RESUMO
OBJECTIVES: Gender-related factors can influence management decisions, treatment outcomes and the overall long-term wellbeing of people living with HIV (PLWH). The Women Against Viruses in Europe (WAVE) Working Group was established to promote the health and wellbeing of women living with HIV (WLWH). WAVE is part of the European AIDS Clinical Society (EACS) and organizes annual workshops to discuss different issues in the management of WLWH. METHODS: In 2016, 34 WAVE members including community representatives, HIV clinicians and researchers met to discuss standards of care for WLWH and to review current guidelines. Participants focused on three different themes: (1) access to and engagement and retention in care; (2) monitoring of women on antiretroviral therapy and management of comorbidities; and (3) review of EACS treatment guidelines. RESULTS: Five priority areas for optimizing the care of WLWH were identified: (1) psychosocial aspects of HIV diagnosis and care; (2) mental health and wellbeing; (3) pharmacokinetics, toxicity and tolerability of antiretroviral therapy; (4) coinfections and comorbidities; and (5) sexual and reproductive health. WAVE recommendations are provided for each of these areas, and gaps in knowledge and needs for changes in currently existing standards are discussed. CONCLUSIONS: This position statement provides an overview of the key recommendations to optimize the care of WLWH that emerged during the 2016 WAVE workshop.
Assuntos
Gerenciamento Clínico , Infecções por HIV/diagnóstico por imagem , Infecções por HIV/tratamento farmacológico , Padrão de Cuidado , Monitoramento de Medicamentos , Europa (Continente) , Feminino , Acessibilidade aos Serviços de Saúde , Humanos , Saúde Mental , Saúde Reprodutiva , Resultado do TratamentoRESUMO
OBJECTIVES: Five to eight per cent of HIV-positive individuals initiating abacavir (ABC) experience potentially fatal hypersensitivity reactions (HSRs). We sought to describe the proportion of individuals initiating ABC and to describe the incidence and factors associated with HSR among those prescribed ABC. METHODS: We calculated the proportion of EuroSIDA individuals receiving ABC-based combination antiretroviral therapy (cART) among those receiving cART after 1 January 2009. Poisson regression was used to identify demographic, and current clinical and laboratory factors associated with ABC utilization and discontinuation. RESULTS: Between 2009 and 2016, of 10 076 individuals receiving cART, 3472 (34%) had ever received ABC-based cART. Temporal trends of ABC utilization were also heterogeneous, with 28% using ABC in 2009, dropping to 26% in 2010 and increasing to 31% in 2016, and varied across regions and over time. Poisson models showed lower ABC utilization in older individuals, and in those with higher CD4 cell counts, higher cART lines, and prior AIDS. Higher ABC utilization was associated with higher HIV RNA and poor renal function, and was more common in Central-East and Eastern Europe and lowest during 2014. During 779 person-years of follow-up (PYFU) in 2139 individuals starting ABC after 1 January 2009, 113 discontinued ABC within 6 weeks of initiation for any reason [incidence rate (IR) 14.5 (95% confidence interval (CI) 12.1, 17.5) per 100 PYFU], 13 because of reported HSR [IR 0.3 (95% CI 0.1, 1.0) per 100 PYFU] and 35 because of reported HSR/any toxicity [IR 4.5 (95% CI 3.2, 6.3) per 100 PYFU]. There were no factors significantly associated with ABC discontinuation because of reported HSR/any toxicity. CONCLUSIONS: ABC remains commonly used across Europe and the incidence of discontinuation because of reported HSR was low in our study population.
Assuntos
Fármacos Anti-HIV/efeitos adversos , Didesoxinucleosídeos/efeitos adversos , Hipersensibilidade a Drogas/epidemiologia , Infecções por HIV/tratamento farmacológico , Adulto , Estudos de Coortes , Hipersensibilidade a Drogas/etiologia , Uso de Medicamentos , Europa (Continente)/epidemiologia , Feminino , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Distribuição de PoissonRESUMO
Infection with hepatitis B virus (HBV) can result in spontaneous resolution or chronic infection, which can remain asymptomatic or can progress to cirrhosis and/or hepatocellular carcinoma. The host immune response is thought to be a major determinant of the outcome of HBV infection and virus-specific cytotoxic T lymphocytes (CTL) can mediate immunity against the virus and cause liver pathology. Antigen-nonspecific innate lymphocytes may also contribute to HBV infection and liver disease, therefore, we examined the frequencies, phenotypes, cytolytic activities and cytokine profiles of circulating natural killer (NK) cells, CD1d-restricted invariant natural killer T (iNKT) cells and CD56(+) T cells in 102 asymptomatic HBV-infected patients and compared them with those in 66 uninfected control subjects. NK cells expressing low levels of CD56 (CD56(dim)) and CD56(+) T cells were significantly expanded in the circulation of HBV-infected patients compared with control subjects. CD1d expression and iNKT cell frequencies were similar in both groups. Despite these expansions, we did not detect augmented natural or cytokine-induced cytotoxicity in the HBV-infected subjects. All lymphocyte populations studied produced interferon-γ (IFN-γ) significantly more frequently when taken from HBV-infected patients compared with when taken from healthy controls. Additionally, NK cells from the patients more frequently produced interleukin-10. As our HBV-infected cohort consisted of asymptomatic patients with low viral loads, we propose that CD56(dim) NK cells and CD56(+) T cells control HBV infection by noncytolytic mechanisms.
