Browsing by Author "Charlebois, Edwin"

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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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    Assessing the Quality of Tuberculosis Evaluation for Children with Prolonged Cough Presenting to Routine Community Health Care Settings in Rural Uganda
    (PloS one, 2014) Marquez, Carina; Davis, J. Lucian; Katamba, Achilles; Haguma, Priscilla; Ochomi, Emmanuel; Ayakaka, Irene; Chamie, Gabriel; Dorsey, Grant; Kamya, Moses R.; Charlebois, Edwin; Havlir, Diane V.; Cattamanchi, Adithya
    Improving childhood tuberculosis (TB) evaluation and care is a global priority, but data on performance at community health centers in TB endemic regions are sparse. Objective: To describe the current practices and quality of TB evaluation for children with cough $2 weeks’ duration presenting to community health centers in Uganda. Methods: Cross-sectional analysis of children (,15 years) receiving care at five Level IV community health centers in rural Uganda for any reason between 2009–2012. Quality of TB care was assessed using indicators derived from the International Standards of Tuberculosis Care (ISTC). Results: From 2009–2012, 1713 of 187,601 (0.9%, 95% CI: 0.4–1.4%) children presenting to community health centers had cough $ 2 weeks’ duration. Of those children, only 299 (17.5%, 95% CI: 15.7–19.3%) were referred for sputum microscopy, but 251 (84%, 95% CI: 79.8–88.1%) completed sputum examination if referred. The yield of sputum microscopy was only 3.6% (95% CI: 1.3–5.9%), and only 55.6% (95% CI: 21.2–86.3%) of children with acid-fast bacilli positive sputum were started on treatment. Children under age 5 were less likely to be referred for sputum examination and to receive care in accordance with ISTC. The proportion of children evaluated in accordance with ISTC increased over time (4.6% in 2009 to 27.9% in 2012, p = 0.03), though this did not result in increased case-detection. Conclusion: The quality of TB evaluation was poor for children with cough $2 weeks’ duration presenting for health care. Referrals for sputum smear microscopy and linkage to TB treatment were key gaps in the TB evaluation process, especially for children under the age of five.
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    Association of Implementation of a Universal Testing and Treatment Intervention With HIV Diagnosis, Receipt of Antiretroviral Therapy, and Viral Suppression in East Africa
    (Jama, 2017) Maya, Petersen; Balzer, Laura; Kwarsiima, Dalsone; Ayieko, James; Kabami, Jane; Owaraganise, Asiphas; Mwangwa, Florence; Kadede, Kevin; Bukusi, Elizabeth A.; Tamara, D. Clark; Charlebois, Edwin; Kamya, Moses; Havlir, Diane
    Antiretroviral treatment (ART) is now recommended for all HIV-positive persons. UNAIDS has set global targets to diagnose 90% of HIV-positive individuals, treat 90% of diagnosed individuals with ART, and suppress viral replication among 90% of treated individuals, for a population-level target of 73% of all HIV-positive persons with HIV viral suppression. To describe changes in the proportions of HIV-positive individuals with HIV viral suppression, HIV-positive individuals who had received a diagnosis, diagnosed individuals treated with ART, and treated individuals with HIV viral suppression, following implementation of a community-based testing and treatment program in rural East Africa. Observational analysis based on interim data from 16 rural Kenyan (n = 6) and Ugandan (n = 10) intervention communities in the SEARCH Study, an ongoing cluster randomized trial. Community residents who were 15 years or older (N = 77 774) were followed up for 2 years (2013-2014 to 2015-2016). HIV serostatus and plasma HIV RNA level were measured annually at multidisease health campaigns followed by home-based testing for nonattendees. All HIV-positive individuals were offered ART using a streamlined delivery model designed to reduce structural barriers, improve patient-clinician relationships, and enhance patient knowledge and attitudes about HIV. Primary outcome was viral suppression (plasma HIV RNA<500 copies/mL) among all HIV-positive individuals, assessed at baseline and after 1 and 2 years. Secondary outcomes included HIV diagnosis, ART among previously diagnosed individuals, and viral suppression among those who had initiated ART. Among 77 774 residents (male, 45.3%; age 15-24 years, 35.1%), baseline HIV prevalence was 10.3% (7108 of 69 283 residents). The proportion of HIV-positive individuals with HIV viral suppression at baseline was 44.7% (95% CI, 43.5%-45.9%; 3464 of 7745 residents) and after 2 years of intervention was 80.2% (95% CI, 79.1%-81.2%; 5666 of 7068 residents), an increase of 35.5 percentage points (95% CI, 34.4-36.6). After 2 years, 95.9% of HIV-positive individuals had been previously diagnosed (95% CI, 95.3%-96.5%; 6780 of 7068 residents); 93.4% of those previously diagnosed had received ART (95% CI, 92.8%-94.0%; 6334 of 6780 residents); and 89.5% of those treated had achieved HIV viral suppression (95% CI, 88.6%-90.3%; 5666 of 6334 residents). Among individuals with HIV in rural Kenya and Uganda, implementation of community-based testing and treatment was associated with an increased proportion of HIV-positive adults who achieved viral suppression, along with increased HIV diagnosis and initiation of antiretroviral therapy. In these communities, the UNAIDS population-level viral suppression target was exceeded within 2 years after program implementation.
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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.