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Biomedical subjects

Giovanni Rezza

Publications and source records attributed to Giovanni Rezza.

At least 19 recordsLinked to original sources

Temporal trends in postseroconversion CD4 cell count and HIV load: the Concerted Action on Seroconversion to AIDS and Death in Europe Collaboration, 1985-2002.

OBJECTIVE: To determine whether early postseroconversion CD4 cell counts and human immunodeficiency virus (HIV) loads have changed over time. METHODS: Our analysis was based on 22 cohorts of people with known dates of seroconversion from Europe, Australia, and Canada (Concerted Action on Seroconversion to AIDS and Death in Europe Collaboration). We focused on individuals seroconverting between 1985 and 2002 who had the first CD4 cell count (n=3687) or HIV load (n=1584) measured within 2 years of seroconversion and before antiretroviral use. Linear regression models were used to assess time trends in postseroconversion CD4 cell count and HIV load. Trends in time to key thresholds were also assessed, using survival analysis. RESULTS: The overall median initial CD4 cell count was 570 cells/ microL (interquartile range [IQR], 413-780 cells/ microL). The median initial HIV load was 35,542 copies/mL (IQR, 7600-153,050 copies/mL; on log(10) scale, 3.9-5.2 log(10) copies/mL). The postseroconversion CD4 cell count changed by an average of -6.33 cells/ microL/year (95% confidence interval [CI], -8.47 to -4.20 cells/ microL/year; P<.001), whereas an increase was observed in log(10) HIV load (+0.044 log(10) copies/mL/year; 95% CI, +0.034 to +0.053 log(10) copies/mL/year). These trends remained after adjusting for potential confounders. The probability of progressing to a CD4 cell count of <500 cells/ microL by 24 months from seroconversion increased from 0.66 (95% CI, 0.63-0.69) for individuals who seroconverted before 1991 to 0.80 (95% CI, 0.75-0.84) for those who seroconverted during 1999-2002. CONCLUSION: These data suggest that, in Europe, there has been a trend of decrease in the early CD4 cell count and of increase in the early HIV load. Additional research will be necessary to determine whether similar trends exist in other geographical areas.

Adult↗

Molecular epidemiology: HIV-1 and HCV sequences from Libyan outbreak.

In 1998, outbreaks of human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) infection were reported in children attending Al-Fateh Hospital in Benghazi, Libya. Here we use molecular phylogenetic techniques to analyse new virus sequences from these outbreaks. We find that the HIV-1 and HCV strains were already circulating and prevalent in this hospital and its environs before the arrival in March 1998 of the foreign medical staff (five Bulgarian nurses and a Palestinian doctor) who stand accused of transmitting the HIV strain to the children.

Child↗

The impact of transmitted drug resistance on the natural history of HIV infection and response to first-line therapy.

BACKGROUND: Transmission of drug-resistant HIV-1 is well recognized. However, the impact of such transmission on natural history of infection remains unknown. METHODS: Three hundred HIV-1-infected, antiretroviral-naive individuals, recruited between 1987 and 1993, and with resistance tests undertaken within 18 months of infection were assessed. We estimated the impact of transmitted drug resistance (TDR) on subsequent CD4 cell count decline in the absence of treatment. We also used Kaplan-Meier methods to assess the response to antiretroviral therapy based on the number of active drugs utilized (according to genotypic resistance results). RESULTS: Infection with any form of drug-resistant HIV-1 was associated with a steeper decline of CD4 cell count over the first year of infection. Estimated rates of decline in the first year were 5.0 [95% confidence interval (CI), 2.8-7.3] and 1.7 (95% CI, 0.8-2.6) radicalCD4 cells per year for TDR and no TDR, respectively (P = 0.005). For an individual at a CD4 cell count of 500 cells/microl at seroconversion, these rates correspond to a CD4 cell loss of 199 and 73 cells/microl, respectively, in the first year. Thereafter we found no evidence of a difference in the rate of CD4 cell decline (P = 0.32). Initiation of HAART after calendar year 2000, but not number of active drugs, was associated with improved responses. CONCLUSIONS: The impact of transmitted HIV-1 drug resistance on CD4 cell decline is time dependent, with greater rates of decline in the first year following infection. We found no evidence of a longer term effect of TDR on natural history of HIV-1 infection.

Adult↗

Prevalence of antibodies against A and B influenza viruses in South-Western Papua New Guinea.

