RESUMO
We report a case of agenesis of the infrarenal inferior vena cava in a 16-year-old male presenting with venous stasis dermatitis and ulceration in the gaiter region bilaterally. Duplex imaging was performed revealing absence of infrarenal inferior vena cava and iliofemoral venous system. Magnetic resonance venography then confirmed the above findings along with revealing extensive lumbar and pelvic collateralization. This patient's condition has been successfully managed conservatively with compression therapy and wound care. This case is a rare example of a congenital malformation of the inferior vena cava and represents the only reported case with presenting symptoms of venous stasis ulceration in a pediatric patient.
Assuntos
Úlcera Varicosa/etiologia , Malformações Vasculares/complicações , Veia Cava Inferior/anormalidades , Adolescente , Circulação Colateral , Dermatite/etiologia , Humanos , Angiografia por Ressonância Magnética , Masculino , Flebografia/métodos , Fluxo Sanguíneo Regional , Meias de Compressão , Resultado do Tratamento , Ultrassonografia Doppler Dupla , Úlcera Varicosa/diagnóstico , Úlcera Varicosa/fisiopatologia , Úlcera Varicosa/terapia , Malformações Vasculares/diagnóstico , Malformações Vasculares/fisiopatologia , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/fisiopatologia , CicatrizaçãoRESUMO
We examined the characteristics associated with hepatitis C virus (HCV) antibody (anti-HCV) prevalence and HCV clearance between injection drug using (IDU) and non-IDU men who have sex with men (MSM). Stored serum and plasma samples were tested for anti-HCV and HCV RNA to determine the HCV status of 6925 MSM at enrolment into the Multicentre AIDS Cohort Study (MACS). Prevalence and clearance ratios were calculated to determine the characteristics associated with HCV prevalence and clearance. Multivariable analyses were performed using Poisson regression methods with robust variance estimation. Anti-HCV prevalence was significantly higher among IDU than among non-IDU MSM (42.9% vs 4.0%), while clearance was significantly lower among IDU MSM (11.5% vs 34.5% among non-IDU MSM). HIV infection, Black race, and older age were independently associated with higher prevalence in both groups, while smoking, transfusion history, and syphilis were significantly associated with prevalence only among non-IDU MSM. The rs12979860-C/C genotype was the only characteristic independently associated with HCV clearance in both groups, but the effects of both rs12979860-C/C genotype [clearance ratio (CR) = 4.16 IDUs vs 1.71 non-IDUs; P = 0.03] and HBsAg positivity (CR = 5.06 IDUs vs 1.62 non-IDUs; P = 0.03) were significantly larger among IDU MSM. HIV infection was independently associated with lower HCV clearance only among non-IDU MSM (CR = 0.59, 95% CI = 0.40-0.87). IDU MSM have higher anti-HCV prevalence and lower HCV clearance than non-IDU MSM. Differences in the factors associated with HCV clearance suggest that the mechanisms driving the response to HCV may differ according to the mode of acquisition.
Assuntos
Hepacivirus/isolamento & purificação , Hepatite C/epidemiologia , Hepatite C/transmissão , Homossexualidade Masculina , Adolescente , Adulto , Idoso , Estudos Transversais , Hepacivirus/genética , Hepacivirus/imunologia , Anticorpos Anti-Hepatite C/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Plasma/virologia , Prevalência , RNA Viral/sangue , Abuso de Substâncias por Via Intravenosa/complicações , Adulto JovemRESUMO
Reports of kidney transplantation (KTX) in recipients with hepatitis C virus (HCV+), human immunodeficiency virus (HIV+) or coinfection often do not provide adequate adjustment for donor risk factors. We evaluated paired deceased-donor kidneys (derived from the same donor transplanted to different recipients) in which one kidney was transplanted into a patient with viral infection (HCV+, n = 1700; HIV+, n = 243) and the other transplanted into a recipient without infection (HCV- n = 1700; HIV- n = 243) using Scientific Registry of Transplant Recipients data between 2000 and 2013. On multivariable analysis (adjusted for recipient risk factors), HCV+ conferred increased risks of death-censored graft survival (DCGS) (adjusted hazard ratio [aHR] 1.24, 95% confidence interval [CI] 1.04-1.47) and patient survival (aHR 1.24, 95% CI 1.06-1.45) compared with HCV-. HIV+ conferred similar DCGS (aHR 0.85, 95% CI 0.48-1.51) and patient survival (aHR 0.80, 95% CI 0.39-1.64) compared with HIV-. HCV coinfection was a significant independent risk factor for DCGS (aHR 2.33; 95% CI 1.06, 5.12) and patient survival (aHR 2.88; 95% CI 1.35, 6.12). On multivariable analysis, 1-year acute rejection was not associated with HCV+, HIV+ or coinfection. Whereas KTX in HIV+ recipients were associated with similar outcomes relative to noninfected recipients, HCV monoinfection and, to a greater extent, coinfection were associated with poor patient and graft survival.
