Showing papers by "Moses R. Kamya published in 2006"
TL;DR: The HIV-1 seroprevalence rate was surprisingly high in adults presenting with malaria, and this finding supports the implementation of routine HIV counseling and testing for adults with uncomplicated falciparum malaria.
Abstract: Human immunodeficiency virus (HIV) infection may increase the burden of malaria by increasing susceptibility to infection or by decreasing the response to antimalarial treatment. We investigated the seroprevalence rate of HIV-1 infection and its effect on antimalarial treatment outcomes in adults and children with uncomplicated falciparum malaria in Uganda. This retrospective study included 1965 patients = 18 months old who were randomized to receive 1 of 3 antimalarial regimens at 7 sites in Uganda. HIV-1 testing was performed using 2 enzyme-linked immunosorbent assays and Western blot analysis of stored blood spots. The primary study outcome was clinical treatment failure at 28 days after antimalarial treatment. Molecular genotyping was used to distinguish clinical treatment failures due to new infections from those due to recrudescences. The HIV-1 seroprevalence rate was 2.5% in 1802 patients 3-fold (hazard ratio [HR] 3.28 [95% confidence interval {CI} 1.25-8.59]) increased risk of clinical treatment failure for adults but there was no increased risk for HIV-1-infected children. Molecular genotyping revealed that clinical treatment failures were due to new infections (HR 6.35 [95% CI 1.64-24.5]) rather than to recrudescences (HR 1.51 [95% CI 0.27-8.58]). The HIV-1 seroprevalence rate was surprisingly high in adults presenting with malaria. This finding supports the implementation of routine HIV counseling and testing for adults with uncomplicated falciparum malaria. HIV-1 infection increased the susceptibility to new malarial infections but did not increase the risk of recrudescences in adults. (authors)
164 citations
TL;DR: Although many HIV-infected people treated in Kampala, Uganda, have advanced HIV disease, the majority of patients who received antiretroviral therapy experienced viral suppression and clinical benefit.
Abstract: Background. Access to antiretroviral therapy and human immunodeficiency virus (HIV) care is increasing in resource-limited settings. We evaluated clinical, behavioral, and demographic risk factors associated with virologic suppression in a public, urban clinic in Kampala, Uganda. Methods. We conducted a cross-sectional, observational study of 137 HIV-infected patients who were receiving antiretroviral therapy at the infectious diseases clinic at Mulago Hospital (Kampala). We measured the prevalence of viral suppression, evaluated risk factors associated with virologic failure, and documented phenotypic resistance patterns and genotypic mutations. Results. A total of 91 (66%) of 137 participants had an undetectable viral load (<400 copies/mL) after a median duration of 38 weeks (interquartile range, 24-62 weeks) of antiretroviral therapy. Median CD4 cell count was 163 cells/mm 3 (interquartile range, 95-260 cells/mm 3 ). The majority of the patients (91%) were treated with nonnucleoside reverse-transcriptase inhibitor-based 3-drug regimens. In multivariate analysis, treatment with the first antiretroviral regimen was associated with viral suppression (odds ratio, 2.6; 95% confidence interval, 1.1-6.1). In contrast, a history of unplanned treatment interruption was associated with virologic treatment failure (odds ratio, 0.2; 95% confidence interval, 0.1-0.6). Of 124 participants treated with nonnucleoside reverse-transcriptase inhibitors, 27 (22%) were documented to have experienced virologic treatment failure. The most common mutation detected was K103N (found in 14 of 27 patients with virologic treatment failure). Conclusions. Although many HIV-infected people treated in Kampala, Uganda, have advanced HIV disease, the majority of patients who received antiretroviral therapy experienced viral suppression and clinical benefit. Because of the frequent use of nonnucleoside reverse-transcriptase inhibitor-based therapy, the majority of resistance was against this drug class. In resource-limited settings, initiation of therapy with a potent, durable regimen, accompanied by stable drug supplies, will optimize the likelihood of viral suppression.
122 citations
TL;DR: The findings strongly suggest that geographic differences in response to antimalarial therapy in Uganda are primarily mediated by acquired immunity associated with malaria transmission intensity, rather than by parasite factors.
