Showing papers by "Giovanni Rezza published in 2003"

Human herpesvirus 8 epidemiology: what we do and do not know.

Abstract: Human herpesvirus 8 (HHV-8), also known as ‘Kapo-si’s sarcoma-associated herpesvirus’ (KSHV), was firstidentified in 1994 [1]. Its discovery is a good exampleof how epidemiological and molecular-biological datacan be combined to evaluate causality for a putativeagent [2]. In fact, before the discovery of HHV-8,the analysis of surveillance data had suggested that, inHIV-infected individuals, there existed an infectiousco-factor other than HIV that was critical to thedevelopment of Kaposi’s sarcoma (KS), leading to theidentification of HHV-8 in KS tissues [3].HHV-8 is now considered to be the necessary cause ofall variants of KS, including AIDS KS, classic KS,endemic KS and iatrogenic KS, and is a determinant ofother rare diseases, such as primary effusion lymphoma,or body cavity-based lymphoma and multicentric Cas-tleman’s disease [4,5]. However, various aspects of theepidemiology of HHV-8 infection still need to beclearly defined: in particular, the evolution of theHHV-8 epidemic, the appropriate serological assaysand their application, the distinct distribution featuresof HHV-8 in relation to KS, transmission modalities,and the natural history of infection. In the present text,we provide a synopsis of what we do and do not knowabout the epidemiology of HHV-8 infection, especiallywith regard to Africa. It is therefore not intended toprovide an exhaustive review but to highlight thecurrent thinking about HHV-8, as guided by thepioneering research performed to date.

Effect of Maternal HIV and Malaria Infection on Pregnancy and Perinatal Outcome in Zimbabwe

Abstract: Objective: To investigate the effect of isolated or concomitant infection with malaria and HIV on pregnancy and neonatal outcome. Methods: Data were collected on pregnant women admitted during the rainy seasons in the obstetric division of a district referral hospital in northern Zimbabwe in 2000 and 2001. The effects of malaria and HIV infection were determined by multivariate analysis. Results: The prevalence of HIV seropositivity and symptomatic malaria in 986 pregnant women was 8.3% and 14.7% respectively. HIV infected women were more likely to develop malaria attacks during pregnancy than seronegative women (odds ratio [OR] = 3.96 95% confidence interval (CI): 2.42–6.46). Malaria and HIV infections were associated with increased risk of stillbirth (OR = 4.74 95% CI: 1.34–16.78) and preterm delivery (OR = 4.10 95% CI: 2.17–7.75) respectively. They were independently associated with increased risk of low birth weight (malaria: OR = 10.09 95% CI: 6.50–15.65; HIV: OR = 3.16 95% CI: 1.80–5.54) and very low birth weight (malaria: OR = 5.04 95% CI: 1.00–25.43; HIV: OR = 10.74 95% CI: 2.12– 54.41) low Apgar score (malaria: OR = 4.45 95% CI: 1.42–13.94; HIV: OR = 5.94 95% CI: 1.66–21.30) and fetal growth restriction (malaria: OR = 3.98 95% CI: 2.51–6.30; HIV: OR = 4.07 95% CI: 2.40–6.92). Dual infection with malaria and HIV was associated with increased risk of maternal perinatal and early infant death. Conclusions: Women with single HIV or malaria infection have a significantly increased risk of adverse outcomes of pregnancy and childbirth. Dual infection has additional detrimental effects on maternal and infant survival in an area where HIV and malaria coexist. (authors)

Identifying recent HIV infections using the avidity index and an automated enzyme immunoassay.

