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1.
Euro Surveill ; 27(22)2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35656834

RESUMO

Between 7 and 25 May, 86 monkeypox cases were confirmed in the United Kingdom (UK). Only one case is known to have travelled to a monkeypox virus (MPXV) endemic country. Seventy-nine cases with information were male and 66 reported being gay, bisexual, or other men who have sex with men. This is the first reported sustained MPXV transmission in the UK, with human-to-human transmission through close contacts, including in sexual networks. Improving case ascertainment and onward-transmission preventive measures are ongoing.


Assuntos
Mpox , Minorias Sexuais e de Gênero , Feminino , Homossexualidade Masculina , Humanos , Masculino , Mpox/diagnóstico , Mpox/epidemiologia , Mpox/transmissão , Monkeypox virus/genética , Reino Unido/epidemiologia
2.
J Neurovirol ; 26(5): 754-763, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32500477

RESUMO

We assessed changes in functional connectivity by fMRI (functional magnetic resonance imaging) and cognitive measures in otherwise neurologically asymptomatic people with HIV (PWH) switching combination antiretroviral therapy (cART). In a prospective study (baseline and follow-up after at least 4 months), virologically suppressed PWH switched non-nuclease reverse-transcriptase inhibitors (NNRTI; tenofovir-DF/emtricitabine with efavirenz to rilpivirine) and integrase-strand-transfer inhibitors (INSTI; tenofovir-DF/emtricitabine with raltegravir to dolutegravir). PWH were assessed by resting-state fMRI and stop-signal reaction time (SSRT) task fMRI as well as with a cognitive battery (CogState™) at baseline and follow-up. Switching from efavirenz to rilpivirine (n = 10) was associated with increased functional connectivity in the dorsal attention network (DAN) and a reduction in SSRTs (p = 0.025) that positively correlated with the time previously on efavirenz (mean = 4.8 years, p = 0.02). Switching from raltegravir to dolutegravir (n = 12) was associated with increased connectivity in the left DAN and bilateral sensory-motor and associative visual networks. In the NNRTI study, significant improvements in the cognitive domains of executive function, working memory and speed of visual processing were observed, whereas no significant changes in cognitive function were observed in the INSTI study. Changes in fMRI are evident in PWH without perceived neuropsychiatric complaints switching cART. fMRI may be a useful tool in assisting to elucidate the underlying pathogenic mechanisms of cART-related neuropsychiatric effects.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Disfunção Cognitiva/tratamento farmacológico , Conectoma/métodos , Substituição de Medicamentos/métodos , Infecções por HIV/tratamento farmacológico , Adulto , Alcinos/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Doenças Assintomáticas , Benzoxazinas/uso terapêutico , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/virologia , Ciclopropanos/uso terapêutico , Emtricitabina/uso terapêutico , Função Executiva/efeitos dos fármacos , Função Executiva/fisiologia , Feminino , Infecções por HIV/diagnóstico por imagem , Infecções por HIV/fisiopatologia , Infecções por HIV/virologia , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Imageamento por Ressonância Magnética , Masculino , Memória de Curto Prazo/efeitos dos fármacos , Memória de Curto Prazo/fisiologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Oxazinas/uso terapêutico , Piperazinas/uso terapêutico , Estudos Prospectivos , Piridonas/uso terapêutico , Raltegravir Potássico/uso terapêutico , Rilpivirina/uso terapêutico , Tenofovir/uso terapêutico
3.
J Antimicrob Chemother ; 71(1): 235-43, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26472771

