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Biomedical subjects

Massimo Andreoni

Publications and source records attributed to Massimo Andreoni.

At least 19 recordsLinked to original sources
PubMed2005

Gender differences in clinical progression of HIV-1-infected individuals during long-term highly active antiretroviral therapy.

OBJECTIVE: To assess gender differences in the long-term clinical, virological and immunological outcomes during highly active antiretroviral therapy (HAART). METHODS: This longitudinal observational multicentre study followed 2460 HIV-infected patients who had begun a protease inhibitor-based regimen for a median period of 43 months. Outcome measures were virological suppression (< 500 copies/ml), confirmed virological rebound after suppression, and death or new AIDS-defining illness (ADI). RESULTS: At baseline, 690 female patients (28.0%) had significantly lower age, higher prevalence of heterosexual contact and lower prevalence of intravenous drug use as risk factors for HIV infection compared with males. Furthermore, females had a lower number of AIDS-defining illnesses, higher CD4 cell counts and lower viral loads. No gender differences were reported in terms of proportion of patients achieving viral suppression or exhibiting rebound after achieving viral suppression. Female patients experienced reduced clinical progression during follow-up compared with males (P = 0.008) by Kaplan-Meier analysis; however this difference was not significant in an adjusted analysis. In a multivariate model, the interaction between gender and risk factor for HIV or viral load showed that female drug users and female patients with a baseline HIV RNA viral load of 10(4)-10(5) copies/ml had a favourable clinical outcome compared with males (P = 0.035 and P = 0.015, respectively). CONCLUSION: No differences were found between genders in terms of virological and immunological outcomes during long-term HAART. Nevertheless, a lower risk of clinical progression was reported among female patients with intermediate baseline viral load than in males.

Adult↗
PubMed2005

Clinical outcome after 4 years follow-up of HIV-seropositive subjects with incomplete virologic or immunologic response to HAART.

The duration of the clinical, virologic, and immunologic response to HAART, is not well defined. In this observational multi-center study 2,143 patients were enrolled classified according to virologic suppression (<500 cp/ml) and immune recovery (>100 CD4+ cells/mul from baseline) at month 12 of HAART as complete responders, virologic only responders, immunologic only responders and non-responders. Kaplan Meyer curves, multivariate and politomous regression analysis were used. Complete responders patients were 781 (36.4%), immunologic only responders 441 (20.6%), virologic only responders 336 (15.7%), and non-responders 585 (27.3%). Using multivariate analysis, being antiretroviral-naive increased the probability of having both a virologic only or a complete response and reduced the probability of an immunologic only response (P < 0.001 for all tests). Older age was associated directly with a virologic only response and inversely associated with an immunologic only response (P = 0.027 and P = 0.035, respectively). Using politomous analysis, patients baseline HIV-RNA level more than 5 log cp/ml had a 1.9-fold higher probability of an immunologic response than of a complete response (P = 0.001). After 4 years, the clinical progression rate was six times greater in non-responders, 1.9 times greater in virologic only responders, and 2.3 times greater in immunologic only responders than for responders. However, patients with virologic only response or with immunologic only response had a significantly reduced risk for clinical progression than non-responders (P < 0.001). After 4 years of HAART, the risk of clinical progression in patients with immunologic only or virologic only response is low but still higher than in complete responder patients.

Adult↗
PubMed2004

Human herpesvirus-8 infection in pregnancy and labor: lack of evidence of vertical transmission.

