Browsing by Author "Gasasira, Anne F."

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    The effect of HIV on malaria in the context of the current standard of care for HIV-infected populations in Africa
    (Future virology, 2012) Kamya, Moses R.; Byakika-Kibwika, Pauline; Gasasira, Anne F.; Havlir, Diane; Rosenthal, Philip J.; Dorsey, Grant; Achan, Jane
    HIV infection affects the clinical pattern of malaria. There is emerging evidence to suggest that previously documented interactions may be modified by recently scaled-up HIV and malaria interventions. Prophylaxis with trimethoprim– sulfamethoxazole (TS) in combination with use of insecticide-treated nets can markedly decrease the incidence of malaria in HIV-infected pregnant and nonpregnant adults and children even in the setting of antifolate resistanceconferring mutations that are currently common in Africa. Nonetheless, additional interventions are needed to protect HIV-infected people that reside in highmalaria- transmission areas. Artemether–lumefantrine and dihydroartemisinin– piperaquine are highly efficacious and safe for the treatment of uncomplicated malaria in HIV-infected persons. Coadministration of antiretroviral and antimalarial drugs creates the potential for pharmacokinetic drug interactions that may increase (causing enhancement of malaria treatment efficacy and posttreatment prophylaxis and/or unanticipated toxicity) or reduce (creating risk for treatment failure) antimalarial drug exposure. Further studies are needed to elucidate potentially important pharmacokinetic interactions between commonly used antimalarials, antiretrovirals and TS and their clinical implications. Data on the benefits of long-term TS prophylaxis among HIV patients on antiretroviral therapy who have achieved immune-reconstitution are limited. Studies to address these questions are ongoing or planned, and the results should provide the evidence base required to guide the prevention and treatment of malaria in HIV-infected patients.
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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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    Predictors of Long-Term Viral Failure Among Ugandan Children and Adults Treated With Antiretroviral Therapy
    (JAIDS Journal of Acquired Immune Deficiency Syndromes, 2007) Kamya, Moses R.; Mayanja-Kizza, Harriet; Kambugu, Andrew; Bakeera-Kitaka, Sabrina; Semitala, Fred; Mwebaze-Songa, Patricia; Castelnuovo, Barbara; Gasasira, Anne F.; Katabira, Elly; Kekitiinwa, Adeodata; Thomas, David L.; the Academic Alliance for AIDS Care and Prevention in Africa
    HIV RNA viral load testing is costly and is generally unavailable in resource-limited settings. We identified predictors of viral failure and documented genotypic mutations in a subset of patients with viral failure after 12 months on antiretroviral therapy (ART).From April 2004 to June 2005, consecutive treatment-naive patients beginning ART at a university clinic in Uganda were enrolled. Clinical information, CD4 cell count, and HIV RNA level were collected at baseline and every 3 to 6 months. Independent predictors of viral failure were identified using multivariate logistic regression. Genotypic drug resistance for 8 patients with viral failure at 12 months was measured at baseline and at 6 and 12 months.Five hundred twenty-six adults and 250 children (0 to 18 years of age) were started on first-line ART regimens and followed for 12 months. Outcomes could not be assessed in 13% of patients (79 died and 21 were withdrawn). Children were almost twice as likely to have viral failure compared with adults (26% vs. 14%; P = 0.0001). In adults, the sole independent predictor of viral failure was treatment with stavudine (d4T)/lamivudine (3TC)/nevirapine (NVP) versus zidovudine (ZDV)/3TC/efavirenz (EFV) (odds ratio [OR] = 2.59, 95% confidence interval [CI]: 1.20 to 5.59). In children, independent predictors of viral failure included male gender (OR = 2.44, 95% CI: 1.20 to 4.93), baseline CD4% <5 (OR = 2.69, 95% CI: 1.28 to 5.63), and treatment with d4T/3TC/NVP versus ZDV/3TC/EFV (OR = 2.46, 95% CI: 1.23 to 4.90). All 8 patients with viral breakthrough and genotypic drug resistance results had nonnucleoside reverse transcriptase inhibitor (NNRTI)- and 3TC-associated mutations.These data demonstrate the effectiveness of ART in a low-resource setting. Children and patients of all ages taking the d4T/3TC/NVP regimen were more likely to have viral failure. Our data suggest that viral failure occurring 6 months or more after the start of ART regimens commonly used in Uganda is likely to be associated with NNRTI- and 3TC-resistant virus.
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    Short-Term Risk of HIV-Disease Progression and Death in Ugandan Children Not Eligible for Antiretroviral Therapy
    (Journal of acquired immune deficiency syndromes, 2010) Charlebois, Edwin D; Ruel, Theodore D; Gasasira, Anne F.; Achan, Jane; Kateera, Frederick; Akello, Caroline; Cao, Huyen; Dorsey, Grant; Rosenthal, Philip J; Ssewanyana, Isaac; Kamya, Moses R; Havlir, Diane V
    Background—Increasing numbers of HIV-infected children not yet eligible for antiretroviral therapy (ART) are entering health care in Africa. We sought to characterize the risk of short-term disease progression in this population. Methods—In a cohort of HIV-infected ART-naive and -ineligible Ugandan children >1 year old, the rates of clinical/immunologic progression within 2 years were assessed using Kaplan–Meier survival analysis and multivariate Cox proportional-hazards modeling. Results—Among 192 children (mean age: 6.4 years, CD4%:25), 19% progressed within 2 years by WHO-stage 3/4 event(n=22), death (n=3), or WHO-defined CD4 threshold for ARTinitiation( n=12). Significant univariate predictors were CD4%(HR=2.0 per 10% decrease, p=0.005), HIV-RNA level(HR=2.4 per log10 increase, p=0.002), male gender (HR:2.0, p=0.04), age < 3 years (HR=3.7, p=0.001), CD4-activation [%CD4+CD38+HLADR+] (HR=1.6 per 10% increase, p=0.05) and CD8-activation [%CD8+CD38+HLADR+](HR=1.3 per 10% increase, p=0.05] (HR=1.3, p=0.5). In multivariate analysis, CD4%(HR=2.0, p=0.034), HIV-RNA level(HR=1.8, p=0.013) and age < 3 years (HR:3.0, p=0.008) were independently predictive. Children with HIV-RNA >105 copies/ml and CD4% <25 had progression rates of 29% (1 year) and 34% (2 years). Conclusions—Even with frequent CD4 monitoring, HIV-infected Ugandan children experienced significant clinical events while ineligible for ART. Alternate strategies for monitoring or ART-initiation may be needed to improve outcomes