Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 130
Filtrar
1.
J Int Assoc Provid AIDS Care ; 20: 23259582211041423, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34476989

RESUMO

During the COVID-19 pandemic, HIV clinics had to transform care delivery for people with HIV (PWH). We developed a multifaceted telehealth implementation strategy and monitored number of out of care patients (OOC), medical visit frequency (MVF), gap in care (GiC) and viral suppression (VS), and compared measures to baseline data. Between April and October 2020, 1559 visits were scheduled; 328 (21%) were missed, and 63 (4%) were new to care. Of the remaining 1168 follow-up visits, 412 (35%) were telehealth visits. As of October 2020, there were 53 patients OOC, MVF was 55% and GiC was 24% compared to 34, 69% and 14% at baseline, respectively. Overall VS rate remained high at 93% (97% for telehealth and 91% for in-person visits, p = 0.0001). Our implementation strategy facilitated quick provision of telehealth to a third of PWH receiving care in our clinic. While MVF decreased and GiC increased, VS rates remained high.


Assuntos
COVID-19 , Infecções por HIV , Telemedicina , Infecções por HIV/epidemiologia , Humanos , Pandemias , SARS-CoV-2
2.
Hum Brain Mapp ; 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34464488

RESUMO

People with HIV (PWH) use cannabis at a higher rate than the general population, but the influence on neural activity is not well characterized. Cannabis use among PWH may have a beneficial effect, as neuroinflammation is known to be a critical problem in PWH and cannabis use has been associated with a reduction in proinflammatory markers. Thus, it is important to understand the net impact of cannabis use on brain and cognitive function in PWH. In this study, we collected magnetoencephalographic (MEG) brain imaging data on 81 participants split across four demographically matched groups (i.e., PWH using cannabis, controls using cannabis, non-using PWH, and non-using controls). Participants completed a visuospatial processing task during MEG. Time-frequency resolved voxel time series were extracted to identify the dynamics of oscillatory and pre-stimulus baseline neural activity. Our results indicated strong theta (4-8 Hz), alpha (10-16 Hz), and gamma (62-72 Hz) visual oscillations in parietal-occipital brain regions across all participants. PWH exhibited significant behavioral deficits in visuospatial processing, as well as reduced theta oscillations and elevated pre-stimulus gamma activity in visual cortices, all of which replicate prior work. Strikingly, chronic cannabis use was associated with a significant reduction in pre-stimulus gamma activity in the visual cortices, such that PWH no longer statistically differed from controls. These results provide initial evidence that cannabis use may normalize some neural aberrations in PWH. This study fills an important gap in understanding the impact of cannabis use on brain and cognitive function in PWH.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34403326

RESUMO

RATIONALE: There is accumulating evidence that higher-than-standard doses of isoniazid are effective against low-to-intermediate-level isoniazid-resistant strains of Mycobacterium tuberculosis, but the optimal dose remains unknown. OBJECTIVE: Characterizing the association between isoniazid pharmacokinetics (standard or high-dose) and early bactericidal activity against M. tuberculosis (drug-sensitive and inhA-mutated) and N-acetyltransferase 2 status. METHODS: ACTG A5312/INHindsight is 7-day early bactericidal activity study with isoniazid at normal dose (5 mg/kg) for patients with drug-sensitive bacteria and 5, 10, and 15 mg/kg doses for patients with inhA mutants. Participants with pulmonary TB received daily isoniazid monotherapy and collected sputum daily. Colony-forming units (CFU) on solid culture and time-to-positivity (TTP) in liquid culture were jointly analyzed using nonlinear mixed-effects modeling. RESULTS: Fifty-nine adults were included in this analysis. Decline in sputum CFU was described by a one-compartment model, while an exponential bacterial growth model was used to interpret TTP data. The model found bacterial kill is modulated by isoniazid concentration using an effect compartment and a sigmoidal Emax relationship. The model predicted lower potency but similar maximum-kill of isoniazid against inhA-mutated isolates compared to drug-sensitive. Based on simulations from the PK/PD model, to achieve a drop in bacterial load comparable to 5mg/kg against drug-sensitive TB, 10- and 15-mg/kg doses are necessary against inhA-mutated isolates in slow and intermediate N-acetyltransferase 2 acetylators, respectively. Fast acetylators underperformed even at 15 mg/kg. CONCLUSIONS: Dosing of isoniazid based on N-acetyltransferase 2 acetylator status may help patients attain effective exposures against inhA-mutated isolates while mitigating toxicity risks associated with higher doses. Clinical trial registration available at www.clinicaltrials.gov, ID: NCT01936831.

