Lowenthal, Elizabeth D
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Publication Association Between Efavirenz-Based Compared With Nevirapine-Based Antiretroviral Regimens and Virological Failure in HIV-Infected Children(2013-05-01) Lowenthal, Elizabeth D; Ellenberg, Jonas H; Steenhoff, Andrew P; Rutstein, Richard M; Machine, Edwin; Sagdeo, Aditi; Gross, Robert; Boiditswe, Sefelani; Anabwani, GabrielImportance 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.Publication Validation of the Pediatric Symptom Checklist in HIV-Infected Batswana(2011-08-22) Lowenthal, Elizabeth D; Lawler, Kathy; Harari, Nurit; Moamogwe, Lesedi; Masunge, Japhter; Masedi, Motshodi; Matome, Bolefela; Seloilwe, Esther; Gross, Robert; Jellinek, Michael; Murphy, MichaelObjective—To determine the validity of the Pediatric Symptom Checklist (PSC), a brief measure of psychosocial health, for screening HIV+ Batswana children. Method—Setswana versions of the parent and child PSC were administered to 509 HIV+ Batswana children (age 8–16) and their parents/guardians. Test properties were evaluated and cutoff scores were derived using receiver operating characteristic curve analysis. Scores on the parent-completed PSC and the child-completed PSC-Y were compared to parental and clinic staff reports of concern about the child’s psychosocial health and to scores on the Children’s Depression Inventory and the Revised Children’s Manifest Anxiety Scale. Results—The Setswana PSC has high internal consistency (Cronbach’s alpha 0.87 for the parent-completed version). Comparing PSC scores to parental reports of concern and childreported depression symptoms, a cut-off score of 20 on the PSC and PSC-Y maximised the sensitivity and specificity. Conclusions—The PSC performed well in Setswana-speaking children and is a promising screening tool for paediatric psychosocial problems in busy clinical settings. Screening with the PSC may allow for early detection and treatment of psychosocial problems. This is likely to be of particular value for HIV+ children for whom HIV treatment non-adherence may result from untreated psychosocial dysfunction.Publication Perinatally Acquired HIV Infection in Adolescents From Sub-Saharan Africa: A Review of Emerging Challenges(2014-07-01) Lowenthal, Elizabeth D; Bakeera-Kitaka, Sabrina; Chapman, Jennifer; Marukutira, Tafireyi; Goldrath, Kathryn; Ferrand, Rashida AWorldwide, more than three million children are infected with HIV, 90% of whom live in sub-Saharan Africa. As the HIV epidemic matures and antiretroviral treatment is scaled up, children with HIV are reaching adolescence in large numbers. The growing population of adolescents with perinatally acquired HIV infection living within this region presents not only unprecedented challenges but also opportunities to learn about the pathogenesis of HIV infection. In this Review, we discuss the changing epidemiology of paediatric HIV and the particular features of HIV infection in adolescents in sub-Saharan Africa. Longstanding HIV infection acquired when the immune system is not developed results in distinctive chronic clinical complications that cause severe morbidity. As well as dealing with chronic illness, HIV-infected adolescents have to confront psychosocial issues, maintain adherence to drugs, and learn to negotiate sexual relationships, while undergoing rapid physical and psychological development. Context-specific strategies for early identification of HIV infection in children and prompt linkage to care need to be developed. Clinical HIV care should integrate age-appropriate sexual and reproductive health and psychological, educational, and social services. Health-care workers will need to be trained to recognise and manage the needs of these young people so that the increasing numbers of children surviving to adolescence can access quality care beyond specialist services at low-level health-care facilities.Publication Risk Factors for Suboptimal Antiretroviral Therapy Adherence in HIV-Infected Adolescents in Gaborone, Botswana: A Pilot Cross-Sectional Study(2013-09-11) Ndiaye, Maimouna; Nyasulu, Peter; Lowenthal, Elizabeth D; Nguyen, Hoang; Gross, Robert; Mills, Edward J; Nachega, Jean BObjective: Little is known about factors associated with suboptimal antiretroviral treatment (ART) adherence among adolescents in Sub-Saharan Africa. Our objective was to determine the level of ART adherence and predictors of non-adherence among human immunodeficiency virus (HIV)-infected adolescents at the Botswana-Baylor Children's Clinical Centre of Excellence in Gaborone, Botswana. Methods: In a cross-sectional study, 82 HIV-infected adolescents receiving ART and their caregivers were administered a structured questionnaire. The patient's clinical information was retrieved from medical records. Outcome measures included excellent pill count ART adherence (>95%) and virologic suppression (HIV viral load <400 copies/mL). Multivariate logistic regression analysis was performed to identify independent predictors of ART non-adherence. Results: The overall median (interquartile range) ART adherence was 99% (96.5–100) (N = 82). Seventy-six percent of adolescents had excellent pill count ART adherence levels and 94% achieved virologic suppression. Male adolescents made up 65% of the non-adherent group (P = 0.02). Those who displayed suboptimal ART adherence were more likely to report having ever missed ART doses due to failure to pick up medication at the pharmacy (30.0% versus 9.7%, P = 0.03). In the multivariate logistic regression model, male sex (odds ratio [OR] 3.29, 95% confidence interval [CI] 1.13–9.54; P = 0.03) was the only factor which was independently associated with suboptimal ART adherence. Conclusions: A high proportion of HIV-infected adolescents studied had excellent ART adherence and virologic suppression, with male adolescents at higher risk of suboptimal adherence than females. Further research to investigate how gender relates to suboptimal adherence may aid in the design of targeted intervention strategies.