RESUMO
Gentamicin is widely used to treat neonatal infections caused by both Gram-negative and Gram-positive bacteria, and the WHO recommends its use while monitoring serum creatinine and gentamicin concentrations to avoid drug-induced nephrotoxicity and ototoxicity. Yet in some resource-limited settings, the drug is used without monitoring. A population pharmacokinetics study involving term neonates with neonatal infection admitted to a neonatal unit. Participants were started on intravenous gentamicin 5 mg/kg once a day in combination with ampicilin-cloxacillin. Blood samples for serum gentamicin concentration were taken at 0.25, 0.5, 1, 2, 3, 5, 6, 8, 10, 12, 14, 16, 18, 20, 23, and 24 hours after the initial dose, each participant contributing two samples to the 24 hour sampling schedule. An additional sample for trough concentration was taken from each participant just before the third gentamicin dose while serum creatinine concentration was measured before and after treatment. Twenty-four participants were enrolled into the study and included in the final analysis. Mean (SD) peak and trough serum gentamicin concentrations were 16.66 (0.64) µg/mL and 3.28 (0.70) µg/mL, respectively. Gentamicin clearance (CL) was 0.40 mL min-1 kg-1 and volume of distribution (VD) was 0.31 L kg-1. Mean (SD) serum creatinine level after treatment was 209.7 (70.4) µmol/L compared to 103.3 (23.6) µmol/L before treatment [mean difference (106.4 ± 67.1; 95% confidence interval (CI): 78.1; 134.7 µmol/L; t (23) = 7.77; P < 0.001]. All participants fulfilled the Kidney Disease Improving Global Outcomes (KDIGO) criteria for acute kidney injury after treatment. Treatment of neonatal infection with antimicrobial regimen containing gentamicin, without renal function and gentamicin concentration monitoring, carries a significant risk for drug-induced acute kidney injury.
RESUMO
Multi-omics approaches have been successfully applied to investigate pregnancy and health outcomes at a molecular and genetic level in several studies. As omics technologies advance, research areas are open to study further. Here we discuss overall trends and examples of successfully using omics technologies and techniques (e.g., genomics, proteomics, metabolomics, and metagenomics) to investigate the molecular epidemiology of pregnancy. In addition, we outline omics applications and study characteristics of pregnancy for understanding fundamental biology, causal health, and physiological relationships, risk and prediction modeling, diagnostics, and correlations.
Assuntos
Genômica , Proteômica , Humanos , Gravidez , Feminino , Epidemiologia Molecular , Genômica/métodos , Proteômica/métodos , Metabolômica/métodos , MetagenômicaRESUMO
AIMS: Methadone maintenance therapy (MMT) exhibits significant variability in pharmacokinetics and clinical response, partly due to genetic variations. However, data from sub-Saharan African populations are lacking. We examined plasma methadone variability and pharmacogenetic influences among opioid-addicted Tanzanian patients. METHODS: Patients attending MMT clinics (n = 119) in Tanzania were genotyped for common functional variants of the CYP3A4, CYP3A5, CYP2A6, CYP2B6, CYP2C19, CYP2D6, ABCB1, UGT2B7 and SLCO1B1 genotypes. Trough plasma concentrations of total methadone, S-methadone (S-MTD) and R-methadone (R-MTD), with their respective metabolites, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The methadone-to-EDDP metabolic ratio (MMR) was used to categorize the phenotype. RESULTS: The proportions of MMR-predicted ultrarapid, extensive, intermediate and slow methadone metabolizer phenotypes were 2.5%, 58.2%, 23.7% and 15.6%, respectively. CYP2B6 genotype significantly correlated with S-methadone (P = .006), total methadone (P = .03), and dose-normalized methadone plasma concentrations (P = .001). Metabolic ratios of R-methadone (R-MTD/R-EDDP), S-methadone (S-MTD/S-EDDP), and total methadone (MMR) were significantly higher among patients homozygous for defective variants (*6 or *18) than heterozygous or CYP2B6*1/*1 genotypes (P < .001). The metabolic ratio for S-MTD and total methadone was significantly higher among ABCB1c.3435T/T than in the C/C genotype. No significant effect of CYP2D6, CYP2C19, CYP3A4, CYP3A5, CYP2A6, UGT2B7 and SLCO1B1 genotypes on S-methadone, R-methadone, or total methadone was observed. CONCLUSIONS: Approximately one in six opioid-addicted Tanzanian patients are methadone slow metabolizers, influenced by genetic factors. Both the CYP2B6 and ABCB1 genotypes are strong predictors of methadone metabolic capacity and plasma exposure. Further investigation is needed to determine their predictive value for methadone treatment outcomes and to develop genotype-based dosing algorithms for safe and effective therapy.