4.
Neuroimage Clin ; 31: 102775, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34375884

RESUMO

BACKGROUND: Current diagnostic criteria of HIV-associated neurocognitive disorders (HAND) rely on neuropsychological assessments. The aim of this study was to evaluate if gray matter volumes (GMV) can distinguish people with HAND, neurocognitively unimpaired people with HIV (unimpaired PWH), and uninfected controls using linear discriminant analyses. METHODS: A total of 231 participants, including 110 PWH and 121 uninfected controls, completed a neuropsychological assessment and an MRI protocol. Among PWH, HAND (n = 48) and unimpaired PWH (n = 62) designations were determined using the widely accepted Frascati criteria. We then assessed the extent to which GMV, corrected for intracranial volume, could accurately distinguish the three groups using linear discriminant analysis. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, area under the curve (AUC), and accuracy were computed for each model using the classification results based on GMV compared to the neuropsychological assessment. RESULTS: The best performing model was comprised of bilaterally combined GMV and was stratified by sex. Among males, sensitivity was 85.2% (95% CI: 66.3%-95.8%), specificity was 97.0% (95% CI: 91.6%-99.4%), and the AUC was 0.91 (95% CI: 0.83-0.99). Among females, sensitivity was 100.0% (95% CI: 83.9%-100.0%), specificity was 98.8% (95% CI: 93.4%-100.0%), and the AUC was 0.99 (95% CI: 0.98-1.00). CONCLUSIONS: GMV accurately discriminated HAND from unimpaired PWH and controls. Measures of GMV may be highly sensitive to HAND, and revisions to the Frascati criteria should consider including GMV in conjunction with a neuropsychological assessment to diagnose HAND.


Assuntos
Substância Cinzenta , Infecções por HIV , Córtex Cerebral , Feminino , Substância Cinzenta/diagnóstico por imagem , Infecções por HIV/complicações , Infecções por HIV/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos
5.
AIDS ; 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34261093

RESUMO

BACKGROUND: ATLAS (NCT02951052), a Phase 3, multicenter, open-label study, demonstrated that switching to injectable cabotegravir (CAB) + rilpivirine (RPV) long-acting (LA) dosed every 4 weeks was noninferior at Week (W) 48 to continuing three-drug daily oral antiretroviral therapy (CAR). Results from the W96 analysis are presented. METHODS AND DESIGN: Participants completing W52 of ATLAS were given the option to withdraw, transition to ATLAS-2 M (NCT03299049), or enter an Extension Phase (EP) to continue LA therapy (LA arm) or switch from CAR to LA therapy (Switch arm). Endpoints assessed at W96 included proportion of participants with plasma HIV-1 RNA <50 copies/mL, incidence of confirmed virologic failure (CVF; two consecutive HIV-1 RNA ≥200 copies/mL), safety and tolerability, pharmacokinetics, and patient-reported outcomes. RESULTS: Most participants completing the Maintenance Phase transitioned to ATLAS-2 M (88%, n = 502/572). Overall, 52 participants were included in the W96 analysis of ATLAS; of these, 100% (n = 23/23) and 97% (n = 28/29) in the LA and Switch arms had plasma HIV-1 RNA <50 copies/mL at W96, respectively. One participant had plasma HIV-1 RNA ≥50 copies/mL in the Switch arm (173 copies/mL). No participants met the CVF criterion during the EP. No new safety signals were identified. All Switch arm participants surveyed preferred LA therapy to their previous daily oral regimen (100%, n = 27/27). CONCLUSIONS: In this subgroup of ATLAS, 98% (n = 51/52) of participants at the EP W96 analysis maintained virologic suppression with LA therapy. Safety, efficacy, and participant preference results support the therapeutic potential of CAB+RPV LA treatment for virologically suppressed people living with HIV-1.

6.
EBioMedicine ; 70: 103487, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34280780

RESUMO

BACKGROUND: Despite effective combination antiretroviral therapy (cART), people living with HIV (PLWH) remain at risk for developing neurocognitive impairment primarily due to systemic inflammation that persists despite virologic suppression, albeit the mechanisms underlying such inflammation are poorly understood. METHODS: Herein, we evaluate the predictive capacity of the mitochondrial redox environment on circulating neuro- and T-lymphocyte-related inflammation and concomitant cognitive function in 40 virally-suppressed PLWH and 40 demographically-matched controls using structural equation modeling. We used state-of-the-art systems biology approaches including Seahorse Analyzer of mitochondrial function, electron paramagnetic resonance (EPR) spectroscopy to measure superoxide levels, antioxidant activity assays, and Meso Scale multiplex technology to quantify inflammatory proteins in the periphery. FINDINGS: We observed disturbances in mitochondrial function and the redox environment in PLWH compared to controls, which included reduced mitochondrial capacity (t(76) = -1.85, p = 0.034, 95% CI: -∞,-0.13), elevated levels of superoxide (t(75) = 1.70, p = 0.047, 95% CI: 8.01 E 3, ∞) and alterations in antioxidant defense mechanisms (t(74) = 1.76, p = 0.041, 95% CI: -710.92, ∞). Interestingly, alterations in both superoxide- and hydrogen peroxide-sensitive redox environments were differentially predictive of neuro-, but not T-lymphocyte-related inflammatory profiles in PLWH and controls, respectively (ps < 0.026). Finally, when accounting for superoxide-sensitive redox pathways, neuroinflammatory profiles significantly predicted domain-specific cognitive function across our sample (ß = -0.24, p = 0.034, 95% CI: -0.09, -0.004 for attention; ß = -0.26, p = 0.018, 95% CI: -0.10, -0.01 for premorbid function). INTERPRETATION: Our results suggest that precursors to neuroinflammation apparent in PLWH (i.e., mitochondrial function and redox environments) predict overall functionality and cognitive dysfunction and importantly, may serve as a proxy for characterizing inflammation-related functional decline in the future. FUNDING: National Institute of Mental Health, National Institute for Neurological Disorders and Stroke, National Institute on Drug Abuse, National Science Foundation.

