Does the risk of abortion increase in women with high human herpesvirus-8 antibody titers?
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Biomedical subjects
Publications and source records attributed to Giovanni Rezza.
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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 +/- 0.16 (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 > or = 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.
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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.
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.
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.
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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.
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.
BACKGROUND: Classical Kaposi's sarcoma (KS) is a malignancy of lymphatic endothelial skin cells. Although all forms of KS are associated with the KS-associated herpesvirus (KSHV), classical KS occurs in a small fraction of KSHV-infected people. We sought to identify risk factors for classical KS in KSHV-infected individuals. METHODS: Lifestyle and medical history data from case patients with biopsy-proven non-AIDS (non-acquired immunodeficiency syndrome) KS in Italy were compared by logistic regression analysis with data from population-based KSHV-seropositive control subjects of comparable age and sex. After KSHV immunofluorescence testing, randomly selected patients on the rosters of local physicians were identified as control subjects. Risk of KS was estimated by odds ratios (ORs) and 95% confidence intervals (CIs). All statistical tests were two-sided. RESULTS: From April 13, 1998, through October 8, 2001, we enrolled 141 classical KS case patients and 192 KSHV-seropositive control subjects of similar age (mean = 72 years for case patients and 73 years for control subjects) and sex (30% female case patients and 35% female control subjects). The strongest association was a reduced risk of KS with cigarette smoking (OR = 0.25, 95% CI = 0.14 to 0.45). Cigarette smoking intensity and duration could be evaluated for men, among whom the risk for KS was inversely related to the amount of cumulative smoking (P(trend)<.001). KS risk decreased approximately 20% (OR = 0.81, 95% CI = 0.74 to 0.89) for each 10 pack-years reported, and it was decreased sevenfold (OR = 0.14, 95% CI = 0.07 to 0.30) with more than 40 pack-years. In multivariable analysis, a decreased KS risk was associated with smoking (OR = 0.23, 95% CI = 0.12 to 0.44); but an increased KS risk was associated with topical corticosteroid use (OR = 2.73, 95% CI = 1.35 to 5.51), infrequent bathing (OR = 1.85, 95% CI = 1.04 to 3.33), and a history of asthma (OR = 2.18, 95% CI = 0.95 to 4.97) or of allergy among men (OR = 2.59, 95% CI = 1.15 to 5.83) but not among women (OR = 0.09, 95% CI = 0.003 to 2.76). KS was not related to other exposures or illnesses examined. CONCLUSION: Risk for classical KS was approximately fourfold lower in cigarette smokers, a result that requires confirmation by other studies. Identification of how smoking affects KS risk may lead to a better understanding of the pathogenesis of this malignancy and interventions for its prevention.
CONTEXT: Human herpesvirus 8 (HHV-8) infection causes Kaposi sarcoma and lymphoproliferative disorders in immunosuppressed adults. Its manifestations in immunocompetent hosts are unknown. OBJECTIVES: To determine whether HHV-8 primary infection is symptomatic in immunocompetent children and to identify the epidemiological and virological correlates of HHV-8 infection. DESIGN AND SETTING: Prospective cohort study conducted in the pediatric emergency department of a hospital in Alexandria, Egypt, between December 1, 1999, and April 30, 2000. PATIENTS: Eighty-six children aged 1 to 4 years who were evaluated for a febrile syndrome of undetermined origin. MAIN OUTCOME MEASURES: Serological assay and polymerase chain reaction of blood and saliva samples for HHV-8. Information on potential risk factors for HHV-8 infection was also collected. RESULTS: Thirty-six children (41.9%) were seropositive; HHV-8 DNA sequences were detected in 14 (38.9%) of these 36 children (detected in saliva in 11 of 14). Significant associations were found between HHV-8 infection and close contact with at least 2 other children in the community (36 of 63 vs 6 of 23 for <2 children; adjusted odds ratio [OR], 3.50; 95% confidence interval [CI], 1.11-12.22) and admission to the emergency department in December or January (28 of 47 vs 14 of 39 for February-April; adjusted OR, 3.15; 95% CI, 1.23-8.58). Six children had suspected primary HHV-8 infection; all but 1 had a febrile cutaneous craniocaudal maculopapular rash, which was more common among these children (5 of 6 vs 10 of 75; P<.001). For 3 of these 6 children, a second blood sample was obtained after the convalescence phase, and all 3 seroconverted for HHV-8. CONCLUSIONS: Primary infection with HHV-8 may be associated with a febrile maculopapular skin rash among immunocompetent children. The finding of HHV-8 DNA sequences in saliva supports the hypothesis that transmission through saliva is the main mode of transmission in the pediatric age group.
To assess the circulation of human herpesvirus (HHV)-8 infection over the years, two seroprevalence surveys were conducted, which tested sera from HIV-infected individuals recruited 10 years apart (206 individuals from 1986 to 1988 and 177 individuals from 1997 to 1998). For all patients, antibodies to hepatitis C virus (HCV), hepatitis B virus (HBV), and HHV-8 lytic and latent antigens were evaluated.HHV-8 seroprevalence was higher among individuals recruited in the 1990s (31.6% for anti-lytic, 8.5% for anti-latent antibodies) compared with similar findings in those seen in the late 1980s (14.6% and 3.4% for anti-lytic and anti-latent antibodies, respectively), with a twofold increase of the risk of HHV-8 infection. However, the increase was observed only among injecting drug users, whereas seroprevalence tended to slightly increase among those infected by sexual contact. At univariate analysis, time of recruitment and being homosexual men were factors associated with HHV-8 infection, an association that remained after adjusting for age. HBV infection was significantly associated with HHV-8 infection (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.3-3.6), whereas those infected with HCV had a lower probability of having HHV-8 antibodies (OR, 0.3; 95% CI, 0.20-0.6). After controlling for age and gender, time of recruitment remained independently associated with HHV-8 infection among injecting drug users. In conclusion, HHV-8 seroprevalence appears to be increased during 10 years among HIV-infected injection drug users but not among homosexual men, who remain those at the highest risk of infection.
