HIV-1 reverse transcriptase inhibitors: current issues and future perspectives.

One of the major advances in the recent history of the treatment of HIV infections has been the development of different classes of effective antiretroviral drugs. In particular, the reverse transcriptase (RT) inhibitors still represent the majority of the clinically used anti-HIV drugs and constitute the main backbone of currently employed combinatorial regimens. Highly active antiretroviral combination chemotherapy (HAART), combining RT and protease inhibitors, has proven the most effective approach to treat HIV disease, since it has been shown to markedly suppress viral replication and appearance of drug resistance for a relatively long period. These therapies, however, do not constitute a definitive cure, since they are not able to completely eradicate the virus from the infected individual. Beside drug toxicity problems, the emergence of drug resistance associated with the particular regimen employed further complicates the situation. This review will summarise the most recent achievements, as well as the future directions in the development of novel anti-RT compounds.

Isolation and identification of adenovirus in hospitalized children, under five years, with acute respiratory disease, in Havana, Cuba.

Nine Adenovirus (Ad) strains isolated in Cuba, from 128 nasopharingeal swab specimens of children below five years old, with acute respiratory diseases, during 1996 and 1997, were studied by restriction enzyme analysis of genomic DNA with two endonucleases BamH I and Sma I. All different fragment patterns were compared with the respective prototypes. The identified adenoviruses were Ad 1 (n=4), Ad 2 (n=1) and Ad 6 (n=4). Males were more frequently infected than females. The analysis of the occurrence of these Adenovirus strains of subgenus C revealed that Ad 1 and Ad 6 were the predominant serotypes in 1996 and in 1997, respectively.

[Rapid diagnosis of principal respiratory viruses in the city of Havana, 1995-97]. / Diagnóstico rápido de los principales virus respiratorios en Ciudad de la Habana, 1995-97.

Acute respiratory diseases (ARD) are the most common infections in humans and difficult to prevent. Viruses have been recognized as predominant ethiological agents. In Cuba, ARD constitute a major problem of health and are the first cause of morbidity and important cause of mortality. In this paper, rapid diagnosis was performed to 516 clinical samples which arrived to the Reference Respiratory Viruses Laboratory of the Pedro Kourí Institute of Tropical Medicine (IPK) from different parts of Havana City during 1995, 1996 and 1997. The results obtained have shown 218 positive samples (Influenza A, 89; respiratory syncytial virus 52; Influenza B, 45; Adenovirus, 13; human parainfluenza virus(HPIV)-1, 6; HPIV-2, 3 and HPIV-3, 10). Influenza A was the virus most frequently found in adults, whereas in closed population of teen-agers and adults, Influenza B was frequently found. Furthermore, respiratory syncytial virus was the most important pathogen in children's under 1 year of age.

Detection of respiratory syncytial virus in nasopharyngeal secretions by 24-well plate precentrifugation assay using a monoclonal antibody against F protein.

BACKGROUND: Respiratory syncytial virus (RSV) is responsible for 50% of all bronchiolitis and 25% of pneumonia cases during the first month of life. Detection of the RSV antigen by immunofluorescence in exfoliated nasal epithelium or by other methods in nasopharyngeal swabs is useful in the potentially infected patient because results are available within a few hours. In contrast, RSV antigen detection in cell culture may require as much as 3 weeks. METHODS: Three methods for detection of respiratory syncytial virus in 131 clinical respiratory specimens from patients with acute respiratory disease and bronchiolitis were compared utilizing the following: a precentrifugation immunofluorescence assay using Hep-2 cells, indirect immunofluorescence assay, and conventional tube cell culture using Hep-2 cells. RESULTS: Respiratory syncytial virus was identified in 36 specimens by the three methods previously described. The virus was recovered in 41 (31.3%) samples by precentrifugation immunofluorescence assay, 40 (30.5%) were identified by the immunofluorescence technique, and 38 (29.0%) cases were positive by conventional cell culture. The sensitivity of the precentrifugation assay in relation to the immunofluorescence technique was 90%, the specificity 94.5%, and the agreement, 96.2%. A positive predictive value of 90.2% was obtained. Sensitivity, specificity, agreement, and positive predictive values obtained by the precentrifugation assay variant compared to the conventional cell were 90.8%, 94.5%, 93.1%, and 87.8%, respectively. CONCLUSIONS: The precentrifugation immunofluorescence assay method was as sensitive as the remainder of the methods used in our study and represents a valid alternative for rapid detection of respiratory syncytial virus in clinical samples.

Diagnóstico rápido de los principales virus respiratorios en Ciudad de la Habana, 1995-97 / Rapid diagnosis of principal respiratory viruses in the city of Havana, 1995-97

Acute respiratory diseases (ARD) are the most common infections in humans and difficult to prevent. Viruses have been recognized as predominant ethiological agents. In Cuba, ARD constitute a major problem of health and are the first cause of morbidity and important cause of mortality. In this paper, rapid diagnosis was performed to 516 clinical samples which arrived to the Reference Respiratory Viruses Laboratory of the Pedro KourÝ Institute of Tropical Medicine (IPK) from different parts of Havana City during 1995, 1996 and 1997. The results obtained have shown 218 positive samples (Influenza A, 89; respiratory syncytial virus 52; Influenza B, 45; Adenovirus, 13; human parainfluenza virus(HPIV)-1, 6; HPIV-2, 3 and HPIV-3, 10). Influenza A was the virus most frequently found in adults, whereas in closed population of teen-agers and adults, Influenza B was frequently found. Furthermore, respiratory syncytial virus was the most important pathogen in children's under 1 year of age.

