Different impact of NNRTI and PI-including HAART on bone mineral density loss in HIV-infected patients.

OBJECTIVE: To evaluate the changes in Bone Mineral Density (BMD) and bone remodelling markers in a group of HIV patients treated with HAART and controlled in a long follow-up and to identify possible risk factors for accelerated bone mass loss. PATIENTS AND METHODS: In a series of 172 HIV patients treated with HAART a total of 67 patients (44 males and 33 females) underwent repeated bone mineral density measurement by DEXA in lumbar spine and in femur; the patients were classified according to T-score WHO criteria. Serum bone alkaline phosphatase (BAP), by IRMA, and urine pyridinoline/deoxypyridinoline (PYD&DPD), by EIA, were also assayed in all cases. RESULTS: At baseline, 62/67 patients were on HAART, while 5 were naïve; 44.8% were previous intravenous drug users (IVDU), 46.3% heterosexual and 8.9% homosexual, mean age being 40.2 ± 6.5 years, and 23.9% had previous AIDS diagnosis. Fifteen/67 (22.4%) of treated patients had osteoporosis and 25/67 (37.3%) osteopenia in spine and/or femur including 3 naïve, 27/67 (40.3%), including 2 naïve, had normal BMD in both sites. Fifty-one/67 patients were monitored during follow-up (56.8 ± 5.3 months); 27 (52.9%) of these (Group 1), received protease inhibitors (PI) and 24 (47.1%), including naïve, (Group 2) received not nucleoside reverse transcriptase inhibitors (NNRTI) for > 50% of follow-up period. In Group 1 patients, BMD reduction was observed after follow-up in respect of basal condition in both spine and femur, but significantly (p = 0.011) only for the latter. However, mean BMD values remained stable in both sites in Group 2 patients. Basal BAP and PYD&DPD levels were higher in Group 1 than Group 2, but not significantly. Moreover, only PYD&DPD levels at the follow-up evaluation were significantly (p = 0.031) higher in Group 1 than Group 2. Of the remaining 16/67 patients with osteoporosis/osteopenia, 10 received PI and 6 NNRTI and were treated with therapies that could increase bone density, in particular, 9 with Alendronate/Vitamin D/Calcium and 7 with only vitamin D/calcium; these patients were excluded from statistical analysis of 51 Group 1/Group 2 cases. In the 16 patients, after these specific treatments, mean spine and femur BMD increased over time, but significantly only in those cases including alendronate in their protocol. CONCLUSIONS: The study showed that in HIV patients on HAART BMD decrease, even osteoporosis, can be present persisting over time, particularly in PI in respect of NNRTI treated patients. The pathogenesis is probably multifactorial, the different antiviral drugs seeming to differently affect bone metabolism. Alendronate/Vitamin D/Calcium therapy can be useful to slow down bone mass loss and also improve osteoporosis/osteopenia conditions, thus, reducing fracture risk also continuing HAART.

Chronic obstructive pulmonary disease: an emerging comorbidity in HIV-infected patients in the HAART era?

PURPOSE: The objective of our study was to evaluate the presence of respiratory symptoms and chronic obstructive pulmonary disease (COPD) in a human immunodeficiency virus (HIV)-infected outpatient population and to further investigate the role of highly active antiretroviral therapy (HAART) and other possibly associated risk factors. METHODS: We consecutively enrolled in a cross-sectional study HIV-infected patients and HIV-negative age, sex and smoking status matched controls. All participants completed a questionnaire for pulmonary symptoms and underwent a complete spirometry. RESULTS: We enrolled 111 HIV-infected patients and 65 HIV-negative age- and sex-matched controls. HIV-infected patients had a significantly higher prevalence of any respiratory symptom (p = 0.002), cough (p = 0.006) and dyspnoea (p = 0.02). HIV-infected patients also had a significantly higher prevalence of COPD in respect of HIV-negative controls (p = 0.008). Furthermore, HIV-infected individuals had significantly (p = 0.002) lower forced expiratory volume at one second (FEV1) and FEV1/forced vital capacity (FVC) ratio (Tiffeneau index) (p = 0.028), whereas the total lung capacity (TLC) was significantly higher (p = 0.018). In the multivariate analysis, significant predictors of respiratory symptoms were current smoking [adjusted odds ratio (AOR) 11.18; 95 % confidence interval (CI) 3.89-32.12] and previous bacterial pneumonia (AOR 4.41; 95 % CI 1.13-17.13), whereas the only significant predictor of COPD was current smoking (AOR 5.94; 95 % CI 1.77-19.96). HAART receipt was not associated with respiratory symptoms nor with COPD. CONCLUSIONS: We evidenced a high prevalence of respiratory symptoms and COPD among HIV-infected patients. HIV infection, current cigarette smoking and previous bacterial pneumonia seem to play a significant role in the development of respiratory symptoms and COPD. Thus, our results suggest that the most at-risk HIV-infected patients should be screened for COPD to early identify those who may need specific treatment.