RESUMO

BACKGROUND: The concentration of antiretrovirals in CSF is often utilized as a surrogate for CNS drug exposure. This measurement does not consider pharmacodynamic or combinative effects of ART. We have developed a novel endpoint measurement to assess antiretroviral activity of CSF from subjects on ART. METHODS: CSF samples were obtained from patients receiving tenofovir/emtricitabine (245/200 mg once daily) with either rilpivirine (25 mg once daily) or lopinavir/ritonavir/maraviroc (400/100/150 mg twice daily) and HIV-uninfected controls. Antiviral activity of ART-containing CSF was assessed in cell cultures using PBMCs and neuro-derived glial (U87) and astrocyte (373) cell lines. Infectivity model half-maximal inhibitory concentration (IMIC50) values were calculated and expressed as -log2IMIC50. Results were correlated with CSF antiretroviral concentrations. RESULTS: Compared with controls, CSF from both ART studies demonstrated in vitro antiretroviral activity in all models. CSF antiretroviral activity of patients on lopinavir/ritonavir/maraviroc was significantly greater than that of patients on rilpivirine [-log2IMIC50 (95% CI) 4.82 (4.74-4.89) versus 3.43 (3.33-3.54) in PBMCs, 3.06 (2.98-3.15) versus 2.56 (2.46-2.65) in U87 cells and 6.00 (6.11-5.88) versus 4.90 (5.09-4.72) in 373 cells, respectively]. Positive correlations were observed for individual CSF antiretroviral activity in different cellular models with CSF concentrations of rilpivirine (P = 0.040 in 373 cells) and lopinavir (P = 0.048 in 373 cells), but not maraviroc. CONCLUSIONS: Antiviral activity of CSF from patients on ART was successfully calculated and was greater with a regimen containing four active drugs compared with three active drugs. The use of neuro-derived cell lines alongside PBMCs to assess the effect of ART on CSF may act as a useful future clinical research tool.


Assuntos
Fármacos Anti-HIV/análise , Líquido Cefalorraquidiano/química , Monitoramento de Medicamentos/métodos , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/farmacologia , Terapia Antirretroviral de Alta Atividade , Astrócitos/fisiologia , Astrócitos/virologia , Técnicas de Cultura de Células , Células Cultivadas , Feminino , Humanos , Concentração Inibidora 50 , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Neuroglia/fisiologia , Neuroglia/virologia , Cultura de Vírus
4.
AIDS Res Ther ; 13: 20, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27081393

RESUMO

BACKGROUND: Cognitive function is reported to improve after the initiation of combination antiretroviral therapy (cART). Data on the evolution of such changes are limited. We assessed the dynamics of changes in cognitive parameters, in HIV-positive subjects initiating cART. METHODS: Cognitive function in seven domains was evaluated for HIV-infected patients without clinically significant cognitive impairment prior to the initiation of cART, and 24 and 48 weeks after. Cognitive scores were transformed using standardised z-scores according to the pooled baseline standard deviation. Global, speed, and accuracy composite z-scores were calculated with changes calculated using a paired t test. RESULTS: In 14 subjects, change in global cognitive z-scores from baseline was by 0.08 at week 24 (p = 0.59) and 0.15 at week 48 (p = 0.43). Change in composite speed and accuracy z-scores from baseline at weeks 24/48 were 0.07/0.05 (p = 0.45/0.82) and 0.13/0.23 (p = 0.47/0.45), respectively. In two of the cognitive domains assessing speed (learning and monitoring time), a continued improvement from baseline to weeks 24 and 48 was observed (changes of 0.06-0.08 and 0.10-0.19, respectively), whereas in two domains (detection and identification) an initial improvement at week 24 (changes of -0.10 and 0.04 from baseline, respectively) was followed by a deterioration in score at week 48 (changes of -0.12 and -0.08 from baseline, respectively). None of these changes were statistically significant. CONCLUSIONS: A trend for improvement in cognitive function was observed in naïve HIV-positive patients starting cART. The dynamics of this improvement differed both between cognitive domains and the time-points assessed.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Transtornos Cognitivos/etiologia , Infecções por HIV/complicações , Adulto , Sulfato de Atazanavir/administração & dosagem , Sulfato de Atazanavir/uso terapêutico , Cognição/efeitos dos fármacos , Combinação Emtricitabina e Fumarato de Tenofovir Desoproxila/administração & dosagem , Combinação Emtricitabina e Fumarato de Tenofovir Desoproxila/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Nevirapina/administração & dosagem , Nevirapina/uso terapêutico , Ritonavir/administração & dosagem , Ritonavir/uso terapêutico , Adulto Jovem
5.
J Antimicrob Chemother ; 70(6): 1812-5, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25693997

