Browsing by Author "Natukunda, Eva"

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    A Case of Cryptococcal Lymphadenitis in an HIV-Infected Child
    (AIDS research and human retroviruses, 2011) Natukunda, Eva; Musiime, Victor; Ssali, Francis; Kizito, Hilda; Kityo, Cissy; Mugyenyi, Peter
    An 8-year-old HIV-positive antiretroviral therapy-naive child developed severe headache and generalized lymphadenopathy. The serum cryptococcal antigen (CRAG) test was positive, the histology on the lymph node biopsy revealed budding yeast cells, and Cryptococcus neoformans was isolated on culture of his cerebrospinal fluid. He was treated with intravenous amphotericin B followed by oral fluconazole with a good response. Therefore cryptococcal lymphadenitis should be considered in the differential diagnosis of children presenting with lymphadenopathy and a positive serum CRAG.
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    Efficacy and Safety of Bictegravir/Emtricitabine/Tenofovir Alafenamide in Females Living With HIV: An Integrated Analysis of 5 Trials
    (Journal of Acquired Immune Deficiency Syndromes, 1999) Orkin, Chloe; Ajana, Faiza; Kityo, Cissy; Koenig, Ellen; Natukunda, Eva; Gandhi-Patel, Bhumi; Wang, Hui; Liu, Yapei; Wei, Xuelian; White, Kirsten; Makadzange, Tariro; Pikora, Cheryl; McNicholl, Ian; Collins, Sean E.; Brainard, Diana; Chuck, Susan K.
    We characterized the efficacy and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in a broad population of pediatric/adolescent/adult/elderly females living with HIV (FWH). Setting: Integrated analysis. Methods: Available data from 5 trials were integrated. Week 48 virologic suppression (HIV-1 RNA ,50 copies/mL), resistance, adverse events (AEs), and laboratory parameters were assessed. Results: Three hundred and seventy-three FWH [304 virologically suppressed; 69 antiretroviral therapy (ART)-naive] received B/F/TAF [data from comparator regimens available for 306 individuals (236 virologically suppressed and 70 ART-naive participants)]. Virologic suppression rates with B/F/TAF at week 48 were high regardless of age in participants virologically suppressed at baseline ($95%) and in ART-naive participants ($87%). Virologic suppression rates were similar in B/F/TAF and comparator regimens (both virologically suppressed and ART-naive groups). Treatment-emergent resistance was not detected in the B/F/TAF group. AEs considered related to study drugs were experienced by 9.2% (B/F/TAF) and 5.5% (comparator regimen) of virologically suppressed participants and 15.9% (B/F/TAF) and 31.4% (comparator regimen) of ART-naive participants. For virologically suppressed and ART-naive FWH combined, only 1 of the 373 B/F/TAF–treated and 2 of the 306 comparator-regimen participants discontinued because of AEs (none were bone/renal/hepatic AEs); grade 3/4 AEs were experienced by 5.1% (B/F/TAF) and 7.8% (comparator regimen); and grade 3/4 elevation of low-density lipoprotein/total cholesterol occurred in 2.7%/ 0.3% (B/F/TAF) and 5.9%/2.0% (comparator regimen). At week 48, median changes from baseline estimated glomerular filtration rate in adults were ,5 mL/min; results were similar in B/F/TAF and comparator-regimen groups. Conclusion: B/F/TAF treatment was effective and well tolerated over 48 weeks, confirming B/F/TAF as an option for a broad population of FWH.
