[Show abstract][Hide abstract] ABSTRACT: Identification of the determinants of access to investigational drugs is important to promote equity and scientific validity in clinical research. We aimed to analyze factors associated with the use of experimental antiretrovirals in Italy.
We studied participants in the Italian Cohort of Antiretroviral-Naive Patients (ICoNA). All patients 18 years or older who had started cART (≥ 3 drugs including at least two NRTI) after their enrolment and during 1997-2007 were included in this analysis. We performed a random effect logistic regression analysis to take into account clustering observations within clinical units. The outcome variable was the use of an experimental antiretroviral, defined as an antiretroviral started before commercial availability, in any episode of therapy initiation/change. Use of an experimental antiretroviral obtained through a clinical trial or an expanded access program (EAP) was also analyzed separately.
A total of 9,441 episodes of therapy initiation/change were analyzed in 3,752 patients. 392 episodes (360 patients) involved an experimental antiretroviral. In multivariable analysis, factors associated with the overall use of experimental antiretrovirals were: number of experienced drugs (≥ 8 drugs versus "naive": adjusted odds ratio [AOR] = 3.71) or failed antiretrovirals(3-4 drugs and ≥ 5 drugs versus 0-2 drugs: AOR = 1.42 and 2.38 respectively); calendar year (AOR = 0.80 per year) and plasma HIV-RNA copies/ml at therapy change (≥ 4 log versus < 2 log: AOR = 1.55). The probability of taking an experimental antiretroviral through a trial was significantly lower for patients suffering from liver co-morbidity(AOR = 0.65) and for those who experienced 3-4 drugs (vs naive) (AOR = 0.55), while it increased for multi-treated patients(AOR = 2.60). The probability to start an experimental antiretroviral trough an EAP progressively increased with the increasing number of experienced and of failed drugs and also increased for patients with liver co-morbidity (AOR = 1.44; p = 0.053). and for male homosexuals (vs heterosexuals: AOR = 1.67). Variability of the random effect associated to clinical units was statistically significant (p < 0.001) although no association was found with specific characteristics of clinical unit examined.
Among patients with HIV infection in Italy, access to experimental antiretrovirals seems to be influenced mainly by exhaustion of treatment options and not by socio-demographic factors.
BMC Health Services Research 02/2012; 12:38. · 1.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Bacterial brain abscesses remain a serious central nervous system problem despite advances in neurosurgical, neuroimaging, and microbiological techniques and the availability of new antibiotics. The successful treatment of brain abscesses requires surgery, appropriate antibiotic therapy, and eradication of the primary source; nevertheless many controversial issues on the management of this serious infection remain unresolved. CONTROVERSIAL ISSUES: The aim of this GISIG (Gruppo Italiano di Studio sulle Infezioni Gravi) working group - a panel of multidisciplinary experts - was to define recommendations for some controversial issues using an evidence-based and analytical approach. The controversial issues were: (1) Which patients with bacterial brain abscesses can be managed safely using medical treatment alone? (1a) What is the efficacy in terms of outcome, tolerability, cost/efficacy, and quality of life of the different antibiotic regimens used to treat bacterial cerebral abscesses? (1b) Which antibiotics have the best pharmacokinetics and/or tissue penetration of brain and/or brain abscess? 2) What is the best surgical approach in terms of outcome in managing bacterial brain abscesses? Results are presented and discussed in detail. METHODS: A systematic literature search using the MEDLINE database for the period 1988 to 2008 of randomized controlled trials and/or non-randomized studies was performed. A matrix was created to extract evidence from original studies using the CONSORT method to evaluate randomized clinical trials and the Newcastle-Ottawa Quality Assessment Scale for case-control studies, longitudinal cohorts, and retrospective studies. The GRADE method for grading quality of evidence and strength of recommendation was applied.
International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases 10/2010; 14 Suppl 4:S79-92. · 2.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There are few data concerning the risk of specific opportunistic diseases in patients with and without hepatitis C virus (HCV) infection. We evaluated the correlation between the occurrence of different AIDS-defining illnesses (ADIs) and chronic HCV infection or HCV-related liver cirrhosis in a large Italian cohort of human immunodeficiency virus (HIV)-infected subjects.
Subjects were stratified into 2 groups: patients without HCV coinfection and with persistently normal aminotransferase levels and patients with HCV coinfection. The patients with HCV coinfection were stratified according to the diagnosis of liver cirrhosis. The incidences of new ADIs were calculated as the number of events per 1000 person-years of follow-up. The rates in the 2 groups were compared using a Poisson regression model adjusted for potential confounders.
