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1.
Pharmacogenomics ; 22(14): 881-884, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34505542

RESUMO

Tweetable abstract The large interindividual variability in nevirapine pharmacokinetics and clinical effects that remains unexplained by pharmacogenetic prediction is a major limitation for individualized nevirapine treatment.

2.
BMC Infect Dis ; 21(1): 731, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34340689

RESUMO

BACKGROUND: Children living with human immunodeficiency virus (HIV) infection require lifelong effective antiretroviral therapy (ART). The goal of ART in HIV-infected persons is sustained viral suppression. There is limited information on virological non-suppression or failure and its associated factors in children in resource limited countries, particularly Ghana. METHODS: A cross-sectional study of 250 children aged 8 months to 15 years who had been on ART for at least 6 months attending the Paediatric HIV clinic at Korle Bu Teaching hospital in Ghana was performed. Socio-demographic, clinical, laboratory and ART Adherence related data were collected using questionnaires as well as medical records review. Blood samples were obtained for viral load and CD4+ count determination. Viral load levels > 1000 copies/ml on ART was considered virological non-suppression. Logistic regression was used to identify factors associated with virological non-suppression. RESULTS: The mean (±SD) age of the study participants was 11.4 ± 2.4 years and the proportion of males was 53.2%. Of the 250 study participants, 96 (38.4%) had virological non-suppression. After adjustment for significant variables, the factors associated with non-suppressed viral load were female gender (AOR 2.51 [95% CI 1.04-6.07], p = 0.041), having a previous history of treatment of tuberculosis (AOR 4.95 [95% CI 1.58-15.5], p = 0.006), severe CD4 immune suppression status at study recruitment (AOR 24.93 [95% CI 4.92-126.31], p < 0.001) and being on a nevirapine (NVP) based regimen (AOR 7.93 [95% CI 1.58-1.15], p = 0.005). CONCLUSION: The prevelance of virological non-suppression was high. Virological non-suppression was associated with a previous history of TB treatment, female gender, severe CD4 immune suppression status at study recruitment and being on a NVP based regimen. Early initiation of ART and phasing out NVP-based regimen might improve viral load suppression in children. In addition, children with a history of TB may need focused measures to maximize virological suppression.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Adolescente , Contagem de Linfócito CD4 , Criança , Pré-Escolar , Estudos Transversais , Feminino , Gana , HIV/isolamento & purificação , Infecções por HIV/complicações , Infecções por HIV/virologia , Humanos , Lactente , Modelos Logísticos , Masculino , Nevirapina/uso terapêutico , Fatores de Risco , Fatores Sexuais , Falha de Tratamento , Tuberculose/complicações , Carga Viral
3.
Infect Genet Evol ; 92: 104856, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33839311

RESUMO

Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor that is used in the treatment of human immunodeficiency virus (HIV) infection in children younger than 3 years old. Identifying genetic predictors of NVP pharmacokinetics (PK) in young children is important because inter-individual variability in NVP concentrations contributes to variable treatment response and the information may be used to individualize dosing decisions. We examined the relationship between genetic variations in relevant drug disposition genes and NVP PK parameters in Ghanaian children living with HIV eligible to initiate NVP-based antiretroviral therapy. Participants received NVP plus zidovudine and lamivudine or abacavir and lamivudine twice daily, and those with tuberculosis (TB) coinfection received concurrent anti-TB therapy with NVP. Pharmacokinetic sampling was performed after at least 4 weeks of antiretroviral therapy. Nevirapine minimum concentration (Cmin), area under the concentration-time curve from time 0 to 12 h (AUC0-12h), and apparent clearance (CL/F) were calculated using non-compartmental analysis using Phoenix v8.0 software. Genotyping for CYP2B6, CYP2A6, CYP3A5, ABCB1, NR1I2, and NR1I3 single nucleotide polymorphism (SNPs) was performed by TaqMan® allelic discrimination method. The median (range) NVP dose received was 10 (7-14) mg/kg. Of the 53 participants, the median (range) Cmin was 3.3 (0.0-14.0) mg/L and AUC0-12h was 56.0 (16.7-202.6) mg.hr/L. Using step-wise regression, CYP2B6 rs3745274 and NR1I2 rs6785049 SNPs were independent as well as joint predictors of NVP AUC0-12h, Cmin, and CL/F. We concluded that genotyping for CYP2B6 rs3745274, and the NR1I2 rs6785049 G > A SNP (which encodes the transcriptional factor, pregnane X receptor), could improve prediction of NVP PK for individualized therapy.

