Migrant and Italian HIV-infected patients (n = 5773) enrolled in the ICONA cohort in 2004–2014 were compared for disparities in access to an initial antiretroviral regimen and/or risk of virologic ...failure (VF), and determinants of failure were evaluated. Variables associated with initiating antiretroviral therapy (ART) were analysed. Primary endpoint was time to failure after at least 6 months of ART and was defined as: VF, first of two consecutive virus loads (VL) >200 copies/mL; treatment discontinuation (TD) for any reason; and treatment failure as confirmed VL >200 copies/mL or TD. A Poisson multivariable analysis was performed to control for confounders. Migrants presented significantly lower CD4 counts and more frequent AIDS events at baseline. When adjusting for baseline confounders, migrants presented a lower likelihood to begin ART (odds ratio 0.80, 95% confidence interval (CI) 0.67–0.95, p 0.012). After initiating ART, the incidence VF rate was 6.4 per 100 person-years (95% CI 4.8–8.5) in migrants and 2.7 in natives (95% CI 2.2–3.3). Multivariable analysis confirmed that migrants had a higher risk of VF (incidence rate ratio 1.90, 95% CI 1.25–2.91, p 0.003) and treatment failure (incidence rate ratio 1.16, 95% CI 1.01–1.33, p 0.031), with no differences for TD. Among migrants, variables associated with VF were age, unemployment and use of a boosted protease inhibitor–based regimen versus nonnucleoside reverse transcriptase inhibitors. Despite the use of more potent and safer drugs in the last 10 years, and even in a universal health care setting, migrants living with HIV still present barriers to initiating ART and an increased risk of VF compared to natives.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objectives
The aim of this study was to compare the durabilities of efavirenz (EFV) and rilpivirine (RPV) in combination with tenofovir/emtricitabine (TDF/FTC) in first‐line regimens.
Methods
A ...multicentre prospective and observational study was carried out. We included all patients participating in the Italian Cohort Naive Antiretrovirals (ICONA) Foundation Study who started first‐line combination antiretroviral therapy (cART) with TDF/FTC in combination with RPV or EFV, with a baseline viral load < 100 000 HIV‐1 RNA copies/mL. Survival analyses using Kaplan–Meier (KM) curves and Cox regression with time‐fixed covariates at baseline were employed.
Results
Overall, 1490 ART‐naïve patients were included in the study, of whom 704 were initiating their first cART with EFV and 786 with RPV. Patients treated with EFV, compared with those on RPV, were older median 36 (interquartile range (IQR) 30–43) years vs. 33 (IQR 27–39) years, respectively; P < 0.001, were more frequently at Centers for Disease Control and Prevention (CDC) stage C (3.1% vs. 1.4%, respectively; P = 0.024), and had a lower median baseline CD4 count 340 (IQR 257–421) cells/μL vs. 447 (IQR 347–580) cells/μL, respectively; P < 0.001 and a higher median viral load 4.38 (IQR 3.92–4.74) log10 copies/mL vs. 4.23 (IQR 3.81–4.59) log10 copies/mL, respectively, (P = 0.004). A total of 343 patients discontinued at least one drug of those included in the first cART regimen, more often EFV (26%) than RPV (13%), by 2 years (P < 0.0001). After adjustment, patients treated with EFV were more likely to discontinue at least one drug for any cause relative hazard (RH) 4.09; 95% confidence interval (CI) 2.89–5.80, for toxicity (RH 2.23; 95% CI 1.05–4.73) for intolerance (RH 5.17; 95% CI 2.66–10.07) and for proactive switch (RH 10.96; 95% CI 3.17–37.87) than those starting RPV.
Conclusions
In our nonrandomized comparison, RPV was better tolerated, less toxic and showed longer durability than EFV, without a significant difference in rates of discontinuation because of failures.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Acute hepatitis C virus (HCV) infection evolves to chronicity in 50–84% cases. Treatment with interferon‐α (IFN‐α) was repeatedly found to provide sustained cure rates higher than that in chronic HCV ...infection, but the optimal treatment strategy has not yet been defined. In a multicentre open‐label study, we investigated the therapeutic performance of a short course of pegylated (peg) IFN‐α in patients with acute HCV hepatitis. Peg IFN‐α2b, 1.0–1.5 μg/kg weekly, was administered for 12 weeks. Forty‐six patients were enrolled; 26 of them were intravenous drug users. Eleven patients had jaundice. Treatment was started within 1–90 days from the peak alanine aminotransferase. Treatment was well tolerated with a single dropout (2%). Thirty‐three of 46 patients (72%) had a sustained virological response (SVR) after a 6 months post‐treatment follow‐up, 8 (17%) relapsed after treatment and 4 were nonresponders (9%). A lower peak viraemia, receiving at least 1.2 μg/kg of peg IFN‐α, and a negative HCV‐RNA at week 4 and week 12 were predictors of SVR. Thus, in patients with early (week 4) viral response, a short course of peg IFN‐α at a weekly dose >1.2 μg/kg, may be a valuable option for the treatment of acute HCV hepatitis.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Anisakis pathology is due mainly to two mechanisms: allergic reactions (from isolated urticaria and angioedema to life-threatening anaphylactic shock associated with gastrointestinal symptoms or ...‘gastroallergic anisakiasis’), and direct tissue damage, due to invasion of the gut wall, development of eosinophilic granuloma, or perforation (gastric or intestinal anisakiasis). Anisakiasis is a misdiagnosed and underestimated cause of acute abdomen: most patients undergo laparotomy, and virtually no cases are diagnosed before surgery. In some cases, diagnosis is obtained accidentally during other pathologic investigations. We report a case of acute abdomen due to terminal ileum involvement. Microscopic examination of the resected segment showed the presence of helminthic sections consistent with larvae of Anisakis spp. A history of raw fish ingestion was recorded. Histopathologic features are illustrated. A short but up-to-date review of the literature on diagnostic devices (particularly imaging and serology), clinical aspects and therapy is presented.