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1.
BMJ Open ; 11(3): e037602, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33771822

RESUMO

OBJECTIVES: We determined the prevalence of controlled prescription drug (CPD) non-medical and lifetime use and their predictors among patients at three public psychiatric clinics in Uganda to identify missed care opportunities, enhanced screening priorities, and drug control needs. METHODS: A cross-sectional survey of 1275 patients was performed from November to December 2018. Interviewer-administered semi-structured questionnaires, desk review guide and urine drug assays were employed. Questionnaire recorded CPD non-medical and illicit drug use history from patients' files, CPD lifetime use and risk factors. Desk review guide recorded recently prescribed drugs in patients' files to corroborate with urine assays. Predictors were analysed by multivariate logistic regression. RESULTS: From desk review, 145 (11.4%) patients had history of CPD non-medical use and 36 (2.8%) had used illicit drugs. Of 988 patients who provided urine, 166 (16.8%) self-medicated CPDs, particularly benzodiazepines while 12 (1.2%) used illicit drugs. Of those with drug-positive urine, 123 (69.1%) had no documented history of CPD non-medical and illicit drug use. Being an inpatient (OR=10.90, p<0.001) was independently associated with CPD non-medical use. Additionally, being an inpatient (OR=8.29, p<0.001) and tobacco consumption (OR=1.85, p=0.041) were associated with CPD non-medical and illicit drug use combined. Among participants, 119 (9.3%) reported CPD lifetime use, and this was independently associated with education level (OR=2.71, p<0.001) and history of treatment for substance abuse (OR=2.08, p=0.018). CONCLUSIONS: CPD non-medical use is common among Uganda's psychiatric patients, and more prevalent than illicit drug use. Rapid diagnostic assays may be needed in psychiatric care in resource limited settings. It is necessary to assess how CPD non-medical use impacts mental care outcomes and patient safety. High risk groups like inpatients and tobacco consumers should be prioritised in psychiatric screening.

2.
PLoS One ; 15(11): e0240838, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33175844

RESUMO

BACKGROUND: Although WHO recommends cotrimoxazole (CTX) discontinuation among HIV patients who have undergone immune recovery and are living in areas of low prevalence of malaria, some countries including Uganda recommend CTX discontinuation despite having a high malaria burden. We estimated the prevalence and factors associated with malaria parasitaemia among adults living with HIV attending hospital outpatient clinic before and after discontinuation of CTX prophylaxis. METHODS: Between March and April 2019, 599 participants aged 18 years and above, and attending Kitgum hospital HIV clinic in Uganda were enrolled in a cross study. A standardized questionnaire was administered and physical examination conducted. A finger-prick blood sample was collected for identification of malaria parasites by microscopy. The prevalence of parasitaemia was estimated and compared among participants on and those who had discontinued CTX prophylaxis, and factors associated with malaria parasitaemia assessed. RESULTS: Of the enrolled participants, 27 (4.5%) had malaria parasites and 452 (75.5%) had stopped CTX prophylaxis. Prevalence of malaria parasitaemia was significantly higher in participants who had stopped CTX prophylaxis (5.5% versus 1.4% p = 0.03) and increased with increasing duration since the discontinuation of prophylaxis. Compared to participants taking CTX, those who discontinued prophylaxis for 3-5 months and >5 months were more likely to have malaria parasites (adjusted prevalence ratio (aPR) = 1.64, 95% CI 0.37-7.29, p = 0.51, and aPR = 6.06, 95% CI 1.34-27.3, P = 0.02). Low CD4 count (< 250cells/mm3) was also associated with increased risk of having parasites (aPR = 4.31, 95% CI 2.13-8.73, p <0.001). CONCLUSION: People from malaria endemic settings living with HIV have a higher prevalence of malaria parasitaemia following discontinuation of CTX compared to those still on prophylaxis. The risk increased with increasing duration since discontinuation of the prophylaxis. HIV patients should not discontinue CTX prophylaxis in areas of Uganda where the burden of malaria remains high. Other proven malaria control interventions may also be encouraged in HIV patients following discontinuation of CTX prophylaxis.

3.
BMC Nephrol ; 21(1): 440, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33081706

RESUMO

BACKGROUND: HIV infection affects multiple organs and the kidney is a common target making renal disease, one of the recognized complications. Microalbuminuria represents an early, important marker of kidney damage in several populations including HIV-infected antiretroviral therapy (ART) naïve patients. Early detection of microalbuminuria is critical to slowing down progression to chronic kidney disease (CKD) in HIV-infected patients, however, the burden of microalbuminuria in HIV-infected antiretroviral therapy (ART) naïve patients in Uganda is unclear. METHODS: A cross-sectional study was conducted in the Mulago Immune suppression syndrome (ISS) clinic among adult HIV - infected ART naïve outpatients. Data on patient demographics, medical history was collected. Physical examination was performed to assess body mass index (BMI) and hypertension. A single spot morning urine sample from each participant was analysed for microalbuminuria using spectrophotometry and colorimetry. Microalbuminuria was defined by a urine albumin creatinine ratio (UACR) 30-299 mg/g and macroalbuminuria by a UACR > 300 mg/g. To assess the factors associated with microalbuminuria, chi-square, Fisher's exact test, quantile regression and logistic regression were used. RESULTS: A total of 185 adult participants were consecutively enrolled with median age and CD4+ counts of 33(IQR = 28-40) years and 428 (IQR = 145-689) cells/µL respectively. The prevalence of microalbuminuria was 18.9% (95% CI, 14-25%). None of the participants had macroalbuminuria. CD4+ count <350cells/µL was associated with increased risk of microalbuminuria (OR: 0.27, 95% CI: 0.12-0.59), P value = 0.001). Diabetes mellitus, hypertension, smoking, alcohol intake were not found to be significantly associated with microalbuminuria. CONCLUSION: Microalbuminuria was highly prevalent in adult HIV - infected ART naive patients especially those with low CD4+ count. There is need to study the effect of ART on microalbuminuria in adult HIV - infected patients.