4.
Clin Ther ; 42(9): 1818-1825, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32811669

RESUMO

PURPOSE: The updated World Health Organization guidelines recommend efavirenz (EFV) 400 mg as the preferred alternate first-line antiretroviral therapy to dolutegravir, with EFV 600 mg recommended only in special situations. We examined the pharmacokinetic (PK) properties of EFV 600 mg/d during pregnancy and post partum to inform EFV dosing decisions in pregnant women. METHODS: Ghanaian pregnant women with HIV infection initiating tenofovir disoproxil fumarate 300 mg/lamivudine 300 mg/EFV 600 mg fixed-dose combination tablet once daily were enrolled. Efavirenz concentrations were measured at 4 weeks of antiretroviral therapy initiation during pregnancy and 6 weeks post partum using validated LC-MS/MS assays. Efavirenz PK parameters were calculated using noncompartmental analysis, and within-group parameters between the 2 periods were compared. FINDINGS: Of 25 enrolled women, 19 completed PK sampling during pregnancy and post partum. The Cmax, Cmin, AUC0-24h, and CL/F for EFV during pregnancy were similar to values at 6 weeks post partum. The pregnancy/postpartum geometric mean ratios for EFV Cmax, Cmin, AUC0-24, and CL/F were 1.10 (95% CI, 0.93-1.31), 0.88 (95% CI, 0.67-1.17), 0.84 (95% CI, 0.71-0.98), and 1.20 (95% CI, 1.02-1.40), respectively. Viral load suppression (HIV RNA <200 copies/mL) was achieved in 16 of 17 participants (94%) by the time of delivery. There was 1 maternal-to-child transmission. IMPLICATIONS: We found that the PK parameters of EFV 600 mg once daily during pregnancy were similar to those in the postpartum period. Our findings suggest that EFV dose adjustment during pregnancy is not necessary in our study population.


Assuntos
Alcinos/farmacocinética , Fármacos Anti-HIV/farmacocinética , Benzoxazinas/farmacocinética , Ciclopropanos/farmacocinética , Infecções por HIV/tratamento farmacológico , Adulto , Alcinos/administração & dosagem , Benzoxazinas/administração & dosagem , Cromatografia Líquida , Ciclopropanos/administração & dosagem , Feminino , Gana , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Lamivudina/uso terapêutico , Período Pós-Parto , Gravidez , Espectrometria de Massas em Tandem , Tenofovir/uso terapêutico , Carga Viral , Adulto Jovem
6.
Pan Afr Med J ; 33: 111, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31489089

RESUMO

Introduction: High mortality among individuals receiving retreatment for tuberculosis (RT-TB) persists, although reasons for these poor outcomes remain unclear. Methods: We retrospectively reviewed 394 RT-TB patients diagnosed between January 2010 and June 2016 in Accra, Ghana. Results: Of RT-TB patients, 161 (40.9%) were treated empirically (negative/absent smear, culture or Xpert), of whom 30.4% (49/161) had only extrapulmonary TB signs or symptoms. Mortality during treatment was 19.4%; 15-day mortality was 10.8%. In multivariable proportional hazards regression, living with HIV (aHR=2.69 [95 CI: 1.51, 4.80], p<0.01) and previous loss-to-follow up (aHR=8.27 (95 CI: 1.10, 62.25), p=0.04) were associated with mortality, while drug susceptibility testing (DST, aHR=0.36 (95 CI: 0.13, 1.01), p=0.052) was protective. Isoniazid resistance was observed in 40% (23/58 tested) and rifampin resistance in 19.1% (12/63 tested). Conclusion: High rates of extrapulmonary TB and smear/culture negative disease highlight the barriers to achieving DST-driven RT-TB regimens and the need for improved diagnostics. Our finding of poly-drug resistance in rifampin-susceptible cases supports access to comprehensive first line DST. Additionally, interventions to reduce mortality, especially in HIV co-infected RT-TB patients, are urgently needed.


