A novel frame-shift deletion causing analbuminaemia in an Italian paediatric patient.

BACKGROUND: Analbuminaemia (OMIM #103600) is a rare autosomal recessive disorder manifested by the absence or severe reduction of circulating serum albumin in homozygous or compound heterozygous subjects. The trait is caused by a variety of mutations within the albumin gene. DESIGN: We report here the clinical and molecular characterization of a new case of congenital analbuminaemia in a 4-year-old Italian girl diagnosed on the basis of the low level of circulating albumin (= 10.0 g L(-1)). The albumin gene was screened by single-strand conformation polymorphism and heteroduplex analysis and the mutated region submitted to DNA sequencing. RESULTS: The proband was found to be homozygous, and both parents heterozygous, for a novel deletion in exon 8 (c.920delT). The subsequent frame-shift should have given rise to a putative polypeptide chain of 304 amino acid residues, which we could not identify in the proband's serum. CONCLUSIONS: A novel analbuminaemia causing mutation was identified and characterized at the clinical level in a child. The molecular diagnosis of the trait is based on the rapid localization of the mutation within the albumin gene by single-strand conformation polymorphism and heteroduplex analysis, followed by DNA sequencing of the mutated region.

Cardiovascular risk factors and ultrasound evaluation of carotid atherosclerosis in patients with HIV-1 infection.

A cross-sectional study was performed to evaluate classical risk factors for cardiovascular diseases and subclinical atherosclerosis by carotid ultrasonography in HIV-positive subjects, naïve or treated with antiretroviral agents. A total of 66 patients were enrolled into the study: 21 subjects were naïve to all antiretroviral agents (group A) and 45 patients were treated with antiretroviral therapy for >or=36 months (group B). The prevalence of carotid plaques was significantly higher in group B than in group A (44.7% versus 0%; P = 0.014). In group B, patients with high 10-year risk of coronary heart disease showed a significantly higher intima-media thickness and prevalence of carotid lesions than those with low risk. Moreover, carotid lesions were structurally comparable to classical atherosclerotique plaques observed in the general population, with iso-hyperechonegic aspects and irregular surfaces. The prevalence of carotid atherosclerosis in experienced patients is higher than in those naïve to highly active antiretroviral therapy and seems mostly associated with a longer duration of HIV infection, more severe lipid metabolism alterations, presence of lipodystrophy syndrome and a more elevated 10-year risk of cardiovascular diseases.

Measles outbreak in the city of Bologna, December 2007 to May 2008.

Several outbreaks of measles were reported after the year 2006 in various Italian regions, including Piemonte, Lombardy, Tuscany, Veneto and Emilia Romagna. Most reported cases occurred in the Piemonte region where a major outbreak began in September 2007 among a group of unvaccinated adolescents. This report is a preliminary description of the main epidemiological, clinical and laboratory features of 26 confirmed cases of measles diagnosed at the Institute of Infectious Diseases of the S. Orsola Hospital in Bologna in the northern Italian region of Emilia Romagna between December 2007 and May 2008.

Efficacy and tolerability of a fosamprenavir-ritonavir-based versus a lopinavir-ritonavir-based antiretroviral treatment in 82 therapy-naïve patients with HIV-1 infection.

Recent data indicate that fosamprenavir/ritonavir as part of an initial antiretroviral regimen in HIV-1-infected patients is associated with favourable efficacy and tolerability and in the KLEAN study (kaletra versus lexiva with epivir and abacavir in antiretroviral-naive patients) it was found to be non-inferior to lopinavir/ritonavir in association with abacavir/lamivudine. In our open-label, observational study conducted in 82 therapy-nasmall yi, Ukrainianve HIV-1-infected patients followed-up for 18 months, virological and immunological efficacy was comparable in subjects receiving a fosamprenavir/ritonavir-based and a lopinavir/ritonavir-based treatment (proportions of patients with HIV RNA <50 copies/mL at month 18 were 76.9% and 74.4%, respectively, when discontinuations were counted as failures). At the same time, frequency of treatment discontinuations and adverse events were similar in both groups, whereas incidence of diarrhoea and hypertriglyceridaemia was significantly higher in lopinavir-treated patients than in fosamprenavir-treated ones (53.5% vs. 25.6% and 69.8% vs. 43.6%, respectively; P < 0.01). In subjects with virological failure, no viral protease resistance mutations were detected by genotype analysis.

