Browsing by Author "Ruel, Theodore"

Now showing 1 - 5 of 5
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    Antiretroviral Agents and Prevention of Malaria in HIV-Infected Ugandan Children
    (The New England Journal of Medicine, 2012) Achan, Jane; Kakuru, Abel; Ikilezi, Gloria; Ruel, Theodore; Clark, Tamara D.; Nsanzabana, Christian; Charlebois, Edwin; Aweeka, Francesca; Dorsey, Grant; Rosenthal, Philip J.; Havlir, Diane; Kamya, Moses R
    Human immunodeficiency virus (HIV) protease inhibitors show activity against Plasmodium falciparum in vitro. We hypothesized that the incidence of malaria in HIV infected children would be lower among children receiving lopinavir–ritonavir– based antiretroviral therapy (ART) than among those receiving nonnucleosidereverse transcriptase inhibitor (NNRTI)–based ART.
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    Artemisinin-Based Combination Therapies Are Efficacious and Safe for Treatment of Uncomplicated Malaria in HIV-Infected Ugandan Children
    (Clinical infectious diseases, 2014) Kakuru, Abel; Achan, Jane; Muhindo, Mary K.; Ikilezi, Gloria; Arinaitwe, Emmanuel; Mwangwa, Florence; Ruel, Theodore; Clark, Tamara D.; Charlebois, Edwin; Kamya, Moses R.; Tappero, Jordan W.; Dorsey, Grant
    Artemisinin-based combination therapies (ACTs) are highly efficacious and safe, but data from human immunodeficiency virus (HIV)–infected children concurrently receiving antiretroviral therapy (ART) and ACTs are limited. We evaluated 28-day outcomes following malaria treatment with artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) in 2 cohorts of HIV-infected Ugandan children taking various ART regimens. In one cohort, children <6 years of age were randomized to lopinavir/ritonavir (LPV/r) or nonnucleoside reverse transcriptase inhibitor–based ART and treated with AL for uncomplicated malaria. In another cohort, children <12 months of age were started on nevirapine-based ART if they were eligible, and randomized to AL or DP for the treatment of their first and all subsequent uncomplicated malaria episodes. There were 773 and 165 treatments for malaria with AL and DP, respectively. Initial response to therapy was excellent, with 99% clearance of parasites and <1% risk of repeat therapy within 3 days. Recurrent parasitemia within 28 days was common following AL treatment. The risk of recurrent parasitemia was significantly lower among children taking LPV/r-based ART compared with children taking nevirapine-based ART following AL treatment (15.3% vs 35.5%, P = .009), and those treated with DP compared with AL (8.6% vs 36.2%, P < .001). Both ACT regimens were safe and well tolerated. Treatment of uncomplicated malaria with AL or DP was efficacious and safe in HIV-infected children taking ART. However, there was a high risk of recurrent parasitemia following AL treatment, which was significantly lower in children taking LPV/r-based ART compared with nevirapine-based ART.
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    Growth Recovery Among HIV-Infected Children Randomized to Lopinavir/Ritonavir or NNRTI-Based Antiretroviral Therapy
    (The Pediatric infectious disease journal, 2016) Achan, Jane; Kakuru, Abel; Ikilezi, Gloria; Mwangwa, Florence; Charlebois, Edwin; Young, Sera; Havlir, Diane; Kamya, Moses; Ruel, Theodore
    Diminished growth is highly prevalent among HIV-infected children and might be improved by antiretroviral therapy (ART). We examined growth recovery in a rural Ugandan cohort of HIV-infected children randomized to lopinavir/ritonavir or non-nucleoside-reverse-transcription-inhibitor-based ART. HIV-infected children 2 months to 6 years of age were randomized to Lopinavir/ritonavir- or non-nucleoside-reverse-transcription-inhibitor-based ART. Changes in weight-for-age (WAZ), height-for-age (HAZ), and weight-for-height (WHZ) Z-scores for 24 months were evaluated using generalized linear repeated-measures models. Recovery from being underweight (WAZ<−2), stunted (HAZ<−2) and wasted (WHZ<−2) to Z-scores > −2 was also compared by arm using Kaplan-Meier survival and Cox proportional hazard modeling. A total of 129 children with median age of 3 years initiated therapy; 64 received Lopinavir/ritonavir-based and 65 non-nucleoside-reverse-transcription-inhibitor-based ART (nevirapine: 36 and efavirenz: 29). The median (IQR) difference in growth measures between baseline and 24 months for Lopinavir/ritonavir (n= 45) vs. non-nucleoside-reverse-transcription-inhibitor-based therapy (n=40) were as follows, WAZ: 0.47 (0.10, 1.62) vs. 0.53 (0.03, 1.14) (p=0.59) and HAZ: median 1.55 (0.78, 1.86) vs. 1.19 (0.62, 1.65) (p=0.23), respectively. ART regimen was not predictive of change in WAZ (beta: −0.02, 95%CI: −0.25, 0.20) or HAZ (beta: 0.05, 95%CI: −0.10, 0.19). Presence of confirmed virologic failure was not associated with growth. Most ART-naive children experienced recovery of both WAZ and HAZ over the 24 months following ART-initiation, with no significant difference between those receiving Lopinavir/ritonavir vs. non-nucleoside-reverse-transcriptase-inhibitor-based ART. However, the persistence of median Z-scores below zero underscores the need for additional strategies to improve growth outcomes in HIV+ African children.
