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We describe 2 cases of infectious proctitis secondary to human monkeypox in patients presenting with rectal pain. These cases highlight the importance of multidisciplinary management of monkeypox and in expanding case definitions and enabling clinical recognition in patients presenting without skin rash.
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Exantema , Infecções Intra-Abdominais , Mpox , Proctite , Humanos , Proctite/diagnóstico , Proctite/tratamento farmacológico , DorRESUMO
OBJECTIVES: International lockdowns during the COVID-19 pandemic impacted antiretroviral drug supplies in Indonesia. We assessed the impact of antiretroviral treatment (ART) provision and being lost to follow-up (LTFU) on people living with HIV, attending a key population-focused HIV clinic in Denpasar, Bali. METHODS: This was a retrospective note review of anonymized data from adult Indonesian patients living with HIV. We collected demographic data and information on being LTFU, and assessed the numbers of patients impacted by ART switches from fixed-dose combination (FDC) tenofovir/lamivudine/efavirenz to multi-pill zidovudine-based regimens, during the first international lockdown from March 2020. RESULTS: Records of 260 Indonesian adult patients registered for HIV care and prescribed ART were reviewed; 240 (92.3%) were men, and 90% were men who have sex with men. Between 13 March and 28 May 2020, 214 (87%) out of 247 patients (previously diagnosed with HIV) had to switch to individual, multi-pill zidovudine-based regimens from their FDC. The switch lasted a mean of 35 days (range 10-85). Twenty-five patients (10%) were LTFU; patients who switched were more likely to remain in care. Data on viral load status and toxicity are lacking as laboratory testing requires self-payment. CONCLUSIONS: The majority of patients living with HIV had no choice but to switch to multi-pill, zidovudine-based regimens. Despite significant efforts to minimize the impact of lockdown on care, 10% of patients were LTFU. Patients switching ART required greater clinic attention and support, improving retention. Complete national data are needed to understand the impact of ART stockouts on virological suppression and drug resistance throughout Indonesia.
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Fármacos Anti-HIV , COVID-19 , Infecções por HIV , Minorias Sexuais e de Gênero , Adulto , Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/uso terapêutico , COVID-19/prevenção & controle , Controle de Doenças Transmissíveis , Feminino , Seguimentos , Infecções por HIV/tratamento farmacológico , Homossexualidade Masculina , Humanos , Indonésia/epidemiologia , Masculino , Pandemias , Estudos Retrospectivos , Carga Viral , Zidovudina/uso terapêuticoRESUMO
The 56 Dean Street combination prevention model, a strong engagement with the LGBTQI community and flexible services adapted to users' changing needs led to an 80% drop in HIV diagnoses in gay, bisexual and other men who have sex with men (GBMSM) from 2015 to 2017. We describe the service changes at 56 Dean Street since 2012 which resulted in an increase in the frequency of HIV testing, the introduction of pre-exposure prophylaxis, earlier HIV diagnosis and a shorter time to viral suppression in those living with HIV. This model could be adapted to deliver similar results in those settings of high HIV prevalence among GBMSM and where access to technological innovation in healthcare and engagement with the community can be achieved.
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Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Bissexualidade , Infecções por HIV/tratamento farmacológico , Homossexualidade Masculina , Humanos , Masculino , Profilaxia Pré-Exposição/métodosRESUMO
PURPOSE: To evaluate the utility of ¹8F-FDG PET/CT in suspected cerebral pathology in HIV-infected individuals. METHODS: ¹8F-FDG PET/CT scans from 29 HIV-infected individuals (29 brain scans, 22 whole-body scans) who presented with neurological symptoms and signs were retrospectively reviewed and compared with subsequent clinical investigations. RESULTS: The majority of patients (n=25) were referred to differentiate infection from malignant causes of cerebral pathology. Ten of the 11 patients with an eventual diagnosis of toxoplasmosis infection were correctly diagnosed by ¹8F-FDG PET/CT showing lesional uptake less than that of normal brain cortex (mean SUVmax 3.5, range 1.9 - 5.8). All five patients with a final diagnosis of primary central nervous system lymphoma (PCNSL) were correctly diagnosed by ¹8F-FDG PET/CT showing lesional uptake greater than that of normal brain cortex (mean SUVmax 18.8, range 12.4 - 29.9). Four of the five patients with ¹8F-FDG PET/CT features suggesting a vasculitic process had vasculitis confirmed as the final diagnosis. Three patients showed variable uptake in multiple cerebral lesions (including final diagnoses of tuberculosis and metastases from lung cancer in two patients) and there were four other miscellaneous diagnoses. In 12 patients biopsies were performed at sites guided by PET abnormality (7 brain, 5 lymph nodes) confirming or excluding significant disease in 11. CONCLUSION: ¹8F-FDG PET/CT is particularly useful for differentiating between infection and PCNSL in HIV-infected patients with a cerebral lesion on MRI or CT. ¹8F-FDG PET/CT was also a helpful tool in the diagnostic work-up of patients with other HIV-related cerebral pathology. Additional advantages of ¹8F-FDG PET/CT are the abilities to assess abnormally increased glucose metabolism in the body and to identify potential sites for biopsy.
