Drug-resistant mutants of HIV-1 in patients exhibiting increasing CD4 cell count despite virological failure of highly active antiretroviral therapy.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
E Girardi
Publications and source records attributed to E Girardi.
Estimating duration of HIV infection with CD4 cell count and HIV-1 RNA at presentation.
Explore the source record for details and available documents.
Adult↗
Female sex and the use of anti-allergic agents increase the risk of developing cutaneous rash associated with nevirapine therapy.
To identify factors associated with cutaneous rash, we performed a retrospective multicentre analysis of HIV outpatients starting a highly active antiretroviral therapy regimen containing nevirapine. A total of 62 cutaneous adverse events were observed in 429 patients. Rash hazard was increased in women, by the prophylactic use of glucocorticoids or antihistaminics, and was reduced by escalating the initial dose of nevirapine. Women receiving glucocorticoids had a 3 month cumulative probability of rash of 0.41.
Adult↗
Changing clinical presentation and survival in HIV-associated tuberculosis after highly active antiretroviral therapy.
OBJECTIVE: To assess changes in clinical presentation and outcome of HIV-associated tuberculosis (TB) before and after widespread implementation of highly active antiretroviral therapy (HAART). METHODS: We reviewed clinical charts of HIV-infected patients with culture-confirmed pulmonary TB in two referral clinical centers in Rome, Italy. The 67 patients diagnosed in 1995 to 1996 were compared with 51 patients diagnosed in 1997 to 1998. To analyze factors associated with survival we used a Cox model including antiretroviral therapy as a time-dependent covariate. RESULTS: Patients diagnosed in 1997 to 1998 were more likely to have TB as the first AIDS-defining illness (78% versus 58%, p <.05), to have HIV diagnosed <2 months before TB (33% vs. 7%, p <.005) and to have typical chest radiograph pattern (45% vs. 25%, p <.05), and had a higher CD4(+) count (median 105 vs. 43, p <.005). Survival at 1 year was 80% for patients diagnosed in 1997 to 1998 vs. 65% for those diagnosed in 1995 to 1996 (p by log-rank =.02). After adjusting at multivariate analysis, time period of diagnosis was not confirmed as associated with survival (hazard ratio, 1.05; 95% confidence interval, 0.39--2.81). Age, CD4+ cell count <25/mm(3), and AIDS-defining illnesses before TB diagnosis were all associated with an higher risk of death, whereas a decreased risk of death was observed in patients starting a triple combination antiretroviral therapy after TB diagnosis (hazard ratio, 0.14; 95% confidence interval, 0.03--0.57). CONCLUSIONS: Cases of HIV-associated TB occurring in patients with advanced immunosuppression and presenting with atypical radiologic appearance tend to be relatively less common in the HAART era. HAART is a major factor in prolonging survival in these patients.
Adult↗
Changing patterns in the etiology of HIV-associated bacterial pneumonia in the era of highly active antiretroviral therapy.
Explore the source record for details and available documents.
Adult↗
Seizure activity produces differential changes in adenosine A1 receptors within rat hippocampus.
Specific ligand binding to rat hippocampal adenosine A1 receptor after administration of the convulsant drug 3-mercaptopropionic acid (MP) was studied by means of a quantitative autoradiographic method. 2-Chloro-N6-[cyclopentyl-2,3,4,5-3H adenosine] ([3H]CCPA), a potent and selective A1 receptor ligand, was selected for binding studies. MP administration (150 mg/kg, i.p.), at seizure, caused significant increases in the following CA1 layers: pyramidal (45%), radiatum (18%) and lacunosum molecular (35%); in CA2 area, a significant decrease in stratum oriens (36%) and an increase in stratum radiatum (14%) and lacunosum molecular (33%) layers was observed. In CA3 area a rise in pyramidal (40%) and radiatum layers (26%), as well as in hillus (97%) was found. At postseizure, changes were restricted to CA1, CA2 and CA3 pyramidal layers and to CA1 lacunosum molecular layer, with increases ranging from 22 to 50%. These results show that [3H]CCPA binding is modified diversely in intrahippocampal layers and areas, thus indicating their dissimilar role in seizure activity.