[Hyperlactacidemia during antiretroviral therapy: frequency and clinical-therapeutic correlations]. / Iperlattacidemia in corso di terapia antiretrovirale: frequenza e correlazioni clinico-terapeutiche.

While asymptomatic hyperlactacidemia is quite a frequent phenomenon among HIV-infected patients treated with highly active antiretroviral therapy (HAART), lactic acidosis is a rare, but potentially life-threatening occurrence. Epidemiology, clinical and laboratory presentation, evolution, and outcome of this phenomenon are currently under intensive investigation, and the most likely pathogenetic pathways seem to involve mitochondrial toxicity prompted by the administration of nucleoside reverse transcriptase inhibitors. Our case-control study on an extensive, single centre population treated for HIV infection provides novel insights on these emerging issues, reported and discussed on the basis of the most recently published findings.

Bartonellosis: light and shadows in diagnostic and therapeutic issues.

Cat-scratch disease involves a prolonged and/or complicated course, and lymph node drainage is usually required. Culture and molecular techniques often yield negative results, but immunofluorescence assays may give early information, and elevated antibodies may persist for months. Cat-scratch disease should be suspected in patients with prominent swelling of lymph nodes draining from the upper limbs, limited systemic involvement, and typical epidemiological-clinical features. The temporal antibody response during the sub-acute course remains unknown. Although biomolecular assays are available, the time between onset and investigation is an obstacle to positive results. The role of surgical debridement and the unpredictable activity of antimicrobial agents warrant further investigation.

Changing epidemiology of hepatitis A in the Bologna metropolitan area, northern Italy: importance of counselling and prophylactic measures for the male homo/bisexual population.

During a 6-year observational study, 122 cases of hepatitis A virus (HAV) infection were detected in Bologna, Italy, with a c. 300% increase in cases between 1999 and 2004. There were 104 cases (85.2%) in male adults, of whom nearly 70% had unprotected sexual contact as the probable risk-factor. There were increasing numbers of cases in immigrants between 1999 and 2004 (p 0.036), and concurrent cases of infection with human immunodeficiency virus, hepatitis B and C viruses and syphilis were also noted in adult males (p 0.0032). There is a need to re-emphasise targeted educational programmes and anti-HAV vaccination for at-risk subjects.

Fluconazole as prophylaxis against fungal infection in patients with advanced HIV infection.

BACKGROUND: There is limited information regarding the usefulness of primary antifungal prophylaxis in patients with advanced human immunodeficiency virus (HIV) disease. OBJECTIVE: To evaluate the efficacy and safety of oral fluconazole treatment for the prevention of systemic fungal diseases related to the acquired immunodeficiency syndrome. METHODS: We evaluated the clinical records of more than 1300 HIV-infected patients followed up for 6 years to identify subjects with a CD4+ lymphocyte count less than 0.20 x 10(9)/L (200/microL) and no prior systemic fungal disease. We compared 128 patients who received oral fluconazole (100 mg/d every third week) with 121 subjects who received no antifungal treatment. MAIN OUTCOME MEASURES: The occurrence of visceral mycoses or death was considered an end point. The frequency of esophageal candidiasis and extrapulmonary cryptococcosis and their related clinical and laboratory features, as well as overall patient survival, were assessed and compared between the 2 study groups. RESULTS: Subjects not treated with fluconazole experienced a significantly higher incidence of systemic mycoses than patients who received fluconazole: 28.4 vs 8.8 cases per 100 patient-years (P < .001). Fluconazole treatment was more effective in preventing esophageal candidiasis than cryptococcosis and was more effective in subjects with a CD4+ cell count less than 0.10 x 10(9)/L. Moreover, fungal complications occurred later and were associated with a significantly lower CD4+ cell count among treated vs untreated patients, while the duration of antiretroviral therapy did not play a significant role. Although mortality rates were similar in the 2 study groups, the fatal outcome of disease was less frequently caused by a fungal disease in subjects who underwent fluconazole prophylaxis. Fluconazole had a favorable tolerability profile. CONCLUSIONS: In our experience, primary fluconazole prophylaxis proved safe and effective in the prevention of systemic candidiasis and cryptococcosis in patients with advanced HIV disease but it did not improve overall survival. Prospective controlled trials are advisable to confirm efficacy, to find the drug of choice and its best dosage and schedule of administration, to identify patient subgroups showing the most favorable cost-benefit ratios, and to evaluate the effects on overall life expectancy and the risk of emergence and spread of antifungal drug resistance.

Detection of circulating p24 antigen-positive CD4+ cells during HIV infection by flow cytometry.