Serum leptin and bone metabolism in HIV patients treated with highly active antiretroviral therapy.

AIM: The role of leptin in bone metabolism has not yet been fully elucidated and results remain controversial. We investigated whether changes in serum leptin correlated to bone mineral density (BMD) occur in human immunodeficiency virus (HIV) patients on highly active antiretroviral therapy (HAART). METHODS: The study population was 117 HIV patients (67 men, 50 women) on HAART and 50 healthy controls, all with normal body mass index (BMI). Based on whole body BMD as measured by dual energy x-ray absorptiometry (DEXA), patients were classified as having a low (< -1) T-score (L) or a normal (> -1) T-score (N); DEXA scans were also used to determine total body fat (TFM) and percent fat (F%); radioimmunologic assays were used to measure leptin, osteocalcin (OC), bone alkaline phosphatase (BAP), 1,25 (OH)2 D in serum, and pyridinium cross-links (PYD & DPD) in urine. RESULTS: Of the 117 HIV patients, 54 (46.1%) were classified as L and 63 (53.9%) as N; BMD in both sexes was lower (P <0.01) among the L patients than among either the N patients or the controls; 25/32 L men and 19/22 women were osteopenic, the remaining were osteoporotic. The mean TFM, F%, OC, BAP and PYD & DPD values were higher and the mean 1,25 (OH)2 D values were lower in the L than in the N patients; leptin was higher among the L men (P <0.002) and the L women (P <0.03) than in the N patients. In both sexes. leptin positively correlated with TFM, F%, BAP and PYD & DPD; however, leptin, TFM and F% correlated negatively with BMD. A negative correlation was found between 1,25 (OH)2 D and PYD & DPD in women. At follow-up assessment of 56 HIV patients continuing HAART, leptin and BAP increased and 1,25 (OH)2 D decreased, but not significantly; BMD significantly decreased in women and PYD & DPD increased in men (P <0.02). CONCLUSIONS: An inverse relationship was found between leptin and BMD in HIV patients with osteopenia/osteoporosis treated with HAART. While the role of leptin in bone metabolism in a setting of HIV is still unclear, an inhibitory effect of leptin associated with a negative action by HAART may be hypothesized.

The changing face of the HIV epidemic in Northern Sardinia: increased diagnoses among pregnant women.