Diagnóstico rápido de los principales virus respiratorios en Ciudad de la Habana, 1995-97 / Rapid diagnosis of principal respiratory viruses in the city of Havana, 1995-97

Acute respiratory diseases (ARD) are the most common infections in humans and difficult to prevent. Viruses have been recognized as predominant ethiological agents. In Cuba, ARD constitute a major problem of health and are the first cause of morbidity and important cause of mortality. In this paper, rapid diagnosis was performed to 516 clinical samples which arrived to the Reference Respiratory Viruses Laboratory of the Pedro KourY Institute of Tropical Medicine (IPK) from different parts of Havana City during 1995, 1996 and 1997. The results obtained have shown 218 positive samples (Influenza A, 89; respiratory syncytial virus 52; Influenza B, 45; Adenovirus, 13; human parainfluenza virus(HPIV)-1, 6; HPIV-2, 3 and HPIV-3, 10). Influenza A was the virus most frequently found in adults, whereas in closed population of teen-agers and adults, Influenza B was frequently found. Furthermore, respiratory syncytial virus was the most important pathogen in childrens under 1 year of age.(AU)

Diagnóstico rápido de los principales virus respiratorios en Ciudad de la Habana, 1995-97. / [Rapid diagnosis of principal respiratory viruses in the city of Havana, 1995-97]

Acute respiratory diseases (ARD) are the most common infections in humans and difficult to prevent. Viruses have been recognized as predominant ethiological agents. In Cuba, ARD constitute a major problem of health and are the first cause of morbidity and important cause of mortality. In this paper, rapid diagnosis was performed to 516 clinical samples which arrived to the Reference Respiratory Viruses Laboratory of the Pedro Kourí Institute of Tropical Medicine (IPK) from different parts of Havana City during 1995, 1996 and 1997. The results obtained have shown 218 positive samples (Influenza A, 89; respiratory syncytial virus 52; Influenza B, 45; Adenovirus, 13; human parainfluenza virus(HPIV)-1, 6; HPIV-2, 3 and HPIV-3, 10). Influenza A was the virus most frequently found in adults, whereas in closed population of teen-agers and adults, Influenza B was frequently found. Furthermore, respiratory syncytial virus was the most important pathogen in childrens under 1 year of age.

Antigenic and genetic characterization of twenty-six strains of human respiratory syncytial virus (subgroup A) isolated during three consecutive outbreaks in Havana city, Cuba.

Twenty-six human respiratory syncytial virus strains (subgroup A) isolated from three outbreaks in Havana City during the period 1994/95, 1995/96 and 1996/97 were analyzed to determine their antigenic and genetic relationships. Analyses were performed by monoclonal antibodies and restriction mapping (N gene) following amplification of the select region of the virus genome by polymerase chain reaction. All isolated strains were classified as subgroup A by monoclonal antibodies and they showed a restriction pattern NP4 that belonged to subgroup A. Thus the results obtained in this work, showed a close relation (100%) between antigenic and genetic characterization of the isolated strains in our laboratory. These methods permit the examination of large numbers of isolates by molecular techniques, simplifying the researchs into the molecular epidemiology of the virus.

Unusual antigenic and genetic characteristics of human respiratory syncytial viruses isolated in Cuba.

The G protein of 23 strains of human respiratory syncytial virus isolated in Havana, Cuba, between October 1994 and January 1995 was analyzed at the antigenic and genetic level. All viruses reacted with 10 of 11 antibodies specific for the Long strain. Moreover, the G protein gene of the Cuban isolates had only five nucleotide differences from the sequence of the Long gene. The homogeneity of the Cuban isolates and their resemblance to an ancient strain, such as Long, are at odds with previous findings for viruses isolated in countries with a temperate climate and different socioeconomic status. The G proteins of three of four other viruses isolated in Havana 2 years later (1996) were also identical to those of the 1994-to-1995 isolates, and the fourth virus had a single extra nucleotide difference. This, again, is unusual, since no identical viruses had been isolated in different epidemics previously. The singular characteristics of the Cuban isolates reported here are discussed in terms of the epidemiological, climatic, and socioeconomic characteristics of Cuba.

[A comparison of the NCI-H292 line with other continuous lines for the multiplication of respiratory viruses]. / Comparación de la línea NCI-H292 con otras líneas continuas para la multiplicación de virus respiratorios.

The NCI-H292 continual line of mucoepidermoid cells of the human lungs has been reported to be useful for the propagation of many viruses, mainly Adenovirus and Paramyxovirus. It is stated the possible substitution of primary cultures of monkey kidney for NCI-H292 in order to isolate such agents. In the present paper it is evaluated the utility of this line for multiplying the respiratory syncytial viruses Adenovirus 3 and 7, and the parainfluenza viruses 1, 2, and 3, in comparison with the continual cellular lines traditionally used for the propagation of these viruses, whose strains were inoculated this time in the Vero, HEp-2, and HeLa lines, according to their know sensitivities as well as in NCI-H292 simultaneously. The viral multiplication was detected by the appearance of the cytopathic effect or by hemadsorption. As a result, it was demonstrated the multiplication capacity of the NCI-H292 line for Adenoviruses 3 and 7 and parainfluenza 3, being more useful for their multiplication than the traditionally used lines.