4.
BMC Nephrol ; 21(1): 232, 2020 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-32571236

RESUMO

BACKGROUND: There is an increasing burden of non-communicable disease globally. Tenofovir disoproxil fumarate (TDF) is the most commonly prescribed antiretroviral drug globally. Studies show that patients receiving TDF are more prone to renal dysfunction at some point in time during treatment. Evaluation of kidney function is not routinely done in most HIV public clinics. Identification of renal dysfunction is key in resource constrained settings because managing patients with end stage renal disease is costly. METHOD: This was a cross-sectional study conducted at an outpatient clinic in 2018 involving patients on TDF for at least 6 months who were 18 years or older. Patients with documented kidney disease and pregnancy were excluded. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-Epi formula. Renal dysfunction was defined as any of the following; either eGFR< 60 mL/min/1.73m2,or proteinuria of ≥2+ on urine dipstick, glycosuria with normal blood glucose. Electrolyte abnormalities were also documented. RESULTS: We enrolled 278 participants. One hundred sixty nine (60.8%) were females, majority 234(84.2%) were < 50 years old, 205 (73.74%) were in WHO stage 1, most participants 271(97.5%) in addition to TDF were receiving lamivudine/efavirenz. The median age was 37(IQR 29-45) years; median duration on ART was 36 (IQR 24-60) months. The prevalence of renal dysfunction was 2.52% (7/278). Most noted electrolyte abnormality was hypocalcaemia (15.44%). CONCLUSIONS: The prevalence of renal dysfunction was low though some participants had hypocalcaemia. Screening for kidney disease should be done in symptomatic HIV infected patients on TDF.

5.
Trop Med Health ; 48: 34, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32476983

RESUMO

Background: Pulmonary multi-drug-resistant tuberculosis (MDR TB) alters lung architecture and involves lengthy treatment duration, high pill burden, drug adverse effects, travel restrictions, and stigma. Literature about pulmonary function and health-related quality of life (QoL) of patients treated for MDR TB is limited. This study sought to determine the prevalence of chronic obstructive pulmonary disease (COPD) and QoL of patients who were treated for pulmonary MDR TB. Methods: Participants who completed 18 months of pulmonary MDR TB treatment and considered cured were eligible to be evaluated in a cross-sectional study. We performed post-bronchodilator spirometry to measure forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC). COPD was defined as FEV1/FVC < 0.7; health-related QoL was assessed using the Medical Outcomes Survey for HIV (MOS-HIV) and St. George's Respiratory Questionnaire (SGRQ). Linear and logistic regression models were used to assess associations with COPD, health-related QoL, and other characteristics of the cohort. Results: A total of 95 participants were enrolled. Median age of the cohort was 39 years (interquartile range (IQR), 29-45), and 55 (58%) were HIV-positive. COPD prevalence was 23% (22/95). Median SGRQ score was normal at 7.8 (IQR, 3.1-14.8). Median mental and physical health summary scores were significantly impaired, at 58.6 (IQR, 52.0-61.5) and 52.9 (IQR, 47.8-57.9), respectively, on a scale of 0 to 100 where 100 represents excellent physical or mental health. In this sample, 19% (18/95) of participants were in the lowest relative socioeconomic position (SEP) while 34% (32/95) were in the highest relative SEP. Belonging in the lowest SEP group was the strongest predictor of COPD. Conclusion: Individuals who have completed MDR TB treatment have a high prevalence of COPD and low mental and physical health summary scores. Our study highlights the need for pulmonary rehabilitation programs in patients with a low socioeconomic position (SEP) after MDR TB treatment.

6.
Subst Abuse Treat Prev Policy ; 15(1): 16, 2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-32070374

RESUMO

BACKGROUND: Controlled prescription drug use disorders are a growing global health challenge in Sub-Saharan Africa. Effective supply chain regulations on dispensing and stock control are important for controlling this epidemic. Since compliance with these regulations in resource-limited countries is poor, there is need to understand its predictors in order to reduce the risk of prescription drug use disorders. METHODS: A mixed-methods study utilizing a structured questionnaire and a simulated client guide was undertaken in Kampala and Mbale towns in Uganda. The questionnaire recorded self-reported dispensing and verified stock control practices and their covariates from 101 private pharmacies. The guide recorded actual dispensing practices from 27 pharmacies. Snowball sampling was done to enrich the sample with pharmacies that stock opioids. The mean compliance with good dispensing and stock control practices was calculated. Multivariate logistic regression analyses were applied to identify predictors of compliance. RESULTS: The mean compliance with dispensing and stock control requirements was 82.9% and 23%, respectively. Twenty percent and 40% of the pharmacies dispensed pethidine without a prescription and with invalid prescriptions, respectively. Having a pharmacist on duty (OR = 5.17; p = 0.02), prior in-service training on narcotics regulations (OR = 3.51; p = 0.04), and previous narcotics audits by the regulator (OR = 5.11; p = 0.01) were independent predictors of compliance with stock control requirements. Pharmacies with a previous history of poor compliance with dispensing requirements were less likely to demonstrate good compliance (OR = 0.21; p = 0.01). CONCLUSIONS: There is suboptimal compliance to controlled prescription drug regulations among Uganda's pharmacies. A previous history of poor compliance to dispensing requirements predicted low compliance in subsequent assessments. Training and regulatory audits increased compliance in stock control but not dispensing. Expansion of training and audits to more pharmacies and/or incentives for compliance are necessary.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32071050