Abstract: We evaluated a procedure for identifying recent HIV infections. using sequential serum samples from 47 HIV-positive persons for whom the seroconversion date could be accurately estimated. Each serum sample was divided into two aliquots: one diluted with phosphate-buffered saline and the other diluted with 1 M guanidine. We assayed the aliquots with the automated AxSYM HIV1/2gO test (Abbott Diagnostics Division), without modifying the manufacturer's protocol. We then calculated the avidity index (AI): the ratio of the sample/cutoff value for the guanidine aliquot to that of the phosphate-buffered saline aliquot. We analyzed 216 serum samples: 34 samples were collected within 6 months of seroconversion (recent seroconversions). and 182 were collected after 6 months. The mean AIs, by time from seroconversion, were 0.68 ± 0. l6(within 6 months) and 0.98 ± 0.10 (after 6 months) (P < (0.0001). AI of <0.90 correctly identified 88.2% of recent infections but misclassified as recent infections 13.2% of serum samples collected afterward. The probability of an infection being classified as recent and having AI of ≥0.90 would be 0.7% in a population with 5% recent infections. AI can identify with a certain degree of accuracy recent HIV infections, and being a quantitative index, it provides different levels of sensitivity and specificity, depending on the selected cutoff value. The standard assay procedure is not modified. This test is simple and inexpensive and could be used for surveillance, decision-making in treatment, and prevention.

Sequence Conservation and Antibody Cross-Recognition of Clade B Human Immunodeficiency Virus (HIV) Type 1 Tat Protein in HIV-1–Infected Italians, Ugandans, and South Africans

Abstract: We determined immune cross-recognition and the degree of Tat conservation in patients infected by local human immunodeficiency virus (HIV) type 1 strains. The data indicated a similar prevalence of total and epitope-specific anti-Tat IgG in 578 serum samples from HIV-infected Italian (n=302), Ugandan (n=139), and South African (n=137) subjects, using the same B clade Tat protein that is being used in vaccine trials. In particular, anti-Tat antibodies were detected in 13.2%, 10.8%, and 13.9% of HIV-1-infected individuals from Italy, Uganda, and South Africa, respectively. Sequence analysis results indicated a high similarity of Tat from the different circulating viruses with BH-10 Tat, particularly in the 1-58 amino acid region, which contains most of the immunogenic epitopes. These data indicate an effective cross-recognition of a B-clade laboratory strain-derived Tat protein vaccine by individuals infected with different local viruses, owing to the high similarity of Tat epitopes.

Incidence of AIDS-defining cancers after AIDS diagnosis among people with AIDS in Italy, 1986-1998.

Abstract: A record linkage was carried out between the Italian National Registry of AIDS and 19 cancer registries. The aim was to evaluate the 1986 through 1998 trends in incidence rate (IR) of AIDS-defining cancers (ADCs) among persons with AIDS (PWA) in Italy overall and according to various characteristics. A steady decrease in IRs was found for Kaposi sarcoma (KS) in men between 1986–1992 (2.5 per 100 person-years [py]) and 1997–1998 (1.0 per 100 py). Conversely, the first decrease in IRs of KS in women (from 0.9 to 0.6 per 100 py) and of non-Hodgkin lymphoma in both genders (from 1.7 to 0.7 per 100 py) was seen between 1993–1996 and 1997–1998, thus pointing to a favorable impact of highly active antiretroviral therapies. The decline was consistent across different age and HIV transmission groups, but it was more marked in PWA with a CD4 count >50 cells/μL than in PWA with more severe immune suppression. As a proportion of AIDS cases, invasive cervical cancer increased from 1.5% in 1993–1996 to 2.4% in 1997–1998, but IRs after AIDS could not be evaluated. On account of the marked decline of KS in men in 1997–1998, the overall burden of ADCs in Italy became similar in both genders.

Infection with human herpesvirus-8 and its correlation with hepatitis b virus and hepatitis c virus markers among rural populations in cambodia

Abstract: 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.

Estimating the cumulative number of human immunodeficiency virus diagnoses by cross-linking from four different sources

