RESUMO
There is increasing concern that HIV treatment failure may result from inadequate central nervous system (CNS) penetration of antiretroviral drugs, allowing compartmentalized viral replication and development of resistance. We discuss a patient who maintained a suppressed plasma viral load for four years on antiretroviral therapy (ART) before developing HIV encephalitis with a cerebrospinal fluid (CSF) HIV viral load of 861 copies/mL and newly detectable plasma viral load of 68 copies/mL. Identification of major resistance mutations to his combination therapy supported concerns that resistant HIV had developed within the CNS. His ART was changed to optimize CNS penetration, leading to maintained clinical improvement. Imaging presented demonstrates corresponding radiological improvement. The report illustrates the need to exclude CNS viral rebound or incomplete suppression in HIV patients with neurological symptoms, and suggests that the extent of this emerging problem is only beginning to be recognized as the implications of long-term peripheral HIV suppression unfold.
Assuntos
Complexo AIDS Demência/virologia , Fármacos Anti-HIV/uso terapêutico , Líquido Cefalorraquidiano/virologia , Infecções por HIV/complicações , HIV-1/efeitos dos fármacos , Viremia/tratamento farmacológico , Replicação Viral , Complexo AIDS Demência/diagnóstico por imagem , Complexo AIDS Demência/tratamento farmacológico , Adulto , Fármacos Anti-HIV/farmacocinética , Fármacos Anti-HIV/farmacologia , Encéfalo/patologia , Encéfalo/virologia , Infecções por HIV/diagnóstico por imagem , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/fisiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , RNA Viral/sangue , RNA Viral/líquido cefalorraquidiano , Radiografia , Carga Viral , Viremia/virologiaRESUMO
A hazardous waste assessment has been completed on ash samples obtained from seven sewage sludge incinerators operating in the UK, using the methods recommended in the EU Hazardous Waste Directive. Using these methods, the assumed speciation of zinc (Zn) ultimately determines if the samples are hazardous due to ecotoxicity hazard. Leaching test results showed that two of the seven sewage sludge ash samples would require disposal in a hazardous waste landfill because they exceed EU landfill waste acceptance criteria for stabilised non-reactive hazardous waste cells for soluble selenium (Se). Because Zn cannot be proven to exist predominantly as a phosphate or oxide in the ashes, it is recommended they be considered as non-hazardous waste. However leaching test results demonstrate that these ashes cannot be considered as inert waste, and this has significant implications for the management, disposal and re-use of sewage sludge ash.
Assuntos
Resíduos Perigosos/legislação & jurisprudência , Eliminação de Resíduos/legislação & jurisprudência , Esgotos , Conservação dos Recursos Naturais , Cristalização , Desenho de Equipamento , União Europeia , Concentração de Íons de Hidrogênio , Metais/química , Metais Pesados/análise , Metais Pesados/química , Óxidos/química , Fosfatos/química , Eliminação de Resíduos/métodos , Temperatura , Difração de Raios X , Zinco/análiseRESUMO
Heavy metal-bearing waste usually needs solidification/stabilization (s/s) prior to landfill to lower the leaching rate. Cement is the most adaptable binder currently available for the immobilisation of heavy metals. The selection of cements and operating parameters depends upon an understanding of chemistry of the system. This paper discusses interactions of heavy metals and cement phases in the solidification/stabilisation process. It provides a clarification of heavy metal effects on cement hydration. According to the decomposition rate of minerals, heavy metals accelerate the hydration of tricalcium silicate (C3S) and Portland cement, although they retard the precipitation of portlandite due to the reduction of pH resulted from hydrolyses of heavy metal ions. The chemical mechanism relevant to the accelerating effect of heavy metals is considered to be H+ attacks on cement phases and the precipitation of calcium heavy metal double hydroxides, which consumes calcium ions and then promotes the decomposition of C3S. In this work, molecular models of calcium silicate hydrate gel are presented based on the examination of 29Si solid-state magic angle spinning/nuclear magnetic resonance (MAS/NMR). This paper also reviews immobilisation mechanisms of heavy metals in hydrated cement matrices, focusing on the sorption, precipitation and chemical incorporation of cement hydration products. It is concluded that further research on the phase development during cement hydration in the presence of heavy metals and thermodynamic modelling is needed to improve effectiveness of cement-based s/s and extend this waste management technique.
