Chiodo F

Mutation patterns of the reverse transcriptase genes in HIV-1 infected patients receiving combinations of nucleoside and non nucleoside inhibitors

A genotyping assay was used to define human immunodeficiency virus type 1 (HIV-1) reverse transcriptase codons in plasma samples from 80 HIV-1 patients extensively treated with two nucleoside reverse transcriptase (zidovudine and lamivudine) and one non nucleoside reverse transcriptase (nevirapine) inhibitor. The frequencies of T215S/Y/F, M41L, D67N, L210W K70R, K219Q mutations, detectable in plasma samples, conferring resistance to zidovudine were 61.2, 56.2, 36.2, 31.5, 27.5 and 17.5%, respectively. Mutations (M184V or M184I) conferring resistance to lamivudine were detected in an extremely high percentage of patients (61%). Among mutations correlated to high (K103N, V106A, Y181C/I, Y188C/H/L, G190A/C/E/Q/S/T) or moderate (V108I, V118I) levels of nevirapine resistance, the predominant amino acid change was a substitution at 103 codon, present in 24 of 80 samples tested. Finally Q151M, the marker mutation able to confer resistance to all nucleoside analogues, was detected in seven patients with a viral load of between 1 x 10(4) and 9 x 10(4) HIV-1 RNA copies/ml. The relationship between the genotype and the viral load showed that the incidence of some specific mutations [M41L, T215Y (correlated to zidovudine resistance) and K103N (correlated to all NNRTIs drugs)] significantly (P=0.001) increased with higher viral load. Our results, albeit limited to a small cohort, showed a high frequency of mutations correlated to drugs in use, suggesting a need for therapeutic change in the near future and demonstrating that the development of genotyping tests helps to guide the therapeutic management of HIV-1 infected people. Our data highlight the dangers of selecting antiretroviral therapy without previous antiretroviral drug testing. Although the cost of these assays is a concern, prescribing inefficacious drugs could create serious problems for HIV-1 patients.

Serological study of subjects with seroconversion to human immunodeficiency virus

Twelve homosexual males who seroconverted to human immunodeficiency virus (HIV) were followed-up for over two years. Analysis of sera by immunoblotting showed that seroconversion was characterized by the presence of specific IgM that reacted mainly with viral polypeptides of molecular weights ranging from 17 Kd to 55 Kd. Specific IgG to all HIV proteins was detected. Immunoblotting showed that antibodies to 24 Kd core protein alone or in association with 17 Kd polypeptide appeared first in some cases. Virus antigen was detected in six patients: five subjects were positive at the time of seroconversion, and one became positive afterwards. It is concluded that detection of IgG and IgM antibody against the different viral polypeptides, together with detection of viral antigen is necessary in order to determine the stage of HIV infection.

Efficacy of penicillin G benzathine as antimicrobial treatment of cutaneous secondary syphilis in patients with HIV infection.

The frequently reported cases of late cardiovascular syphilitic complications, neurosyphilis and invasion of cerebrospinal f luid by Treponema pallidum in subjects with advanced HIV disease have led to doubts about the efficacy of the recommended antibiotic therapy with penicillin G benzathine for early syphilis. Moreover, the microbiological and clinical adequacy of this conventional antimicrobial treatment is also questioned because HIV patients usually have a less significant serological response than individuals without HIV infection, and serological failure may be associated with clinical failure in the setting of HIV disease 1-3. This letter deals with three cases with cutaneous secondary syphilis out of a cohort of 1,115 HIV-infected patients coming to our reference center between July and December 2001. Syphilis occurred in two males and one female (two homosexuals and one intravenous drug user), aged 37 to 43 years, who have been diagnosed as HIV-positive for 1-11 years. Journal of Chemotherapy Vol. 14 n. 5 (533-534) 2002

Prevalence and Virologic Consequences of HIV-1 Genotype Mutations Detected in a Cohort of 161 Italian Patients Receiving a Nelfinavir-Based Highly Active Antiretroviral Therapy

Abstract A cross-sectional study was carried out in our tertiary care hospital between January 1998 and December 2001. All 161 consecutive patients naïve to nelfinavir and who had received a nelfinavir-based highly active antiretroviral therapy (HAART) of at least 24-week duration were extrapolated from the 802 adult HIV-infected subjects treated with antiretroviral therapy. All cases of virologic failure were considered and viral genotyped. Virologic failure occurred in 80 out of 161 nelfinavir-treated patients, all belonging to the experienced group. On the whole, only 11 patients (7%) developed the D30N substitution, whose 6 was in association with the N88D mutation. Among the 80 failed patients, the M184V mutation was detected in 52 (65%), while only 7patients showed simultaneously the M184V, T215Y and K103N substitutions. In our HIV-infected population receiving a nelfinavir-based HAART, the D30N mutation has shown a low absolute frequency, while the detection of M184V substitution and the simultaneous occurrence of M184V, T215Y and K103N mutations were related to a more favorable virological response.

PI and OPG/RANKL levels in human osteoblast cells

Purpose of the study The association between loss of bone mineral density (BMD) and PI use is evidenced on several in vitro models and seems to have different etiology depending on specific molecule. Although an HAART regimen always contains one or more transcriptase inhibitors, there are no specific data available regarding specific PI action on BMD. However, some in vitro experiments showed that these compounds might induce the differentiation of osteoclast cells. In order to analyse the specific effect of each PI on human osteoblast we analysed OPG and RANKL levels after exposing the cells to each PI.