OBJECTIVES: To determine the amount of circulating CD4+ cells positive for intracellular p24 antigen during HIV infection, and to correlate the results with clinical, virological and therapeutic parameters. METHODS: Data were obtained from 24 anti-HIV-negative subjects (controls) and 47 anti-HIV-positive patients classified according to clinical diagnosis, serum p24-antigen assay results, and antiretroviral treatment with zidovudine, using a modified flow cytometric assay for the detection of intracellular HIV p24 antigen (p24-FCA) in circulating CD4+ lymphocytes. RESULTS: The proportion of CD4+ lymphocytes positive for p24-FCA correlated well with HIV infection (1.685 +/- 1.902 versus 0.160 +/- 0.152 in controls; P < 0.001) and clinical progression [Centers for Disease Control (CDC) stage II: 1.310 +/- 1.187; CDC stage III 1.145 +/- 1.442; CDC stage IVA/C2: 2.335 +/- 2.112; CDC stage IVC1: 2.066 +/- 2.420]. The percentage of CD4+ cells positive for HIV p24-FCA was inversely correlated with an absolute peripheral blood CD4+ lymphocyte count (Spearman's rank correlation = -0.324; P < 0.05). However, there was no statistically significant difference between patients in presence (n = 27; 1.938 +/- 2.095) or absence (n = 20; 1.343 +/- 1.594) of serum p24 Ag. The variable linked most strongly to the detection of intracellular p24 in anti-HIV-positive patients was zidovudine treatment: the proportion of p24-FCA-positive CD4+ lymphocytes was significantly lower (0.825 +/- 0.910) in the treated patients (n = 25) than in the untreated patients (n = 22; 2.662 +/- 2.248; P < 0.001). CONCLUSIONS: Our results suggest that CD4+ p24 Ag-FCA is a rapid and easy test for the identification of the proportion of CD4+ lymphocytes with intracellular p24 Ag, and that it could be more appropriate than serum p24 Ag assay in evaluating disease progression and efficacy of antiretroviral treatment.

Elevated plasma levels of vasoactive intestinal peptide in AIDS patients with refractory idiopathic diarrhoea. Effects of treatment with octreotide.

OBJECTIVE: To evaluate plasma levels of vasoactive intestinal peptide (VIP) in AIDS patients with refractory idiopathic diarrhoea, and to assess the role of treatment with octreotide. PATIENTS: Three AIDS patients were evaluated for severe watery diarrhoea of 2-6 months' duration, which was complicated by weight loss, weakness, and fluid and electrolyte abnormalities. They had not shown a significant response to several regimens of empirical antimicrobial chemotherapy, or symptomatic antidiarrhoeal treatment. METHODS: A complete diagnostic examination, including repeated microbiological evaluation and radiological, ultrasonographic, endoscopic and histological examination, was performed. Plasma levels of VIP were determined by radioimmunoassay and compared with concentrations in a group of healthy subjects. RESULTS: Since no clinically significant results were obtained from standard diagnostic evaluation and empirical therapeutical attempts, idiopathic refractory diarrhoea was diagnosed. Plasma concentrations of VIP were moderately elevated in all three subjects examined, with levels of 11.5, 17.5 and 9.5 pmol/l (values < 8.8 pmol/l in the control group). One patient received 50-100 micrograms octreotide three times daily subcutaneously for 6 months, resulting in complete resolution of diarrhoea and significant improvement in body weight and quality of life, together with a reduction in VIP concentration to within normal values. CONCLUSIONS: Although the somatostatin analogue octreotide has been used successfully in the management of both infectious and non-infectious AIDS-related diarrhoea, gastrointestinal neuroendocrine function and circulating humoral mediators of diarrhoea have not hitherto been investigated extensively in HIV-infected subjects. Our data on the association of idiopathic secretory diarrhoea and elevated plasma VIP levels provide a possible pathophysiological rationale for identifying AIDS patients whose refractory diarrhoea may be more responsive to octreotide treatment.

C-reactive protein elevation and early outcome in patients with unstable angina pectoris.

