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INTRODUCTION: Long-acting injectable cabotegravir + rilpivirine (CAB + RPV LAI) was approved for use in virally suppressed adults in the England and Wales national health service in November 2021. We describe a service evaluation of delivery processes and outcomes in 12 clinics. METHODS: Centres populated a database using information from local policies and clinical records. Services were asked to describe approval processes, clinic pathways, and adherence to national guidelines. Additional data were collected on reasons for regimen choice, treatment discontinuations, and management of viraemia. RESULTS: In total, 518 adults from 12 clinics were approved for CAB + RPV LAI between February 2022 and December 2023. Of the 518 people approved for CAB + RPV LAI, 423 received at least one injection. Median duration on CAB + RPV was 7.5 months (interquartile range 3.7-11.3). In total, 97% of injections were administered within the ±7-day window. Virological failure occurred in 0.7%, and 6% discontinued CAB + RPV. CONCLUSION: In this large UK-based cohort, robust approval processes and clinic protocols facilitated on-time injections and low rates of both discontinuation and virological failure.
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OBJECTIVE: Our objectives were to investigate the recent frequency of cerebrospinal fluid (CSF) HIV RNA escape and other CSF viral nucleic acid detection in people with HIV with neurological symptoms and to assess associated clinical factors. METHOD: This was a retrospective cohort analysis of people with HIV who underwent CSF examination for clinical indications between 2017 and 2022. Individuals were identified from pathology records, and clinical data were recorded. CSF HIV RNA escape was defined as CSF HIV RNA concentrations greater than in plasma. CSF viral screen included herpes simplex virus types 1 (HSV-1) and 2 (HSV-2), varicella zoster virus (VZV), Epstein Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6) and JC virus. When cases were detected in five or more people with HIV, associated clinical factors were assessed using linear regression modelling. RESULTS: CSF HIV RNA escape was observed in 19 of 114 individuals (17%) and was associated with the presence of HIV drug resistance mutations and non-integrase strand transfer inhibitor-based antiretroviral therapy (p < 0.05 for all) when compared to people with HIV without escape. Positive viral nucleic acid testing included EBV (n = 10), VZV (3), CMV (2), HHV-6 (2) and JC virus (4). Detectable CSF EBV was not considered related to neurological symptoms and was associated with concomitant CSF infections in eight of ten individuals and with CSF pleocytosis, previous AIDS, lower nadir and current CD4 T-cell count (p < 0.05 for all). CONCLUSION: In people with HIV with neurological symptoms, the frequency of CSF HIV RNA escape remains similar to that in historical reports. Detectable EBV viral nucleic acid in the CSF was observed frequently and, in the absence of clinical manifestations, may be a consequence of CSF pleocytosis.
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Infecções por Citomegalovirus , Infecções por Vírus Epstein-Barr , Infecções por HIV , Infecções por Herpesviridae , Humanos , Infecções por Herpesviridae/líquido cefalorraquidiano , Infecções por Herpesviridae/diagnóstico , Herpesvirus Humano 4/genética , Infecções por Vírus Epstein-Barr/complicações , Estudos Retrospectivos , Leucocitose/complicações , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Herpesvirus Humano 3/genética , Citomegalovirus , RNA , Líquido Cefalorraquidiano , DNA ViralRESUMO
OBJECTIVES: We examined follicle-stimulating hormone (FSH) levels in women living with HIV aged > 45 reporting ≥ 12 months' amenorrhoea, and investigated correlation with menopausal symptoms. METHODS: A cross-sectional substudy of 85 women from the Positive Transitions through the Menopause (PRIME) Study who reported irregular periods at entry into the PRIME Study and ≥ 12 months' amenorrhoea at recruitment into this substudy. Serum FSH was supplemented with clinical data and menopausal symptom assessment. Serum FSH > 30 mIU/mL was defined as consistent with postmenopausal status. Associations between FSH and menopausal symptom severity were assessed using Pearson's correlation and the Kruskal-Wallis test. RESULTS: Median age was 53 years [interquartile range (IQR): 51-55]; all were on antiretroviral therapy, three-quarters (n = 65) had a CD4 T-cell count > 500 cells/µL and 91.8% (n = 78) had an HIV viral load (VL) < 50 copies/mL. Median FSH was 65.9 mIU/mL (IQR: 49.1-78.6). Only four women (4.7%) had FSH ≤ 30 mIU/mL; none reported smoking or drug use, all had CD4 T-cell count ≥ 200 cells/µL, and one had viral load (VL) ≥ 50 copies/mL. Median body mass index (BMI) was elevated compared with women with FSH > 30 mIU/mL (40.8 vs. 30.5 kg/m2 ). Over a quarter (28.2%) reported severe menopausal symptoms, with no correlation between FSH and severity of menopausal symptoms (p = 0.21), or hot flushes (p = 0.37). CONCLUSIONS: Four women in this small substudy had low FSH despite being amenorrhoeic; all had BMI ≥ 35 kg/m2 . We found that 95% of women with HIV aged > 45 years reporting ≥ 12 months' amenorrhoea had elevated FSH, suggesting that menopausal status can be ascertained from menstrual history alone in this group.