Influenza viruses remain a major cause of respiratory disease in both developed and developing countries. Nevertheless, there is little information on the prevalence of this respiratory infection in many developing countries, such as Papua New Guinea, since most of the available data originate from studies carried out in industrialized countries. In the present study, a serosurvey among residents of 47 remote villages of Papua New Guinea was conducted to evaluate the intensity of exposure to human influenza A and B viruses. The data obtained confirm the co-circulation of these antigenic variants, reported having circulated in the Southern Hemisphere. Variations in seroprevalence of influenza A and B virus infection were found within the study area.

Adolescent↗

An outbreak of influenza in a residential drug-rehabilitation community.

Influenza outbreaks can be difficult to control in confined settings where high-risk individuals are concentrated. Following the occurrence of a large number of cases of influenza-like illness in a rehabilitation community for drug users, between February and March 2004, surveillance activities were implemented. Attack rates of influenza-like illness were calculated, and risk factors for the development of disease and complications were evaluated through the use of relative risks (RR) with 95% confidence intervals (CI). Nasal-pharyngeal samples were collected for virological studies. Of 1,310 persons who were living in the community, 209 were diagnosed with influenza-like illness: the attack rate (15.9% overall) was higher for HIV-infected persons (RR: 1.77, 95% CI: 1.32-2.37), older individuals, and dormitory residents. HIV-infected participants were also more likely to develop complications compared with HIV-uninfected persons diagnosed with influenza-like illness (RR: 5.13, 95% CI: 2.52-10.20). The outbreak was attributable to Christchurch-like influenza A strains. Vaccination was ineffective because of the mismatch between wild and vaccine strains.

Adult↗

H5N1 influenza virus evolution: a comparison of different epidemics in birds and humans (1997-2004).

The selection pressure acting along the entire genome sequence of H5N1 avian influenza viruses isolated from several bird species and humans infected in the 1997 and 2004 outbreaks, and on the HA1 genes from H5N1 viruses isolated during the entire study period, in eastern Asia was evaluated. According to maximum-likelihood analysis, viral genes appeared to be, in both epidemics, under strong purifying selection, with only the PB2, HA and NS1 genes under positive selection. Specific codons under positive selection were detected by using codon-based substitution models. Positive-selection analysis performed on single-codon sites might be helpful in clarifying the driving force of avian and human influenza virus evolution and in selecting specific targets for vaccines and antiviral drugs.

Animals↗

Associations of classic Kaposi sarcoma with common variants in genes that modulate host immunity.

Classic Kaposi sarcoma (CKS) is an inflammatory-mediated neoplasm primarily caused by Kaposi sarcoma-associated herpesvirus (KSHV). Kaposi sarcoma lesions are characterized, in part, by the presence of proinflammatory cytokines and growth factors thought to regulate KSHV replication and CKS pathogenesis. Using genomic DNA extracted from 133 CKS cases and 172 KSHV-latent nuclear antigen-positive, population-based controls in Italy without HIV infection, we examined the risk of CKS associated with 28 common genetic variants in 14 immune-modulating genes. Haplotypes were estimated for IL1A, IL1B, IL4, IL8, IL8RB, IL10, IL12A, IL13, and TNF. Compared with controls, CKS risk was decreased with 1235T/-1010G-containing diplotypes of IL8RB (odds ratio, 0.49; 95% confidence interval, 0.30-0.78; P = 0.003), whereas risk was increased with diplotypes of IL13 containing the promoter region variant 98A (rs20541, alias +130; odds ratio, 1.88; 95% confidence interval, 1.15-3.08; P = 0.01) when considered in multivariate analysis. Risk estimates did not substantially vary by age, sex, incident disease, or disease burden. Our data provide preliminary evidence for variants in immune-modulating genes that could influence the risk of CKS. Among KSHV-seropositive Italians, CKS risk was associated with diplotypes of IL8RB and IL13, supporting laboratory evidence of immune-mediated pathogenesis.

Adult↗

[The HIV/AIDS epidemic in the Province of Sassari in the combination antiretroviral therapy era].

Combined antiretroviral therapy has reduced both AIDS mortality and morbidity. An unknown proportion of patients is identified early and starts therapy before developing AIDS, thus escaping epidemiological surveillance. For this reason it is important to monitor the trend of new diagnoses of HIV infection. From the comparison of patients living in the Province of Sassari with new diagnoses of HIV infection or AIDS in the period 1997-2003 some differences emerge. Males are the most affected, but the difference tends to decrease among new HIV cases. Sexual contact is the most common route of transmission among new HIV diagnoses, whereas the parenteral route prevails among AIDS cases. An increase in the percentage of foreigners has been found only among new HIV cases. The difference found between new AIDS and HIV cases emphasises the importance to implement HIV infection based surveillance systems, in order to better guide informative campaigns and other interventions.