Assuntos
Antituberculosos/administração & dosagem , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose/tratamento farmacológico , Adulto , Antituberculosos/farmacologia , Estudos de Coortes , Farmacorresistência Bacteriana Múltipla , Feminino , Gana , Infecções por HIV/epidemiologia , Humanos , Isoniazida/farmacologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Retratamento , Estudos Retrospectivos , Rifampina/farmacologia , Tuberculose/microbiologia , Tuberculose/mortalidade , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/mortalidade
7.
Virus Genes ; 55(5): 707-712, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31346975

RESUMO

Hepatitis B virus (HBV) exhibits a high degree of heterogeneity with at least 10 genotypes (A-J) identified to date. Intergenotypic recombination is relatively common. Previously, we investigated HBV drug resistance in HIV/HBV co-infected individuals in Ghana. After identifying multiple circulating genotypes and a novel D/E recombinant, we sought to determine if additional individuals were also infected with recombinant HBV. Partial genome sequences from three individuals were initially identified as genotype A4. Full-length HBV genomes were obtained using rolling circle amplification followed by PCR and shown to cluster with known A/E recombinant viruses. Similar recombination breakpoints were observed in these three individuals suggesting local spread of this novel recombinant HBV in Ghana.


Assuntos
Genótipo , Vírus da Hepatite B/classificação , Vírus da Hepatite B/genética , Hepatite B/virologia , Recombinação Genética , Adulto , Análise por Conglomerados , Feminino , Gana , Vírus da Hepatite B/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , Sequenciamento Completo do Genoma
8.
J Acquir Immune Defic Syndr ; 82(4): 421-425, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31335591

RESUMO

BACKGROUND: Incomplete hepatitis B virus (HBV) suppression during antiretroviral therapy (ART) in HIV and HBV coinfected patients is common, but underlying factors are not fully elucidated. We hypothesize that genetic factors that influence nucleoside analog pharmacokinetics will affect HBV treatment response. METHODS: HIV/HBV coinfected patients on tenofovir disoproxil fumarate/lamivudine (TDF/3TC)-containing ART were enrolled. Selected ABCC4 single nucleotide polymorphisms (SNPs) with known effects on nucleoside pharmacokinetics were genotyped using TaqMan assays. Relationship between ABCC4 SNPs and unsuppressed HBV DNA (HBV DNA ≥20 IU/mL) were examined. RESULTS: Of the 50 participants on TDF/3TC-containing ART for a median (range) of 1.5 (1-7.4) years, 20 (40%) had unsuppressed HBV DNA. Participants with unsuppressed compared with those with suppressed HBV DNA were more likely to have negative HBe antibody, lower body mass index, and lower CD4 count at enrollment. Carriers of ABCC4 rs11568695 (G3724A) variant allele were more likely than noncarriers to have unsuppressed HBV (61.1% vs. 29.0%, P = 0.038). Among 36 patients with suppressed HIV RNA (presumed good ART adherence), ABCC4 rs11568695 variant carriers were more likely than noncarriers to have unsuppressed HBV (58.8% vs. 20.0% P = 0.021). Logistic regression analysis that included genetic and nongenetic factors identified ABCC4 rs11568695 variant allele, body mass index, and male sex as predictors of unsuppressed HBV DNA. CONCLUSIONS: We identified a novel association between ABCC4 rs11568695 SNP and poor HBV treatment response. If confirmed in further studies, ABCC4 genotyping could be used to identify individuals who may need intensified HBV therapy.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Coinfecção/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Hepatite B/tratamento farmacológico , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Polimorfismo de Nucleotídeo Único , Tenofovir/uso terapêutico , Adulto , DNA Viral/análise , Feminino , Infecções por HIV/virologia , Hepatite B/virologia , Vírus da Hepatite B/efeitos dos fármacos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade
9.
Artigo em Inglês | MEDLINE | ID: mdl-31332062

RESUMO

Nevirapine-based antiretroviral therapy (ART) is one of the limited options in HIV-infected children younger than 3 years old (young children) with tuberculosis (TB) coinfection. To date, there are insufficient data to recommend nevirapine-based therapy during first-line antituberculosis (anti-TB) therapy in young children. We compared nevirapine pharmacokinetics (PK) in HIV-infected young children with and without TB coinfection. In the coinfected group, nevirapine PK was evaluated while on anti-TB therapy and after completing an anti-TB therapy regimen. Of 53 participants, 23 (43%) had TB-HIV coinfection. While the mean difference in nevirapine PK parameters between the two groups was not significant (P > 0.05), 14/23 (61%) of the children with TB-HIV coinfection and 9/30 (30%) with HIV infection had a nevirapine minimum concentration (C min) below the proposed target of 3.0 mg/liter (P = 0.03). In multivariate analysis, anti-TB therapy and the CYP2B6 516G>T genotype were joint predictors of nevirapine PK parameters. Differences in nevirapine PK parameters between the two groups were significant in children with CYP2B6 516GG but not the GT or TT genotype. Among 14 TB-HIV-coinfected participants with paired data, the geometric mean C min and area under the drug concentration-time curve from time zero to 12 h (AUC0-12) were about 34% lower when patients were taking anti-TB therapy, while the nevirapine apparent oral clearance (CL/F) was about 45% higher. While the induction effect of anti-TB therapy on nevirapine PK in our study was modest, the CYP2B6 genotype-dependent variability in the TB drug regimen effect would complicate any dose adjustment strategy in young children with TB-HIV coinfection. Alternate ART regimens that are more compatible with TB treatment in this age group are needed. (This study has been registered at ClinicalTrials.gov under identifier NCT01699633.).