7.
Ann Intern Med ; 174(8): 1151-1158, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34125574

RESUMO

The development of the National Institutes of Health (NIH) COVID-19 Treatment Guidelines began in March 2020 in response to a request from the White House Coronavirus Task Force. Within 4 days of the request, the NIH COVID-19 Treatment Guidelines Panel was established and the first meeting took place (virtually-as did subsequent meetings). The Panel comprises 57 individuals representing 6 governmental agencies, 11 professional societies, and 33 medical centers, plus 2 community members, who have worked together to create and frequently update the guidelines on the basis of evidence from the most recent clinical studies available. The initial version of the guidelines was completed within 2 weeks and posted online on 21 April 2020. Initially, sparse evidence was available to guide COVID-19 treatment recommendations. However, treatment data rapidly accrued based on results from clinical studies that used various study designs and evaluated different therapeutic agents and approaches. Data have continued to evolve at a rapid pace, leading to 24 revisions and updates of the guidelines in the first year. This process has provided important lessons for responding to an unprecedented public health emergency: Providers and stakeholders are eager to access credible, current treatment guidelines; governmental agencies, professional societies, and health care leaders can work together effectively and expeditiously; panelists from various disciplines, including biostatistics, are important for quickly developing well-informed recommendations; well-powered randomized clinical trials continue to provide the most compelling evidence to guide treatment recommendations; treatment recommendations need to be developed in a confidential setting free from external pressures; development of a user-friendly, web-based format for communicating with health care providers requires substantial administrative support; and frequent updates are necessary as clinical evidence rapidly emerges.


Assuntos
COVID-19/terapia , Pandemias , Guias de Prática Clínica como Assunto , Comitês Consultivos , COVID-19/tratamento farmacológico , COVID-19/epidemiologia , Criança , Interpretação Estatística de Dados , Aprovação de Drogas , Medicina Baseada em Evidências , Feminino , Humanos , Relações Interprofissionais , National Institutes of Health (U.S.) , Gravidez , SARS-CoV-2 , Participação dos Interessados , Estados Unidos
8.
Patient ; 2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34056699

RESUMO

BACKGROUND: Advances in HIV-1 therapeutics have led to the development of a range of daily oral treatment regimens, which share similar high efficacy rates. Consequently, more emphasis is being placed upon the individual's experience of treatment and impact on quality of life. The first long-acting injectable antiretroviral therapy for HIV-1 (long-acting cabotegravir + rilpivirine [CAB + RPV LA]) may address challenges associated with oral treatment for HIV-1, such as stigma, pill burden/fatigue, drug-food interactions, and adherence. Patient-reported outcomes (PROs) collected in an HIV-1 clinical trial (ATLAS-2M; NCT03299049) comparing participants' experience with two dosing regimens (every 4 weeks [Q4W] vs. every 8 weeks [Q8W]) of CAB + RPV LA are presented herein. METHODS: PRO endpoints evaluated through 48 weeks of therapy included treatment satisfaction (HIV Treatment Satisfaction Questionnaire [HIVTSQ]), treatment acceptance ("General Acceptance" domain of the Chronic Treatment Acceptance [ACCEPT®] questionnaire), acceptability of injections (Perception of Injection [PIN] questionnaire), treatment preference (questionnaire), and reasons for switching to/continuing long-acting therapy (exploratory endpoint; questionnaire). Participants were randomized 1:1 to receive CAB + RPV LA Q8W or Q4W. Results were stratified by prior CAB + RPV exposure in either preplanned or post hoc analyses. RESULTS: Overall, 1045 participants were randomized to the Q8W (n = 522) and Q4W (n = 523) regimens; 37% (n = 391/1045) had previously received CAB + RPV in ATLAS. For participants without prior CAB + RPV exposure, large increases from baseline were reported in treatment satisfaction in both long-acting arms (HIVTSQ status version), with Q8W dosing statistically significantly favored at Weeks 24 (p = 0.036) and 48 (p = 0.004). Additionally, improvements from baseline were also observed in the "General Acceptance" domain of the ACCEPT questionnaire in both long-acting arms for participants without prior CAB + RPV exposure; however, no statistically significant difference was observed between arms at either timepoint (Week 24, p = 0.379; Week 48, p = 0.525). Significant improvements (p < 0.001) in the "Acceptance of Injection Site Reactions" domain of the PIN questionnaire were observed from Week 8 to Weeks 24 and 48 in both arms for participants without prior CAB + RPV exposure. Participants with prior CAB + RPV exposure reported high treatment satisfaction (mean [HIVTSQ status version]: Q8W 62.2/66.0; Q4W 62.0/66.0), treatment acceptance (mean: Q8W 89.3/100; Q4W 91.2/100), and acceptance of injection site reactions (mean [5 = not at all acceptable; 1 = totally acceptable]: Q8W 1.72; Q4W 1.59) at baseline/Week 8 that were maintained over time. Participants without prior CAB + RPV exposure who received Q8W dosing preferred this regimen over oral CAB + RPV (98%, n = 300/306). Among those with prior Q4W exposure, 94% (n = 179/191) preferred Q8W dosing versus Q4W dosing (3%, n = 6/191) or oral CAB + RPV (2%, n = 4/191). CONCLUSIONS: Both long-acting regimens provided high treatment satisfaction and acceptance, irrespective of prior CAB + RPV exposure, with most participants preferring Q8W dosing over both the Q4W regimen and their previous daily oral regimen. The PRO data collected at Week 48 support the therapeutic potential of CAB + RPV LA. FUNDING: ViiV Healthcare and Janssen. TRIAL REGISTRATION: ATLAS-2M: ClinicalTrials.gov NCT03299049, registered October 2, 2017.

