Giuseppe Ippolito

A case-control study of HIV seroconversion in health care workers after percutaneous exposure

BACKGROUND The average risk of human immunodeficiency virus (HIV) infection after percutaneous exposure to HIV-infected blood is 0.3 percent, but the factors that influence this risk are not well understood. METHODS We conducted a case-control study of health care workers with occupational, percutaneous exposure to HIV-infected blood. The case patients were those who became seropositive after exposure to HIV, as reported by national surveillance systems in France, Italy, the United Kingdom, and the United States. The controls were health care workers in a prospective surveillance project who were exposed to HIV but did not seroconvert. RESULTS Logistic-regression analysis based on 33 case patients and 665 controls showed that significant risk factors for seroconversion were deep injury (odds ratio= 15; 95 percent confidence interval, 6.0 to 41), injury with a device that was visibly contaminated with the source patients blood (odds ratio= 6.2; 95 percent confidence interval, 2.2 to 21), a procedure involving a needle placed in the source patients artery or vein (odds ratio=4.3; 95 percent confidence interval, 1.7 to 12), and exposure to a source patient who died of the acquired immunodeficiency syndrome within two months afterward (odds ratio=5.6; 95 percent confidence interval, 2.0 to 16). The case patients were significantly less likely than the controls to have taken zidovudine after the exposure (odds ratio=0.19; 95 percent confidence interval, 0.06 to 0.52). CONCLUSIONS The risk of HIV infection after percutaneous exposure increases with a larger volume of blood and, probably, a higher titer of HIV in the source patients blood. Postexposure prophylaxis with zidovudine appears to be protective.Background The average risk of human immunodeficiency virus (HIV) infection after percutaneous exposure to HIV-infected blood is 0.3 percent, but the factors that influence this risk are not well understood. Methods We conducted a case–control study of health care workers with occupational, percutaneous exposure to HIV-infected blood. The case patients were those who became seropositive after exposure to HIV, as reported by national surveillance systems in France, Italy, the United Kingdom, and the United States. The controls were health care workers in a prospective surveillance project who were exposed to HIV but did not seroconvert. Results Logistic-regression analysis based on 33 case patients and 665 controls showed that significant risk factors for seroconversion were deep injury (odds ratio = 15; 95 percent confidence interval, 6.0 to 41), injury with a device that was visibly contaminated with the source patients blood (odds ratio = 6.2; 95 percent confidence interval, 2.2 to 21), a procedure inv...

Insights into the reasons for discontinuation of the first highly active antiretroviral therapy (HAART) regimen in a cohort of antiretroviral naive patients

Objective:To evaluate the frequency of discontinuation of the first highly active antiretroviral regimen (HAART) and the factors predictive of discontinuing for toxicity and failure in a population-based cohort of HIV-positive individuals in Italy, naïve from antiretrovirals at enrolment. Methods:The study population consisted of individuals who initiated HAART and had at least one follow-up visit. The primary end-points were discontinuation of any component of HAART for drug toxicity and discontinuation for failure. Survival analyses were performed to identify predictive factors for reaching the two end-points. Results:Eight hundred and sixty-two individuals initiated HAART; in 727 of them (84.3%) this consisted of two nucleoside reverse transcriptase inhibitors (NRTI) and one protease inhibitor (PI). Over a median follow-up of 45 weeks, 312 patients (36.2%) discontinued therapy: 182 (21.1%) discontinued due to toxicity, 44 (5.1%) due to failure. The probability of discontinuing HAART at 1 year was 25.5% [95% confidence interval (CI), 21.9–28.9] due to toxicity and 7.6% (95% CI, 4.9–10.3) due to failure. Independent factors associated with discontinuation for toxicity were: gender [relative hazard (RH) = 0.51; 95% CI, 0.32–0.80 for men versus women], type of treatment (indinavir-containing regimens, RH = 1.94; 95% CI, 1.10–3.41 and ritonavir-containing regimens, RH = 3.83; 95% CI, 2.09–7.03 versus hard-gell saquinavir) and time spent on treatment (RH = 0.89; 95% CI, 0.80–0.98 for each additional month). Discontinuation due to failure was independently associated with the most recent HIV-RNA (RH = 3.20; 95% CI, 1.74–5.88 for log10 copies/ml higher), and with type of treatment (indinavir-containing regimens, RH = 0.21; 95% CI, 0.06–0.78 and ritonavir-containing regimens, RH = 0.23; 95% CI, 0.04–1.26 versus hard-gell saquinavir). Conclusions:If the current HAART regimen caused no toxicity, less than 10% of naïve patients discontinue their first HAART regimen because of failure after 1 year from starting therapy.