We observed a total of 496 ADIs among 5397 patients with 25,105 person-years of follow-up (50% tested positive for HCV). HCV coinfection was associated with increased risk of developing an ADI (adjusted relative rate [ARR], 2.61; 95% confidence interval [CI], 1.88-3.61), specifically bacterial infection (ARR, 3.15; 95% CI, 1.76-5.67), HIV-related disease (ARR, 2.68; 95% CI, 1.03-6.97), and mycotic disease (ARR, 3.87; 95% CI, 2.28-6.59) but not non-Hodgkin lymphoma (ARR, 0.88; 95% CI, 0.22-3.48). The rate of mycotic infection, bacterial infection, toxoplasmosis, and HIV-related ADI among patients with cirrhosis were significantly higher than that among HIV-monoinfected patients, and the risk was greater than that estimated for HCV antibody-positive patients without cirrhosis.
HIV-related bacterial and mycotic infections are strongly associated with positive HCV serostatus and HCV-related cirrhosis. Clinicians should take into account these data when making decisions on initiation of antiretroviral therapy for HCV-coinfected individuals.
[Show abstract][Hide abstract] ABSTRACT: Our objective was to compare the rate of viral rebound and therapy failure in patients receiving abacavir or efavirenz as the third drug (in addition to 2 non-abacavir nucleosides) in combination antiretroviral therapy (cART) and to compare the rate of metabolic alteration associated with these regimens.
We conducted a multicohort prospective observational study of human immunodeficiency virus-infected patients who had attained viral loads < or = 80 copies/mL while receiving cART, without having previously received antiretrovirals. The rates of virological rebound, therapy failure, and lipid-level alteration during follow-up were calculated as the number of events divided by person-years of follow-up (PYFU). A multivariable analysis was performed using a Poisson regression model.
We studied a total of 744 patients; the median age was 37 years, 27% of the patients were female, and 41% were heterosexual. There was a total of 854 PYFU spent receiving efavirenz and 285 spent receiving abacavir. The nucleoside reverse-transcriptase inhibitor pairs most frequently used were zidovudine/lamivudine (66% of PYFU), stavudine/lamivudine (17.6%), and stavudine/didanosine (5.4%). The adjusted relative rates of virological failure and therapy failure for abacavir, compared with those for efavirenz, were 2.17 (95% confidence interval [CI], 1.12-4.18; P = .02) and 1.41 (95% CI, 1.01-2.01; P = .05), respectively.
Patients with virological suppression while receiving regimens containing abacavir appear more likely to experience virological and therapy failure than those receiving efavirenz as their third drug. Although this is a selected group of adherent patients, bias cannot be ruled out, because this is a nonrandomized comparison.
The Journal of Infectious Diseases 07/2006; 194(1):20-8. · 5.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the risk of clinical progression (CP) according to the duration of time spent without complete viral load (VL) suppression compared with that associated with periods of stably suppressed viremia in HIV-infected people who started highly active antiretroviral therapy (HAART) when previously naïve to antiretrovirals.
A cohort study of patients having started HAART after enrollment in the Italian Cohort of Antiretroviral-Naive Patients (ICoNA) and being followed for at least 6 months.
Person-years spent in different categories according to the VL level and the change in VL from the most recent value before the initiation of HAART were calculated. A multivariable Poisson regression model, including potential confounders, was constructed.
A total of 3023 patients were studied. The overall rate of CP was 13.4 per 1000 person-years. Evidence for a higher risk of CP was observed for people with a current VL >10,000 copies/mL. For each year longer spent on HAART with a VL >100,000 copies/mL, a 5-fold increased risk was observed (relative risk [RR] = 5.34, 95% confidence interval [CI]: 2.83 to 1.08; P = 0.0001). An increased risk of CP in patients with current suppression <1.5 log10 copies/mL (RR = 2.34, 95% CI: 1.16 to 4.74; P = 0.02) and in those with no suppression or a VL higher than their set point (RR = 2.39, 95% CI: 1.17 to 4.89; P = 0.02) was observed compared with those with suppression of >3 log10 copies/mL, although it was not significant. Longer duration on HAART with a VL suppressed below set point seemed to confer protection against CP.
Virologic failure to antiretroviral drugs is common. The risk of CP may remain low despite a low but detectable level of HIV viremia.
