Modelling the impact of protein-kinase R allelic variant on HIV biomarkers trajectories by means of latent class mixed models.

This paper is based on a retrospective longitudinal study on people living with HIV under antiretroviral treatment (ART) where allelic variants (either heterozygous CT genotype or homozygous CC genotype) have been evaluated at position -168 of the promoter region of the protein kinase R (-168/PKR). In general, antiviral effects of interferon are partially mediated by a RNA-dependent protein kinase (PKR) that, once activated, inhibits protein synthesis. Indeed, activation of PKR response can inhibit HIV replication. To explore the role of allelic variants in shaping dynamics of commonly monitored HIV biomarkers, CD4 cells, CD8 cells and HIV-load were modelled within a latent class mixed model (LCMM) to account for participants' heterogeneity over time. The estimated models identified two sub-groups from CD4 and HIV-load dynamics, revealing better outcomes for subgroups of participants with the heterozygous CT genotype. Heterozygous CT subjects in one of the two identified subgroups exhibited higher increase of CD4 cells and more marked decrease of HIV-load, over time, with respect to the homozygous CC subjects assigned to the same group.

Risk of HIV viral rebound in HIV infected patients on direct acting antivirals (DAAs) treatment for HCV.

BACKGROUND: The dynamic of HIV-viral load (VL) remains poorly investigated in HIV/HCV patients under direct acting antivirals (DAAs). METHODS: We retrospectively evaluated HIV-VL at baseline (BL) during and up to 24 weeks post-DAAs in a cohort of 305 HIV-1/HCV patients, on ART and with no HIV virological failure (VF) in the 6 months before treatment with DAAs; during the period of observation VF was defined as confirmed VL≥50 copies/mL; virological blips (VB, transient, not confirmed, VL ≥50 copies/mL). Stepwise Cox regression models were fitted to estimate adjusted hazard ratios (aHR) of VF. RESULTS: Fifteen VF occurred in 13 patients over 187 person-years of follow-up (PYFU): incidence rate (IR) of 8.0 per 100-PYFU (95% CI = 4.0-12.1); 29 VBs were detected in 26 patients over 184 PYFU: IR = 15.8 per 100-PYFU (95% CI = 10.0-21.5). The most prominent factor associated with VF was the presence of BL HIV residual viremia (RV = HIV-RNA detectable but not precisely quantifiable) [aHR = 12.26 (95% CI = 3.74-40.17), P<0.0001]. Other factors were ≥1 VBs in the 6 months before DAAs [aHR = 6.95 (95% CI = 1.77-27.37) P = 0.006] number of ART regimens failed before DAAs initiation [aHR (per more regimen) = 1.22 (95% CI = 1.04-1.42), P = 0.012] and age [aHR (per year older) = 1.16 (95% CI = 1.04-1.29), P = 0.010]. CONCLUSIONS: Our findings underline the importance for close monitoring HIV-VL in selected patients. Whether this phenomenon is triggered by the rapid clearance of HCV remains to be established.

HIV-1 recombinant forms in immigrants regularly residing in Milan, northern Italy.

To assess the HIV -1subtypes distribution in HIV-1 positive migrants living in Milan we studied 77 HIV-1 patients followed at the San Raffaele Hospital of Milan. Twenty subjects were born in Europe, 43 in the Americas, 10 in Africa and 4 in Asia. Unsafe heterosexual activity prevailed in migrants born in Africa and male homosexuality in those born in European, American and Asian countries (p = 0.05). The phylogeny showed that 38/77 (49.3%) subjects carried HIV-B subtype while the remaining strains were classified as not pure HIV-1 B subtypes 13/77 (16.9%) or recombinant forms 26/77 (33.8%). Female gender more frequently showed HIV-1 non-B strains and rarely HIV-1 B subtypes (12/39, 30.8% vs. 3/38, 7.9%, p = 0.02). Transmitted drug resistance was identified in 10/77 (13%) patients predominately with B subtype. Our data underscore a large heterogeneity in HIV-1 subtypes and a large proportion of recombinant forms.

Molecular epidemiology of HIV-1 infection in immigrant population in northern Italy.