Assuntos
Materiais de Construção/análise , Metais Pesados/química , Eliminação de Resíduos/métodos , Conservação dos Recursos Naturais/métodos , Poluição Ambiental/prevenção & controleRESUMO
OBJECTIVE: More and more highly treatment-experienced patients are achieving viral suppression. However, the durability of suppression remains unclear. METHODS: Patients from Royal Free Hospital (London, UK) and JW Goethe University Hospital (Frankfurt, Germany) who had failed > or = 1 antiretroviral (ARV) regimen in all three main drug classes and > or = 3 previous ARV regimens and subsequently achieved viral load < 50 HIV-1 RNA copies/mL were included. They were followed until stopping pre-combination antiretroviral therapy, end of follow-up or viral rebound (two viral loads >400 copies/mL). RESULTS: Two hundred and forty-seven patients contributed 723 person-years and 114 viral rebounds [rate=15.8 per 100 person-years; 95% confidence interval (CI) 12.9-18.7]. More recent calendar years of viral suppression [relative risk (RR)=0.90 per year later; 95% CI 0.81-1.00; P=0.05] and greater number of ARVs in the regimen not previously failed (RR=0.78 per 1 ARV more; 95% CI 0.65-0.95; P=0.01) were associated with lower viral rebound rates. At 0-1, 1-2, 2-3 and > 3 years after achieving suppression, the rebound rates were 30.9, 9.2, 4.3 and 3.5 per 100 person-years, respectively. Compared to 0-1 years, the adjusted RRs (95% CIs) after 1-2, 2-3 and > 3 years were 0.33 (0.18-0.58), 0.21 (0.09-0.48) and 0.14 (0.06-0.33), respectively (P<0.0001). CONCLUSIONS: Although rebound rates are high, especially in the first year after viral suppression, this risk reduces substantially if highly treatment-experienced patients can maintain viral suppression.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1 , Adulto , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Esquema de Medicação , Feminino , Alemanha , Infecções por HIV/virologia , Humanos , Londres , Masculino , Recidiva , Fatores de Tempo , Falha de Tratamento , Carga ViralRESUMO
The fine fraction (<14 mm) of incinerator bottom ash (IBA) obtained from a UK energy from waste plant has been milled and thermally treated at 600, 700, 800 and 880 degrees C. Treated materials have been activated with Ca(OH)(2) (10 wt%) and the setting times and compressive strengths at different curing times measured. In addition to decomposition of CaCO(3) to CaO, thermal treatment increases the content of gehlenite (Ca(2)Al(2)SiO(7)), wollastonite (CaSiO(3)) and mayenite (Ca(12)Al(14)O(33)). Thermally treated samples were significantly more reactive than milled IBA and heating to 700 degrees C produced a material which rapidly set. Silica, gehlenite and wollastonite were the main crystalline phases present in hydrated samples and a mixed sulphate-carbonate AFm-type phase (Ca(4)Al(2)O(6)(CO(3))(0.67)(SO(3))(0.33).11H(2)O) formed. Significant volumes of gas were generated during curing and this produced a macro-porous microstructure that limited strength to 2.8 MPa. The new materials may have potential for use as controlled low-strength materials.
