerging role understandings. Prior to this study there had been few practical components in the compulsory undergraduate inclusive education subject which meant that previously student teachers gained theoretical knowledge without the opportunity to apply their learning. Many student teachers had expressed their feelings of anxiety and uneasiness about what they should do and say to a person with a disability. Thus, the community experiences were selected in order to give a specific context for student teachers’ learning and to provide participants with expanded opportunities to consider their professional identity, social awareness and acceptance of people with disabilities. iii An analysis of the data demonstrated the centrality of reflection within a situated teaching and learning framework. Understandings of prior experiences and motivation were shown to interact with the outcomes of the community experiences through an on-going process of reflection and reflexivity. This reconstructing process encouraged learners to reflect on past, present and projected future experiences and reframe actions from multiple perspectives as a way of exploring alternatives within broader contexts. The data reveal the participants’ engagement in the community experiences facilitated their awareness of wider socio-cultural educational issues, while focusing their attention on more appropriate inclusive teaching and learning strategies. The reflective inquiry process of identifying diverse issues led participants to consider other possible alternatives to current community practices for better ways to support their changing perspectives on ideal inclusive classroom practices. The dialogic nature of participants’ on-going deliberations contributed to the construction of their deeper understandings of an inclusive educator’s role. The findings of the study identified external environmental and internal personal factors as contributing biographical influences which shaped the student teachers’ emerging role understandings. The results emphasised the value of contextual influences in promoting desirable personal and professional qualities in student teachers. Importantly, situated learning enhanced participants’ unique interpretations of their prospective roles. As a result of analysing their insights from interactions in community contexts, the student teachers had increased their personal and professional understandings of individuals with disabilities and broadened their perceptions of their roles as inclusive educators. Thus, the study found that encouraging a biographical reflexive and reflective orientation in participants was conducive iv to facilitating changes in their understandings. Overall, the outcomes had benefits for student teachers and teacher educators in finding innovative ways for integrating biographical perspectives into situated teaching and learning approaches. The study showed that contextual influences facilitated deeper understanding of role identity and produced new ideas about the nature of reflexivity and reflection in guiding student teachers’ learning. (Note: Appendices not included in digital version of thesis

Predicting Patterns of Long-Term CD4 Reconstitution in HIV-Infected Children Starting Antiretroviral Therapy in Sub-Saharan Africa: A Cohort-Based Modelling Study

Long-term immune reconstitution on antiretroviral therapy (ART) has important implications for HIV-infected children, who increasingly survive into adulthood. Children's response to ART differs from adults', and better descriptive and predictive models of reconstitution are needed to guide policy and direct research. We present statistical models characterising, qualitatively and quantitatively, patterns of long-term CD4 recovery

A randomized trial of prolonged co-trimoxazole in HIV-infected children in Africa

Co-trimoxazole (fixed-dose trimethoprim-sulfamethoxazole) prophylaxis administered before antiretroviral therapy (ART) reduces morbidity in children infected with the human immunodeficiency virus (HIV). We investigated whether children and adolescents receiving long-term ART in sub-Saharan Africa could discontinue co-trimoxazole

HIV-associated anemia after 96 weeks on therapy: determinants across age ranges in Uganda and Zimbabwe.

Given the detrimental effects of HIV-associated anemia on morbidity, we determined factors associated with anemia after 96 weeks of antiretroviral therapy (ART) across age groups. An HIV-positive cohort (n=3,580) of children age 5-14, reproductive age adults 18-49, and older adults ≥50 from two randomized trials in Uganda and Zimbabwe were evaluated from initiation of therapy through 96 weeks. We conducted logistic and multinomial regression to evaluate common and differential determinants for anemia at 96 weeks on therapy. Prior to initiation of ART, the prevalence of anemia (age 5-11 &lt;10.5 g/dl, 12-14 &lt;11 g/dl, adult females &lt;11 g/dl, adult males &lt;12 g/dl) was 43%, which decreased to 13% at week 96 (p&lt;0.001). Older adults had a significantly higher likelihood of anemia compared to reproductive age adults (OR 2.60, 95% CI 1.44-4.70, p=0.002). Reproductive age females had a significantly higher odds of anemia compared to men at week 96 (OR 2.56, 95% CI 1.92-3.40, p&lt;0.001), and particularly a greater odds for microcytic anemia compared to males in the same age group (p=0.001). Other common factors associated with anemia included low body mass index (BMI) and microcytosis; greater increases in CD4 count to week 96 were protective. Thus, while ART significantly reduced the prevalence of anemia at 96 weeks, 13% of the population continued to be anemic. Specific groups, such as reproductive age females and older adults, have a greater odds of anemia and may guide clinicians to pursue further evaluation and management

Pubertal development in HIV-infected African children on first-line antiretroviral therapy.