Human immunodeficiency virus-1 (HIV-1) is characterised by a vast genetic diversity classified into distinct phylogenetic strains and recombinant forms. We describe the HIV-1 molecular epidemiology and evolution of 129 consecutive HIV-1 positive migrants living in Milan (northern Italy). Polymerase gene sequences of 116 HIV-1 subtype-B positive patients were aligned with HIV-1 reference sequences (https://www.ncbi.nlm.nih.gov/) by using MAFFT alignment and edited by using Bioedit software. A maximum likelihood (ML) phylogenetic tree was performed by MEGA7 and was visualised by using FigTree v1.4.3. Of 129 migrants, 35 were born in Europe (28 in Eastern Europe), 70 in the Americas (67 in South America), 15 in Africa and nine in Asia; 76.4% were men who have sex with men (MSM). The serotype HIV-1-B prevailed (89.9%), followed by -C, -F1, -D and -A. Compared with 116 HIV-B patients, the 13 with HIV-non-B showed lower Nadir of CD4+ cell/mmc (P = 0.043), more frequently had sub Saharan origin (38.5 vs. 1.72%, P = 0.0001) and less frequently were MSM (40 vs. 74.5%, P = 0.02). The ML phylogenetic tree of the 116 HIV-1 subtype-B positive patients showed 13 statistically supported nodes (bootstrap > 70%). Most of the sequences included in these nodes have been isolated from male patients from the Americas and the most common risk factor was MSM. The low number of HIV-1 non-B subtype patients did not allow to perform this analysis. These results suggest a shift of HIV-1 prevention projects' focus and a continuous monitoring of HIV-1 molecular epidemiology among entry populations. Prevention efforts based on HIV molecular epidemiology may improve public health surveillance setting.

Brief Report: Outcome of Acute Hepatitis B Virus Infection in HIV-1-Infected Patients: Possible Factors Associated With Resolution or Chronicity.

BACKGROUND: HIV-1 infection impairs cellular immunity, causing a detrimental effect on the natural course of hepatitis B virus (HBV) infection. HBV vaccination is less effective in HIV-1-infected patients. This study aimed to gain insight into HIV-1 infection with persistence of hepatitis B surface antigen (HBsAg) defining chronic hepatitis B infection (CBI) after a primary infection and the possible associated factors. SETTING: Division of Infectious Diseases, San Raffaele Hospital, Italy. METHODS: This retrospective study analyzed HIV-1-infected patients diagnosed with acute hepatitis B infection (AHB) based on clinical or laboratory records. CBI was defined as a positive HBsAg result recorded >6 months after an AHB diagnosis. Multivariate logistic regression was applied to assess factors (evaluated at AHB diagnosis) that were associated with CBI. RESULTS: Of 63 HIV-1-infected patients with AHB, 23 (36.5%) developed CBI. On multivariate analysis, CBI risk was less likely in patients with HIV-RNA of >50 copies/mL (adjusted odds ratio = 0.03, 95% confidence interval: 0.001 to 0.58, P = 0.021). Dually acting antiretroviral treatment, including one or more drugs active against HIV/HBV (lamivudine, emtricitabine, and tenofovir), seemed to be protective in terms of the clinical outcome of CBI (adjusted odds ratio = 0.07, 95% confidence interval: 0.01 to 1.02, P = 0.050). Among the 23 patients with CBI, 15 (65.2%) lost the hepatitis B e-antigen, while 11 (47.8%) had HBsAg seroclearance during follow-up. CONCLUSIONS: In HIV-1-infected subjects with AHB, the persistence of HBsAg seemed to occur frequently. Factors associated with a lower CBI risk were detectable HIV load and the use of dually acting antiretroviral treatment during AHB.

Cannabinoid receptor 2-63 RR variant is independently associated with severe necroinflammation in HIV/HCV coinfected patients.

