Better drug therapy for the children of Africa: current impediments to success and potential strategies for improvement

A commentary is presented on the urgent need for a comprehensive effort to improve the practice of pediatric therapeutics in Africa. A call for action is addressed to a variety of practitioners internationally, many of whom possess skills that could be fruitfully applied to the improvement of health outcomes for African children. Successful engagement with the many challenges requires the complementary effort of researchers in basic and clinical pharmacology and toxicology, nurses, pharmacists, physicians, clinical pharmacologists, clinical pharmacists, and political leaders and civil servants. While a comprehensive or systematic review of the relevant literature has not been attempted, the authors have highlighted promising initiatives driven by international agencies and academic networks. Two African perspectives are presented to reinforce the prospect of child health gains that can be achieved through consistent pursuit of optimal therapy for conditions such as respiratory infection, diarrhea, malaria, and HIV/AIDS. There is an imperative for development of north-south and south-south partnerships that will amplify current research efforts and mobilize existing knowledge concerning pediatric drugs. The overall goal is a multidisciplinary commitment to making essential medicines available at the right time, the right place, and in the right formulation for African children from infancy to adolescence

Association Between Efavirenz-Based Compared With Nevirapine-Based Antiretroviral Regimens and Virological Failure in HIV-Infected Children

Importance Worldwide, the nonnucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz and nevirapine are commonly used in first-line antiretroviral regimens in both adults and children with human immunodeficiency virus (HIV) infection. Data on the comparative effectiveness of these medications in children are limited. Objective To investigate whether virological failure is more likely among children who initiated 1 or the other NNRTI-based HIV treatment. Design, Setting, and Participants Retrospective cohort study of children (aged 3–16 years) who initiated efavirenz-based (n=421) or nevirapine-based (n=383) treatment between April 2002 and January 2011 at a large pediatric HIV care setting in Botswana. Main Outcomes and Measures The primary outcome was time from initiation of therapy to virological failure. Virological failure was defined as lack of plasma HIV RNA suppression to less than 400 copies/mL by 6 months or confirmed HIV RNA of 400 copies/mL or greater after suppression. Cox proportional hazards regression analysis compared time to virological failure by regimen. Multivariable Cox regression controlled for age, sex, baseline immunologic category, baseline clinical category, baseline viral load, nutritional status, NRTIs used, receipt of single-dose nevirapine, and treatment for tuberculosis. Results With a median follow-up time of 69 months (range, 6–112 months; interquartile range, 23–87 months), 57 children (13.5%; 95% CI, 10.4%–17.2%) initiating treatment with efavirenz and 101 children (26.4%; 95% CI, 22.0%–31.1%) initiating treatment with nevirapine had virological failure. There were 11 children (2.6%; 95% CI, 1.3%–4.6%) receiving efavirenz and 20 children (5.2%; 95% CI, 3.2%–7.9%) receiving nevirapine who never achieved virological suppression. The Cox proportional hazard ratio for the combined virological failure end point was 2.0 (95% CI, 1.4–2.7; log rank P Conclusions and Relevance Among children aged 3 to 16 years infected with HIV and treated at a clinic in Botswana, the use of efavirenz compared with nevirapine as initial antiretroviral treatment was associated with less virological failure. These findings may warrant additional research evaluating the use of efavirenz and nevirapine for pediatric patients

HIV management by nurse prescribers compared with doctors at a paediatric centre in Gaborone, Botswana

Objectives. To compare compliance with national paediatric HIV treatment guidelines between nurse prescribers and doctors at a paediatric referral centre in Gaborone, Botswana. Methods. A cross-sectional study was conducted in 2009 at the Botswana-Baylor Children’s Clinical Centre of Excellence (COE), Gaborone, Botswana, comparing the performance of nurse prescribers and physicians caring for HIV-infected paediatric patients. Selected by stratified random sampling, 100 physician and 97 nurse prescriber encounters were retrospectively reviewed for successful documentation of eight separate clinically relevant variables: pill count charted; chief complaint listed; social history updated; disclosure reviewed; physical exam; laboratory testing; World Health Organization (WHO) staging documented; paediatric dosing. Results. Nurse prescribers and physicians correctly documented 96.0% and 94.9% of the time, respectively. There was a trend towards a higher proportion of social history documentation by the nurses, but no significant difference in any other documentation items. Conclusions. Our findings support the continued investment in programmes employing properly trained nurses in southern Africa to provide quality care and ART services to HIV-infected children who are stable on therapy. Task shifting remains a promising strategy to scale up and sustain adult and paediatric ART more effectively, particularly where provider shortages threaten ART rollout. Policies guiding ART services in southern Africa should avoid restricting the delivery of crucial services to doctors, especially where their numbers are limited

A phase I trial to evaluate the safety and pharmacokinetics of low-dose methotrexate as an anti-malarial drug in Kenyan adult healthy volunteers

<p>Abstract</p> <p>Background</p> <p>Previous investigations indicate that methotrexate, an old anticancer drug, could be used at low doses to treat malaria. A phase I evaluation was conducted to assess the safety and pharmacokinetic profile of this drug in healthy adult male Kenyan volunteers.</p> <p>Methods</p> <p>Twenty five healthy adult volunteers were recruited and admitted to receive a 5 mg dose of methotrexate/day/5 days. Pharmacokinetics blood sampling was carried out at 2, 4, 6, 12 and 24 hours following each dose. Nausea, vomiting, oral ulcers and other adverse events were solicited during follow up of 42 days.</p> <p>Results</p> <p>The mean age of participants was 23.9 ± 3.3 years. Adherence to protocol was 100%. No grade 3 solicited adverse events were observed. However, one case of transiently elevated liver enzymes, and one serious adverse event (not related to the product) were reported. The maximum concentration (C_max) was 160-200 nM and after 6 hours, the effective concentration (C_eff) was <150 nM.</p> <p>Conclusion</p> <p>Low-dose methotraxate had an acceptable safety profile. However, methotrexate blood levels did not reach the desirable C_effof 250-400-nM required to clear malaria infection <it>in vivo</it>. Further dose finding and safety studies are necessary to confirm suitability of this drug as an anti-malarial agent.</p

Examining psychosocial correlates of physical activity and sedentary behavior in youth with and without HIV.