Assuntos
Fármacos Anti-HIV/farmacocinética , Fármacos Anti-HIV/uso terapêutico , Antituberculosos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Nevirapina/farmacocinética , Nevirapina/uso terapêutico , Tuberculose/tratamento farmacológico , Pré-Escolar , Coinfecção/tratamento farmacológico , Coinfecção/metabolismo , Citocromo P-450 CYP2B6/metabolismo , Feminino , Genótipo , Infecções por HIV/metabolismo , Humanos , Lactente , Masculino , Tuberculose/metabolismo
10.
Pan Afr Med J ; 32: 206, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31312318

RESUMO

Introduction: Tuberculosis (TB) is currently causing more deaths than Human Immunodeficiency Virus (HIV) globally. Ghana as one of the 30 high burden TB/HIV countries has a high annual TB case-fatality rate of 10%. The study sought to assess the effect of HIV infection on TB treatment outcomes and assess the time to mortality after treatment onset. Methods: We conducted a review of treatment files of TB patients who were treated from January 2013 to December 2015 in two urban hospitals in the Accra Metropolis. Modified Poisson regression analysis was used to measure the association between HIV infection and TB treatment outcomes. Kaplan-Meier survival estimates were used to plot survival curves. Results: Seventy-seven percent (83/107) of HIV infected individuals had successful treatment, compared to 91.2% (382/419) treatment success among HIV non-infected individuals. The proportion of HIV-positive individuals who died was 21.5% (23/107) whilst that of HIV-negative individuals was 5.5% (23/419). Being HIV-positive increased the risk of adverse outcome relative to successful outcome by a factor of 2.89(95% CI 1.76-4.74). The total number of deaths recorded within the treatment period was 46; of which 29(63%) occurred within the first two months of TB treatment. The highest mortality rate observed was among HIV infected persons (38.6/1000 person months). Of the 107 TB/HIV co-infected patients, 4(3.7%) initiated ART during TB treatment. Conclusion: The uptake of ART in co-infected individuals in this study was very low. Measures should be put in place to improve ART coverage among persons with TB/HIV co-infection to help reduce mortality.


Assuntos
Antituberculosos/uso terapêutico , Infecções por HIV/epidemiologia , Tuberculose/tratamento farmacológico , Adolescente , Adulto , Estudos de Coortes , Coinfecção , Feminino , Gana/epidemiologia , Infecções por HIV/mortalidade , Soropositividade para HIV/epidemiologia , Hospitais Urbanos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Distribuição de Poisson , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Tuberculose/mortalidade , Adulto Jovem
11.
J Antimicrob Chemother ; 74(9): 2698-2706, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31243456

RESUMO

OBJECTIVES: The current WHO weight-based dosing recommendations for efavirenz result in a wide variability of drug exposure in children. Our objectives are to characterize the effects of rifampicin- and isoniazid-containing anti-TB therapy and CYP2B6 activity on efavirenz concentrations in children, using non-linear mixed-effects modelling. METHODS: This is a pharmacokinetic (PK) substudy of a prospective study that examined the interactions between anti-TB therapy and efavirenz in HIV-infected children with and without TB. PK samples were obtained 4 weeks after starting efavirenz (PK1) and repeated 4 weeks after completing TB therapy (PK2) in TB/HIV coinfected patients. Drug concentrations were measured using LC-MS/MS. Composite CYP2B6 516/983/15582 genotype was determined. Population PK modelling was performed in Monolix. Simulations were performed to obtain the predicted mid-dose concentrations (C12). RESULTS: One hundred and five HIV-infected Ghanaian children (46 with TB/HIV) were included. The median age and weight were 7 years and 19 kg. The efavirenz concentrations over time were adequately described using a one-compartment model. Weight, composite CYP2B6 genotype and PK visit had a significant influence on the PK parameters, while TB therapy had no significant effect. Simulations showed adequate C12 for intermediate composite CYP2B6 metabolizers only. CONCLUSIONS: Our model showed that rifampicin- and isoniazid-containing anti-TB therapy does not influence efavirenz PK parameters. On the other hand, it describes the effect of efavirenz autoinduction after completing TB treatment. In addition, dosing efavirenz in children based only on weight results in a large variability in drug exposure. We propose dose adjustments for slow and extensive composite CYP2B6 metabolizers.