Assuntos
Incineração , Resíduos Industriais/análise , Compostos de Cálcio/análise , Hidróxido de Cálcio/química , Força Compressiva , Temperatura Alta , Teste de Materiais , Microscopia Eletrônica de Varredura , Fatores de Tempo , Volatilização , Difração de Raios XRESUMO
The hydration of tricalcium silicate (C(3)S) in the presence of heavy metal is very important to cement-based solidification/stabilisation (s/s) of waste. In this work, tricalcium silicate pastes and aqueous suspensions doped with nitrate salts of Zn(2+), Pb(2+), Cu(2+) and Cr(3+) were examined at different ages by X-ray powder diffraction (XRD), thermal analysis (DTA/TG) and (29)Si solid-state magic angle spinning/nuclear magnetic resonance (MAS/NMR). It was found that heavy metal doping accelerated C(3)S hydration, even though Zn(2+) doping exhibited a severe retardation effect at an early period of time of C(3)S hydration. Heavy metals retarded the precipitation of portlandite due to the reduction of pH resulted from the hydrolysis of heavy metal ions during C(3)S hydration. The contents of portlandite in the control, Cr(3+)-doped, Cu(2+)-doped, Pb(2+)-doped and Zn(2+)-doped C(3)S pastes aged 28 days were 16.7, 5.5, 5.5, 5.5, and <0.7%, respectively. Heavy metals co-precipitated with calcium as double hydroxides such as (Ca(2)Cr(OH)(7).3H(2)O, Ca(2)(OH)(4)4Cu(OH)(2).2H(2)O and CaZn(2)(OH)(6).2H(2)O). These compounds were identified as crystalline phases in heavy metal doping C(3)S suspensions and amorphous phases in heavy metal doping C(3)S pastes. (29)Si NMR data confirmed that heavy metals promoted the polymerisation of C-S-H gel in 1-year-old of C(3)S pastes. The average numbers of Si in C-S-H gel for the Zn(2+)-doped, Cu(2+)-doped, Cr(3+)-doped, control, and Pb(2+)-doped C(3)S pastes were 5.86, 5.11, 3.66, 3.62, and 3.52. And the corresponding Ca/Si ratios were 1.36, 1.41, 1.56, 1.57 and 1.56, respectively. This study also revealed that the presence of heavy metal facilitated the formation of calcium carbonate during C(3)S hydration process in the presence of carbon dioxide.
Assuntos
Compostos de Cálcio/química , Poluentes Ambientais/química , Metais Pesados/química , Eliminação de Resíduos , Silicatos/química , Poluição Ambiental/prevenção & controle , Concentração de Íons de Hidrogênio , Espectroscopia de Ressonância Magnética , Nitratos/química , Eliminação de Resíduos/métodos , Solubilidade , Temperatura , Difração de Raios XRESUMO
OBJECTIVE: To describe outcomes in patients starting first-line antiretroviral regimens including lopinavir/ritonavir (LPV/r) in a routine clinic setting. METHODS: Previously naïve patients starting LPV/r-containing antiretroviral therapy were included in the study. Virological failure was defined as the first of two viral loads >500 HIV-1 RNA copies/mL more than 6 months after starting LPV/r. Cumulative percentages experiencing virological failure were calculated using Kaplan-Meier methods. RESULTS: A total of 195 individuals had a median follow-up time of 1.7 years. At 48 weeks, 87.9, 77.4 and 71.6% of patients with pretreatment CD4 counts of <50, 50-200 and >200 cells/microL, respectively, remained on LPV/r. By 48, 72 and 96 weeks, 2.2, 3.0 and 5.0% of patients, respectively, had experienced virological failure, ignoring treatment changes but censoring follow-up at discontinuation of all antiretrovirals; these percentages became 24.0, 33.7 and 42.3% when LPV/r discontinuation was considered as virological failure. Censoring those who stopped LPV/r with a viral load <50 copies/mL and considering as virological failures those who stopped LPV/r with a viral load >50 copies/mL gave 12.1, 14.6 and 17.0% virological failure at 48, 72 and 96 weeks, respectively. Median CD4 count increases at 24, 48 and 72 weeks were 167, 230 and 253 cells/microL, respectively. CONCLUSIONS: Few patients experienced virological failure whilst on a LPV/r-based regimen, although it was not uncommon for patients in our clinic with higher baseline CD4 counts to discontinue LPV/r.
Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , HIV-1 , Pirimidinonas/uso terapêutico , Ritonavir/uso terapêutico , Adulto , Contagem de Linfócito CD4 , Quimioterapia Combinada , Feminino , Humanos , Londres , Lopinavir , Masculino , Resultado do Tratamento , Carga ViralRESUMO
A case of avascular osteonecrosis of the right knee is described in a patient with HIV infection. The patient had been receiving highly active antiretroviral therapy for two years prior to presentation. Osteonecrosis is an uncommon albeit serious complication of HIV infection and is associated with use of antiretroviral agents.
Assuntos
Terapia Antirretroviral de Alta Atividade/efeitos adversos , Articulação do Joelho/patologia , Osteonecrose/induzido quimicamente , Adulto , Feminino , Infecções por HIV/tratamento farmacológico , HumanosRESUMO
AIMS: Common variable immunodeficiency (CVID) is the most common serious primary immunodeficiency. This paper describes the immunological consequences of human immunodeficiency virus (HIV) infection in a patient with familial CVID subsequently treated with highly active antiretroviral therapy (HAART). METHODS: Serial measurements over 11 years of serum immunoglobulins, specific antibodies to tetanus toxoid and pneumococcal polysaccharides, lymphocyte phenotypes, and HIV viral load were made. RESULTS: The patient recovered total serum IgG and IgM, but not IgA production, with adequate concentrations of specific antibodies, allowing withdrawal of intravenous immunoglobulin without an increase in infections. T cell numbers gradually declined and the patient developed a high grade B cell lymphoma. After successful chemotherapy, HAART was commenced, viral load fell from 472 000 to < 50 copies/ml, and CD4+ T cell numbers increased from 13 to 661 x 10(6)/litre. Antibody production was maintained after suppression of viral load. CONCLUSIONS: This is the first definitive report of reversal of IgG and IgM deficiency in familial CVID after HIV infection. Failure to normalise IgA supports the concept of separate predisposing genetic factors for selective IgA deficiency, which when combined with others lead to CVID. Furthermore, a persistently high viraemia is not required to maintain the recovery of immunoglobulin values, suggesting this depends either on a transitory effect of a high viral load, or a persistence of low amounts of virus.
Assuntos
Imunodeficiência de Variável Comum/imunologia , Infecções por HIV/imunologia , Imunoglobulina G/biossíntese , Imunoglobulina M/biossíntese , Adulto , Terapia Antirretroviral de Alta Atividade , Imunodeficiência de Variável Comum/complicações , Seguimentos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , MasculinoRESUMO
OBJECTIVE: To describe the reasons for, and factors associated with, modification and discontinuation of highly active antiretroviral therapy (HAART) regimens at a single clinic. SUBJECTS: A total of 556 patients who started HAART at the Royal Free Hospital were included in analyses. Modification was defined as stopping or switching any antiretrovirals in the regimen, whereas discontinuation was defined as the simultaneous stopping of all antiretrovirals included in the initial regimen. Reasons were classified as immunological/virological failure (IVF) and toxicities and patient choice/poor compliance (TPC). RESULTS: The median CD4 count at starting HAART was 171 x 10(6) cells/l and viral load 5.07 log copies/ml. During a median follow-up of 14.2 months, 247 patients (44.4%) modified their HAART regimen, 72 due to IVF (29.1%) and 159 due to TPC (64.4%) and a total of 148 patients (26.6%) discontinued HAART. Older patients were less likely to modify HAART [relative hazard (RH), 0.73 per 10 years; P = 0.0008], as were previously treatment-naive patients (RH, 0.65; P = 0.0050), those in a clinical trial (RH, 0.64; P = 0.027) and those who started nelfinavir (RH, 0.57; P = 0.035). Patients who started with four or more drugs (RH, 2.21, P < 0.0001), who included ritonavir in the initial regimen (RH, 1.41; P = 0.035) or who had higher viral loads during follow-up (RH per log increase, 1.51; P < 0.0001) were more likely to modify HAART. CONCLUSIONS: There was a high rate of modification and discontinuation of HAART regimens in the first 12 months, particularly due to toxicities, patient choice or poor compliance.