Adenosine↗
Changing patterns of "hospital-at-home" care use by persons with AIDS in the era of combination antiretroviral therapy.
This study describes how hospital-at-home care (HHC) use by persons with acquired immune deficiency syndrome (PWA) has changed since the introduction of combination antiretroviral therapy (ART). For this study, all adult PWA (877) admitted for the first time to the HHC program, established for PWAs in the metropolitan area of Rome, between January 1994 and December 1998, were enrolled. Temporal changes in sociodemographic and clinical characteristics were evaluated. For subjects who concluded their first HHC cycle (851/877), the reasons for ending the service were assessed over time. From 1994 to 1998, the proportion of patients admitted to HHC of those living with AIDS in the Rome area decreased significantly (from 15.1% to 7.5%), while the median CD4+ cell count at HHC entry increased significantly. The proportion of patients referred to outpatient services at the end of their cycle of HHC increased sevenfold from 1994 to 1998, with a steep increase between 1996 and 1997. In multivariate analysis, only the use of triple-combination ART was significantly associated with referral to outpatient care (odds ratio [OR] = 4.26; 95%, confidence interval [CI] = 1.94-9.34). The results suggest that HHC use by PWAs in the ART era has diminished, while the HHC use pattern has also changed: there is a growing tendency to provide care to patients with less advanced human immunodeficiency virus (HIV) disease, prior to the beneficial effects of drugs, and the consequent referral to outpatient care.
Acquired Immunodeficiency Syndrome↗
The changing picture of the HIV/AIDS epidemic.
Twenty years after it was first recognized, the HIV/AIDS epidemic continues to expand, but its impact varies greatly in different parts of the World. The worst of the epidemic is now centered in developing countries, especially sub-Saharan Africa, and areas such as Eastern Europe, which was only marginally involved a few years ago but has recently experienced the largest growth in the epidemic. In industrialized countries Highly Active Antiretroviral Therapy (HAART) has changed the natural history of HIV/AIDS, causing a reduction in mortality and morbidity due to HIV/AIDS and related diseases. Many interlocking factors determine the impact of HAART at the population level, including reduction of morbidity and mortality, changes in the natural history of HIV/AIDS and associated illnesses, and the effects of HAART on HIV transmission. To fully appreciate the potential benefits of HAART, the epidemic should continue to be monitored in the future, and the effects of HAART on reducing HIV transmission should also be evaluated. Interventions addressed to encourage the adoption of safer sex practices are badly needed, since a "rebound" in risky sexual behaviors was recently reported among high risk groups, which is, at least in part, attributable to the optimism about new treatments.
Acquired Immunodeficiency Syndrome↗
Sexual behaviour of heterosexual individuals with HIV infection naive for antiretroviral therapy in Italy.
BACKGROUND: Specific information about determinants of sexual behaviour of HIV infected heterosexuals, like injecting drug use (IDU), are essential to design interventions aimed at promoting safer sex practices. METHODS: We analysed data on sexual behaviour collected, between March 1997 and March 1999, through a self administered questionnaire among 1050 IDUs and 642 non-IDU heterosexuals enrolled in a prospective multicentre cohort study on the natural history of HIV infection. RESULTS: Among non-IDU heterosexuals, more women (48.5%) than men (25.1%) (p<0.001) reported that they were infected by HIV positive regular partners whose HIV status they were not aware of. Among the 1119 heterosexual males, one fifth reported having had more than 25 sexual partners during their lifetime. Condom use in the last sexual intercourse was more common among heterosexual IDUs (64.9%) than among non-IDU heterosexual males (58.3%) (p=0.05). Heterosexual IDU males were more likely (66.7%) than non-IDU heterosexuals (50.6%) to have an HIV negative partner (p<0.001). Of the 573 heterosexual females studied, 10.2% reported having had more than 25 lifetime sex partners. This proportion was higher among heterosexual IDUs (18.8%) than among non-IDU heterosexuals (4.3%) (p<0.001). Nearly 50% of the women in both groups reported having used a condom in the last intercourse. Almost 57% of heterosexual IDUs had a current HIV negative partner, compared with 34.9% non-IDU heterosexuals (p<0.001). In both sexes, the findings from univariate analysis were confirmed by multiple logistic regression analysis. CONCLUSIONS: This study identified some important differences, in both males and females, in sexual lifestyles according to injecting drug use (for example, in terms of HIV negative partners). This observation indicates the need to tailor HIV prevention messages according to history of injecting drug use.
