[Show abstract][Hide abstract] ABSTRACT: Non-invasive markers of liver fibrosis have been recently developed as a possible alternative to liver biopsy. The clinical management of hepatic diseases is dependent on the extent of liver fibrosis. Liver biopsy remains the gold standard but severe complications are found in about 0.5% of cases. Studies involving sequential liver biopsies are impractical, costly, and risky. Therefore non-invasive markers of liver fibrosis could be useful. These drawbacks justify an intensive research on non-invasive alternatives. Several serum markers are either directly involved in fibrosis remodelling or are indirectly associated with the presence of significant liver fibrosis. More recently, fibrosis scores calculated from statistical models have been described. This review describes the role of non-invasive markers in assessing hepatic fibrosis in both HCV mono-infected and HIV/HCV co-infected subjects.
[Show abstract][Hide abstract] ABSTRACT: Subjects at risk of infection with human immunodeficiency virus (HIV) are also at high risk of acute and chronic hepatitis B virus (HBV) infection. HIV is associated with higher HBV viraemia and with the risk of HBV reactivation, chronic active HBV infection, cirrhosis and death. Therefore, hepatitis B vaccination is recommended for all HIV-infected subjects lacking prior immunity. However, the immune response to hepatitis B vaccine is frequently suboptimal in this population. High CD4+ cell counts and low HIV viraemia are well known factors associated with a better rate of response. Moreover, higher hepatitis B vaccine doses and/or prolongation of the vaccination schedule, as implemented for patients with immune deficiencies other than HIV, may be considered. New vaccination cycles should be considered if post-vaccination titers of antibodies to hepatitis B surface antigen are < 10 mIU/mL (< 10 UI/L). The immunization of all young and middle-aged adults appears to be the most useful strategy to protect all patient-populations at high risk of sexually transmitted diseases.
Current Molecular Pharmacology 11/2008; 1(3):191-4.
[Show abstract][Hide abstract] ABSTRACT: The predictive factors of intima media thickness (IMT) in the HIV-infected population are still poorly understood.
We studied three groups of subjects, aged 30-50 years, to find potential predictive factors of carotid and/or femoral thickening (IMT > 1 mm in at least one area): healthy controls (G1, n = 54), HIV-infected naive (G2, n = 53) and highly active antiretroviral treatment (HAART)-treated subjects (G3, n = 133). All the subjects underwent ultrasonography of the carotid and femoral vessels to evaluate IMT.
Demographic characteristics of the three groups were comparable, except for gender (G1 had a higher percentage of females) and lipid levels (higher in G3). A total of 115 subjects (47.9%) had carotid and/or femoral IMT: 26 in G1 (48.1%), 21 in G2 (39.6%) and 68 in G3 (51.1%). Independent predictive factors of carotid and/or femoral IMT were older age (OR: 2.81, 95% CI: 1.95-4.04, P < 0.01, for each additional 5 years), triglycerides >or=150 mg/dL (OR: 2.66, 95% CI: 1.27-5.57, P < 0.001), serum glucose >or=110 mg/dL (OR: 5.24, 95% CI: 1.02-27.05, P = 0.04), high homocysteinaemia (OR: 2.75, 95% CI: 1.17-6.46, P = 0.02) and high body mass index (OR: 1.10, 95% CI: 1-1.22, P = 0.05 for each additional unit); females had a lower risk (OR: 0.38, 95% CI: 0.18-0.79, P < 0.01 versus males). HAART use was not associated with IMT (OR: 0.64, 95% CI: 0.27-1.53, P = 0.32 and OR: 0.80, 95% CI: 0.30-2.13, P = 0.20 for G3 and G2 versus G1, respectively).
This study demonstrates that traditional risk factors for cardiovascular diseases overshadow the role of HAART in determining premature vascular lesions.
