Success with antiretroviral treatment for children in Kigali, Rwanda: Experience with health center/nurse-based care

BACKGROUND: Although a number of studies have shown good results in treating children with antiretroviral drugs (ARVs) in hospital settings, there is limited published information on results in pediatric programs that are nurse-centered and based in health centers, in particular on the psychosocial aspects of care. METHODS: Program treatment and outcome data were reported from two government-run health centers that were supported by Médecins Sans Frontières (MSF) in Kigali, Rwanda between October 2003 and June 2007. Interviews were held with health center staff and MSF program records were reviewed to describe the organization of the program. Important aspects included adequate training and supervision of nurses to manage ARV treatment. The program also emphasized family-centered care addressing the psychosocial needs of both caregivers and children to encourage early diagnosis, good adherence and follow-up. RESULTS: A total of 315 children (< 15 years) were started on ARVs, at a median age of 7.2 years (range: 0.7-14.9). Sixty percent were in WHO clinical stage I/II, with a median CD4% of 14%. Eighty-nine percent (n = 281) started a stavudine-containing regimen, mainly using the adult fixed-dose combination. The median follow-up time after ARV initiation was 2 years (interquartile range 1.2-2.6). Eighty-four percent (n = 265) of children were still on treatment in the program. Thirty (9.5%) were transferred out, eight (2.6%) died and 12 (3.8%) were lost to follow-up. An important feature of the study was that viral loads were done at a median time period of 18 months after starting ARVs and were available for 87% of the children. Of the 174 samples, VL was < 400 copies/ml in 82.8% (n = 144). Two children were started on second-line ARVs. Treatment was changed due to toxicity for 26 children (8.3%), mainly related to nevirapine. CONCLUSION: This report suggests that providing ARVs to children in a health center/nurse-based program is both feasible and very effective. Adequate numbers and training of nursing staff and an emphasis on the psychosocial needs of caregivers and children have been key elements for the successful scaling-up of ARVs at this level of the health system

Preliminary outcomes of a paediatric highly active antiretroviral therapy cohort from KwaZulu-Natal, South Africa

BACKGROUND: Few studies address the use of paediatric highly active antiretroviral therapy (HAART) in Africa. METHODS: We performed a retrospective cohort study to investigate preliminary outcomes of all children eligible for HAART at Sinikithemba HIV/AIDS clinic in KwaZulu-Natal, South Africa. Immunologic, virologic, clinical, mortality, primary caregiver, and psychosocial variables were collected and analyzed. RESULTS: From August 31, 2003 until October 31, 2005, 151 children initiated HAART. The median age at HAART initiation was 5.7 years (range 0.3–15.4). Median follow-up time of the cohort after HAART initiation was 8 months (IQR 3.5–13.5). The median change in CD4% from baseline (p < 0.001) was 10.2 (IQR 5.0–13.8) at 6 months (n = 90), and 16.2 (IQR 9.6–20.3) at 12 months (n = 59). Viral loads (VLs) were available for 100 children at 6 months of which 84% had HIV-1 RNA levels ≤ 50 copies/mL. At 12 months, 80.3% (n = 61) had undetectable VLs. Sixty-five out of 88 children (73.8%) reported a significant increase (p < 0.001) in weight after the first month. Eighty-nine percent of the cohort (n = 132) reported ≤ 2 missed doses during any given treatment month (> 95%adherence). Seventeen patients (11.3%) had a regimen change; two (1.3%) were due to antiretroviral toxicity. The Kaplan-Meier one year survival estimate was 90.9% (95%confidence interval (CI) 84.8–94.6). Thirteen children died during follow-up (8.6%), one changed service provider, and no children were lost to follow-up. All 13 deaths occurred in children with advanced HIV disease within 5 months of treatment initiation. In multivariate analysis of baseline variables against mortality using Cox proportional-hazards model, chronic gastroenteritis was associated with death [hazard ratio (HR), 12.34; 95%CI, 1.27–119.71) and an HIV-positive primary caregiver was found to be protective against mortality [HR, 0.12; 95%CI, 0.02–0.88). Age, orphanhood, baseline CD4%, and hemoglobin were not predicators of mortality in our cohort. Fifty-two percent of the cohort had at least one HIV-positive primary caregiver, and 38.4% had at least one primary caregiver also on HAART at Sinikithemba clinic. CONCLUSION: This report suggests that paediatric HAART can be effective despite the challenges of a resource-limited setting

Multiple Measures Reveal Antiretroviral Adherence Successes and Challenges in HIV-Infected Ugandan Children