9.
N Engl J Med ; 384(18): 1705-1718, 2021 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-33951360

RESUMO

BACKGROUND: Rifapentine-based regimens have potent antimycobacterial activity that may allow for a shorter course in patients with drug-susceptible pulmonary tuberculosis. METHODS: In an open-label, phase 3, randomized, controlled trial involving persons with newly diagnosed pulmonary tuberculosis from 13 countries, we compared two 4-month rifapentine-based regimens with a standard 6-month regimen consisting of rifampin, isoniazid, pyrazinamide, and ethambutol (control) using a noninferiority margin of 6.6 percentage points. In one 4-month regimen, rifampin was replaced with rifapentine; in the other, rifampin was replaced with rifapentine and ethambutol with moxifloxacin. The primary efficacy outcome was survival free of tuberculosis at 12 months. RESULTS: Among 2516 participants who had undergone randomization, 2343 had a culture positive for Mycobacterium tuberculosis that was not resistant to isoniazid, rifampin, or fluoroquinolones (microbiologically eligible population; 768 in the control group, 791 in the rifapentine-moxifloxacin group, and 784 in the rifapentine group), of whom 194 were coinfected with human immunodeficiency virus and 1703 had cavitation on chest radiography. A total of 2234 participants could be assessed for the primary outcome (assessable population; 726 in the control group, 756 in the rifapentine-moxifloxacin group, and 752 in the rifapentine group). Rifapentine with moxifloxacin was noninferior to the control in the microbiologically eligible population (15.5% vs. 14.6% had an unfavorable outcome; difference, 1.0 percentage point; 95% confidence interval [CI], -2.6 to 4.5) and in the assessable population (11.6% vs. 9.6%; difference, 2.0 percentage points; 95% CI, -1.1 to 5.1). Noninferiority was shown in the secondary and sensitivity analyses. Rifapentine without moxifloxacin was not shown to be noninferior to the control in either population (17.7% vs. 14.6% with an unfavorable outcome in the microbiologically eligible population; difference, 3.0 percentage points [95% CI, -0.6 to 6.6]; and 14.2% vs. 9.6% in the assessable population; difference, 4.4 percentage points [95% CI, 1.2 to 7.7]). Adverse events of grade 3 or higher occurred during the on-treatment period in 19.3% of participants in the control group, 18.8% in the rifapentine-moxifloxacin group, and 14.3% in the rifapentine group. CONCLUSIONS: The efficacy of a 4-month rifapentine-based regimen containing moxifloxacin was noninferior to the standard 6-month regimen in the treatment of tuberculosis. (Funded by the Centers for Disease Control and Prevention and others; Study 31/A5349 ClinicalTrials.gov number, NCT02410772.).


Assuntos
Antibióticos Antituberculose/administração & dosagem , Antituberculosos/uso terapêutico , Moxifloxacina/administração & dosagem , Mycobacterium tuberculosis/isolamento & purificação , Rifampina/administração & dosagem , Tuberculose Pulmonar/tratamento farmacológico , Adolescente , Adulto , Antibióticos Antituberculose/efeitos adversos , Antituberculosos/efeitos adversos , Criança , Intervalos de Confiança , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Masculino , Moxifloxacina/efeitos adversos , Rifampina/efeitos adversos , Adulto Jovem
10.
J Int Assoc Provid AIDS Care ; 20: 23259582211009011, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33902356