Journal of Antimicrobial Chemotherapy 01/2008; 61(1):195-9. · 5.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We evaluated the efficacy of tenofovir (TDF) - and didanosine (ddI)-containing backbones in HIV-infected experienced subjects. We included in the study 245 subjects who started a TDF/ddI-containing HAART with HIV-RNA > 3 log(10) cp/ml and an available genotypic resistance test at baseline. At baseline, median CD4 counts and HIV-RNA were 278 cell/mmc and 4.32 log(10) cp/ml, respectively. Seventy-four subjects (30.2%) discontinued TDF and/or ddI, 23 of them for drug-related toxicities or intolerance. One-hundred and twenty-six (51.4%) subjects achieved virologic success (HIV-RNA < 50 copies/ml in two consecutive determinations) in a median time of 6.1 months; higher HIV-RNA levels (HR: 0.66, 95% CI: 0.54- 0.79, p < 0.001 for each additional log(10) copies/ml), and the total number of mutations either for PI and NNRTI at baseline (HR: 0.87, 95% CI: 0.81-0.92, p < 0.001 for each additional mutation) were both predictors of virologic success. M184V was marginally associated with virologic success (HR: 1.34, 95% CI: 0.94-1.90, p = 0.10 vs no M184V), whilst the number of TAMs was not associated. One-hundred-thirty-three (54.3%) subjects achieved immunologic success (increase of > or = 100 cells/mm(3) from baseline) in a median time of 7.5 months; immunologic success was associated with HIV-RNA levels at baseline (HR: 0.91, 95% CI: 0.79-0.98, p = 0.04 for each additional log(10) copies/ml), the total number of mutations either for PI or NNRTI (HR: 0.91, 95% CI: 0.85-0.98, p = 0.01 for each additional mutation) and CD4 count at baseline (HR: 1.11, 95% CI: 1.00-1.23, p = 0.05 for each additional 100 cells/mm(3)). Results obtained by the on-treatment analyses were comparable. In our study, HAART containing TDF/ddI seem associated with a virologic and immunologic response, when such regimens are chosen according to a genotypic resistance test.
[Show abstract][Hide abstract] ABSTRACT: Antiretroviral medications have significantly improved the prognosis of subjects infected by human immunodeficiency virus (HIV). However, long-term complications of these drugs are increasingly recognized as significant causes of morbidity and mortality. Non-alcoholic fatty liver disease (NAFLD), which can evolve into non-alcoholic steato-hepatitis (NASH), cirrhosis and ultimately hepatic failure is one of the more often observed complications in the current clinical practice and the correlation with liver enzyme elevations is controversial. Multiple factors have been considered as possibly correlated to this event in the HIV-infected population, including metabolic abnormalities (such as hyperlipidaemia, hyperglycaemia and being overweight), chronic inflammation, concurrent infection with hepatitis C and B viruses, and treatment with certain nucleoside reverse transcriptase inhibitors (NRTI). HIV-associated syndromes such as lactic acidosis and lypodystrophy are frequently associated with fatty liver disease and a mitochondrial injury has been considered as its possible pathogenetic factor. In particular, treatment containing stavudine and didanosine have proven to be the most commonly implicated in the occurrence of mitochondrial abnormalities. Epidemiologic data to better define the role of predictive factors and drugs associated with the development of NAFLD are still lacking. Furthermore, it remains unclear the better therapeutic management for this condition, even if the current best therapeutic option for NAFLD is the treatment of the underlying disease. Other studies are mandatory to better elucidate the pathogenesis of NAFLD and the optimal therapeutic strategy for the underlying conditions.
Current HIV research 10/2007; 5(5):490-8. · 1.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recently, it was shown that cirrhotic patients without human immunodeficiency virus (HIV) infection had low CD4 cell counts and normal CD4 cell percentages, suggesting that, for HIV-infected persons, the CD4 cell percentage might be a more accurate marker of disease progression than the absolute CD4 cell count. In cirrhotic HIV-infected persons in the Italian Cohort of Antiretroviral-Naive Patients, the absolute CD4 cell count seemed to be better predictor of the risk of developing an acquired immunodeficiency syndrome-defining illness than the CD4 cell percentage.
[Show abstract][Hide abstract] ABSTRACT: The long-term immunological efficacy of regimens including lopinavir/ritonavir (LPV/r) has not been assessed in HIV-infected HAART-experienced subjects. The present study included 452 consecutive HIV-infected outpatients starting LPV/r before May 2003 after failing (HIV-RNA > 1000 copies/ml) HAART. Four groups were considered according to CD4 cell counts at LPV/r initiation: group 1 (G1, n = 115) < 100 cells/mm(3); group 2 (G2, n = 113) 100-199 cells/mm(3); group 3 (G3, n = 115) 200-349 cells/mm(3); group 4 (G4, n = 109) >/= 350 cells/mm(3). The majority of patients were males (n = 320, 70.8%), the median age was 38 years, and 180 (39.6%) were on CDC stage C. The median time of previous HAART was 51.1 months (12-81.7) and a median of 7 antiretroviral regimens and of 3 protease inhibitors was changed before LPV/r. The mean CD4 cell count increase was 105, 113, 128, and 144 cells/mm(3) after 12 months (p < 0.01 for each group) and 128, 106, 90, and 100 cells/mm(3) at month 48 (p < 0.01 for each group) in G1, G2, G3, and G4, respectively. The mean increase was comparable among the four groups. The on treatment analysis showed a better immunologic response among G1 and G2 patients from month 36. Forty-seven patients (10.4%), mainly in G1 and G2, maintained LPV/r despite persistent HIV-RNA > 1000 copies/ml. A mean increase of 64 and 65 cells/mm(3) and of 88 and 56 cells/mm(3) at month 12 and 48 was observed in G1 and G2, respectively. The use of LPV/r-based regimens also provided a durable immunologic recovery in highly pretreated HIV-infected subjects.