C-reactive protein, a reactant of the acute phase of inflammation, has been shown to be increased in patients with unstable angina. Moreover, it has recently been found that increased C-reactive protein is associated with a poor outcome during hospitalization in selected patients with severe unstable angina. The aim of this study was to investigate the prognostic value of C-reactive protein elevation in a large population with unstable angina. We measured serum levels of this marker in 140 patients hospitalized with unstable angina (class IIIB of the Braunwald classification, mean time from last anginal episode 5 +/- 5 hours). Thirty-nine of them (28%) had increased serum levels on hospital admission and 33 (24%) experienced an adverse outcome (myocardial infarction or refractory angina) during hospitalization. Kaplan-Meier analysis showed that the probability of developing cardiac events during hospitalization was not different between patients with and without abnormal C-reactive protein levels. Furthermore, the incidence of ischemia at Holter monitoring during the first 72 hours after hospitalization was not different between patients with and without abnormal C-reactive protein. In a representative population of patients with unstable angina, a sizable proportion had increased serum C-reactive protein levels; however, abnormal concentrations of C-reactive protein do not predict an adverse outcome in the early phase after the acute episode.

Gabexate mesilate and/or octreotide in human immunodeficiency virus-associated pancreatic abnormalities.

BACKGROUND: Human immunodeficiency virus (HIV)-associated pancreatic alterations are frequent, but poorly investigated, notwithstanding their potential consequences on the course and management of HIV infection. No epidemiological or clinical data on pancreatic alterations have been published since the introduction of highly active antiretroviral therapy, and no indications of the pharmacological management of symptomatic or prolonged laboratory pancreatic abnormalities have been reported. AIM: To investigate the therapeutic role of gabexate mesilate and octreotide in HIV-infected patients with elevated, symptomatic or instrumentally confirmed pancreatic anomalies persisting for more than 3 months. METHODS AND RESULTS: An open-label, prospective, 5-year case-control study was conducted involving 185 consecutive patients with pancreatic alterations. Treatment of patients with severe laboratory and/or clinical involvement with low-dose gabexate mesilate and/or somatostatin was effective and safe and led to a lower recurrence rate and a better tolerability of concomitant drug regimens compared with supportive therapy taken by control patients. Combined gabexate-octreotide proved to be more active than single drug administration. CONCLUSIONS: Epidemiological and therapeutic data on the frequency, risk factors and clinical significance of pancreatic abnormalities during HIV infection are required, as are studies investigating the need for and choice of antisecretory and/or antiprotease compounds.

Type 1 autoimmune hepatitis: patterns of clinical presentation and differential diagnosis of the 'acute' type.

BACKGROUND: Autoimmune hepatitis (AIH) has three different presentations: chronic, acute and asymptomatic. AIM: To evaluate AIH presentation in Italian patients and investigate criteria that differentiate between acute-type AIH and acute viral hepatitis. DESIGN: Prospective observational study. METHODS: Eighty-six consecutive patients with type 1 AIH and 41 with acute viral hepatitis (controls) were studied. 'Acute' AIH was defined as recent-onset (<30 days) symptoms (jaundice and/or fatigue and/or fever) with marked alterations in serum liver tests; the 'asymptomatic' pattern as the occasional detection of liver abnormalities, and the 'chronic' pattern as the presence of signs and/or symptoms of long-lasting liver disease. RESULTS: Of 86 AIH patients, 59 (68%) presented with the chronic pattern, 22 (26%) with the acute pattern, and 5 (6%) were asymptomatic. 'Acute' patients had higher AST, ALT and bilirubin serum levels (p < 0.0001). No differences were detected with respect to age and serum levels of alkaline phosphatase, gamma-GT, albumin or gamma-globulin. All three groups had similar prevalences of moderate/severe (vs. mild) histological findings and liver cirrhosis. When compared with controls with acute viral hepatitis, 'acute' AIH patients were more often female (82% vs. 24%, p < 0.0001) and had higher serum gamma-globulin levels (26.9 vs. 13.4 g/l, p < 0.0001) and AST/ALT ratio (1.20 vs. 0.61, p < 0.0001). DISCUSSION: Although in Italy type 1 AIH patients usually present with a chronic pattern, some 25% have an acute presentation resembling that of viral hepatitis. 'Acute' AIH and viral hepatitis can be reliably differentiated by simple parameters such as gender, gamma-globulin serum levels and AST/ALT ratio.

The use of efavirenz as a part of late rescue antiretroviral treatment.