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Hormônio Foliculoestimulante , Infecções por HIV , Pré-Escolar , Estudos Transversais , Estradiol , Feminino , Infecções por HIV/epidemiologia , Humanos , Pessoa de Meia-Idade , Pós-MenopausaRESUMO
BACKGROUND: There is currently little evidence exploring menopausal status, age at last menstrual period (LMP) and management of menopause among women living with HIV aged 45-60 years in England. METHODS: Socio-demographic, lifestyle and clinical data were collected through a self-completed cross-sectional survey. Longitudinal CD4 count and viral load data were available from linkage to clinical records, if consent was provided. Women were categorised as pre-, peri- or post-menopausal. Factors associated with menopausal stage were examined using ordinal logistic regression adjusting for age. Age at LMP was estimated using Kaplan-Meier survival analysis. RESULTS: The 847 women had a median age of 49 [interquartile range (IQR): 47-52] years. Most were of black ethnicity (81.3%), were born outside the UK (85.0%) and had completed secondary education (88.7%); 177 (20.4%), 373 (43.0%) and 297 (34.2%) were pre-, peri- or post-menopausal, respectively. After adjusting for age, associations of menopausal status with non-cohabiting relationship [adjusted odds ratio = 0.63 (95% confidence interval: 0.43-0.91)], baseline viral load ≥ 100 000 copies/mL [2.67 (1.20-5.94)] and unemployment [1.34 (0.97-1.84)] remained significant. Median (IQR) age at LMP was 54 (51-55) years in the group. In total, 27.9% (233/836) of women reported severe menopausal symptoms; 45.6% of those with somatic symptoms had heard of hormone replacement therapy and 8.7% had used it. Only 5.6% of women with urogenital symptoms had used topical oestrogen. CONCLUSIONS: Our findings highlight the importance of educating both women and their healthcare providers about menopausal symptoms and management options.
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Infecções por HIV , Estudos Transversais , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Estilo de Vida , Menopausa , Pessoa de Meia-Idade , Reino Unido/epidemiologiaRESUMO
Increasing numbers of women living with HIV are reaching their midlife. We explore the association of HIV status with sexual function (SF) in women aged 45-60 using two national cross-sectional surveys: the third British National Survey of Sexual Attitudes and Lifestyles ("Natsal-3") and "PRIME", a survey of women living with HIV attending HIV clinics across England. Both studies asked the same questions about SF that take account not only sexual difficulties but also the relationship context and overall level of satisfaction, which collectively allowed an overall SF score to be derived. We undertook analyses of sexually-active women aged 45-60 from Natsal-3 (N = 1228, presumed HIV-negative given the low estimated prevalence of HIV in Britain) and PRIME (N = 386 women living with HIV). Women living with HIV were compared to Natsal-3 participants using multivariable logistic regression (adjusting for key confounders identified a priori: ethnicity, ongoing relationship status, depression and number of chronic conditions) and propensity scoring. Relative to Natsal-3 participants, women living with HIV were more likely to: have low overall SF (adjusted odds ratio (AOR) 3.75 [2.15-6.56]), report ≥1 sexual problem(s) lasting ≥3 months (AOR 2.44 [1.49-4.00]), and report almost all 8 sexual problems asked about (AORs all ≥2.30). The association between HIV status and low SF remained statistically significant when using propensity scoring (AOR 2.43 [1.68-3.51]). Among women living with HIV (only), low SF was more common in those who were postmenopausal vs. Premenopausal (55.6% vs. 40.4%). This study suggests a negative association between HIV status and sexual function in women aged 45-60. We recommend routine assessment of SF in women living with HIV.