To investigate whether vertical transmission of the human herpesvirus 8 (HHV-8) may occur during pregnancy or at delivery, we enrolled 295 women recruited attending the Division of Obstetrics and Gynecology of a University Teaching of Rome Tor Vergata, S. Eugenio Hospital. The study population was divided in two groups: 245 pregnant women who underwent amniocentesis for genetic screening at 16-18 weeks gestation (group 1) and 50 women at the childbirth (group 2). Maternal blood was obtained from all women. Amniotic fluid (group 1) and cord blood (group 2) were obtained at midtrimester and at delivery, respectively. The presence of anti-HHV-8 antibodies in serum samples was investigated by an immunfluorescence assay. All amniotic fluids, maternal blood, and cord blood samples from HHV-8 seropositive women were tested for the presence of HHV-8 DNA sequences by the polymerase chain reaction. Thirty women, 27 of the group 1 and three of the group 2, were found to have anti-HHV-8 antibodies. Two neonates of the three seropositive mothers of the group 2 had anti-HHV-8 antibodies in cord blood. HHV-8 DNA sequences were detected in the blood of one woman of the group 2. None of the amniotic fluid and cord blood samples had detectable HHV-8 DNA sequences. This study suggests that vertical transmission of HHV-8 is unlikely or, at least, very rare.

Adult↗
PubMed2004

In vitro fluconazole susceptibility of 1565 clinical isolates of Candida species evaluated by the disk diffusion method performed using NCCLS M44-A guidelines.

We determined the in vitro activity of fluconazole against 1565 clinical Candida spp. isolates collected from different specimens of non-AIDS outpatients and inpatients in 3 different regions of Italy. Susceptibility testing was performed by agar disk diffusion using the NCCLS document M44-A guidelines. Candida albicans was the most frequently isolated yeast (68%) followed by C. glabrata (15%), C. tropicalis (5%), C. parapsilosis (5%), and C. krusei (5%). Other yeasts represented 4% of all isolates. Of the 1565 isolates tested, 1449 (92.6%) were susceptible (S) to fluconazole, 43 (2.7%) were susceptible dose-dependent (S-DD) and 73 (4.7%) were resistant (R). Almost all (98.2%) of the C. albicans isolates were classified as S or S-DD. Despite its widespread use, fluconazole displayed good activity against the isolates we tested, and the disk diffusion method was confirmed as a reliable approach to the evaluation of in vitro susceptibility of yeasts to this antimycotic agent.

Antifungal Agents↗
PubMed2004

Viral growth assay to evaluate the replicative capacity of HIV-1 isolates.

The replicative capacity of HIV is studied by carrying out replication-competition experiments with the insertion of the gene of interest. These assays cannot capture the complicated patterns of mutations of different genes.A cross sectional study was carried out on 10 HIV-infected nai;ve patients and on 15 patients failing HAART. The CD8-depleted PBMCs, with known proviral DNA and cellular HIV-RNA copy numbers, were cultured. A reference curve was determined using the data obtained from 10 nai;ve patients. The replicative capacity was calculated as the ratio multiplied by 100 of the p24 antigen level of isolates over the p24 antigen level determined on the reference curve.A linear correlation between p24 antigen level and the infectious doses of HIV-DNA alone or plus cellular RNA copy number of PBMCs was found in naive patients (r=0.63, P<0.001 and r=0.67, P<0.001, respectively). Although all patients failing therapy had strains with impaired replicative capacity, a wide range of values (0.1-74.5%) was detected. All strains with a replicative capacity above 10% had non-nucleoside reverse transcriptase inhibitors related mutations.A viral assay to evaluate the HIV replicative capacity is described. The high variability of replicative capacity confirms the need to undertake replicative capacity assay using the whole virus.

Antiretroviral Therapy, Highly Active↗
PubMed2004

Prevalence of HHV-8 infection in Albanian adults and association with HBV and HCV.

To estimate the prevalence of human herpesvirus type 8 (HHV-8) in Albania and its correlation with HBV and HCV, we tested 196 serum samples collected from apparently healthy adults (i.e., 154 women and 42 men). We found 20% anti-HHV-8 antibodies, about 10% HbsAg-positive, and 67% anti-HBc antibodies; anti-HCV antibody prevalence was 3%. It remains to be determined whether HHV-8 infection and HCV infection have common modes of transmission.

Adolescent↗
PubMed2003

Replication capacity, biological phenotype, and drug resistance of HIV strains isolated from patients failing antiretroviral therapy.