RESUMO

Treating malaria in HIV-coinfected individuals should consider potential drug-drug interactions. Artemether-lumefantrine is the most widely recommended treatment for uncomplicated malaria globally. Lumefantrine is metabolized by CYP3A4, an enzyme that commonly used antiretrovirals often induce or inhibit. A population pharmacokinetic meta-analysis was conducted using individual participant data from 10 studies with 6,100 lumefantrine concentrations from 793 nonpregnant adult participants (41% HIV-malaria-coinfected, 36% malaria-infected, 20% HIV-infected, and 3% healthy volunteers). Lumefantrine exposure increased 3.4-fold with coadministration of lopinavir-ritonavir-based antiretroviral therapy (ART), while it decreased by 47% with efavirenz-based ART and by 59% in the patients with rifampin-based antituberculosis treatment. Nevirapine- or dolutegravir-based ART and malaria or HIV infection were not associated with significant effects. Monte Carlo simulations showed that those on concomitant efavirenz or rifampin have 49% and 80% probability of day 7 concentrations <200 ng/ml, respectively, a threshold associated with an increased risk of treatment failure. The risk of achieving subtherapeutic concentrations increases with larger body weight. An extended 5-day and 6-day artemether-lumefantrine regimen is predicted to overcome these drug-drug interactions with efavirenz and rifampin, respectively.

8.
Afr Health Sci ; 20(1): 132-141, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33402901

RESUMO

Background: The World Health Organization recommends antiretroviral therapy (ART) for all HIV-infected patients at all CD4 counts. However, there are concerns that asymptomatic patients may have poorer viral suppression and high attrition. Objectives: We sought to determine attrition and viral suppression among healthy HIV-infected patients initiated on ART in program settings. Methods: This cross-sectional study enrolled ART-experienced patients attending two PEPFAR-supported, high-volume clinics in Kampala, Uganda. Eligible patients were >18 years and had completed at least six months on ART. Participants were interviewed on socio-demographics, ART history and plasma viral load (VL) determined using Abbott Real-time. Predictors of viral suppression (<75 copies/ml) were determined using multivariate logistic regression. Results: Overall, 267 participants were screened, 228 were eligible and 203 (89%) retained in care (visit within 90 days). Of the 203 participants, 115 (56.7%) were key-populations. Viral suppression was achieved in 173 patients (85%; 95% CI, 80.3%-90.1%). The factors associated with viral suppression were prior VL tests (AOR 6.98; p-value <0.001) and receiving care from a general clinic (AOR 5.41; p=0.009). Conclusion: Asymptomatic patients initiated on ART with high baseline CD4 counts, achieve high viral suppression with low risk of attrition. VL monitoring and clinic type are associated with viral suppression.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Assistência à Saúde/estatística & dados numéricos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Carga Viral/efeitos dos fármacos , Adulto , Instituições de Assistência Ambulatorial , Contagem de Linfócito CD4 , Estudos Transversais , Feminino , Infecções por HIV/epidemiologia , Humanos , Masculino , Uganda/epidemiologia
9.
BMC Infect Dis ; 19(1): 1025, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31795967

RESUMO

BACKGROUND: Treatment for severe malaria must be prompt with effective parenteral antimalarial drugs for at least 24 h to achieve fast parasite clearance, and when the patient can tolerate oral therapy, treatment should be completed with effective artemisinin based combination therapy (ACT) for complete parasite clearance and to prevent recrudescence. We evaluated piperaquine concentration and malaria treatment outcomes among Ugandan children treated for severe malaria with intravenous artesunate (AS) or quinine (QN) plus dihydroartemisinin-piperaquine (DP), in Tororo District Hospital in Eastern Uganda. METHODS: Capillary blood piperaquine concentration data were obtained from a randomized clinical trial whose objective was to evaluate parasite clearance, 42-day parasitological treatment outcomes and safety, following treatment of severe malaria with intravenous AS or QN, plus artemether-lumefantrine or DP among children in Tororo District Hospital, in Eastern Uganda. RESULTS: Piperaquine concentration data from 150 participants who received DP were analyzed. Participants with unadjusted treatment failure had lower median day 7 capillary piperaquine concentration than those with treatment success (34.7 (IQR) (17.9-49.1) vs 66.7 (IQR) (41.8-81.9), p < 0.001), and lower than the recommended day 7 cut off level of 57 ng/mL. There was no difference in median capillary piperaquine concentrations among participants with re-infection and recrudescence (35.3 (IQR) (17.9-55.2) vs 34.8 (IQR) (18.1-45.1), p = 0.847). The risk of treatment failure was two times higher among children with low (< 57 ng/mL) day 7 capillary piperaquine concentration (relative risk: 2.1 CI 1.4-3.1), p < 0.001) compared to children with high day 7 capillary piperaquine concentrations (> 57 ng/mL). CONCLUSION: Considering the low day 7 concentrations of piperaquine reported in the patients studied here, we suggest to adopt the recently recommended higher dose of DP in young children or a prolonged 5-day dosing in children living in malaria endemic areas who have suffered an initial episode of severe malaria in order to achieve adequate drug exposures for effective post-treatment prophylactic effects. TRIAL REGISTRATION: The study was registered with the Pan African Clinical Trial Registry (PACTR201110000321348). Registered 7th October 2011.