Assuntos
Antígenos E da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Hepatite B/imunologia , Hepatite B/virologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/metabolismo , Adolescente , Adulto , Antígenos CD1d/genética , Antígenos CD1d/metabolismo , Doenças Assintomáticas , Antígeno CD56/metabolismo , Estudos de Casos e Controles , Citotoxicidade Imunológica , Etnicidade , Feminino , Expressão Gênica , Hepatite B/genética , Hepatite B/metabolismo , Humanos , Interferon gama/biossíntese , Interferon gama/genética , Interleucina-10/biossíntese , Interleucina-10/genética , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Células T Matadoras Naturais/imunologia , Células T Matadoras Naturais/metabolismo , Adulto JovemRESUMO
OBJECTIVES: Syphilis recognition in HIV-positive patients has important implications. Initial data from this study, established in June 2012 to better understand the natural history of syphilis and treatment response, examine the characteristics of patients including sexual behaviour, rates of concurrent sexually transmitted infections (STI) and type of treatment given. METHODS: Patients were recruited from Ireland, Poland and Germany. Data gathered included demographics, method of syphilis acquisition, stage of syphilis infection, HIV status, nadir and current CD4 counts and HIV viral suppression rates. Data were then subanalysed into HIV-positive and HIV-negative groups. RESULTS: Of 175 patients recruited, 68% were HIV-positive and 86.3% were men who have sex with men. Most HIV-positive patients presented with secondary syphilis (55.7% vs 13.2%) (p=0.0001) while the majority of HIV-negative patients had primary syphilis noted at the time of recruitment (47.2% vs18.9%, p=0.0002). Approximately half of all patients had a HIV RNA viral load <40 copies/mL (55%). Previous syphilis infection occurred more frequently in HIV-positive than HIV-negative patients (p=0.0001). Concurrent STIs at the time of syphilis diagnosis were found in 26.8%, of whom 31 (25.4%) were HIV-positive (p=0.64). HIV-positive patients received doxycycline more frequently than their HIV-negative counterparts (33.6% vs 1.9%, p=0.0001) while HIV-negative patients were treated with long-acting penicillin in 88.7% of cases vs 58% of HIV-positive patients (p=0.0002). CONCLUSIONS: A 40% rate of unsuppressed viraemia, high levels of STIs and varying treatment regimens represent a public health risk for Europe, suggesting the model of sexual healthcare delivery in HIV-positive patients requires further evaluation.
