Does HHV-8 have a protective role on the development of HIV encephalopathy? Italian HIV-Seroconversion Study.

OBJECTIVE: To evaluate risk factors for HIV encephalopathy and whether Kaposi's sarcoma (KS) and coinfection with human herpesvirus 8 (HHV-8) protect against this disease in a cohort of HIV seroconverters. METHODS: Individuals with known dates of HIV seroconversion belonging to different HIV exposure categories (intravenous drug users, homosexual men, heterosexual contacts) were recruited by 17 clinical centers throughout Italy. Antibodies to HHV-8 lytic antigens were detected in a subgroup of participants using an immunofluorescence assay. Risk factors for HIV encephalopathy were evaluated using Cox proportional models. The association between KS or HHV-8 infection and HIV encephalopathy was evaluated using standard statistical techniques. RESULTS: During the study period, 485 of the 1,520 participants developed acquired immunodeficiency syndrome, 38 of whom developed HIV encephalopathy. HHV-8 serologic status was determined for 390 participants. Male gender, injecting drug use, and low CD4 T-cell count were associated with HIV encephalopathy; none of the 63 participants with KS developed this disease. The risk of HIV encephalopathy did not differ significantly by HHV-8 serologic status. CONCLUSIONS: HIV encephalopathy was found to be associated with male gender and intravenous drug use. The risk increased at lower CD4 T-cell counts. Although HIV encephalopathy occurred less frequently in patients with KS, no association with HHV-8 infection was found.

Serum IgG antibodies to human herpesvirus-6 (HHV-6) do not predict the progression of HIV disease to AIDS. Italian Seroconversion Study group.

OBJECTIVES: To evaluate if different levels of human herpesvirus 6 (HHV-6) antibodies can predict HIV disease progression. DESIGN: Longitudinal study of individuals with a documented date of HIV seroconversion. SETTING: Clinical centers located throughout Italy. PATIENTS: Individuals who serconverted for HIV between 1983 and 1995 in Italy. METHODS: Sera were tested for IgG antibodies to HHV-6 using a commercial enzyme immunoassay. A serum sample with an optical density (OD) > or =242 (i.e. the mean value of 10 negative controls +4x standard deviation) was considered as HHV-6 positive; the progression of HIV disease was evaluated estimating the relative hazards (RH) of AIDS (by Cox models) for individuals with higher levels vs. lower levels of HHV-6 antibodies or considering levels of antibodies based on 10% increase of the distribution (deciles). Rates of CD4 decline fitting linear regression were also estimated. RESULTS: A total of 381 persons were followed for a median time of 4 years (range: 0.15-9 years) following the date of collection of the serum sample. The median OD value of HHV-6 antibodies was 306, with an interquartile range of 241-440 and a range of 48-2330. A slight inverse correlation was found between HHV-6 antibody levels and age of the individual at the time of serum collection (Spearman rank correlation coefficient, -0.16; p = 0.0013). No association was found between HHV-6 and CD4 level or between HHV-6 and CD8 level at the date of serum collection. The unadjusted RH of progression to AIDS was 0.63 (95% CI: 0.42-0.96) for HHV-6 positive individuals vs. HHV-6 negative; when adjusting for possible confounders (CD4, age, pre-AIDS HIV-related pathologies at the date of sera collection, and previous anti-herpes treatment), the RH of AIDS increased to 0.80 (95% CI: 0.51-1.23). No particular association with HIV disease progression was found when using the deciles of the distribution of HHV-6 antibodies. The median CD4 cell loss was 5.0x10(6) cells/l per month among HHV-6 positive individuals and 5.7x10(6) cells/l per month among the others. CONCLUSIONS: The presence of high levels of HHV-6 antibodies does not seem to predict the clinical or immunologic progression of HIV disease.

Cancer incidence in a cohort of human immunodeficiency virus seroconverters. HIV Italian Seroconversion Study Group.