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Kaposi's sarcoma (KS) develops upon reactivation of human herpesvirus 8 (HHV8) infection and virus dissemination to blood and tissue cells, including endothelial and KS spindle cells where the virus is mostly present in a latent form. However, this may likely require the presence of compromised host immune responses and/or the evasion of infected cells from the host immune response. In this regard, mechanisms of evasion of productively infected cells from both CTL and NK cell responses, and resistance of latently infected cells from specific CTL, have already been shown. Here we show that cells which are latently infected by HHV8 are indeed efficiently lysed by NK cells from individuals with a normal immune response. Notably, NK cell-mediated immunity was found to be significantly reduced in AIDS patients with progressing KS as compared to both HIV-negative patients with indolent classic KS or normal blood donors. However, it was restored after treatment with the highly active antiretroviral therapy (HAART) in AIDS-KS patients, that showed regression and clearance of HHV8 from PBMC. By contrast, AIDS-KS patients with a more aggressive disease and no clinical response had persistent HHV8 viremia associated with reduced NK cell cytotoxicity. These results suggest a key role for NK cells in the control of HHV8 latent infection, KS development, and in disease remission upon HAART.
Treatment with HIV-1 protease inhibitors (PI) is associated with a reduced incidence or regression of Kaposi sarcoma (KS). Here we show that systemic administration of the PIs indinavir or saquinavir to nude mice blocks the development and induces regression of angioproliferative KS-like lesions promoted by primary human KS cells, basic fibroblast growth factor (bFGF), or bFGF and vascular endothelial growth factor (VEGF) combined. These PIs also block bFGF or VEGF-induced angiogenesis in the chorioallantoic membrane assay with a potency similar to paclitaxel (Taxol). These effects are mediated by the inhibition of endothelial- and KS-cell invasion and of matrix metalloproteinase-2 proteolytic activation by PIs at concentrations present in plasma of treated individuals. As PIs also inhibit the in vivo growth and invasion of an angiogenic tumor-cell line, these data indicate that PIs are potent anti-angiogenic and anti-tumor molecules that might be used in treating non-HIV KS and in other HIV-associated tumors.
BACKGROUND: Although studies have reported large reductions in the risks of AIDS and death since the introduction of potent anti-retroviral therapies, few have evaluated whether this has been similar for all AIDS-defining diseases. We wished to evaluate changes over time in the risk of specific AIDS-defining diseases, as first events, using data from individuals with known dates of HIV seroconversion. METHODS: Using a competing risks proportional hazards model on pooled data from 20 cohorts (CASCADE), we evaluated time from HIV seroconversion to each first AIDS-defining disease (16 groups) and to death without AIDS for four calendar periods, adjusting for exposure category, age, sex, acute infection, and stratifying by cohort. We compared results to those obtained from a cause-specific hazards model. RESULTS: Of 6,941, 2,021 (29%) developed AIDS and 437 (6%) died without AIDS. The risk of AIDS or death remained constant to 1996 then reduced; relative hazard = 0.89 (95% CI: 0.77-1.03); 0.90 (95% CI: 0.81-1.01); and 0.32 (95% CI: 0.28-0.37) for 1979-1990, 1991-1993, and 1997-2001, respectively, compared to 1994-1996. Significant risk reductions in 1997-2001 were observed in all but two AIDS-defining groups and death without AIDS in a competing risks model (with similar results from a cause-specific model). There was significant heterogeneity in the risk reduction across events; from 96% for cryptosporidiosis, to 17% for death without AIDS (P < 0.0001). CONCLUSION: These findings suggest that studies reporting a stable trend for particular AIDS diseases over the period 1979-2001 may not have accounted for the competing risks among other events or lack the power to detect smaller trends.
BACKGROUND: Herpes simplex virus type 2 (HSV-2) infections may be a risk factor for the transmission of HIV. Data on the prevalence of HSV-2 infection among HIV-positive individuals are scarce. GOAL: The goal was to study the seroprevalence of and risk factors for HSV-2 infection among a cohort of Italian HIV-positive individuals. STUDY DESIGN: This was a cross-sectional study. HSV-2 serologic testing was performed for individuals with known date of HIV seroconversion, on the serum specimen obtained on the date closest to the estimated date of seroconversion. Antibodies to HSV-2 (anti-HSV-2) were detected by a gG2-specific ELISA. RESULTS: A total of 380 HIV-positive individuals were tested for anti-HSV-2; 126 (33.2%) of them were positive. Older age at HIV seroconversion and homosexuality were significantly associated with HSV-2 infection in the multivariate analysis. CONCLUSIONS: These data stress the need for including anti-HSV-2 testing and therapy in the management of HIV positivity, especially for reducing the risk of transmission of HIV through herpetic lesions.