AIDS Research and Human Retroviruses 12/2006; 22(11):1096-105. · 2.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The correlation between subclinical hypothyroidism [thyroid stimulating hormone (TSH)>4 mIU/L with normal free triiodothyroxine and free thyroxine levels], HIV infection and HAART is still unclear.
To evaluate the predictive factors of subclinical hypothyroidism in an HIV-infected population, we identified three groups of subjects: G1, subjects on stable highly active antiretroviral therapy (HAART) (for at least 1 year) at baseline and at month 24 (n=97); G2, subjects naive at both baseline and month 24 (n=47); G3, subjects starting HAART at baseline (n=46).
The three groups were comparable with respect to age, gender, body weight and prevalence of HCV infection. At baseline, subclinical hypothyroidism was detected in 14 subjects in G1 (14.4%), 5 in G2 (10.6%) and 4 in G3 (8.7%) (P=0.18) and these were excluded from the analysis. At month 24, 15 subjects had developed subclinical hypothyroidism: 4 in G1 (4.8%), 3 in G2 (7.1%) and 8 in G3 (19.0%). In the multivariable analysis, the higher increase in total cholesterol was predictive of subclinical hypothyroidism (RR: 1.53 for each additional 10 mg/dL, 95% CI 1.23-1.90; P<0.01); other variables, which were statistically significant in the univariate analysis, such as G3 group, body weight and higher increase in CD4+ cell count and in triglyceride serum levels were not confirmed to be associated with TSH alterations.
The occurrence of subclinical hypothyroidism in HIV-positive patients seems to be related to the increase in total cholesterol serum levels occurring after HAART initiation. Thyroid function should be monitored in all HIV-infected subjects, especially in those starting HAART.
Journal of Antimicrobial Chemotherapy 11/2006; 58(5):1086-9. · 5.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Despite a high antiviral efficacy, the use of highly active antiretroviral therapy (HAART) in clinical practice is often impaired by the long-term toxicity of antiretroviral treatment, the increased rate of human immunodeficiency virus-1 (HIV-1) drug resistance in treated patients and the cost of therapies, so that possible interruption of HAART has to be considered as part of the current clinical practice. However, this strategy is usually followed by a rapid viral rebound with a substantial loss of CD4 T lymphocytes because the HIV suppression with HAART does not result in reconstitution of the HIV-specific immune response. Structured treatment interruption (STI) has already been investigated in HIV-infected subjects with well-controlled viral replication (initiating treatment during primary or chronic HIV infection) and in those with multiple treatment failures. A clear benefit of STI in patients with chronic infection remains controversial and these benefits are more often observed in patients starting treatment during primary HIV infection.
Journal of Antimicrobial Chemotherapy 10/2006; 58(3):502-5. · 5.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Bone disorders such as osteopenia and osteoporosis have been recently reported in patients infected with the human immunodeficiency virus (HIV), but their etiology remains still unknown. The prevalence estimates vary widely among the different studies and can be affected by concomitant factors such as the overlapping of other possible conditions inducing bone loss as lypodystrophy, advanced HIV-disease, advanced age, low body weight or concomitant use of other drugs. All the reports at the moment available in the literature showed a higher than expected prevalence of reduced bone mineral density (BMD) in HIV-infected subjects both naïve and receiving potent antiretroviral therapy compared to healthy controls. This controversial can suggest a double role played by both antiretroviral drugs and HIV itself due to immune activation and/or cytokines disregulation. An improved understanding of the pathogenesis of bone disorders can result in better preventative and therapeutic measures. However, the clinical relevance and the risk of fractures remains undefined in HIV-population. The clinical management of osteopenia and osteoporosis in HIV-infected subjects is still being evaluated. Addressing potential underlying bone disease risk factors (e.g., smoking and alcohol intake, use of corticosteroids, advanced age, low body weight), evaluating calcium and vitamin D intake, and performing dual x-ray absorptiometry in HIV-infected individuals who have risk factors for bone disease can be important strategies to prevent osteopenia and osteoporosis in this population. The administration of bisphosphonates (e.g., alendronate), with calcium and vitamin D supplementation, may be a reasonable and effective option to treat osteoporosis in these subjects.