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Fluordesoxiglucose F18 , Infecções por HIV/diagnóstico , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X , Arterite do Sistema Nervoso Central Associada a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Adulto , Idoso , Neoplasias Encefálicas/diagnóstico , Feminino , Humanos , Linfoma Relacionado a AIDS/diagnóstico , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Toxoplasmose Cerebral/diagnósticoRESUMO
Background: Chikungunya virus (CHIKV) has expanded its geographical reach in recent decades and is an emerging global health threat. CHIKV can cause significant morbidity and lead to chronic, debilitating arthritis/arthralgia in up to 40% of infected individuals. Prevention, early identification, and clinical management are key for improving outcomes. The aim of this review is to evaluate the quality, availability, inclusivity, and scope of evidence-based clinical management guidelines (CMG) for CHIKV globally. Methods: We conducted a systematic review. Six databases were searched from Jan 1, 1989, to 14 Oct 2021 and grey literature until Sept 16, 2021, for CHIKV guidelines providing supportive care and treatment recommendations. Quality was assessed using the appraisal of Guidelines for Research and Evaluation tool. Findings are presented in a narrative synthesis. PROSPERO registration: CRD42020167361. Findings: 28 CMGs were included; 54% (15/28) were produced more than 5 years ago, and most were of low-quality (median score 2 out of 7 (range 1-7)). There were variations in the CMGs' guidance on the management of different at-risk populations, long-term sequelae, and the prevention of disease transmission. While 54% (15/28) of CMGs recommended hospitalisation for severe cases, only 39% (11/28) provided guidance for severe disease management. Further, 46% (13/28) advocated for steroids in the chronic phase, but 18% (5/28) advised against its use. Interpretation: There was a lack of high-quality CMGs that provided supportive care and treatment guidance, which may impact patient care and outcomes. It is essential that existing guidelines are updated and adapted to provide detailed evidence-based treatment guidelines for different at-risk populations. This study also highlights a need for more research into the management of the acute and chronic phases of CHIKV infection to inform evidence-based care. Funding: The UK Foreign, Commonwealth and Development Office, Wellcome Trust [215091/Z/18/Z] and the Bill & Melinda Gates Foundation [OPP1209135].
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BACKGROUND: Monkeypox (MPX) is an important human Orthopoxvirus infection. There has been an increase in MPX cases and outbreaks in endemic and non-endemic regions in recent decades. We appraised the availability, scope, quality and inclusivity of clinical management guidelines for MPX globally. METHODS: For this systematic review, we searched six databases from inception until 14 October 2021, augmented by a grey literature search until 17 May 2022. MPX guidelines providing treatment and supportive care recommendations were included, with no exclusions for language. Two reviewers assessed the guidelines. Quality was assessed using the Appraisal of Guidelines for Research and Evaluation II tool. RESULTS: Of 2026 records screened, 14 guidelines were included. Overall, most guidelines were of low-quality with a median score of 2 out of 7 (range: 1-7), lacked detail and covered a narrow range of topics. Most guidelines focused on adults, five (36%) provided some advice for children, three (21%) for pregnant women and three (21%) for people living with HIV. Treatment guidance was mostly limited to advice on antivirals; seven guidelines advised cidofovir (four specified for severe MPX only); 29% (4/14) tecovirimat, and 7% (1/14) brincidofovir. Only one guideline provided recommendations on supportive care and treatment of complications. All guidelines recommended vaccination as post-exposure prophylaxis (PEP). Three guidelines advised on vaccinia immune globulin as PEP for severe cases in people with immunosuppression. CONCLUSION: Our results highlight a lack of evidence-based clinical management guidelines for MPX globally. There is a clear and urgent need for research into treatment and prophylaxis including for different risk populations. The current outbreak provides an opportunity to accelerate this research through coordinated high-quality studies. New evidence should be incorporated into globally accessible guidelines, to benefit patient and epidemic outcomes. A 'living guideline' framework is recommended. PROSPERO REGISTRATION NUMBER: CRD42020167361.
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Mpox , Adulto , Antivirais/uso terapêutico , Criança , Bases de Dados Factuais , Surtos de Doenças , Feminino , Humanos , Mpox/epidemiologia , Mpox/terapia , GravidezRESUMO
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.