RESUMO

As with other chronic conditions, adherence to daily medications remains a challenge for many individuals living with HIV due to structural, behavioral, and social barriers. Unfortunately, high levels of adherence to antiretroviral therapy are required to maintain virologic suppression. Alternative approaches are being explored to decrease the burden of daily pill administration, including long-acting injectable, oral, and implantable products. Phase 3 data support the efficacy of nanoformulated injectable cabotegravir and rilpivirine for HIV treatment in patients with undetectable viremia, but we have yet to learn how this strategy may benefit those with medication adherence challenges. Despite this, the affected community and HIV providers are very interested in exploring the role of long-acting therapies to address some types of barriers to medication adherence. This review summarizes available information about the potential for long-acting therapy to improve adherence for some patients and outlines associated opportunities and challenges with the implementation of long-acting therapy for the treatment and prevention of HIV.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Adesão à Medicação , Rilpivirina/uso terapêutico , Combinação de Medicamentos , Humanos , Carga Viral
11.
Cereb Cortex ; 31(8): 3752-3763, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-33822880

RESUMO

A growing literature suggests a relationship between HIV-infection and a molecular profile of age acceleration. However, despite the widely known high prevalence of HIV-related brain atrophy and HIV-associated neurocognitive disorder (HAND), epigenetic age acceleration has not been linked to HIV-related changes in structural MRI. We applied morphological MRI methods to study the brain structure of 110 virally suppressed participants with HIV infection and 122 uninfected controls age 22-72. All participants were assessed for cognitive impairment, and blood samples were collected from a subset of 86 participants with HIV and 83 controls to estimate epigenetic age. We examined the group-level interactive effects of HIV and chronological age and then used individual estimations of epigenetic age to understand the relationship between age acceleration and brain structure. Finally, we studied the effects of HAND. HIV-infection was related to gray matter reductions, independent of age. However, using epigenetic age as a biomarker for age acceleration, individual HIV-related age acceleration was associated with reductions in total gray matter. HAND was associated with decreases in thalamic and hippocampal gray matter. In conclusion, despite viral suppression, accentuated gray matter loss is evident with HIV-infection, and greater biological age acceleration specifically relates to such gray matter loss.

12.
Hum Brain Mapp ; 42(9): 2851-2861, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33738895

RESUMO

HIV-infection has been associated with widespread alterations in brain structure and function, although few studies have examined whether such aberrations are co-localized and the degree to which clinical and cognitive metrics are related. We examine this question in the somatosensory system using high-resolution structural MRI (sMRI) and magnetoencephalographic (MEG) imaging of neural oscillatory activity. Forty-four participants with HIV (PWH) and 55 demographically-matched uninfected controls completed a paired-pulse somatosensory stimulation paradigm during MEG and underwent 3T sMRI. MEG data were transformed into the time-frequency domain; significant sensor level responses were imaged using a beamformer. Virtual sensor time series were derived from the peak responses. These data were used to compute response amplitude, sensory gating metrics, and spontaneous cortical activity power. The T1-weighted sMRI data were processed using morphological methods to derive cortical thickness values across the brain. From these, the cortical thickness of the tissue coinciding with the peak response was estimated. Our findings indicated both PWH and control exhibit somatosensory gating, and that spontaneous cortical activity was significantly stronger in PWH within the left postcentral gyrus. Interestingly, within the same tissue, PWH also had significantly reduced cortical thickness relative to controls. Follow-up analyses indicated that the reduction in cortical thickness was significantly correlated with CD4 nadir and mediated the relationship between HIV and spontaneous cortical activity within the left postcentral gyrus. These data indicate that PWH have abnormally strong spontaneous cortical activity in the left postcentral gyrus and such elevated activity is driven by locally reduced cortical gray matter thickness.

13.
BMC Health Serv Res ; 21(1): 255, 2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33743684

RESUMO

BACKGROUND: Long-acting injectable antiretroviral therapy (LA ART) has been shown to be non-inferior to daily oral ART, with high patient satisfaction and preference to oral standard of care in research to date, and has recently been approved for use in the United States and Europe. This study examined the perspectives of health care providers participating in LA ART clinical trials on potential barriers and solutions to LA ART roll-out into real world settings. METHODS: This analysis draws on two data sources: (1) open-ended questions embedded in a structured online survey of 329 health care providers participating in the ATLAS-2 M trial across 13 countries; and (2) in-depth interviews with 14 providers participating in FLAIR/ ATLAS/ATLAS-2 M trials in the United States and Spain. Both assessments explored provider views and clinic dynamics related to the introduction of LA ART and were analyzed using thematic content analysis. The Consolidated Framework for Implementation Research (CFIR) was drawn on as the conceptual framework underpinning development of a model depicting study findings. RESULTS: Barriers and proposed solutions to LA ART implementation were identified at the individual, clinic and health system levels. Provider perceptions of patient level barriers included challenges with adhering to frequent injection appointments and injection tolerability. Proposed solutions included patient education, having designated staff for clinic visit retention, and clinic flexibility with appointment scheduling. The main provider concern was identifying appropriate candidates for LA ART; proposed solutions focused on patient provider communication and decision making. Clinic level barriers included the need for additional skilled individuals to administer injections, shifts in workflow as demand increases and the logistics of cold-chain storage. Proposed solutions included staff hiring and training, strategic planning around workflow and logistics, and the possibility of offering injections in other settings, including the home. Health system level barriers included cost and approvals from national regulatory bodies. Potential solutions included governments subsidizing treatment, ensuring cost is competitive with oral ART, and offering co-pay assistance. CONCLUSIONS: Results suggest the importance of multi-level support systems to optimize patient-provider communication and treatment decision-making; clinic staffing, workflow, logistics protocols and infrastructure; and cost-related factors within a given health system.