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Soronegatividade para HIV , Soropositividade para HIV , Menopausa/fisiologia , Disfunções Sexuais Fisiológicas/etiologia , Disfunções Sexuais Psicogênicas/etiologia , Estudos Transversais , Inglaterra/epidemiologia , Feminino , Humanos , Menopausa/psicologia , Pessoa de Meia-Idade , Pós-Menopausa , Pré-Menopausa , Prevalência , Comportamento Sexual/psicologia , Disfunções Sexuais Fisiológicas/epidemiologia , Disfunções Sexuais Psicogênicas/epidemiologia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Randomised placebo-controlled trials have shown that daily oral pre-exposure prophylaxis (PrEP) with tenofovir-emtricitabine reduces the risk of HIV infection. However, this benefit could be counteracted by risk compensation in users of PrEP. We did the PROUD study to assess this effect. METHODS: PROUD is an open-label randomised trial done at 13 sexual health clinics in England. We enrolled HIV-negative gay and other men who have sex with men who had had anal intercourse without a condom in the previous 90 days. Participants were randomly assigned (1:1) to receive daily combined tenofovir disoproxil fumarate (245 mg) and emtricitabine (200 mg) either immediately or after a deferral period of 1 year. Randomisation was done via web-based access to a central computer-generated list with variable block sizes (stratified by clinical site). Follow-up was quarterly. The primary outcomes for the pilot phase were time to accrue 500 participants and retention; secondary outcomes included incident HIV infection during the deferral period, safety, adherence, and risk compensation. The trial is registered with ISRCTN (number ISRCTN94465371) and ClinicalTrials.gov (NCT02065986). FINDINGS: We enrolled 544 participants (275 in the immediate group, 269 in the deferred group) between Nov 29, 2012, and April 30, 2014. Based on early evidence of effectiveness, the trial steering committee recommended on Oct 13, 2014, that all deferred participants be offered PrEP. Follow-up for HIV incidence was complete for 243 (94%) of 259 patient-years in the immediate group versus 222 (90%) of 245 patient-years in the deferred group. Three HIV infections occurred in the immediate group (1·2/100 person-years) versus 20 in the deferred group (9·0/100 person-years) despite 174 prescriptions of post-exposure prophylaxis in the deferred group (relative reduction 86%, 90% CI 64-96, p=0·0001; absolute difference 7·8/100 person-years, 90% CI 4·3-11·3). 13 men (90% CI 9-23) in a similar population would need access to 1 year of PrEP to avert one HIV infection. We recorded no serious adverse drug reactions; 28 adverse events, most commonly nausea, headache, and arthralgia, resulted in interruption of PrEp. We detected no difference in the occurrence of sexually transmitted infections, including rectal gonorrhoea and chlamydia, between groups, despite a suggestion of risk compensation among some PrEP recipients. INTERPRETATION: In this high incidence population, daily tenofovir-emtricitabine conferred even higher protection against HIV than in placebo-controlled trials, refuting concerns that effectiveness would be less in a real-world setting. There was no evidence of an increase in other sexually transmitted infections. Our findings strongly support the addition of PrEP to the standard of prevention for men who have sex with men at risk of HIV infection. FUNDING: MRC Clinical Trials Unit at UCL, Public Health England, and Gilead Sciences.
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Fármacos Anti-HIV/uso terapêutico , Combinação Emtricitabina e Fumarato de Tenofovir Desoproxila/uso terapêutico , Infecções por HIV/prevenção & controle , Profilaxia Pré-Exposição/métodos , Sexo sem Proteção , Adulto , Bissexualidade , Preservativos/estatística & dados numéricos , Inglaterra , Infecções por HIV/virologia , HIV-1 , Homossexualidade Masculina , Humanos , Masculino , Projetos Piloto , Resultado do TratamentoRESUMO
BACKGROUND: Darunavir is considered to have a high genetic barrier to resistance. Most darunavir-associated drug resistance mutations (DRMs) have been identified through correlation of baseline genotype with virological response in clinical trials. However, there is little information on DRMs that are directly selected by darunavir in clinical settings. OBJECTIVES: We examined darunavir DRMs emerging in clinical practice in the UK. PATIENTS AND METHODS: Baseline and post-exposure protease genotypes were compared for individuals in the UK Collaborative HIV Cohort Study who had received darunavir; analyses were stratified for PI history. A selection analysis was used to compare the evolution of subtype B proteases in darunavir recipients and matched PI-naive controls. RESULTS: Of 6918 people who had received darunavir, 386 had resistance tests pre- and post-exposure. Overall, 2.8% (11/386) of these participants developed emergent darunavir DRMs. The prevalence of baseline DRMs was 1.0% (2/198) among PI-naive participants and 13.8% (26/188) among PI-experienced participants. Emergent DRMs developed in 2.0% of the PI-naive group (4 mutations) and 3.7% of the PI-experienced group (12 mutations). Codon 77 was positively selected in the PI-naive darunavir cases, but not in the control group. CONCLUSIONS: Our findings suggest that although emergent darunavir resistance is rare, it may be more common among PI-experienced patients than those who are PI-naive. Further investigation is required to explore whether codon 77 is a novel site involved in darunavir susceptibility.