Assuntos
Infecções por HIV/cirurgia , Hepatite C/cirurgia , Transplante de Rim , Adulto , Feminino , Infecções por HIV/complicações , Hepatite C/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Doadores de TecidosRESUMO
We report a case of hypothenar hammer syndrome. The case presents necessary diagnostic measures and discusses the etiology of this syndrome. Additionally, the case reviews treatments, which culminated in the eventual use of ulnar artery bypass with autogenous basilica vein to treat and resolve the ischemic fingers of the patient.
Assuntos
Dedos/irrigação sanguínea , Dedos/patologia , Doença Arterial Periférica/cirurgia , Doença de Raynaud/etiologia , Úlcera Cutânea/patologia , Idoso , Artérias/cirurgia , Implante de Prótese Vascular , Dilatação Patológica , Gangrena , Humanos , Masculino , Doença Arterial Periférica/complicações , Síndrome , Trombose/complicações , Trombose/cirurgia , Veias/cirurgia , Veias/transplanteRESUMO
UNOS guidelines provide inadequate discriminatory criteria for kidneys that should be transplanted as single (SKT) versus dual (DKT). We evaluated the utility of the kidney donor risk index (KDRI) to define kidneys with better outcomes when transplanted as dual. Using SRTR data from 1995 to 2010 of de novo KTX recipients of adult deceased-donor kidneys, we examined outcomes of SKT and DKT stratified by KDRI group ≤1.4 (n = 49 294), 1.41-1.8 (n = 15 674), 1.81-2.2 (n = 6523) and >2.2 (n = 2791). DKT of kidneys with KDRI >2.2 was associated with significantly better overall graft survival [adjusted hazard ratio (aHR) 0.83, 95% confidence interval (CI) 0.72-0.96] compared to single kidneys with KDRI >2.2. DKT was associated with significantly decreased odds of delayed graft function (top 2 KDRI categories) and significantly decreased odds of 1-year serum creatinine level >2 mg/dL (top 3 KDRI categories). Among SKT and DKT from KDRI >2.2 there were 16.1 and 13.9 graft losses per 100 patient follow-up years, respectively. KDRI >2.2 is a useful discriminatory cut-off for the determination of graft survival benefit with the use of DKT; however, the benefit of increased graft years was less than half of single kidneys from donors in the same KDRI range.
Assuntos
Sobrevivência de Enxerto , Transplante de Rim/métodos , Adulto , Idoso , Função Retardada do Enxerto , Feminino , Humanos , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Doadores de Tecidos , Resultado do TratamentoRESUMO
The Multicenter AIDS Cohort (MACS), initiated in 1983 at the Johns Hopkins School of Public Health, the University of Pittsburgh School of Public Health, Northwestern University School of Medicine, and the UCLA School of Public Health, continues to conduct studies and publish key papers on the natural history of untreated and treated HIV infection in 6972 men-who-have-sex-with-men. Through May 2011, 1,490,995 specimens have been collected, 86,883 person-years of data accrued and 1195 scientific papers published in international journals.
