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1.
Contemp Clin Trials Commun ; 24: 100859, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34825101

RESUMO

Safe practices for dispensing investigational product (IP) during clinical trials are not standardized and information in this regard is often limited. ASPIRE was a Phase 3 safety and effectiveness trial of a vaginal matrix ring containing 25 mg of dapivirine for the prevention of HIV-1 in women. The study enrolled 2629 women at 15 clinical research sites in Malawi, Uganda, South Africa and Zimbabwe who were randomized in a 1:1 ratio to receive either a vaginal ring containing 25 mg of dapivirine or a matching placebo vaginal ring. The vaginal rings and packaging were identical in appearance in order to maintain the study blind. A real-time, documented second check of the dispensing process was conducted by a second pharmacy staff. Frequent inventory counts and real time accountability audits were also useful for rapidly identifying a dispensing error. A total of 52,625 vaginal rings were dispensed with only three documented pharmacy dispensing errors. There were zero dispensing errors at 13 of the 15 sites with an overall rate of <1.0 per 10,000 rings dispensed. Our study findings support the implementation of a double check dispensing process and real time accountability audits as standard practice in clinical trials.

2.
Clin Infect Dis ; 70(1): 90-98, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30809633

RESUMO

BACKGROUND: The substitution of moxifloxacin for ethambutol produced promising results for improved tuberculosis treatment outcomes. METHODS: We conducted an open-label, randomized trial to test whether a moxifloxacin-containing treatment regimen was superior to the standard regimen for the treatment of recurrent tuberculosis. The primary and secondary outcomes were the sputum culture conversion rate at the end of 8 weeks and the proportion of participants with a favorable outcome, respectively. RESULTS: We enrolled 196 participants; 69.9% were male and 70.4% were co-infected with human immunodeficiency virus (HIV). There was no significant difference between the study groups in the proportion of patients achieving culture conversion at the end of 8 weeks (83.0% [moxifloxacin] vs 78.5% [control]; P = .463); however, the median time to culture conversion was significantly shorter (6.0 weeks, interquartile range [IQR] 4.0-8.3) in the moxifloxacin group than the control group (7.9 weeks, IQR 4.0- 11.4; P = .018). A favorable end-of-treatment outcome was reported in 86 participants (87.8%) in the moxifloxacin group and 93 participants (94.9%) in the control group, for an adjusted absolute risk difference of -5.5 (95% confidence interval -13.8 to 2.8; P = .193) percentage points. There were significantly higher proportions of participants with Grade 3 or 4 adverse events (43.9% [43/98] vs 25.5% [25/98]; P = .01) and serious adverse events (27.6% [27/98] vs 12.2% [12/98]; P = .012) in the moxifloxacin group. CONCLUSIONS: The replacement of ethambutol with moxifloxacin did not significantly improve either culture conversion rates at the end of 8 weeks or treatment success, and was associated with a higher incidence of adverse events. CLINICAL TRIALS REGISTRATION: NCT02114684.


Assuntos
Preparações Farmacêuticas , Tuberculose Pulmonar , Antituberculosos/uso terapêutico , Quimioterapia Combinada , Feminino , Fluoroquinolonas/uso terapêutico , Humanos , Masculino , Moxifloxacina/uso terapêutico , Resultado do Tratamento , Tuberculose Pulmonar/tratamento farmacológico
3.
Pharmacogenomics ; 20(4): 225-240, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30767706

RESUMO

AIM: We report the prevalence and effect of genetic variability on pharmacokinetic parameters of isoniazid and rifampicin. MATERIALS & METHODS: Genotypes for SLCO1B1, NAT2, PXR, ABCB1 and UGT1A genes were determined using a TaqMan® Genotyping OpenArray™. Nonlinear mixed-effects models were used to describe drug pharmacokinetics. RESULTS: Among 172 patients, 18, 43 and 34% were classified as rapid, intermediate and slow NAT2 acetylators, respectively. Of the 58 patients contributing drug concentrations, rapid and intermediate acetylators had 2.3- and 1.6-times faster isoniazid clearance than slow acetylators. No association was observed between rifampicin pharmacokinetics and SLCO1B1, ABCB1, UGT1A or PXR genotypes. CONCLUSION: Clinical relevance of the effects of genetic variation on isoniazid concentrations and low first-line tuberculosis drug exposures observed require further investigation.