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    Fixed-dose combination bictegravir, emtricitabine, and tenofovir alafenamide in adolescents and children with HIV: week 48 results of a single-arm, open-label, multicentre, phase 2/3 trial
    (The Lancet Child & Adolescent Health, 2021) Gaur, Aditya H.; Cotton, Mark F.; Rodriguez, Carina A.; McGrath, Eric J.; Helström, Elizabeth; Liberty, Afaaf; Natukunda, Eva; Kosalaraksa, Pope; Chokephaibulkit, Kulkanya; Maxwell, Heather; Wong, Pamela; Porter, Danielle; Majeed, Sophia; Sang Yue, Mun; Graham, Hiba; Martin, Hal; Brainard, Diana M.; Pikora, Cheryl
    Bictegravir is a potent integrase strand-transfer inhibitor (INSTI) with a high genetic barrier to resistance. Bictegravir, coformulated with emtricitabine and tenofovir alafenamide, is recommended by key European and US HIV treatment guidelines as the preferred single-tablet regimen for adults and adolescents. The aim of this study was to assess the pharmacokinetics, safety, and efficacy of switching to this regimen in virologically suppressed children and adolescents with HIV. Methods In this single-arm, open-label trial, we enrolled virologically suppressed children and adolescents (aged 6 to <18 years) with HIV at 22 hospital clinics in South Africa, Thailand, Uganda, and the USA. Eligible participants had a bodyweight of at least 25 kg, were virologically suppressed (HIV-1 RNA <50 copies per mL) on a stable ART regimen for at least 6 months before screening, had a CD4 count of at least 200 cells per μL, and an estimated glomerular filtration rate of at least 90 mL/min per 1·73 m² by the Schwartz formula at screening. All participants received the fixed-dose regimen of coformulated bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg once daily. Pharmacokinetic analysis was used for dosing confirmation, and results compared with adult values. The primary outcomes were area under the curve at the end of the dosing interval (AUCtau) and concentration at the end of the dosing interval (Ctau) of bictegravir, and incidence of treatment-emergent adverse events and laboratory abnormalities at week 24. Efficacy and safety analyses included all participants who received at least one dose of study drug. We report the 48-week results. This study is registered with ClinicalTrials.gov, NCT02881320. Findings Between Sept 29, 2016 and Feb 16, 2018, we enrolled 102 participants. 100 participants received bictegravir, emtricitabine, and tenofovir alafenamide (cohort 1 [adolescents aged 12 to <18 years], n=50; cohort 2 [children aged 6 to <12 years], n=50). The mean bictegravir AUCtau was 89 100 ng × h/mL (coefficient of variation 31·0%) in adolescents (cohort 1) and 128 000 ng × h/mL (27·8%) in children (cohort 2). Compared with adults, bictegravir Ctau was 35% lower in adolescents and 11% lower in children. The 90% CIs of both parameters were within the predefined pharmacokinetic equivalence boundary and within overall range of exposures observed in adults and deemed to be safe and efficacious (geometric least-squares mean ratio [GLSM] 86·3% [90% CI 80·0–93·0] for AUCtau and 65·4% [58·3–73·3] for Ctau in adolescents; GLSM 125% [90% CI 117–134] for AUCtau and 88·9% [80·6–98·0] for Ctau for children). Bictegravir, emtricitabine, and tenofovir alafenamide was well tolerated; most adverse events were grade 2 or less in severity and no study drug-related serious adverse events were reported. One participant discontinued study drug due to adverse events (grade 2 insomnia and anxiety). Virological suppression (HIV-1 RNA <50 copies per mL) was maintained by all 100 participants at week 24 and by 98 (98%) of 100 at week 48; no participants had treatment-emergent resistance. Interpretation In adolescents and children with HIV, the bictegravir, emtricitabine, and tenofovir alafenamide singletablet regimen was well tolerated and maintained virological suppression. Our data support the treatment of HIV in adolescents and children with this single-tablet regimen. At present, the single-tablet regimen is recommended as first-line treatment in the USA for adolescents and as an alternative regimen in children and has the potential to represent an important regimen in the paediatric population.
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    Hospitalization for severe malnutrition among HIV-infected children starting antiretroviral therapy
    (Wolters Kluwer Health, 2011) Prendergast, Andrew; Mutsa, F; Bwakura-Dangarembizi; Cook, Adrian D; Bakeera-Kitaka, Sabrina; Natukunda, Eva; Ntege, Patricia Nahirya; Nathoo, Kusum J; Karungi, Christine; Lutaakome, Joseph; Kekitiinwa, Adeodata; Gibb, Diana M
    HIV and malnutrition overlap and interact in resourcelimited settings [1]. There is high HIV prevalence among children with severe malnutrition, and mortality in these children is approximately three-fold higher than in HIV-uninfected children with severe malnutrition [2]. Similarly, malnutrition is a major risk factor for mortality in HIV-infected children. Studies from resource-limited settings, in which the majority of HIV-infected children have severe immunosuppression and poor nutritional status at presentation, consistently report 5–10% early mortality among HIV-infected children starting antiretroviral therapy (ART) [3,4]. Severe malnutrition presents as two main clinical syndromes: nonoedematous malnutrition (marasmus) and oedematous malnutrition (kwashiorkor and marasmic kwashiorkor) [5]. Although several studies report that HIV-infected children are more likely to present with nonoedematous malnutrition [6,7], there are anecdotal reports of oedematous malnutrition occurring soon after ART initiation in sub-Saharan Africa (J. Bunn, B. Amadi, personal communication); however, no study has described the frequency of this clinical observation. To better understand the interaction between malnutrition and HIV in children starting ART, we describe the frequency of hospital admissions for severe malnutrition and assess the impact of severe malnutrition on early mortality in a cohort of ART-treated children in Uganda and Zimbabwe.