Self-reported symptoms and medication side effects influence Adherence to highly active antiretroviral therapy in persons with HIV infection

Objectives: To identify variables predictive of nonadherence to highly active antiretroviral therapy (HAART) and to assess whether self‐reported symptoms or medication side effects are related to adherence. Design: Cross‐sectional multicenter study Adherence Italian Cohort Naive Antiretrovirals [AdICONA] within the Italian Cohort Naive Antiretrovirals (ICONA). Methods: Participants receiving HAART completed a 16‐item self‐administered questionnaire to assess nonadherence in the last 3 days as well as the type and intensity of 24 common HIV‐ and HAART‐related symptoms experienced during the last 4 weeks. Results: From May 1999 to March 2000, 358 persons were enrolled: 22% reported nonadherence and were less likely to have HIV RNA <500 copies/ml (odds ratio = 0.51; 95% confidence interval: 0.31‐0.85). Frequency of moderate/severe symptoms or medication side effects in nonadherent participants ranged from 3.6% to 30%. On univariate analysis, nausea, anxiety, confusion, vision problems, anorexia, insomnia, taste perversion, and abnormal fat distribution were significantly associated with nonadherence. Nonadherent persons had a higher mean overall symptom score (12.3 ± 9.2 versus 8.1 ± 6.6; p < .001) and mean medication side effect score (2.9 ± 2.7 versus 1.9 ± 1.9; p < .001) when compared with adherent participants. In the multivariate analysis, nausea (p = .003); anxiety (p = .006); younger age (p = .007); unemployment (p < .001); not recalling name, color, and timing of drugs (p = .009); running out of pills between visits (p = .002); and being too busy (p = .03) were independently associated with nonadherence in the last 3 days. Conclusions: In addition to patient characteristics, medication‐related variables, and reasons for nonadherence, patient‐reported symptoms and medication side effects were significantly associated with adherence to HAART.

Better response to chemotherapy and prolonged survival in AIDS-related lymphomas responding to highly active antiretroviral therapy

Objectives To evaluate the impact of response to highly active antiretroviral therapy (HAART) on the natural history of AIDS non-Hodgkins lymphoma (NHL) and to analyse the feasibility, efficacy and toxicity of HAART in combination with chemotherapy. Design Prospective observational study in two AIDS clinical centres in Italy. Methods All consecutive HIV-infected patients with NHL were included (n = 44; 48% high-risk group) and prospectively followed for 27 months. HAART was administered concomitantly with chemotherapy. The association between response to HAART and clinical presentation, response to chemotherapy and toxicity was analysed by univariate and multivariate models. Survival analysis was performed by Kaplan–Meier estimates and the Cox proportional hazards regression model. Results A complete response (CR) to chemotherapy was achieved in 71% of HAART responders and 30% of non-responders. Virological response to HAART was the only variable associated with tumour response on multivariate analysis. A higher relative dose intensity (RDI) of chemotherapy was administered in patients with virological response compared with those without. The probability of 1 year survival was higher in patients with virological or immunological response. At Cox regression analysis, immunological response, a higher RDI and a CR to chemotherapy were all associated with a reduced risk of death. Conclusion In HIV-infected patients with NHL, response to HAART was strongly associated with a better response to chemotherapy and prolonged survival. Concurrent treatments were well tolerated, and HAART-responder patients could receive a higher RDI of chemotherapy. In patients with AIDS lymphomas, combining HAART with chemotherapy could be a feasible and effective approach.