Assuntos
Fármacos Anti-HIV/farmacocinética , Benzoxazinas/farmacocinética , Coinfecção , Infecções por HIV/tratamento farmacológico , Testes Farmacogenômicos , Inibidores da Transcriptase Reversa/farmacocinética , Adolescente , Alcinos , Fármacos Anti-HIV/administração & dosagem , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Benzoxazinas/administração & dosagem , Variação Biológica Individual , Criança , Pré-Escolar , Ciclopropanos , Interações Medicamentosas , Monitoramento de Medicamentos , Feminino , Genótipo , Infecções por HIV/genética , Infecções por HIV/virologia , Humanos , Masculino , Modelos Teóricos , Variantes Farmacogenômicos , Inibidores da Transcriptase Reversa/administração & dosagem , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia
12.
J Int Assoc Provid AIDS Care ; 18: 2325958219835786, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30907257

RESUMO

Holding support groups with the same cohort of adolescents during clinic visits promises to increase engagement in care. Participants (N = 35 patients, aged 12-18, 50% female, from an adolescent HIV clinic in Kumasi, Ghana, were divided into 5 teams. Clinic visits were coordinated for members of each team. Team members participated in group discussions and activities while waiting to meet with their medical team. Teams met quarterly for 1 year. Participants reported benefits from talking with peers about the challenges of managing HIV. Clinic attendance improved from the preceding year (54% versus 84%). There were reductions in perceived internal stigma, perceived external stigma, worries about unintended disclosure from taking antiretroviral therapy (ART), and reduced ART concerns. The program demonstrated the feasibility, safety, and acceptability of facilitating increased interaction among adolescents living with HIV during clinic visits. Improvements in clinic attendance, perceived stigma, and concern about medications suggest that the intervention is a promising candidate for additional study.


Assuntos
Infecções por HIV/psicologia , Grupo Associado , Grupos de Autoajuda , Adolescente , Instituições de Assistência Ambulatorial/estatística & dados numéricos , Fármacos Anti-HIV/uso terapêutico , Criança , Estudos de Viabilidade , Feminino , Gana , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Adesão à Medicação , Estigma Social
13.
Artigo em Inglês | MEDLINE | ID: mdl-30397066

RESUMO

We compared efavirenz pharmacokinetic (PK) parameters in children with tuberculosis (TB)/human immunodeficiency virus (HIV) coinfection on and off first-line antituberculosis therapy to that in HIV-infected children. Children 3 to 14 years old with HIV infection, with and without TB, were treated with standard efavirenz-based antiretroviral therapy without any efavirenz dose adjustments. The new World Health Organization-recommended antituberculosis drug dosages were used in the coinfected participants. Steady-state efavirenz concentrations after 4 weeks of antiretroviral therapy were measured using validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) assays. Pharmacokinetic parameters were calculated using noncompartmental analysis. Between groups, PK parameters were compared by Wilcoxon rank-sum test and within group by signed-rank test. Of the 105 participants, 43 (41.0%) had TB coinfection. Children with TB/HIV coinfection compared to those with HIV infection were younger, had lower median weight-for-age Z score, and received a higher median efavirenz weight-adjusted dose. Geometric mean (GM) efavirenz peak concentration (C max), concentration at 12 h (C 12h), C min, and total area under the curve from time 0 to 24 h (AUC0-24h) values were similar in children with HIV infection and those with TB/HIV coinfection during anti-TB therapy. Geometric mean efavirenz C 12h, C min, and AUC0-24h values were lower in TB/HIV-coinfected patients off anti-TB therapy than in the children with HIV infection or TB/HIV coinfection on anti-TB therapy. Efavirenz clearance was lower and AUC0-24h was higher on than in patients off anti-TB therapy. Reduced efavirenz clearance by first-line anti-TB therapy at the population level led to similar PK parameters in HIV-infected children with and without TB coinfection. Our findings do not support modification of efavirenz weight-band dosing guidelines based on TB coinfection status in children. (The study was registered with ClinicalTrials.gov under registration number NCT01704144.).