Assuntos
Terapia Antirretroviral de Alta Atividade/tendências , Infecções por HIV/tratamento farmacológico , Contagem de Linfócito CD4 , Feminino , Seguimentos , Infecções por HIV/imunologia , Infecções por HIV/psicologia , Infecções por HIV/virologia , Humanos , Masculino , Falha de Tratamento , Recusa do Paciente ao Tratamento , Carga ViralRESUMO
In this paper, the authors report that the expression of tau-based reporter genes causes severe defects in the morphology of sensory neurons in adult Drosophila. Targeted expression of tau-green fluorescent protein (tau-GFP) in sensory neurons, using the galactosidase-4 (GAL4) system, produced a range of characteristic defects in expressing neurons. The defects observed included loss of axons, abnormal axon bundling, reduced sensory arborisations, and axonal swellings (beads). Blind comparisons of adult sensory neurons labelled with tau-GFP or CD8-GFP showed that tau-GFP neurons exhibited many more defects than CD8-GFP-expressing neurons. CD8-GFP was found to induce no significant defects on sensory neuron morphology. Expression of tau-lacZ and human tau in sensory neurons produced defects comparable to those seen with tau-GFP. A developmental study showed that tau-expressing axons grow normally and innervate the correct regions of the neuropil. The absence of these axons later in development suggests that tau-expressing axons are lost after initial ingrowth. Examination of silver-stained sections suggests that the absence of axons is due to axon loss rather than failure of the expression system to label the neurons. The results suggest that the expression of tau-based reporter constructs causes severe defects in sensory neurons, resulting in degeneration. The results also indicate that Drosophila may provide a useful model system for examining the role of tau in neurodegenerative disorders.
Assuntos
Vias Aferentes/anormalidades , Diferenciação Celular/genética , Drosophila/crescimento & desenvolvimento , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Genes Reporter/fisiologia , Neurônios Aferentes/metabolismo , Proteínas tau/metabolismo , Vias Aferentes/citologia , Vias Aferentes/metabolismo , Animais , Axônios/metabolismo , Axônios/patologia , Axônios/ultraestrutura , Morte Celular/genética , Drosophila/citologia , Drosophila/metabolismo , Proteínas de Fluorescência Verde , Indicadores e Reagentes/farmacologia , Perna (Membro)/inervação , Perna (Membro)/patologia , Perna (Membro)/fisiologia , Proteínas Luminescentes/farmacologia , Neurônios Aferentes/citologia , Neurônios Aferentes/patologia , Proteínas tau/genéticaRESUMO
BACKGROUND: Highly active antiretroviral therapy (HAART) is now widely used in clinical practice and gives rise to a range of immunological, virological and clinical responses. OBJECTIVES: To describe the immunological, virological and clinical response to HAART and to examine the frequency of modification of the HAART regimen among patients from a single treatment centre. METHODS: Kaplan-Meier estimation and incidence rates were used to describe responses to HAART (a protease inhibitor or non-nucleoside drug in addition to at least two nucleoside analogues) among 421 patients from the Royal Free Hospital in London. RESULTS: The median CD4 cell count at starting HAART was 186 x 10(6) cells/l [interquartile range (IQR) 76-310] and viral load was 5.13 log10 copies/ml (IQR 4.66-5.56). At 6 months after starting HAART, 51.1% of patients were estimated to have experienced a 100 x 10(6) cells/l increase in CD4 cell count; the median time for viral load to fall below 400 copies/ml was 3.7 months (95% confidence interval 3.2-4.4). At 6 months after the first viral load was < 400 copies/ml, 16.4% of patients were estimated to have failed on the basis of a single viral load > 400 copies/ml and 12.4% were estimated to have failed if the more stringent definition of two viral loads above the limit of detection was used. Compared with the pre-HAART era, the incidence of death among patients on HAART was one sixth of that level; new AIDS-defining illnesses was one seventh; and hospital admissions was one fifth. In total, 141 patients (33.5%) stopped at least one of the antiretroviral agents included as part of their HAART regimen; the occurrence of side effects was the most common reason (n = 63; 44.7%). CONCLUSION: A good response occurred to an initial HAART regimen. There was a high rate of virological relapse, which varied considerably according to the definition of failure used. Even so, the rates of clinical progression and hospital admissions observed to date were low. Further follow-up of these patients is required to determine their long-term immunological, virological and clinical outcome.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Feminino , Seguimentos , Infecções por HIV/imunologia , Infecções por HIV/fisiopatologia , Infecções por HIV/virologia , Humanos , Masculino , Carga ViralRESUMO