RESUMO
BACKGROUND: Despite the scale-up of ART and the rollout in Tanzania of dolutegravir, an integrase strand transfer inhibitor (INSTI), treatment success has not been fully realized. HIV drug resistance (HIVDR), including dolutegravir resistance, could be implicated in the notable suboptimal viral load (VL) suppression among HIV patients. OBJECTIVES: To determine the prevalence and patterns of acquired drug resistance mutations (DRMs) among children and adults in Tanzania. METHODS: A national cross-sectional HIVDR survey was conducted among 866 children and 1173 adults. Genotyping was done on dried blood spot and/or plasma of participants with high HIV VL (≥1000 copies/mL). HIV genes (reverse transcriptase, protease and integrase) were amplified by PCR and directly sequenced. The Stanford HIVDR Database was used for HIVDR interpretation. RESULTS: HIVDR genotyping was performed on blood samples from 137 participants (92 children and 45 adults) with VL ≥ 1000 copies/mL. The overall prevalence of HIV DRMs was 71.5%, with DRMs present in 78.3% of children and 57.8% of adults. Importantly, 5.8% of participants had INSTI DRMs including major DRMs: Q148K, E138K, G118R, G140A, T66A and R263K. NNRTI, NRTI and PI DRMs were also detected in 62.8%, 44.5% and 8% of participants, respectively. All the participants with major INSTI DRMs harboured DRMs targeting NRTI backbone drugs. CONCLUSIONS: More than 7 in 10 patients with high HIV viraemia in Tanzania have DRMs. The early emergence of dolutegravir resistance is of concern for the efficacy of the Tanzanian ART programme.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Integrase de HIV , HIV-1 , Humanos , Adulto , Criança , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Tanzânia , Estudos Transversais , Mutação , Integrases/genética , Carga Viral , Farmacorresistência Viral/genética , Integrase de HIV/genética , GenótipoRESUMO
BACKGROUND: Human immunodeficiency virus (HIV) chronicity in the midst of old age multiplies the risk for chronic non communicable diseases. The old are predisposed to drug-drug interactions, overlapping toxicities and impairment of the quality of life (QoL) due to age-related physiological changes. We investigated polypharmacy, QoL and associated factors among older HIV-infected adults at Muhimbili National hospitals in Dar es Salaam Tanzania. METHODS: A hospital-based cross sectional study enrolled adults aged 50 years or older who were on antiretroviral therapy (ART) for ≥ 6 months. Participants' Information including the number and type of medications used in the previous one week were recorded. Polypharmacy was defined as concurrent use of five or more non-HIV medications. A World Health Organization QoL questionnaire for people living with HIV on ART (WHOQoL HIV BREF) was used to assess QoL. A score of ≤ 50 meant poor QoLwhile > 50 meant good QoL. Polypharmacy and QoL are presented as proportions and compared using Chi-square test. Association between various factors and polypharmacy or QoL was assessed using modified Poisson regression. A p-value of < 0.05 was considered significant. RESULTS: A total of 285 patients were enrolled. The mean (SD) age was 57(± 6.88) years. Females were the majority (62.5%), and 42.5% were married. Polypharmacy was seen in 52 (18.2%) of participants. Presence of co-morbidities was independently associated with polypharmacy (p < 0.001). The mean(SD) score QoL for the study participants was 67.37 ± 11.Poor QoL was seen in 40 (14%) participants.All domains' mean score were above 50, however social domain had a relatively lowmean scoreof 68 (± 10.10). Having no formal or primary education was independently associated with poor QoL (p = 0.021). CONCLUSION: The prevalence of polypharmacy was modestly high and was linked to the presence of co-morbidities. No formal and/or primary education was associated with poor QoL, where by social domain of QoL was the most affected.