RESUMO

OBJECTIVES: Boceprevir is a first-generation direct-acting antiviral licensed for the treatment of hepatitis C infection. Sildenafil is an oral therapy for erectile dysfunction. As boceprevir is a potent inhibitor of CYP3A4, potential pharmacokinetic interactions may occur when it is coadministered with sildenafil. The aim of this study was to assess the pharmacokinetic profile of sildenafil and boceprevir when dosed separately and together in healthy volunteers. METHODS: Thirteen male subjects completed the following study procedures: phase 1 (Day 0), a single dose of 25 mg of sildenafil was administered; washout period (Days 1-9); phase 2 (Days 10-15), 800 mg of boceprevir three times a day was administered; and phase 3 (Day 16), 800 mg of boceprevir and 25 mg of sildenafil were administered. All drugs were administered in the fed state. Intensive pharmacokinetic sampling was undertaken on Days 0, 15 and 16. Differences in the pharmacokinetic parameters of sildenafil, N-desmethyl-sildenafil and boceprevir between phase 3 and the earlier phases were evaluated by changes in the geometric mean ratios (GMRs). RESULTS: All the drugs were well tolerated with no safety concerns arising. In the presence of boceprevir (phase 3 versus phase 1), the GMR for the plasma Cmax and the AUC24 for sildenafil increased by 1.9-fold (95% CI 1.5-2.4) and 2.7-fold (95% CI 2.1-3.4), respectively, whereas a reduction in the Cmax of N-desmethyl-sildenafil was observed (GMR 0.5, 95% CI 0.4-0.7). No significant changes in boceprevir exposure were observed between phases 3 and 2. CONCLUSIONS: Exposure of sildenafil is increased in the presence of boceprevir. A dose adjustment of sildenafil is therefore necessary. An initial dose of 25 mg of sildenafil is suggested.


Assuntos
Antivirais/farmacocinética , Prolina/análogos & derivados , Citrato de Sildenafila/farmacocinética , Agentes Urológicos/farmacocinética , Adolescente , Adulto , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Interações Medicamentosas , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Plasma/química , Prolina/administração & dosagem , Prolina/efeitos adversos , Prolina/farmacocinética , Citrato de Sildenafila/administração & dosagem , Citrato de Sildenafila/efeitos adversos , Agentes Urológicos/administração & dosagem , Agentes Urológicos/efeitos adversos , Adulto Jovem
6.
HIV Clin Trials ; 16(1): 39-42, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25777188

RESUMO

BACKGROUND: Antiretroviral safety and efficacy and may differ in older versus younger HIV-infected patients. The objective of this study was to assess the pharmacokinetic (PK) profile in older HIV-infected subjects (>60 years) switching combination antiretroviral therapy (cART) to a raltegravir (RAL) containing regimen. METHODS: Nineteen HIV-infected patients over 60 years of age on effective cART (HIV-RNA < 50 copies/ml) were enrolled in this prospective 24-week study. On day 1, patients switched to tenofovir/emtricitabine (245/200 mg once daily) and RAL (400 mg twice daily). On day 28, intensive PK sampling was undertaken in a fasted state and RAL plasma concentrations determined. Neurocognitive function was assessed at baseline and week 24 using a neuropsychological battery. RAL PK parameters were compared to those of two younger historical HIV-infected control groups that received twice-daily RAL co-administered with darunavir/ritonavir (DRV/r) 800/100 once daily by nonlinear mixed effects modelling. RESULTS: In HIV-infected subjects over the age of 60 (mean ± SD age: 66 ± 3.4 years, n = 19) switching to a RAL containing regimen, we observed no safety concerns, no plasma virological rebounds, and no differences in RAL apparent oral clearance when compared to younger HIV-infected populations (mean ± SD age: 41 ± 9.2 years, n = 38) based on population pharmacokinetic analysis. After 24 weeks of study therapy a decline in cognitive function was observed [change in (SD) global score of (0.91 (1.3), P = 0.018]. CONCLUSIONS: No significant changes in RAL exposure associated with age were observed.