BACKGROUND: Combination antiretroviral therapy has reduced both HIV/AIDS related morbidity and mortality. However, while the number of new AIDS diagnosis progressively declined in Europe from 1997 to 2004, new HIV infection diagnoses showed an increase since 1998. Unfortunately, there is no national HIV reporting system in Italy, and no information is available from the South and the islands. METHODS: Data on new HIV infections diagnosed in northern Sardinia between 1997 and 2004 were retrospectively collected. Thus, two four years periods (1997-2000 vs 2001-2004) were compared in order to assess changes in the characteristics of newly diagnosed individuals. RESULTS: Overall, 156 new HIV infection diagnoses occurred during the study period, 87 (55.8%) in males and 69 (44.2%) in females. The incidence rate per 100,000 inhabitants showed a progressive decline from 1997 (5.9) to 2001 (3.3), followed by a rapid increase in 2002 (5.0) and a new decline in 2004 (3.5). Median age progressively increased over the study period, from 33 years in 1997 to 38 in 2004. Males (55.8%) were more frequently affected than females (44.2%), who showed a trend toward a slight but progressive proportional increase. With regard to the exposure category, 95 (60.9%) individuals were heterosexual contacts, 38 (24.4%) injection drug users (IDU), 17 (10.9%) homosexual men, and 6 (3.8%) not determined (ND). There was a proportional increase for homosexual men (+7.5%) and heterosexual contacts (-7.9%), while IDU showed a slight decrease ( 2.7%). Heterosexual intercourse was the main exposure category both for women (78%) and men (47.1%), but man-to-man sex increased in the last study period. IDU still accounted for 20.3% and 27.5% of the cases among women and men, respectively. An increase in the proportion of new diagnoses in pregnant women, from 8.6% to 20.6%, was also observed. All pregnant women diagnosed in the first four years period were Italian, whereas 4 of the 7 (57.1%) women diagnosed thereafter were foreigner. Finally, the proportion of new HIV diagnoses in foreigners showed a marked increase, from 2.4% to 17.6%; of them 71.4% originated from sub-Saharan Africa. CONCLUSIONS: Our results suggest that the HIV epidemic is far from being controlled in our Region. Prevention campaigns targeted to homosexual men, women and migrants are needed. Non-HIV specialists, such as gynaecologists and obstetricians, as well as general practitioners, should routinely offer HIV testing to pregnant women.

Bone mass loss and vitamin D metabolism impairment in HIV patients receiving highly active antiretroviral therapy.

AIM: Given the few controversial data about the effect of highly active antiretroviral therapy (HAART) on bone mass in HIV patients, we investigated whether a relationship between osteopenia/osteoporosis risk and HAART exists. METHODS: In 172 HIV patients, 152 on HAART, 92 including and 60 not including protease inhibitors (PI), 20 naïve and 64 controls, we measured spine/femur bone mineral density (BMD) by DEXA, and assayed serum osteocalcin (O), bone alkaline phosphatase (BAP), 1,25(OH)2 D, parathormone (PTH), calcium (Ca) and urinary pyridinium cross-links (PYD & DPD). RESULTS: Following WHO BMD t-score criteria, osteopenia was ascertained in >35% of all HAART groups and in 30% of naive. Only HAART patients had osteoporosis, PI patients more frequently, significantly (p<0.03) in spine (21.7% vs 8.3%). Males, intravenous drug users and B-C stage patients have a higher risk for low bone mass. Mean t-score was significantly lower in both spine and femur and O and PYD & DPD higher in PI than non PI patients and controls; 1,25(OH)2 D was significantly lower in all HIV groups than controls, PI patients having the lowest values positively correlating with BMD and negatively with OC and PYD & DPD, and it decreased further in 27 non selected monitored patients continuing on HAART. PTH was higher and Ca lower in HAART patients than controls but not significantly, PTH negatively correlating with BMD. CONCLUSION: HAART could be associated with osteopenia, even osteoporosis, and it could aggravate the loss in bone mass due to HIV infection itself. We hypothesize that HAART may directly affect bone remodelling and/or may indirectly affect vitamin D metabolism.

Cellular proviral HIV-DNA decline and viral isolation in naïve subjects with <5000 copies/ml of HIV-RNA and >500 x 10(6)/l CD4 cells treated with highly active antiretroviral therapy.

OBJECTIVE: To evaluate the decay rate of cellular proviral HIV-DNA and viral replication in patients receiving highly active antiretroviral therapy (HAART) in the very early phase of infection. METHODS: Thirty-four patients treated with HAART and retrospectively selected for progressive decline of plasma viraemia up to undetectable levels (< 20 copies/ml), were stratified according to CD4+ cell count and plasma viraemia at base line: > 500 x 10(6) cells/l with < 5000 copies/ml (group 1) or with > 5000 copies/ml (group 2), > 5000 copies/ml with 300-500 x 10(6) cells/l (group 3) or with < 300 x 10(6) cells/l (group 4). Plasma HIV-RNA and proviral HIV-DNA were analysed at baseline and after 1, 2, 3, 6, 9 and 12 months of treatment. RESULTS: After 1 year of treatment, a significant decrease of proviral DNA titre was observed in all patients and a decrease > 1 log was achieved in 24 of 29 subjects of the first three groups. The more pronounced decay of HIV-DNA (half-life 28 weeks) up to < 50 HIV-DNA copies/10(6) CD4+ cells was detected in patients of group 1. At the year's endpoint, five patients (four in group 1 and one in group 2) had < 20 HIV-DNA copies. However, HIV strains sensitive to antiretroviral drugs were isolated from peripheral lymphocytes of 16 out of 34 patients. CONCLUSION: In patients with undetectable plasma viraemia after 1 year of HAART, the highest reduction of proviral DNA up to < 50 copies/10(6) CD4+ cells was obtained only in subjects in the early asymptomatic phase of infection. Nevertheless, a replication-competent virus can be detected in all phases of antiretroviral therapy.