Assuntos
Infecções por HIV , Qualidade de Vida , Feminino , Humanos , Idoso , Estudos Transversais , Centros de Atenção Terciária , Polimedicação , Tanzânia/epidemiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , HIVRESUMO
PURPOSE: Efavirenz-based combination antiretroviral therapy (cART) is associated with neuropsychiatric adverse events. We investigated the time to onset, duration, clinical implications, impact of pharmacogenetic variations, and anti-tuberculosis co-treatment on efavirenz-associated neuropsychiatric manifestations. METHODS: Prospective cohort study of cART naïve HIV patients with or without tuberculosis (HIV-TB) co-infection treated with efavirenz-based cART. Rifampicin-based anti-tuberculosis therapy was initiated 4 weeks prior to efavirenz-based cART in HIV-TB patients. Data on demographic, clinical, laboratory, and a 29-item questionnaire on neuropsychiatric manifestations were collected for 16 weeks after cART initiation. Genotyping for CYP2B6, CYP3A5, SLCO1B1, and ABCB1 and quantification of efavirenz plasma concentration were done on the 4th and 16th week. RESULTS: Data from 458 patients (243 HIV-only and 215 HIV-TB) were analyzed. Overall incidence of neuropsychiatric manifestations was 57.6% being higher in HIV-only (66.7%) compared to HIV-TB patients (47.4%) (p < 0.01). HIV-only patients were more symptomatic, with proportionately higher grades of manifestations compared to HIV-TB patients. Median time to manifestations was 1 week after cART initiation in HIV-only and 6 weeks after anti-TB (i.e., 2 weeks after cART initiation) in HIV-TB patients. HIV-only patients had significantly higher efavirenz plasma concentrations at 4 weeks after cART compared to HIV-TB patients. No association of sex or genotype was seen in relation to neuropsychiatric manifestations. Risk for neuropsychiatric manifestations was three times more in HIV-only patients compared to HIV-TB (p < 0.01). CONCLUSIONS: Incidence of neuropsychiatric manifestations during early initiation of efavirenz-based cART is high in Tanzanian HIV patients. Risk of neuropsychiatric manifestations is lower in HIV patients co-treated with rifampicin containing anti-TB compared to those treated with efavirenz-based cART only.
Assuntos
Terapia Antirretroviral de Alta Atividade/efeitos adversos , Benzoxazinas/efeitos adversos , Infecções por HIV/tratamento farmacológico , HIV-1/isolamento & purificação , Transtornos Mentais/induzido quimicamente , Rifampina/efeitos adversos , Tuberculose/tratamento farmacológico , Adulto , África Subsaariana , Alcinos , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Antibióticos Antituberculose/administração & dosagem , Antibióticos Antituberculose/efeitos adversos , Terapia Antirretroviral de Alta Atividade/métodos , Antituberculosos/uso terapêutico , Benzoxazinas/administração & dosagem , Benzoxazinas/sangue , Estudos de Coortes , Ciclopropanos , Feminino , Genótipo , Infecções por HIV/sangue , Infecções por HIV/genética , Infecções por HIV/microbiologia , Humanos , Masculino , Transtornos Mentais/sangue , Transtornos Mentais/genética , Transtornos Mentais/microbiologia , Farmacogenética , Estudos Prospectivos , Rifampina/administração & dosagem , Tuberculose/sangue , Tuberculose/genética , Tuberculose/microbiologiaRESUMO
BACKGROUND: Tanzania has made significant progress in improving access to HIV care and treatment. However, virologic suppression among people living with HIV (PLHIV) has not been fully realized. In March 2019, Tanzania introduced a World Health Organization (WHO)-recommended dolutegravir-based regimen as the default first-line regimen. Eighteen months later we investigated the HIV viral suppression rates and the factors associated with lack of viral suppression among PLHIV (children and adults) in Tanzania. METHODOLOGY: A cross-sectional survey was conducted from September to December 2020 among PLHIV on antiretroviral therapy (ART) in Tanzania. Whole blood samples, demographic data and clinical information were obtained from eligible adults (≥15 years) and children (< 15 years) attending thirty-six HIV care and treatment centres located in 22 regions of Tanzania mainland. A whole blood sample from each participant was processed into plasma and HIV viral load was estimated using real-time PCR. HIV viral suppression was defined at a cut-off of < 50 copies/mL as recommended by WHO. Analyses were conducted using descriptive statistics to establish the national representative prevalence of viral suppression, and logistic regression analyses to determine independent factors associated with non-suppression. RESULTS: A total of 2,039 PLHIV on ART were recruited; of these, adults and children were 57.5% (n = 1173) and 42.5% (n = 866), respectively. Among the adult population, the mean age and standard deviation (SD) was 42.1 ± 12.4 years, with 64.7% being female. Among children, the mean age and SD were 9.6 ± 3 years, and 53.2% were female. Overall viral suppression at < 50 copies/mL (undetectable) was achieved in 87.8% of adults and 74.4% of children. Adults and children on dolutegravir-based regimen recorded viral suppression rates of 89.7% and 85.1% respectively. Factors independently associated with lack of viral suppression status in the adult population were age and ART adherence while in the children population, the factors were sex, ART adherence, and current ART regimen (p<0.05). CONCLUSION: Dolutegravir-based regimens are promising to help attain epidemic control in Tanzania. More efforts especially on ART adherence are needed to attain optimal treatment outcomes for children and adults PLHIV in Tanzania.