Abstract: Background We estimated the cumulative number of people diagnosed with human immunodeficiency virus (HIV) infection in a region of Italy by cross-linking data from four surveillance systems and applying capture-recapture methods. Methods The study was conducted using data referring to residents of the Veneto Region (population 4.4 million). We cross-linked data from the AIDS Registry (data 1983-2000), the HIV Registry (1988-2000), the Death Registry (1992-1999), and the Hospital-Discharge Registry (1997-2000), using a code based on name, birth date, and sex. A specific software for capture-recapture models (CARE-1) was used to estimate the size of the target population with two different statistical approaches (sample coverage and log-linear models). Results A total of 2801 people were reported to the AIDS Registry, 6415 to the HIV Registry, 1598 to the Death Registry as HIV/AIDS-related deaths, and 3330 to the Hospital-Discharge Registry with a diagnosis of HIV infection. Overall, 8723 people were present in at least one registry: 4896 people were present in only one registry, 2387 in two registries, 1286 in three registries, and 154 in all four registries. Using the sample coverage approach, we estimated that, since the beginning of the epidemic in Veneto, an estimated 11 281 people (95% CI: 10 981, 11 621) should have been reported to at least one registry; thus the estimated coverage of the four registries was 77.3% (i.e. 8723/11 281). Results obtained applying the log-linear approach were similar, although the fitting of this model was not adequate. Conclusions Cross-linking data from four different sources and applying the capture-recapture method can improve the accuracy of the estimates of the dimensions of the HIV epidemic.

[Survival, progression to AIDS and immunosuppression in HIV-positive individuals before and after the introduction of the highly active antiretroviral therapy (HAART)].

Abstract: We evaluated the changes in the progression to death and AIDS and in the mean level of CD4 lymphocytes by calendar period in HIV-positive individuals before and after the introduction of HAART. Through data collected in a prospective cohort study (Italian Seroconversion Study) of 1899 HIV-infected persons with well estimated date of seroconversion, considered as time-zero of analysis, we calculated Kaplan-Meier curves and Cox models, allowing for staggered entries, to estimate the cumulative probability of survival and hazard-ratios (HR) for death and for AIDS by calendar period (1980-1996: pre-HAART era, 1997-1998: first HAART era, and 1999-2001: second HAART era), age at seroconversion, gender, and exposure category. During 17251 person-years, 660 HIV-positive patients developed AIDS and 510 died. Before 1997, the cumulative probability of survival, at twelve years from seroconversion, was 51.0%. In the period 1997-1998 the probability was 77.3% and in the period 1999-2001 it further increased at 91.2%. In the period 1980-1996 only older age at seroconversion was associated with more rapid progression to death. In the period 1987-2001 individuals infected through injecting drug use had a reduced increase of survival compared to those infected through sexual contact. Similar results were obtained for progression to AIDS. Finally we estimated an improved level of immunesuppression in the period 1987-2001. In fact, while in the period 1980-1996 we estimated a decrease of the CD4 lymphocites of -54.8 cells/mm3 (95% CI: -52.0; -57.6) per year; after 1996, we estimated an increase of CD4 of +39.6 (95% CI +34.1; +45.1)per year. This study provides strong evidence that the efficacy of the HAART estimated in the controlled clinical trials has resulted in a real reduction at the population level of morbidity and mortality.

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

Abstract: 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 × 106 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. J. Med. Virol. 69:182–187, 2003. © 2003 Wiley-Liss, Inc.

Epidemiological changes in AIDS and HIV infection in Italy.

Abstract: This article describes the major changes in the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/ AIDS) epidemic in Italy, using data from the National AIDS Registry and from 5 local surveillance systems for new HIV diagnoses. From 1982 to 2001, 49,063 adults with AIDS were reported to the AIDS Registry. From 1988 to 2000, the 5 local systems reported 23,252 new HIV diagnoses. The AIDS incidence increased until 1995, followed by a progressive decrease. A decrease was also observed for the incidence of new HIV diagnoses after 1989, with an apparent stabilization after 1998. Most AIDS cases have been represented by intravenous drug users (IDU), yet since 1999 the percentage of cases attributable to sexual transmission has exceeded that for IDUs. Similarly, among new HIV diagnoses, the percentage of cases attributable to sexual transmission increased from 23.6% before 1993 to 58.5% in 2000. The percentage of people with AIDS who discovered their seropositivity no earlier than 6 months before AIDS diagnosis increased from 20.6% in 1996 to 48.8% in 2001. Although the incidence of both AIDS and new HIV diagnoses has declined, a possible resurgence of the epidemic cannot be ruled out, in light of various factors that could lead to an increasing number of living infected people.