Acquired Immunodeficiency Syndrome↗

Kaposi's sarcoma in transplant and HIV-infected patients: an epidemiologic study in Italy and France.

BACKGROUND: A follow-up study was conducted in Italy and in France to compare the epidemiology of Kaposi's sarcoma (KS) between human immunodeficiency virus (HIV)-infected people and transplant recipients. METHODS: In all, 8,074 HIV-positive individuals (6,072 from France and 2,002 HIV-seroconverters from Italy) and 2,705 Italian transplant recipients (1,844 kidney transplants, 702 heart transplants, and 159 liver transplants) were followed-up between 1970 and 2004. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were computed to estimate the risk of KS, as compared to sex- and age-matched Italian and French populations. Incidence rate ratios (IRRs) were used to identify risk factors for KS. RESULTS: A 451-fold higher SIR for KS was recorded in HIV-infected subjects and a 128-fold higher SIR was seen in transplant recipients. Significantly increased KS risks were observed in HIV-infected homosexual men (IRR=9.7 in France and IRR=6.7 in Italy vs. intravenous drug users), and in transplant recipients born in southern Italy (IRR=5.2 vs. those born in northern Italy). HIV-infected patients with high CD4+ cell counts and those treated with antiretroviral therapies had reduced KS risks. In relation to duration of immunosuppression, KS occurred earlier in transplant patients than in HIV-seroconverters. CONCLUSIONS: This comparison highlighted that the risk of KS was higher among HIV-infected individuals than in transplant recipients, and that different co-factors are likely to influence the risk of KS. Moreover, the early KS occurrence in transplant recipients could be associated with different patterns of progressive impairment of the immune function.

Adult↗

Increased HIV incidence among men who have sex with men in Rome.

Among 976 men who have sex with men (MSM) who had undergone repeat HIV testing between 1984 and 2003 at a sexually transmitted infection clinic in Rome, Italy, we observed a dramatic increase in HIV incidence in 2002 and 2003, with the cumulative incidence for 2000-2003 being twice as high as that for 1984-1995, and significantly higher than that for 1996-1999. This trend suggests the need for interventions aimed at encouraging behavioural changes among MSM.

Adolescent↗

An outbreak of hepatitis A virus infection with a high case-fatality rate among injecting drug users.

BACKGROUND/AIMS: In 2002, the first reported outbreak of hepatitis A virus (HAV) infection involving mostly intravenous drug users (IDU) occurred in Italy. We attempted a thorough evaluation of the outbreak, including epidemiological, clinical and virological analyses. METHODS: We conducted an epidemiological investigation, including a case-control study, to identify the source and the modes of HAV transmission. Hepatitis B and C (HCV) viruses and human immunodeficiency virus (HIV) coinfections were clinically analysed. Sequence analysis of the VP1/2A junction of the HAV isolates was also performed. RESULTS: Of the 47 symptomatic cases, 35 were IDUs. The only associated risk factor was contact (not related to injecting practices) with a jaundiced person (odds ratio: 5.8; 95% confidence interval: 1.3-29.9). Of the cases, 58% were anti-HCV positive and 4.7% anti-HIV positive. Three individuals died of acute liver failure: 2 were HCV-coinfected alcohol abusers, with underlying liver cirrhosis; 1 was HCV/HIV-coinfected. HAV-RNA was found in 15 of the 24 tested patients: genotype IB (8 cases) and IIIA (7 cases) were detected. CONCLUSIONS: HAV was probably transmitted through the fecal-oral route, although parenteral transmission cannot be excluded. The high fatality rate was probably due to severe underlying liver damage. The occurrence of this outbreak highlights the need for routine HAV vaccination for IDUs.

Adolescent↗

Molecular diversity of HIV in Albania.

Little information is available on circulating human immunodeficiency virus (HIV) subtypes and resistance to antiretroviral drugs in Albania. To fill this gap, we studied 72 plasma samples from HIV-infected individuals from throughout the country. Subtype classification and genotypic resistance analysis were performed on the HIV pol gene region. The analysis was successfully performed on 66 (91.6%) plasma samples and showed that 43 (65.2%) strains were non-B subtypes (mostly subtype A, as determined by analysis of pol gene sequences). No major mutations in the protease gene were found, whereas analysis of the reverse transcriptase gene revealed a few major mutations associated with resistance. In conclusion, non-B subtypes are predominant in Albania, and the prevalence of resistance to antiretroviral drugs is still low.

Albania↗

The presence of anti-Tat antibodies is predictive of long-term nonprogression to AIDS or severe immunodeficiency: findings in a cohort of HIV-1 seroconverters.