Assuntos
Infecções por HIV , Compostos Heterocíclicos com 3 Anéis , Oxazinas , Piperazinas , Piridonas , Carga Viral , Humanos , Feminino , Tanzânia/epidemiologia , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Piridonas/uso terapêutico , Masculino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Infecções por HIV/epidemiologia , Adulto , Oxazinas/uso terapêutico , Piperazinas/uso terapêutico , Criança , Adolescente , Carga Viral/efeitos dos fármacos , Estudos Transversais , Pessoa de Meia-Idade , Adulto Jovem , Pré-Escolar , Inibidores de Integrase de HIV/uso terapêutico , Fármacos Anti-HIV/uso terapêutico , HIV-1/efeitos dos fármacos , HIV-1/genéticaRESUMO
BACKGROUND: The role of copy number variation of the CCL3L1 gene, encoding MIP1α, in contributing to the host variation in susceptibility and response to HIV infection is controversial. Here we analyse a sub-Saharan African cohort from Tanzania and Ethiopia, two countries with a high prevalence of HIV-1 and a high co-morbidity of HIV with tuberculosis. METHODS: We use a form of quantitative PCR called the paralogue ratio test to determine CCL3L1 gene copy number in 1134 individuals and validate our copy number typing using array comparative genomic hybridisation and fiber-FISH. RESULTS: We find no significant association of CCL3L1 gene copy number with HIV load in antiretroviral-naïve patients prior to initiation of combination highly active anti-retroviral therapy. However, we find a significant association of low CCL3L1 gene copy number with improved immune reconstitution following initiation of highly active anti-retroviral therapy (p = 0.012), replicating a previous study. CONCLUSIONS: Our work supports a role for CCL3L1 copy number in immune reconstitution following antiretroviral therapy in HIV, and suggests that the MIP1α -CCR5 axis might be targeted to aid immune reconstitution.
Assuntos
Quimiocinas CC/genética , Variações do Número de Cópias de DNA , Infecções por HIV/genética , Infecções por HIV/imunologia , HIV-1/isolamento & purificação , Adulto , Etiópia/epidemiologia , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Humanos , Masculino , Tanzânia/epidemiologia , Carga ViralRESUMO
AIDS, caused by the retrovirus human immunodeficiency virus (HIV), is the leading cause of death of economically active people (age, 15-59 years) in sub-Saharan Africa. The host genetic variability of immune response to HIV and immune reconstitution following initiation of highly active antiretroviral therapy (HAART) is poorly understood. Here we focused on copy number variation of the ß-defensin genes, which have been shown to have anti-HIV activity, and are important chemoattractants for Th17 lymphocytes via the chemokine receptor CCR6. We determined ß-defensin gene copy number for 1002 Ethiopian and Tanzanian patients. We show that higher ß-defensin copy number variation is associated with increased HIV load prior to HAART (P=.005) and poor immune reconstitution following initiation of HAART (P=.003). We suggest a model where variable amounts of ß-defensin expression by mucosal cells, due to gene copy number variation, alters the efficacy of recruitment of Th17 lymphocytes to the site of infection, altering the dynamics of infection.
Assuntos
Infecções por HIV/genética , Infecções por HIV/virologia , Carga Viral , beta-Defensinas/genética , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Coinfecção , Etiópia , Dosagem de Genes , Estudos de Associação Genética , Genoma Humano , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Humanos , Funções Verossimilhança , Receptores CCR5/genética , Deleção de Sequência , Tanzânia , Tuberculose Pulmonar/genética , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/virologiaRESUMO
Concomitant squamous cell carcinoma (SCC) and renal tuberculosis (TB) are a rare presentation. It is associated with poor prognosis and poses a challenge in the management. To the best of our knowledge, we present a challenging first document case of locally advanced SCC of the bladder with coactive renal tuberculosis.