Adult↗
Primary pulmonary hypertension in HIV patients: a systematic review.
The relationship between grade of pulmonary hypertension and factors associated with human immunodeficiency virus among patients with HIV infection is poorly documented. This report documents the most extensive attempt made thus far to determine whether a relationship exists between degree of pulmonary hypertension and the following conditions: HIV risk factor, degree of immunosuppression, presence or absence of AIDS, and presence or absence of liver cirrhosis. A retrospective study involving a search of the published literature on primary pulmonary hypertension among HIV cases from 1987 to 1998, using the Medline and Aidsline databases was conducted. Patients for whom secondary causes of pulmonary hypertension could be excluded were selected, and the following information for each was recorded: age, gender, risk factors for HIV infection, HIV disease stage according to the Centers for Disease Control, previous opportunistic and neoplastic diseases, CD4+ cell count (cells/L), presence or absence of liver cirrhosis, pulmonary systolic artery pressure level, and lung pathology specimens. Information about the patient's survival time was also recorded. Seventy-six patients were judged to have primary pulmonary hypertension and were included in the study. While no correlation was found between pulmonary systolic artery pressure level and CD4+ cell counts, a statistically significant difference was found between HIV-positive patients with and without AIDS as determined by the Centers for Disease Control criteria with regard to the degree of pulmonary hypertension, expressed as pulmonary systolic artery pressure level (85.4 +/- 17 mm Hg vs 71.8 +/- 15 mm Hg, p < 0.013). Although a higher PAPS was present in HIV cirrhotic patients, a statistically significant difference was not found between degree of pulmonary hypertension and evidence of hepatic cirrhosis (85 +/- 21 mm Hg vs 73.1 +/- 15 mm Hg, p < 0.062). Patients with AIDS and primary pulmonary hypertension present a higher degree of pulmonary hypertension than non-AIDS patients. Pulmonary hypertension associated with HIV seems to be related to a cytokine-related stimulation and proliferation of endothelium. High levels of cytokines present in AIDS patients can favor pulmonary hypertension, but the role of a host response to HIV--determined by one or more HLA subtypes--is suspected to enhance high cytokine production levels.
Adult↗
Guidelines of tuberculosis preventive therapy for HIV-infected persons: a prospective, multicentre study. GISTA (Gruppo Italiano di Studio Tubercolosi e AIDS).
The aim of this study was to assess the degree of implementation of national guidelines for isoniazid preventive therapy (IPT) among human immunodeficiency virus (HIV)-infected individuals and factors affecting the impact of the programme. Twenty-eight infectious disease hospital units in Italy participated in this observational, multicentre, prospective cohort study. A number of HIV-infected subjects, (n=1,705) seen for the first time as outpatients, were included in this analysis. Of the subjects considered, 1,215 out of the 1,705 completed purified protein derivative (PPD) screening. Variables independently associated with offering and completion of PPD screening included having acquired immune deficiency syndrome (AIDS), higher educational levels and currently receiving therapy. Overall, 103 subjects were identified as candidates for IPT. Of these subjects, five had tuberculosis and 15 had contraindications to IPT. Forty subjects agreed to start IPT, and 29 completed a full-course regimen. The incidence of tuberculosis among IPT candidates who either did not begin or discontinued IPT was 6.1 per 100 person-yrs, while no cases of tuberculosis were observed in subjects completing IPT. Several factors may limit the implementation of an isoniazid preventive therapy programme for human immunodeficiency virus-infected persons. Physicians fail to offer purified protein derivative screening to patients with high degrees of immunodeficiency, and those with a more intense workload seem to pay less attention to this test. The high number of contraindications among patients and their low level of acceptance further affects the impact of isoniazid preventive therapy.
AIDS-Related Opportunistic Infections↗
Impact of combination antiretroviral therapy on the risk of tuberculosis among persons with HIV infection.