Assuntos
Arilamina N-Acetiltransferase/genética , Isoniazida/farmacocinética , Rifampina/farmacocinética , Tuberculose/tratamento farmacológico , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Adulto , Feminino , Genótipo , Glucuronosiltransferase/genética , Humanos , Isoniazida/administração & dosagem , Transportador 1 de Ânion Orgânico Específico do Fígado/genética , Masculino , Polimorfismo de Nucleotídeo Único/genética , Recidiva , Rifampina/administração & dosagem , Tuberculose/genética , Tuberculose/patologia
4.
JAC Antimicrob Resist ; 1(3): dlz060, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34222934

RESUMO

Objectives: To map published data of antimicrobial stewardship (AMS) interventions that are currently being carried out in hospitals and clinics in the public and private health sectors of South Africa in line with the antimicrobial resistance (AMR) strategy of South Africa. Methods: A systematic scoping review was conducted to identify AMS initiatives in the public and private health sectors of South Africa for the period 1 January 2000 to 31 March 2019. An electronic search of databases was made including PubMed, Scopus, a key medical journal (South African Medical Journal), University of KwaZulu-Natal (UKZN) WorldCat iCatalogue and AMR networks: Federation of Infectious Diseases Societies in South Africa (FIDSSA). Reference lists of published articles were also reviewed for inclusion. Keywords included 'antimicrobial antibiotic stewardship South Africa'. Findings: Of a total of 411 articles, using a stepwise screening process, 18 articles were selected for inclusion in the review. The interventions/initiatives were divided into four broad categories: (i) AMS intervention: prescription audits and usage; (ii) AMS intervention: education and its impact; (iii) other AMS interventions; and (iv) the role of different healthcare professionals in AMS. Conclusions: The data identifies a need for and the value of AMS in both the public and private health sectors of South Africa. Initiatives are carried out across both sectors but more attention needs to be focused on AMS implementation in line with the National AMR Strategy of South Africa. Collaboration between the different sectors will aid in overcoming the AMR challenge.

5.
Pharmacogenomics ; 19(1): 17-29, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29210323

RESUMO

AIM: We assessed the effect of genetic variability in UGT1A and ABCB1 genes on moxifloxacin pharmacokinetics. METHODS: Genotypes for selected UGT1A and ABCB1 SNPs were determined using a TaqMan® Genotyping OpenArray™ and high-resolution melt analysis for rs8175347. A nonlinear mixed-effects model was used to describe moxifloxacin pharmacokinetics. RESULTS: Genotypes of UGT1A SNPs, rs8175347 and rs3755319 (20.6% lower and 11.6% increased clearance, respectively) and ABCB1 SNP rs2032582 (40% reduced bioavailability in one individual) were significantly associated with changes in moxifloxacin pharmacokinetic parameters. CONCLUSION: Genetic variation in UGT1A as represented by rs8175347 to a lesser extent rs3755319 and the ABCB1 rs2032582 SNP is modestly associated with the interindividual variability reported in moxifloxacin pharmacokinetics and exposure. Clinical relevance of the effects of genetic variation on moxifloxacin pharmacokinetic requires further investigation.


Assuntos
Antibacterianos/farmacocinética , Fluoroquinolonas/farmacocinética , Glucuronosiltransferase/genética , Polimorfismo de Nucleotídeo Único/genética , Tuberculose/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Adulto , Antibacterianos/uso terapêutico , Feminino , Fluoroquinolonas/uso terapêutico , Genótipo , Humanos , Masculino , Moxifloxacina , Estudos Prospectivos , Tuberculose/tratamento farmacológico , Tuberculose/metabolismo
7.
J Clin Pharmacol ; 57(11): 1369-1386, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28741299