Assuntos
Síndrome da Imunodeficiência Adquirida , Estudos de Coortes , Estudos Multicêntricos como Assunto , Síndrome da Imunodeficiência Adquirida/patologia , Síndrome da Imunodeficiência Adquirida/terapia , Coleta de Dados , Homossexualidade Masculina , Humanos , Masculino , Editoração/tendências , Estados UnidosRESUMO
A genome-wide association study of people with incident human immunodeficiency virus (HIV) infection selected from nine different cohorts identified allelic polymorphisms, which associated with either viral set point (HCP5 and 5' HLA-C) or with HIV disease progression (RNF39 and ZNRD1). To determine the influence of these polymorphisms on host control of HIV, we carried out a population-based association study. The analysis revealed complete linkage disequilibrium between HCP5 and HLA-B*5701/HLA-Cw*06, a modest effect of 5' HLA-C on viral set point in the absence of HLA-B*5701, and no influence of the RNF39 /ZNRD1 extended haplotype on HIV disease progression. No correlation was found between the infection status and any of these genetic variants (P>0.1, Fisher's exact test). These findings suggest a pattern of strong linkage disequilibrium consistent with an HLA-B/-C haplotype block, making identification of a causal variant difficult, and underscore the importance of validating polymorphisms in putative determinants for host control by association analysis of independent populations.
Assuntos
Infecções por HIV/genética , Infecções por HIV/imunologia , Antígenos HLA-B/genética , Antígenos HLA-B/imunologia , Antígenos HLA-C/genética , Antígenos HLA-C/imunologia , Haplótipos , Humanos , Masculino , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: The clinical implications of a failure to achieve high CD4 cell counts while receiving virally suppressive highly active antiretroviral therapy (HAART) are uncertain. METHODS: We analysed data from HIV-infected men participating in the Multicenter AIDS Cohort Study (MACS) to elucidate associations between CD4 cell counts achieved during virally suppressive HAART and risks of AIDS or death. Inclusion criteria were: CD4 cell count <200 cells/microL before HAART initiation; >or=2 viral load (VL) determinations after HAART initiation; and sustained viral suppression, defined as all VL <50 HIV-1 RNA copies/mL, but allowing a single VL of 50-1000 copies/mL. RESULTS: One hundred and twenty-one men were included; median age was 42 years. After first VL <50 copies/mL, six participants had a new AIDS diagnosis and seven died. The median CD4 cell count change/year (cells/microL) after first VL <50 copies/mL was zero among patients who either developed AIDS or died vs. 39 among those who did not meet either endpoint (P=0.119). After controlling for time from HAART initiation to first VL <50 copies/mL, age at first VL <50 copies/mL, history of AIDS and antiretroviral therapy (ART) experience before HAART, the hazard ratio for AIDS or death at CD4 cell count of
Assuntos
Síndrome da Imunodeficiência Adquirida/imunologia , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/mortalidade , Adulto , Contagem de Linfócito CD4 , Infecções por HIV/imunologia , Infecções por HIV/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Carga ViralRESUMO
Interleukin-10 (IL-10) is a pleiotropic cytokine with both immunosuppressive and immunostimulatory functions. Its roles in infections and autoimmunity may have resulted in selective pressures on polymorphisms within the gene, leading to genomic coexistence of several semi-conserved haplotypes involved with diverse pathogen interactions during genomic evolution. Previous studies focused either exclusively on promoter haplotypes or on individual SNPs. We genotyped 21 single nucleotide polymorphisms in the human IL10 gene and examined this variation compared to other mammalian species sequences. Haplotype heterogeneity in human populations is centered around 'classic' 'proximal' promoter polymorphisms: -592, -819 and -1082. High-producing GCC haplotypes are by far the most numerous and diverse group, the intermediate IL-10 producing ACC-inclusive haplotypes seem to be related most closely to the ancestral haplotype, and the ATA-inclusive haplotypes cluster a separate branch with strong bootstrap support. We looked at associations of corresponding haplotypes with HIV progression. A haplotype trend regression confirmed that individuals carrying the low-producing ATA-inclusive haplotypes in European Americans progress to AIDS faster, and most likely explain the role of IL10. Our findings are consistent with the hypothesis that existing polymorphisms in this gene may reflect a balance of historic adaptive responses to autoimmune, infectious and other disease agents.