The objectives of this study were to examine differences in physical activity behaviors as a function of human immunodeficiency virus (HIV) status and sex, to test differences in physical activity self-efficacy (PASE), body weight satisfaction (BWS), and enjoyment of physical activity as a function of HIV status, and to determine if PASE, BWS, and enjoyment are associated with daily physical activity (daily PA), muscle strengthening activities, and sedentary behavior of youth with and without HIV. A total of 250 HIV positive (HIV+) and HIV negative (HIV-) youth from Botswana aged 12-23 years (Mean = 17.87, SD = 2.24) participated in the study. The HIV+ group (n = 88) was recruited from a previous 12-month antiretroviral therapy (ART) and nutrition intervention study. The HIV- group (n = 162) was randomly selected from public junior and senior (secondary) high schools in and around Gaborone. Participants' PASE, BWS, enjoyment of physical activity, daily PA, muscle strengthening, body mass index (BMI), and sedentary behavior were obtained using items from the Youth Risk Behavior Surveillance Survey. Multivariate analysis of variance (MANOVA) showed that the HIV- group (M = 1.20, SE = 0.06, CI = 1.08 to 1.32) had significantly higher daily PA than the HIV+ group (M = 0.99, SE = 0.08, CI = 0.82 to 1.15). The HIV- group (M = 0.91, SE = 0.06, CI = 0.79 to 1.03) also reported participating significantly more in muscle strengthening activities than the HIV+ group (M = 0.63, SD = 0.08, CI = 0.47 to 0.78). Multiple regression analyses showed that higher PASE (p < .001) and greater enjoyment of PA (p < .01) were predictive of higher daily PA. HIV- participants had higher PASE but lower BWS compared to HIV+ participants. Sex and age differences were observed in muscle strengthening activities and sedentary behavior. This study supports previous findings on the association of efficacy beliefs to daily PA and muscle strengthening activities. The findings have implications for PA interventions aimed at health promotion and mitigation of the effects of living with HIV/AIDS

Botswana-Baylor children's Centre of Excellence

No abstract available

The prevalence and determinants of short stature in HIV-infected children

Background: Children with HIV infection are often reported to be short. The aim of this study was to assess the prevalence of HIV-associated short stature in HIV endemic setting. Methods: Data were obtained by retrospective review of the electronic medical records. Patients were grouped into various clinical categories. For each category, the proportion of patients with height-for-age Z score of less than −2 standard deviation [SD] and of less than −3 SD was determined. Results: The prevalence of short stature (less than −2 SD) was 28.4%. Severe short stature (less than −3 SD) is more likely with percentage of CD4 &lt;15% (odds ratio [OR]: 3.30, confidence interval [CI]: 1.51-7.09, P = .002) and with males (OR: 1.49, CI: 1.19-1.87, P = .001). Severe short stature is more likely with viral load &gt;400 copies/mL (OR 2.64, CI 1.27-5.38, P = .008) and poor adherence (&lt;95%; OR 1.72, CI 1.03-2.05, P = .037). Conclusion: In Botswana, short stature affects a quarter of HIV-infected children and severe short stature is associated with poor adherence to antiretroviral treatment, severe immunosuppression, and virologic failure

Psychosocial Assessments for HIV+ African Adolescents: Establishing Construct Validity and Exploring Under-Appreciated Correlates of Adherence

<div><p>Study Objectives</p><p>Psychosocial factors such as outcome expectancy, perceived stigma, socio-emotional support, consideration of future consequences, and psychological reactance likely influence adolescent adherence to antiretroviral treatments. Culturally-adapted and validated tools for measuring these factors in African adolescents are lacking. We aimed to identify culturally-specific factors of importance to establishing local construct validity in Botswana.</p><p>Methods</p><p>Using in-depth interviews of 34 HIV+ adolescents, we explored how the psychosocial factors listed above are perceived in this cultural context. We evaluated six scales that have been validated in other contexts. We also probed for additional factors that the adolescents considered important to their HIV medication adherence. Analyses were conducted with an analytic framework approach using NVivo9 software.</p><p>Results</p><p>While the construct validity of some Western-derived assessment tools was confirmed, other tools were poorly representative of their constructs in this cultural context. Tools chosen to evaluate HIV-related outcome expectancy and perceived stigma were well-understood and relevant to the adolescents. Feedback from the adolescents suggested that tools to measure all other constructs need major modifications to obtain construct validity in Botswana. The scale regarding future consequences was poorly understood and contained several items that lacked relevance for the Batswana adolescents. They thought psychological reactance played an important role in adherence, but did not relate well to many components of the reactance scale. Measurement of socio-emotional support needs to focus on the adolescent-parent relationship, rather than peer-support in this cultural context. Denial of being HIV-infected was an unexpectedly common theme. Ambivalence about taking medicines was also expressed.</p><p>Discussion</p><p>In-depth interviews of Batswana adolescents confirmed the construct validity of some Western-developed psychosocial assessment tools, but demonstrated limitations in others. Previously underappreciated factors related to HIV medication adherence, such as denial and ambivalence, should be further explored.</p></div

Denial and Ambivalence Statements from Adolescents.

<p>Denial and Ambivalence Statements from Adolescents.</p