[Alcohol consumption among high school students in Brescia, Italy]. / Indagine sui consumi, atteggiamenti e conoscenze nei confronti delle bevande alcoliche tra gli studenti delle scuole secondarie di secondo grado di Brescia.

A random sample of 1,495 high school student of 9th and 13th grade in Brescia, North Italy, were interviewed about their alcohol consumption, knowledge and attitudes using an anonymous self-administered questionnaire. The percentages of students who usually consumed alcoholic beverage, were 39.7% and 30.3% in males and females, respectively, in 9th grade students and were 51.4% and 23.8% in males and females, respectively, in 13th grade students. The frequency of drunkenness during the month previous the interview was, among 9th graders: 6.9% males and 8.7% females; among 13th graders: 20.7% males and 13.3% females. The following variables were positively associated with alcohol consumption: 1) regular smoking; 2) peer alcohol drinking (best friend and partner); 3) parents' alcohol consumption. When comparing the present survey with a previously carried out in 1989, similar results were found as regards alcohol consumption; on the contrary higher prevalence of drunkenness was found in the 2008 survey, that in the 1989 one.

Secondary mutations in the protease region of human immunodeficiency virus and virologic failure in drug-naive patients treated with protease inhibitor-based therapy.

The role of mutations in protease (PR) and reverse-transcriptase (RT) of human immunodeficiency virus (HIV) in predicting virologic failure was assessed in 248 antiretroviral-naive HIV-positive patients who began a PR inhibitor-containing antiretroviral regimen. Genotypic testing was performed on plasma samples stored before the start of therapy. Twenty-seven patients (10.9%) had mutations in the RT, 5 (2%) carried primary mutations in the PR, and 131 (52.8%) showed only secondary PR mutations. Virologic failure at week 24 occurred in 62 (25.0%) of 248 patients. There was a statistically significant correlation between virologic failure and the number of PR mutations (P= .04, chi(2) test). Mutations at codons 10 and 36 of PR (present in 39.3% and 40.0% of patients in whom treatment failed, respectively) were identified by stepwise logistic regression as the strongest predictors of virologic failure (odds ratio, 2.20; 95% confidence interval, 1.30-3.75; P= .004). If confirmed in independent studies, this result may justify the increased use of HIV genotyping in drug-naive patients requiring antiretroviral therapy.

Increasing prevalence of non-clade B HIV-1 strains in heterosexual men and women, as monitored by analysis of reverse transcriptase and protease sequences.

OBJECTIVE: We evaluated the prevalence of HIV-1 non-clade B over time in a formerly clade B-restricted area. Protease and reverse transcriptase regions of the pol gene were used for phylogenetic and recombination analysis and for clade assignment to HIV-1 A-D, F-H, J, and K strains of the M group. METHODS: The pol gene of 349 HIV-1 patients belonging to the Italian Cohort Naive for Antiretrovirals (ICONA) were genotypically analyzed to study the prevalence of antiretroviral-associated resistance mutations. All HIV-1 pol sequences and 32 HIV reference strains were analyzed, including the reference strains for the major HIV-1 subtypes. The non-clade B sequences according to the HIV-1 Subtyping Tool program were further studied by a bootscan analysis (SimPlot) to investigate the likelihood of recombination between subtypes. RESULTS: Phylogenetic analysis detected 19 of 349 (5.4%) non-clade B subtypes. The proportions of patients carrying non-clade B virus before and after 1997 were 1.9% and 8.4%, respectively (p =.008). Among whites, heterosexual infection and female gender were significantly associated with the presence of non-clade B subtypes (p =.001 and.005, respectively). Non-clade B HIV-1 was harbored by 14.5% of the heterosexuals who were found to be HIV-1 positive after 1997, 60% of whom were women. Bootscan analysis identified four strains as F, two as A, one as C, one as G, and 11 (57.9 %) as non-clade B recombinant subtypes. CONCLUSION: Detection of HIV-1 subtypes and intersubtype recombinants in a previously clade B-homogeneous area indicates that the HIV-1 epidemic is evolving in Italy and that heterosexuals and women are at increased risk of infection with non-clade B HIV-1 subtypes. Sequences inferred from the pol gene yield to establish the subtype of circulating HIV-1 strains. As a consequence, genotyping of pol gene for testing resistance to antiretrovirals warrants concomitant surveillance of non-clade B subtypes.

Prevalence of multiple dideoxynucleoside analogue resistance (MddNR) in a multicenter cohort of HIV-1-infected Italian patients with virologic failure.