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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 SexualRESUMO
Indonesia has one of the fastest growing HIV epidemics in the world. AIDS related deaths in Indonesia have not fallen and have increased significantly since 2010. HIV infection rates remain high and rising in key affected populations. We provide an on the ground, evidence-based perspective of the challenges Indonesia faces. We discuss what is required to adopt tailored public health approaches that address context specific challenges, confront structural barriers and the heterogeneity of the current evolving HIV epidemic.
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Epidemias/prevenção & controle , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , Acessibilidade aos Serviços de Saúde , Humanos , Indonésia/epidemiologia , Política , Assunção de Riscos , Comportamento SexualRESUMO
Screening and treatment of sexually transmissible infections, including HIV, are free in the UK nations; pre-exposure prophylaxis (PrEP) became free in England in October 2017 through the PrEP Impact trial. Doctor-led PrEP clinics started at 56 Dean Street in September 2015, with the drug purchased privately at full price. The service was expanded to other staff to support initiation and monitoring of increasing numbers of attendees purchasing PrEP from online pharmacies. Nonetheless, when the clinic was given a target of 1700 for the PrEP Impact trial, it was clear this could not be achieved in a timely manner through 56 Dean Street alone. To prepare for the trial, all staff with HIV testing competencies were trained in good clinical practice and trial-specific procedures, and a patient group directive was approved to facilitate nurse prescribing and dispensing. Electronic pro formas to capture eligibility for starting or continuing PrEP were adapted for the Dean Street Express clinic, with some information collected directly from service users using touch screens. These interventions, together with an update to the 2016 information leaflet developed by the community, enabled enrolment and follow-up of 1700 participants in 4 months. PrEP advice and monitoring were easily accommodated in the 56 Dean Street sexual health service, but did require additional training and approval for nurse prescribing and dispensing drug in order to achieve the target, which still fell short of the demand.
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Instituições de Assistência Ambulatorial/organização & administração , Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/prevenção & controle , Profilaxia Pré-Exposição , Doenças Virais Sexualmente Transmissíveis/prevenção & controle , Inglaterra , Humanos , Inovação Organizacional , Avaliação de Programas e Projetos de SaúdeAssuntos
Discriminação Psicológica , Infecções por HIV/epidemiologia , Homossexualidade Masculina/estatística & dados numéricos , Adulto , Epidemias , Homossexualidade Masculina/psicologia , Humanos , Indonésia/epidemiologia , Masculino , Vigilância da População , Fatores de Risco , Assunção de Riscos , Meio Social , Transtornos Relacionados ao Uso de Substâncias/epidemiologiaAssuntos
Fármacos Anti-HIV/provisão & distribuição , Infecções por Coronavirus/epidemiologia , Infecções por HIV/tratamento farmacológico , Pneumonia Viral/epidemiologia , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , COVID-19 , Infecções por Coronavirus/psicologia , Feminino , Acessibilidade aos Serviços de Saúde/organização & administração , Humanos , Indonésia , Masculino , Pandemias , Pneumonia Viral/psicologiaRESUMO
The objective of this study was to describe the prevalence of vitamin D deficiency among antiretroviral treatment-naïve, HIV-positive individuals. We reviewed records of consecutive antiretroviral treatment-naïve patients, registering for care for the first time at a London clinic from 01 January 2008 to 31 December 2009. During this period, serum 25-hydroxycholecalciferol was measured routinely for all new patients. 25-hydroxycholecalciferol deficiency and severe deficiency were defined as ≤50 and ≤25 nmol/L, respectively. Among 253 patients (82% men, median age 36 years, 64% white ethnicity), 148 (58.5%) were 25-hydroxycholecalciferol-deficient, including 32 (12.6%) who were severely deficient. In all, 73.5% (61/83) patients of non-white ethnicity were 25-hydroxycholecalciferol-deficient compared with 50.7% (76/150) of those reporting white ethnicity (p < 0.001). Seven of eight (87.5%) patients with hypocalcaemia (<2.12 nmol/L) were 25-hydroxycholecalciferol-deficient. The prevalence of 25-hydroxycholecalciferol-deficiency was higher in winter and spring vs. summer and autumn (89/129 [69.0%] vs. 59/124 [47.6%],p < 0.001). Serum 25-hydroxycholecalciferol deficiency was not associated with gender, CD4 count, HIV viral load or clinical stage. Serum 25-hydroxycholecalciferol deficiency was common among antiretroviral treatment-naïve patients, with those of non-white ethnicity at highest risk. CD4 count, HIV viral load and HIV clinical staging do not help to identify those at risk, but low serum calcium should prompt investigation of 25-hydroxycholecalciferol levels.