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Darunavir/uso terapêutico , Farmacorresistência Viral , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Inibidores da Protease de HIV/uso terapêutico , HIV-1/genética , Mutação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , HIV-1/efeitos dos fármacos , HIV-1/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Reino Unido , Adulto JovemRESUMO
BACKGROUND: The pathogenesis and natural history of HIV-associated immune complex kidney disease (HIVICK) is not well understood. Key questions remain unanswered, including the role of HIV infection and replication in disease development and the efficacy of antiretroviral therapy (ART) in the prevention and treatment of disease. METHODS: In this multicentre study, we describe the renal pathology of HIVICK and compare the clinical characteristics of patients with HIVICK with those with IgA nephropathy and HIV-associated nephropathy (HIVAN). Poisson regression models were used to identify risk factors for each of these pathologies. RESULTS: Between 1998 and 2012, 65 patients were diagnosed with HIVICK, 27 with IgA nephropathy and 70 with HIVAN. Black ethnicity and HIV RNA were associated with HIVICK, receipt of ART with IgA nephropathy and black ethnicity and CD4 cell count with HIVAN. HIVICK was associated with lower rates of progression to end-stage kidney disease compared with HIVAN and IgA nephropathy (P < 0.0001). Patients with HIVICK who initiated ART and achieved suppression of HIV RNA experienced improvements in estimated glomerular filtration rate and proteinuria. CONCLUSIONS: These findings suggest a pathogenic role for HIV replication in the development of HIVICK and that ART may improve kidney function in patients who have detectable HIV RNA at the time of HIVICK diagnosis. Our data also suggest that IgA nephropathy should be viewed as a separate entity and not included in the HIVICK spectrum.
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Nefropatia Associada a AIDS/patologia , Glomerulonefrite por IGA/virologia , Falência Renal Crônica/virologia , Nefropatia Associada a AIDS/sangue , Nefropatia Associada a AIDS/imunologia , Nefropatia Associada a AIDS/terapia , Adulto , Contagem de Linfócito CD4 , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Glomerulonefrite por IGA/sangue , Glomerulonefrite por IGA/imunologia , Glomerulonefrite por IGA/terapia , Humanos , Rim/patologia , Rim/fisiopatologia , Falência Renal Crônica/sangue , Falência Renal Crônica/imunologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Proteinúria/sangue , Proteinúria/imunologia , Proteinúria/virologia , RNA Viral/sangue , Fatores de Risco , Resultado do TratamentoRESUMO
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 CSFâ:âplasma 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 SPâ:âplasma 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.
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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 ViralRESUMO
Contemporary antiretroviral therapy (ART) regimens have high barriers to the development of drug resistance. However, resistance to earlier antiretrovirals and uncommon cases of resistance to contemporary ART illustrate the continued need for good clinical management of HIV drug resistance. Here, we describe HIV drug-resistance mechanisms, the interaction of HIV drug-resistant mutations and the patterns of drug resistance to contemporary ART. We then provide guidance on the management of HIV drug resistance, including how to limit the development of resistance and manage virologic failure that is complicated by resistance. To complement this, links to resources and treatment guidelines are provided that can assist with the interpretation of HIV drug resistance test results and optimal ART selection in the clinic.