Assuntos
Atenção à Saúde/estatística & dados numéricos , Soropositividade para HIV/epidemiologia , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Comportamento Sexual/estatística & dados numéricos , Sífilis/epidemiologia , Contagem de Linfócito CD4 , Feminino , Alemanha/epidemiologia , Soropositividade para HIV/imunologia , Humanos , Irlanda/epidemiologia , Masculino , Polônia/epidemiologia , Estudos Prospectivos , Parceiros Sexuais , Sífilis/imunologia , Carga ViralRESUMO
This study describes the demographics and treatment status of HIV-infected adults accessing ambulatory care in the Republic of Ireland and estimates diagnosed HIV prevalence rates. 3254 HIV-infected adults attended 1 of the 6 specialist HIV centres in the 12- month period 1st July 2009 to 30th June 2010. 2023/3254 (62%) were male, 1761/3133 (56%) Irish and 1048/3133 (34%) African. 1924/3098 (62%) resided in the Dublin area. The mean age was 39.8 years (SD 9.3); probable route of acquisition was available for 2898/3254 (89%); heterosexual acquisition accounted for 1442 (50%), MSM 777 (27%) and IDU 598 (21%). 2574/3202 (80%) were on highly active antiretroviral therapy (HAART). Of these 87% had HIV-RNA levels < 50cpm and 94% < 500cpm. The HIV diagnosed prevalence rate is estimated at 1.09/1000 nationally and at 2.25/1000 in the Dublin area for 15-59 year olds.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Infecções por HIV , Adulto , Assistência Ambulatorial/métodos , Assistência Ambulatorial/estatística & dados numéricos , Terapia Antirretroviral de Alta Atividade/métodos , Terapia Antirretroviral de Alta Atividade/estatística & dados numéricos , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/terapia , Humanos , Irlanda/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de RiscoRESUMO
A recent U.S. survey demonstrated wide variation in the management of syphilis. 25/31 (73.5%) Consultants and Specialist Registrars in Infectious Diseases and Genitourinary Medicine, in Ireland were surveyed. 23 (92%) treat more than 50 HIV patients a year, 18 (72%) had been consulted on a patient with syphilis in the last year. With secondary syphilis, 13 (52%) give 3 doses of benzathine penicillin, while 10 (40%) give one, no statistical difference between consultants and SpRs (p = 0.9). Significant variation in the investigation and management of syphilis in Ireland was identified. There is a need for the development of Irish national guidelines on the management of syphilis.
Assuntos
Padrões de Prática Médica , Sífilis/tratamento farmacológico , Coleta de Dados , Ginecologia , Infecções por HIV/complicações , Humanos , Infectologia , Irlanda , Guias de Prática Clínica como Assunto , Sífilis/complicações , Sífilis/diagnóstico , UrologiaRESUMO
OBJECTIVE: To assess efficacy, adherence and tolerability of once daily antiretroviral therapy containing tenofovir disoproxil fumarate (DF) 300 mg in HIV-1-infected former injecting drug users receiving opiate treatment (IVDU). METHODS: European, 48-week, open-label, single-arm, multicenter study. Patients were either antiretroviral therapy-naive, restarting therapy after treatment discontinuation without prior virological failure or switching from existing stable treatment. RESULTS: Sixty-seven patients were enrolled in the study and 41 patients completed treatment. In the primary analysis (intent-to-treat missing=failure) at week 48, 34% of patients (23/67; 95% CI: 23%-47%) had plasma HIV-1 RNA <50 copies/mL. Using an intent-to-treat missing=excluded approach, the week 48 proportion of patients with plasma HIV-1 RNA <50 copies/mL increased to 56% (23/41; 95% CI: 40%-72%). Mean (standard deviation) increase from baseline in CD4+ cell count at week 48 was 176 (242) cells/mm(3). Although self-reported adherence appeared high, there were high levels of missing data and adherence results should be treated with caution. No new safety issues were identified. CONCLUSIONS: Levels of missing data were high in this difficult-to-treat population, but potent antiretroviral suppression was achieved in a substantial proportion of HIV-infected IVDU-patients.
Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Adesão à Medicação , Metadona/uso terapêutico , Organofosfonatos/uso terapêutico , Abuso de Substâncias por Via Intravenosa/tratamento farmacológico , Adenina/uso terapêutico , Adulto , Analgésicos Opioides/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Feminino , Seguimentos , Infecções por HIV/virologia , HIV-1/genética , HIV-1/patogenicidade , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Taxa de Sobrevida , Tenofovir , Resultado do Tratamento , Carga Viral , Adulto JovemRESUMO
With highly active antiretroviral therapy (HAART), AIDS-defining malignancies are becoming less common. The outcomes with standard chemotherapy are improving. In the last 10 years there have been significant changes in our patient demographics due to immigration. The aim of this study was to review the demographics and outcomes of patients with cancer in the post-HAART era and to assess the impact of changing demographics and HAART through comparing them with previously published pre-HAART data from the same centre. A retrospective chart review of 42 patients diagnosed with malignancy from 2000 to 2007 was performed and compared with pre-HAART (1987-1994) data. The incidence of malignancies has decreased from 5.2% to 2.4%. The incidence of Kaposi's sarcoma and primary cerebral lymphoma has decreased. Non-Hodgkin's lymphoma incidence has remained stable, but survival has improved with 44% of patients achieving remission. Non-AIDS-defining malignancies have increased and were associated with longer duration of HIV infection. The change in patient demographics did not have an impact on the type of malignancies diagnosed. Overall the incidence of malignancy has decreased; however, the increase in non-AIDS-defining malignancies highlights the importance of early diagnosis, use of HAART and prospective surveillance.
Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Neoplasias/epidemiologia , Adulto , Feminino , Humanos , Incidência , Irlanda/epidemiologia , Masculino , Estudos Retrospectivos , População UrbanaRESUMO
INTRODUCTION: CD8 encephalitis is a relatively recently described condition in the setting of HIV infection. It is becoming increasingly recognised in recent years though is still likely underdiagnosed. METHODS: We present three cases of encephalitis in HIV-positive black African females initially presenting with neurological pathology. Two cases concern recent presentations of patients attending HIV services at a large tertiary referral hospital and the third case involves a retrospective analysis of an archived case. RESULTS AND DISCUSSION: MRI brain demonstrated periventricular white matter changes in 2 cases and a cerebellar lesion in the third case. CSF examination revealed lymphocytosis and elevated protein levels. CSF HIV viral load analysis showed viral escape along with new antiretroviral drug resistance mutations. CSF flow cytometry studies demonstrated a reversed CD4:CD8 ratio with a high CD8+ cells percentage. All patients had EBV DNA detected in their CSF. Brain biopsy in two patients confirmed CD8 encephalitis and also revealed isolated cells demonstrating EBV positivity by in-situ hybridization using EBER (Epstein-Barr virus-encoded small RNAs). Treatment with steroids and ART optimisation led to significant clinical and radiological improvements in all cases. DISCUSSION: CD8 encephalitis should be considered as a cause of neurological symptoms and confusion in the HIV-positive patient, particularly if poor ART adherence or viral resistance are suspected. Brain biopsy should be considered in HIV-positive patients with encephalopathy of uncertain cause. Early treatment with high-dose corticosteroids when suspecting this diagnosis is essential for a favourable outcome. The prognosis is variable but can be favourable even following severe encephalopathy. The presence of new INSTI mutations in the CSF but absent peripherally in two INSTI-era patients is a novel finding for this case series in the context of CD8 encephalitis. The role played by EBV in this disease remains unclear and warrants further investigation.
RESUMO
The objective of the study was to evaluate the role of rapid virological response (RVR) in predicting sustained virological response (SVR) rates to hepatitis C virus (HCV) therapy. 65 HIV / HCV co-infected patients commenced HCV treatment per protocol. HIV / HCV patients with a mean CD4 count of 502 were treated for 24-48 weeks depending on genotype. Virological response was assessed at weeks 4 (RVR), 12 [early virological response (EVR)], 24, at end of treatment (EOTR) and 24 weeks post-completion of treatment (SVR). Primary end-point was defined as undetectable HCV RNA at 24 weeks post-treatment completion. Fifty-five per cent of co-infected patients were on highly active anti-retroviral therapy. A majority of patient group were male. 60% of HIV / HCV patients achieved SVR (35% genotype 1 / 4; 77% genotype 2 / 3). 24 HIV / HCV patients achieved undetectable HCV levels compared with baseline by week 4. The positive predictive value (PPV) of RVR at week 4 for subsequent SVR in HIV-HCV co-infected patients was 100%; the negative predictive value (NPV) was 57%. Significant variables associated with SVR were: (i) lower median pre-treatment HCV viral load, (ii) genotype 2 / 3 disease and (iii) achievement of RVR. Independent variables associated with RVR were low pre-treatment HCV viral load and genotype 2 / 3 disease. Achievement of RVR, a negative HCV-PCR, at week 4 of treatment is predictive of SVR in this cohort of patients. This may be used to guide optimal treatment duration in patient groups. More significantly, the data serve to highlight the subgroup of patients who, on achieving RVR, should be actively supported to complete HCV treatment with full dose therapy, especially patients co-infected with G2 / 3 disease for whom 6 months' full dose therapy may be sufficient to obtain a SVR.
Assuntos
Antivirais/uso terapêutico , Infecções por HIV/complicações , Hepacivirus/genética , Hepatite C/complicações , Interferon-alfa/uso terapêutico , Ribavirina/uso terapêutico , Viremia , Adulto , Feminino , Genótipo , Hepacivirus/efeitos dos fármacos , Humanos , Interferon alfa-2 , Masculino , Polietilenoglicóis/uso terapêutico , RNA Viral/sangue , Proteínas Recombinantes , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Women attending sexual health services may be higher risk for cervical cancer than the general population. In the United Kingdom, where a national cervical screening programme is underway, sexual health clinics no longer routinely offer their attendees cervical smears. Abnormal cervical smears add considerably to the workload of a sexual health service. In the absence of an organised national cervical screening programme in Ireland opportunistic screening is heavily relied upon. Opportunistic screening is performed in primary care, sexual health services and other women's health services. In the absence of this opportunistic cervical screening treatable pre-cancerous lesions may go unrecognised.