The fitness of human immunodeficiency virus (HIV) in vivo depends on the interaction of a multitude of viral and host factors. The aim of this study was to analyze the biological phenotype and the intrinsic capacity of the HIV isolates with drug-resistance mutations to replicate efficiently in the absence of drugs. An open label multicenter cross-sectional study was undertaken on 28 HIV-infected patients failing antiretroviral treatment. The subjects were studied for CD4+ cell count, HIV viral load, syncytium-inducing phenotype, genotypic drug-resistance assay, and replication capacity of HIV isolates assessed by co-culture assay. All HIV isolates showed a decreased replication capacity compared with wild-type strains. The lowest replication capacity was detected in HIV strains with more than five drug-resistance mutations. The highest replication capacity was observed in strains carrying the K103N and Y181C primary mutations that emerged after treatment with non-nucleoside analogue inhibitors. Isolates with R5 biological phenotype had a higher number of resistant mutations than X4 isolates (P = 0.004). Particularly, the R5 phenotype was detected in all 6 isolates with more than 14 drug-resistance mutations. Patients with R5 strains had plasma viral load similar to patients with X4 strains, but marginally higher CD4+ cell counts, and their HIV isolates had significantly lower replication capacity of HIV isolates (P = 0.008). No patient carrying HIV with a maintained replication capacity had a viral load less than 30,000 copies/ml. In patients failing HAART, the detection of HIV isolates with the R5 biological phenotype correlates with CD4+ cell count, an impaired replication capacity, and a high number of drug-resistance mutations.

Anti-HIV Agents↗
PubMed2003

Effect of multiple herpesvirus infections on the progression of HIV disease in a cohort of HIV seroconverters.

The effects of herpesviruses infection on the progression of HIV disease remain controversial, with some studies showing accelerated progression and others showing no effect. Furthermore, the effect of concurrent infection with more than one herpesvirus on the progression of HIV disease has never been investigated. To this end, the rates of progression of HIV disease were determined after stratifying for the presence of up to five different herpesvirus infections. The study population consisted of 359 HIV-infected persons for whom the date of seroconversion was estimated (part of the Italian Seroconversion Study). One serum sample from each participant was tested for antibodies to five herpesviruses: HSV-2, CMV, HHV-6, HHV-7, and HHV-8. Univariate analysis showed that HSV-2 and HHV-8 were significantly associated with progression to AIDS, yet when adjusting for age at HIV seroconversion and for the presence of the other herpesvirus infections, only HHV-8 infection showed a significant association. The age-adjusted risk of progression to AIDS with Kaposi's sarcoma increased with the number of herpesvirus infections and was significant in individuals with four infections. The risk of progression to AIDS without Kaposi's sarcoma also increased with the number of infections, although not significantly. Similar results were found when considering CD4+ cell count <200 x 10(6) cells/L as the endpoint. Concurrent infection with more than one herpesvirus does not appear to have a significant effect on the course of HIV disease, except for the known association between HHV-8 and Kaposi's sarcoma. However, even after excluding Kaposi's sarcoma from the AIDS-defining endpoints, a slightly increased risk for participants with four herpesvirus infections remained.

AIDS-Related Opportunistic Infections↗
PubMed2003

Phenotypic resistance testing.

The development of automated assay technology for rapid genotypic and phenotypic characterization of human immunodeficiency virus (HIV) in plasma samples now makes it feasible to use these assays in the management of antiretroviral therapy. In particular, phenotypic assays measure the drug susceptibility of the virus by determining the concentration of drug that inhibits viral replication in tissue culture. Recent experiences suggest that interpreting phenotypes may be more complicated than originally believed. Thus, rather than considering drugs as active or inactive on the basis of cut-offs, it would be more reasonable to consider their relative activity. To complicate matters further, a relatively high incidence of discordance between phenotypic and genotypic results when both tests were performed on plasma samples of antiretroviral treated patients has been reported. These findings could have considerable clinical significance, because the choice of drug regimen could differ depending on which test is used. The result of phenotypic testing may be more important when considering discordant results, because this provides a more quantitative assessment of resistance. However, clinical validation will be necessary to delineate which approach is better.