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Antirretrovirais , Humanos , Antirretrovirais/farmacologia , Antirretrovirais/uso terapêutico , MutaçãoRESUMO
BACKGROUND: Determination of HIV-1 tropism is a pre-requisite to the use of CCR5 antagonists. This study evaluated the potential of population genotypic tropism tests (GTTs) in clinical practice, and the correlation with phenotypic tropism tests (PTTs) in patients accessing routine HIV care. METHODS: Forty-nine consecutive plasma samples for which an original Trofile(TM) assay was performed were obtained from triple-class-experienced patients in need of a therapy change. Viral tropism was defined as the consensus of three or more tropism calls obtained from the combination of two independent population PTT assays (Trofile Biosciences, San Francisco, CA, USA, and Virco, Beerse, Belgium), population GTTs and GTTs based on ultra-deep sequencing. If no consensus was reached, a clonal PTT was performed in order to finalize the tropism call. This two-step approach allowed the definition of a reference tropism call. RESULTS: According to the reference tropism result, 35/49 samples were CCR5 tropic (R5) (patients eligible for maraviroc treatment) and 14/49 were assigned as non-R5 tropic. The non-R5 samples [patients not eligible for maraviroc treatment according to the FDA/European Medicines Agency (EMEA) label] group included both the CXCR4 (X4) samples and the dual and mixed CCR5/CXCR4 (R5/X4) samples. Compared with Trofile(TM) population PTTs, population GTTs showed a higher sensitivity (97%) and a higher negative predictive value (91%), but almost equal specificity and an equal positive predictive value. CONCLUSIONS: In line with recent reports from clinical trial data, our data support the use of population genotypic tropism testing as a tool for tropism determination before the start of maraviroc.
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Cicloexanos/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , HIV-1/genética , Triazóis/uso terapêutico , Tropismo Viral , Genótipo , Infecções por HIV/metabolismo , HIV-1/fisiologia , Humanos , Maraviroc , Fenótipo , Receptores CCR5/metabolismo , Receptores CXCR4/metabolismoRESUMO
BACKGROUND AND OBJECTIVES: Guidelines indicate a plasma HIV-1 RNA load of 500-1000 copies/mL as the minimal threshold for antiretroviral drug resistance testing. Resistance testing at lower viral load levels may be useful to guide timely treatment switches, although data on the clinical utility of this remain limited. We report here the influence of viral load levels on the probability of detecting drug resistance mutations (DRMs) and other mutations by routine genotypic testing in a large multicentre European cohort, with a focus on tests performed at a viral load <1000 copies/mL. METHODS: A total of 16â511 HIV-1 reverse transcriptase and protease sequences from 11â492 treatment-experienced patients were identified, and linked to clinical data on viral load, CD4 T cell counts and antiretroviral treatment history. Test results from 3162 treatment-naive patients served as controls. Multivariable analysis was employed to identify predictors of reverse transcriptase and protease DRMs. RESULTS: Overall, 2500/16â511 (15.14%) test results were obtained at a viral load <1000 copies/mL. Individuals with viral load levels of 1000-10000 copies/mL showed the highest probability of drug resistance to any drug class. Independently from other measurable confounders, treatment-experienced patients showed a trend for DRMs and other mutations to decrease at viral load levels <500 copies/mL. CONCLUSIONS: Genotypic testing at low viral load may identify emerging antiretroviral drug resistance at an early stage, and thus might be successfully employed in guiding prompt management strategies that may reduce the accumulation of resistance and cross-resistance, viral adaptive changes, and larger viral load increases.
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Farmacorresistência Viral , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Mutação de Sentido Incorreto , RNA Viral/genética , Carga Viral , Proteínas Virais/genética , Adulto , Fármacos Anti-HIV/administração & dosagem , Contagem de Linfócito CD4 , Estudos de Coortes , Europa (Continente) , Feminino , Genótipo , Infecções por HIV/tratamento farmacológico , HIV-1/isolamento & purificação , Humanos , Masculino , RNA Viral/isolamento & purificaçãoRESUMO
This study characterized the prevalence and patterns of antiretroviral-drug-resistance mutations according to plasma human immunodeficiency virus type 1 (HIV-1) RNA load in a large population of patients with HIV-1 infection who underwent testing for resistance mutations in routine clinical practice. HIV-1 genotypic resistance test results with linked clinical data were obtained from national resistance and clinical databases in the United Kingdom. Among 7861 tests, detection of > or =1 resistance mutation was most frequent at viral loads of 300-10,000 copies/mL and decreased statistically significantly at viral loads of >10,000 copies/mL. Major resistance mutations were commonly detected in the subset of tests that were performed among patients with viral loads of <1000 copies/mL (1001 [12.7%] of 7861 tests). We conclude that HIV-1 genotypic resistance testing is informative for patients with low viral loads.
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Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Viremia/tratamento farmacológico , Adulto , Fármacos Anti-HIV/farmacologia , Estudos de Coortes , Farmacorresistência Viral , Feminino , Genótipo , HIV-1/genética , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Risco , Reino Unido/epidemiologia , Carga Viral/efeitos dos fármacos , Viremia/virologiaRESUMO
Contact tracing is central to the public health response to COVID-19, but the approach taken has received criticism for failing to make enough of an impact on disease transmission. We discuss what can be learned from contact tracing in other infections, and how the natural history of COVID-19 should shape the strategies used.