BACKGROUND: In addition to Kaposi's sarcoma and non-Hodgkin's lymphomas, it has been postulated that human immunodeficiency virus (HIV) infection may increase the risk of other cancers. The aim of the current study was to compare incidence rates of cancer among individuals who seroconverted for HIV infection with the rates in the general population of Italy. METHODS: This study is part of an ongoing cohort investigation conducted by the HIV Italian Seroconversion Study Group. The study has enrolled 1255 individuals (906 males and 349 females) between the ages of 20 and 49 years who are at risk for HIV infection and have had a documented negative HIV test followed by a positive test. For each individual, the midpoint in time between the negative and positive tests was used to estimate the seroconversion date. The person-years at risk for cancer were then computed from the midpoint date to the last follow-up date or to death, and the number of cases of cancer observed in the cohort was compared with the expected number, based on rates among the general population of the same age and gender. Standardized incidence ratios (SIR) and 95% confidence intervals (CI) were computed. RESULTS: A total of 58 cases of cancer were observed in the cohort. In comparison with rates in the general population, Kaposi's sarcoma was 1051 times more frequent, and non-Hodgkin's lymphomas were 157 times more frequent. Hodgkin's disease was observed in 3 men (i.e., 38 times more often in the cohort of HIV seroconverters [95% CI, 8-111]), in particular among homosexual men (SIR = 103). One woman developed stomach carcinoma. CONCLUSIONS: The findings of the current incidence study are in agreement with previous studies showing excesses of Kaposi's sarcoma and non-Hodgkin's lymphomas in HIV-positive individuals. In addition, the findings suggest an association of HIV infection with Hodgkin's disease. Whether Hodgkin's disease in HIV-infected individuals should be considered an AIDS-defining illness is a question that is worthy of attention.

Antiretroviral treatment and progression to AIDS in HIV seroconverters from different risk groups. HIV Italian Seroconversion Study.

OBJECTIVES: To evaluate the association between time since initiation of pre-AIDS antiretroviral therapy [mainly with zidovudine (ZDV)] and AIDS-free survival in a cohort of HIV seroconverters, and to assess possible differences in this association and in the use of antiretroviral therapy by HIV exposure group. DESIGN: Observational study of HIV-infected individuals, both those treated with antiretroviral therapy and those untreated, enrolled in an ongoing prospective cohort (median follow-up, 5.3. years). SETTING: Sixteen HIV outpatient clinics throughout Italy. PATIENTS: A total of 1,078 individuals infected with HIV through injecting drug use or homo-/heterosexual activity, and with accurately estimated dates of seroconversion. MAIN OUTCOME MEASURES AND METHODS: Kaplan-Meier estimates of the probability of receiving antiretroviral therapy before AIDS. Crude and adjusted relative hazards of AIDS and of death from AIDS using Cox regression models. RESULTS: The cumulative incidence of beginning pre-AIDS antiretroviral therapy within 7 years of seroconversion was 49.2%. Injecting drug users (IDU) were less likely to undergo antiretroviral treatment before AIDS than homosexual men and heterosexual contacts. The adjusted relative hazard of developing AIDS for patients treated with ZDV (relative hazard adjusted for occurrence of acute HIV disease, pre-AIDS HIV-related diseases, CD4 count, and use of prophylaxis for Pneumocystis carinii pneumonia) was 0.57 within the first year of starting zidovudine and 0.92 after 1 year of therapy. Stratifying by HIV exposure category, the adjusted relative hazards of AIDS for individuals who started ZDV less and more than 1 year before AIDS were 0.74 and 0.99 among IDU, 0.31 and 0.89 among homosexual men, and 0.69 and 0.72 among heterosexuals, respectively. Similar results were obtained when using death from AIDS as an endpoint. CONCLUSIONS: IDU began pre-AIDS antiretroviral therapy significantly later than homosexual men and heterosexuals, even after adjusting for CD4 count. Results from this non-randomized study confirm that antiretroviral treatment has only a short-term clinical benefit. There was a stronger association between antiretroviral treatment and lower risk of AIDS in homosexual men than in IDU.