OBJECTIVE: This is the first study to analyze the impact of the rs35761398 variant of the CNR2 gene leading to the substitution of GLN (Q) of codon 63 of the cannabinoid receptor 2 (CB2) with ARG (R) on the clinical presentation of chronic hepatitis in HIV/HCV coinfected patients. METHODS: Enrolled in this study were 166 consecutive HIV/HCV coinfected patients, naïve for HCV treatment. A pathologist unaware of the patients' condition graded liver fibrosis, necroinflammation (Ishak) and steatosis. All patients were screened for the CB2 rs35761398 polymorphism. RESULTS: Of the 166 HIV/HCV coinfected patients, 72.9% were males, 42.5% were infected with HCV-genotype-3 and 60.2% had been intravenous drug users. The median age was 40.6 years and the immunological condition good (median CD4+ cells/mm3 = 507, IQR: 398.0-669.5). Thirty-five (21.1%) patients were naive for ART and 131(78.9%) were on ART. The CB2-RR variant was detected in 45.8% of patients, QR in 38.6% and QQ in 15.7%. Patients with CB2-RR showed a necroinflammation score (HAI) ≥9 more frequently than those with CB2-QQ or CB2-QR (32.9% vs. 11.5% and 14.1%, respectively, p≤0.001). In the multivariate analysis, the CB2-RR variant (p = 0.03) and liver fibrosis were both identified as independent predictors of the entity of liver necroinflammation (p = 0.0001). CONCLUSION: This study shows interesting interplay between the CB2-RR variant and liver necroinflammation in chronic hepatitis patients with HIV/HCV coinfection, an observation of clinical value that coincides with the interest in the use of the CB2 agonists and antagonists in clinical practice emerging from the literature.

Associations of statins and antiretroviral drugs with the onset of type 2 diabetes among HIV-1-infected patients.

BACKGROUND: Statin use is associated with a modest increase in the incidence of type 2 diabetes mellitus (DM) among the general population. However, HIV-infected patients have a higher risk of developing DM, and it is unclear whether statins have a diabetogenic effect in these patients. Therefore, we investigated the associations of statin use and exposure to antiretroviral drugs with type 2 DM onset in a cohort of HIV-infected patients. METHODS: This retrospective, controlled, cohort study identified HIV-1-infected patients who did not have DM and were not receiving statins at their antiretroviral treatment (ART) initiation. Follow-up was accrued from ART initiation to the earliest instance of a DM diagnosis, loss to follow-up, death, or last available visit. The incidence of DM was estimated according to statin use, which was adjusted for periods without statin treatment. The Fine-Gray competing risk model was used in the multivariate analysis to identify risk factors for developing DM. RESULTS: The analyses evaluated 6,195 patients followed for 9.8 years (interquartile range: 4.3-16.3 years). During 64,149 person-years of follow-up (PYFU), 235 patients developed DM (crude incidence: 3.66 [95%CI: 3.20-4.13] per 1,000 PYFU), and 917 (14%) patients used statins. After adjusting for potential confounders, statin use was associated with a non-significant increase in the risk of DM (AHR: 1.21, 95% CI: 0.71-2.07; P = 0.47). DM was more likely among patients who were ever treated with stavudine, and less likely among those ever treated using emtricitabine, tenofovir, abacavir, efavirenz, nevirapine, atazanavir or darunavir. CONCLUSIONS: A higher risk of diabetes mellitus was not associated with statin treatment but with traditional risk factors and stavudine use while a reduced risk of DM was associated with the use of emtricitabine, tenofovir, abacavir, efavirenz, nevirapine, atazanavir or darunavir.

TM6SF2 E167K variant predicts severe liver fibrosis for human immunodeficiency/hepatitis C virus co-infected patients, and severe steatosis only for a non-3 hepatitis C virus genotype.