PURPOSE: Because rescue antiretroviral strategies are increasingly needed, patients' response to a late salvage treatment including efavirenz plus a novel protease inhibitor (PI), with or without at least one novel nucleoside analogue, was assessed. METHOD: 41 consecutive patients, who underwent four or more prior therapeutic failures and received nucleoside analogues alone for > or = 18 months and a PI-based HAART for > or = 15 months, had a 12- to 24-month prospective follow-up. 6 patients who interrupted treatment after 3-8 weeks because of side effects were excluded. In the remaining 35 evaluable participants, the efavirenz-containing rescue regimen included nelfinavir in 23 cases, indinavir in 7, ritonavir in 2, and ritonavir plus hard gel saquinavir in the remaining 3 cases. 17 of 35 patients concurrently introduced one or more novel nucleoside analogues. Initial mean viremia was 4.8 +/- 0.9 log(10) HIV RNA copies/mL, while mean baseline CD4+ lymphocyte count was around 100 cells/microL. Genotyping resistance testing was obtained at the time of treatment modification. RESULTS: The virologic response was both limited and transient. A significant drop of mean viremia was reached at the third month (-0.7 log(10)), but it was not maintained beyond the sixth month; only 4 patients reached viral suppression during the first 6 months. A more evident and sustained benefit on CD4+ cell count was observed throughout the study (p <.007, compared with baseline). The 31 patients who remained evaluable beyond 12 months did not show relevant modifications of laboratory parameters. The patient subgroup that received > or = 1 novel nucleoside analogue at the time of efavirenz adjunct had a significantly more favorable virologic outcome until the ninth month of follow-up and included all cases who reached viral suppression. Antiviral resistance pattern showed frequent mutations of the protease gene, and a cross-resistance with nonnucleoside reverse transcriptase inhibitors (NNRTIs; found in 19 cases of 41), although our patients were not previously exposed to these compounds. CONCLUSION: A late salvage therapy based on efavirenz plus a novel PI is not expected to achieve a complete and sustained virologic success in patients highly experienced with both nucleoside analogues and PIs and with a concurrent elevated viremia, probably due to extensive resistances acquired through time. Our rate of virologic failure proved even greater than that observed in previous studies of salvage therapy including NNRTIs. Prior long-term treatment with isolated nucleoside analogues and HAART, the use of highly sensitive techniques for monitoring of viremia, and a quite prolonged observation period may have played a role. However, the CD4+ response proved to be more evident and sustained than the virologic one, and the concurrent introduction of >/= 1 nucleoside analogue added significantly, especially during the first 9 months of salvage therapy.

Community-acquired Pseudomonas aeruginosa sacro-iliitis in a previously healthy patient.

Pyogenic sacro-iliitis is an uncommon osteo-articular infection that occurs usually in immunocompromised patients and is associated with gram-positive cocci. It is very rarely linked with a gram-negative aetiology. The first case of Pseudomonas aeruginosa sacro-iliitis is described, which occurred in a previously healthy young man, without history of prior traumatic events, hospitalisation or chronic underlying disease.

AZT plus methotrexate in HIV-related non-Hodgkin's lymphomas.

AZT is a thymidine analogue useful in the treatment of AIDS. It has been demonstrated that this compound can possess a significant antineoplastic activity when combined with de novo thymidylate synthesis inhibitors, such as 5-fluorouracil (5FU) and methotrexate (MTX). Here we report a review of our data concerning the efficacy and tolerance of the combination AZT + MTX in HIV-related non Hodgkin's lymphomas (NHL). Twenty-nine patients were treated, at weekly intervals, with three (patient 1 to 10) or six (patient 11 to 29) consecutive courses of MTX 1g/m2 and increasing doses of oral AZT (2, 4 and 6g/m2) with leucovorin rescue. Of 26 evaluable patients, a total (complete + partial) response rate of 77% was obtained. The median complete response duration was 16.8 months. There was one therapy-related death due to septic shock. Grade III-IV neutropenia was observed after 19% of the courses, but was prevented by G-CSF administration in 82/119 courses. Grade III-IV anemia was observed after 9% of the courses. In conclusion, the combination AZT + MTX was effective and well tolerated in our series of HIV-related NHL patients.

The effects of alternative treatments for HIV disease on recommended pharmacological regimens.

