Mariangela Raimondo

HIV virology and pathogenetic mechanisms of infection: a brief overview

Studies on HIV virology and pathogenesis address the complex mechanisms that result in the HIV infection of the cell and destruction of the immune system. These studies are focused on both the structure and the replication characteristics of HIV and on the interaction of the virus with the host. Continuous updating of knowledge on structure, variability and replication of HIV, as well as the characteristics of the host immune response, are essential to refine virological and immunological mechanisms associated with the viral infection and allow us to identify key molecules in the virus life cycle that can be important for the design of new diagnostic assays and specific antiviral drugs and vaccines. In this article we review the characteristics of molecular structure, replication and pathogenesis of HIV, with a particular focus on those aspects that are important for the design of diagnostic assays.

Late presenters among persons with a new HIV diagnosis in Italy, 2010–2011

BackgroundIn Western Europe, about 50% of newly diagnosed HIV-positive individuals are diagnosed at a late stage disease and enter in care late (i.e. with a CD4 count ≤350 μL/μL). The aim of the present study is to analyze the characteristics and the factors associated with being diagnosed late or at an advanced stage of disease among persons with a new HIV diagnosis in Italy, in the period 2010–2011.MethodsWe used individual data on new HIV diagnoses reported by the HIV surveillance system in 2010 and in 2011. Persons with CD4 ≤350 cells/μL or diagnosed with AIDS (regardless of the CD4 cell count) were defined as late presenters (LP); persons with CD4 ≤ 200 cells/μL or AIDS (regardless of the CD4 cell count) were defined as presenting with advanced HIV disease (AHD).ResultsOf the 7,300 new diagnoses reported in 2010–2011 by the included regions, 55.2% were LP; among these, 37.9% was diagnosed with AIDS. Persons presenting with AHD were 37.8%.The median age of LP was 40 years (IQR 33–48), significantly higher (p < 0.001) than that of non-LP (35 years); 73.9% were males; 30.7% were non-nationals. The median age of AHD was 42 years (IQR 35–50), 74.5% were males; 31.1% were non-nationals.The proportion of LP among IDUs was 59.8%, among heterosexuals (HET) 61.1% and among MSM 44.3%. The proportion of AHD among IDUs was 43.6%, among HET 43.2% and among MSM 27.4%.Factors significantly associated with being LP were: age older than 50 years (OR = 4.6 [95% CI 3.8-5.6]); having been diagnosed in Southern Italy (Southern vs Northern Italy OR = 1.5 [95% CI 1.3-1.7]) having been diagnosed in Central Italy (Central vs Northern Italy OR = 1.3 [95% CI 1.1-1.6]); being HET (HET vs MSM, OR = 1.7 [95% CI 1.5-2.0]), being non-national (Non-national vs Italian, OR 1.7 (95% CI 1.5-2.0); being IDU (IDU vs MSM, OR = 1.6 [95% CI 1.2-2.1]). The same factors were significantly associated with being AHD.ConclusionsOlder people, people diagnosed in Central and Southern Italy, non nationals, and persons who acquired the infection through injecting drug use or heterosexual contact showed a higher risk of being diagnosed late. A more active offer of HIV testing and targeted interventions focussed on these populations are needed to optimize early access to care and treatment.

Laboratory diagnostics for HIV infection

Laboratory diagnosis of human immunodeficiency virus (HIV) infection is fundamental for detecting and monitoring infection. Many diagnostic tools are available that are based on both detection of HIV-specific antibodies and virus antigen, or nucleic acid. As technology evolves, HIV testing assays are being improved providing better sensitivity and specificity. In this short review, we summarize the common and new methodologies that are being used in laboratories, from the HIV antibody-based assays to the new tests for the detection of HIV nucleic acids.