AIM: To evaluate the impact of the Glu167Lys (E167K) transmembrane 6 superfamily member 2 (TM6SF2) variant on the biochemical and morphologic expression of liver lesions in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infected patients. METHODS: The study comprised 167 consecutive patients with HIV/HCV coinfection and biopsy-proven chronic hepatitis. A pathologist graded liver fibrosis and necroinflammation using the Ishak scoring system, and steatosis using Kleiner's scoring system. Patients were genotyped for TM6SF2 E167K (rs58542926) by real-time Polymerase chain reaction. The 167 patients, 35 therapy-naive and 132 receiving ART, were prevalently males (73.6%), the median age was 40.7 years and the immunological condition good (median CD4+ cells/mm3 = 505.5). RESULTS: The 17 patients with the TM6SF2 E167K variant, compared with the 150 with TM6SF2-E/E, showed higher AST (P = 0.02) and alanine aminotransferase (P = 0.02) and higher fibrosis score (3.1 ± 2.0 vs 2.3 ± 1.5, P = 0.05). In a multivariate analysis, TM6SF2 E167K was independently associated with severe fibrosis. The same analysis showed that HCV-genotype 3, present in 42.2% of patients was an independent predictor of severe steatosis. The association of TM6SF2 E167K with severe steatosis, absent for the whole group of 167 patients, was re-evaluated separately for HCV-genotype 3 and non-3 patients: No factor was independently associated with severe steatosis in the HCV-genotype-3 subgroup, whereas an independent association was observed between severe steatosis and TM6SF2 E167K in non-3 HCV genotypes. No association between the TM6SF2 E167K variant and severe liver necroinflammation was observed. CONCLUSION: In HIV/HCV coinfection the TM6SF2 E167K variant is an independent predictor of severe fibrosis, but appears to be independently associated with severe steatosis only for patients with a non-3 HCV genotype.

Estimated Glomerular Filtration Rate Trajectories in HIV-Infected Subjects Treated With Different Ritonavir-Boosted Protease Inhibitors and Tenofovir Disoproxil Fumarate or Abacavir.

The aim of the study was to evaluate in human immunodeficiency virus (HIV)-infected patients estimated glomerular filtration rate (eGFR) trajectories during treatment with different protease inhibitors (PIs) or a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus tenofovir (TDF) or abacavir (ABC) and lamivudine or emtricitabine (xTC).Retrospective study of patients followed at a single clinical center; all patients who started TDF or ABC for the first time with a NNRTI or lopinavir/r (LPV/r) or atazanavir/r (ATV/r) or darunavir/r (DRV/r), for whom at least 1 eGFR value before the start and during the studied treatment was known, were included in this analysis. eGFR was calculated by means of the CKD-EPI formula. Univariate and multivariate mixed linear model (MLM) was applied to estimate eGFR slope with the considered antiretroviral treatment.In the 1658 patients treated with TDF/xTC (aged 43 [37-48] years, with an eGFR of 105 [96; 113] mL/min/1.73 m, 80% males, 92% Caucasians, 10% coinfected with HCV, 4% with diabetes, 11% with hypertension, 38% naive for antiretroviral therapy (ART), 37% with HIV-RNA <50 copies/mL) the median follow-up was 2.5 (1.2-4.6) years. Their adjusted eGFR slopes (95% CI) were -1.26 (-1.58; -0.95), -0.43 (-1.20; +0.33), -0.86 (-1.28; -0.44), and -0.20 (-0.42; +0.02) mL/min/1.73 m per year in patients treated with ATV/r, DRV/r, LPV/r, and NNRTI, respectively. Patients receiving ATV/r or LPV/r had a greater adjusted decline in eGFR compared with those receiving NNRTIs (difference -1.06 [-1.44; -0.69] mL/min/1.73 m per year, P <0.001; and -0.66 [-1.13; -0.20] mL/min/1.73 m per year, P = 0.005, respectively); adjusted eGFR slopes were similar in patients receiving DRV/r and in those receiving NNRTIs. Patients receiving ATV/r had a greater adjusted eGFR decline than those treated with DRV/r (difference -0.83 [-1.65; -0.02] mL/min/1.73 m per year; P = 0.04), but not than those receiving LPV/r; no significant difference was observed in adjusted eGFR slopes between patients receiving DRV/r and those receiving LPV/r. In the 286 patients treated with ABC and lamivudine, eGFR slopes were similar, independent of the PI.In patients receiving TDF/xTC, eGFR trajectories were small for all regimens and declined less in patients receiving DRV/r or NNRTIs than in those treated with ATV/r or LPV/r.

Diagnostic accuracy of APRI, FIB-4 and Forns for the detection of liver cirrhosis in HIV/HCV-coinfected patients.