Assuntos
Síndrome da Imunodeficiência Adquirida/genética , HIV-1 , Haplótipos/genética , Interleucina-10/genética , Síndrome da Imunodeficiência Adquirida/mortalidade , Síndrome da Imunodeficiência Adquirida/virologia , Animais , Estudos de Coortes , Progressão da Doença , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Filogenia , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras GenéticasRESUMO
The screening of common genetic polymorphisms among candidate genes for AIDS pathology in HIV exposed cohort populations has led to the description of 20 AIDS restriction genes (ARGs), variants that affect susceptibility to HIV infection or to AIDS progression. The combination of high-throughput genotyping platforms and the recent HapMap annotation of some 3 million human SNP variants has been developed for and applied to gene discovery in complex and multi-factorial diseases. Here, we explore novel computational approaches to ARG discovery which consider interacting analytical models, various genetic influences, and SNP-haplotype/LD structure in AIDS cohort populations to determine if these ARGs could have been discovered using an unbiased genome-wide association approach. The procedures were evaluated by tracking the performance of haplotypes and SNPs within ARG regions to detect genetic association in the same AIDS cohort populations in which the ARGs were originally discovered. The methodology captures the signals of multiple non-independent AIDS-genetic association tests of different disease stages and uses association signal strength (odds ratio or relative hazard), statistical significance (p-values), gene influence, internal replication, and haplotype structure together as a multi-facetted approach to identifying important genetic associations within a deluge of genotyping/test data. The complementary approaches perform rather well and predict the detection of a variety of undiscovered ARGs that affect different stages of HIV/AIDS pathogenesis using genome-wide association analyses.
Assuntos
Síndrome da Imunodeficiência Adquirida/genética , Biologia Computacional/métodos , Predisposição Genética para Doença , Genoma Humano , HIV-1 , Estudos de Coortes , Interpretação Estatística de Dados , Haplótipos , Humanos , Desequilíbrio de Ligação , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNARESUMO
The association of different CD4(+) cell counts with the same disease risk in treated and untreated populations reflects the effectiveness of highly active antiretroviral therapy (HAART) in persons with human immunodeficiency virus (HIV). Clinical progression of disease following initiation of HAART was determined for 679 HIV-infected men in the Multicenter AIDS Cohort Study by means of Kaplan-Meier survival analyses. Cox proportional hazards models were used to assess the effects of markers of HIV disease, antiretroviral history, and demographic factors. Men who had been followed since January 1993 (pre-HAART) were used to identify CD4(+) levels associated with the acquired immunodeficiency syndrome (AIDS)-free time equivalent to that of men starting HAART with CD4(+) cell counts of <200 cells/microl. Within 3.5 years following HAART initiation, 11.3% of the subjects developed AIDS and 8.5% died. Determinants of AIDS were a CD4(+) cell count of <200 cells/microl at initiation (relative hazard = 2.25, 95% confidence interval: 1.13, 4.49) and age >45 years at initiation (relative hazard = 1.92, 95% confidence interval: 0.98, 3.77). An increase in CD4(+) cell count of >50 cells/microl immediately after HAART initiation also improved prognosis (relative hazard = 0.34, 95% confidence interval: 0.16, 0.71). AIDS risk in men starting HAART with CD4(+) counts of <200 cells/microl (median = 132) was similar to that of non-HAART users with CD4(+) counts of 375-475 cells/microl (median = 432). The equivalence of disease progression to that of nonusers with approximately 300 more cells per microl demonstrates that HAART users have a broader reconstitution of the immune system beyond that of observed increases in CD4(+) cell count.
