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Background: The advent of combined antiretroviral therapy effectively undermined the evolution of HIV disease. Nevertheless, clinical observations indicated a clear association between therapy and the impairment of bone mineral density. Objective: We selected some antiretroviral compounds used in clinical practice, to study their impact on bone health and their possible implication in the onset of bone disease. Method: Scalar concentrations of several antiretroviral drugs (used in single and in combination) were tested on an osteoblast-like cell line, HOBIT cells, to analyse cell survival and gene expression of selected bone markers. Results: None of the tested concentrations of Tenofovir, Emtricitabine, Nevirapine, Maraviroc or Raltegravir induced any significant apoptosis activation at our experimental conditions. Only some protease inhibitors and Efavirenz, at high concentration, determined a significant activation of programmed cell death. In parallel experiments, protease inhibitors used in combination with Tenofovir and Emtricitabine, increased apoptosis. Furthermore, we performed a study of mRNA expression of specific genes involved in osteoblast biology and in bone synthesis and observed that some protease inhibitors induced a selective decrease of some osteogenic markers. Conclusion: All the protease inhibitors included in this study trigger apoptosis at the highest concentration analysed, suggesting great caution in HIV-patients co-infected with HBV or HCV, where elevated plasma concentrations of drugs could be reached as a consequence of liver failure. Lastly, an increased apoptosis rate and an impairment of osteogenic markers were recorded only in the presence of Nelfinavir, suggesting a role of protease inhibitors in the alteration of osteoblast biology.

Background The antiretroviral regimens including tenofovir and a ritonavir-boosted protease inhibitor (r/PI) have been associated with a reduced bone mineral density (BMD), increased bone turnover markers and renal tubular dysfunction.Methods An observational, prospective study was performed including HIV-1-infected, virologically suppressed patients treated with tenofovir/emtricitabine plus an r/PI for at least 12 months who switched to raltegravir plus nevirapine. The primary end point was changes after 48 weeks in estimated glomerular filtration rate (eGFR), prevalence of tubular dysfunction, BMD and concentration of two serum markers of bone turnover: collagen type-1 cross-linked C-telopeptide (CTX) and bone-specific alkaline phosphatase (BAP).Results A total of 46 patients were enrolled: 78% were male, 96% were Caucasian, the mean age was 45 years and the mean CD4+T-lymphocyte count was 681 cells/mm3. A renal impairment was present in 72% of patients and was the main reason for the switch. After 48 weeks, prevalence of proximal tubular dysfunction decreased significantly (-72%; P<0.001), whereas the mean value of eGFR did not change significantly. At the same time, after 48 weeks a significant increase in both lumbar spine and total hip BMD, T-score and Z-score was reported (+11.5% in lumbar spine T-score; P<0.001), and there was a significant reduction in both CTX and BAP mean serum concentrations (-15% and -13%, respectively; P<0.001). Two (4.3%) patients had virological failure due to suboptimal adherence and one (2.2%) subject discontinued treatment due to a skin rash.Conclusions Switching virologically suppressed patients from tenofovir/emtricitabine plus one r/PI to raltegravir plus nevirapine after 48 weeks significantly improved proximal tubular function, increased BMD and reduced serum markers of bone turnover.