OBJECTIVE: To assess the association between use of different antiretroviral regimens and incidence of tuberculosis among HIV-infected individuals. DESIGN: Observational, multicenter, prospective cohort study. SETTING AND PATIENTS: Twenty-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 MEASURE: Incidence of active tuberculosis according to different types of antiretroviral therapy. RESULTS: Eighteen 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. CONCLUSIONS: Combination 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.
Adolescent↗
Increasing proportion of late diagnosis of HIV infection among patients with AIDS in Italy following introduction of combination antiretroviral therapy.
We analyzed trends over time and determinants of late diagnosis of HIV infection among people diagnosed with AIDS in 1986 to 1998 in a tertiary care center in Rome, Italy. Information on the date of a first HIV test was collected prospectively, in addition to data routinely collected for AIDS reporting. Patients with AIDS were defined as "late testers" if the time interval between first positive HIV test result and AIDS diagnosis was < or = 3 months. Overall, 503 people with AIDS of 1977 included in the analysis (25.4%) were late testers. the proportion of late testers decreased from 62.5% in 1986 to 16% in 1995. Thereafter, this proportion increased to 20.5% in 1996, 33.7% in 1997, and 36.6% in 1998. In multivariate analysis, the following variables were significantly associated with late testing: AIDS diagnosis in years 1986 to 1993 or 1997 to 1998 compared with 1995, male gender, age > or = 45 years, men who have sex with men, heterosexual contacts, or having unknown transmission mode compared with intravenous drug users, and being born outside Italy. Since 1996, the overall number of AIDS cases diagnosed at our center began to decrease whereas the number of late-testing AIDS patients did not decrease, resulting in an increasing proportion of late testers during the last 3 years of the study. This findings may reflect the effect of combination antiretroviral therapy in slowing progression to AIDS of HIV-infected persons aware of their status. A relevant number of people still discover their HIV infection late and may therefore miss treatment opportunities. New testing strategies are needed to reach more people who engage in high-risk behaviors, especially those at risk for sexual transmission, and those born outside Italy.
Acquired Immunodeficiency Syndrome↗
Effects of an adenosine analogue administration on the striatal NMDA receptors in an experimental model of epilepsy.
Specific [3H]-MK801 binding to rat NMDA receptors following the administration of the convulsant drug 3-mercaptopropionic acid (MP) and the adenosine analogue cyclopentyladenosine (CPA) was studied in striatal membrane fractions. MP administration (150 mg/kg, i.p.) caused an increase of 53% and 82% in [3H]-MK801 binding during seizure and the postseizure period respectively. Administration of CPA (2 mg/kg, i.p.) raised [3H]-MK801 binding by 72%. When CPA was administered 30 min before MP and rats sacrificed at seizure (CPA + MPc), an increase of 64%, was observed. Saturation results indicate that receptor sites increased their maximal binding capacity (Bmax) in all treatments while the apparent dissociation constant (Kd) remained unchanged. MP administration brought about an increase of 52% and 42% in [3H]-MK801 binding sites during seizure and postseizure respectively. Administration of CPA raised receptor density by 75%. When CPA was administered 30 min before MP and rats sacrificed at seizure (CPA + MPc), an increase of 62%, was observed. These results show that striatal NMDA receptors have a selective role in seizure activity in the basal ganglia and that the adenosine analogue administration may modify [3H]-MK801 binding in a way similar to that of the convulsant drug.
3-Mercaptopropionic Acid↗
Decreased CD95 expression on naive T cells from HIV-infected persons undergoing highly active anti-retroviral therapy (HAART) and the influence of IL-2 low dose administration. Irhan Study Group.