Prevalence of HHV-8 Infection in Albanian Adults and Association with HBV and HCV

Abstract: 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.

The effect of aging on the incidence of Kaposi's sarcoma among HIV-positive individuals with known dates of seroconversion.

Abstract: In the general population, the incidence of the most common types of cancer (i.e., carcinomas of the lung, breast, colon, stomach, prostate and bladder) increases with age among both males and females and in different geographic areas.1,2 This pattern is explained by the multistage model for carcinogenesis, which posits that cancer arises as a consequence of multiple genetic hits acquired with aging.3 Alternatively, it has been hypothesized that this age-related increase in incidence can be attributed, at least in part, to the diminishing immunologic function associated with aging. However, among persons with severe immunosuppression, such as those who are iatrogenically immunosuppressed after organ transplantation or persons infected with the human immunodeficiency virus (HIV), the incidence of the most common types of cancer is no higher than that among immunocompetent persons. By contrast, the incidence of both non-Hodgkin’s lymphoma (NHL) and Kaposi’s sarcoma (KS), which are rare in immunocompetent persons younger than 40 years of age, has been reported to be quite high among persons with severe immunosuppression.4,5 KS is a mesenchymal tumor that, until the appearance of the HIV epidemic, was rare in the general population of industrialized countries; it was generally found in elderly men of Mediterranean or Eastern European origin.6 With regard to the pathogenesis of KS, an infectious agent – the human herpesvirus 8 (HHV-8)—has been isolated in all forms of the disease,7,8 and epidemiologic, serologic and molecular evidence has proved that infection with HHV-8 is necessary for the development of KS. Nonetheless, it has been difficult to determine the magnitude of the association between KS and HHV-8 infection because the currently used serologic assays are limited in terms of their sensitivity and specificity9 and because other, as yet unknown, cofactors exist that are likely to play a role in the development of KS.10,11 Given that HIV-infected individuals have been shown to live longer since highly active antiretroviral therapy (HAART) was introduced,12 it is now possible to study thoroughly the relationship among immunosuppression, aging and cancer. In a study13 that investigated whether or not aging affects the risk of developing HIV-associated KS and lung cancer, using data from the AIDS-Cancer Registry Match Study, the incidence of KS appeared to increase through 39 years of age and to decline thereafter. However, no information was available from this study on the duration of HIV infection, the level of immunosuppression or the prevalence of HHV-8 infection (i.e., the main determinant of KS8). We investigated the relationship among HIV-induced immunosuppression, aging and KS, taking into account the duration of HIV infection, the level of immunosuppression and, for a subgroup of the study population, the prevalence of HHV-8 infection. This study used data from the Italian HIV-Seroconversion Study. The Seroconversion Study, which was begun in 1987, is a prospective incident cohort study of HIV seroconverters who belong to different HIV exposure categories and for whom it is possible to estimate the date of seroconversion with a certain degree of accuracy, specifically, persons for whom the results of a negative HIV test followed by a positive test within 24 months are available; the date of seroconversion is estimated as the midpoint in time between the most recent negative HIV test result and the first positive result. A detailed description of the Seroconversion Study has been published elsewhere.14,15 Residual sera samples for detection of antibodies against HHV-8 were available for some of the individuals enrolled as of June 1996 in the Seroconversion Study. A single HHV-8 serologic measurement was performed: the median time that had elapsed from the date of HIV seroconversion to the date of HHV-8 testing was 0.7 years (interquartile range: 0.4–1.6 years). HHV-8 seropositivity was determined by HHV-8 lytic antigens, using an immunofluoroscence assay with a body cavity B-cell lymphoma cell line. A detailed description of the methodology used has been reported elsewhere.16 For the present analysis, we applied the Kaplan-Meier method and the Cox proportional hazards model.17 The date of HIV seroconversion was considered time-zero of the analyses, and KS was considered the end point. In particular, we estimated the KS-free survival time as the time that had elapsed from the date of HIV seroconversion to the date of diagnosis of KS (independently of whether or not it was the first AIDS-defining disease), or the date of death or the end of the study (i.e., December 2000). The