Assuntos
Antirretrovirais/sangue , Antituberculosos/uso terapêutico , Benzoxazinas/sangue , Infecções por HIV/tratamento farmacológico , Isoniazida/uso terapêutico , Inibidores da Transcriptase Reversa/sangue , Rifampina/uso terapêutico , Tuberculose Pulmonar/tratamento farmacológico , Adolescente , Alcinos , Antirretrovirais/uso terapêutico , Benzoxazinas/farmacocinética , Benzoxazinas/uso terapêutico , Criança , Pré-Escolar , Cromatografia Líquida , Coinfecção/tratamento farmacológico , Ciclopropanos , Interações Medicamentosas , Feminino , Humanos , Masculino , Inibidores da Transcriptase Reversa/uso terapêutico , Espectrometria de Massas em Tandem
14.
Clin Pharmacokinet ; 58(6): 747-766, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30406475

RESUMO

INTRODUCTION: Contrasting findings have been published regarding the effect of human immunodeficiency virus (HIV) on tuberculosis (TB) drug pharmacokinetics (PK). OBJECTIVES: The aim of this systematic review was to investigate the effect of HIV infection on the PK of the first-line TB drugs (FLDs) rifampicin, isoniazid, pyrazinamide and ethambutol by assessing all published literature. METHODS: Searches were performed in MEDLINE (through PubMed) and EMBASE to find original studies evaluating the effect of HIV infection on the PK of FLDs. The included studies were assessed for bias and clinical relevance. PK data were extracted to provide insight into the difference of FLD PK between HIV-positive and HIV-negative TB patients. This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and its protocol was registered at PROSPERO (registration number CRD42017067250). RESULTS: Overall, 27 studies were eligible for inclusion. The available studies provide a heterogeneous dataset from which consistent results could not be obtained. In both HIV-positive and HIV-negative TB groups, rifampicin (13 of 15) and ethambutol (4 of 8) peak concentration (Cmax) often did not achieve the minimum reference values. More than half of the studies (11 of 20) that included both HIV-positive and HIV-negative TB groups showed statistically significantly altered FLD area under the concentration-time curve and/or Cmax for at least one FLD. CONCLUSIONS: HIV infection may be one of several factors that reduce FLD exposure. We could not make general recommendations with respect to the role of dosing. There is a need for consistent and homogeneous studies to be conducted.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/metabolismo , Antituberculosos/farmacocinética , Infecções por HIV/metabolismo , Tuberculose/metabolismo , Infecções Oportunistas Relacionadas com a AIDS/sangue , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Antituberculosos/administração & dosagem , Antituberculosos/sangue , Área Sob a Curva , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Humanos , Tuberculose/sangue , Tuberculose/tratamento farmacológico
15.
AIDS Behav ; 23(2): 433-444, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29968140

RESUMO

Care for low birthweight (LBW) infants can contribute to psychological difficulties and stigma among mothers living with HIV, creating challenges for antiretroviral therapy (ART) adherence and retention in HIV care. We explored how caring for LBW infants affects maternal ART adherence and retention in care. We conducted 30 in-depth interviews with postpartum women living with HIV in Accra, Ghana: 15 with LBW infants and 15 with normal birthweight (NBW) infants. Compared to mothers with NBW infants, mothers with LBW infants described how caring for their newborns led to increased caregiver burden, prolonged hospital stays, and stigma-contributing to incomplete ART adherence and missed clinical appointments. For a few women, care for LBW infants created opportunities for re-engagement in HIV care and motivation to adhere to ART. Results suggest women living with HIV and LBW babies in Ghana face increased challenges that impact their adherence to care and ART.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Cuidado do Lactente/psicologia , Adesão à Medicação/psicologia , Mães/psicologia , Período Pós-Parto/psicologia , Adulto , Feminino , Gana , Infecções por HIV/psicologia , Humanos , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Tempo de Internação , Gravidez , Complicações Infecciosas na Gravidez , Pesquisa Qualitativa , Estigma Social , Adulto Jovem
16.
J Health Popul Nutr ; 37(1): 26, 2018 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-30509309