Assuntos
Fármacos Anti-HIV/farmacocinética , Emtricitabina/farmacocinética , Infecções por HIV/tratamento farmacológico , Raltegravir Potássico/farmacocinética , Tenofovir/farmacocinética , Adulto , Fármacos Anti-HIV/farmacologia , Área Sob a Curva , Contagem de Linfócito CD4 , Quimioterapia Combinada , Emtricitabina/farmacologia , Feminino , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Humanos , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Estudos Prospectivos , Raltegravir Potássico/farmacologia , Tenofovir/farmacologia , Reino Unido , Carga Viral/efeitos dos fármacos
7.
J Antimicrob Chemother ; 69(6): 1642-7, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24521854

RESUMO

OBJECTIVES: Pharmacokinetic parameters following modifications to antiretroviral therapy and sanctuary site exposure are often unknown for recently licensed antiretrovirals. We assessed plasma, CSF and seminal plasma (SP) exposure of rilpivirine after switching from nevirapine. METHODS: HIV-infected male subjects receiving tenofovir/emtricitabine/nevirapine (245/200/400 mg) once daily switched to tenofovir/emtricitabine/rilpivirine (245/200/25 mg) once daily for 60 days when CSF and semen samples were collected. Mean and individual plasma concentrations of nevirapine and rilpivirine were compared with the proposed plasma target concentration for nevirapine (3000 ng/mL) and the protein binding-adjusted EC90 for rilpivirine (12.1 ng/mL). Mean rilpivirine CSF and SP concentrations were calculated and individual values compared with the EC50 and EC90 for wild-type virus (0.27 and 0.66 ng/mL, respectively). RESULTS: Of 13 subjects completing study procedures including CSF examination, 8 provided seminal samples. By day 3, the mean plasma rilpivirine trough concentration was 29.7 ng/mL (95% CI: 23.8-37). No patient presented rilpivirine plasma concentrations under the proposed threshold. The mean rilpivirine concentration in CSF was 0.8 ng/mL (95% CI: 0.7-1.0), representing a CSF : plasma ratio of 1.4%, with concentrations above the EC90 in 85% (11/13) of patients. In SP, the mean rilpivirine concentration was 4.9 ng/mL (95% CI: 3.3-7.2), representing an SP : plasma ratio of 9.5%, with all concentrations above the EC90. CONCLUSIONS: Switching from nevirapine- to rilpivirine-containing antiretroviral therapy was safe and well tolerated, with plasma rilpivirine concentrations above the protein binding-adjusted EC90 in all subjects. Rilpivirine concentrations were always above the EC50 in the CSF and the EC90 in SP.


Assuntos
Fármacos Anti-HIV/farmacocinética , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Nevirapina/farmacocinética , Nitrilas/farmacocinética , Pirimidinas/farmacocinética , Adulto , Fármacos Anti-HIV/administração & dosagem , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Líquido Cefalorraquidiano/metabolismo , Substituição de Medicamentos , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Nevirapina/administração & dosagem , Nitrilas/administração & dosagem , Pirimidinas/administração & dosagem , Rilpivirina , Sêmen/metabolismo , Carga Viral
8.
J Antimicrob Chemother ; 68(6): 1348-53, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23364475

RESUMO

BACKGROUND: Once-daily nucleoside-sparing combination antiretroviral therapy regimens are attractive options for the treatment of HIV infection. However, the pharmacokinetic profiles of such regimens are often not established. METHODS: HIV-infected subjects receiving 245/200 mg of tenofovir/emtricitabine plus 800/100 mg of darunavir/ritonavir once daily with plasma HIV RNA <50 copies/mL were eligible. On day 1 (period 1), 150 mg of maraviroc daily was added and on day 11 (period 2), tenofovir/emtricitabine discontinued. At steady-state (days 10 and 20), intensive pharmacokinetic sampling was undertaken. We assessed (i) the number of subjects with trough (C(trough)) and average (C(avg)) maraviroc concentrations <25 and <75 ng/mL, respectively; (ii) geometric mean (GM) ratios for pharmacokinetic parameters for period 2 versus period 1; and (iii) factors associated with total maraviroc exposure. RESULTS: Eleven subjects completed the study procedures (mean age 49 years; range 35-59 years). In three subjects, maraviroc C(trough) and C(avg) were <25 and <75 ng/mL, respectively (C(avg), 68 ng/mL and C(trough), 14 and 21 ng/mL). Although not statistically significant, a trend was observed towards lower maraviroc, darunavir and ritonavir concentrations in period 2 versus period 1; total maraviroc exposure was 3579 ng·â€Šh/mL (95% CI: 2983-4294) and 2996 ng·â€Šh/mL (95% CI: 2374-3782) in periods 1 and 2, respectively, and the GM ratio was 0.84 (95% CI: 0.67-1.05). Only total ritonavir exposure was significantly associated with total maraviroc exposure (P=0.049; 95% CI: 0.01-0.91). No clinical safety concerns were observed. CONCLUSIONS: Within this novel nucleoside-sparing regimen, maraviroc exposure is dependent on ritonavir exposure, which was slightly reduced in the absence of tenofovir/emtricitabine.