Background: Adherence to HIV antiretroviral therapy (ART) among children in developing settings is poorly understood. Methodology/Principal Findings: To understand the level, distribution, and correlates of ART adherence behavior, we prospectively determined monthly ART adherence through multiple measures and six-monthly HIV RNA levels among 121 Ugandan children aged 2–10 years for one year. Median adherence levels were 100% by three-day recall, 97.4% by 30-day visual analog scale, 97.3% by unannounced pill count/liquid formulation weights, and 96.3% by medication event monitors (MEMS). Interruptions in MEMS adherence of $\geq$48 hours were seen in 57.0% of children; 36.3% had detectable HIV RNA at one year. Only MEMS correlated significantly with HIV RNA levels (r = −0.25, p = 0.04). Multivariable regression found the following to be associated with <90% MEMS adherence: hospitalization of child (adjusted odds ratio [AOR] 3.0, 95% confidence interval [CI] 1.6–5.5; p = 0.001), liquid formulation use (AOR 1.4, 95%CI 1.0–2.0; p = 0.04), and caregiver’s alcohol use (AOR 3.1, 95%CI 1.8–5.2; p<0.0001). Child’s use of co-trimoxazole (AOR 0.5, 95%CI 0.4–0.9; p = 0.009), caregiver’s use of ART (AOR 0.6, 95%CI 0.4–0.9; p = 0.03), possible caregiver depression (AOR 0.6, 95%CI 0.4–0.8; p = 0.001), and caregiver feeling ashamed of child’s HIV status (AOR 0.5, 95%CI 0.3–0.6; p<0.0001) were protective against <90% MEMS adherence. Change in drug manufacturer (AOR 4.1, 95%CI 1.5–11.5; p = 0.009) and caregiver’s alcohol use (AOR 5.5, 95%CI 2.8–10.7; p<0.0001) were associated with $\geq$48-hour interruptions by MEMS, while second-line ART (AOR 0.3, 95%CI 0.1–0.99; p = 0.049) and increasing assets (AOR 0.7, 95%CI 0.6–0.9; p = 0.0007) were protective against these interruptions. Conclusions/Significance: Adherence success depends on a well-established medication taking routine, including caregiver support and adequate education on medication changes. Caregiver-reported depression and shame may reflect fear of poor outcomes, functioning as motivation for the child to adhere. Further research is needed to better understand and build on these key influential factors for adherence intervention development

Regulatory T cells and their role in rheumatic diseases: a potential target for novel therapeutic development

Regulatory T cells have an important role in limiting immune reactions and are essential regulators of self-tolerance. Among them, CD4+CD25high regulatory T cells are the best-described subset. In this article, we summarize current knowledge on the phenotype, function, and development of CD4+CD25high regulatory T cells. We also review the literature on the role of these T cells in rheumatic diseases and discuss the potential for their use in immunotherapy

Track D Social Science, Human Rights and Political Science

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138414/1/jia218442.pd

Sex in the shadow of HIV:A systematic review of prevalence, risk factors, and interventions to reduce sexual risk-taking among HIVpositive adolescents and youth in sub-Saharan Africa

Background Evidence on sexual risk-taking among HIV-positive adolescents and youth in sub-Saharan Africa is urgently needed. This systematic review synthesizes the extant research on prevalence, factors associated with, and interventions to reduce sexual risk-taking among HIV-positive adolescents and youth in sub-Saharan Africa. Methods Studies were located through electronic databases, grey literature, reference harvesting, and contact with researchers. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Quantitative studies that reported on HIV-positive participants (10-24 year olds), included data on at least one of eight outcomes (early sexual debut, inconsistent condom use, older partner, transactional sex, multiple sexual partners, sex while intoxicated, sexually transmitted infections, and pregnancy), and were conducted in sub-Saharan Africa were included. Two authors piloted all processes, screened studies, extracted data independently, and resolved any discrepancies. Due to variance in reported rates and factors associated with sexual risk-taking, meta-analyses were not conducted. Results 610 potentially relevant titles/abstracts resulted in the full text review of 251 records. Forty-two records (n=35 studies) reported one or multiple sexual practices for 13,536 HIV-positive adolescents/youth from 13 sub-Saharan African countries. Seventeen cross-sectional studies reported on individual, relationship, family, structural, and HIV-related factors associated with sexual risk-taking. However, the majority of the findings were inconsistent across studies, and most studies scored Conclusions Sexual risk-taking among HIV-positive adolescents and youth is high, with inconclusive evidence on potential determinants. Few known studies test secondary HIV-prevention interventions for HIV-positive youth. Effective and feasible low-cost interventions to reduce risk are urgently needed for this group.</p