The prevalence of osteopenia in HIV-infected patients on HAART is high. Loss of BMD is associated with PI therapy, low plasma albumin level, and male sex. Osteopenia does not progress after 1 year of continued HAART.

The aim of the present study was to examine the causes of death, the mortality attributable to liver failure, and the impact of hepatitis virus infections on the survival of a cohort of HIV-infected patients before and after the extensive use of highly active antiretroviral therapy (HAART). Liver disease associated with hepatitis C virus (HCV) seems to be accelerated in patients infected with the human immunodeficiency virus (HIV). On the other hand, the effect of HCV on HIV progression was controversial before the introduction of HAART. However, the last study to report changes in mortality due to liver failure was published in 1997, and the impact of HCV carriage on the survival of HIV-infected patients receiving HAART needs to be clarified. In this investigation, 492 patients who were prescribed antiretroviral drugs between April 1989 and September 2000 were included in the study cohort. The median duration of follow-up of the cohort was 1,392 days. HCV infection was present in 323 (68%). Mortality attributable to AIDS decreased from 4.5 to 1.8 per 100 persons per year. Mortality due to liver failure increased from 0.3 to 0.5 per 100 persons per year ( P<0.01). The survival of patients with and without HCV infection was similar ( P=0.8). Although liver failure is an increasing cause of death among HIV-infected patients receiving HAART, HCV infection has still no impact on the survival of HIV-infected patients.

The prevalence of osteopenia in HIV-infected patients is high. However, the mechanisms implicated in bone mass loss in HIV infection are unclear. Because of this, we analyzed serum free testosterone and vitamin D3 hydroxylated metabolites in HIV-infected patients, with and without antiretroviral treatment, and the relation between them and osteopenia. Seventy-four HIV-infected patients were selected because they had frozen sera available at a date close to a DEXA evaluation. Free testosterone, 25(OH)D3, and 1,25(OH)2D3 were determined in frozen serum. There were no differences in free testosterone, 25(OH)D3, and 1,25(OH)2D3 levels between patients with and without osteopenia. 25(OH)D3 levels in naive and HAART-treated patients were 26.2 (10.3-32.8) and 33.1 (20.6-46.8) ng/ml, respectively (p = 0.04). 1,25(OH)2D3 levels in naive and HAART treated patients were 60.3 (49.2-80.8) and 85.5 (68-111.6) pmol/liter (p = 0.01). Free testosterone levels in 9 naive men and in 50 HAART-treated men were 42.6 (24.1-67.3) and 69.2 (47.5-112.1) pmol/liter, respectively (p = 0.04). In conclusion, HIV-infected patients with and without osteopenia showed similar levels of vitamin D metabolites and free testosterone. However, antiretroviral drug-naive patients showed lower serum levels of vitamin D metabolites and free testosterone than HAART-treated patients.

ObjectiveNoninvasive tests that can be used in place of liver biopsy to diagnose fibrosis have major limitations. They either leave a significant proportion of patients without a definitive diagnosis or produce inaccurate results. Moreover, the performance of these tests is lower in HIV/hepatitis C virus (HCV) coinfection. Against this background, we examined the utility of serum matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase 1 (TIMP-1) measurements in combination with routine clinical data to predict fibrosis in HIV/HCV-coinfected patients. MethodsPatients with a liver biopsy who had not received anti-HCV therapy were included in the study. A model including variables independently associated with fibrosis was constructed. Diagnostic accuracy was determined by measuring the area under the receiver operating characteristic curve (AUROC). Positive (PPV) and negative (NPV) predictive values were calculated. ResultsNinety patients were included in the study. Aspartate aminotransferase (AST), platelet count and MMP-2 were predictors of significant fibrosis (F ! 2) and cirrhosis (F4). A score constructed using these variables yielded an AUROC of 0.76 for F ! 2 and 0.88 for F4. Score cut-offs detected (value ! 3.5) and excluded (value 1.5) F ! 2 with a PPV of 87% and an NPV of 88%. Thirty-one patients (34%) were correctly diagnosed using these cut-offs, with four (13%) incorrect classifications. Cirrhosis was excluded with a certainty of 98% and diagnosed with a probability of 83%. Two (17%) of 12 patients were misclassified as having cirrhosis. The AST to platelet count index and MMP-2 levels were sequentially applied to detect F ! 2. Forty-one patients (46%) were identified with this approach, with six (15%) misclassifications. ConclusionMMP-2 levels can be used in combination with AST and platelet count to aid the diagnosis of liver fibrosis in HIV/HCV-coinfected patients.Keywords: aspartate aminotransferase to platelet count index, hepatitis C virus, liver fibrosis, matrix metalloproteinase 2, noninvasive diagnosis of fibrosis IntroductionThe extent of liver fibrosis has prognostic and management implications in chronic hepatitis C. The diagnosis of fibrosis has traditionally relied on liver biopsy. However, this procedure is invasive, limited because of variability issues [1,2] and difficult to apply sequentially. Because of these issues, noninvasive tests that can be used in place of liver biopsy are needed. Among such tests, those employing simple blood indexes, based on routinely available data, and transient elastometry (TE) have been validated in patients with chronic hepatitis C virus (HCV) and HIV coinfection [3][4][5][6].Simple indexes are easy to implement and cost-effective. However, the diagnostic yield of these indexes is lower in HIV/HCV-coinfected patients [3,4]. In particular, the DOI: 10.1111/j.1468-1293.2010.00836.x HIV Medicine (2011 r 2010 British HIV Association 14 diagnosis of cirrhosis cannot be established confidently [3]. TE seems a promising technique for ...