Assuntos
Cicloexanos/efeitos adversos , Cicloexanos/farmacocinética , Inibidores da Fusão de HIV/efeitos adversos , Inibidores da Fusão de HIV/farmacocinética , Infecções por HIV/tratamento farmacológico , Infecções por HIV/metabolismo , Inibidores da Protease de HIV/uso terapêutico , Ritonavir/uso terapêutico , Sulfonamidas/uso terapêutico , Triazóis/efeitos adversos , Triazóis/farmacocinética , Adulto , Terapia Antirretroviral de Alta Atividade , Área Sob a Curva , Contagem de Linfócito CD4 , Cicloexanos/uso terapêutico , Darunavir , Quimioterapia Combinada , Feminino , Inibidores da Fusão de HIV/uso terapêutico , Meia-Vida , Humanos , Masculino , Maraviroc , Pessoa de Meia-Idade , Estudos Prospectivos , RNA Viral/sangue , Triazóis/uso terapêutico
9.
Int J Infect Dis ; 126: 48-53, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36410691

RESUMO

OBJECTIVES: Since May 2022, cases of human monkeypox virus (hMPXV) with human-to-human cross-transmission have significantly increased in nonendemic countries. Our aim was to characterize diagnostic features of patients with confirmed and possible monkeypox to guide future risk stratification and to describe a virtual care model. METHODS: We performed a retrospective case-control study of 140 patients assessed and screened for suspected monkeypox; on hMPXV polymerase chain reaction testing, 70 were confirmed positive, and 70 were negative. Data were compared to generate odds ratios of demographic and clinical features. RESULTS: Patients who tested positive were predominantly cis-male (99%) and self-identified as gay, bisexual, and other men who have sex with men (94%). Lymphadenopathy at presentation was associated with a higher likelihood of a positive result (odds ratio [OR] 7.69 [95% confidence interval (CI) 3.58, 16.51]). Patients who tested positive were more likely to have a rash affecting the genital (OR 5.38 [95% CI 2.57, 11.23]) or buttocks/perianal region (OR 3.79 [1.70, 8.45]) than negative controls. A total of 79% of patients were engaged with a virtual ward follow-up. CONCLUSION: These data can inform a risk-based approach to the management of suspected monkeypox in gay, bisexual, and other men who have sex with men populations. Lymphadenopathy at presentation and the location of the rash were more associated with a positive hMPXV result. Health authorities can consider a virtual ward approach in the hMPHXV outbreak.


Assuntos
Exantema , Linfadenopatia , Mpox , Minorias Sexuais e de Gênero , Humanos , Masculino , Estudos de Casos e Controles , Estudos Retrospectivos , Mpox/diagnóstico , Mpox/epidemiologia , Homossexualidade Masculina , Londres
10.
Open Forum Infect Dis ; 10(5): ofad108, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37152187

RESUMO

Background: We report outcomes and novel characterization of a unique cohort of 42 individuals with persistently indeterminate human immunodeficiency virus (HIV) status, the majority of whom are HIV viral controllers. Methods: Eligible individuals had indeterminate or positive HIV serology, but persistently undetectable HIV ribonucleic acid (RNA) by commercial assays and were not taking antiretroviral therapy (ART). Routine investigations included HIV Western blot, HIV viral load, qualitative HIV-1 deoxyribonucleic acid (DNA), coinfection screen, and T-cell quantification. Research assays included T-cell activation, ART measurement, single-copy assays detecting HIV-1 RNA and DNA, and plasma cytokine quantification. Human immunodeficiency virus seropositivity was defined as ≥3 bands on Western blot; molecular positivity was defined as detection of HIV RNA or DNA. Results: Human immunodeficiency virus infection was excluded in 10 of 42 referrals, remained unconfirmed in 2 of 42, and was confirmed in 30 of 42, who were identified as HIV elite controllers (ECs), normal CD4 T-cell counts (median 820/mL, range 805-1336), and normal CD4/CD8 ratio (median 1.8, range 1.2-1.9). Elite controllers had a median duration of elite control of 6 years (interquartile range = 4-14). Antiretroviral therapy was undetected in all 23 subjects tested. Two distinct categories of ECs were identified: molecular positive (n = 20) and molecular negative (n = 10). Conclusions: Human immunodeficiency virus status was resolved for 95% of referrals with the majority diagnosed as EC. The clinical significance of the 2 molecular categories among ECs requires further investigation.