Assuntos
Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Artesunato/uso terapêutico , Malária Falciparum/tratamento farmacológico , Quinina/uso terapêutico , Quinolinas/sangue , Quinolinas/uso terapêutico , Administração Intravenosa , Antimaláricos/administração & dosagem , Artemisininas/administração & dosagem , Artesunato/administração & dosagem , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Malária Falciparum/parasitologia , Masculino , Concentração Osmolar , Plasmodium falciparum/isolamento & purificação , Quinina/administração & dosagem , Quinolinas/administração & dosagem , Recidiva , Resultado do Tratamento , Uganda
10.
PLoS Med ; 16(9): e1002895, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31539371

RESUMO

BACKGROUND: The global transition to use of dolutegravir (DTG) in WHO-preferred regimens for HIV treatment is limited by lack of knowledge on use in pregnancy. Here we assessed the relationship between drug concentrations (pharmacokinetics, PK), including in breastmilk, and impact on viral suppression when initiated in the third trimester (T3). METHODS AND FINDINGS: In DolPHIN-1, HIV-infected treatment-naïve pregnant women (28-36 weeks of gestation, age 26 (19-42), weight 67kg (45-119), all Black African) in Uganda and South Africa were randomised 1:1 to dolutegravir (DTG) or efavirenz (EFV)-containing ART until 2 weeks post-partum (2wPP), between 9th March 2017 and 16th January 2018, with follow-up until six months postpartum. The primary endpoint was pharmacokinetics of DTG in women and breastfed infants; secondary endpoints included maternal and infant safety and viral suppression. Intensive pharmacokinetic sampling of DTG was undertaken at day 14 and 2wPP following administration of a medium-fat breakfast, with additional paired sampling between maternal plasma and cord blood, breastmilk and infant plasma. No differences in median baseline maternal age, gestation (31 vs 30 weeks), weight, obstetric history, viral load (4.5 log10 copies/mL both arms) and CD4 count (343 vs 466 cells/mm3) were observed between DTG (n = 29) and EFV (n = 31) arms. Although DTG Ctrough was below the target 324ng/mL (clinical EC90) in 9/28 (32%) mothers in the third trimester, transfer across the placenta (121% of plasma concentrations) and into breastmilk (3% of plasma concentrations), coupled with slower elimination, led to significant infant plasma exposures (3-8% of maternal exposures). Both regimens were well-tolerated with no significant differences in frequency of adverse events (two on DTG-ART, one on EFV-ART, all considered unrelated to drug). No congenital abnormalities were observed. DTG resulted in significantly faster viral suppression (P = 0.02) at the 2wPP visit, with median time to <50 copies/mL of 32 vs 72 days. Limitations related to the requirement to initiate EFV-ART prior to randomisation, and to continue DTG for only two weeks postpartum. CONCLUSION: Despite low plasma DTG exposures in the third trimester, transfer across the placenta and through breastfeeding was observed in this study, with persistence in infants likely due to slower metabolic clearance. HIV RNA suppression <50 copies/mL was twice as fast with DTG compared to EFV, suggesting DTG has potential to reduce risk of vertical transmission in mothers who are initiated on treatment late in pregnancy. TRIAL REGISTRATION: clinicaltrials.gov NCT02245022.


Assuntos
Benzoxazinas/farmacocinética , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/farmacocinética , HIV/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/farmacocinética , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Inibidores da Transcriptase Reversa/farmacocinética , Adulto , Alquinos , Benzoxazinas/administração & dosagem , Benzoxazinas/efeitos adversos , Ciclopropanos , Feminino , HIV/genética , HIV/crescimento & desenvolvimento , Infecções por HIV/diagnóstico , Infecções por HIV/transmissão , Infecções por HIV/virologia , Inibidores de Integrase de HIV/administração & dosagem , Inibidores de Integrase de HIV/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Recém-Nascido , Troca Materno-Fetal , Leite Humano/metabolismo , Oxazinas , Piperazinas , Gravidez , Piridonas , Inibidores da Transcriptase Reversa/administração & dosagem , Inibidores da Transcriptase Reversa/efeitos adversos , Medição de Risco , África do Sul , Resultado do Tratamento , Uganda , Carga Viral , Adulto Jovem
11.
J Trop Med ; 2019: 3741294, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31428162

RESUMO

The prevalence of malaria and tuberculosis (TB) coinfection is not well established in countries that are highly burdened for both diseases. Malaria could impair TB containment and increase mortality of TB patients. The objective of this study was to determine the prevalence of malaria/TB coinfection among bacteriologically confirmed adult TB patients at a national TB treatment centre in Uganda. Using a cross-sectional study design we enrolled 363 bacteriologically confirmed adult TB patients, and data on demographics and medical history was collected. Blood samples were tested for malaria blood smear, rapid malaria diagnostic test (RDT), complete blood count, haematological film analysis, HIV serology, and CD4+ and CD8+ cell counts. Malaria was defined as either a positive blood smear or RDT. The study participants were mostly male (61.4%), with a median age of 31 (interquartile range, IQR: 25-39) years, and 35.8% were HIV positive. The prevalence of malaria was 2.2% (8/363) on the overall and 5% (3/58) among participants with rifampicin resistance. A triple infection of HIV, malaria, and rifampicin resistant TB was observed in 3 participants. The prevalence of malaria among TB patients is low, and further evaluation of the epidemiological, clinical, and immunological interaction of the two diseases is warranted.

