Benedetta Longo

Increasing proportion of late testers among AIDS cases in Italy, 1996–2002

Abstract In recent years, the proportion of individuals who are unaware of being infected with HIV when diagnosed with AIDS (defined as ‘late testers’) has dramatically increased in several European countries, including Italy. We evaluated the extent and determinants of late testing and its impact in terms of AIDS-defining illnesses among AIDS cases reported to the Italian National AIDS Registry since 1996. Late testers were defined as those persons whose first positive HIV test result was within six months of the AIDS diagnosis. Late testers were more likely to be heterosexual contacts or MSWM, as opposed to IDUs. They were also more likely to come from low prevalence areas of Italy or from foreign countries. At AIDS diagnosis, late testers were less likely to be undergoing HAART or prophylaxis against PCP/toxoplasmosis, compared to non-late testers. The mean CD4 cell count at AIDS diagnosis was significantly lower among late testers. PCP, toxoplasmosis and Kaposis sarcoma were more frequently diagnosed as an AIDS-defining illness in late testers, who also had a significantly higher risk of presenting with multiple concomitant AIDS-defining illnesses. In conclusion, late testing results in missed opportunities for preventing and treating HIV infection, leading to an increased risk of developing preventable opportunistic infections and death.

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.

Tuberculoid leprosy in a patient with AIDS: a manifestation of immune restoration syndrome

An HIV positive male from Brazil, living in Italy since 1989, developed a single non-itching, papulo-erythematous infiltrative lesion on the face after 2 months from the beginning of HAART. A diagnosis of leprosy was made, suggesting that the immunodeficiency masked the disease, until the skin manifestation became evident with immune-recovery.

Community-acquired pneumonia.

Purpose of review Community-acquired pneumonia (CAP) is a major cause of morbidity, mortality and expenditure of resources. When followed, guidelines for CAP management have been demonstrated to improve clinical outcomes; however, several issues are still open. This review summarizes the recent advances in this field and the priority needs for future research. Recent findings Recently identified clinical and biochemical tools promise to improve the assessment of CAP severity; however, definition of the most accurate and feasible rule(s) for clinical practice is now necessary. Some empirical antimicrobial regimens are still being debated, such as the need for atypical pathogen coverage in home-treated and nonsevere hospitalized patients and the inclusion of respiratory fluoroquinolones among first-choice molecules. New drugs such as tigecycline and cethromycin appear promising. Pharmacokinetically enhanced amoxicillin/clavulanate is highly effective, even for treating CAP caused by multiple-drug-resistant Streptococcus pneumoniae. Other aspects recently clarified include the inappropriateness of rigid time-to-first-antibiotic-dose rules, the advantages of shorter antibiotic treatments for nonsevere patients and the need of special clinical attention for acute myocardial infarction among patients with severe CAP or clinical failure. Summary Recent developments have significantly contributed to refine the management of CAP patients. However, various hot topics remain undefined as yet and urgently require ad-hoc research in order to optimize the outcomes and the costs of this highly social-impacting disease.

HIV‐1 diversity among inmates of Italian prisons

In Italy, the prevalence of non‐B HIV‐1 subtypes ranges reportedly from 5.4% to 12.6%, yet there are no data on their circulation in prisons, where the prevalence of HIV infection is high. A retrospective study was conducted to evaluate the circulation of non‐B subtypes and to characterize their determinants in five Italian prisons. To this end an aliquot of samples of blood was taken in the period 2001–2006 from all 262 HIV‐positive inmates in whom antiretroviral treatment had failed. Complete HIV‐1 PR and RT regions were sequenced for all samples and subjected to phylogenetic analysis; 250 (95.4%) sequences clustered with subtype B. The non‐B subtype was found in 4% of Italian prison inmates and 16.7% of non‐Italian prison inmates; the overall percentage increased from 1.8% for inmates infected in 1982–1990 to 4.4% in 1991–1999 and 21.9% in 2000–2006. Factors significantly associated with non‐B subtypes were an exposure to other than injecting drug use and a first positive HIV test in 2000–2006. Non‐B subtypes were distributed within five monophyletic clades. In all cases but one, it was possible to correlate the history of HIV‐exposure to the origin of the clade, with high bootstrap values. In conclusion, although the sample may not be representative of the prison inmate population in Italy, the data suggest strongly that the circulation of non‐B subtypes has apparently increased. Non‐B subtypes were found to have been associated with heterosexual contact and time of the first HIV‐positive test. Knowledge of the different subtypes circulating in prisons may be useful for tracking the epidemiology of HIV infection and for choosing antiretroviral therapy. J. Med. Virol. 80:1689–1694, 2008.