RESUMO

BACKGROUND: Optimal nutrition is a determinant of health in all persons. In persons living with HIV (PLHIV), nutrition is particularly important. Various factors, including dietary practices, play a role in guaranteeing nutritional health. OBJECTIVES: We investigated multiple non-prescription drugs use among HIV-positive persons receiving antiretroviral therapy (ART) from four treatment centers in southern Ghana. This paper, however, focuses on nutrient supplement use, food elimination, and food substitution practices by the PLHIV. METHODS: Using quantitative and qualitative methods, we collected data from 540 HIV-positive persons at the health facility level. This paper focuses on only the quantitative data. Individual study participants were selected using a systematic random sampling procedure. Participants were interviewed after informed consent. We used univariate analysis to generate descriptive tabulations for key variables. Multivariable logistic regression modeling identified predictors of three practices (nutrient supplementation, food elimination, and food substitution). P value less than 0.05 or 95% confidence intervals facilitated determination of statistical significance. All analyses were performed using IBM SPSS Statistics for Windows, version 20.0. RESULTS: The use of nutrient supplements was a popular practice; 72% of the PLHIV used various kinds. The primary motive for the practice was to boost appetite and to gain weight. A little over 20% of the participants reportedly eliminated certain foods and beverages, while 17% introduced new foods since their initial HIV diagnosis. All the three practices were largely driven by the quest for improved health status. We determined predictors of nutrient supplementation to be ART clinic location and having an ART adherence monitor. Having an ART adherence monitor was significantly associated with reduced odds of nutrient supplementation (AOR = 0.34; 95% CI 0.12-0.95). The only predictor for food elimination was education level (AOR = 0.29; 95% CI 0.30-0.92); predictors of food substitution were ART clinic location (AOR = 0.11; 95% CI 0.02-0.69) and anemia (defined as hemoglobin concentration less than 11.0 g/dl) (AOR = 0.21; 95% CI 0.12-0.85). CONCLUSIONS: The practice of supplementation is popular among this group of PLHIV. Food elimination and substitution are practiced, albeit in moderation. The predictors identified may prove helpful in provider-client encounters as well as local HIV programming.


Assuntos
Instituições de Assistência Ambulatorial , Fármacos Anti-HIV/uso terapêutico , Dieta , Suplementos Nutricionais , Comportamento Alimentar , Infecções por HIV , Adesão à Medicação , Adolescente , Adulto , Idoso , Anemia/etiologia , Estudos Transversais , Escolaridade , Feminino , Gana , Infecções por HIV/dietoterapia , Infecções por HIV/tratamento farmacológico , Hemoglobinas/metabolismo , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Motivação , Aceitação pelo Paciente de Cuidados de Saúde , Inquéritos e Questionários , Adulto Jovem
17.
Artigo em Inglês | MEDLINE | ID: mdl-29914960

RESUMO

Optimal doses for antituberculosis (anti-TB) drugs in children have yet to be established. In 2010, the World Health Organization (WHO) recommended revised dosages of the first-line anti-TB drugs for children. Pharmacokinetic (PK) studies that investigated the adequacy of the WHO revised dosages to date have yielded conflicting results. We performed population PK modeling using data from one of these studies to identify optimal dosage ranges. Ghanaian children with tuberculosis on recommended therapy with rifampin (RIF), isoniazid (INH), pyrazinamide (PZA), and ethambutol (EMB) for at least 4 weeks had blood samples collected predose and at 1, 2, 4, and 8 hours postdose. Drug concentrations were determined by validated liquid chromatography-mass spectrometry methods. Nonlinear mixed-effects models were applied to describe the population PK of those drugs using MonolixSuite2016R1 (Lixoft, France). Bayesian estimation was performed, the correlation coefficient, bias, and precision between the observed and predicted areas under the concentration-time curve (AUCs) were calculated, and Bland-Altman plots were analyzed. The population PK of RIF and PZA was described by a one-compartment model and that for INH and EMB by a two-compartment model. Plasma maximum concentration (Cmax) and AUC targets were based on published results for children from India. The lowest target values for pediatric TB patients were attainable at the WHO-recommended dosage schedule for RIF and INH, except for N-acetyltransferase 2 non-slow acetylators (rapid and intermediate acetylators) in the lower-weight bands. However, higher published adult targets were not attainable for RIF and INH. The targets were not achieved for PZA and EMB. (This study has been registered at ClinicalTrials.gov under identifier NCT01687504.).


