Analysis of the protease sequences of HIV-1 infected individuals after Indinavir monotherapy.

BACKGROUND: Protease inhibitors (PI) are an important HIV-1 treatment tool. The HIV-1 genetic diversity as a result of antiretroviral exposure is a potential barrier to successful antiretroviral therapy. OBJECTIVES: To describe the impact of the selective pressure of the PI Indinavir in the protease region of the pol gene of HIV-1. STUDY DESIGN: We have examined the extent of protease sequence heterogeneity in previously antiretroviral drug naive HIV-1 infected individuals receiving Indinavir as monotherapy for at least 48 weeks. RESULTS: Analysis based on the consensus of this group of sequences showed regions with higher and lower polymorphism. The degree of genetic variation was greater in regions less critical for the structure and function of the enzyme. To investigate the selective pressure imposed by drug therapy, we have analyzed the rate of synonymous (ds) and nonsynonymous (dn) substitutions. The three critical regions for enzyme activity showed ds/dn ratio >1. whereas other regions had ds/dn ratio <1. The detected amino acid mutations had a trend to be conservative, thus maintaining the physical chemical amino acid characteristics. Phylogenetic analysis established the presence of subtype B (n=38), subtype F (n=9), and B/F recombinants within the protease region of pol gene (n=3). More prevalent detected mutations, thought to contribute to antiretroviral resistance, were L63P (42%), L10I (35%), M36I (30%), V82A/T/F (26%). CONCLUSIONS: A great deal of predicted cross-resistance between PIs was observed. Out of the 50 individuals, 34% were considered to have major mutations to Indinavir, and 66% had minor or no mutations to Indinavir. Viral loads were significantly higher among patients with major mutations, compared with patients minor/no mutations, although no differences in the CD4 counts were found. The viral load at baseline and nadir (week 4) was able to predict the group of individuals with greater chances of selecting drug resistance related mutations.

Padräo radiológico das afecçöes pulmonares em pacientes com síndrome de imunodeficiência adquirida (AIDS) / Chest X-rays pattern in lung affections in patients with acquired immunodeficiency syndrome (AIDS)

O pulmäo é o órgäo mais acometido na AIDS, evidenciado em geral nos estádios iniciais da doença. O comportamento pulmonar pode ser devido tanto às afecçöes oportunistas, que na maioria das vezes decorre de reativaçäo de infecçöes latentes, como a neoplasias ou outras doenças näo-infecciosas. Com o objetivo de determinar o padräo radiológico das afecçöes pulmonares que acometem os pacientes portadores de HIV acompanhados no Serviço de Doenças Infecciosas e Parasitárias do Hospital Säo Paulo/Escola Paulista de Medicina, foram realizadas 82 broncoscopias com biópsia transbrônquica (BTB) e coleta de lavado bronquíolo-alveolar (LBA) em 81 pacientes no período de julho de 1989 a dezembro de 1990. Infiltrado interstício-nodular difuso, com ausência de derrame pleural, cavitaçäo ou condensaçäo, foi o achado radiológico mais freqüente, sendo encontrado em 43// doa pacientes com micobacteriose, 43// dos pacientes com pneumonia por Pneumocystis carinii (PPC), 64// dos pacientes com pneumonite intersticial inespecífica (PII) e 73// dos pacientes com pneumonia bacteriana. O diagnóstico de PPC foi estabelecido em apenas 11// dos pacientes que apresentavam somente infiltrado interstício-nodular difuso à radiografia de tórax. Nossos dados permitiram concluir que o infiltrado interstício-nodular difuso (HND) e o padräo radiológico mais freqüente nas principais afecçöes pulmonares que acometem pacientes com AIDS e que apenas uma pequena porcentagem dos pacientes que apresentam sinais e sintomas pulmonares inespecíficos, com HND à radiografia de tórax, tem o diagnóstico confirmado de PPC