Assuntos
Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , RNA Viral/sangue , Síndrome da Imunodeficiência Adquirida/epidemiologia , Síndrome da Imunodeficiência Adquirida/prevenção & controle , Adulto , Biomarcadores/sangue , Estudos de Coortes , Progressão da Doença , Intervalo Livre de Doença , Feminino , Infecções por HIV/imunologia , Infecções por HIV/mortalidade , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Razão de Chances , Análise de Sobrevida , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
The presence of clinical manifestations of HIV-1 infection is one measure of immune function failure. We examined the occurrence of clinical manifestations of HIV-1 infection, in particular fever and oral thrush, before and after the initiation of highly active antiretroviral therapy (HAART). Using data collected from 645 participants in the Multicenter AIDS Cohort Study (MACS) who used HAART, 7517 person-visits from January 1992 through March 2000 were stratified by time relative to HAART initiation (> or =1 year preinitiation, <1 year preinitiation, >1 year postinitiation, and > or =1 year postinitiation) and CD4+ T cell count (< or =100, 101-200, 201-350, and >350 cells/microl). Multivariate logistic regression was used to assess the relationship between HAART, CD4+ T cell count, and each self-reported symptom (oral hairy leukoplakia, diarrhea, fever, and oral thrush). After initiation of HAART, clinical manifestations of HIV-1 infection continued to occur and, similar to patterns seen before HAART, were more likely at lower CD4+ T cell counts than at higher (p < 0.001). Except for diarrhea, symptoms did not occur more frequently after HAART. Rather, beyond 1 year after initiation of HAART, there was less oral thrush even at the same CD4+ T cell count. These results provide evidence that increases in CD4+ T cell count due to HAART represent a reconstitution of immune function.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/imunologia , Síndrome da Imunodeficiência Adquirida/imunologia , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Candidíase Bucal/imunologia , Febre/imunologia , Imunocompetência , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Adulto , Fármacos Anti-HIV/administração & dosagem , Antígenos de Diferenciação/análise , Antígenos de Diferenciação/imunologia , Biomarcadores/sangue , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/imunologia , Candidíase Bucal/epidemiologia , Candidíase Bucal/etiologia , Estudos de Coortes , Interpretação Estatística de Dados , Febre/etiologia , HIV-1 , Humanos , Linfonodos/citologia , NAD+ Nucleosidase/análise , NAD+ Nucleosidase/imunologiaRESUMO
Two methods are presented for measuring population effectiveness (i.e., reduction of disease in a population in which only some receive treatment) of antiretroviral therapy among human immunodeficiency virus (HIV)-infected men at risk for acquired immunodeficiency syndrome (AIDS) and followed between January 1, 1986, and June 30, 1999, in the Multicenter AIDS Cohort Study. Method I, requiring use of a seroincident cohort, estimates relative hazards of AIDS for persons at equal duration of infection. Method II, allowing use of a seroprevalent cohort, estimates relative hazards since the beginning of therapy eras for persons starting at equal levels of prognostic markers of disease stage (CD4 cell count and HIV type 1 RNA). The follow-up interval was divided into four calendar periods to characterize different eras of antiretroviral therapy. For method I, the relative hazards were 1.52 (95% confidence interval (CI): 0.93, 2.49), 0.91 (95% CI: 0.66, 1.26), and 0.30 (95% CI: 0.18, 0.51) for the eras of no therapy, dual nucleoside therapy, and potent combination antiretroviral therapy, respectively (monotherapy was the reference era). For method II, the corresponding relative hazards were 1.52 (95% CI: 1.10, 2.09), 1.03 (95% CI: 0.77, 1.38), and 0.31 (95% CI: 0.21, 0.45). These results extend the measurement of population effectiveness from incident to prevalent cohorts and demonstrate the ability of cohort studies to complement information provided by clinical trials.
Assuntos
Infecções por HIV/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/prevenção & controle , Fármacos Anti-HIV/uso terapêutico , Biomarcadores , Contagem de Linfócito CD4 , Estudos de Coortes , Progressão da Doença , Métodos Epidemiológicos , HIV/isolamento & purificação , Infecções por HIV/diagnóstico , Humanos , Masculino , Prognóstico , RNA Viral/análise , Fatores de Risco , Estudos Soroepidemiológicos , Resultado do TratamentoRESUMO
Longitudinal measurements of plasma HIV RNA were analyzed using novel segmented regression models for 62 men in the Multicenter AIDS Cohort Study who at enrollment in 1985 were HIV seropositive and who had stable CD4+ lymphocyte counts and no clinical disease progression for a 6-year period between 1985 and 1991. Through 1996, 20 of the men developed clinical AIDS or died (late progressors) and 42 remained asymptomatic (nonprogressors). Using segmented regression model methods, we estimated, for each individual, the time when a change in HIV RNA trajectory was most likely to have occurred. Prior to this time, late progressors and nonprogressors had stable plasma HIV RNA levels, although the mean level in late progressors was 0.42 log10 copies/ml higher than in nonprogressors (p = 0.018). Furthermore, late progressors showed significant increases in HIV RNA levels of 0.23 log10 copies/ml/year (1.7-fold increase/year). This increase in HIV RNA in the late progressors began approximately 1.1 years prior to the onset of their decline in CD4+ lymphocytes, and 4.8 years prior to the onset of AIDS. These results provide evidence that an increase in the slope of plasma levels of HIV RNA is a sign of incipient progression of HIV disease.