Avidity Index for Anti-HIV Antibodies: Comparison between Third- and Fourth-Generation Automated Immunoassays

ABSTRACT The development of assays for detecting recent HIV infections has become crucial for analyzing trends in infection in different populations, both for surveillance and prevention activities. The anti-HIV avidity index (AI), measured with third-generation immunoassays (which detect anti-HIV antibody), has been shown to be an accurate tool for discriminating recent HIV infections (<6 months) from established infections (≥6 months). We compared a third-generation immunoassay (AxSYM HIV 1/2 gO; Abbott Diagnostics) to a fourth-generation immunoassay (Architect HIV Ag/Ab Combo; Abbott Diagnostics; which detects anti-HIV antibody and p24 antigen) in terms of AI performance in distinguishing between recent and established HIV infections. A total of 142 samples from 75 HIV-infected individuals with an estimated date of seroconversion were assayed. The two assays showed the same accuracy in identifying a recent infection (91.5%), using an AI cutoff of 0.80, although Architect HIV Ag/Ab Combo was slightly more sensitive (89.4% versus 84.8%; P > 0.05) and yet less specific (93.4% versus 97.4%; P > 0.05). The correlation between assays was high (r = 0.87). When 20 specimens falling in the gray zone around the cutoff point (0.75 ≤ AI ≤ 0.84) were excluded, the accuracy of AI with Architect HIV Ag/Ab Combo was 94.7%, and the concordance between the two assays was 99.2%. The anti-HIV AI is a serological marker that accurately discriminates recent from established HIV infections. It can be successfully applied on fully automated fourth-generation HIV Ab/Ag immunoassays, which have several advantages, including increased throughput, high reproducibility, no need for specific technical skills, and easy comparability of results obtained in different settings.

Estimates of the Number of People Living with HIV in Italy

Objective. To estimate the HIV prevalence and the number of people living with HIV (PLHIV) in Italy with a projection for 2020. Methods. Two methods elaborated by Joint United Nations Programme on HIV/AIDS (UNAIDS) were used: Estimate and Projection Package and Spectrum. Results. A total of 123,000 (115,000–145,000) individuals aged 15 or more were estimated to be living with HIV in Italy at the end of 2012 and the estimated HIV prevalence was 0.28 (0.24–0.32) per 100 residents aged 15 or more. In 2012, the estimated number of new HIV infections among adults was 3,000 (2,700–4,000), and the number of adults in need for ART was 93,000 (80,000–110,000). The projection estimates that 130,000 (110,000–150,000) adults will live with HIV/AIDS in 2020 in Italy. Conclusion. Estimates of PLHIV in Italy stress the high number of PLHIV in need of care and treatment, as well as the need for more information and prevention campaigns.

Identification of recent HIV infections and of factors associated with virus acquisition among pregnant women in 2004 and 2006 in Swaziland

BACKGROUND HIV continues to spread at high rates in sub-Saharan Africa. In particular, Swaziland is one of the countries most affected by the HIV/AIDS pandemic. Monitoring of HIV infection in Swaziland is being made by periodical investigations on HIV prevalence in pregnant women. However, knowledge of proportion of recent HIV infections is important for epidemiologic purposes to assess HIV transmission patterns. OBJECTIVES To evaluate the proportion of recent HIV infections among pregnant women and its change overtime and to analyze factors associated with recent HIV infection in Swaziland. STUDY DESIGN HIV-positive sera from pregnant women were collected during the 2004 and 2006 National HIV Serosurveys conducted in Swaziland and tested for the HIV antibody avidity, in order to identify recent HIV infections. Socio-demographic and clinical information was also collected. A multivariate analysis was conducted to assess the association between recent HIV infection and socio-demographic and clinical factors. RESULTS A total of 1636 serum samples were tested for HIV antibody avidity. The overall proportion of recent infections was 13.8%, with no significant difference between 2004 and 2006 (14.6% vs. 13.1%, P>0.05, respectively). At the multivariate analysis, the younger age [14-19 vs. >or=20 years; adjusted odds ratio (aOR) 2.17, 95% CI: 1.45-3.24], as well as being at first pregnancy (1 vs. >or=2; aOR 1.61, 95% CI: 1.10-2.35) was independently associated with recent HIV infection. CONCLUSIONS This study shows no significant difference in the proportion of recent infections between 2004 and 2006 and suggests that young women and women at their first pregnancy are currently high-risk groups for HIV acquisition, highlighting the importance of developing targeted youth programmes to reduce the spread of HIV infection in the country.