We evaluated the prevalence of both Q151M and 6-bp insert at position 69 of RT region responsible for multiple dideoxynucleoside analogue-resistant (MddNR) HIV-1 variants in 177 patients who failed to respond to combination therapy. Patients had received protease inhibitors (PI) and/or nonnucleoside reverse transcriptase inhibitors (NNRTIs) after a long-term experience with nucleoside reverse transcriptase inhibitors (NRTIs) (including zidovudine monotherapy). Two of 177 patients (1.1%) showed the specific complex of Q151M mutation, while 4 (2.3%) had the 69 6-bp insert. Mutations that belong to the 151 set in the absence of the pivotal Q151M substitution were detected in as many as 3.9% of the patients. One patient exhibited a 69S [VG] insert that has not been previously phenotypically characterized. This HIV-1 isolate had high levels of resistance to all NRTIs except stavudine. MddNR is an emerging problem after sequential therapy with this class of compounds among HIV-1-infected patients. Either didanosine (ddI) or zidovudine (ZDV) monotherapy allowed the emergence of MddNR variants containing Q151M complex. Monotherapy with ZDV and ddI or subsequent treatments with various NRTI combinations were the common background in the patients with the 69 insert. The overall prevalence of MddNR (3.4%) in Italy is comparable with that observed in several other European countries (3.4%-6.5%). These data suggest that patients failed by NRTI regimens should be analyzed for the presence of both patterns of MddNR.

Prevalence of transmitted nucleoside analogue-resistant HIV-1 strains and pre-existing mutations in pol reverse transcriptase and protease region: outcome after treatment in recently infected individuals.

We retrospectively studied 38 Italian recently HIV-1-infected subjects who seroconverted from 1994 to 1997 to investigate: (i) the prevalence of nucleoside reverse transcriptase inhibitors (NRTI)-related mutations at primary infection; (ii) the proportion of naturally occurring mutations in reverse transcriptase (RT) and protease regions of patients naive for non-nucleoside RT inhibitors (NNRTIs) and protease inhibitors (PIs); (iii) the drug-susceptibility to NRTIs and PIs in subjects with NRTI- and/or PI-related mutations; and (iv) the outcome of seroconverters treated with various NRTIs or NRTI/PI regimens. Baseline HIV-1 plasma viraemia and absolute CD4 count at baseline could not be used to distinguish patients with NRTI- and/or PI-related pre-existing mutations from those with wild-type virus (P = 0.693 and P = 0.542, respectively). The frequency of zidovudine-related mutations was 21% in the study period. The response to treatment was not significantly different in subjects with or without genotypic zidovudine-related mutations at primary infection (P = 0.744 for HIV-1 RNA and P = 0.102 for CD4 cells). Some natural variation (2.6%) was present within regions 98-108 and 179-190 of RT involved in NNRTI resistance. The high natural polymorphism in the protease region present in our patients was similar to that reported by others. In our study some PI-associated substitutions, thought to be compensatory in protease enzymatic function, could confer intermediate to high PI-resistance. As discrepancies between genotypic and phenotypic results may exist in recent seroconverters, our data suggest that the role of transmitted NRTI- and PI-resistant variants remain to be fully elucidated in vivo.

Prevalence of HIV-1 resistant strains in recent seroconverters.

Twenty-nine HIV-1 recently infected subjects were retrospectively studied to investigate both the prevalence of nucleoside reverse transcriptase inhibitors (NRTI)-related mutations at primary infection and the proportion of naturally occurring mutations in protease inhibitor (PI)-naive patients. Neither HIV-1 plasma viremia nor CD4 absolute count at baseline could distinguish patients with NRTI pre-existing mutations from those with wild-type virus. An increasing proportion of ZDV-related mutations was observed over time with an overall frequency of 20.7% in the study period. Only 1 out of 6 patients (16.7%) with ZDV-related mutations showed a phenotypically ZDV resistant isolate. A striking proportion of polymorphic changes was present in the protease region of pol gene in newly infected individuals. As many as 80% of seroconverters presented at least one naturally occurring substitution. Some PI-associated substitutions, thought to be compensatory in protease enzymatic function, could confer intermediate to high PI-resistance. Their role following PI administration remains to be elucidated. Our data suggest that the choice of drugs should be oriented by both genotypic and phenotypic evaluations to tailor individual regimens in seroconverters.

Identification of two distinct subsets of long-term nonprogressors with divergent viral activity by stromal-derived factor 1 chemokine gene polymorphism analysis.

Stromal-derived factor (SDF)-1, the natural ligand for CXCR4, is present in a common polymorphic variant defined by a G-->A transition in the 3' untranslated region of the gene. In persons infected with human immunodeficiency virus type 1 (HIV-1), the homozygous genotype (SDF1-3'A/3'A) has been postulated to interfere with the appearance of T-tropic syncytium-inducing strains. The polymorphism of SDF1 was correlated with HIV-1 phenotype, plasma viremia, and unspliced and multiply spliced specific transcripts in 158 virologically characterized HIV-1-infected patients (39 recent seroconverters, 75 typical progressors, and 44 AIDS patients) and in 42 HIV-1-infected long-term nonprogressors (LTNPs). Analysis of SDF1 allele distribution revealed that SDF1-3'A/3'A status is associated with low CD4 cell count (P=.0449) but not with a specific HIV-1 phenotype. In LTNPs, SDF1-+/+ condition defined a subset of persons with lower HIV-1 replication than in heterozygous subjects. The low viral activity in SDF1-+/+ LTNPs suggests that other factors play a major role in vivo in determining the course of HIV-1 infection.