Assuntos
Infecções por HIV/virologia , HIV-1/crescimento & desenvolvimento , HIV-1/genética , RNA Viral/sangue , Síndrome da Imunodeficiência Adquirida/imunologia , Síndrome da Imunodeficiência Adquirida/virologia , Antígenos CD4/imunologia , Contagem de Linfócito CD4 , Estudos de Coortes , Progressão da Doença , Infecções por HIV/imunologia , HIV-1/imunologia , Humanos , Estudos Longitudinais , Masculino , Análise de Regressão , Carga ViralRESUMO
BACKGROUND: From studies of genetic polymorphisms and the rate of progression from human immunodeficiency virus type 1 (HIV-1) infection to the acquired immunodeficiency syndrome (AIDS), it appears that the strongest susceptibility is conferred by the major-histocompatibility-complex (MHC) class I type HLA-B*35,Cw*04 allele. However, cytotoxic T-lymphocyte responses have been observed against HIV-1 epitopes presented by HLA-B*3501, the most common HLA-B*35 subtype. We examined subtypes of HLA-B*35 in five cohorts and analyzed the relation of structural differences between HLA-B*35 subtypes to the risk of progression to AIDS. METHODS: Genotyping of HLA class I loci was performed for 850 patients who seroconverted and had known dates of HIV-1 infection. Survival analyses with respect to the rate of progression to AIDS were performed to identify the effects of closely related HLA-B*35 subtypes with different peptide-binding specificities. RESULTS: HLA-B*35 subtypes were divided into two groups according to peptide-binding specificity: the HLA-B*35-PY group, which consists primarily of HLA-B*3501 and binds epitopes with proline in position 2 and tyrosine in position 9; and the more broadly reactive HLA-B*35-Px group, which also binds epitopes with proline in position 2 but can bind several different amino acids (not including tyrosine) in position 9. The influence of HLA-B*35 in accelerating progression to AIDS was completely attributable to HLA-B*35-Px alleles, some of which differ from HLA-B*35-PY alleles by only one amino acid residue. CONCLUSIONS: This analysis shows that, in patients with HIV-1 infection, a single amino acid change in HLA molecules has a substantial effect on the rate of progression to AIDS. The different consequences of HLA-B*35-PY and HLA-B*35-Px in terms of disease progression highlight the importance of the epitope specificities of closely related class I molecules in the immune defense against HIV-1.