OBJECTIVES: To estimate age at attaining Tanner stages in Ugandan/Zimbabwean HIV-infected children initiating antiretroviral therapy (ART) in older childhood and investigate predictors of delayed puberty, particularly age at ART initiation. DESIGN: Observational analysis within a randomized trial. METHODS: Tanner staging was assessed every 24 weeks from 10 years of age, menarche every 12 weeks and height every 4-6 weeks. Age at attaining different Tanner stages was estimated using normal interval regression, considering predictors using multivariable regression. Growth was estimated using multilevel models with child-specific intercepts and trajectories. RESULTS: Median age at ART initiation was 9.4 years (inter-quartile range 7.8, 11.3) (n = 582). At the first assessment, the majority (80.2%) were in Tanner stage 1; median follow-up with staging was 2.8 years. There was a strong delaying effect of older age at ART initiation on age at attaining all Tanner stages (P &lt; 0.05) and menarche (P = 0.02); in boys the delaying effect generally weakened with older age. There were additional significant delays associated with greater impairments in pre-ART height-for-age Z-score (P &lt; 0.05) in both sexes and pre-ART BMI-for-age in girls (P &lt; 0.05). There was no evidence that pre-ART immuno-suppression independently delayed puberty or menarche. However, older children/adolescents had significant growth spurts in intermediate Tanner stages, and were still significantly increasing their height when in Tanner stage 5 (P &lt; 0.01). CONCLUSION: Delaying ART initiation until older childhood substantially delays pubertal development and menarche, independently of immuno-suppression. This highlights that factors other than CD4, such as pubertal development, need consideration when making decisions about timing of ART initiation in older children

Virologic response to first-line efavirenz- or nevirapine-based antiretroviral therapy in HIV-infected African children

BACKGROUND: Poorer virologic response to nevirapine- versus efavirenz-based antiretroviral therapy (ART) has been reported in adult systematic reviews and pediatric studies. METHODS: We compared drug discontinuation and viral load (VL) response in ART-naïve Ugandan/Zimbabwean children ≥3 years of age initiating ART with clinician-chosen nevirapine versus efavirenz in the ARROW trial. Predictors of suppression &lt;80, &lt;400 and &lt;1000 copies/mL at 36, 48 and 144 weeks were identified using multivariable logistic regression with backwards elimination (P = 0.1). RESULTS: A total of 445 (53%) children received efavirenz and 391 (47%) nevirapine. Children receiving efavirenz were older (median age, 8.6 vs. 7.5 years nevirapine, P &lt; 0.001) and had higher CD4% (12% vs. 10%, P = 0.05), but similar pre-ART VL (P = 0.17). The initial non-nucleoside-reverse-transcriptase-inhibitor (NNRTI) was permanently discontinued for adverse events in 7 of 445 (2%) children initiating efavirenz versus 9 of 391 (2%) initiating nevirapine (P = 0.46); at switch to second line in 17 versus 23, for tuberculosis in 0 versus 26, for pregnancy in 6 versus 0 and for other reasons in 15 versus 5. Early (36-48 weeks) virologic suppression &lt;80 copies/mL was superior with efavirenz, particularly in children with higher pre-ART VL (P = 0.0004); longer-term suppression was superior with nevirapine in older children (P = 0.05). Early suppression was poorer in the youngest and oldest children, regardless of NNRTI (P = 0.02); longer-term suppression was poorer in those with higher pre-ART VL regardless of NNRTI (P = 0.05). Results were broadly similar for &lt;400 and &lt;1000 copies/mL. CONCLUSION: Short-term VL suppression favored efavirenz, but long-term relative performance was age dependent, with better suppression in older children with nevirapine, supporting World Health Organization recommendation that nevirapine remains an alternative NNRTI.</p

Virologic response to first-line efavirenz- or nevirapine-based antiretroviral therapy in HIV-infected African children

Background Poorer virologic response to nevirapine vs efavirenz-based antiretroviral therapy (ART) has been reported in adult systematic reviews and paediatric studies. Methods We compared drug discontinuation and viral load (VL) response in ART-naïve Ugandan/Zimbabwean children aged ≥3 years initiating ART with clinician-chosen nevirapine vs efavirenz in the ARROW trial. Predictors of suppression Results 445(53%) children received efavirenz and 391(47%) nevirapine. Children receiving efavirenz were older (median 8.6 years vs 7.5 nevirapine, p Conclusion Short-term VL suppression favoured efavirenz, but long-term relative performance was age-dependent, with better suppression in older children with nevirapine, supporting WHO’s recommendation that nevirapine remain an alternative NNRTI.</p

Pharmacokinetics of zidovudine dosed twice daily according to World Health Organization weight bands in Ugandan HIV-infected children.

Data on zidovudine pharmacokinetics in children dosed using World Health Organization weight bands are limited. About 45 HIV-infected, Ugandan children, 3.4 (2.6-6.2) years, had intensive pharmacokinetic sampling. Geometric mean zidovudine AUC0-12h was 3.0 h.mg/L, which is higher than previously observed in adults, and was independently higher in those receiving higher doses, younger and underweight children. Higher exposure was also marginally associated with lower hemoglobin