RESUMO
BACKGROUND: The emergence of HIV drug resistance mutations (DRMs) is of significant threat to achieving viral suppression (VS) in the quest to achieve global elimination targets. We hereby report virologic outcomes and patterns of acquired DRMs and its associated factors among adolescents and young adults (AYA) from a broader HIV drug resistance surveillance conducted in Tanzania. METHODS: Data of AYA was extracted from a cross-sectional study conducted in 36 selected facilities using a two-stage cluster sampling design. Dried blood spot (DBS) samples were collected and samples with a viral load (VL) ≥1000 copies/mL underwent genotyping for the HIV-1 pol gene. Stanford HIV database algorithm predicted acquired DRMs, Fisher's exact test and multivariable logistic regression assessed factors associated with DRMs and VS, respectively. FINDINGS: We analyzed data of 578 AYA on antiretroviral therapy (ART) for 9-15 and ≥ 36 months; among them, 91.5% and 88.2% had VS (VL<1000copies/mL) at early and late time points, respectively. Genotyping of 64 participants (11.2%) who had VL ≥1000 copies/ml detected 71.9% of any DRM. Clinically relevant DRMs were K103N, M184V, M41L, T215Y/F, L210W/L, K70R, D67N, L89V/T, G118R, E138K, T66A, T97A and unexpectedly absent K65R. Participants on a protease inhibitor (PI) based regimen were twice as likely to not achieve VS compared to those on integrase strand transfer inhibitors (INSTI). The initial VL done 6 months after ART initiation of ≥1000copies/mL was the primary factor associated with detecting DRMs (p = .019). CONCLUSIONS: VS amongst AYA is lower than the third UNAIDs target. Additionally, a high prevalence of ADR and high levels of circulating clinically relevant DRMs may compromise the long-term VS in AYA. Furthermore, the first VL result of ≥1000copies/ml after ART initiation is a significant risk factor for developing DRMs. Thus, strict VL monitoring for early identification of treatment failure and genotypic testing during any ART switch is recommended to improve treatment outcomes for AYA.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Humanos , Adolescente , Adulto Jovem , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Estudos Transversais , Tanzânia/epidemiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Mutação , Farmacorresistência Viral/genética , Carga Viral , GenótipoRESUMO
OBJECTIVES: There are limited data on factors influencing antibiotic prescription among insured patients. We assessed for correlates of an antibiotic prescription among insured patients. DESIGN: A cross-sectional study. SETTING: The study was conducted at the National Health Insurance Fund offices, Dar es Salaam, Tanzania. DATA SOURCE: We captured data from the claim forms, containing inpatient and outpatient treatment information for insured patients, for the month of September 2019. OUTCOME VARIABLE: Receipt of an antibiotic prescription. EXPOSURE VARIABLES: Age, sex, diagnosis, prescriber qualification, health facility level, ownership and department were exposure variables. Predictors of receipt of an antibiotic prescription were determined by Poisson regression analysis. RESULTS: Of 993 analysed patients, the mean (±SD) age was 36.3 (±23.2) years, 581 (58.5%) were females and 535 (53.9%) were adults. The prevalence of antibiotic prescription was 46.4% (95% CI 42.8% to 50.0%). Strong predictors of an antibiotic prescription were being a child (1.7, 95% CI 1.3 to 2.2); acute upper respiratory tract infection (URTI) of multiple and unspecified sites (1.6, 95% CI 1.3 to 1.4); chronic rhinitis, nasopharyngitis and pharyngitis (4.0, 95% CI 2.4 to 6.4); being attended by a clinical officer (1.9, 95% CI 1.2 to 3.0); attending a health centre (1.5, 95% CI 1.1 to 2.0); attending a public facility (1.2, 95% CI 1.0 to 1.4) and visiting an inpatient department (2.0, 95% CI 1.2 to 3.4). CONCLUSIONS: Among insured patients, being a child, acute URTI, being attended by a clinical officer or dental therapist, being attended by an assistant medical/dental officer, attending a health centre or a district hospital, attending a public health facility and visiting an inpatient department predicted an antibiotic prescription. Incorporation of these findings in revisions or establishment of targeted antimicrobial stewardship programmes may lead to better antibiotic prescribing practices that are critical for combating antibiotic resistance.
Assuntos
Antibacterianos , Infecções Respiratórias , Criança , Adulto , Feminino , Humanos , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Masculino , Antibacterianos/uso terapêutico , Estudos Transversais , Tanzânia/epidemiologia , Padrões de Prática Médica , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/epidemiologia , PrescriçõesRESUMO
PURPOSE: The 388A>G and the 521T>C polymorphism of the SLCO1B1 gene affect the activity of the uptake transporter OATP1B1, thus influencing kinetics, safety, and efficacy of substrate drugs. To evaluate the impact of these polymorphisms in populations of different ethnic origins, it is important to know their frequencies and to develop fast and reliable methods for genotyping. We therefore established a new, high-throughput method and determined the genotype and allelic frequencies of these polymorphisms in Tanzanians, for which the frequencies were unknown thus far. METHODS: New LightCycler® 480-based methods with hybridization probes were established and used to genotype 366 Tanzanian and 236 European individuals for 388A>G (rs2306283) and 521T>C (rs4149056) in the SLCO1B1 gene. The methods were validated by direct sequencing of the polymerase chain reaction (PCR) products of heterozygous individuals and checked for intrarun precision repeatability, interrun precision reproducibility, robustness, and deviations from the Hardy-Weinberg equilibrium. RESULTS: The new methods allow unambiguous identification of the corresponding genotypes. There was a clear difference in allelic distribution between Tanzanians and Europeans, with the 388A>G (rs2306283) being much more prevalent in Tanzanians (87% vs 41%) and the 521T>C (rs4149056) being very rare in this African population (6% vs 17%). CONCLUSIONS: We developed robust and high-throughput methods to genotype common SLCO1B1 allelic variants with the LightCycler® 480. In Tanzanians, we identified the highest frequency of the 388A>G and 521T>C polymorphisms ever reported from black populations. The clinical relevance of SLCO1B1 genetic variation in the African population remains to be investigated.