Assuntos
Infecções por HIV , Antirretrovirais/uso terapêutico , Europa (Continente) , Infecções por HIV/tratamento farmacológico , Pessoal de Saúde , Humanos , Espanha
14.
Clin Infect Dis ; 73(6): 1037-1045, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-33772550

RESUMO

BACKGROUND: Some contacts of patients with tuberculosis remain negative on tests for tuberculosis infection, despite prolonged exposure, suggesting they might be resistant to Mycobacterium tuberculosis infection. The objective of this multinational study was to estimate the proportion of household contacts resistant to M. tuberculosis (resisters). METHODS: We conducted a longitudinal study enrolling index patients enrolled in treatment for pulmonary multidrug- or rifampin-resistant tuberculosis and their household contacts. Contacts were tested for tuberculosis infection with a tuberculin skin test (TST) and interferon-gamma release assay (IGRA) at baseline and after 1 year. Exposure was quantified based on index patients' infectiousness, index patient and household contact interaction, and age. We explored multiple definitions of resistance to tuberculosis infection by varying TST negativity cutoffs (0 vs <5 mm), classification of missing test results, and exposure level. RESULTS: In total, 1016 contacts were evaluated from 284 households; 572 contacts aged ≥5 years had TST and longitudinal IGRA results available. And 77 (13%) or 71 (12%) contacts were classified as resisters with a <5 mm or 0 mm TST threshold, respectively. Among 263 highly exposed contacts, 29 (11%) or 26 (10%) were classified as resisters using TST cutoffs of <5 mm and 0 mm, respectively. The prevalence of resisters did not differ substantially by sex, age, human immunodeficiency virus (HIV) coinfection, or comorbid conditions. CONCLUSIONS: At least 10% of household contacts can be classified as resistant to tuberculosis infection, depending on the definition used, including those with high exposure. Further studies to understand genetic or immunologic mechanisms underlying the resister phenotype may inform novel strategies for therapeutics and vaccines.


Assuntos
Tuberculose Latente , Mycobacterium tuberculosis , Tuberculose , Humanos , Testes de Liberação de Interferon-gama , Tuberculose Latente/diagnóstico , Tuberculose Latente/epidemiologia , Estudos Longitudinais , Teste Tuberculínico
15.
BMC Infect Dis ; 21(1): 205, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33627075

RESUMO

BACKGROUND: Drug susceptibility testing (DST) patterns of Mycobacterium tuberculosis (MTB) from patients with rifampicin-resistant tuberculosis (RR-TB) or multidrug-resistant TB (MDR-TB; or resistant to rifampicin and isoniazid (INH)), are important to guide preventive therapy for their household contacts (HHCs). METHODS: As part of a feasibility study done in preparation for an MDR-TB preventive therapy trial in HHCs, smear, Xpert MTB/RIF, Hain MTBDRplus, culture and DST results of index MDR-TB patients were obtained from routine TB programs. A sputum sample was collected at study entry and evaluated by the same tests. Not all tests were performed on all specimens due to variations in test availability. RESULTS: Three hundred eight adults with reported RR/MDR-TB were enrolled from 16 participating sites in 8 countries. Their median age was 36 years, and 36% were HIV-infected. Routine testing on all 308 were confirmed as having RR-TB, but only 75% were documented as having MDR-TB. The majority of those not classified as having MDR-TB were because only rifampicin resistance was tested. At study entry (median 59 days after MDR-TB treatment initiation), 280 participants (91%) were able to produce sputum for the study, of whom 147 (53%) still had detectable MTB. All but 2 of these 147 had rifampicin DST done, with resistance detected in 89%. Almost half (47%) of the 147 specimens had INH DST done, with 83% resistance. Therefore, 20% of the 280 study specimens had MDR-TB confirmed. Overall, DST for second-line drugs were available in only 35% of the 308 routine specimens and 15% of 280 study specimens. CONCLUSIONS: RR-TB was detected in all routine specimens but only 75% had documented MDR-TB, illustrating the need for expanded DST beyond Xpert MTB/RIF to target preventive therapy for HHC.


Assuntos
Isoniazida/uso terapêutico , Mycobacterium tuberculosis/isolamento & purificação , Rifampina/uso terapêutico , Escarro/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adulto , Antituberculosos/uso terapêutico , Estudos Transversais , Estudos de Viabilidade , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia
16.
Clin Infect Dis ; 72(10): e642-e645, 2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32845985

RESUMO

Combating disparities is a crucial goal of ongoing efforts to end the human immunodeficiency virus (HIV) epidemic. In a multivariable analysis of a cohort in the Midwestern United States, racial/ethnic disparities in HIV viral suppression were no longer robust after accounting for other sociodemographic factors. Neighborhood deprivation and low income were independently inversely associated with viral suppression.