11.
Lancet Infect Dis ; 23(6): e218-e226, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36773621

RESUMO

A 48-year-old man with poorly controlled HIV presented with severe human monkeypox virus (hMPXV) infection, having completed 2 weeks of tecovirimat at another hospital. He had painful, ulcerating skin lesions on most of his body and oropharyngeal cavity, with subsequent Ludwig's angina requiring repeated surgical interventions. Despite commencing a second, prolonged course of tecovirimat, he did not objectively improve, and new lesions were still noted at day 24. Discussion at the UK National Health Service England High Consequence Infectious Diseases Network recommended the use of 3% topical and then intravenous cidofovir, which was given at 5 mg/kg; the patient made a noticeable improvement after the first intravenous dose. He received further intravenous doses at 7 days and 21 days after the dose and was discharged at day 52. Cidofovir is not licensed for use in treatment of hMPXV infection. Data for cidofovir use in hMPXV are restricted to studies in animals. Four other documented cases of cidofovir use against hMPXV have been reported in the USA in 2022, but we present its first use in the UK. The scarcity of studies into the use of cidofovir in this condition clearly shows the need for robust studies to assess efficacy, optimum dosage, timing, and route of administration.


Assuntos
Infecções por HIV , Mpox , Organofosfonatos , Masculino , Humanos , Pessoa de Meia-Idade , Cidofovir/uso terapêutico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Organofosfonatos/uso terapêutico , Mpox/tratamento farmacológico , Medicina Estatal , Citosina/uso terapêutico , Antivirais/uso terapêutico
12.
Lancet Infect Dis ; 22(9): 1321-1328, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35785793

RESUMO

BACKGROUND: Historically, human monkeypox virus cases in the UK have been limited to imported infections from west Africa. Currently, the UK and several other countries are reporting a rapid increase in monkeypox cases among individuals attending sexual health clinics, with no apparent epidemiological links to endemic areas. We describe demographic and clinical characteristics of patients diagnosed with human monkeypox virus attending a sexual health centre. METHODS: In this observational analysis, we considered patients with confirmed monkeypox virus infection via PCR detection attending open-access sexual health clinics in London, UK, between May 14 and May 25, 2022. We report hospital admissions and concurrent sexually transmitted infection (STI) proportions, and describe our local response within the first 2 weeks of the outbreak. FINDINGS: Monkeypox virus infection was confirmed in 54 individuals, all identifying as men who have sex with men (MSM), with a median age of 41 years (IQR 34-45). 38 (70%) of 54 individuals were White, 26 (48%) were born in the UK, and 13 (24%) were living with HIV. 36 (67%) of 54 individuals reported fatigue or lethargy, 31 (57%) reported fever, and ten (18%) had no prodromal symptoms. All patients presented with skin lesions, of which 51 (94%) were anogenital. 37 (89%) of 54 individuals had skin lesions affecting more than one anatomical site and four (7%) had oropharyngeal lesions. 30 (55%) of 54 individuals had lymphadenopathy. One in four patients had a concurrent STI. Five (9%) of 54 individuals required admission to hospital, mainly due to pain or localised bacterial cellulitis requiring antibiotic intervention or analgesia. We recorded no fatal outcomes. INTERPRETATION: Autochthonous community monkeypox virus transmission is currently observed among MSM in the UK. We found a high proportion of concomitant STIs and frequent anogenital symptoms, suggesting transmissibility through local inoculation during close skin-to-skin or mucosal contact, during sexual activity. Additional resources are required to support sexual health and other specialist services in managing this condition. A review of the case definition and better understanding of viral transmission routes are needed to shape infection control policies, education and prevention strategies, and contact tracing. FUNDING: None.