RESUMO

Moxifloxacin, an 8-methoxy quinolone, is an important drug in the treatment of multidrug-resistant tuberculosis and is being investigated in novel drug regimens with pretomanid, bedaquiline, and pyrazinamide, or rifapentine, for the treatment of drug-susceptible tuberculosis. Early results of these studies are promising. Although current evidence does not support the use of moxifloxacin in treatment-shortening regimens for drug-susceptible tuberculosis, it may be recommended in patients unable to tolerate standard first-line drug regimens or for isoniazid monoresistance. Evidence suggests that the standard 400-mg dose of moxifloxacin used in the treatment of tuberculosis may be suboptimal in some patients, leading to worse tuberculosis treatment outcomes and emergence of drug resistance. Furthermore, a drug interaction with the rifamycins results in up to 31% reduced plasma concentrations of moxifloxacin when these are combined for treatment of drug-susceptible tuberculosis, although the clinical relevance of this interaction is unclear. Moxifloxacin exhibits extensive interindividual pharmacokinetic variability. Higher doses of moxifloxacin may be needed to achieve drug exposures required for improved clinical outcomes. Further study is, however, needed to determine the safety of proposed higher doses and clinically validated targets for drug exposure to moxifloxacin associated with improved tuberculosis treatment outcomes. We discuss in this review the evidence for the use of moxifloxacin in drug-susceptible tuberculosis and explore the role of moxifloxacin pharmacokinetics, pharmacodynamics, and drug interactions with rifamycins, on tuberculosis treatment outcomes when used in first-line tuberculosis drug regimens.


Assuntos
Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Fluoroquinolonas/farmacologia , Fluoroquinolonas/uso terapêutico , Tuberculose/tratamento farmacológico , Animais , Interações Medicamentosas/fisiologia , Humanos , Moxifloxacina , Rifampina/análogos & derivados , Rifampina/farmacologia , Rifampina/uso terapêutico
8.
J Antimicrob Chemother ; 72(5): 1441-1449, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28175315

RESUMO

Objectives: We compared the pharmacokinetics of moxifloxacin during rifampicin co-treatment or when dosed alone in African patients with drug-susceptible recurrent TB. Methods: Patients in the intervention arm of the Improving Retreatment Success (IMPRESS) randomized controlled TB trial received 400 mg of moxifloxacin, with rifampicin, isoniazid and pyrazinamide in the treatment regimen. Moxifloxacin concentrations were measured in plasma during rifampicin-based TB treatment and again 4 weeks after treatment completion, when given alone as a single dose. Moxifloxacin concentration-time data were analysed using non-linear mixed-effects models. Results: We included 58 patients; 42 (72.4%) were HIV co-infected and 40 (95%) of these were on efavirenz-based ART. Moxifloxacin pharmacokinetics was best described using a two-compartment disposition model with first-order lagged absorption and elimination using a semi-mechanistic model describing hepatic extraction. Oral clearance (CL/F) of moxifloxacin during rifampicin-based TB treatment was 24.3 L/h for a typical patient (fat-free mass of 47 kg), resulting in an AUC of 16.5 mg·h/L. This exposure was 7.8% lower than the AUC following the single dose of moxifloxacin given alone after TB treatment completion. In HIV-co-infected patients taking efavirenz-based ART, CL/F of moxifloxacin was increased by 42.4%, resulting in a further 30% reduction in moxifloxacin AUC. Conclusions: Moxifloxacin clearance was high and plasma concentrations low in our patients overall. Moxifloxacin AUC was further decreased by co-administration of efavirenz-based ART and, to a lesser extent, rifampicin. The clinical relevance of the low moxifloxacin concentrations for TB treatment outcomes and the need for moxifloxacin dose adjustment in the presence of rifampicin and efavirenz co-treatment need further investigation.