12.
Artigo em Inglês | MEDLINE | ID: mdl-30420479

RESUMO

Across sub-Saharan Africa, patients with HIV on antiretrovirals often get malaria and need cotreatment with artemisinin-containing therapies. We undertook two pharmacokinetic studies in healthy volunteers, using standard adult doses of artemether-lumefantrine or artesunate-amodiaquine given with 50 mg once daily dolutegravir (DTG) to investigate the drug-drug interaction between artemether-lumefantrine or artesunate-amodiaquine and dolutegravir. The dolutegravir/artemether-lumefantrine interaction was evaluated in a two-way crossover study and measured artemether, dihydroartemisinin, lumefantrine, and desbutyl-lumefantrine over 264 h. The dolutegravir/artesunate-amodiaquine interaction was investigated using a parallel study design due to long half-life of the amodiaquine metabolite, desethylamodiaquine and measured artesunate, amodiaquine, and desethylamodiaquine over 624 h. Noncompartmental analysis was performed, and geometric mean ratios and 90% confidence intervals were generated for evaluation of both interactions. Dolutegravir did not significantly change the maximum concentration in plasma, the time to maximum concentration, and the area under the concentration-time curve (AUC) for artemether, dihydroartemisinin, lumefantrine, and desbutyl-lumefantrine, nor did it significantly alter the AUC for artesunate, dihydroartemisinin, amodiaquine, and desethylamodiaquine. Coadministration of dolutegravir with artemether-lumefantrine resulted in a 37% decrease in DTG trough concentrations. Coadministration of dolutegravir with artesunate-amodiaquine resulted in 42 and 24% approximate decreases in the DTG trough concentrations and the AUC, respectively. The significant decreases in DTG trough concentrations with artemether-lumefantrine and artesunate-amodiaquine and dolutegravir exposure with artesunate-amodiaquine are unlikely to be of clinical significance since the DTG trough concentrations were above dolutegravir target concentrations of 300 ng/ml. Study drugs were well tolerated with no serious adverse events. Standard doses of artemether-lumefantrine and artesunate-amodiaquine should be used in patients receiving dolutegravir. (This study has been registered at ClinicalTrials.gov under identifier NCT02242799.).


Assuntos
Antimaláricos/uso terapêutico , Artemeter/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Adulto , Amodiaquina/farmacocinética , Amodiaquina/uso terapêutico , Artemeter/farmacocinética , Artesunato/farmacocinética , Artesunato/uso terapêutico , Aleitamento Materno , Estudos Cross-Over , Interações Medicamentosas , Feminino , Compostos Heterocíclicos com 3 Anéis/farmacocinética , Humanos , Lumefantrina/farmacocinética , Lumefantrina/uso terapêutico , Masculino , Oxazinas , Piperazinas , Piridonas
13.
Malar J ; 17(1): 400, 2018 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-30376860

RESUMO

BACKGROUND: Malaria control largely depends on availability of highly efficacious drugs, however, over the years, has been threatened by emergence of drug resistance. It is, therefore, important to monitor the impact of recurrent anti-malarial treatment on the long-term efficacy of anti-malarial regimens, especially in sub-Saharan African countries with high malaria transmission. Evaluation of parasite clearance following treatment of severe malaria with intravenous artesunate among patients in Eastern Uganda, was performed, as a contribution to monitoring anti-malarial effectiveness. METHODS: Parasite clearance data obtained from a clinical trial whose objective was to evaluate the 42-day parasitological treatment outcomes and safety following treatment of severe malaria with intravenous artesunate plus artemisinin-based combination therapy among patients attending Tororo District Hospital in Eastern Uganda, were analysed. Serial blood smears were performed at 0, 1, 2, 4, 6, 8, 10, 12, 16, 20, 24 h, followed by 6-hourly blood smears post start of treatment until 6 h post the first negative blood smear when parasite clearance was achieved. Study endpoints were; parasite clearance half-life (the time required for parasitaemia to decrease by 50% based on the linear portion of the parasite clearance slope) and parasite clearance time (time required for complete clearance of initial parasitaemia). RESULTS: One hundred and fifty participants with severe malaria were enrolled. All participants were treated with intravenous artesunate. All study participants tolerated artesunate well with rapid recovery from symptoms and ability to take oral mediation within 24 h. No immediate adverse events were recorded. The median (IQR) number of days to complete parasite clearance was of 2 (1-2). The median (IQR) time to clear 50% and 99% parasites was 4.8 (3.61-7.10) and 17.55 (14.66-20.66) h, respectively. The median estimated clearance rate constant per hour was 0.32. The median (IQR) slope half-life was 2.15 (1.64, 2.61) h. CONCLUSION: Parasite clearance following treatment with intravenous artesunate was rapid and adequate. This finding provides supportive evidence that resistance to artemisinins is unlikely to have emerged in this study area. Continuous monitoring of artemisinin effectiveness for malaria treatment should be established in high malaria transmission areas in sub-Saharan Africa where spread of resistance would be disastrous. Trial registration The study was registered with the Pan African Clinical Trial Registry (PACTR201110000321348). Registered 7th October 2011, http://www.pactr.org/ ).