17.
AIDS Care ; 33(6): 801-809, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32408771

RESUMO

The study evaluates the acceptability and preferences for long-acting antiretroviral therapy (LA-ART) among a diverse cohort of people with HIV infection (PWH). It consists of a self-administered survey and chart review of PWH presenting to an HIV clinic in Houston, Texas, between February and June 2018; 374 participants were included; 61% indicated that they were likely or very likely to use LA-ART formulations. When asked about preference, 41% preferred pills, 40% preferred injections, and 18% preferred an implant. The most common benefit reported was eliminating the need to remember taking daily HIV pills (74%); 43% were worried that LA-ART will not be as effective as pills. Participants with a college degree, men who have sex with men, and ART-experienced were more willing to use LA-ART. Participants who reported poor or fair health, or who screened positive for depression or anxiety were significantly less willing to use LA-ART. The likelihood of using LA-ART did not correlate with self-reported adherence and HIV suppression. Patients with difficulty scheduling and attending clinic visits preferred injections and implant over pills. Most participants indicated a willingness to use new LA ART formulations. However, 41% still prefers pills, and those more interested in LA-ART were not less adherent.


Assuntos
Infecções por HIV , Minorias Sexuais e de Gênero , Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Homossexualidade Masculina , Humanos , Masculino , Texas
18.
Int J Antimicrob Agents ; 57(1): 106220, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33166693

RESUMO

Long-acting and extended-release formulations represent one of the most important approaches to improving the treatment and prevention of chronic HIV infection. Long-acting small molecules and monoclonal antibodies have demonstrated potent anti-HIV activity in early- and late-stage clinical trials. Strategies to manage toxicity and falling drug concentrations after missed doses, as well as primary and secondary resistance to current drugs and monoclonal antibodies are important considerations. Long-acting injectable nanoformulations of the integrase inhibitor cabotegravir and the non-nucleoside reverse transcriptase inhibitor rilpivirine were safe, well tolerated and efficacious in large randomised phase 3 studies. Regulatory approval for this two-drug combination for HIV maintenance therapy was granted in Canada in 2020 and is expected in the USA during 2021. 4'-Ethynyl-2-fluoro-2'-deoxyadenosine (islatravir) is a novel nucleoside reverse transcriptase inhibitor in clinical development as a long-acting oral drug and as a long-acting subcutaneous polymer implant. GS-6207 is a novel HIV capsid inhibitor that is injected subcutaneously every 3 months. Broadly-neutralising monoclonal antibodies have potent antiviral activity in early human trials, however there is substantial baseline resistance and rapid development of resistance to these antibodies if used as monotherapy. Limitations of these antiretroviral approaches include management of toxicities and prevention of drug resistance when these drugs are discontinued and drug concentrations are slowly reduced over time. These approaches appear to be especially attractive for patients complaining of pill fatigue and for those experiencing HIV-associated stigma. As these formulations are shown to be safe, well tolerated and economical, they are likely to gain broader appeal.

19.
Pharmacogenet Genomics ; 31(1): 17-27, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32815870

RESUMO

OBJECTIVES: The effect of rifapentine plus isoniazid on efavirenz pharmacokinetics was characterized in AIDS Clinical Trials Group protocol A5279 (NCT01404312). The present analyses characterize pharmacogenetic interactions between these drugs, and with nevirapine. METHODS: A subset of HIV-positive individuals receiving efavirenz- or nevirapine-containing antiretroviral therapy in A5279 underwent pharmacokinetic evaluations at baseline, and again weeks 2 and 4 after initiating daily rifapentine plus isoniazid. Associations with polymorphisms relevant to efavirenz, nevirapine, isoniazid, and rifapentine pharmacokinetics were assessed. RESULTS: Of 128 participants, 101 were evaluable for associations with rifapentine and its active 25-desacetyl metabolite, 87 with efavirenz, and 38 with nevirapine. In multivariable analyses, NAT2 slow acetylators had greater week 4 plasma concentrations of rifapentine (P = 2.6 × 10) and 25-desacetyl rifapentine (P = 7.0 × 10) among all participants, and in efavirenz and nevirapine subgroups. NAT2 slow acetylators also had greater plasma efavirenz and nevirapine concentration increases from baseline to week 4, and greater decreases from baseline in clearance. CYP2B6 poor metabolizers had greater efavirenz concentrations at all weeks and greater nevirapine concentrations at baseline. None of 47 additional polymorphisms in 11 genes were significantly associated with pharmacokinetics. CONCLUSIONS: Among HIV-positive individuals receiving efavirenz or nevirapine, and who then initiated rifapentine plus isoniazid in A5279, NAT2 slow acetylators had greater rifapentine and 25-desacetyl rifapentine concentrations, and greater increases from baseline in plasma efavirenz and nevirapine concentrations. These associations are likely mediated by greater isoniazid exposure in NAT2 slow acetylators.