[Show abstract][Hide abstract] ABSTRACT: Protease inhibitor treatment of human immunodeficiency virus (HIV)-infected individuals has been linked to the development of lipodystrophy. The effects of atazanavir on body fat distribution and related metabolic parameters were examined in antiretroviral-naive patients.
HIV-positive patients with CD4 cell counts > or = 100 cells/mm3 were randomized to 1 of 2 treatment arms: (1) atazanavir, 400 mg given once daily, plus efavirenz placebo; or (2) efavirenz, 600 mg given once daily, plus atazanavir placebo; each drug was administered with fixed-dose zidovudine (300 mg) and lamivudine (150 mg) given twice daily, and patients were treated for at least 48 weeks. Fat distribution measurements (visceral adipose tissue [VAT], subcutaneous adipose tissue [SAT], and total adipose tissue [TAT], as measured by computed tomography; and appendicular fat, truncal fat, and total fat levels, as measured by dual-energy x-ray absorptiometry), metabolic measurements (cholesterol and fasting triglyceride levels), and measurements of insulin resistance (fasting glucose and fasting insulin levels) were made at baseline and at week 48 of treatment for a subgroup of 111 atazanavir recipients and 100 efavirenz recipients.
Atazanavir and efavirenz treatments resulted in minimal to modest increases in fat accumulation, as measured by VAT, SAT, TAT, appendicular fat, truncal fat, and total fat levels; results were comparable in both arms. In addition, atazanavir was associated with none of the metabolic abnormalities seen with many other protease inhibitors.
Use of atazanavir for 48 weeks neither resulted in abnormal fat redistribution in antiretroviral-naive patients nor induced other metabolic disturbances commonly associated with HIV-related lipodystrophy. Longer-term assessments (e.g., at 96 weeks) will be important to confirm these findings.
[Show abstract][Hide abstract] ABSTRACT: Objectives of the study were to assess the differences between sexes in the likelihood of starting antiretroviral therapy (ART), in rates of sustained discontinuation from highly active antiretroviral therapy (HAART), and in clinical progression. In a multicenter cohort study (I.Co.N.A. Study), 2323 men and 1335 women previously naive to antiretrovirals were enrolled. As of September 2002, 807 women and 1480 men started ART. The median time to starting ART was 28 weeks for women and 17 weeks for men (P = 0.0003 by log-rank test). This difference was no longer significant after adjusting for either HIV RNA (P = 0.21) or CD4 count (P = 0.28) at enrollment. Women tend to start HAART less frequently than mono/dual ART after adjusting for potential confounders (odds ratio = 0.78, 95% confidence interval [CI]: 0.60-1.01; P = 0.06). Women who started HAART were 1.4 times more likely than men (95% CI: 1.00-1.99; P = 0.05) to interrupt at least 1 drug because of toxicity. Twenty-one percent of women and 19% of men interrupted HAART altogether for more than 3 months (P = 0.3). Clinical progression was observed in 53 women (22.6%) and 137 men (23.4%; P = 0.56). Risk of developing a clinical event was found to be no different between women and men (relative hazard = 0.84, 95% CI: 0.56-1.26; P = 0.40).
[Show abstract][Hide abstract] ABSTRACT: According to recent studies, women have lower plasma HIV RNA concentrations than men. However, these studies did not take into account the duration of HIV infection.
To analyze the relationship between viral load and gender among individuals with known date of seroconversion.
Sixty infectious disease clinics in Italy.
Cross-sectional analysis of data collected at enrollment in a cohort study.
Injecting drug users and heterosexual contacts naive to antiretroviral therapy at enrollment (245 men; 170 women).
Plasma HIV RNA concentrations, measured using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) or signal amplification b-DNA assays before antiretroviral therapy.
Plasma HIV RNA concentrations were similar by age and exposure category (p =.80 and p =.39, respectively). Median viral load among women was roughly half that of men (p =.002). The association between viral load and gender remained significant after fitting a two-way analysis of variance (p =.03) and after adjusting for CD4 count, modality of HIV transmission, and age at enrollment in a regression model. Viral load was 0.27 log10 copies/ml (95% confidence interval, 0.05-0.40; p =.01) lower in women (i.e., 50% lower in the raw scale).
Plasma HIV RNA concentrations were found to be lower among women, even when considering the duration of HIV infection. Compared with men, it is possible women should be given highly aggressive antiretroviral therapy at lower HIV-RNA concentrations.