OBJECTIVE: To describe the short-term changes in CD4 lymphocyte counts after the interruption of antiretroviral HIV therapy in order to increase the understanding of CD4 lymphocyte dynamics, and so that appropriate monitoring strategies can be designed. METHODS: We studied 35 HIV-infected patients with late-stage disease who had therapy interruptions leading to high viral load levels, median greater than 750 000 RNA log10 copies/ml, and in whom two CD4 cell counts (median 28 days apart) were available before beginning a salvage regimen. RESULTS: Overall, there was a substantial decline in CD4 cell counts from a median of 125 to 83 cells/mm3 in the average 28 day period, with median proportionate and absolute losses of 26% and 24 cells/mm3 per month, respectively (P < 0.008). This tended to be greater in individuals studied sooner after interrupting therapy (P = 0.03) and in those with CD4 cell counts above the pre-therapy baseline (P = 0.06). There was a strong negative correlation between the proportionate increase in viral load and the absolute change in CD4 cell count (-0.66, P = 0.0002). CONCLUSION: Patients with relatively advanced HIV infection interrupting antiretroviral therapy after failing a protease inhibitor-containing regimen require frequent monitoring because CD4 cell counts appear to fall quite rapidly, at least in the first few weeks after interruption.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , HIV/fisiologia , Adulto , Feminino , HIV/efeitos dos fármacos , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Masculino , RNA Viral/sangue , Fatores de Tempo , Carga ViralRESUMO
OBJECTIVE: To examine a complete population of clinic attenders in order to compare the demographics of patients who participated in a clinical study with those who had not. These were subdivided into trials of antivirals, trials for drugs used in opportunistic infections or symptomatic HIV and epidemiological studies. The setting was an established London teaching hospital. All patients diagnosed HIV-positive and attending between July 1983 and 1 January 1999 with one measured CD4 count and at least one follow-up visit were included. METHODS: The demographics of those participating in a clinical study were compared to those not enrolling using chi2 tests and Wilcoxon tests. Cox models were used to determine factors related to participation in clinical studies. RESULTS: Data from 2703 patients representing 5342.7 person-years' follow-up were assessed. Median time of follow-up was 23.6 months. Six hundred and eighty-seven (33%) patients had ever participated in a clinical study. After adjustment for demographic factors in multivariate analysis using Cox models, homosexuals were more likely to participate compared with heterosexuals or injecting drug users (IDU) (P = 0.0035 and P = 0.0001, respectively). Women were more likely to enter a study (P = 0.02) and there was no difference between Caucasians and black Africans (P = 0.35). Between the three types of studies few differences were seen. CONCLUSION: High rates of participation in clinical trials and epidemiological studies were seen in this cohort. In keeping with other studies, homosexual men were well represented but IDU were under-represented. However, women and black African patients showed good uptake of all clinical studies. Hence in this population there is some success in targeting representative groups to participate in clinical studies, but more effort needs to be made with IDU.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Participação do Paciente/estatística & dados numéricos , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Adulto , Distribuição por Idade , Análise de Variância , Ensaios Clínicos como Assunto , Feminino , Infecções por HIV/epidemiologia , Hospitais de Ensino , Humanos , Londres/epidemiologia , Masculino , Análise Multivariada , Modelos de Riscos Proporcionais , Distribuição por SexoRESUMO
