Barbara Suligoi

Pattern of cancer risk in persons with AIDS in Italy in the HAART era

A record-linkage study was carried out between the Italian AIDS Registry and 24 Italian cancer registries to compare cancer excess among persons with HIV/AIDS (PWHA) before and after the introduction of highly active antiretroviral therapy (HAART) in 1996. Standardised incidence ratios (SIR) were computed in 21951 AIDS cases aged 16–69 years reported between 1986 and 2005. Of 101 669 person-years available, 45 026 were after 1996. SIR for Kaposi sarcoma (KS) and non-Hodgkin lymphoma greatly decreased in 1997–2004 compared with 1986–1996, but high SIRs for KS persisted in the increasingly large fraction of PWHA who had an interval of <1 year between first HIV-positive test and AIDS diagnosis. A significant excess of liver cancer (SIR=6.4) emerged in 1997–2004, whereas the SIRs for cancer of the cervix (41.5), anus (44.0), lung (4.1), brain (3.2), skin (non-melanoma, 1.8), Hodgkin lymphoma (20.7), myeloma (3.9), and non-AIDS-defining cancers (2.2) were similarly elevated in the two periods. The excess of some potentially preventable cancers in PWHA suggests that HAART use must be accompanied by cancer-prevention strategies, notably antismoking and cervical cancer screening programmes. Improvements in the timely identification of HIV-positive individuals are also a priority in Italy to avoid the adverse consequences of delayed HAART use.

Precision and Accuracy of a Procedure for Detecting Recent Human Immunodeficiency Virus Infections by Calculating the Antibody Avidity Index by an Automated Immunoassay-Based Method

ABSTRACT We evaluated the precision and accuracy of a procedure for detecting recent human immunodeficiency virus (HIV) infections, specifically, the avidity index (AI) calculated using a method based on an automated AxSYM HIV 1/2gO assay (Abbott). To evaluate precision, we performed multiple replicates on eight HIV-positive serum samples. To evaluate the accuracy in identifying recent infections (i.e., within 6 months of seroconversion), we used 216 serum samples from 47 persons whose dates of seroconversion were known. To evaluate the sensitivity and specificity of the procedure for different AI cutoff values, we performed receiver operating characteristic (ROC) analysis. To determine the effects of antiretroviral treatment, advanced stage of the disease (i.e., low CD4-cell count), and low HIV viral load on the AI, we analyzed 15 serum samples from 15 persons whose dates of seroconversion were unknown. The precision study showed that the procedure was robust (i.e., the total variance of the AI was lower than 10%). Regarding accuracy, the mean AI was significantly lower for samples collected within 6 months of seroconversion, compared to those collected afterwards (0.68 ± 0.16 versus 0.99 ± 0.10; P < 0.0001), with no overlap of the 95% confidence intervals. The ROC analysis revealed that an AI lower than 0.6 had a sensitivity of 33.3% and a specificity of 98.4%, compared to 87.9 and 86.3%, respectively, for an AI lower than 0.9. Antiretroviral treatment, low CD4-cell count, and low viral load had no apparent effect on the AI. In conclusion, this procedure is reproducible and accurate in identifying recent infections; it is automated, inexpensive, and easy to perform, and it provides a quantitative result with different levels of sensitivity and specificity depending on the selected cutoff.

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

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 manufacturers 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.

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.

Cancer incidence in people with AIDS in Italy

People with HIV/AIDS (PWHA) have increased risk of some cancers. The introduction of highly active antiretroviral therapies (HAART) has improved their life expectancy, exposing them to the combined consequences of aging and of a prolonged exposure to cancer risk factors. The aim of this study was to estimate incidence rates (IR) in PWHA in Italy, before and after the introduction of HAART, after adjusting for sex and age through direct standardization. An anonymous record linkage between Italian AIDS Registry (21,951 cases) and Cancer Registries (17.3 million, 30% of Italian population) was performed. In PWHA, crude IR, sex‐ and age‐standardized IR and age‐specific IR were estimated. The standardized IR for Kaposi sarcoma and non‐Hodgkin lymphoma greatly declined in the HAART period. Although the crude IR for all non‐AIDS‐defining cancers increased in the HAART period, standardized IR did not significantly differ in the 2 periods (352 and 379/100,000, respectively). Increases were seen only for cancer of the liver (IR ratio = 4.6, 95% CI: 1.3–17.0) and lung (IR ratio = 1.8, 95% CI: 1.0–3.2). Age‐specific IRs for liver and lung cancers, however, largely overlapped in the 2 periods pointing to the strong influence of the shift in the age distribution of PWHA on the observed upward trends. In conclusion, standardized IRs for non‐AIDS‐defining cancers have not risen in the HAART period, even if crude IRs of these cancers increased. This scenario calls, however, for the intensification of cancer‐prevention strategies, notably smoking cessation and screening programs, in middle‐aged HIV‐patients.