Risk of death among Italian AIDS cases with AIDS-defining cancers in the post-HAART era

This study intended to quantify the impact of AIDS-defining cancers on the risk of death in the post-HAART era. With this aim in mind, data regarding all Italian AIDS cases reported to the National AIDS Registry were analyzed. Between 1999 and 2005, a total of 12,433 individuals were diagnosed with AIDS in Italy. Specifically excluded from this analysis were people with AIDS who were: 1) not-Italian citizen (n = 1918); 2) resident in Italian areas where individual information on death was not available (n = 108); 3) resident in unknown areas (n = 119); 4) pediatric or vertical transmission cases (n = 50); 5) diagnosed solely at autopsy (n = 576). The presence of AIDS-defining cancers (i.e., Kaposis sarcoma-KS, non-Hodgkin lymphoma-NHL, and invasive cervical cancer-ICC) at AIDS diagnosis is routinely ascertained at the National AIDS Registry, together with some other information, including age, sex, date of AIDS diagnosis, HIV transmission category, CD4+ cells count. Information on vital status of AIDS cases, as of December 2006, was assessed through a semi-automated linkage procedure, ensuring confidentiality of individual data, with the national death certificates database. Survival function was estimated by the Kaplan-Meier method; Cox regression model was used to estimate death hazard ratios (HR), and corresponding 95% confidence intervals (CI), associated to the presence of AIDS-defining cancers at diagnosis, adjusted for age at AIDS diagnosis, sex, HIV transmission category, and CD4+ cells count at diagnosis. Of the 9,662 AIDS cases included in the present study, 478 had KS, 429 immunoblastic NHL, 158 Burkitts lymphoma, 69 ICC, and 58 NHL of the central nervous system (CNS). As of December 2006, 3,096 deaths were registered: of these deaths, 505 occurred among cases with AIDS-defining cancers. The proportion of AIDS cases still alive 5 years after AIDS diagnosis was 66.6 percent. The shortest survival period was seen among individuals diagnosed with CNS NHL (median survival = 4 months), followed by those with immunoblastic NHL or Burkitts lymphoma (median survival = 16 and 38 months, respectively), whereas the longest ones were recorded among cases with ICC or KS (median not reached). In comparison with AIDS cases without AIDS-defining cancers, those with a CNS NHL had a 4.7-fold higher risk of death (95% CI: 3.5–6.4), those with immunoblastic NHL or Burkitts lymphoma had more than twice the risk (HR = 2.6, 95% CI: 2.2–2.9; and HR = 2.3, 95% CI: 1.8–2.8, respectively), and, among women, those with ICC had a 1.8-fold elevated risk (95% CI: 1.2–2.7). Conversely, among individuals with KS (HR = 0.7, 95% CI: 0.6–0.9) the risk of death was lower than that of cases without AIDS-defining cancers. In conclusion, this exhaustive survival analysis of Italian AIDS cases in the post-HAART era highlighted the persisting lethality of NHL and the long survival of cases with KS and ICC.

Combined antiretroviral therapy and the incidence of acquired immunodeficiency syndrome–related central nervous system diseases

Controversial results of neuropathological studies assessing the effect of antiretroviral treatment on central nervous system (CNS) diseases have emphasized the need for longitudinal studies. A recent article published by d’Arminio Monforte and colleagues provides evidence of a decreased incidence of acquired immunodeficiency syndrome (AIDS) dementia complex (ADC) and other CNS diseases in a European cohort of human immunodeficiency virus (HIV)–infected individuals between 1994 and 2002. The decrease, similar to that of non-CNS AIDS-defining illnesses, is almost completely explained by improved immunological conditions and inhibition of viral replication. Although the findings are convincing, this study has potential limits and biases, specifically, missing information on CNS diseases diagnosed after first AIDS-defining illnesses, short time of observation before the introduction of combined antiretroviral therapy, and lack of availability of HIV seroconversion dates. To confirm the results of the above-mentioned study, we repeated the analysis using data from the Italian Seroconversion Study, a cohort of individuals with known dates of HIV serconversion. Kaplan–Meier curves were used to estimate the risk of developing ADC and other CNS diseases (ie cerebral toxoplasmosis, cryptococcosis, progressive multifocal leukoencephalopathy, primary brain lymphoma) after HIV seroconversion (estimated as the midpoint in time between the last negative and first positive test), before and after the introduction of highly active antiretroviral therapy. Adjusted relative hazards (RHs) and their 95% confidence intervals (CIs) were obtained by multivariate Cox models, with calendar year used as dichotomous time-dependent variable, adjusting for age, sex, and transmission category. Overall, 2,045 individuals were enrolled. The median age was 27 years (range, 14–75); 70% were male subjects. During a median follow-up time of 9 years, 191 participants developed an event (78 ADC, 95 other CNS diseases, and 18 both). The incidence of CNS diseases decreased from 2.3 per 100 person-years in 1996 to 0.3 in 2001–02. The risk of developing any CNS disease at 10 years after HIV seroconversion was 0.15 (95% CI, 0.13–0.19) and 0.05 (95% CI, 0.04–0.07) before and after 1997, respectively. At the multivariate analysis (Table), the risk of developing ADC and/or any CNS disease decreased significantly since 1997 (tripletherapy era), whereas no effect was observed in 1995–96 (double-therapy era). In conclusion, we confirm the decline of the incidence of ADC and other CNS diseases, also when controlling for duration of HIV infection. The decline began after the introduction of triple therapy and has continued over the following years. The study was funded by “Programma Ricerche AIDS, Sottoprogetto Epidemiologia,” Istituto Superiore di Sanità.