OBJECTIVES: To describe the incidence of AIDS-defining illnesses within a single large clinic setting, to describe temporal changes over a 10-year period in the overall incidence and of individual AIDS-defining illnesses and to investigate the impact of HIV treatment regimen on the incidence of AIDS-defining illnesses. SUBJECTS AND METHODS: A person-years analysis was used to determine the incidence of AIDS-defining illnesses according to calendar year and stratification by CD4 lymphocyte count and treatment regimen in 1806 patients from the Royal Free Centre for HIV Medicine with at least one CD4 lymphocyte count and follow-up visit. RESULTS: Prior to 1992, the incidence of all AIDS-defining illnesses was 27.4/100 person-years of follow-up (PYFU; 95% confidence interval [CI], 22.8-32.0) and during 1997 this incidence had dropped to 6.9/100 PYFU (95% CI, 4.7-9.1; p < .0001, test for trend). The decline in incidence over time occurred in esophageal candidiasis, cytomegalovirus disease (including retinitis), Kaposi's sarcoma, lymphoma, wasting syndrome, and Pneumocystis carinii pneumonia (p < .05, test for trend), but there was no evidence of a decline in AIDS dementia or in Mycobacterium avium complex. In 1997, among patients with CD4 lymphocyte counts of < or =200 cells/mm3, the incidence rates for any AIDS-defining illness was 51.1/100 PYFU for patients taking no therapy (95% CI, 27.9-85.7), 34.5 among patients on monotherapy (95% CI, 4.2-124.6), 13.2 among patients taking dual combination therapy (95% CI, 3.6-33.8) and 6.1 among patients taking triple therapy or more complex regimens (95% CI, 0.7-22.0; p < .0001, test for trend). CONCLUSIONS: There was a considerable decline in AIDS-defining illnesses during 1996 and 1997, coinciding with the rapid development of new antiretroviral treatments and combinations of treatment. Further follow-up of large observational cohorts is essential to monitor the incidence of diagnoses less common than we were able to consider, such as tuberculosis, cryptosporidiosis, and cryptococcosis, and also to investigate whether the incidence of disease continues to fall, or whether it starts to rise again, as toxicities, compliance, drug resistance, and long-term side effects begin to appear.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/epidemiologia , Fármacos Anti-HIV/uso terapêutico , Sarcoma de Kaposi/epidemiologia , Complexo AIDS Demência/epidemiologia , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/transmissão , Adolescente , Adulto , Contagem de Linfócito CD4 , Candidíase Bucal/epidemiologia , Intervalos de Confiança , Infecções por Citomegalovirus/epidemiologia , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Incidência , Londres/epidemiologia , Linfoma Relacionado a AIDS/epidemiologia , Masculino , Infecção por Mycobacterium avium-intracellulare/epidemiologia , Ambulatório Hospitalar/estatística & dados numéricos , Pneumonia por Pneumocystis/epidemiologia , Síndrome de Emaciação/epidemiologiaRESUMO
OBJECTIVE: Previous studies on patients treated with potent antiretroviral therapy have shown that viral clearance rates do not tend to change between early and advanced HIV-1 infection. Our objective was to investigate whether the other major aspect of virus dynamics, viral replicative capacity, does change. In vitro work has indicated that the viral replicative, capacity increases but in vivo evidence has been lacking. METHODS: As an in vivo measure of the viral replicative capacity, we studied the rate of rebound of plasma HIV RNA level during a 1-week therapy interruption in previously untreated patients who had received 2 weeks of antiretroviral therapy. RESULTS: Such therapy in five previously drug-naive patients with high CD4 lymphocyte counts (mean, 611 x 10(6)/l) and five patients with low counts (mean, 49 x 10(6)/l) led to a mean 2.2 log10 copies/ml decrease in plasma HIV-1 levels (from 5-6 log10 copies/ml) in 2 weeks. This was similar in the two groups. Interruption of therapy for the ensuing week resulted in a stable HIV-1 level for approximately 2 days followed by a rebound towards pretherapy level, which was much more marked in the patients with low CD4 cell counts (estimated mean rise 2.22 log10 versus 1.06 log10 copies/ml; P < 0.02). After restarting therapy, HIV RNA levels returned to pre-interruption levels. CONCLUSIONS: These findings need confirmation, but the ability of HIV-1 to replicate in vivo appears to increase during HIV-1 infection. This increased replicative capacity, for which there are several potential explanations, may be the cause of gradual CD4 lymphocyte depletion.