[Show abstract][Hide abstract] ABSTRACT: Context: According to recent studies, women have lower plasma HIV RNA concentrations than men. However, these studies did not take into account the duration of HIV infection.
Objectives: To analyze the relationship between viral load and gender among individuals with known date of seroconversion.
Setting: Sixty infectious disease clinics in Italy.
Design: Cross-sectional analysis of data collected at enrollment in a cohort study.
Participants: Injecting drug users and heterosexual contacts naive to antiretroviral therapy at enrollment (245 men; 170 women).
Main Outcome Measures: Plasma HIV RNA concentrations, measured using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) or signal amplification b-DNA assays before antiretroviral therapy.
Results: Plasma HIV RNA concentrations were similar by age and exposure category (p = .80 and p = .39, respectively). Median viral load among women was roughly half that of men (p = .002). The association between viral load and gender remained significant after fitting a two-way analysis of variance (p = .03) and after adjusting for CD4 count, modality of HIV transmission, and age at enrollment in a regression model. Viral load was 0.27 log10 copies/ml (95% confidence interval, 0.05-0.40; p = .01) lower in women (i.e., 50% lower in the raw scale).
Conclusions: Plasma HIV RNA concentrations were found to be lower among women, even when considering the duration of HIV infection. Compared with men, it is possible women should be given highly aggressive antiretroviral therapy at lower HIV-RNA concentrations.
(C) 2000 Lippincott Williams & Wilkins, Inc.
[Show abstract][Hide abstract] ABSTRACT: The aim of the present study, a multicentre trial of didanosine (ddI) compassionate use, was to identify factors associated with a better outcome in patients given ddI monotherapy. Enrolled were 1047 HIV-positive patients intolerant of and/or unresponsive to zidovudine (ZDV) therapy, with CD4+ cell counts of < 200/microliter or AIDS. Didanosine was given at a dose of 250 mg b.i.d. (patients > or = 60 kg) or 167 mg b.i.d. (patients < 60 kg). Clinical examinations and laboratory tests were performed every two months. Endpoints included death, the occurrence of a new AIDS-defining disease, or permanent discontinuation of ddI for a severe adverse event. At entry, the median CD41 cell count was 47/microliter and the median duration of prior ZDV treatment 19 months; 446 patients (43%) were classified as having AIDS. Severe toxicity occurred in 143 subjects (14%); the frequency of pancreatitis was very low (0.2%). The benefit in terms of CD4+ cell counts was greater for patients whose counts exceeded 100/microliter at entry and remained at this level until month 12 in those patients still receiving treatment. Death and/or new AIDS-defining events were observed in 374 cases (36%) over a median follow-up of eight months. AIDS dementia was observed in 11 patients (1%). Multivariate analysis of survival without disease progression showed that the factors associated with a worse outcome include the severity of immunodepression, a diagnosis of AIDS at entry, and a history of both intolerance of and clinical resistance to ZDV. Surprisingly, the patients who had received previous prolonged treatment with ZDV had a better outcome. In conclusion, severely immunodepressed patients previously administered long-term monotherapy may receive a short-term benefit from being switched to another antiretroviral drug.
European Journal of Clinical Microbiology 03/1997; 16(2):135-42. · 3.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although the association among bacterial pneumonia, human immunodeficiency virus (HIV) infection, and injection-drug use seems to have been well established, accurate estimates of the risk of community-acquired pneumonia among HIV-positive and HIV-negative injection-drug users (IDUs) are still needed. To estimate the incidence of pneumonia in a community of former IDUs, we followed 4,236 persons between 1991 and 1994; 1,114 (26.3%) were HIV-positive and 3,122 (73.7%) were HIV-negative. All patients were evaluated for pneumonia by standard criteria, a serum sample was obtained from each participant at least once a year, and laboratory values were monitored. Overall, 149 episodes of pneumonia occurred among HIV-positive patients and 61 among HIV-negative patients; incidence rates were 90.5 and 14.2 (per 1,000 person-years), respectively. The most common etiologic agents were Streptococcus pneumoniae, Chlamydia pneumoniae, and Haemophilus influenzae. Among the HIV-positive former IDUs, there was a 1.37-fold increase in the relative risk of pneumonia for every decrease of 100/mm3 in the CD4 cell count (95% confidence interval, 1.16-1.61). The incidence of community-acquired pneumonia was markedly higher among HIV-positive participants than among HIV-negative ones, a finding similar to that concerning the general population.