Assuntos
Antibióticos Antituberculose/uso terapêutico , Benzoxazinas/uso terapêutico , Fluoroquinolonas/farmacocinética , Infecções por HIV/complicações , Rifampina/uso terapêutico , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/tratamento farmacológico , Adulto , África , Alcinos , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Antibióticos Antituberculose/administração & dosagem , Antibióticos Antituberculose/efeitos adversos , Antibióticos Antituberculose/farmacocinética , Benzoxazinas/administração & dosagem , Benzoxazinas/sangue , Coinfecção/tratamento farmacológico , Coinfecção/microbiologia , Coinfecção/virologia , Ciclopropanos , Interações Medicamentosas , Quimioterapia Combinada , Feminino , Fluoroquinolonas/administração & dosagem , Fluoroquinolonas/sangue , Fluoroquinolonas/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Masculino , Moxifloxacina , Inibidores da Transcriptase Reversa/administração & dosagem , Inibidores da Transcriptase Reversa/efeitos adversos , Inibidores da Transcriptase Reversa/uso terapêutico , Rifampina/administração & dosagem , Rifampina/efeitos adversos , Rifampina/sangue , Tuberculose Pulmonar/metabolismo , Tuberculose Pulmonar/microbiologia
9.
Antivir Ther ; 22(4): 287-293, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27835613

RESUMO

BACKGROUND: We assessed whether women who acquired HIV during tenofovir gel prophylaxis trials can be safely and effectively treated with tenofovir-containing antiretroviral therapy (ART). METHODS: Between May 2011 and October 2014, HIV seroconvertors from two tenofovir gel trials were recruited when eligible for ART (CD4+ T-cell count <350 cells/µl, pregnancy or AIDS-defining illness). Women were randomized to tenofovir-containing (tenofovir + lamivudine/emtricitabine + efavirenz) or tenofovir-sparing (zidovudine + lamivudine/emtricitabine + efavirenz) antiretroviral treatment regimens. The proportion with virological suppression, adverse events and drug switches were compared. RESULTS: Fifty-nine women were enrolled and followed-up for median 18 months (IQR 6-24). Twenty-nine women (7 tenofovir gel exposed, 22 tenofovir gel unexposed) were randomized to a tenofovir-containing and 30 (9 tenofovir gel exposed, 21 tenofovir gel unexposed) to a tenofovir-sparing regimen. Median baseline CD4+ T-cell count and viral load (VL) were 345 cells/µl (IQR 280-423) and 4.5 log copies/ml (sd 0.79), and did not differ by ART assignment. Overall VL suppression rates were 88.0% and 78.3% at 6 months (P=0.454) and 85.7% and 79.0% at 12 months (P=0.689) in women on the tenofovir-containing and tenofovir-sparing regimens, respectively. Toxicity-related drug switches were more frequent in women on the tenofovir-sparing than tenofovir-containing regimen (36.7% versus 0.0%, P<0.001). CONCLUSIONS: Preliminary data show that tenofovir-containing ART was effective and more tolerable in HIV seroconvertors from tenofovir gel prophylaxis trials and may be considered for use in women with prior tenofovir gel exposure. Clinical trials.gov NCT01387022.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Soropositividade para HIV/diagnóstico , HIV-1/efeitos dos fármacos , RNA Viral/genética , Tenofovir/uso terapêutico , Adulto , Alcinos , Terapia Antirretroviral de Alta Atividade , Benzoxazinas/uso terapêutico , Contagem de Linfócito CD4 , Ciclopropanos , Emtricitabina/uso terapêutico , Feminino , Infecções por HIV/imunologia , Infecções por HIV/prevenção & controle , Infecções por HIV/virologia , Soropositividade para HIV/imunologia , Soropositividade para HIV/virologia , HIV-1/patogenicidade , HIV-1/fisiologia , Humanos , Lamivudina/uso terapêutico , Segurança do Paciente , Gravidez , Prevenção Primária/métodos , RNA Viral/antagonistas & inibidores , RNA Viral/metabolismo , África do Sul , Resultado do Tratamento , Cremes, Espumas e Géis Vaginais/administração & dosagem , Carga Viral/efeitos dos fármacos , Zidovudina/uso terapêutico
10.
AIDS Behav ; 18(5): 833-40, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24643314