Assuntos
Instituições de Assistência Ambulatorial , Programas de Rastreamento/métodos , Infecções Sexualmente Transmissíveis/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , Serviços de Saúde da Mulher , Adolescente , Adulto , Feminino , Humanos , Irlanda/epidemiologia , Pessoa de Meia-Idade , Atenção Primária à Saúde/métodos , Estudos Retrospectivos , Fatores de Risco , Esfregaço VaginalRESUMO
Management of HIV-1 in pregnancy has reduced the mother-to-child-transmission (MTCT) rate from 25-30% to <2% in the developed world, including Ireland. In Ireland most HIV positive pregnant women are diagnosed through antenatal screening many of whom arrive here late in pregnancy. Geographic dispersal and subsequent involvement of obstetric units throughout the country has resulted in a need for clear, accessible management guidelines. The Irish Infection Society first published guidelines for the management of HIV-1 in pregnancy in 2001 (1). The updated guidelines became operational in January 2002 with some amendments in March 2003 and July 2004. These guidelines offer a broad management outline for HIV positive pregnant women. Ultimately, each woman is assessed individually by a multidisciplinary team and a careful plan is determined.
Assuntos
Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/transmissão , HIV-1 , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez/tratamento farmacológico , Feminino , Infecções por HIV/prevenção & controle , Humanos , Recém-Nascido , Irlanda , Guias de Prática Clínica como Assunto , GravidezRESUMO
BACKGROUND: HIV-positive substance dependent patients contribute disproportionally to HIV morbidity and mortality as a result of poor compliance with their HIV treatment. For HIV-positive opiate-dependent patients integrating HIV and addiction care improves HIV morbidity but the effect on addiction morbidity is not known. AIMS: This study aims to establish if integrating HIV and addiction care has a significant effect on addiction and HIV morbidity for non-engaging HIV-positive opiate-dependent patients. METHODS: Patients attending the National Drug Treatment Centre who had disengaged from their HIV treatment in St James's Hospital were recruited to receive HIV care integrated into their methadone maintenance programme. Outcome was investigated in terms of urine toxicology (opiates, cocaine, cannabis and amphetamines); adherence to methadone; proportion receiving directly observed antiretroviral therapy; proportion HIV virally suppressed; and the CD4 cell count. RESULTS: No significant change in substance use or methadone adherence was demonstrated in the 19 recruited participants. There was a significant increase in the proportion receiving directly observed antiretroviral therapy, and in the CD4 cell count. CONCLUSION: Integration of HIV and addiction care optimises the physical health of non-engaging HIV-positive opiate-dependent patients with no substantial effect on their methadone maintenance programme.
Assuntos
Infecções por HIV/tratamento farmacológico , Metadona/uso terapêutico , Tratamento de Substituição de Opiáceos/métodos , Transtornos Relacionados ao Uso de Substâncias/terapia , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: The 2NN Study was a randomised comparison of the non-nucleoside reverse-transcriptase inhibitors (NNRTI) nevirapine and efavirenz. METHODS: In this multicentre, open-label, randomised trial, 1216 antiretroviral-therapy-naive patients were assigned nevirapine 400 mg once daily, nevirapine 200 mg twice daily, efavirenz 600 mg once daily, or nevirapine (400 mg) and efavirenz (800 mg) once daily, plus stavudine and lamivudine, for 48 weeks. The primary endpoint was the proportion of patients with treatment failure (less than 1 log(10) decline in plasma HIV-1 RNA in the first 12 weeks or two consecutive measurements of more than 50 copies per mL from week 24 onwards, disease progression [new Centers for Disease Control and Prevention grade C event or death], or change of allocated treatment). Analyses were by intention to treat. FINDINGS: Treatment failure occurred in 96 (43.6%) of 220 patients assigned nevirapine once daily, 169 (43.7%) of 387 assigned nevirapine twice daily, 151 (37.8%) of 400 assigned efavirenz, and 111 (53.1%) of 209 assigned nevirapine plus efavirenz. The difference between nevirapine twice daily and efavirenz was 5.9% (95% CI -0.9 to 12.8). There were no significant differences among the study groups in the proportions with plasma HIV-1 RNA concentrations below 50 copies per mL at week 48 (p=0.193) or the increases in CD4-positive cells (p=0.800). Nevirapine plus efavirenz was associated with the highest frequency of clinical adverse events, and nevirapine once daily with significantly more hepatobiliary laboratory toxicities than efavirenz. Of 25 observed deaths, two were attributed to nevirapine. INTERPRETATION: Antiretroviral therapy with nevirapine or efavirenz showed similar efficacy, so triple-drug regimens with either NNRTI are valid for first-line treatment. There are, however, differences in safety profiles. Combination of nevirapine and efavirenz did not improve efficacy but caused more adverse events.
Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/tratamento farmacológico , HIV-1 , Nevirapina/administração & dosagem , Oxazinas/administração & dosagem , Inibidores da Transcriptase Reversa/administração & dosagem , Adulto , Alcinos , Fármacos Anti-HIV/efeitos adversos , Benzoxazinas , Ciclopropanos , Esquema de Medicação , Quimioterapia Combinada , Feminino , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Humanos , Masculino , Nevirapina/efeitos adversos , Oxazinas/efeitos adversos , RNA Viral/sangue , Inibidores da Transcriptase Reversa/efeitos adversos , Falha de TratamentoRESUMO
Neisseria gonorrhoeae cases are increasing in Ireland. Ciprofloxacin is often used as first line treatment for this infection in STI clinics. A retrospective study to analyze resistance in two Dublin clinics was undertaken. Cases were defined as patients from whom an isolate of N. gonorrhoea was recovered. All cases from two clinics between January 1997 and June 2003 were included. Antimicrobial resistance data was correlated with sex and sexuality. One thousand one hundred and eighty laboratory-confirmed cases were identified. Eighty seven percent were male. Sixty nine percent were MSM. Twenty seven percent of isolates demonstrated reduced susceptibility to penicillin and 6% to ciprofloxacin. Isolates with reduced susceptibility to ciprofloxacin increased year on year from 3.8% in 1997 to 15% in 2003. Prevalence of isolates of N. gonorrhoea with reduced susceptibility to ciprofloxacin has exceeded 10% in these clinics since 2002. In concordance with international guidelines, ceftriaxone became the treatment of choice for gonorrhoea in July 2003.
Assuntos
Anti-Infecciosos/uso terapêutico , Ciprofloxacina/uso terapêutico , Farmacorresistência Bacteriana , Gonorreia/tratamento farmacológico , Instituições de Assistência Ambulatorial , Feminino , Gonorreia/epidemiologia , Homossexualidade Masculina/estatística & dados numéricos , Humanos , Irlanda/epidemiologia , Masculino , Neisseria gonorrhoeae , Estudos RetrospectivosRESUMO
Increased research-based imaging has led to an increase in clinically significant extra-cardiac findings. HIV patients are at increased risk of having polypathology at a younger age; therefore, it may be hypothesised that they would have more incidental findings on imaging. We reviewed the magnetic resonance imaging results of 169 HIV-positive and 40 HIV-negative, clinically well volunteers undergoing cardiac magnetic resonance imaging scanning to assess the prevalence of subclinical cardiac pathology. This sub-study assessed the prevalence of clinically significant extra-cardiac findings. Associated risk factors were assessed and clinical follow-up and outcome were ascertained. Of the HIV-positive study group, 12/169 (7.1%) vs. 1/40 (2.5%) control patients had a clinically significant extra-cardiac finding which warranted further radiological or clinical intervention (p = 0.28). A total of three out of 169 (1.1%) were highly clinically significant findings. On logistic regression analysis, age was the only significant contributing factor (p = 0.049); no HIV-associated factors were found to be significant. The prevalence of clinically significant extra-cardiac findings of 7.1% in this HIV-positive cohort is comparable to the prevalence found in previous studies carried out on an older, sicker general population. This highlights the need for planning for unexpected outcomes and also the high rate of clinically significant findings in a seemingly well HIV-positive population.