Assuntos
Alcinos/administração & dosagem , Benzoxazinas/administração & dosagem , Ciclopropanos/administração & dosagem , Infecções por HIV/tratamento farmacológico , Isoniazida/administração & dosagem , Nevirapina/administração & dosagem , Rifampina/análogos & derivados , Adolescente , Adulto , Alcinos/efeitos adversos , Fármacos Anti-HIV/administração & dosagem , Arilamina N-Acetiltransferase/genética , Benzoxazinas/efeitos adversos , Ciclopropanos/efeitos adversos , Sinergismo Farmacológico , Infecções por HIV/genética , Infecções por HIV/virologia , Humanos , Isoniazida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Nevirapina/efeitos adversos , Farmacogenética , Rifampina/administração & dosagem , Rifampina/efeitos adversos , Adulto Jovem
20.
Lancet ; 396(10267): 1994-2005, 2021 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-33308425

RESUMO

BACKGROUND: Phase 3 clinical studies showed non-inferiority of long-acting intramuscular cabotegravir and rilpivirine dosed every 4 weeks to oral antiretroviral therapy. Important phase 2 results of every 8 weeks dosing, and supportive modelling, underpin further evaluation of every 8 weeks dosing in this trial, which has the potential to offer greater convenience. Our objective was to compare the week 48 antiviral efficacy of cabotegravir plus rilpivirine long-acting dosed every 8 weeks with that of every 4 weeks dosing. METHODS: ATLAS-2M is an ongoing, randomised, multicentre (13 countries; Australia, Argentina, Canada, France, Germany, Italy, Mexico, Russia, South Africa, South Korea, Spain, Sweden, and the USA), open-label, phase 3b, non-inferiority study of cabotegravir plus rilpivirine long-acting maintenance therapy administered intramuscularly every 8 weeks (cabotegravir 600 mg plus rilpivirine 900 mg) or every 4 weeks (cabotegravir 400 mg plus rilpivirine 600 mg) to treatment-experienced adults living with HIV-1. Eligible newly recruited individuals must have received an uninterrupted first or second oral standard-of-care regimen for at least 6 months without virological failure and be aged 18 years or older. Eligible participants from the ATLAS trial, from both the oral standard-of-care and long-acting groups, must have completed the 52-week comparative phase with an ATLAS-2M screening plasma HIV-1 RNA less than 50 copies per mL. Participants were randomly assigned 1:1 to receive cabotegravir plus rilpivirine long-acting every 8 weeks or every 4 weeks. The randomisation schedule was generated by means of the GlaxoSmithKline validated randomisation software RANDALL NG. The primary endpoint at week 48 was HIV-1 RNA ≥50 copies per mL (Snapshot, intention-to-treat exposed), with a non-inferiority margin of 4%. The trial is registered at ClinicalTrials.gov, NCT03299049 and is ongoing. FINDINGS: Screening occurred between Oct 27, 2017, and May 31, 2018. Of 1149 individuals screened, 1045 participants were randomised to the every 8 weeks (n=522) or every 4 weeks (n=523) groups; 37% (n=391) transitioned from every 4 weeks cabotegravir plus rilpivirine long-acting in ATLAS. Median participant age was 42 years (IQR 34-50); 27% (n=280) female at birth; 73% (n=763) white race. Cabotegravir plus rilpivirine long-acting every 8 weeks was non-inferior to dosing every 4 weeks (HIV-1 RNA ≥50 copies per mL; 2% vs 1%) with an adjusted treatment difference of 0·8 (95% CI -0·6-2·2). There were eight (2%, every 8 weeks group) and two (<1%, every 4 weeks group) confirmed virological failures (two sequential measures ≥200 copies per mL). For the every 8 weeks group, five (63%) of eight had archived non-nucleoside reverse transcriptase inhibitor resistance-associated mutations to rilpivirine at baseline. The safety profile was similar between dosing groups, with 844 (81%) of 1045 participants having adverse events (excluding injection site reactions); no treatment-related deaths occurred. INTERPRETATION: The efficacy and safety profiles of dosing every 8 weeks and dosing every 4 weeks were similar. These results support the use of cabotegravir plus rilpivirine long-acting administered every 2 months as a therapeutic option for people living with HIV-1. FUNDING: ViiV Healthcare and Janssen.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/tratamento farmacológico , HIV-1 , Piridonas/administração & dosagem , Rilpivirina/administração & dosagem , Adulto , Alanina Transaminase/sangue , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/sangue , Preparações de Ação Retardada , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Injeções Intramusculares , Masculino , Pessoa de Meia-Idade , Piridonas/efeitos adversos , Piridonas/sangue , RNA Viral/sangue , Rilpivirina/efeitos adversos , Rilpivirina/sangue , Carga Viral
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...