Risk of hepatitis C seroconversion after occupational exposures in health care workers

BACKGROUND To determine the incidence of hepatitis C virus (HCV) seroconversion, health care workers reporting an occupational exposure with blood or other risk-prone body materials from a patient known to be seropositive for HCV antibody were enrolled. METHODS HCV seroconversion within 6 months of a reported exposure was assessed by second-generation enzyme immunoassay and immunoblot assay. RESULTS From January 1992 through December 1993, 331 (51%) hollow-bore needlesticks, 105 (16.5%) suture needle or sharp object injuries, 85 (13%) mucous membrane contaminations, and 125 (19.5%) skin contaminations were reported. Four HCV seroconversions were observed after hollow-bore needlesticks (1.2%; 95% CI 0.3% to 3.0%); no seroconversions occurred after other routes of exposure. Blood-filled needlesticks and source patient coinfection with HIV appeared to be associated with a higher risk of seroconversion. CONCLUSIONS The risk of HCV seroconversion after occupational exposure appears to be low but is not negligible. Aggressive implementation of universal precautions is important for preventing risk-prone exposure, but safer devices are also needed.

Impact of combination antiretroviral therapy on the risk of tuberculosis among persons with HIV infection

ObjectiveTo assess the association between use of different antiretroviral regimens and incidence of tuberculosis among HIV-infected individuals. DesignObservational, multicenter, prospective cohort study. Setting and patientsTwenty-eight infectious diseases hospital units in Italy. A total of 2160 HIV-infected persons were considered for enrolment in a study on the implementation of tuberculosis preventive therapy between 1 May 1995 and 30 April 1996. The 1360 subjects who completed tuberculin screening at base-line were included in this analysis. Information on the use of antiretroviral therapies over time was collected. The median duration of follow-up was 104 weeks and 997 subjects (73.3%) completed the study. Main outcome measureIncidence of active tuberculosis according to different types of antiretroviral therapy. ResultsEighteen cases of tuberculosis were observed with an overall incidence rate of 0.79 per 100 person–years of observation [95% confidence interval (CI), 0.51–1.31]. Tuberculin positivity and low CD4+ lymphocyte count were the only base-line variables independently associated with the risk of tuberculosis. During follow-up, 637 patients took double combination antiretroviral therapy and 387 took triple combination therapy. After adjusting for base-line characteristics of enrolled individuals, the relative hazard of tuberculosis was 0.16 (95% CI, 0.03–0.74) for double combination therapy and 0.08 (95% CI, 0.01–0.88) for triple combination therapy compared with no therapy or monotherapy. ConclusionsCombination antiretroviral therapy significantly reduced the risk of tuberculosis in HIV-infected persons. In industrialized countries, the widespread use of this treatment may determine a decrease in the incidence of HIV-associated tuberculosis, possibly contributing to a reduction in the overall incidence of tuberculosis.

Use of Massively Parallel Ultradeep Pyrosequencing To Characterize the Genetic Diversity of Hepatitis B Virus in Drug-Resistant and Drug-Naive Patients and To Detect Minor Variants in Reverse Transcriptase and Hepatitis B S Antigen