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Infecções por HIV/diagnóstico , HIV-1 , Deficiência de Vitamina D/epidemiologia , Vitamina D/análogos & derivados , Adolescente , Adulto , Idoso , Contagem de Linfócito CD4 , Feminino , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Humanos , Londres/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Carga Viral , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Adulto JovemRESUMO
BACKGROUND: Here, we aimed to investigate the pharmacokinetics of abacavir and carbovir triphosphate (CBV-TP) with darunavir/ritonavir 900/100 mg once daily or raltegravir 400 mg twice daily. METHODS: HIV-infected subjects on abacavir (600 mg once daily) underwent steady-state pharmacokinetic assessments without and with darunavir/ritonavir or raltegravir. Within-subject changes in plasma and intracellular pharmacokinetic parameters were evaluated by geometric mean ratios (GMRs) and 90% CIs. RESULTS: A total of 19 patients completed the study. With darunavir/ritonavir (versus abacavir alone), abacavir GMRs (90% CI) were 0.73 (0.66, 0.80), 0.62 (0.50, 0.77) and 0.78 (0.69, 0.87) for area under the curve (AUC), trough concentration (C(trough)) and maximum concentration (C(max)), respectively. With raltegravir, they were 1.03 (0.97, 1.10), 0.83 (0.62, 1.11) and 1.06 (0.95, 1.18), respectively. Intracellular CBV-TP GMRs (90% CI) were 0.88 (0.72, 1.07), 0.68 (0.48, 0.95) and 0.98 (0.79, 1.23) for AUC, C(trough) and C(max), respectively, with darunavir/ritonavir, and 0.96 (0.76, 1.20), 0.57 (0.33, 1.00) and 1.07 (0.85, 1.35), respectively, with raltegravir. CONCLUSIONS: There was a 27% decrease in abacavir plasma exposure with darunavir/ritonavir and no changes with raltegravir. CBV-TP C(trough) was significantly decreased with darunavir/ritonavir (32%) and showed a high inter-individual variability with raltegravir.
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Nucleotídeos de Desoxiguanina/farmacocinética , Didesoxinucleosídeos/farmacocinética , Infecções por HIV/tratamento farmacológico , Pirrolidinonas/farmacocinética , Ritonavir/farmacocinética , Sulfonamidas/farmacocinética , Adulto , Fármacos Anti-HIV/sangue , Fármacos Anti-HIV/farmacocinética , Área Sob a Curva , Estudos Cross-Over , Darunavir , Nucleotídeos de Desoxiguanina/sangue , Didesoxinucleosídeos/sangue , Esquema de Medicação , Quimioterapia Combinada , Feminino , Infecções por HIV/sangue , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Pirrolidinonas/sangue , RNA Viral/análise , Raltegravir Potássico , Ritonavir/sangue , Sulfonamidas/sangue , Carga Viral/efeitos dos fármacosRESUMO
OBJECTIVES: To investigate the pharmacokinetics of darunavir/ritonavir and raltegravir, in HIV-infected subjects, in both plasma and at the intracellular (IC) site of action. METHODS: HIV-infected patients on antiretroviral therapy received raltegravir 400 mg twice daily for 21 days (period 1); darunavir/ritonavir 800/100 mg once daily was added for 14 days (period 2), and patients were randomized to continue raltegravir twice daily (group 1) or to switch to 800 mg once daily (group 2), then they all stopped raltegravir intake and continued darunavir/ritonavir once daily for 14 days (period 3). Drug concentrations in plasma and cells (peripheral blood mononuclear cell) were measured, and differences in geometric mean ratios (GMR) and 90% confidence intervals (CI) between period 2 versus period 3 and period 2 versus period 1 were assessed. RESULTS: Twenty-four patients completed the study. Group 1 GMR (90% CI) of darunavir area under the curve (AUC) with and without raltegravir was 1.24 (1.13 to 1.45) for plasma and 1.24 (1.07 to 1.73) for cells and for group 2 was 1.14 (1.07 to 1.24) and 1.03 (0.94 to 1.16). GMR (90% CI) of raltegravir AUC without and with darunavir/ritonavir (plasma and cells) for group 1 was 0.90 (0.73 to 1.44) and 1.02 (0.81 to 1.67) and for group 2 was 1.21 (1.03 to 1.77) and 1.27 (1.07 to 1.94). Geometric mean IC to plasma AUC ratios were 5.3 and 4.9 for darunavir in groups 1 and 2 when darunavir/ritonavir was given alone and 4.9 and 5.6 for raltegravir when given alone. These ratios were not altered by the coadministered drug. CONCLUSIONS: No remarkable interactions between darunavir/ritonavir and raltegravir in plasma or cells were seen. Raltegravir IC concentrations are higher than previously reported; the difference being due to modified cell isolation procedures that reduced drug loss caused by washing.