Assuntos
Testes Genéticos/métodos , Ensaios de Triagem em Larga Escala/métodos , Transportadores de Ânions Orgânicos/genética , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA/métodos , População Negra/genética , DNA/sangue , DNA/genética , Feminino , Frequência do Gene , Genótipo , Humanos , Desequilíbrio de Ligação , Transportador 1 de Ânion Orgânico Específico do Fígado , Masculino , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Tanzânia , População Branca/genéticaRESUMO
INTRODUCTION: high prevalence of antibiotic prescriptions may contribute to the problem of antibiotic resistance. Understanding the pattern of antibiotic prescriptions in a country may inform monitoring and stewardship activities, which are crucial in the fight against antibiotic resistance. We aimed to determine the prevalence and describe the pattern of antibiotic prescriptions among National Health Insurance Fund (NHIF) insured patients receiving treatment at health facilities in Ilala Municipality, Dar es Salaam, Tanzania. METHODS: a cross-sectional analysis of claim forms of NHIF insured patients. A data extraction form was used to capture data for September, 2019 submitted to the Ilala NHIF offices. RESULTS: among 993 insured patients (mean [±SD] age 36.3 [±23.2] years; 581 [58.5%] females; 535 [53.9%] adults) a total of 357 (46.4%, 95% CI, 42.8-50.0) received an antibiotic prescription. Of the 357 patients who received an antibiotic prescription, 71(19.9%) received more than one antibiotic prescription. The most common antibiotic prescribed was amoxicillin/clavulanate (17.1%) followed by amoxicillin (16.5%) whereas the most commonly prescribed antibiotic class was the penicillins (51.3%) followed by the nitroimidazoles (14.0%). Among patients who received more than one antibiotic, the most commonly co-prescribed antibiotics were Ampicillin/Cloxacillin plus Metronidazole (11.4%) followed by Amoxicillin plus Metronidazole (7.1%). According to 2019 WHO Access, Watch, Reserve (AWaRe) Classification of antibiotics, 60.8% of patients received the access antibiotics, 33.3% received the watch antibiotics whereas 17.4% of patients received antibiotics that were not recommended. No patient received an antibiotic from the reserve group. CONCLUSION: the prevalence of antibiotic prescriptions in Tanzania is high and some antibiotics not recommended by the WHO are still prescribed. We recommend revision of the current Tanzania treatment guideline on antibiotics to reflect WHO recommendations, and further research to address local factors influencing antibiotic prescriptions is warranted.
Assuntos
Antibacterianos , Prescrições , Adulto , Antibacterianos/uso terapêutico , Estudos Transversais , Feminino , Humanos , Prevalência , TanzâniaRESUMO
INTRODUCTION: An increase in cardiovascular disease (CVD) among people living with HIV infection is linked to platelet and immune activation, a phenomenon unabolished by antiretroviral (ARV) drugs alone. In small studies, aspirin (acetylsalicylic acid [ASA]) has been shown to control immune activation, increase CD4+ count, halt HIV disease progression and reduce HIV viral load (HVL). We present a protocol for a larger ongoing randomised placebo controlled trial on the effect of an addition of ASA to ARV drugs on HIV disease progression. METHODS AND ANALYSIS: A single-centre phase IIA double-blind, parallel-group randomised controlled trial intends to recruit 454 consenting ARV drug-naïve, HIV-infected adults initiating ART. Participants are randomised in blocks of 10 in a 1:1 ratio to receive, in addition to ARV drugs, 75 mg ASA or placebo for 6 months. The primary outcome is the proportion of participants attaining HVL of <50 copies/mL by 8, 12 and 24 weeks. Secondary outcomes include proportions of participants with HVL of >1000 copies/mL at week 24, attaining a >30% rise of CD4 count from baseline value at week 12, experiencing adverse events, with normal levels of biomarkers of platelet and immune activation at weeks 12 and 24 and rates of morbidity and all-cause mortality. Intention-to-treat analysis will be done for all study outcomes. ETHICS AND DISSEMINATION: Ethical approval has been obtained from institutional and national ethics review committees. Findings will be submitted to peer-reviewed journals and presented in scientific conferences. TRIAL REGISTRATION NUMBER: PACTR202003522049711.