Lactose absorption in patients with ovarian cancer.

To determine whether lactase persistence might be related to ovarian cancer risk, in 1994-1995 the authors assessed the capacity to digest lactose by measuring breath hydrogen production after oral administration of lactose in 50 women with ovarian cancer and 100 healthy controls. All of the women came from Sassari (Sardinia), Italy, an area where the population has a high frequency of lactose malabsorption. Thirty percent of cases were lactose absorbers, as compared with 15% of controls. The odds ratio for ovarian cancer among lactose absorbers was 2.51 (95% confidence interval 1.10-5.68). These results provide some support for a role of lactose ingestion and galactose cytotoxicity in the pathogenesis of ovarian cancer.

IDDM and early infant feeding. Sardinian case-control study.

OBJECTIVE: To further investigate the association between the type of feeding in infancy and the development of IDDM. RESEARCH DESIGN AND METHODS: We have carried out a case-control study in the area of Sassari (northern Sardinia, Italy), which is characterized by an ethnically homogenous population at high risk of IDDM. The study subjects comprised 100 IDDM patients and 100 control subjects, matched for sex and age and selected from children admitted at the Department of Pediatrics of the University of Sassari. Diabetic children (53 boys, 47 girls) had been diagnosed between 1983 and 1994, and their age at diagnosis ranged between 1 and 15 years. Information on feeding patterns during the 1st year of life was collected through questionnaires administered to the mothers. The questionnaire was designed to evaluate the duration of complete or partial breast-feeding and the age at which dietary products containing cow's milk were introduced into the diet. RESULTS: A larger proportion of the diabetic children rather than the control children had been breast-fed, and the risk of IDDM among children who had not been breast-fed was below unity (odds ratio [OR] 0.41; 95% CI 0.19-0.91). No clear difference was observed between diabetic and control subjects in the duration of breast-feeding (medians: 3 and 2 months, respectively), even if, overall, the data suggested a slight increase in the risk of IDDM with longer duration of breast-feeding (OR 1.10; 95% CI 0.99-1.22 per month). Although a larger proportion of control children rather than diabetic children had been given cow's milk-derived formula and solid food before the age of 3 months, there was no time-risk relationship. CONCLUSIONS: Our data do not support the existence of a protective effect of breast-feeding on the risk of IDDM, nor do the data indicate that early exposure to cow's milk and dairy products has any influence on the development of IDDM in a high-risk population.

Lactose absorption in patients with glucose 6-phosphate dehydrogenase deficiency with and without favism.

BACKGROUND: It has recently been suggested that primary lactase deficiency might have been selected for by malaria, as has been previously shown to occur for thalasaemia and glucose 6-phosphate dehydrogenase (G6PD) deficiency. AIMS: To test this hypothesis, the prevalence of primary lactase deficiency in G6PD deficient subjects and in controls from the area of Sassari (Northern Sardinia) was determined, which in the past was characterised by an intermediate malarial endemicity. SUBJECTS: 70 adult subjects with G6PD deficiency, 34 of whom had a past history of favism, and 50 age matched control subjects. METHODS: The capacity to absorb lactose was assessed by measuring breath hydrogen production after oral administration of lactose (50 g) by a gas chromatographic method. RESULTS: Twenty per cent of G6PD deficient subjects with a positive history of favism and 22% of G6PD deficient subjects without a positive history of favism were lactose absorbers compared with 14% lactose absorbers in the control group. The differences were not statistically significant. CONCLUSIONS: These data show that the prevalence of primary lactase deficiency in the area of Sassari is relatively high, but comparable to that seen in the adult population from another area of southern Italy (Naples) where malaria was less endemic.