The functional recovery of the immune system in HIV-infected persons receiving HAART and the role of adjuvant immune therapy are still matters of intensive investigation. We analysed the effects of HAART combined with cytokines in 22 naive asymptomatic individuals, randomized to receive HAART (n = 6), HAART plus a low dose (1000 000 U/daily) of rIL-2 (n = 8), and HAART plus rIL-2 after previous administration of granulocyte colony-stimulating factor (n = 8). After 3 months of therapy, increased CD4+ T cell counts and diminished viral loads were observed in all patients, independently of cytokine addition. A decreased expression of CD95 (Apo 1/Fas) was evident in all groups when compared with values before therapy. The percentages of peripheral blood mononuclear cells (PBMC) expressing CD95 after therapy decreased by 15%, 22% and 18% in the three treatment groups, respectively (P < 0.05). Analysis of PBMC subsets demonstrated that CD95 expression was significantly reduced on CD45RA+CD62L+ naive T cells (25.3%, 22.4%, and 18.6%, respectively; P < 0.05) in each group, after therapy. Accordingly, all patients showed a reduced rate of in vitro spontaneous apoptosis (P < 0.05). Another effect induced by HAART was a significant increase in IL-2Ralpha expression on total PBMC (P < 0.05), independently of cytokine addition. Altogether, our results suggest that very low dose administration of rIL-2 (1000 000 U/daily) may be not enough to induce a significant improvement in the immune system as regards HAART alone. The employment of higher doses of recombinant cytokines and/or different administration protocols in clinical trials might however contribute to ameliorate the immune reconstitution in patients undergoing HAART.
Adult↗
Sexual behaviour of women living with HIV/AIDS naïve for antiretroviral therapy: the ICONA-BEHEPI Study.
This study describes the sexual behaviours of women living with HIV, and assesses differences by history of drug use. Its general aim is to contribute in the design of programmes to help people with HIV/AIDS (PWH/A) adopt and maintain safe sexual behaviours. A self-administered questionnaire on sexual and drug use behaviours was distributed to study participants. Between 1997 and 1999, 573 women with HIV infection naive to antiretroviral therapies completed the questionnaire (of whom 234 reported a history of injection drug use (IDU) and were enrolled in the study. Non-IDU women reported fewer sexual partners, both in their lifetime and in the preceding month, than IDU women: 19% of IDU and 4% of non-IDU women reported more than 25 lifetime sexual partners (p < 0.001). Interestingly, 83% of non-IDU women were infected by their regular partners: these women reported the lowest number of sexual partners. No difference emerged between IDU and non-IDU women in terms of number of sexual intercourse in the two weeks preceding the interview or in terms of condom use in the last intercourse (reported, overall, by 54% of these 573 women). Among women who had sex partners at the time of interview, more non-IDU (65%) than IDU (43%) women reported HIV-positive partners (p < 0.001). Overall, these findings stress a marked heterogeneity in the levels of past and recent sexual promiscuity according to history of drug use. It suggests the need to differentiate and individualize messages about self-protection and behaviours that may prevent further spread of HIV infection.
Adult↗
Evaluation of a western blot test as a potential screening tool for occupational exposure to Mycobacterium tuberculosis in health care workers.
Health care workers (HCWs) have a higher than average risk for contracting Mycobacterium tuberculosis (MTB) infection and tuberculosis (TB). No markers of MTB-exposure are available, and TB risk assessment is performed by tuberculin screening, identifying individuals with acquired MTB infection. This study evaluated a western blot (WB) anti-M. bovis A60 complex antibody as a MTB-exposure marker. WB reactivity was evaluated on 127 exposed and 28 non-exposed HCWs from four divisions of the Policlinico Hospital of Modena, and 140 non-exposed bacille Calmette-Guérin-vaccinated controls. Excess of occupational TB risk according to the Occupational Safety and Health Administration (OSHA) was calculated in each division. WB-positivity (%) was: (1) significantly higher in exposed HCWs compared with non-exposed (72% vs 25%, P < 0.00001), (2) highly related (r = 0.99) to OSHA risk excess in all divisions, (3) higher than non-exposed in HCWs with short (< 5 years) MTB-exposure (purified protein derivative [PPD], P > 0.18; WB, P < 0.04). PPD-positivity (%) was higher than controls only in HCWs with longer (> 5 years) MTB-exposure. The study suggests that the WB antibody might represent a more sensitive biological marker of MTB contact among exposed HCWs, related to the level of TB risk and detectable earlier than the PPD skin test, thus providing new tools for TB risk assessment in health care facilities.
Adult↗
HIV infections: the global epidemiology and goals for vaccine research.
Explore the source record for details and available documents.
AIDS Vaccines↗