Assuntos
Antituberculosos/administração & dosagem , Antituberculosos/farmacocinética , Tuberculose/tratamento farmacológico , Área Sob a Curva , Teorema de Bayes , Criança , Pré-Escolar , Feminino , França , Gana , Humanos , Índia , Masculino , Organização Mundial da Saúde
19.
BMC Infect Dis ; 18(1): 149, 2018 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-29606091

RESUMO

BACKGROUND: Mycobacterium tuberculosis drug resistance is a major challenge to the use of standardized regimens for tuberculosis (TB) therapy, especially among previously treated patients. We aimed to investigate the frequency and pattern of drug resistance among previously treated patients with smear-positive pulmonary tuberculosis at the Korle-Bu Teaching Hospital Chest Clinic, Accra. METHODS: This was a cross-sectional survey of mycobacterial isolates from previously treated patients referred to the Chest Clinic Laboratory between October 2010 and October 2013. The Bactec MGIT 960 system for mycobactrerial culture and drug sensitivity testing (DST) was used for sputum culture of AFB smear-positive patients with relapse, treatment failure, failure of smear conversion, or default. Descriptive statistics were used to summarize patient characteristics, and frequency and patterns of drug resistance. RESULTS: A total of 112 isolates were studied out of 155 from previously treated patients. Twenty contaminated (12.9%) and 23 non-viable isolates (14.8%) were excluded. Of the 112 studied isolates, 53 (47.3%) were pan-sensitive to all first-line drugs tested Any resistance (mono and poly resistance) to isoniazid was found in 44 isolates (39.3%) and any resistance to streptomycin in 43 (38.4%). Thirty-one (27.7%) were MDR-TB. Eleven (35.5%) out of 31 MDR-TB isolates were pre-XDR. MDR-TB isolates were more likely than non-MDR isolates to have streptomycin and ethambutol resistance. CONCLUSIONS: The main findings of this study were the high prevalence of MDR-TB and streptomycin resistance among previously treated TB patients, as well as a high prevalence of pre-XDR-TB among the MDR-TB patients, which suggest that first-line and second-line DST is essential to aid the design of effective regimens for these groups of patients in Ghana.


Assuntos
Antituberculosos/uso terapêutico , Farmacorresistência Bacteriana , Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/epidemiologia , Adulto , Estudos Transversais , Farmacorresistência Bacteriana/efeitos dos fármacos , Feminino , Gana/epidemiologia , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Prevalência , Saúde Pública/normas , Padrão de Cuidado , Centros de Atenção Terciária , Adulto Jovem
20.
Virus Genes ; 54(3): 361-367, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29551002

RESUMO

Human pegivirus (HPgV) is a positive single-stranded RNA virus in the Flaviviridae family. Phylogenetic analysis reveals the presence of multiple HPgV genotypes with distinct geographic locations. HPgV is of interest because of its potential beneficial impact on HIV disease progression. Despite this, the effects of HPgV in the context of other viral infections, such as hepatitis B virus (HBV), are poorly understood, and data from resource-limited settings are scarce. Therefore, we conducted a cross-sectional analysis of HPgV in HIV/HBV co-infected patients in Ghana. Sera from 100 HIV/HBV co-infected individuals were evaluated for HPgV RNA, and the genotype determined by sequencing the 5' untranslated region. HPgV RNA was detected in 27 samples (27%). Of these, 26 were genotyped successfully with 23 belonging to HPgV genotype 1 and 3 belonging to HPgV genotype 2. The presence of HPgV RNA had no statistically significant impact on CD4 cell count or HBV DNA titers in the HIV/HBV co-infected patients. However, there was a trend towards decreased HBV DNA levels in HPgV RNA-positive patients with CD4 cell count < 200 (p = 0.0626). HPgV co-infection is common in Ghana. The effect of HPgV on HIV or HBV disease among HIV/HBV co-infected patients was minimal. However, decreased HBV DNA levels in HPgV RNA-positive patients with low CD4 cell counts highlight the need for prospective studies of HPgV in HIV and hepatitis co-infected patients, especially in those with advanced HIV disease, to study further the effects of HPgV on liver disease.


Assuntos
Coinfecção/epidemiologia , Infecções por Flaviviridae/complicações , Vírus GB C , Infecções por HIV/complicações , Hepatite B/complicações , Hepatite Viral Humana/complicações , Adulto , Coinfecção/virologia , Feminino , Infecções por Flaviviridae/epidemiologia , Gana/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade
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