The human immunodeficiency virus (HIV) type 1 Tat protein plays a key role in the life cycle of the virus and in pathogenesis and is highly conserved among HIV subtypes. On the basis of this and of safety, immunogenicity, and efficacy findings in monkeys, Tat is being tested as a vaccine in phase 1 trials. Here, we evaluated the incidence and risk of progression to advanced HIV disease by anti-Tat serostatus in a cohort of 252 HIV-1 seroconverters. The risk of progression was lower in the anti-Tat-positive subjects than in the anti-Tat-negative subjects. Progression was faster in the persistently anti-Tat-negative subjects than in the transiently anti-Tat-positive subjects, and no progression was observed in the persistently anti-Tat-positive subjects.

Acquired Immunodeficiency Syndrome↗

Changes over time in post-seroconversion CD4 cell counts in the Italian HIV-Seroconversion Study: 1985-2002.

OBJECTIVE: To determine whether there has been a tendency for early post-seroconversion CD4 cell counts to change over calendar time. DESIGN: A prospective cohort study of individuals with well-estimated dates of seroconversion. METHODS: We studied 1251 individuals who seroconverted to HIV in Italy between 1985 and 2002, and for whom the first CD4 count was measured within 2 years of seroconversion and before any use of antiretrovirals. Linear regression models were used to assess evidence for a trend in post-seroconversion CD4 cell count over time. RESULTS: The median post-seroconversion CD4 cell count was 674 x 10 cells/l in those seroconverting between 1985 and 1990, 588 x 10 cells/l for 1991 to 1994, 559 x 10 cells/l for 1995 to 1998 and 494 x 10 cells/l for 1999 to 2002. The post-seroconversion CD4 cell count decreased by an average of 8.4 x 10 cells/l per year (95% confidence interval, 4.0-12.9; P < 0.001), after adjustment for potential confounders, including interval between HIV-negative and HIV-positive tests, lag time for first CD4 cell count measurement, age at seroconversion, gender, HIV-transmission group, and clinical centre. The finding was consistent in sensitivity analyses restricted to those with information on acute infection. CONCLUSION: These data suggest a possible decreasing trend in CD4 cell count immediately following seroconversion in Italy which requires further investigation.

AIDS-Related Opportunistic Infections↗

The epidemiological contribution to the preparation of field trials for HIV and STI vaccines: objectives and methods of feasibility studies.

Feasibility studies are an important component of preparations for efficacy field trials of vaccine candidates, but represent a neglected area in clinical trial literature. These studies are designed to identify cohorts of higher-risk individuals with sufficiently high incidence to support a vaccine trial; to determine the readiness of these individuals to participate in a trial; to develop cost-effective recruitment and retention strategies, educational methods that ensure ethical informed consent, and instruments that accurately assess risk behaviours; to measure incidence rates over time and the effect of risk reduction interventions on incidence; to contribute estimates of incidence and loss to follow-up rates to sample size calculations; to assess the level of acceptability of a future efficacious vaccine in the target population and, in the case of several viruses, to identify circulating subtypes. Feasibility study methods have been largely developed in the context of HIV, but may also be used in the preparation of preventive intervention trials for other STI.

AIDS Vaccines↗

Human herpesvirus type 8 infection in an area of Northern Italy with high incidence of classical Kaposi's sarcoma.

Previous studies have reported a large variation in the incidence of classical Kaposi's sarcoma across different Districts of the province of Mantua (Northern Italy). To assess whether such differences might be explained by different anti-HHV8 antibody prevalence, a serological study was conducted in 343 healthy elderly individuals resident in two adjacent Districts, at the highest and the lowest classical Kaposi's sarcoma incidence rate, respectively. Qualitative and quantitative determinations of IgG antibodies against both latent and lytic HHV-8 antigens were performed by indirect immunofluorescence assay. The assay's sensitivity was studied in 26 patients with classical Kaposi's sarcoma. Overall, anti-HHV8 antibodies were detected in 25 out of 26 patients (96%), confirming the high sensitivity of this assay. The prevalence of anti-HHV-8 antibodies was higher among individuals living in the District had a high incidence of classical Kaposi's sarcoma compared to those living in the District with low incidence (19.4% vs 9.8%, and 15.9% vs 8%; P<0.05, for latent and lytic antibodies, respectively). Anti-lytic antibody GMT was higher in people living in the District at high incidence rate compared to those of the other area (328.9 vs. 180.4; P<0.01). A higher prevalence of HHV-8 infection was found among persons living in municipalities surrounded by watercourses (OR 2.2, 95% CI: 1.10-4.32). In conclusion, variation in HHV-8 prevalence appears to explain differences in the incidence rates of classical Kaposi's sarcoma observed in different areas of the province.

Aged↗