RESUMO

Accurate estimation of the effectiveness of a microbicide for HIV prevention requires valid measurement of adherence to product use. A microbicide gel applicator container (Wisebag), fitted with cell phone technology to transmit opening events and text message reminders, was developed to monitor each opening event of the container as a proxy for gel use and adherence. Ten women were enrolled in a pilot study and followed for up to 4 months. Wisebag opening (WBO) dates and times were recorded and correlated with self-reported sex acts and gel applicator returns. During the 33 monthly follow-up visits, 47.8 % (77/161) of the recorded number of WBO events were concordant with the number of empty (used) applicators returned. The discrepancies were likely due to removal of more than one applicator during a single opening event. When the date and time of the WBO event data was assessed in relation to three different self-report adherence measures, agreement was fairly modest. The Wisebag was found to be acceptable as a storage container and the cell phone reminders generated were useful in supporting the dosing strategy. We recommend that the Wisebag be considered for larger scale and lengthier testing in microbicide trials.


Assuntos
Anti-Infecciosos/administração & dosagem , Sistemas de Liberação de Medicamentos/instrumentação , Infecções por HIV/prevenção & controle , Adesão à Medicação , Administração Intravaginal , Adulto , Telefone Celular , Coito , Estudos de Viabilidade , Feminino , Seguimentos , Géis , Humanos , Projetos Piloto , Inquéritos e Questionários , Envio de Mensagens de Texto
11.
AIDS Behav ; 18(5): 820-5, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24623069

RESUMO

In the CAPRISA 004 trial, adherence was estimated as the proportion of reported sex acts covered by two gel doses, which was assessed by counting returned empty gel applicators. The returned empty applicators were inspected visually in a standardized manner for residue on the outside of the applicator, as an indicator of vaginal insertion. Over 15 months, spanning 11,839 study visits by 838 women, a total of 59,800 returned empty applicators were inspected. By visual assessment, 77.5 % of these applicators appeared to have been inserted. To test the accuracy of the assessment we fitted a Cox model and found that the risk for HIV infection was doubled when less than half of the returned empty applicators had been assessed as not inserted in the vagina. Visual inspection enhanced both the accuracy of the adherence measurement and aided identification of mechanical problems with applicator use experienced by women in the trial.


Assuntos
Adenina/análogos & derivados , Anti-Infecciosos/administração & dosagem , Coito , Sistemas de Liberação de Medicamentos/instrumentação , Infecções por HIV/prevenção & controle , Organofosfonatos/administração & dosagem , Cooperação do Paciente/estatística & dados numéricos , Adenina/administração & dosagem , Administração Intravaginal , Adulto , Método Duplo-Cego , Feminino , Seguimentos , Géis , Humanos , Análise Multivariada , Modelos de Riscos Proporcionais , População Rural/estatística & dados numéricos , África do Sul , Tenofovir , População Urbana/estatística & dados numéricos
12.
Antivir Ther ; 19(2): 161-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24176943

RESUMO

BACKGROUND: Frequency of drug changes in combination antiretroviral therapy among patients starting both tuberculosis (TB) and HIV therapy, as a result of treatment-limiting toxicity or virological failure, is not well established. METHODS: Patients in the Starting Antiretroviral Therapy at Three Points in Tuberculosis (SAPiT) trial were randomized to initiate antiretroviral therapy (ART) either early or late during TB treatment or after completion of TB treatment. Drug changes due to toxicity (defined as due to grade 3 or 4 adverse events) or virological failure (defined as viral load >1,000 copies/ml on two occasions, taken ≥4 weeks apart) were assessed in these patients. RESULTS: A total of 501 TB-HIV-coinfected patients were followed for a mean of 16.0 months (95% CI 15.5, 16.6) after ART initiation. The standard first-line antiretrovirals used were efavirenz, lamivudine and didanosine. Individual drug switches for toxicity occurred in 14 patients (incidence rate 2.1 per 100 person-years, 95% CI 1.1, 3.5), and complete regimen changes due to virological failure in 25 patients (incidence rate 3.7 per 100 person-years, 95% CI 2.4, 5.5). The most common treatment limiting toxicities were neuropsychiatric effects (n=4, 0.8%), elevated transaminase levels and hyperlactataemia (n=3, 0.6%), and peripheral neuropathy (n=2, 0.4%). Complete regimen change due to treatment failure was more common in patients with CD4(+) T-cell count <50 cells/mm(3) (P<0.001) at ART initiation and body mass index >25 kg/m(2) (P=0.01) at entry into the study. CONCLUSIONS: Both drug switches and complete regimen change were uncommon in patients cotreated for TB-HIV with the chosen regimen. Patients with severe immunosuppression need to be monitored carefully, as they were most at risk for treatment failure requiring regimen change.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Antituberculosos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Tuberculose/tratamento farmacológico , Adulto , Fármacos Anti-HIV/efeitos adversos , Antituberculosos/efeitos adversos , Feminino , Infecções por HIV/complicações , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Tuberculose/complicações
13.
Int J Clin Pharm ; 36(1): 70-85, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24129582