Assuntos
Mpox , Saúde Sexual , Minorias Sexuais e de Gênero , Infecções Sexualmente Transmissíveis , Adulto , Demografia , Homossexualidade Masculina , Humanos , Londres , Masculino , Pessoa de Meia-Idade , Monkeypox virus , Estudos Observacionais como Assunto , Comportamento Sexual
13.
HIV Res Clin Pract ; 22(6): 151-159, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34743666

RESUMO

Background: Different antiretroviral therapies (ARTs) may have differing effects on central nervous system (CNS) function. We assessed CNS pharmacodynamic effects of switching integrase inhibitors in people-with-HIV (PWH).Methods: PWH on tenofovir-DF/emtricitabine plus raltegravir 400 mg twice daily with suppressed plasma HIV RNA and without overt neuropsychiatric symptoms were randomly allocated on a 1:2 basis to remain on raltegravir or switch to dolutegravir 50 mg once daily for 120 days. Pharmacodynamic parameters assessed included cognitive function (z-score of 7 domains), patient-reported outcome measures (PROMs; PHQ-9 and Beck's depression questionnaires), cerebral metabolite ratios measured by proton magnetic resonance spectroscopy (H1-MRS) and plasma and cerebrospinal fluid (CSF) HIV RNA. Pharmacokinetic parameters were also assessed in plasma and CSF. Changes and factors associated with changes in pharmacodynamics parameters were assessed.Results:In 20 subjects (19 male, 14 white ethnicity, median age 43 years (IQR: 11.5) and CD4 + count 717 (SD: 298) cells/µL), over 120 days there were no statistically significant changes in cognitive function [mean z-score difference (95%CI) -0.004 (-0.38/0.37); p = 0.98], PROMs [PHQ-9 median score change: 0 in control arm, -0.5 switch arm (p = 0.57); Beck's depression questionnaire: -1.5 control arm, -1.0 switch arm (p = 0.38)], nor cerebral metabolite ratios between study arms. CSF HIV RNA was <5 copies/mL at baseline and day 120 in all subjects. Geometric mean pre-dose CSF dolutegravir concentration was 7.6 ng/mL (95% CI: 5.2-11.1).Conclusions:Switching integrase inhibitor in virologically suppressed PWH without overt neuropsychiatric symptoms resulted in no significant changes in an extensive panel of CNS pharmacodynamics parameters.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Inibidores de Integrase de HIV , Adulto , Fármacos Anti-HIV/uso terapêutico , Emtricitabina , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/uso terapêutico , Humanos , Masculino , Raltegravir Potássico/uso terapêutico
14.
BMJ Case Rep ; 12(2)2019 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-30755430

RESUMO

We present a case of haemophagocytic lymphohistiocytosis (HLH) in the context of disseminated cytomegalovirus (CMV) viraemia in a 50-year-old man with well-controlled HIV infection and ulcerative colitis (UC), for which he was receiving azathioprine. Peak CMV viral load was 371 000 copies/ml with evidence of end-organ CMV in the lungs and colon. A bone marrow biopsy showed evidence of haemophagocytosis of platelets, neutrophils and erythrocytes. The azathioprine was stopped, and he received intravenous ganciclovir and corticosteroids with suppression of the CMV viral load and resolution of the HLH.


Assuntos
Antivirais/uso terapêutico , Azatioprina/efeitos adversos , Colite Ulcerativa/tratamento farmacológico , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/diagnóstico , Corticosteroides/uso terapêutico , Azatioprina/uso terapêutico , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/imunologia , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/imunologia , Ganciclovir/uso terapêutico , Infecções por HIV/imunologia , Humanos , Hospedeiro Imunocomprometido , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/imunologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
15.
AIDS ; 32(8): 1007-1015, 2018 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-29438199