Anti-HIV Agents↗
PubMed2003

Drug-associated resistance mutations in plasma and peripheral blood mononuclear cells of human immunodeficiency virus type 1-infected patients for whom highly active antiretroviral therapy is failing.

In 32 patients for whom highly active antiretroviral therapy was failing, a good agreement between drug resistance-associated mutations in plasma and peripheral blood mononuclear cells (PBMCs) was found (k = 0.85). The mutations with the lowest agreement were 20R, 63P, and 84V in the protease gene and 184V in the reverse transcriptase gene. In eight patients, primary drug resistance mutations were detected only in PBMCs.

Adult↗
PubMed2003

High prevalence of M184 mutation among patients with viroimmunologic discordant responses to highly active antiretroviral therapy and outcomes after change of therapy guided by genotypic analysis.

Whether highly active antiretroviral therapy (HAART) should be modified in patients with persistent increases in CD4(+) T cells despite detectable viral loads is an unresolved question. Forty-three heavily pretreated human immunodeficiency virus (HIV)-infected patients with virologic failure during HAART were studied before a change of therapy guided by genotypic analysis and during follow-up. Patients with an increase in CD4(+) cell count (>100 cells/ml) over pre-HAART values were considered to be discordant patients (20 individuals), whereas patients with a lower increase or no increase in CD4(+) cell count were considered failing patients (23 individuals). Based on univariate analysis, a high CD4(+) cell count before antiretroviral treatment, homosexual behavior as a risk factor for HIV infection, reduced drug exposure to nonnucleoside reverse transcriptase inhibitors, low replicative capacity of HIV isolates, and more frequent detection of HIV isolates with a non-B subtype, an R5 biological phenotype, and M184V and T215Y/F mutations were factors associated with a discordant response to HAART. Based on multivariate analysis, only the M184V mutation remained significantly associated with a viroimmunologic discordant response (odds ratio, 25.48; 95% confidence interval, 1.43 to 453.93). No difference in lamivudine exposure was found between discordant (95%) and failing (91%) patients. Twelve months after the genotypic analysis-guided change of therapy, 3 discordant (15%) and 6 failing patients (26%) achieved undetectable viral loads (<50 copies/ml), whereas in patients with HIV RNA loads of >500 copies/ml, discordant responses were observed in 5 out of 15 discordant patients and in 4 out of 16 failing patients. A relationship between the M184V mutation and a viroimmunologic discordant response to HAART was found. After the genotypic analysis-driven change of therapy, similar rates of virologic suppression were detected in the two groups.

Antiretroviral Therapy, Highly Active↗
PubMed2003

Infection with human herpesvirus-8 and its correlation with hepatitis B virus and hepatitis C virus markers among rural populations in Cambodia.

Among 164 individuals in a rural population of Cambodia, antibodies to human herpesvirus-8 (HHV-8) were found among 56.6% of the women and 50.6% of the men. Seropositivity for HHV-8 tended to decrease with age (P < 0.001) and was not associated with exposure to hepatitis B virus (HBV) or HCV. Human herpesvirus-8, which shows a high rate of infection during childhood, does not seem to have the same pattern of transmission as HBV. This suggests very early acquisition of infection with HHV-8 in Cambodia.

Adolescent↗
PubMed2003

[HIV and related infections in Italian penal institutions: epidemiological and health organization note].

HIV and other infections represent an important health problem in Italian jails. In particular, HIV prevalence is high, due to the characteristics of the prison population, which is constituted by a large proportion of injecting drug users and foreigners. In addition, data from other countries suggest that risky behaviour are not uncommon during imprisonment, and transmission of HIV and other infection in this setting may also occur. Data from surveys conducted by the Penitentiary Authority in Italian jails show a decline of HIV seroprevalence from 9.7% in 1990 to 2.6% in 2001. However, these data are largely incomplete and do not account for possible biases due to self-selection of inmates toward HIV serological testing or to variations in the access to screening activities. More accurate data, possibly obtained through anonymous unlinked surveys, are needed in order to better plan health services and preventive measures.

AIDS-Related Opportunistic Infections↗