Background:
There is very less information on the use of antiretroviral (ARV) drugs and viro-immunological outcome over calendar years in Italy.
Patients and Methods:
We performed an analysis of a ...prospective observational cohort (MASTER) to assess antiretroviral drug use in first line HAART and explore whether initial treatment response changed over the years.
Results:
3,648 ARV-naive patients with available HIV-RNA and CD4+ T cell count at baseline who started their first HAART between 1997 and 2004 were studied. Mean age was 37.7 years; they were mostly males (72.3%) and Italians (81.4%). Prescription of non-nucleoside reverse transcriptase inhibitors and protease inhibitors boosted with ritonavir rose from 0.3% in 1997 to 58% in 2004 and from 0.3%in 1997 to 33.4% in 2004, respectively. Virological failures decreased over calendar years: from 42.9% in 1997 to 8.1%in 2004 after 6 months of HAART (p < 0.001); from 42.1%(1997) to 10.7% (2004) after 12 months (p < 0.001) and; from 39.5% (1997) to 8.2% (2004) after 18 months (p < 0.001). The same trend, but less striking, was found for immunological failure rates.
Conclusions:
In the general Italian population of HIV-positive patients, evolution of treatment prescription correlated with improved viro-immunological outcome.
To evaluate the evolution of HIV-1 coreceptor tropism in proviral DNA of patients during maraviroc-based therapy.
Fourteen heavily high active antiretroviral therapy (HAART)-treated patients with a ...CCR5 Trofile profile were monitored over a 24 month period from the start of maraviroc therapy. Whole-blood samples were obtained at different timepoints, and coreceptor tropism was determined for proviral DNA from the V3-loop region sequence using the Geno2Pheno algorithm false positive rate (FPR): 20%.
At the start of maraviroc treatment, 13/14 patients were viraemic (median: 4.33 log copies/mL). Concordance in R5 tropism (R5/R5) was observed between circulating HIV-RNA (Trofile) and HIV-DNA provirus in 10/14 patients (median FPR = 54.0%), while 4 patients showed a CXCR4-tropic R5/X4 variant in their provirus (FPR: 5.8%, 5.7%, 16.6% and 1.1%, respectively). All R5/R5 patients showed a stable HIV-1 DNA coreceptor usage. Two out of four R5/X4 patients showed a tropism shift in their archived provirus and, after 6 months a prevalence of R5-tropic virus was detected in DNA. The other two R5/X4 patients harboured the 11/25 genotype, and maintained X4 tropism in provirus during the study. Virological response did not reveal differences in RNA decay and CD4+ cell recovery in patients with discordant tropism.
A relatively good correlation between RNA and DNA tropism was observed at baseline. Proviral DNA tropism remained stable over 24 months of maraviroc-based therapy, indicating that determination of proviral DNA V3 sequence could be used in tropism prediction in clinical practice. The data also confirm the importance of the 11/25 rule in predicting viral tropism.
To evaluate the correlation between antiretroviral therapy (ART) and lesions of the carotid vessels using an ultrasound colour-Doppler technique.
A total of 293 HIV-1 infected patients underwent ...epiaortic vessel ultrasonography: 105 on treatment with protease inhibitors (PI) (group I), 125 PI-naive patients treated with a non-nucleoside reverse transcriptase inhibitor-including regimen (group II), and 63 patients treated with two nucleoside reverse transcriptase inhibitors or naive to ART (group III).
Intima characteristics, pulsation and resistance indexes, and minimal, peak and mean speed were evaluated using a colour power doppler. Atherosclerotic plaques were described. Independent risk factors and values for glycaemia, cholesterolaemia and triglyceridaemia were considered. Statistical analysis included the Wilcoxon tests, the chi test, the Cochran Armitage trend test and the Mantel-Haenszel test and, when necessary, logistic regression analysis.
Of the 150 group I patients, 55 (52.4%) presented acquired lesions of the vascular wall at ultrasonography, whereas similar lesions were found in 19 out of 125 (15.2%) patients in group II and in nine of 63 (14.3%) in group III. ART, age, smoking and CD4 T-cell count were the main predictive risk factors for vascular lesions. However, the highest significance was with the use of PI.
These data confirm the higher prevalence of premature carotid lesions in the PI-treated patients. A periodic ultrasonographic study of the vascular wall should be included in the follow-up of HIV infected patients.
Randomized trials and observational cohorts reported higher rates of virological suppression after highly active antiretroviral therapy (HAART) including efavirenz (EFV), compared with boosted ...protease inhibitors (PIs). Correlations with immunological and clinical outcomes are unclear. Patients of the Italian MASTER cohort who started HAART from 2000 to 2010 were selected. Outstanding outcome (composite outcome for success (COS)) was introduced. We evaluated predictors of COS (no AIDS plus CD4+ count >500/mm3plus HIV-RNA <500 copies/mL) and of eight single outcomes either at month 6 or at year 3. Multivariable logistic regression was conducted. There were 6259 patients selected. Patients on EFV (43%) were younger, had greater CD4+ count, presented with AIDS less frequently, and more were Italians. At year 3, 90% of patients had HIV RNA <500 copies/mL, but only 41.4% were prescribed EFV, vs. 34.1% prescribed boosted PIs achieved COS (p <0.0001). At multivariable analysis, patients on lopinavir/ritonavir had an odds ratio of 0.70 for COS at year 3 (p <0.0001). Foreign origin and positive hepatitis C virus-Ab were independently associated with worse outcome (OR 0.54, p <0.0001 and OR 0.70, p 0.01, respectively). Patients on boosted PIs developed AIDS more frequently either at month 6 (13.8% vs. 7.6%, p <0.0001) or at year 3 (17.1% vs. 13.8%, p <0.0001). At year 3, deaths of patients starting EFV were 3%, vs. 5% on boosted PIs (p 0.008). In this study, naïve patients on EFV performed better than those on boosted PIs after adjustment for imbalances at baseline. Even when virological control is achieved, COS is relatively rare. Hepatitis C virus-positive patients and those of foreign origin are at risk of not obtaining COS.
Objective: Enfuvirtide is the first of a new class of antiretroviral agents. The drug is safe and well tolerated; injection site reactions are the most common adverse events. The aim of this study ...was the clinical and histopathological evaluation of injection site reactions in patients treated for 80 weeks. Materials and methods: Six patients were evaluated. Five of them underwent cutaneous biopsies using a 4 mm punch. Sections were stained with haematoxylin–eosin, periodic acid-Schiff stain and Verhoeff’s stain. Moreover, immunohistochemical studies were carried out using CD20, CD45Ro and CD34 antibodies. Results: Four different macroscopic patterns were presented: (a) no evidence of cutaneous lesions; (b) transient infiltrative lesions which auto-resolved within 24 h; (c) transient nodular lesions which auto-resolved within 7–15 days; and (d) stable lesions after more than 30 days with a scleroderma-like aspect. Histological examination showed three patterns: (1) an acute urticaria/vasculitis-like pattern with inflammation of the fat tissue; (2) a sub-acute pattern with an initial dermal sclerosis; (3) a chronic scleroderma-like pattern with connective tissue disposed around the adnexa, whose structure was intact. The immunohistochemical study evidenced a prevalence of T lymphocytes and a moderate neoangiogenesis. Conclusions: In our experience, after a rather long period of treatment, cutaneous reactions comprised a variety of features largely independent of the virological and immunological outcome. The adnexa was unaltered in all patients, this indicating a tendency to a possible regression of the sclerotic lesions. Therefore, patients should be encouraged to rotate the sites of injection thus permitting the tissues to regenerate.
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