Associations of CCR5, CCR2, and Stromal Cell–Derived Factor 1 Genotypes with Human Immunodeficiency Virus Disease Progression in Patients Receiving Nucleoside Therapy

Genotype data for CCR5, CCR2, and stromal cell–derived factor 1 (SDF-1) were obtained from 354 human immunodeficiency virus type 1 (HIV-1)–positive subjects who were being treated with nucleosides. Associations with HIV-1 load, HIV syncytium-inducing (SI) phenotype, CD4 cell count, and disease progression were analyzed. No differences in HIV-1 load or CD4 cell count were observed between wild type (+) and variant genotypes. Changes from non-SI to SI viral phenotype were more frequent in heterozygotes with a 32-bp deletion (Δ32) in the CCR5 gene than in + homozygotes (40% vs. 7%; P=.01). In a multivariate analysis, heterozygous CCR5 Δ32 was associated with reduced hazard of progression (hazard ratio, 0.32; P=.02). Subjects homozygous for the SDF-1 3′A variant had more-rapid disease progression (P=.008). The SDF-1 homozygous 3′A variant was related to more-rapid disease progression, and CCR5 Δ32 was associated with reduced rates of hazard for disease progression in nucleoside-treated subject

Association of Efavirenz Hypersusceptibility with Virologic Response in ACTG 368, a Randomized Trial of Abacavir (ABC) in Combination with Efavirenz (EFV) and Indinavir (IDV) in HIV-Infected Subjects with Prior Nucleoside Analog Experience

PURPOSE: To evaluate the association of efavirenz hypersusceptibility (EFV-HS) with clinical outcome in a double-blind, placebo-controlled, randomized trial of EFV plus indinavir (EFV+IDV) vs. EFV+IDV plus abacavir (ABC) in 283 nucleoside-experienced HIV-infected patients. METHODS AND RESULTS: Rates of virologic failure were similar in the 2 arms at week 16 (p=0.509). Treatment discontinuations were more common in the ABC arm (p=0.001). Using logistic regression, there was no association between virologic failure and either baseline ABC resistance or regimen sensitivity score. Using 3 different genotypic scoring systems, EFV-HS was significantly associated with reduced virologic failure at week 16, independent of treatment assignment. In some patients on the nucleoside-sparing arm, the nucleoside-resistant mutant L74V was selected for in combination with the uncommonly occurring EFV-resistant mutant K103N+L100I; L74V was not detected as a minority variant, using clonal sequence analysis, when the nucleoside-sparing regimen was initiated. CONCLUSIONS: Premature treatment discontinuations in the ABC arm and the presence of EFV-hypersusceptible HIV variants in this patient population likely made it difficult to detect a benefit of adding ABC to EFV+IDV. In addition, L74V, when combined with K103N+L100I, may confer a selective advantage to the virus that is independent of its effects on nucleoside resistance

Fatores prognósticos no carcinoma espinocelular de cavidade oral Prognostic factors in squamous cell carcinoma of the oral cavity

Devido à incerteza da evolução do câncer oral é que os pesquisadores procuram fatores que possam influenciar no prognóstico. OBJETIVO: Avaliar em pacientes com carcinoma espinocelular de cavidade oral variáveis que possam influenciar no tempo de sobrevida. MATERIAIS E MÉTODOS: Analisados dados de 45 pacientes no período de Janeiro de 2001 a Janeiro de 2006. As curvas de sobrevida foram estimadas pelo método de Kaplan-Meier e para compará-las os testes de log-rank e o modelo de regressão de Cox. Desenho do Estudo: Análise retrospectiva. RESULTADOS: A sobrevida global foi de 39% em 5 anos. Apenas as variáveis, metástase cervical (p=0,017), radioterapia pós-operatória (p=0,056) e margens comprometidas (p=0,004) tiveram significância estatística. A sobrevida foi menor em pacientes: com metástase cervical; com margens comprometidas e os submetidos à radioterapia pós-operatória, ou seja, nos tumores mais agressivos. Após ajustamento, a radioterapia não mostrou significância estatística. Provavelmente a sobrevida de 39% seja pelo elevado número de pacientes com metástase (52,2%) e pelo fato da amostra ser basicamente de cânceres de língua e assoalho (82%), os de controle mais difícil. CONCLUSÃO: A metástase cervical e o comprometimento das margens cirúrgicas são os fatores prognósticos no carcinoma de cavidade oral que influenciaram na sobrevida.<br>Researchers have been looking for factors that can influence the prognosis of oral cancer, because its outcome is highly uncertain. AIM: To evaluate variables that can impact the survival rate of patients with squamous-cell carcinoma of the oral cavity. MATERIAL AND METHODS: Data analysis of 45 patients from January, 2001 to January, 2006. Survival rate curves have been estimated using the Kaplan-Meier method and they have been compared through the log-rank test and the Cox regression standard. Study design: Retrospective analysis. RESULTS: Total five-year survival rate was of 39% fpr these patients. Only the neck metastases (p=0.017), postoperative radiotherapy (p=0.056) and diseased margin(p=0.004) variables had statistic relevance. Survival rate was lower in patients with neck metastases, margins involved and those who underwent postoperative radiotherapy, in other words, those with the most aggressive tumors. After adjustment, radiotherapy did not prove to be statistically relevant. It is likely that the survival rate of 39% was due to the high number of patients with metastasis (52%) and because the samples were mostly of tongue and mouth floor diseases (82%), which are the hardest to control. CONCLUSION: Neck metastases and diseased margins of oral cavity carcinomas are the prognostic factors that can most impact the survival rate