Assuntos
Síndrome da Imunodeficiência Adquirida/genética , Genes MHC Classe I , Infecções por HIV/genética , Antígeno HLA-B35/genética , Alelos , Sequência de Aminoácidos , Sítios de Ligação/genética , População Negra/genética , Progressão da Doença , Intervalo Livre de Doença , Genótipo , Infecções por HIV/etnologia , Infecções por HIV/imunologia , Antígeno HLA-B35/química , Antígenos HLA-C , Humanos , Peptídeos/metabolismo , Modelos de Riscos Proporcionais , Receptores de Peptídeos/química , Receptores de Peptídeos/genética , Receptores de Peptídeos/metabolismo , População Branca/genéticaRESUMO
We evaluated CD4 cell counts over a 3(1/2) year period following the initiation of potent antiretroviral therapy (ART) in the Multicenter AIDS Cohort Study. The study population included 314 HIV-infected gay men who provided CD4 cell counts for at least 2 years after the initiation of potent ART. Trends in CD4 cell counts and plasma HIV-RNA were analyzed by regression methods that incorporated the statistical dependencies of outcomes measured over time within individuals. Regardless of CD4 cell count at initiation of potent ART, CD4 cell counts increased significantly (p <.05) in the first 2 years after initiation. However, between 2 and 3(1/2) years after initiation, these counts neither increased nor decreased. The pattern of the proportion with plasma HIV-RNA <400 copies/ml was similar to CD4 cell count (i.e., increased significantly after initiation and plateau in the subsequent 1(1/2) years). The single most important predictor of the steady state CD4 cell count that was maintained between 2 and 3(1/2) years after initiation was the change in plasma HIV-RNA in the first year after initiation of potent ART.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Inibidores da Transcriptase Reversa/uso terapêutico , Estudos de Coortes , Quimioterapia Combinada , Infecções por HIV/epidemiologia , HIV-1/fisiologia , Homossexualidade , Humanos , Estudos Longitudinais , Masculino , RNA Viral/sangueRESUMO
OBJECTIVES: To evaluate prior antiretroviral therapy experience and host characteristics as determinants of immunologic and virologic response to highly active antiretroviral therapy (HAART). METHODS: We studied 397 men from the Multicenter AIDS Cohort Study (MACS) who initiated HAART between October 1995 and March 1999. CD4 cell count and HIV-1 RNA responses to HAART were measured at the first visit following HAART (short-term) and extending from the first visit to approximately 33 months after HAART (long-term). Prior antiretroviral experience was classified into three groups based on antiretroviral therapy use during the 5 years prior to HAART. Age, race and host genetic characteristics also were assessed for their effects on treatment response. RESULTS: Better short- and long-term CD4 cell and HIV-1 RNA responses were observed in the treatment-naive users. Intermittently and consistently experienced users did not significantly differ in response. Whereas race did not independently affect response, among those initiating HAART with > 400 x 10(6) CD4 cells/l, younger age and the Delta32 CCR5 genotype were associated with a better short-term CD4 cell response. There was a suggestion that having the protective CCR5 genotype also was associated with a better long-term CD4 cell response. CONCLUSION: Immunologic and virologic response to HAART was stronger in individuals who had no prior experience with the antiretroviral therapy agents subsequently included in their initial HAART regimen. Age, level of immune competence and immunogenetics appeared to play a role in the subsequent immune reconstitution following use of highly effective HIV therapy.
Assuntos
Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Terapia Antirretroviral de Alta Atividade , HIV-1 , Síndrome da Imunodeficiência Adquirida/genética , Síndrome da Imunodeficiência Adquirida/imunologia , Adulto , Fatores Etários , Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , Interpretação Estatística de Dados , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Regiões Promotoras Genéticas , Estudos Prospectivos , RNA Viral/sangue , Grupos Raciais , Receptores CCR2 , Receptores CCR5/genética , Receptores de Quimiocinas/genética , Fatores de TempoRESUMO
BACKGROUND: The timing of initiation of antiretroviral therapy is controversial. Current guidelines are heavily based on the principle of 'hit early, hit hard', although the long-term implications of this approach are unknown. METHODS: Using Markov modeling and decision analysis we modeled the virologic outcomes over 10 years in a hypothetical population of 10 000 HIV-infected patients in which therapy (with the possibility of three sequential regimens before the development of multidrug-resistant virus) is started immediately versus starting progressively at rates of 5, 10, 15, 20 or 30% of the original population each year. The model used inputs from available clinical trial data: virologic success rate and durability of the response of the first and subsequent regimens. We performed one-way and two-way sensitivity analysis to evaluate changes in the input