Current Molecular Medicine 07/2006; 6(4):395-400. · 3.61 Impact Factor
[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. · 5.78 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recent reports showed a high frequency of osteopenia/osteoporosis in HIV-infected subjects. Mechanism on the basis of this alteration is still unclear, as the direct effect of virus or of antiretroviral drugs. One hundred sixty-one consecutive HIV-infected outpatients aged 30-50 years, both naive and HAART-treated for >1 year, were included. An interview questionnaire was performed to establish prior pathological, toxic, epidemiological histories, medications intake, physical activity and eating habits. Blood and urinary tests were checked to exclude concomitant diseases, as were markers of bone metabolism and vitamin D3-metabolites. Each subject underwent to a lumbar spine and left hipbone mineral density by DEXA, using WHO criteria for diagnosis of osteopenia/osteoporosis. Radiologist was unaware if the subject was receiving HAART or not. For groups' homogeneity Chi-square, Fisher's exact and Student's t tests were used. Logistic regression analysis was used to find predictors of osteopenia/osteoporosis and linear regression model to find differences in bone mass density. The demographic characteristics of the 48 naive subjects and the 113 on HAART were comparable. Eighty subjects (49.7%) showed osteopenia/osteoporosis: 22 (45.8%) naive and 58 (51.3%) on HAART (P = 0.46). Independent predictors of osteopenia/osteoporosis were female gender (OR: 3.02, 95% CI: 1.26-7.25, P = 0.01 vs. male), older age (OR: 1.10, 95% CI: 1.01-1.20, P = 0.03, for each additional year), low body mass index (OR: 0.78, 95% CI: 0.68-0.91, P = 0.001 for each additional unit) and higher HIV-RNA levels at DEXA (OR: 1.97, 95% CI: 1.16-3.34, P = 0.01 for each additional Log(10)), whereas the use of HAART (OR: 2.61, 95% CI: 0.66-10.27, P = 0.17 vs. naive) and the alterations of markers of bone metabolism were not significantly related to osteopenia/osteoporosis. Similar findings were obtained using linear regression model analysis. HIV-infected subjects have a high frequency of osteopenia/osteoporosis. Traditional risk factors are predictive of osteopenia/osteoporosis also in HIV-subjects; the association with higher HIV-RNA levels can suggest a direct role of HIV itself in the occurrence of bone disease.
[Show abstract][Hide abstract] ABSTRACT: Historically, older patients have shown a higher risk of HIV-1-associated dementia (HIVD). The objective of this study was to evaluate the association of aging with HIVD and minor cognitive motor disorders (MCMDs) during the late-highly active antiretroviral therapy (HAART) era and to analyze characteristics, predictive factors, and survival of older HIV-1-infected individuals affected by these disorders. A nested longitudinal study was designed for a cohort of HIV-1-infected individuals with neurological diseases. Multiple logistic regression and Cox regression for survival were employed. From 2000 to 2003, 195 patients with HIVD (53%) or MCMD (47%) were enrolled. The cumulative prevalence of these two disorders was 21%, with an increasing rate for calendar year (p < 0.001). Previous antiretroviral exposure occurred in 46% of patients. Mean CD4(+) cell count and plasma HIV-1 RNA were 144 cells/microl and 4.5 log10 copies/ml, respectively. The mean age was 44 years (SD, 9.9), with 35% of patients aged 20-39 years (I), 45% aged 40-49 years (II), and 20% aged >/=50 years (III). Among drug-naive patients, the prevalence of HIVD progressively increased in older subjects: 7.2% (I), 15.3% (II), and 27.3% (III) (p < 0.001), whereas no significant increase in HIVD with older age was observed in drug-treated subjects. Older age was independently associated with an increased risk of HIVD (odds ratio, 6.44; 95% confidence interval, 2.82-14.69) in naive but not in experienced individuals, but had no significant effect on survival. No significant effect of age was observed for MCMD. We conclude that in our cohort, HAART seems to alter the relationship between aging and HIVD, conferring a neuroprotective effect to older patients. These results may have significant implications for the clinical management of the older HIV population.
AIDS Research and Human Retroviruses 06/2006; 22(5):386-92. · 2.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Nucleoside reverse transcriptase inhibitors (NRTI) are essential components of highly active antiretroviral treatment (HAART). Although several combinations can be used as NRTI backbones, not all are associated with good virological and/or immunological results. In particular, some NRTI combinations should be avoided due to antagonism (zidovudine plus stavudine) or to high rate of toxicity (didanosine plus stavudine). Tenofovir (TDF) and didanosine (ddI) are among the more often prescribed NRTI for their convenient posology (one pill each per day), relatively high genetic barrier for resistance, quite acceptable safety profile and remarkable antiviral potency when such drugs have been used as single drug or in combinations with other NRTIs. However, antiretroviral regimens containing TDF and ddI have been associated with a high rate of virological failure in HIV-infected naïve patients due to possible drug-interactions. The virological efficacy of this backbone in HIV-infected, HAART pre-treated subjects, is still controversial. Aim of this review is to assess the possible role that antiretroviral regimens containing TDF and ddI can have in the treatment of HIV-positive subjects, focusing on their plasmatic and/or intracellular interactions to optimize the antiretroviral efficacy and minimize the toxicities of this combination.
Current Medicinal Chemistry 02/2006; 13(23):2789-93. · 3.72 Impact Factor