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background. Chronic cytomegalovirus (CMV) infection has been associated with immunosenescence and immunoactivation in the general population. In human immunodeficiency virus type 1 (HIV-1)-infected ...people, CMV coinfection, in addition to residual HIV replication and microbial translocation, has been proposed as a key factor in sustaining immune activation, even in individuals with a controlled HIV load. Methods. Patients from the ICONA Study with at least 1 CMV immunoglobulin G (IgG) test available without active CMV disease were included in the analysis. AIDS-defining event or AIDS-related death and severe non-AIDS-defining event or non-AIDS-related death were taken as clinical progression end points. Independent predictors of CMV were identified by multivariable logistic regression. Probabilities of reaching the end points were estimated by survival analyses. Results. A total of 6111 subjects were included, of whom 5119 (83.3%) were CMV IgG positive at baseline. Patients with CMV IgG positivity at baseline were more likely to develop a severe non-AIDS-defining event/non-AIDS-related death (adjusted hazard ratio HR, 1.53 95% confidence interval {CI}, 1.08-2.16. In particular, CMV seropositivity was an independent risk factor for cardiovascular and cerebrovascular diseases (adjusted HR, 2.27 95% CI, .97-5.32). Conclusions. In our study population, CMV/HIV coinfection was associated with the risk of severe non-AIDS-defining events/non-AIDS-related death, especially with cardiovascular and cerebrovascular events, independently of other prognostic factors. This finding supports a potential independent role of CMV coinfection in vascular/degenerative organ disorders in HIV-infected subjects.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD ...would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice.
A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with ≥3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR ≤ 60 ml/min/1.73 m2. Poisson regression was used to develop a risk score, externally validated on two independent cohorts. In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1:393 chance of developing CKD in the next 5 y in the low risk group (risk score < 0, 33 events), rising to 1:47 and 1:6 in the medium (risk score 0-4, 103 events) and high risk groups (risk score ≥ 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria.
Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In patients with HIV, immune reconstitution after antiretroviral therapy (ART) is often incomplete. We assessed the probability of patients reaching a CD4/CD8 ratio of 1 or more after the start of ...ART and its association with the onset of non-AIDS-defining events and death.
We did an analysis of the ICONA cohort, which recruited treatment-naive patients with HIV in Italy. We included participants in the cohort who started ART, reached an undetectable viral load (≤80 copies per mL), and had a CD4/CD8 ratio of less than 0·8 at the time of an undetectable viral load. We defined ratio normalisation in patients as two consecutive values of 1 or more. We used Kaplan-Meier curves to estimate the cumulative probability of ratio normalisation. We then used Poisson regression models to identify factors independently associated with normalisation and with progression to non-AIDS-defining events or death.
We included 3236 participants, enrolled between Jan 22, 1997, and Feb 25, 2013. At the start of ART, median CD4/CD8 ratio in our population was 0·39 (IQR 0·26-0·55). 458 (14%) patients reached a CD4/CD8 ratio of 1 or more; the estimated probability of normalisation was 4·4% (95% CI 3·7-5·2) by 1 year from baseline, 11·5% (10·2-13·0) by 2 years, and 29·4% (26·7-32·4) by 5 years. Factors associated with normalisation were high pre-ART CD4 cell counts, a high CD4/CD8 ratio at baseline, and negative cytomegalovirus serological findings. The incidence rate of non-AIDS-defining events for patients with a CD4/CD8 ratio of less than 0·30 (4·2 per 100 patient-years, 95% CI 3·4-5·3) was double that for those with a ratio of 0·30-0·45 (2·3, 2·1-2·5) or more than 0·45 (2·2, 1·7-2·9). A ratio of less than 0·30 was independently associated with an increased risk of non-AIDS-defining events or death compared with one of more than 0·45.
Few patients had normalised CD4/CD8 ratios, even though they had viral suppression. Low ratios were associated with increased risk of serious events and deaths. The CD4/CD8 ratio could be used by clinicians to identity patients at risk of non-AIDS-related events.
AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Merck Sharp & Dohme, ViiV Italy.
It is still debated if pre-existing minority drug-resistant HIV-1 variants (MVs) affect the virological outcomes of first-line NNRTI-containing ART.
This Europe-wide case-control study included ...ART-naive subjects infected with drug-susceptible HIV-1 as revealed by population sequencing, who achieved virological suppression on first-line ART including one NNRTI. Cases experienced virological failure and controls were subjects from the same cohort whose viraemia remained suppressed at a matched time since initiation of ART. Blinded, centralized 454 pyrosequencing with parallel bioinformatic analysis in two laboratories was used to identify MVs in the 1%-25% frequency range. ORs of virological failure according to MV detection were estimated by logistic regression.
Two hundred and sixty samples (76 cases and 184 controls), mostly subtype B (73.5%), were used for the analysis. Identical MVs were detected in the two laboratories. 31.6% of cases and 16.8% of controls harboured pre-existing MVs. Detection of at least one MV versus no MVs was associated with an increased risk of virological failure (OR = 2.75, 95% CI = 1.35-5.60, P = 0.005); similar associations were observed for at least one MV versus no NRTI MVs (OR = 2.27, 95% CI = 0.76-6.77, P = 0.140) and at least one MV versus no NNRTI MVs (OR = 2.41, 95% CI = 1.12-5.18, P = 0.024). A dose-effect relationship between virological failure and mutational load was found.
Pre-existing MVs more than double the risk of virological failure to first-line NNRTI-based ART.
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