Assuntos
Antimaláricos/uso terapêutico , Artesunato/uso terapêutico , Malária Falciparum/prevenção & controle , Parasitemia/prevenção & controle , Plasmodium falciparum/efeitos dos fármacos , Administração Intravenosa , Pré-Escolar , Feminino , Humanos , Lactente , Malária Falciparum/parasitologia , Masculino , Parasitemia/parasitologia , Uganda
14.
BMJ Open ; 8(10): e022338, 2018 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-30341126

RESUMO

OBJECTIVE: To determine the prevalence and factors associated with dyslipidaemias in women using hormonal contraceptives. DESIGN: Cross-sectional study SETTING: Mulago Hospital, Kampala, Uganda PARTICIPANTS: Three hundred and eighty-four consenting women, aged 18-49 years, who had used hormonal contraceptives for at least 3 months prior to the study. STUDY OUTCOME: Dyslipidaemias (defined as derangements in lipid profile levels which included total cholesterol ≥200 mg/dL, high-density lipoprotein <40 mg/dL, triglyceride >150 mg/dL or low-density lipoprotein ≥160 mg/dL) for which the prevalence and associated factors were obtained. RESULTS: The prevalence of dyslipidaemias was 63.3% (95% CI: 58.4 to 68.1). Body mass index (BMI) (PR=1.33, 95% CI: 1.15 to 1.54, p<0.001) and use of antiretroviral therapy (ART) (PR=1.21, 95% CI: 1.03 to 1.42, p=0.020) were the factors significantly associated with dyslipidaemias. CONCLUSION: Dyslipidaemias were present in more than half the participants, and this puts them at risk for cardiovascular diseases. The high-risk groups were women with a BMI greater than 25 Kg/m2 and those who were on ART. Therefore, lipid profiles should be assessed in women using hormonal contraceptives in order to manage them better.


Assuntos
Antirretrovirais/efeitos adversos , Anticoncepcionais Orais Hormonais/uso terapêutico , Dislipidemias/induzido quimicamente , Infecções por HIV/tratamento farmacológico , Lipídeos/sangue , Adolescente , Adulto , Índice de Massa Corporal , Estudos Transversais , Dislipidemias/epidemiologia , Serviços de Planejamento Familiar , Feminino , Infecções por HIV/epidemiologia , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Prevalência , Análise de Regressão , Fatores de Risco , Uganda/epidemiologia , Adulto Jovem
15.
Clin Infect Dis ; 67(5): 785-790, 2018 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-30124823

RESUMO

Background: A clinical trial showed that efavirenz 400 mg once daily (EFV400) is as effective as the standard adult dose. World Health Organization recommends EFV400 as an alternative first-line agent, but data are lacking in the third trimester of pregnancy (TT). We investigated the pharmacokinetics, efficacy, and CYP2B6 pharmacogenetics in HIV-infected women (WLWH) on EFV400 during TT and post-partum (PP). Methods: An open-label 2-center study (United Kingdom, Uganda) was conducted in WLWH receiving antiretroviral regimens containing efavirenz 600 mg, who had their efavirenz dose reduced to EFV400. Weekly therapeutic drug monitoring (TDM), steady-state pharmacokinetic profiles (TT and PP), safety, virological efficacy, and CYP2B6 polymorphisms at positions 516 (C > T) and 938 (T > C) were evaluated. Results: Twenty-five WLWH of African origin were enrolled. All had viral loads <50 copies/mL at baseline, which were maintained throughout the study. No infant was HIV infected. No WLWH were withdrawn due to low EFV400 TDM results. Geometric mean ratios (TT/PP; 90% confidence interval) for EFV400 maximum observed plasma concentration, area under the curve, and plasma concentration measured 24 hours after the observed dose were 0.97 (.85-1.10), 0.87 (.76-.99), and 0.77 (.65-.91), respectively. Five of 25 WLWH were slow metabolizers. Conclusions: Although EFV400 pharmacokinetic parameters were slightly lower for TT compared with PP values, efavirenz concentrations exceeded cutoff levels established by the study and those measured in antiretroviral-naive patients receiving EFV400 in ENCORE1. All subjects maintained a viral load <50 copies/mL, suggesting that EFV400 can be used in pregnant WLWH.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/farmacocinética , Benzoxazinas/administração & dosagem , Benzoxazinas/farmacocinética , Infecções por HIV/tratamento farmacológico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Adulto , Alquinos , Ciclopropanos , Monitoramento de Medicamentos , Feminino , HIV-1/efeitos dos fármacos , Humanos , Farmacogenética , Período Pós-Parto , Gravidez , Complicações Infecciosas na Gravidez/virologia , Uganda , Reino Unido , Carga Viral
16.
Clin Infect Dis ; 67(5): 708-716, 2018 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-29514175

RESUMO

Background: The relationship between concentrations of antituberculosis drugs, sputum culture conversion, and treatment outcome remains unclear. We sought to determine the association between antituberculosis drug concentrations and sputum conversion among patients coinfected with tuberculosis and human immunodeficiency virus (HIV) and receiving first-line antituberculosis drugs. Methods: We enrolled HIV-infected Ugandans with pulmonary tuberculosis. Estimation of first-line antituberculosis drug concentrations was performed 1, 2, and 4 hours after drug intake at 2, 8, and 24 weeks of tuberculosis treatment. Serial sputum cultures were performed at each visit. Time-to-event analysis was used to determine factors associated with sputum culture conversion. Results: We enrolled 268 HIV-infected patients. Patients with low isoniazid and rifampicin concentrations were less likely to have sputum culture conversion before the end of tuberculosis treatment (hazard ratio, 0.54; 95% confidence interval, .37-.77; P = .001) or by the end of follow-up (0.61; .44-.85; P = .003). Patients in the highest quartile for area under the rifampicin and isoniazid concentration-time curves for were twice as likely to experience sputum conversion than those in the lowest quartile. Rifampicin and isoniazid concentrations below the thresholds and weight <55 kg were both risk factors for unfavorable tuberculosis treatment outcomes. Only 4.4% of the participants had treatment failure. Conclusion: Although low antituberculosis drug concentrations did not translate to a high proportion of patients with treatment failure, the association between low concentrations of rifampicin and isoniazid and delayed culture conversion may have implications for tuberculosis transmission. Clinical Trials Registration: NCT01782950.