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    Pediatric Underdosing of Efavirenz: A Pharmacokinetic Study in Uganda
    (JAIDS Journal of Acquired Immune Deficiency Syndromes, 2011) Fillekes, Quirine; Natukunda, Eva; Balungi, Jackie; Kendall, Lindsay; Bwakura-Dangarembizi, Mutsa; Keishanyu, Rosette; Ferrier, Alex; Lutakome, Joseph; Gibb, Diana M.; Burger, David M.; Walker, A. Sarah
    Objectives: To evaluate international pediatric efavirenz dosing recommendations using full pharmacokinetic (PK) information. Design: Open-label, multicenter, PK study. Methods: Forty-one HIV-infected Ugandan children (3–12 years) on efavirenz + lamivudine + abacavir were enrolled in a study of twice-daily to once-daily lamivudine + abacavir 36 weeks after antiretroviral therapy initiation in the ARROW trial. Once-daily efavirenz doses were 200, 250, 300, 350 mg for children weighing 10 to ,15, 15 to ,20, 20 to ,25, 25 to ,30 kg, respectively, using 200/50 mg capsules or halved 600 mg tablets in case of 300 and 350 mg doses. Intensive plasma PK sampling (t = 0, 1, 2, 4, 6, 8, 12 hours postobserved ingestion) was performed at steady state (PK1) and repeated 4 weeks later (PK2, including a further 24-hour sample). Results: Forty-one and 39 children had evaluable efavirenz profiles at PK1 and PK2, respectively. Seventeen (41%) were boys. Five, 16, 17, 3 were in the 10 to ,15, 15 to ,20, 20 to ,25, 25 to ,30 kg weight bands. The geometric mean (%CV) the area under the concentration– time curve 0–24 hours postdose was 50.8 (90.8%) and 55.5 (82.7%) h$mg$L-1 at PK1 and PK2, respectively. Six children at PK1 and 7 at PK2 had subtherapeutic C8h and/or C12h (,1.0 mg/L), 7 of 41 (17%) at either visit. At PK2, 15 of 39 (38%) children had C24h ,1.0 mg/L (median (interquartile range) [range] 1.1 (0.7–2.9) [0.3–18.4]). Ten children at PK1 and 11 at PK2 had C8h and/or C12h .4.0 mg/L; 12 of 41 (29%) at either visit. Conclusions: African children aged 3–12 years, on efavirenz dosed according to 2006 WHO/manufacturer’s recommendations, had lower and highly variable efavirenz PK parameters compared with adult data from manufacturer’s leaflet. There were no differences across weight bands, suggesting no major effect of using half tablets. Higher pediatric efavirenz doses, as per WHO 2010 recommendations, should be used and investigated further but may risk increasing the proportion of children with potentially toxic levels.
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    Safety, efficacy, and pharmacokinetics of single-tablet elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in virologically suppressed, HIV-infected children: a single-arm, open-label trial
    (The Lancet Child & Adolescent Health, 2017) Natukunda, Eva; Gaur, Aditya H.; Kosalaraksa, Pope; Batra, Jagmohan; Rakhmanina, Natella; Porter, Danielle; Rhee, Martin S.
    No once-daily single-tablet regimen is available for HIV-infected children under 12 years. The single-tablet, fixed-dose combination of elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide is a once-daily, integrase strand transfer inhibitor-based regimen approved in the USA and European Union for individuals aged 12 years or older. In this study, we aimed to assess the pharmacokinetics, safety, and efficacy of this regimen in virologically suppressed, HIV-infected children. Methods In this single-arm, open-label trial, we enrolled virologically suppressed, HIV-infected children from five hospital clinics in Uganda, the USA, and Thailand. Eligible participants were aged 6–11 years, weighed 25 kg or more, had virological suppression (<50 copies of HIV-1 RNA per mL) on a stable regimen for at least 6 months, CD4 count of more than 100 cells per μL, and no history of resistance to elvitegravir, emtricitabine, tenofovir alafenamide, or tenofovir. All participants received the available fixed-dose oral formulation of elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir alafenamide 10 mg once per day. Primary outcomes were the pharmacokinetic parameters area under the curve (AUC) concentration at the end of the dosing interval (AUCtau) for elvitegravir and the AUC from time zero to the last quantifiable concentration (AUClast) of tenofovir alafenamide, treatment-emergent serious adverse events, and all treatment-emergent adverse events. Results from baseline to week 24 are reported, unless specified otherwise. Primary and safety analyses included all enrolled participants who received one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT01854775.