How many HIV-infected individuals may be defined as long-term nonprogressors? A report from the Italian Seroconversion Study. Italian Seroconversion Study Group (ISS)

We prospectively examined a cohort of HIV-positive persons with an accurately estimated date of HIV seroconversion who were infected through injecting drug use or sexual contact to estimate the proportion of long-term nonprogressors (LTNP), considering four definitions of LTNPs. We also evaluated whether factors such as gender, age, and HIV-exposure category were associated with being LTNP; we determined the overlap among the definitions and compared the CD4 and CD8 counts and the CD4/CD8 decline among LTNPs and "moderate" and "fast" progressors. Of the 528 persons selected for analysis, 2 to 4% were considered LTNPs, depending on the definition. The proportion of LTNPs varied by definition, and there was little overlap among definitions. The LTNPs did not appear to differ from "moderate" and "fast" progressors with regard to main demographic characteristics, and they showed a better trend of immunological parameters, appearing to have a slower progression rather than a permanently arrested infection.

Incidence and consequences of pregnancy in women with known duration of HIV infection. Italian Seroconversion Study Group.

BACKGROUND: The increasing incidence of human immunodeficiency virus (HIV) infection in women of childbearing age led us to evaluate whether pregnancy affects the natural history of this disease. OBJECTIVES: To conduct a prospective study of women with known dates of HIV seroconversion to describe the incidence and outcome of pregnancy and to assess differences according to age and exposure group. To compare the rate of disease progression between pregnant and nonpregnant women. PATIENTS: All participants, recruited from 14 clinical centers in Italy, had documented HIV-seronegative test results followed by confirmed positive test results within 2 years. RESULTS: A total of 331 women, who had seroconversion between 1981 and 1994, were followed up for a median of 5.5 years from seroconversion; 94 developed HIV-related diseases, 47 developed acquired immunodeficiency syndrome, and 53 had at least 1 CD4 cell count lower than 0.10 x 10(9)/L (< 100 cells/mm3). Thirty-eight women (11.5%) were pregnant at the time of HIV seroconversion and 31 (9.4%) became pregnant after HIV seroconversion (cumulative incidence of pregnancy within 8 years of seroconversion, 28.9%; 95% confidence interval, 21.6%-36.2%). Forty-five (65.2%) of the 69 pregnancies were carried to term. There were no discernible differences in these findings by age or exposure group. Pregnant women did not experience a more rapid rate of progression of disease, even when adjusting for age, exposure group, CD4 cell count, or use of treatment (adjusted relative hazards: HIV-related diseases, 0.72; acquired immunodeficiency syndrome, 0.69; CD4 cell count <0.10 x 10(9)/L, 1.24). CONCLUSION: Women infected with HIV continue to become pregnant after seroconversion, yet pregnancy does not appear to influence the rate of progression of HIV disease.

Herpes zoster and progression to AIDS in a cohort of individuals who seroconverted to human immunodeficiency virus. Italian HIV Seroconversion Study.

A prospective study of 1,198 individuals who seroconverted to human immunodeficiency virus (HIV) was conducted to estimate the incidence and determinants of herpes zoster and to determine whether herpes zoster can accelerate the progression to AIDS. Herpes zoster was diagnosed for 48 individuals (4%). After adjusting for the CD4 cell count, individuals acquiring HIV infection through sexual contact were more likely to have herpes zoster than were injection drug users (relative hazard, 1.50). The crude relative hazard of AIDS for individuals who had herpes zoster compared with those without herpes zoster was 2.44; the adjusted relative hazard was 1.08. After adjusting for the CD4 cell count, fever was the only specific characteristic of herpes zoster that was significantly associated with a more rapid progression to AIDS (relative hazard, 6.52). Data suggest that herpes zoster occurs more frequently in individuals acquiring HIV infection through sexual transmission. There was no evidence that herpes zoster per se is an independent cofactor of progression of HIV disease, although febrile episodes of herpes zoster may predict a faster progression to AIDS.

[Prevalence of HIV infection in Italian drug users attending drug treatment centers in the years 1990-92]. / Andamento della prevalenza dell'infezione da HIV fra i tossicodipendenti italiani afferenti ai servizi di assistenza nel periodo 1990-1992.

Repeated cross-sectional surveys have been conducted to collect information on the trend of HIV prevalence among drug users attending drug treatment centers in Italy in the years 1990-92. Annual HIV prevalence was 31.5% in 1990, 29.1% in 1991, and 24.6% in 1992, showing a declining trend. HIV prevalence was higher in the North than in the South of the country, and among females than in males. Drug users entering treatment for the first time during the study period were less likely to be infected than old clients.