variables. RESULTS: If therapy is started immediately in all patients, by 10 years 57% would be undetectable, but 38% would have detectable multidrug-resistant virus. In contrast, the population as a whole would have had better virologic outcomes if one waited before starting treatment at any progression rate; for example, initiating therapy in 10% of the subjects per year results in 64% of patients being undetectable and 24% with multidrug-resistant virus. Two-way sensitivity analysis demonstrates that immediate initiation should be at least 15 to 20% better than delayed antiretroviral therapy to justify immediate initiation of therapy over a wide range of success rates of the delayed start. CONCLUSION: Our analysis, utilizing optimistic outcomes based on short-term clinical trials, provides a theoretical basis for questioning the current aggressive early use of therapy and should help prompt studies that look at when and how to start antiretroviral therapy.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Árvores de Decisões , Infecções por HIV/tratamento farmacológico , HIV-1 , Cadeias de Markov , Modelos Estatísticos , Humanos , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: To determine the effectiveness of potent antiretroviral therapy in reducing opportunistic infections (OI) as both a presenting event and subsequent to an AIDS-defining event. DESIGN AND METHODS: A total of 543 seroconverters and 1470 men with AIDS were compared for the time to development of OI as the presenting AIDS event and as a subsequent event in the 1984-1989, 1990-1992, 1993-1995, and 1996-1998 periods, when the major treatments were no therapy, monotherapy, combination therapy, and potent antiretroviral therapy, respectively. RESULTS: The seroconverters suffered 132 OI and the participants with AIDS had 717 OI. The relative hazard (RH) of OI as the presenting AIDS event declined by 81% in the calendar period when potent antiretroviral therapy was available compared with the monotherapy period. Declines were observed for Mycobacterium avium complex, cytomegalovirus disease, and esophageal candidiasis, but were statistically significant only for Pneumocystis carinii pneumonia. The RH of OI as a secondary infection dropped by 77% in the last calendar period compared with the monotherapy period. A significant decline was observed for all four OI. Prophylactic drug use did not increase in the era of potent antiretroviral therapy. CONCLUSION: The hazard of OI in the era of potent antiretroviral therapy has declined dramatically compared with the era of monotherapy, despite the concurrent decrease in the use of prophylactic drugs. Physicians should consider whether it is necessary to include prophylactic drugs as part of the complex drug regimen for patients on potent antiretroviral therapy.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Terapia Antirretroviral de Alta Atividade , Soropositividade para HIV/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Adulto , Negro ou Afro-Americano , População Negra , Candidíase Bucal/epidemiologia , Estudos de Coortes , Progressão da Doença , Humanos , Incidência , Masculino , Infecção por Mycobacterium avium-intracellulare/epidemiologia , Infecções por Pneumocystis/epidemiologia , Infecções por Pneumocystis/prevenção & controle , Prevalência , Fatores de Risco , Fatores de Tempo , Estados Unidos/epidemiologiaRESUMO
Assessment of adherence to HIV antiretroviral therapy (ART) is required for studying therapeutic effectiveness and identifying subgroups needing focused education. The study's goals were to describe the level of ART adherence using self-reported recall over a 4-day period and to characterize determinants of lower adherence. The interaction between adherence and drug holidays on level of HIV RNA also was investigated. Perfect self-reported adherence was defined as taking all doses and numbers of pills as prescribed for current HIV medications. Independent predictors of <100% adherence were determined using multivariate logistic regression. Among 539 men, 419 (77.7%) were 100% adherent by the algorithm using self-reported data. HIV-1 RNA was <50 copies/ml in 48.2% of the adherent group versus 33.7% in the less adherent group (p = .015). This proportion dropped to 28% if a drug holiday was reported in addition to lower adherence. A drug holiday was not virologically detrimental if the participant was otherwise adherent. Determinants of lower adherence included African American race (odds ratio [OR], 2.4; p = .008), income Assuntos
Fármacos Anti-HIV/administração & dosagem
, Fármacos Anti-HIV/uso terapêutico
, Infecções por HIV/tratamento farmacológico
, Cooperação do Paciente/estatística & dados numéricos
, Adulto
, Negro ou Afro-Americano
, Algoritmos
, Contagem de Linfócito CD4
, Estudos de Coortes
, Esquema de Medicação
, Quimioterapia Combinada
, Infecções por HIV/imunologia
, Infecções por HIV/virologia
, Humanos
, Renda
, Pessoa de Meia-Idade
, Razão de Chances
, Pacientes Ambulatoriais
, Cooperação do Paciente/psicologia
, Reprodutibilidade dos Testes
, Autoadministração
, Autorrevelação
, Inquéritos e Questionários