Assuntos
Infecções por HIV/complicações , Coração/fisiopatologia , Imagem Cinética por Ressonância Magnética/estatística & dados numéricos , Adulto , Antirretrovirais/uso terapêutico , Estudos de Casos e Controles , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Achados Incidentais , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Análise de Regressão , Fatores de Risco , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To analyse the pattern of survival for patients diagnosed with AIDS in Dublin. METHODS: Data on 193 patients visiting the Department of Genitourinary Medicine of a Dublin Hospital, over a period of 7 years with AIDS, were analysed, and survival patterns were investigated. RESULTS: The cumulative probability of survival for the cohort was 69.0 +/- 3.3% at 1 year and 6.5 +/- 2.5% at 5 years. Median survival was 576 days. Year of diagnosis and disease group to which the patient belonged at diagnosis had a significant influence on the survival of the cohort (P < 0.0006 and P < 0.02, respectively). Age group, disease group, and year of diagnosis showed significant differences between strata (P < 0.01, P < 0.002, and P < 0.04, respectively). Patients aged 35-39 years showed longer median survival times (715 days) than all other age groups (median survival = 547 days; P < 0.04). Patients whose disease group at diagnosis was opportunistic disease(s) alone (Centers for Disease Control 1987 criteria, stage IV group C1) had a significantly longer median survival (672 days) than all others (median survival 281 days; P < 0.0002). Survival did not differ significantly by sex or risk group alone, nor did it differ significantly by manifestation of disease when grouped according to recognised criteria. Treatment with antiretroviral therapy had a significant influence on the survival of the cohort (P < 0.0002), and the treatment group showed a significant difference between strata (P < 0.0002). This result must be qualified by the fact that, first, 11 of the 26 patients not receiving therapy died within 1 month of diagnosis and people who survived longer had a greater chance of beginning treatment, and that, secondly, criteria for antiretroviral therapy allocation were not entirely clear. CONCLUSIONS: The overall survival time found by this study is comparable to that found in other studies in developed countries of the survival of persons with AIDS. Patterns of survival for age groups and manifestation of disease show some contrasting features, mainly owing to the demographic profile of the patients and the high proportion of intravenous drug users.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Síndrome da Imunodeficiência Adquirida/mortalidade , Tábuas de Vida , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Adulto , Fatores Etários , Fármacos Anti-HIV/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Irlanda/epidemiologia , Expectativa de Vida , Masculino , Análise Multivariada , Modelos de Riscos Proporcionais , Fatores Sexuais , Abuso de Substâncias por Via Intravenosa , Análise de SobrevidaRESUMO
OBJECTIVE: To investigate the pharmacokinetics of saquinavir (SQV) hard gel when administered alone and in combination with nelfinavir (NLF) to HIV-positive patients. DESIGN: Six patients receiving triple therapy (dual nucleoside plus SQV 600 mg three times daily) were studied. On the first study day blood samples were drawn for assay of SQV. Prior to the second study day, patients received their usual medication plus NLF 750 mg three times daily for 2 days. METHODS: Blood samples were obtained at times 0, 1, 2, 4, 6 and 8 h after dosing on study days 1 and 2. Following centrifugation, separated plasma was heated at 58 degrees C for at least 30 min to inactivate HIV and stored at -80 degrees C until analysis using high performance liquid chromatography. RESULTS: The geometric mean Cmax and AUC0-8 h on the first study day were 253 ng/ml (range, < 25-1200 ng/ml) and 1106 ng/ml.h (range, < 100-3479 ng/ml.h), respectively, and on the second study day were 1204 ng/ml (range, 379-2755 ng/ml) and 5472 ng/ml.h (range, 1434-12,538 ng/ml.h), respectively. The geometric mean ratio for Cmax was 4.75 and for AUC0-8 h was 4.94. CONCLUSIONS: NLF increases the oral bioavailability of SQV (hard gel) approximately fivefold. For some patients the addition of NLF to SQV will increase the drug levels from subtherapeutic to the therapeutic range. In one of our patients the addition of NLF resulted in SQV levels that were much higher than previous work suggests are necessary for maximum antiviral effect. The variability in SQV concentrations both at baseline and following addition of NLF suggest that dosing may best be adjusted by individual therapeutic drug monitoring.