Assuntos
Infecções por HIV , Adulto , Antirretrovirais/uso terapêutico , Aspirina/uso terapêutico , Contagem de Linfócito CD4 , Progressão da Doença , Infecções por HIV/tratamento farmacológico , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Sub-Saharan Africa has been severely affected by the HIV and AIDS pandemic. Global efforts at improving care and treatment has included scaling up use of antiretroviral therapy (ART). In Tanzania, HIV care and treatment program, including the provision of free ART started in 2004 with a pilot program at Muhimbili National Hospital in Dar es Salaam. This study describes the socio-demographic and clinical features of patients enrolled at the care and treatment clinic at MNH, Dar es Salaam, Tanzania. METHODS: A cross-sectional study looking at baseline characteristics of patients enrolled at the HIV clinic at MNH between June 2004-Dec 2005 compared to those enrolled between 2006 and September 2008. RESULTS: Of all enrolled patients, 2408 (58.5%) were used for analysis. More females than males were attending the clinic. Their baseline median CD4 cell count was low (136 cells/microl) with 65.7% having below 200 cells/microl. Females had higher CD4 cell counts (150 cells/microl) than males (109 cells/microl) p < 0.001). The most common presenting features were skin rash and/or itching (51.6%); progressive weight loss (32.7%) and fever (23.4). Patients enrolled earlier at the clinic (2004-5) were significantly more symptomatic and had significantly lower CD4 cell count (127 cells/microl) compared to CD4 of 167 cells/microl in those seen later (2006-8) (p < 0.001). CONCLUSION: Patients enrolled to the MNH HIV clinic were predominantly females, and presented with advanced immune-deficiency. Improved access to HIV care and treatment services seems to be associated with patients' early presentation to the clinics in the course of HIV disease.
Assuntos
Antirretrovirais/uso terapêutico , Serviços de Saúde Comunitária/estatística & dados numéricos , Infecções por HIV/tratamento farmacológico , Acessibilidade aos Serviços de Saúde , Adolescente , Adulto , Contagem de Linfócito CD4 , Estudos Transversais , Feminino , Febre/etiologia , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Classe Social , Tanzânia , Redução de Peso , Adulto JovemRESUMO
Efavirenz-based combination antiretroviral-therapy (cART) is the recommended regimen during tuberculosis (TB) therapy. In a multi-national parallel prospective-cohort study, we investigated the impact of population and pharmacogenetic variations for efavirenz pharmacokinetics, auto-induction, and immunologic outcome during antituberculosis treatment. A total of 921 treatment-naïve HIV patients with (196 Ethiopians and 231 Tanzanians) or without TB co-infection (285 Ethiopians and 209 Tanzanians) were enrolled and treated with efavirenz-based cART. TB-HIV patients started rifampicin-based anti-TB therapy 4 weeks before cART. Efavirenz plasma concentrations were measured on the 4th and 16th weeks of cART. Genotyping for CYP2B6, CYP3A5, ABCB1, UGT2B7, and SLCO1B1 was done. CD4 cells-count was measured at baseline, 12th, 24th, and 48th weeks of cART. Among HIV-only cohort, plasma efavirenz concentration and median CD4 cell count were significantly higher in Tanzanians than Ethiopians, and both CYP2B6 genotype and population-variation were significant predictors of efavirenz plasma concentration. Within-population analyses indicated a pronounced efavirenz autoinduction in Tanzanians as reflected by a significant decrease of plasma efavirenz concentration over time (p = 0.0001), but not in Ethiopians. Among TB-HIV cohort, there were no significant between-population differences in plasma efavirenz concentrations or CD4 cell-recovery, and CYP2B6 genotype but not population-variation was a significant predictor of efavirenz plasma exposure. In Tanzanian patients, short-term anti-TB co-treatment significantly reduced the mean plasma efavirenz concentration in CYP2B6*1/*1 genotype at week-4 (p = 0.005), but not at week-16 of cART. In Ethiopian patients, anti-TB cotreatment increased the mean plasma efavirenz concentration among CYP2B6*6 carriers at week-4 (p = 0.003) and week-16 (p = 0.035) of cART. In general, long-term anti-TB co-treatment increased plasma efavirenz concentration at week 16 of cART in both Ethiopians and Tanzanians being higher in CYP2B6*6/*6 > *1/*6 > *1/*1 genotypes. In TB-HIV patients, baseline body mass index (BMI), viral load, and WHO clinical-stage but not genotype, population-variation, or efavirenz concentration were significant predictors of immunologic outcome at week-48. In summary efavirenz auto-induction, pharmacokinetics, and the immunologic outcome are influenced by population-variation, anti-TB co-medication, and CYP2B6 genotype. CYP2B6 genotype is a significant predictor of efavirenz plasma exposure regardless of population-variation or antituberculosis co-treatment, but population-variation is insignificant during antituberculosis treatment. CYP2B6 genotype, population, and geographic differences need to be considered for efavirenz dosage-optimization.