Abstract: Recent clinical trials from Uganda have shown that the risk of failure following antimalarial therapy varies geographically. We tested the hypothesis that geographic differences in the response to therapy could be explained by differences in the prevalence of known molecular markers of drug resistance. Samples from 2084 patients treated with chloroquine (CQ) plus sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) plus SP were tested for the presence of known molecular markers of resistance. Differences in the risk of treatment failure across 6 sites were compared and age and complexity of infection were controlled for. The prevalence of molecular markers of drug resistance was high at all of the sites: 61%-91% of patients were infected with parasites containing the pfcrt Thr-76 mutation and dhfr/dhps quintuple mutation. The risk of treatment failure decreased with increasing transmission intensity for both CQ plus SP (73% to 19%) and AQ plus SP (38% to 2%). Restricting the analyses to patients infected with parasites containing all 6 mutations of interest did not affect these trends. The risk of treatment failure was inversely proportional to transmission intensity and was not explained by differences in molecular markers of antimalarial drug resistance. Our findings strongly suggest that geographic differences in response to antimalarial therapy in Uganda are primarily mediated by acquired immunity associated with malaria transmission intensity rather than by parasite factors. (authors)
88 citations
TL;DR: The clearance of circulating EBV after antimalaria treatment suggests a direct relationship between active malaria infection and viral reactivation, and the positive plasma samples clustered around 7-9 years of age, the peak incidence of BL.
Abstract: Children living in malaria-endemic regions have a high incidence of Burkitt lymphoma (BL), the etiology of which involves Plasmodium falciparum malaria and Epstein-Barr virus (EBV) infections. In the present study, we compared EBV DNA loads in plasma and saliva samples from Ugandan children with acute malaria (M + ) at the time of diagnosis and 14 days after antimalaria treatment, children without malaria (M), and children with BL. EBV DNA was detected, by real-time polymerase chain reaction, in 31% of the plasma and in 79% of the saliva samples from children in the M + group. Antimalaria treatment led to clearance of plasma viral load in 85% of the cases but did not affect the levels in saliva. There was a significant difference in plasma EBV loads across the groups. The lowest levels were detected in samples from the M group, increased levels were detected in samples from the M + group, and levels reached the highest values in samples from children with BL. The same trend was evident in the frequency and levels of anti-BZLF1 antibodies, which is indicative of viral reactivation. In the M + group, the positive plasma samples clustered around 7‐9 years of age, the peak incidence of BL. The clearance of circulating EBV after antimalaria treatment suggests a direct relationship between active malaria infection and viral reactivation.
71 citations
TL;DR: Two HIV enzyme immunoassays (EIAs) were evaluated by testing 1,965 Ugandans with malaria and found poor positive predictive values (53% and 76%), particularly with younger age.
Abstract: Malaria may impact upon human immunodeficiency virus (HIV) test results. We evaluated two HIV enzyme immunoassays (EIAs) by testing 1,965 Ugandans with malaria. We found poor positive predictive values (53% and 76%), particularly with younger age. Combining EIAs eliminated false positives but missed 21% of true positives. Performance of HIV EIAs in malaria may be unsatisfactory.
52 citations
TL;DR: The Infectious Diseases Institute's 4-week course for African doctors on comprehensive management of HIV including antiretroviral therapy improved the clinical skills of doctors.
Abstract: OBJECTIVE: To evaluate the effects of the Infectious Diseases Institute's 4-week course for African doctors on comprehensive management of HIV including antiretroviral therapy on four outcomes: (1) clinical skills, (2) clinical activities, (3) monitoring of HIV patients, and (4) training activities DESIGN: Clinical exam at beginning and end of course and at follow-up 3 to 4 months later, and a cross-section telephone survey. METHODS: Forty-seven doctors attending the course (October 2004, November 2004, March 2005, and April 2005) agreed to participate. A 17-item Clinical Exam Checklist was used to assess clinical skills. A telephone survey was conducted 1 month after the course to collect data in four areas: clinical activities, monitoring of HIV patients, case studies on initiation of ART, and training activities. RESULTS: The course improved the clinical skills of doctors. Between the beginning and end of the course, their clinical skills improved significantly in 11 of 17 areas (n = 34). Between the end of the course and follow-up, their skills improved significantly in three areas (n = 14). The trainees were practicing HIV care and training. The telephone survey (n = 46) showed that 93% of trainees treated HIV patients, 35% provided training on HIV, and 47% monitored the weight of the last HIV patient treated (patient's weight was a clinical end point to measure health status). At follow-up, everyone provided training and trained an average of 20 people per month.
15 citations
TL;DR: The results highlight the complexity of malaria in Africa and have implications for efficacy trials, because missing late reappearances of strains could lead to misclassification of outcomes.
Abstract: We followed parasite genotypes of 75 patients for 42 days after treatment of uncomplicated malaria with chloroquine + sulfadoxine-pyrimethamine in Kampala, Uganda. Infections were complex (mean, 2.88 strains) and followed three patterns: 27% of patients eliminated all strains and remained parasite-free, 48% had a long aparasitemic interval followed by reappearance of original strains after 3-33 days (mean, 9.2 days), and 25% failed to clear original strains and required therapy after 3-35 days (mean, 17 days). These results highlight the complexity of malaria in Africa and have implications for efficacy trials, because missing late reappearances of strains could lead to misclassification of outcomes.
6 citations
Journal Article•
3 citations