The use of alternative treatments for HIV disease was assessed before and after the introduction of highly active antiretroviral therapy (HAART) by the use of a standardised questionnaire. These data were related to epidemiological, clinical and laboratory parameters and compliance levels to recommended antiretroviral and anti-Pneumocystis carinii regimens. Compared with the 476 evaluable patients interviewed during the first 9 months of 1996, the 549 evaluable subjects screened in January-September 1998 showed less frequent recourse to alternative treatments (22.8 vs. 35.7% of patients; P < 0.001). A significant correlation between use of alternatives, poor compliance to antiretroviral drugs and anti-P. carinii chemoprophylaxis and clinical and immunological progression of HIV disease was shown in 1996, but was not maintained in 1998. No relevant differences were found in the selection of most non-conventional treatments and in the number of strategies followed and their duration of use. Unorthodox treatments were used by most patients concurrently rather than instead of official therapeutic regimens. No correlation was found between the use of alternative treatment and the patients' age, gender, type of risk for HIV disease and duration of HIV seropositivity. The correlations between alternative and official treatments for HIV disease before and during the HAART era shows that a considerable percentage of patients still resort to alternatives in 1998 compared with 1996 but that this does not interfere with compliance with recommended pharmacological regimens or the progression of the disease.

Limits of deep salvage antiretroviral therapy with nelfinavir plus either efavirenz or nevirapine, in highly pre-treated patients with HIV disease.

The virological and immunological response to an efavirenz-containing rescue regimen was compared with that of a nevirapine-containing one in a prospective, open-label 12-month study performed in patients previously treated with > or = 12 months of nucleoside analogue monotherapy, and > or = 15 months of indinavir- or ritonavir-containing HAART. Pooled laboratory data were assessed according to change or continuation of nucleoside analogues, at the time of start of salvage treatment. An improvement of markers of HIV disease progression occurred in all 59 evaluable patients (with a higher viral load decrease in the efavirenz over the nevirapine group at the third month), but the virological response was neither complete nor sustained at the end of study, irrespective of efavirenz or nevirapine adjunct, and complete viral suppression was attained in only 16.9% of subjects. A progressively increasing mean CD4+ lymphocyte count characterized the immunological response of all patients. The 35 patients who changed at least one nucleoside analogue when introducing salvage therapy had a better outcome, irrespective of the non-nucleoside reverse transcriptase inhibitor chosen. Rescue strategies are increasingly needed in HIV-infected patients treated for a long time with HAART. The association of nelfinavir, a non-nucleoside reverse transcriptase inhibitor, and dual nucleoside analogues, is popular among patients who fail first-line HAART. When prolonged prior treatment with nucleoside analogue monotherapy and HAART are of concern, and a quite elevated viral load is present, this salvage regimen may not allow a complete and sustained virological response in a 1-year period, while a more favourable immunological recovery can be expected. However, the concurrent change of nucleoside analogues significantly improves treatment outcome.

Conflicting interpretations of the prevalence of mutations associated with drug resistance in antiviral naïve HIV-1 patients with acute and chronic infection.

The routine determination of drug resistance in newly HIV-1 infected individuals records a potential increase in transmissions of drug-resistant variants. Plasma samples from 38 individuals classified as newly infected (seroconversion time <12 months) and twenty four individuals with an established infection (seroconversion time ranging from 3 to 10 years) were analyzed for the presence of mutations by Trugene HIV-1 genotyping assay and Virtual phenotype. Results on the newly infected and the chronically infected individuals showed a limited number of relevant mutations associated with substantial resistance to reverse transcriptase and protease inhibitors. In particular, three patients (4.8%) carried viral major mutations (T69D and M41L) associated with resistance to reverse transcriptase inhibitors, whereas only one showed the presence of M46L, which is correlated with partial resistance to some protease inhibitors. The clinical interpretation based on different approaches to monitor resistance showed that the Virconet interpretation was less grave than Trugene, suggesting that these interpretations need standardization for the currently used sequencing methods and that they may be associated with different outcomes when eventually are used.

Prevalence of multiple dideoxynucleoside analogue resistance (MddNR) in a cohort of Italian HIV-1 seropositive patients extensively treated with antiretroviral drugs.

As the emergence of highly resistant virus might compromise antiretroviral regimens in HIV-1 infected patients, a constant analysis of genotypic mutations should be performed to establish the magnitude of mutation prevalence and gauge their impact in patients treated extensively with combination therapy. The frequency of multiple dideoxynucleoside analogue resistance (MddNR) was evaluated in a group of Italian HIV-1 seropositive patients who failed to respond to therapy despite a long-lasting drug treatment. Results showed the presence of one or more mutations (A62V, V75I, F77L, F116Y and Q151M) able to confer resistance to all NRTIs in a relatively high percentage (7.9%) of patients enrolled in the study. Moreover, a significantly lower HIV-1 viral replication in patients with MddNR, suggested the importance of monitoring HIV-1 subjects not only by viral load, but also by drug resistance testing, so that a correct drug regimen may be chosen.