Assuntos
Fármacos Anti-HIV/farmacocinética , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/farmacocinética , Nelfinavir/uso terapêutico , Saquinavir/farmacocinética , Adulto , Fármacos Anti-HIV/uso terapêutico , Quimioterapia Combinada , Infecções por HIV/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Saquinavir/sangue , Saquinavir/uso terapêuticoRESUMO
OBJECTIVE: The most important hepatic enzyme involved in the metabolism of protease inhibitors is cytochrome P450 3A4 (CYP3A4). Ritonavir (RIT) is a potent inhibitor of CYP3A4 and inhibits saquinavir (SQV) metabolism in healthy volunteers. In this study we investigated the kinetics of SQV when administered alone and in combination with RIT in HIV-infected patients. DESIGN: SQV pharmacokinetics were determined in seven patients who had advanced HIV disease. Steady-state SQV profiles were obtained on two occasions following treatment with SQV 600 mg three times daily alone and when administered with RIT 300 mg twice daily. METHODS: Blood samples were obtained at times 0, 1, 2, 4, 6 and 8 h post-dosing. Following centrifugation, separated plasma was heated at 58 degrees C for at least 30 min to inactivate HIV and stored at -80 degrees C until analysis using high performance liquid chromatography. RESULTS: For patients treated with SQV alone there was a 12-fold variability in the area under the SQV concentration-time curve (AUC0-8h) ranging from 293 to 3446 ng.h/ml. When combined with RIT there was a marked increase in the maximum plasma concentration of SQV [median (range), 146 (57-702) versus 4795 (1420-15810) ng/ml; approximately 95% confidence interval (CI), 2988-6819; P = 0.0006, Mann-Whitney U test]. The AUC0-8h for SQV was also significantly increased in the presence of RIT [median (range), 470 (29-3446) versus 27,458 (7357-108,001) ng.h/ml; approximately 95% CI, 16,628-35,111; P = 0.0006]. CONCLUSIONS: For some patients, administration of SQV 600 mg three times daily results in very low SQV plasma levels and possibly little antiviral effect. Combination of SQV with RIT results in a significant drug interaction mediated by enzyme inhibition which exposes patients to very high SQV concentrations and potential toxicity. If combination therapy with SQV plus RIT is considered then the dose of SQV should be greatly reduced.
Assuntos
Fármacos Anti-HIV/farmacocinética , Inibidores das Enzimas do Citocromo P-450 , Infecções por HIV/tratamento farmacológico , Oxigenases de Função Mista/antagonistas & inibidores , Ritonavir/administração & dosagem , Saquinavir/farmacocinética , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/sangue , Citocromo P-450 CYP3A , Sistema Enzimático do Citocromo P-450/metabolismo , Quimioterapia Combinada , Inibidores Enzimáticos/administração & dosagem , Infecções por HIV/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Oxigenases de Função Mista/metabolismo , Saquinavir/administração & dosagem , Saquinavir/sangueRESUMO
OBJECTIVES: The prevalence of erectile dysfunction in HIV-infected men is estimated to be 33%. Sildenafil citrate (Viagra; Pfizer Ltd, Sandwich, Kent, UK) is the first oral drug for this condition. Since sildenafil and the protease inhibitors are both metabolized by, and act as inhibitors of cytochrome P450 3A4, we evaluated the pharmacokinetics of the combination sildenafil plus indinavir in HIV-infected patients. DESIGN AND METHODS: Six patients at steady state in treatment with indinavir participated in the study. On the first day blood samples for indinavir assay were drawn at times 0, 1, 2, 3, 4, 6 and 8 h after dosing. On the second study day patients received a single dose of 25 mg of sildenafil in addition to their routine morning medication. Blood samples were taken as described. Separated plasma was stored at -80 degrees C until analysis by high performance liquid chromatography. In a parallel study, the effect of indinavir, ritonavir, saquinavir and nelfinavir on the in vitro hepatic metabolism of sildenafil was assessed. RESULTS: The geometric mean area under the concentration curve for 0-8 h (AUC0-8h) and maximum plasma concentration (Cmax) for indinavir were 19.69 microg/ml h (range, 9.19-31.99 microg/ml h) and 7.02 microg/ml (range, 2.33-16.17 microg/ml), respectively, on the first study day. In the presence of sildenafil, the mean AUC0-8h and Cmax of indinavir were 22.37 microg/ml h [range, 10.08-37.25 microg/ml h; 95% confidence interval (CI) for difference between means, -15 to 13.25) and 9.11 microg/ml (range, 3.41-22.78 microg/ml; 95% CI, -13 to 6.37), respectively. The geometric mean AUC0-8h and Cmax for sildenafil were 1631 ng/ml h (range, 643-2970 ng/ml h) and 384 ng/ml (range, 209-766 ng/ml) respectively. The AUC for sildenafil was 4.4 times higher than data from historical controls given either 50 mg or 100 mg of sildenafil and dose normalized to 25 mg. Indinavir was a potent inhibitor of sildenafil hepatic metabolism in vitro [concentration producing 50% inhibition of control enzyme activity (IC50) = 0.39 +/- 0.17 microM, mean +/- SD]. CONCLUSIONS: Co-administration of sildenafil 25 mg did not significantly alter the plasma indinavir levels. However, plasma sildenafil AUC was markedly increased in the presence of indinavir compared with historical controls. From the in vitro data, the mechanism of increase is indinavir inhibition of the hepatic metabolism of sildenafil. The magnitude of this interaction suggests a lower starting dose of sildenafil may be more appropriate in this clinical setting.