The epidemic of HIV infection and AIDS, promotion of testing, and innovative strategies

In Europe, the incidence of new diagnoses of HIV infection in 2008 was 86.7 cases per one million population, and most cases were attributable to sexual transmission. In Italy, in 2007, the incidence was 60.0 cases per one million population (in the areas in which surveillance exists), and 73.7% of the cases were attributable to sexual transmission. At present, there are an estimated 170,000-180,000 persons living with HIV/AIDS in Italy, some of whom are unaware of being infected. Based on available epidemiological data and taking into consideration the level of risk of exposure to HIV, we describe several proposals for promoting access to HIV testing in diverse population groups and contexts, including some innovative approaches. The promotion of HIV testing is fundamental for public health and human rights and must be associated with treatment, care and prevention activities, which must be guaranteed for the entire population.

Epidemiology of human immunodeficiency virus infection in blood donations in Europe and Italy

BACKGROUND The safety of blood with regards to transmission of infectious diseases is guaranteed by European laws that regulate both the selection of donors through pre-donation questionnaires and serological screening. However, variability in the epidemiology of human immunodeficiency virus (HIV) infection in different countries and some differences in the selection of donors can influence the efficacy (with regards to the safety of blood) of these processes. In this study we compared the prevalence of HIV in blood donations in the three macro-areas of Europe and in various western European countries, analysed the criteria of selection and rewarding of donors in western European countries, and studied the trend in the prevalence of HIV in Italy from to 1995 and 2006. METHODS European data were derived from the European Centre for the Surveillance of HIV; Italian data were obtained from the Transfusion-Transmitted Infections Surveillance System and National and Regional Register of blood and plasma. The information on eligibility criteria and rewarding offered to donors was derived from international sources. RESULTS The prevalence of HIV in blood donations was highest in eastern Europe, followed by central Europe and western Europe. Among the western European countries, Spain, Italy and Israel had the highest prevalences; the prevalence was noted to be higher in countries which did not offer any rewarding to the donor. In Italy the prevalence of HIV was 3.8 cases per 100,000 donations in 2006 and increased between 1995 and 2006, both among donations from repeat donors and first time donors. CONCLUSIONS The data highlight the need to continue improving the selection of donors and the coverage of the surveillance systems for HIV infection in transfusion services.

Suggested strategies for the laboratory diagnosis of HIV infection in Italy

HIV/AIDS surveillance data indicate that, in 2008, approximately one-fourth of all HIV infections in adults remain undiagnosed in Italy and that close to 60% of AIDS diagnosed individuals discovered their seropositivity at the diagnosis of AIDS. Late diagnosis of HIV infection is associated with increased mortality and morbidity and increased cost to healthcare services. From a public health perspective, knowledge of HIV status is associated with a reduction in risk behaviour. Thus, a routine screening for HIV infection is important for both a better prognostic outcome, and control of HIV spreading in the population. In Italy there are not shared guidelines for the laboratory diagnosis. In this paper, we suggest two algorithms that can be adopted for the diagnosis of HIV infection in individuals undergoing HIV testing.

HIV-positive blood donors unaware of their sexual at-risk behaviours before donation in Italy

Despite the procedures adopted for the selection of blood donors, in Italy the HIV prevalence per 100 000 repeat tested donors (RTD) and first‐time tested donors (FTD) is high compared to most other Council of Europe member states. To evaluate the effectiveness of predonation procedures, we studied both the characteristics and the undisclosed risk behaviours of HIV‐positive donors.