RESUMO

BACKGROUND: There are 34 million people living with human immunodeficiency virus (HIV) worldwide and each year this number increases. Until a vaccine is discovered, the prevention of new HIV infections remains an urgent priority. Several trials studying the use of oral and topical agents for the prevention of HIV infection have already been completed. Adherence has proved to be a major challenge in achieving product efficacy. AIM OF THE REVIEW: To provide the clinical pharmacist with an understanding of the oral pre-exposure prophylaxis (PrEP) and topical microbicide product pipeline whilst emphasizing the critical importance of adherence to these drugs to avert HIV infection. METHODS: PubMed/Medline and the web-based clinical trials registry (ClinTrials.gov) were searched using appropriate key words. For the time period 1992-2013--all phase II and phase III safety and effectiveness studies--testing agents for prevention of HIV infection were included in the review. Efficacy estimates, adherence estimates and reported challenges with adherence were extracted. RESULTS: Twenty-four phase II and III clinical trials were found during review. Of these, 20 trials have been completed, and six trials show effectiveness in preventing HIV infection. The majority of the successful trials were to oral PrEP and to date only one microbicide trial of a vaginal antiretroviral microbicide gel has showed effectiveness. Adherence to study product played a major role in trial outcomes and there are several reasons for non-adherence. These include high on-trial pregnancy rates, low trial retention rates, low participant perception of risk, participant characteristics such as age <25 years, single status, migratory partners and trial fatigue. Study product characteristics such as dosage form, dosing interval, as well as associated adverse events may also influence adherence. CONCLUSION: Moderate to high adherence is critical to demonstrate efficacy of drugs for HIV prevention. For topical agents, intermittent use associated with coitus is more effective than daily use, particularly if sex is infrequent or partners migrant. For oral agents, daily use is effective but the motivation to use the drug and high risk perception is important. In serodiscordant couples, early initiation of highly active antiretroviral therapy in the infected partner affords almost complete protection to the negative partner. Drugs need to be tailored to the population at risk and availability of multiple drug options are important.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/farmacologia , Infecções por HIV/prevenção & controle , Infecções por HIV/psicologia , Adesão à Medicação/psicologia , Administração Oral , Administração Tópica , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Humanos
14.
AIDS Behav ; 17(2): 640-8, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23054042

RESUMO

The Wisebag™, a lunchbag-style container with an electronic events-monitoring system, was designed as a real-time indirect objective measure of microbicide gel use. Due to cost, alternative functionalities (i.e. use of offline and dummy versions) were explored. We conducted a three-arm, double-blinded pilot study among 50 HIV-negative women in Durban, South Africa to assess participant adherence and Wisebag acceptability and performance. Participants were randomized 2:2:1 to Wisebag with online (events transmitted via cellular signal in real-time), offline (events stored in device memory) or inactive "dummy" devices. Participants were instructed to open the Wisebag daily for 2 weeks, retrieve a study sticker and affix it on a diary card. All participants completed the study. At exit, 94 % did not know which device they had received, nor could they differentiate the Wisebag types when presented with the three options. Five offline devices failed (no data recorded). Per Wisebag events, 26 % of women were perfectly adherent compared to 48 % by self-report and 46 % per diary card. Of reported non-adherence, 92 % did not open the Wisebag (travelling or forgot) and 22 % opened Wisebag >1×/day (curiosity). Participants liked and were comfortable carrying Wisebag. Successful blinding will allow inclusion of offline and/or dummy Wisebags in future study designs. Perfect adherence by opening events was significantly lower than by self-report, highlighting the importance of objective measures of adherence in clinical trials. Additional studies to validate Wisebag data with actual products, with and without SMS and online functionality, in different populations and settings, and in comparison to biomarkers are warranted.