We determined the diagnostic accuracy and optimal cut off of three indirect fibrosis biomarkers (APRI, FIB-4, Forns) compared with liver stiffness (LS) for the detection of liver cirrhosis in HIV/HCV-coinfected patients. An observational retrospective study on HIV/HCV-coinfected patients with concomitant LS measurement and APRI, FIB-4 and Forns was performed. The presence of liver cirrhosis was defined as a LS ≥13 KPa. The diagnostic accuracy and optimal cut-off values, compared with LS categorization (<13 vs ≥13 KPa), were determined by receiver operating characteristics (ROC) curves. The study sample included 646 patients. The area-under-the ROC curve (95% confidence interval) for the detection of liver cirrhosis were 0.84 (0.81-0.88), 0.87 (0.84-0.91) and 0.87 (0.84-0.90) for APRI, FIB-4 and Forns, respectively. According to the optimal cut off values for liver cirrhosis (≥0.97 for APRI, ≥2.02 for FIB-4 and ≥7.8 for Forns), 80%, 80% and 82% of subjects were correctly classified by the three indirect fibrosis biomarkers, respectively. Misclassifications were mostly due to false positive cases. The study suggests that indirect fibrosis biomarkers can help clinicians to exclude liver cirrhosis in the management of HIV/HCV co-infected patients, reducing the frequency of more expensive or invasive assessments.

Unboosted atazanavir with lamivudine/emtricitabine for patients with long-lasting virological suppression.

INTRODUCTION: Unboosted atazanavir (ATV) including regimens have been investigated as a ritonavir-sparing simplification strategy. No data are available on removal of one NRTI in subjects effectively treated with unboosted atazanavir+2NRTIs. We present the 48-week virological efficacy and safety of unboosted atazanavir plus lamivudine (3TC) or emtricitabine (FTC) (lamivudine/emtricitabine/Reyataz(©), LAREY Study). MATERIALS AND METHODS: Single arm, prospective, pilot study on HIV-treated patients, HBsAg negative, with HIV-RNA<50 cps/mL since at least 2 years, who switched from ATV+2NRTIs to ATV 400 mg QD +3TC or FTC. Virological failure was defined as 2 consecutive values of HIV-RNA>50 cps/ml; viral blip was defined as a single HIV-RNA value>50 cps/ml not subsequently confirmed. RESULTS as median (IQR). Changes between baseline (BL) and week 48 assessed by the Wilcoxon signed rank test. RESULTS: Forty patients enrolled: 75% males, 51 (47-54) years, 14% HCV co-infected, infected with HIV since 16 (9-21) years, on antiretroviral therapy since 13 (5-16) years, with a nadir CD4+ of 254 (157-307) cells/mm(3), virologically suppressed since 4.2 (2.2-5.4) years; 53 patients switched from a tenofovir (TDF)-based regimens; ATV was associated with 3TC in 83% patients. No virological failures or discontinuations were observed; three patients had a single viral blip in the range 50-250 copies/mL; CD4+ increased from 610 (518-829) cells/mm(3) at BL to 697 (579-858) cells/mm(3) at week 48 [48-week change: 39 (-63/+160) cells/mm(3) p=0.081]. Three clinical events were observed (one herpes zoster, one pneumonia, one syphilis) in absence of renal lithiasis, AIDS-defining or drug-related events or death. Overall, significant 48-week amelioration of ALP [BL: 83 (71-107) mg/dL; 48-week change: -15 (-27/-8) mg/dL p<0.0001] and CKD-EPI [BL: 100 (86-108) ml/min/1.73 m(2); 48-week change: 1.5 (-3/+8) ml/min/1.73 m(2), p=0.042] were observed. Patients switching from TDF (Table 1) significantly improved CD4+, lymphocytes, hepatic profile, renal profile and ALP; these patients had also a modest but significant decrease in haemoglobin. CONCLUSIONS: Switch from an unboosted atazanavir-based regimen to ATV+3TC or FTC regimen was effective and safe in this small sample, supporting the hypothesis of a potential two-steps de-intensification (removal of ritonavir and removal of one NRTI) in patients on long-lasting virological suppression.

Use of statins and risk of AIDS-defining and non-AIDS-defining malignancies among HIV-1 infected patients on antiretroviral therapy.