Assuntos
Infecções por HIV/virologia , HIV-1/fisiologia , Replicação Viral , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/fisiopatologia , HIV-1/genética , HumanosRESUMO
OBJECTIVE: Following the publication of results of large-scale clinical trials, antiretroviral treatment for HIV has changed dramatically. The aim of this study was to describe changes in antiretroviral treatment and the way treatments were combined among 1806 patients with HIV seen at a single centre at the Royal Free Hospital, London, UK. DESIGN AND METHOD: Each calendar year was divided into quarters, and the number of patients receiving treatment and participating in clinical trials was determined. RESULTS: The proportion of patients on no therapy decreased from over 90% at the beginning of 1988 to under 15% at the end of 1997. Monotherapy was the only form of treatment available before 1992 but its use dropped to 2% by the end of 1997. The standard of care at the end of 1997 was triple combination therapy, used in over 40% of patients. There were dramatic changes in the use of individual agents; use of zidovudine decreased from 50% during 1989 to 25% during 1997, while use of lamivudine and stavudine saw an exponential rise in 1997. The protease inhibitors were used in equal proportions in this clinic population; the use of dual protease therapy began in 1997 and was rising rapidly by the end of the year. CONCLUSIONS: There have been major changes in the use of antiretroviral therapy at this centre, particularly during 1996 and 1997. The long-term cost implications and side-effects of intensive treatment regimens remain to be addressed.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Protocolos Clínicos/normas , Infecções por HIV/tratamento farmacológico , Adulto , Ensaios Clínicos como Assunto , Quimioterapia Combinada , Feminino , Humanos , Londres , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica , Estudos RetrospectivosAssuntos
Infecções Oportunistas Relacionadas com a AIDS/complicações , Fármacos Anti-HIV/uso terapêutico , Tuberculoma Intracraniano/complicações , Tuberculose Miliar/complicações , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Adulto , Quimioterapia Combinada , Humanos , Imageamento por Ressonância Magnética , Masculino , Tomografia Computadorizada por Raios X , Tuberculose Miliar/tratamento farmacológico , Tuberculose Miliar/microbiologiaRESUMO
Simple models of CD4 lymphocyte interactions with human immunodeficiency virus (HIV) lead to the hypothesis that progression of HIV infection involves an increase in viral replicative capacity, due either to changes in the virus or in the host environment, or both. In order to consider how changes in plasma virus load after transient, potent antiretroviral therapy can be used to test the above hypothesis--a simple mathematical model that encompasses the processes of (1) arrival of new CD4 lymphocytes, (2) death/removal of these cells by HIV-independent mechanisms, (3) infection of susceptible CD4 lymphocytes by HIV, and (4) death/removal of infected cells was investigated. This showed that the in vivo rate of increase in plasma virus load immediately after transient therapy provides a measure of the viral replicative capacity. Thus, the hypothesis that progression of HIV infection involves an increase in viral replicative capacity can be tested by measuring this viral growth rate in patients with high CD4 counts and in patients with low CD4 counts. Studies should thus investigate dynamics of changes in virus levels after stopping antiretroviral therapy and, in particular, measure rates of increase in virus in patients at high and low CD4 counts. In practice, such data may assist in therapeutic management of patients with HIV infection.