Assuntos
Antituberculosos/farmacocinética , Infecções por HIV/microbiologia , Isoniazida/farmacocinética , Rifampina/farmacocinética , Escarro/microbiologia , Tuberculose Pulmonar/tratamento farmacológico , Adulto , Antituberculosos/uso terapêutico , Coinfecção/microbiologia , Coinfecção/virologia , Quimioterapia Combinada , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Isoniazida/uso terapêutico , Masculino , Estudos Prospectivos , Rifampina/uso terapêutico , Fatores de Risco , Falha de Tratamento , Resultado do Tratamento , Uganda
17.
BMC Infect Dis ; 17(1): 794, 2017 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-29281988

RESUMO

BACKGROUND: Severe malaria is a medical emergency associated with high mortality. Adequate treatment requires initial parenteral therapy for fast parasite clearance followed by longer acting oral antimalarial drugs for cure and prevention of recrudescence. METHODS: In a randomized controlled clinical trial, we evaluated the 42-day parasitological outcomes of severe malaria treatment with intravenous artesunate (AS) or intravenous quinine (QNN) followed by oral artemisinin based combination therapy (ACT) in children living in a high malaria transmission setting in Eastern Uganda. RESULTS: We enrolled 300 participants and all were included in the intention to treat analysis. Baseline characteristics were similar across treatment arms. The median and interquartile range for number of days from baseline to parasite clearance was significantly lower among participants who received intravenous AS (2 (1-2) vs 3 (2-3), P < 0.001). Overall, 63.3% (178/281) of the participants had unadjusted parasitological treatment failure over the 42-day follow-up period. Molecular genotyping to distinguish re-infection from recrudescence was performed in a sample of 127 of the 178 participants, of whom majority 93 (73.2%) had re-infection and 34 (26.8%) had recrudescence. The 42 day risk of recrudescence did not differ with ACT administered. Adverse events were of mild to moderate severity and consistent with malaria symptoms. CONCLUSION: In this high transmission setting, we observed adequate initial treatment outcomes followed by very high rates of malaria re-infection post severe malaria treatment. The impact of recurrent antimalarial treatment on the long term efficacy of antimalarial regimens needs to be investigated and surveillance mechanisms for resistance markers established since recurrent malaria infections are likely to be exposed to sub-therapeutic drug concentrations. More strategies for prevention of recurrent malaria infections in the most at risk populations are needed. TRIAL REGISTRATION: The study was registered with the Pan African Clinical Trial Registry ( PACTR201110000321348 ).


Assuntos
Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Malária/tratamento farmacológico , Quinina/uso terapêutico , Administração Intravenosa , Artesunato , Pré-Escolar , Quimioterapia Combinada , Feminino , Humanos , Lactente , Estimativa de Kaplan-Meier , Malária/mortalidade , Masculino , Fatores de Risco , Resultado do Tratamento , Uganda
18.
Clin Infect Dis ; 62(6): 675-682, 2016 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-26646680

RESUMO

BACKGROUND: Levonorgestrel subdermal implants are preferred contraceptives with an expected failure rate of <1% over 5 years. We assessed the effect of efavirenz- or nevirapine-based antiretroviral therapy (ART) coadministration on levonorgestrel pharmacokinetics. METHODS: This nonrandomized, parallel group, pharmacokinetic evaluation was conducted in three groups of human immunodeficiency virus-infected Ugandan women: ART-naive (n = 17), efavirenz-based ART (n = 20), and nevirapine-based ART (n = 20). Levonorgestrel implants were inserted at baseline in all women. Blood was collected at 1, 4, 12, 24, 36, and 48 weeks. The primary endpoint was week 24 levonorgestrel concentrations, compared between the ART-naive group and each ART group by geometric mean ratio (GMR) with 90% confidence interval (CI). Secondary endpoints included week 48 levonorgestrel concentrations and unintended pregnancies. RESULTS: Week 24 geometric mean levonorgestrel concentrations were 528, 280, and 710 pg/mL in the ART-naive, efavirenz, and nevirapine groups, respectively (efavirenz: ART-naive GMR, 0.53; 90% CI, .50, .55 and nevirapine: ART-naive GMR, 1.35; 90% CI, 1.29, 1.43). Week 48 levonorgestrel concentrations were 580, 247, and 664 pg/mL in the ART-naive, efavirenz, and nevirapine groups, respectively (efavirenz: ART-naive GMR, 0.43; 90% CI, .42, .44 and nevirapine: ART-naive GMR, 1.14; 90% CI, 1.14, 1.16). Three pregnancies (3/20, 15%) occurred in the efavirenz group between weeks 36 and 48. No pregnancies occurred in the ART-naive or nevirapine groups. CONCLUSIONS: Within 1 year of combined use, levonorgestrel exposure was markedly reduced in participants who received efavirenz-based ART, accompanied by contraceptive failures. In contrast, nevirapine-based ART did not adversely affect levonorgestrel exposure or efficacy. CLINICAL TRIALS REGISTRATION: NCT01789879.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Benzoxazinas/uso terapêutico , Anticoncepcionais Femininos/farmacocinética , Infecções por HIV/tratamento farmacológico , Levanogestrel/farmacocinética , Gravidez não Planejada , Adolescente , Adulto , Alquinos , Anticoncepcionais Femininos/administração & dosagem , Anticoncepcionais Femininos/efeitos adversos , Anticoncepcionais Femininos/sangue , Ciclopropanos , Interações Medicamentosas , Feminino , Infecções por HIV/etnologia , HIV-1/efeitos dos fármacos , Humanos , Levanogestrel/administração & dosagem , Levanogestrel/efeitos adversos , Levanogestrel/sangue , Nevirapina/uso terapêutico , Gravidez , Inibidores da Transcriptase Reversa/uso terapêutico , Fatores de Tempo , Uganda
19.
BMC Res Notes ; 8: 598, 2015 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-26498749