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.

HIV infection increases the risk of squamous intra‐epithelial lesions in women with HPV infection: An analysis of HPV genotypes

We assessed the association between different HPV genotypes, HIV infection, and cervical squamous intra‐epithelial lesions (SIL) in 236 women with known HIV serostatus enrolled in a longitudinal multicentric study in Italy. Of these women, 135 were HIV‐infected, and were not markedly different from HIV‐negative women with regard to demographic characteristics, sexual practices, smoking, or intravenous drug use. We obtained 232 cervical smears suitable for cytological examination and HPV‐genotype analysis (134 from HIV‐positive women and 98 from HIV‐negative women). For 86 HIV‐positive and 89 HIV‐negative women, the smears appeared normal at cytomorphological analysis. Cytological dysplasia of varying degrees was detected in 48 smears from HIV‐positive women and in 9 from HIV‐negative women. HPV prevalence, assessed using polymerase‐chain‐reaction analysis, did not significantly differ between HIV‐positive and HIV‐negative women. The prevalence of HPV‐associated SIL was much greater among HIV‐infected women. The most frequently detected genotypes in both groups were HPV 16 and HPV 18. The prevalence of HPV 16 among HIV‐positive women was similar to that for HIV‐negative women; this was also true for HPV 18. However, in the HIV‐positive group, most of these genotypes were associated with SIL. HIV‐positive women showed a wider spectrum of genotypes, including non‐oncogenic and rare types. An association between SIL and HIV infection was confirmed for all HPV genotype classes. Int. J. Cancer 72:982–986, 1997.

Comparison of the Avidity Index Method and the Serologic Testing Algorithm for Recent Human Immunodeficiency Virus (HIV) Seroconversion, Two Methods Using a Single Serum Sample for Identification of Recent HIV Infections

ABSTRACT A study was designed to compare an avidity index method to the serologic testing algorithm for recent human immunodeficiency virus (HIV) seroconversion (STARHS) for the detection of recent HIV infection. One hundred sixty HIV-positive sera were tested. Both techniques performed similarly in identifying recent infections, although STARHS tended to misclassify more individuals that had long-standing infection as being recently infected.

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.

The effect of hepatitis C on progression to AIDS before and after highly active antiretroviral therapy.

Objectives: To assess the effect of infection with hepatitis C virus (HCV) on the progression of human immunodeficiency virus (HIV) disease, before and after the introduction of highly active antiretroviral therapy (HAART). Methods: We used data from a multi-centre prospective study of HIV seroconverters. Survival analyses were performed to compare the progression to AIDS by HCV serostatus in the period before HAART (i.e. June 1991–May 1996) and in the HAART era (i.e. June 1996–June 2001), controlling for duration of HIV infection. Results: Among the 1052 persons enrolled, 595 (56.6%) were co-infected; the median follow-up time was 9.7 years. Adjusting for demographic variables (age at HIV seroconversion and gender), HCV infection had no effect on the progression to AIDS in the pre-HAART era [relative hazard (RH) = 0.84; 95% confidence interval (CI), 0.63–1.11], whereas it increased the risk in the HAART era (RH = 1.77; 95% CI, 1.15–2.73). In the HAART era, the proportion of person-time spent on HAART out of the total time at risk was significantly lower among co-infected persons (30 versus 40% for non-co-infected persons; P-value = 0.001); no significant difference was found for dual-therapy (29 versus 25%, respectively; P-value = 0.205); a significant difference was found for mono-therapy (15 versus 8%, respectively; P-value < 0.001). Conclusions: HCV infection was not a determinant of HIV disease progression in the pre-HAART era, whereas since the introduction of HAART, co-infected individuals seem to have had a faster disease progression. This may in part be explained by differences in person-time spent on different antiretroviral regimens.