RESUMO

BACKGROUND: Maraviroc-intensified antiretroviral therapy (ART) may be associated with cognitive benefits. METHODS: Therapy-naive, cognitively asymptomatic, HIV-positive individuals were randomly allocated on a 1 : 1 basis to standard ART (Arm1: tenofovir-emtricitabine and atazanavir/ritonavir) or maraviroc intensified ART (Arm2: abacavir-lamivudine and darunavir/ritonavir/maraviroc). Over 48 weeks, detailed assessments of cognitive function tests were undertaken and cerebral metabolites measured using proton magnetic resonance spectroscopy. Our primary endpoint was mean change in cognitive function across treatment arms with factors associated with cognitive function changes also assessed. RESULTS: Of 60 individuals randomized (30 Arm1 and 30 Arm2), 58 were men and 44 of white ethnicity. Treatment groups had similar disease characteristics including overall mean (SD) baseline CD4 cell count 428 (209) and 414 (229) cells/µl, Arms1 and 2, respectively. At week 48, plasma HIV RNA was less than 50 copies/ml in 55 of 56 of those completing study procedures. Cognitive function improved over 48 weeks [mean change z-score (SD) 0.16 (0.09) Arm1 and 0.25 (0.08) Arm2, P = 0.96 for differences between study arms]. A greater increase in frontal grey matter N-acetyl aspartate/creatine ratio was observed in Arm1 [ratio change of 0.071 (SD 0.16)] versus Arm2 [change -0.097 (SD 0.18), P = 0.009], although this was not associated with changes in cognitive function (P = 0.17). CONCLUSION: Maraviroc-intensified ART had no demonstrable benefit on cognitive function in individuals initiating ART. Greater improvement in neuronal metabolites (N-acetyl aspartate/creatine) was observed with standard ART. Future work should focus on maraviroc-intensified ART in individuals with cognitive impairment.


Assuntos
Complexo AIDS Demência/prevenção & controle , Fármacos Anti-HIV/administração & dosagem , Antirretrovirais/administração & dosagem , Infecções por HIV/tratamento farmacológico , Maraviroc/administração & dosagem , Complexo AIDS Demência/patologia , Adulto , Terapia Antirretroviral de Alta Atividade/métodos , Química Encefálica , Feminino , Infecções por HIV/complicações , Humanos , Imageamento por Ressonância Magnética , Masculino , Resultado do Tratamento
17.
Br J Radiol ; 89(1060): 20150979, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26954329

RESUMO

OBJECTIVE: Non-invasive biomarkers to monitor cerebral function in treated human immunodeficiency virus (HIV) disease are required. Cerebral metabolite ratios (CMRs) measured by proton-MR spectroscopy ((1)H-MRS) are a potential biomarker. Here, we compare two post-processing software packages to quantify CMRs. METHODS: Cerebral (1)H-MRS data from 11 HIV-positive subjects before and after antiretroviral therapy intensification with maraviroc were quantified using a java-based version of the MR user interface package (jMRUI) and the totally automatic robust quantitation in nuclear MR (TARQUIN). (1)H-MRS data included N-acetylaspartate (NAA), creatine (Cr), choline (Cho) and myo-inositol (mI) from three cerebral locations. Differences in quantification and clinical associations of CMRs measured by the two packages were evaluated. RESULTS: Mean CMRs were generally lower when measured by TARQUIN than by jMRUI (NAA/Cr, Cho/Cr, mI/Cr ratios of 1.78, 0.83, 0.81 for jMRUI, and 1.27, 0.25, 0.81 for TARQUIN). Longitudinal changes were observed in CMRs in the basal ganglia voxel although these changes were not statistically significant [+7.1% (p = 0.18), +0.0% (p = 0.91) and -6.6% (p = 0.61) and +14.8% (p = 0.18), +17.9% (p = 0.07) and +34.8% (p = 0.17) for NAA/Cr, Cho/Cr and mI/Cr ratios measured by TARQUIN and jMRUI, respectively]. Plasma maraviroc concentration was associated with a decrease in mI/Cr ratio measured via TARQUIN (p = 0.049). CONCLUSION: Although CMRs differed when quantified by jMRUI vs TARQUIN, these differences were consistently observed across three cerebral locations, and clinical associations were evident by both methods. ADVANCES IN KNOWLEDGE: TARQUIN and jMRUI are viable options to use in the post-processing of cerebral MRS data acquired in HIV disease.


Assuntos
Encefalopatias/diagnóstico , Encéfalo/metabolismo , Infecções por HIV/diagnóstico , Espectroscopia de Prótons por Ressonância Magnética/métodos , Biomarcadores/metabolismo , Antagonistas dos Receptores CCR5/sangue , Antagonistas dos Receptores CCR5/uso terapêutico , Cicloexanos/sangue , Cicloexanos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Humanos , Maraviroc , Triazóis/sangue , Triazóis/uso terapêutico
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