RESUMO
BACKGROUND: Adherence to combination antiretroviral therapy (cART) among HIV-infected children is often complicated by various factors including medication formulation, dosing frequency, drug toxicities, age and developmental stage, psychosocial and behavioural characteristics of both children and caregivers and can additionally be complicated by being an orphan. OBJECTIVES: This study was aimed at determining the factors and the extent of their influence on cART adherence among HIV-infected orphaned children attending Care and Treatment Centres (CTCs) in Dar es Salaam, Tanzania. METHODS: A cross-sectional study was performed, which assessed adherence in HIV-positive orphaned children aged 2-14 years receiving nevirapine (NVP) based cART for at least 6 months. Data was collected using questionnaires administered to primary caregivers of HIV-infected orphaned children, the review of medical files, and the laboratory measurement of NVP plasma concentrations and CD4 counts. Adherence to cART was determined based on caregivers' self-report, consistency of clinic attendance and NVP plasma concentrations. RESULTS: Among the 216 enrolled orphaned children, adherence to cART was found to be 79.6%, 82.9% and 72.2% respectively based on caregivers' self-report, clinic attendance and NVP plasma levels. Significant reductions in NVP concentrations (< 3 µg/mL) were seen among children with poor immunological outcomes, poor clinic attendance (p < 0.05) and were suggested by caregivers' self-reported adherence (p = 0.06). Adherence challenges identified by caregivers included financial constraints (87.5%), lengthy waiting times at clinics (75.5% spent > 2 h at the clinic) and low HIV knowledge among caregivers. CONCLUSION: Significant numbers of HIV-infected orphans have poor adherence to cART ranging between 17% and 28% based on different assessment methods. Inadequate caregiver knowledge of HIV/AIDS, long clinic waiting times and forgetfulness were identified as barriers to cART adherence in these orphans.
RESUMO
INTRODUCTION: Serum alanine aminotransferase (ALT) elevations are common among HIV-infected patients on combination antiretroviral therapy (cART). APPROACH: We conducted a prospective cohort study of 3023 HIV-infected Tanzanian adults initiating cART. We assessed risk factors for mild/moderate ALT elevations >40 IU/L and severe ALT elevations >200 IU/L. RESULTS: We found that over a median follow-up of 32.5 months (interquartile range: 19.4-41.5), 44.8% of participants had at least 1 incident ALT elevation >40 IU/L of which 50.1% were persistent elevations. Risk factors for incident ALT elevation >40 IU/L included male sex, CD4 count <100 cells/µL, d4T+3TC+NVP cART, and triglycerides ≥150 mg/dL (P values <.05). Hepatitis B coinfection and alcohol consumption increased the risk of severe ALT elevations >200 IU/L (P values: <.05). CONCLUSION: Incident mild and moderate ALT elevations are common among Tanzanians initiating cART, and the clinical and demographic information can identify patients at increased risk.
Assuntos
Alanina Transaminase/sangue , Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Adolescente , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Contagem de Linfócito CD4 , Coinfecção/virologia , Feminino , Infecções por HIV/sangue , Infecções por HIV/epidemiologia , Hepatite B/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Fatores Sexuais , Tanzânia/epidemiologia , Carga Viral , Adulto JovemRESUMO
BACKGROUND: Children are subject to varying drug pharmacokinetics which influence plasma drug levels, and hence treatment outcomes especially for drugs like efavirenz whose plasma concentrations are directly related to treatment outcomes. This study is aimed at determining plasma efavirenz concentrations among Tanzanian pediatric HIV-1 patients on efavirenz-based combination antiretroviral therapy (cART) and relating it to clinical, immunological and virologic treatment responses. METHODS: A cross sectional study involving pediatric HIV patients aged 5-15 years on efavirenz-based cART for ≥ 6 months were recruited in Dar es Salaam. Data on demographics, cART regimens, efavirenz dose and time of the last dose were collected using structured questionnaires and checklists. Venous blood samples were drawn at 10-19 h post-dosing for efavirenz plasma analysis. RESULTS: A total of 145 children with a mean ± SD age of 10.83 ± 2.75 years, on cART for a mean ± SD of 3.7 ± 2.56 years were recruited. Median [IQR] efavirenz concentration was 2.56 [IQR = 1.5-4.6] µg/mL with wide inter-patient variability (CV 111%). Poor virologic response was observed in 70.8%, 20.8% and 15.9% of patients with efavirenz levels < 1 µg/mL, 1-4 µg/mL and > 4 µg/mL respectively. Patients with efavirenz levels of < 1 µg/mL were 11 times more likely to have detectable viral loads. Immunologically, 31.8% of children who had low levels (< 1 µg/mL) of efavirenz had a CD4 count of < 350 cells/µL. CONCLUSION: Wide inter-individual variability in efavirenz plasma concentrations is seen among Tanzanian children in routine clinical practice with many being outside the recommended therapeutic range. Virologic failure is very high in children with sub-therapeutic levels. Concentrations outside the therapeutic window suggest the need for dose adjustment on the basis of therapeutic drug monitoring to optimize treatment.