Assuntos
Anti-Infecciosos Locais/administração & dosagem , Desenho de Equipamento , Infecções por HIV/epidemiologia , Adesão à Medicação , Cremes, Espumas e Géis Vaginais/administração & dosagem , Adolescente , Adulto , Método Duplo-Cego , Monitoramento de Medicamentos , Desenho de Equipamento/estatística & dados numéricos , Estudos de Viabilidade , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Humanos , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , Satisfação do Paciente , Projetos Piloto , Reprodutibilidade dos Testes , África do Sul/epidemiologia
15.
N Engl J Med ; 365(16): 1492-501, 2011 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-22010915

RESUMO

BACKGROUND: We previously reported that integrating antiretroviral therapy (ART) with tuberculosis treatment reduces mortality. However, the timing for the initiation of ART during tuberculosis treatment remains unresolved. METHODS: We conducted a three-group, open-label, randomized, controlled trial in South Africa involving 642 ambulatory patients, all with tuberculosis (confirmed by a positive sputum smear for acid-fast bacilli), human immunodeficiency virus infection, and a CD4+ T-cell count of less than 500 per cubic millimeter. Findings in the earlier-ART group (ART initiated within 4 weeks after the start of tuberculosis treatment, 214 patients) and later-ART group (ART initiated during the first 4 weeks of the continuation phase of tuberculosis treatment, 215 patients) are presented here. RESULTS: At baseline, the median CD4+ T-cell count was 150 per cubic millimeter, and the median viral load was 161,000 copies per milliliter, with no significant differences between the two groups. The incidence rate of the acquired immunodeficiency syndrome (AIDS) or death was 6.9 cases per 100 person-years in the earlier-ART group (18 cases) as compared with 7.8 per 100 person-years in the later-ART group (19 cases) (incidence-rate ratio, 0.89; 95% confidence interval [CI], 0.44 to 1.79; P=0.73). However, among patients with CD4+ T-cell counts of less than 50 per cubic millimeter, the incidence rates of AIDS or death were 8.5 and 26.3 cases per 100 person-years, respectively (incidence-rate ratio, 0.32; 95% CI, 0.07 to 1.13; P=0.06). The incidence rates of the immune reconstitution inflammatory syndrome (IRIS) were 20.1 and 7.7 cases per 100 person-years, respectively (incidence-rate ratio, 2.62; 95% CI, 1.48 to 4.82; P<0.001). Adverse events requiring a switching of antiretroviral drugs occurred in 10 patients in the earlier-ART group and 1 patient in the later-ART group (P=0.006). CONCLUSIONS: Early initiation of ART in patients with CD4+ T-cell counts of less than 50 per cubic millimeter increased AIDS-free survival. Deferral of the initiation of ART to the first 4 weeks of the continuation phase of tuberculosis therapy in those with higher CD4+ T-cell counts reduced the risks of IRIS and other adverse events related to ART without increasing the risk of AIDS or death. (Funded by the U.S. President's Emergency Plan for AIDS Relief and others; SAPIT ClinicalTrials.gov number, NCT00398996.).


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Antirretrovirais/administração & dosagem , Antituberculosos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Tuberculose/tratamento farmacológico , Adulto , Contagem de Linfócito CD4 , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Infecções por HIV/complicações , Infecções por HIV/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Tuberculose/complicações , Carga Viral
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