The accuracy of LiPA 2.0 for hepatitis C virus 1 (HCV-1) subtype classification was analyzed. LiPA 2.0 genotype results from 101 HCV-1-infected patients were compared to genotype findings determined by direct core sequencing. Eleven (11%) samples were misclassified. Given the influence of the HCV-1-subtype in the anti-HCV therapy response, an alternative classification method is warranted.T he effect of the hepatitis C virus (HCV) genotype 1 subtype on the response to treatment can be dramatic for some direct antiviral agent (DAA)-containing regimens (1)(2)(3)(4)(5)(6)(7)(8)(9). This is the case for simeprevir, a DAA recently approved for clinical use, that in combination with pegylated interferon and ribavirin (peg-IFN/ RBV) has a lower sustained virological response (SVR) rate for subtype 1a than for 1b (2). Simeprevir plus peg-IFN/RBV treatment achieves rates of SVR similar to those for peg-IFN/RBV treatment in HCV-1a-infected patients who present the viral variation Q80K. This variation is frequent in the HCV-1a subtype, but it is not found in HCV-1b (2, 5). Similarly, daclatasvir plus peg-IFN/RBV treatment also achieves higher SVR rates among HCV1b-infected patients than among HCV-1a-infected individuals (4). For interferon-free regimens, DAA combinations such as asunaprevir plus daclatasvir may only be indicated for subtype 1b, because of high relapse rates observed among patients with subtype 1a (3, 4). Because of these, accurate subtyping of HCV genotype 1-infected patients is needed for those who are candidates for DAAs.Sequencing of specific HCV genome regions with subsequent phylogenetic analysis is considered the gold standard of HCV genotyping (10). However, it includes several complex techniques and is time consuming. For these reasons, LiPA 2.0 is currently one of the most widely used genotyping assays. However, several studies have reported HCV genotyping errors using this commercial method (11-13). Those studies were not designed to evaluate the frequency of HCV-1 subtyping misclassifications, and they included few HCV-1-infected patients. Therefore, due to the high prevalence of HCV-1 infections in western countries and the importance of correct subtyping in clinical decisions, the accuracy of this method for HCV-1 subtyping needs to be evaluated in larger samples. For these reasons, we aimed to evaluate the accuracy of LiPA 2.0 for classifying HCV-1 by subtypes.This study was performed according to the ethical guidelines of the 1975 Declaration of Helsinki, and it was approved by the ethics committee of the Hospital Universitario de Valme (Seville, Spain).The first 110 consecutive patients starting from October 2001, who received a course of peg-IFN/RBV treatment in our hospital and who were infected with HCV-1, according to the LiPA 2.0 determination, were selected. All of them were Caucasian with a median age (quartile 1 to quartile 3) of 42 years (range, 39 to 46 years). Among the patients, 82 (81%) were male, and 48 (47.5%) were infected with HIV.To determine the HCV-1 subtype, we analyzed...