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    High Risk of Neutropenia in HIV-Infected Children following Treatment with Artesunate plus Amodiaquine for Uncomplicated Malaria in Uganda
    (Clinical infectious diseases, 2008) Gasasira, Anne F.; Kamya, Moses R.; Achan, Jane; Mebrahtu, Tsedal; Kalyango, Joan N.; Ruel, Theodore; Charlebois, Edwin; Staedke, Sarah G.; Kekitiinwa, Adeodata; Rosenthal, Philip J.; Havlir, Diane; Dorsey, Grant
    Artemisinin-based combination therapies are rapidly being adopted for the treatment of malaria in Africa; however, there are limited data on their safety and efficacy among human immunodeficiency virus (HIV)–infected populations. Methods. We compared malaria treatment outcomes between cohorts of HIV-infected and HIV-uninfected children in Uganda who were observed for 18 and 29 months, respectively. Malaria was treated with artesunate plus amodiaquine, and outcomes were assessed using standardized guidelines. HIV-infected children received trimethoprim-sulfamethoxazole prophylaxis and antiretroviral therapy in accordance with current guidelines. Results. Twenty-six HIV-infected participants experiencing 35 episodes of malaria and 134 HIV-uninfected children experiencing 258 episodes of malaria were included in the study. Twelve HIV-infected children were receiving antiretroviral therapy, 11 of whom were receiving zidovudine. Malaria treatment was highly efficacious in both the HIV-infected and HIV-uninfected cohorts (28-day risk of recrudescence, 0% and 3.6%, respectively); however, there was a trend towards increased risk of recurrent malaria among the HIV-uninfected children (2.9% vs. 13.2%; Pp.08). Importantly, the risk of neutropenia 14 days after initiation of treatment with artesunate plus amodiaquine was higher among HIV-infected children than among HIV-uninfected children (45% vs. 6%; P ! .001). The severity of all episodes of neutropenia in HIV-uninfected children was mild to moderate, and 16% of episodes of neutropenia in the HIV-infected cohort were severe or life-threatening (neutrophil count, !750 cells/ mm3). In the HIV-infected cohort, the risk of neutropenia was significantly higher among children who received antiretroviral therapy than among those who did not receive antiretroviral therapy (75% vs. 26%; Pp.001). Conclusions. Artesunate plus amodiaquine was highly efficacious for malaria treatment in HIV-infected children but was associated with a high risk of neutropenia, especially in the context of concurrent antiretroviral use. Our findings highlight an urgent need for evaluation of alternative antimalarial therapies for HIV-infected individuals.
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    Quality of Inpatient Pediatric Case Management for Four Leading Causes of Child Mortality at Six Government-Run Ugandan Hospitals
    (PLoS One, 2015) Sears, David; Mpimbaza, Arthur; Kigozi, Ruth; Sserwanga, Asadu; Chang, Michelle A.; Kapella, Bryan K.; Yoon, Steven; Kamya, Moses R.; Dorsey, Grant; Ruel, Theodore
    A better understanding of case management practices is required to improve inpatient pediatric care in resource-limited settings. Here we utilize data from a unique health facilitybased surveillance system at six Ugandan hospitals to evaluate the quality of pediatric case management and the factors associated with appropriate care. Methods All children up to the age of 14 years admitted to six district or regional hospitals over 15 months were included in the study. Four case management categories were defined for analysis: suspected malaria, selected illnesses requiring antibiotics, suspected anemia, and diarrhea. The quality of case management for each category was determined by comparing recorded treatments with evidence-based best practices as defined in national guidelines. Associations between variables of interest and the receipt of appropriate case management were estimated using multivariable logistic regression. Results A total of 30,351 admissions were screened for inclusion in the analysis. Ninety-two percent of children met criteria for suspected malaria and 81% received appropriate case management. Thirty-two percent of children had selected illnesses requiring antibiotics and 89% received appropriate antibiotics. Thirty percent of children met criteria for suspected anemia and 38% received appropriate case management. Twelve percent of children had diarrhea and 18% received appropriate case management. Multivariable logistic regression revealed large differences in the quality of care between health facilities. There was also a strong association between a positive malaria diagnostic test result and the odds of receiving appropriate case management for comorbid non-malarial illnesses - children with a positive malaria test were more likely to receive appropriate care for anemia and less likely for illnesses requiring antibiotics and diarrhea. Conclusions Appropriate management of suspected anemia and diarrhea occurred infrequently. Pediatric quality improvement initiatives should target deficiencies in care unique to each health facility, and interventions should focus on the simultaneous management of multiple diagnoses.