RESUMO

BACKGROUND: Students at Makerere University College of Health Sciences (MakCHS) are introduced to ethics and professionalism using the inter-professional education (IPE) model. Ethics and professionalism should be running themes throughout succeeding years of study during which students are expected to develop qualities and skills for future inter-professional practice (IPP). We performed a situation analysis of IPE and IPP among students and teaching health professionals at MakCHS to guide development of a relevant training curriculum of ethics and professionalism. METHODS: A cross sectional study with quantitative and qualitative methods which included questionnaires, focus group discussions and key informant interviews. RESULTS: We interviewed 236 undergraduate students (148, 63 % male) and 32 teaching health professionals (25, 78 % male). Two hundred fifteen (91 %) students indicated they had joint learning activities with students of other professions and 166 (70 %) stated there was benefit in having an IPE model training curriculum. Most students (140, 59 %) strongly agreed that learning with other students will make them more effective members of the health team. Whereas the respondents reported inter professionalism as being well articulated in their course curricula, more than half said IPE is only implemented in the pre-clinical years of study. They noted that IPE and IPP concepts were not well programmed, health professionals engaged in teaching had poor attitudes towards IPE and IPP, there were limited numbers of skilled health care workers to implement IPP and there was poor communication between students and teaching health professionals. Majority of teaching health professionals noted challenges in implementation of IPE such as poor coordination and large student population and major factors influencing ethics and professionalism in healthcare such as limited government support, low pay for the health care workers, disrespect and lack of appreciation of the health workers by the public. CONCLUSIONS: Our findings demonstrate that IPE, IPP, ethics and professionalism are not emphasized in the clinical years of study at MakCHS. We recommend increased sensitization on the concepts of IPE and IPP plus enhanced mentorship for both students and teaching health professionals. Innovative strategies of implementation of IPE and IPP for training in ethics and professionalism must be introduced.


Assuntos
Ética Profissional/educação , Competência Profissional , Universidades , Adulto , Estudos Transversais , Currículo , Feminino , Grupos Focais , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Estudantes , Inquéritos e Questionários , Uganda
20.
PLoS One ; 10(7): e0133756, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26222142

RESUMO

BACKGROUND: The existing World Health Organization diagnostic algorithms for smear-negative TB perform poorly in HIV-infected individuals. New TB diagnostics such as urine TB lipoarabinomannan (LAM) could improve the accuracy and reduce delays in TB diagnosis in HIV-infected smear-negative presumptive TB. We sought to determine predictors for MTB culture-positivity among these patients. METHODS: This study was nested into a prospective evaluation of HIV-infected outpatients and inpatients clinically suspected to have TB who were screened by smear-microscopy on two spot sputum samples. Data on socio-demographics, clinical symptoms, antiretroviral therapy, CXR, CD4 count, mycobacterial sputum and blood cultures and TB-LAM were collected. Logistic regression and conditional inference tree analysis were used to determine the most predictive indicators for MTB culture-positivity. RESULTS: Of the 418 smear-negative participants [female, 64%; median age (IQR) 32 (28-39) years, median CD4 106 (IQR 22 - 298) cells/mm3], 96/418 (23%) were sputum and/ or blood culture-positive for Mycobacterium tuberculosis (MTB) complex. Abnormal CXR (aOR 3.68, 95% CI 1.76- 7.71, p=0.001) and positive urine TB-LAM (aOR 6.21, 95% CI 3.14-12.27, p< 0.001) were significantly associated with MTB culture-positivity. Previous TB treatment (aOR 0.41, 95% CI 0.17-0.99, p=0.049) reduced the likelihood of a positive MTB culture. A conditional inference tree analysis showed that positive urine TB-LAM and abnormal CXR were the most predictive indicators of MTB culture-positivity. A combination of urine TB-LAM test and CXR had sensitivity and specificity of 50% and 86.1% respectively overall, and 70.8% and 84.1% respectively among those with CD4<100 cells/mm3. CONCLUSIONS: A positive urine TB-LAM test and an abnormal CXR significantly predict MTB culture-positivity among smear-negative HIV-infected presumptive TB patients while previous TB treatment reduces the likelihood of a positive MTB culture. Validation studies to assess the performance of diagnostic algorithms that include urine TB-LAM in the diagnosis of smear-negative TB in HIV-infected individuals are warranted.


Assuntos
Técnicas e Procedimentos Diagnósticos , Infecções por HIV/complicações , Mycobacterium tuberculosis/fisiologia , Tuberculose/complicações , Tuberculose/diagnóstico , Adulto , Técnicas de Cultura , Feminino , Humanos , Lipopolissacarídeos/urina , Masculino , Mycobacterium tuberculosis/crescimento & desenvolvimento , Sensibilidade e Especificidade , Fatores de Tempo , Tuberculose/urina , Uganda
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