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COVID-19 , Busca de Comunicante , Saúde Pública , Humanos , SARS-CoV-2RESUMO
BACKGROUND AND OBJECTIVE: Integrase strand transfer inhibitors (INSTIs) have become the preferred first-line antiretroviral therapy in adults. There is paucity of published data on their use in children outside of clinical trials, particularly long-term safety and tolerability. This study aimed to describe INSTI use including the number of, and reasons for INSTI discontinuation. METHODS: We conducted a retrospective cohort analysis by database and electronic record review of children aged under 18 years with perinatally acquired human immunodeficiency virus who started INSTI-based antiretroviral therapy between May 2009 and March 2018, in a single tertiary centre. RESULTS: Fifty-six INSTI-based regimens were prescribed in 54 children, 64.9% from 2015 onwards. Twenty-one of 56 (37.5%) regimens commenced with raltegravir, 29 (51.8%) with dolutegravir and six (10.7%) with elvitegravir. The median age at the start of treatment was 15 years (interquartile range 13.5-16.4) with a median duration of INSTI-antiretroviral therapy of 1.65 years (range 0.01-8.8). Twenty-four children had a detectable viral load at the start INSTI therapy; 20 (83%) achieving viral suppression in a median of 26 days (interquartile range 19.5-34.5). There were 26 discontinuations of INSTI-based antiretroviral therapy after a median of 183 days; 9/26 because of adverse events. Four of nine adverse events were attributed to INSTI use, all in patients taking dolutegravir and the adverse events were neuropsychiatric and gastrointestinal in nature. CONCLUSIONS: INSTI-based regimens were generally efficacious and well tolerated in this paediatric cohort, with 4/26 discontinuations due to INSTI-attributed adverse events. Further post-marketing surveillance of INSTI use in children is warranted.
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Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Quinolonas/administração & dosagem , Raltegravir Potássico/administração & dosagem , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Masculino , Oxazinas , Piperazinas , Piridonas , Raltegravir Potássico/uso terapêutico , Estudos Retrospectivos , Carga Viral/efeitos dos fármacosRESUMO
To understand the pathogenesis of low level viraemia (LLV) in HIV-infected patients on boosted protease inhibitors (PI/b), we enrolled 34 subjects with a median HIV-RNA 79 copies/mL and followed them for 15 months. Samples for next generation sequencing were collected at three time-points. Two showed resistance-associated mutations (RAMs) in the protease gene, while 95-100% had RAMs in the gag gene, which evolved in approximately a quarter of subjects, suggesting a potential clinical role of these kind of mutations.
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Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , HIV-1/genética , Viremia/tratamento farmacológico , Adulto , Terapia Antirretroviral de Alta Atividade , Farmacorresistência Viral Múltipla/genética , Feminino , Protease de HIV/genética , HIV-1/efeitos dos fármacos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Reino Unido , Carga Viral , Produtos do Gene gag do Vírus da Imunodeficiência Humana/genéticaRESUMO
Following changes in national antiretroviral therapy (ART) guidelines removing the CD4 threshold for initiation of ART, we evaluated the time to ART initiation and reasons for delayed or non-initiation. A retrospective notes review of 292 newly diagnosed HIV-positive individuals attending two London clinics between August 2015 and December 2016 was performed. Two hundred and fifty-four of 292 (87%) individuals started ART. Median time to ART initiation was 29 days (range: 0-514). Thirty of 292 (13%) did not start ART. Rates of virological suppression at six months were similar regardless of time to ART initiation. People who inject drugs (16.7% vs. 3.6%) (p = 0.009), having a higher median baseline CD4 cell count (500 vs. 388 cells/mm3, p = 0.001), and having gastrointestinal/liver co-morbidities (23% vs. 9%, p = 0.001) were associated with delayed ART initiation. The cohort not on ART had a higher median baseline CD4 cell count (500 vs. 388 cells/mm3, p < 0.001). Documented reasons for delayed or ART non-initiation included patient's choice, prolonged adjustment periods, and difficulty leaving work. We conclude that delayed or non-initiation of ART was associated with injecting drug use and prolonged adjustment to a new HIV diagnosis. Clinician factors may include lack of urgency with higher baseline CD4 cell counts. Improved linkage to care and drug services pathways may encourage timely ART initiation.