Background: The association between abacavir use and increased risk of myocardial infarction has been heavily debated, but cohort studies and randomized trials have provided conflicting results. Aim of our study is to compare the effect of abacavir and tenofovir on the inflammation and endothelial activation markers. Methods: We performed an observational study of HIV-infected naïve patients starting tenofovir/emtricitabine (group A) or abacavir/lamivudine (group B) plus efavirenz. In the present analysis, we measured serum levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), tumor necrosis factor- (TNF-), soluble vascular adhesion molecule-1 (VCAM-1), soluble intercellular adhesion molecule-1 (ICAM-1), E-selectin and P-selectin at baseline and during a 48-week follow-up. Results: As a whole, 118 patients (93 males; mean age ± SD of 42.8 ± 10.1 years) were enrolled: 61 in group A and 57 in group B. In group A at weeks 24 and 48 the mean concentrations of IL-6, TNF-, ICAM-1, VCAM-1, E-selectin and Pselectin decreased significantly in comparison with respective baseline values. In group B at week 24 a significant increase in mean values of these markers was reported in comparison with group A, but after 48 weeks they significantly decreased in group B too and no significant differences between groups A and B were found. Conclusion: In our study, naïve patients starting tenofovir/emtricitabine or abacavir/lamivudine plus efavirenz showed after 48 weeks a significant and comparable decrease in serum concentrations of IL-6, TNF-, ICAM-1, VCAM-1, Eselectin and P-selectin, while the mean level of hs-CRP did not change significantly in any group.

The aim of our study was to evaluate the prevalence of osteopenia/osteoporosis in patients with human immunodeficiency virus (HIV) type 1 infection and to assess their possible correlation with antiretroviral therapy. Patients were enrolled among adult subjects with HIV type 1 infection referring to our tertiary care outpatient center. Bone mineral density was measured in the lumbar spine and femoral proximal head by dual-energy x-ray absorptiometry. A total of 95 HIV-infected patients (45 men) were enrolled 12 subjects were naive to antiretroviral therapy, 18 received 3 nucleoside reverse-transcriptase inhibitors (NRTIs), 28 were treated with 2 NRTIs plus 1 non-NRTI, and 37 received 2 NRTIs plus 1 protease inhibitor (PI). Prevalence of osteopenia and osteoporosis according to lumbar T score was 37.9% and 9.5%, respectively, and osteoporosis was significantly more frequent in men than in women (20% vs. 0%; P< 0.001). The mean value of lumbar T score was significantly lower in PI-treated patients (−1.32 ± 0.48) than in naive subjects (−0.62 ± 0.24) or in those receiving 3 NRTIs (−0.68 ± 0.34) or 1 non-NRTI (−0.86 ± 0.44) (P< 0.05). Bone metabolism alterations associated with HIV infection probably have a multifactorial pathogenesis, but in our study, bone mass loss seems prompted by the male sex and a PI-based therapy.

Objective: To gain more understanding about the relationship between human immunodeficiency virus type 1 (HIV-1) infection and new-onset psychosis, we compared clinical and immunological findings, psychiatric symptoms, global cognitive performance and, when available, computerized tomography (CT) findings between HIV-1-seropositive patients with new-onset psychosis and well-matched nonpsychotic HIV-1-seropositives.Methods: Two groups of subjects: HIV-1-seropositives with new-onset psychosis (n= 12) and HIV-1-seropositives without psychosis (n= 15) were recruited through outpatient departments. Organic Delusional Syndrome and Organic Hallucinosis were clinically diagnosed using DSM-III-R diagnostic criteria. Of the baseline participants, twenty-two participated in the two-year follow-up examination.Results: The prevalence of new-onset psychosis in HIV-1-infected subjects was 3.7 per 100 (95% C.I. = 1.6–5.7). HIV-1-seropositive persons with new-onset psychosis had more frequently a positive past psychiatric history, no antiretroviral therapy, and a lower global cognitive performance than did the nonpsychotic HIV-1-seropositives. CT was positive, showing generalized brain atrophy, in three out of nine patients. Remission of psychotic symptoms was observed only in two HIV-1-seropositive persons with new-onset psychosis. Death occurred in two psychotic HIV-1-seropositives with simple loosely held delusions. Autopsy results showed that cortical sulci and ventricle size were graded as with moderate/severe enlargement.Conclusions: New-onset psychosis in HIV infected patients could raise considerable problems in deciding whether a presentation is organic or functional. An interaction of the disease or of psychologically “having” the disease with the presence of a psychotic reaction should also be considered. Interestingly, a protective effect of antiretroviral therapy for new-onset psychosis is suggested.