ABSTRACT Direct population sequencing and reverse hybridization (line probe assay [LiPA])-based methods are the most common methods for detecting hepatitis B virus (HBV) drug resistance mutations, although only mutations present in viral quasispecies with a prevalence of ≥20% can be detected by sequencing, and only known mutations are detected by LiPA. Massively parallel ultradeep pyrosequencing (UDPS; GS FLX platform) was used to analyze HBV quasispecies in reverse transcriptase (RT) and hepatitis B S antigen (HBsAg) from five drug-naive patients and eight drug-resistant patients. Eight primer pairs were used to obtain partially overlapping amplicons, covering the RT gene from codons 1 to 288 and the complete overlapping HBsAg sequence. A 1% mutation frequency was selected as the cutoff based on an error rate estimated on plasmid DNA. This technology enabled simultaneous analysis of between 2,852 and 18,016 clonally amplified fragments from each patient. The results indicate that UDPS has a relative sensitivity much higher than both direct sequencing and LiPA. In addition, the UDPS results are quantitative, allowing establishment of the relative frequency of both known mutations and novel substitutions. Some of the detected RT substitutions led to changes also in HBsAg. On the whole, genotype D presented a higher heterogeneity than genotype A. Considering the high quantity of information that can be provided by a single test from one patient, the short turnaround time, the information on substitution frequency, and the detection of rare variants, there are strong advantages conferred by UDPS, and the new method could play a relevant role in the clinical management of HBV infection and therapy.

Delayed presentation and late testing for HIV: Demographic and behavioral risk factors in a multicenter study in Italy

Summary:Ensuring timely access to care for persons with HIV is an important public health goal. To identify factors associated with delayed presentation to medical care after testing HIV-positive or with late HIV testing, we studied 968 patients at their first HIV care visit, enrolled in a multicenter study in Italy from 1997–2000. Patients completed a questionnaire on HIV-testing history, sexual behavior, and drug use behavior. Delayed presenters were patients with >6 months between their first HIV-positive test and presentation for HIV care; late testers were patients with CD4 count < 200 /mm3 or clinically defined AIDS at their first HIV-positive test. Among the study patients, 255 (26.3%) were delayed presenters, and 280 (28.9%) were late testers. In multinomial logistic regression analysis, injection drug use significantly increased (odds ratio [OR]= 5.04) the probability of delayed presentation but reduced (OR = 0.55) the chance of late testing. A previous HIV-negative test was associated with a reduced risk of both delayed presentation (OR = 0.39) and late testing (OR = 0.36). Unemployment was positively associated with delayed presentation and increasing age with late testing, whereas HIV counseling at the time of first positive HIV test strongly (OR = 0.42) reduced the odds of delayed presentation. Interventions aimed at promoting timely access to care of HIV-infected persons should consider differentiated programs for delayed presentation and late testing.

Occupational Human Immunodeficiency Virus Infection in Health Care Workers: Worldwide Cases Through September 1997

The average estimated risk of human immunodeficiency virus (HIV) infection for health care workers following a percutaneous or mucous exposure is <0.5% in incidence studies, although a case-control study suggests it is much higher for highest-risk percutaneous exposure. To characterize exposures resulting in HIV transmission, we reviewed available data on occupational cases reported worldwide, identifying 94 documented and 170 possible cases. The majority of documented infections occurred in nurses, after contact with the blood of a patient with AIDS by means of percutaneous exposure, with a device placed in an artery or vein. High-exposure job categories, e.g., midwives and surgeons, are represented mostly among possible cases. Transmission occurred also through splashes, cuts, and skin contaminations, and in some cases despite postexposure prophylaxis with zidovudine. Health care workers could benefit if these data were incorporated in educational programs designed to prevent occupational bloodborne infections.

Persistent detection of Zika virus RNA in semen for six months after symptom onset in a traveller returning from Haiti to Italy, February 2016

A man in his early 30s reported in January 2016 a history of fever, asthenia and erythematous rash during a stay in Haiti. On his return to Italy, ZIKV RNA was detected in his urine and saliva 91 days after symptom onset, and in his semen on day 188, six months after symptom onset. Our findings support the possibility of sexual transmission of ZIKV and highlight the importance of continuing to investigate non-vector-borne ZIKV infection.