OBJECTIVE: Previous studies have shown that statins use is associated with a lower mortality risk or occurrence of non-Hodgkin's lymphoma or non-AIDS-defining malignancies (NADMs) in HIV-positive patients. We evaluated the effect of statin therapy on the occurrence of all AIDS-defining malignancy (ADM) and NADM among HIV-positive patients. DESIGN: A chart study on HIV-1 infected patients attending the Infectious Diseases Department of the San Raffaele Scientific Institute, Italy. METHODS: Incident malignancies diagnosed since antiretroviral treatment (ART) initiation until October 2012 among treated patients not taking statins at ART initiation. Statin therapy had to precede cancer diagnosis, if it occurred. Malignancies that occurred before ART or statin initiation were excluded. Follow-up was calculated since ART initiation until the first cancer diagnosis or loss to follow-up or death or last available visit, whichever occurred first. Results are described as median (interquartile range, IQR). RESULTS: Five thousand, three hundred and fifty-seven HIV-1 treated patients were included. During 52 663 person-years, 740 (14%) patients had a history of statin use; 375 malignancies occurred: 12 (1.6%) malignancies (0 ADM; 12 NADM, crude incidence rate, 1.3/1000 person-years) among statin users and 363 (7.9%) malignancies (194 ADM; 169 NADM, crude incidence rate, 8.4/1000 person-years) among non-statin users. By multivariate Fine-Gray regression, statin use was associated with a lower risk of cancer [adjusted hazard ratio (95% confidence interval) for ever use: 0.45 (0.17-0.71)]. CONCLUSION: Among HIV-1 treated patients, statin use was associated with a lower risk of cancer; the benefit was mainly related to AIDS-defining malignancies. Confirmatory studies are needed to consider the residual confounding likely present in this study.

Cost analysis of initial highly active antiretroviral therapy regimens for managing human immunodeficiency virus-infected patients according to clinical practice in a hospital setting.

OBJECTIVE: In the study reported here, single-tablet regimen (STR) versus (vs) multi-tablet regimen (MTR) strategies were evaluated through a cost analysis in a large cohort of patients starting their first highly active antiretroviral therapy (HAART). Adult human immunodeficiency virus (HIV) 1-naïve patients, followed at the San Raffaele Hospital, Milan, Italy, starting their first-line regimen from June 2008 to April 2012 were included in the analysis. METHODS: The most frequently used first-line HAART regimens (>10%) were grouped into two classes: 1) STR of tenofovir disoproxil fumarate (TDF) + emtricitabine (FTC) + efavirenz (EFV) and 2) MTR including TDF + FTC + EFV, TDF + FTC + atazanavir/ritonavir (ATV/r), TDF + FTC + darunavir/ritonavir (DRV/r), and TDF + FTC + lopinavir/ritoavir (LPV/r). Data were analyzed from the point of view of the Lombardy Regional Health Service. HAART, hospitalizations, visits, medical examinations, and other concomitant non-HAART drug costs were evaluated and price variations included. Descriptive statistics were calculated for baseline demographic, clinical, and laboratory characteristics; associations between categorical variables and type of antiretroviral strategy (STR vs MTR) were examined using chi-square or Fisher's exact tests. At multivariate analysis, the generalized linear model was used to identify the predictive factors of the overall costs of the first-line HAART regimens. RESULTS: A total of 474 naïve patients (90% male, mean age 42.2 years, mean baseline HIV-RNA 4.50 log 10 copies/mL, and cluster of differentiation 4 [CD4+] count of 310 cells/µL, with a mean follow-up of 28 months) were included. Patients starting an STR treatment were less frequently antibody-hepatitis C virus positive (4% vs 11%, P=0.040), and had higher mean CD4+ values (351 vs 297 cells/µL, P=0.004) than MTR patients. The mean annual cost per patient in the STR group was €9,213.00 (range: €6,574.71-€33,570.00) and €14,277.00 (range: €5,908.89-€82,310.30) among MTR patients. At multivariate analysis, after adjustment for age, sex, antibody-hepatitis C virus status, HIV risk factors, baseline CD4+, and HIV-RNA, the cost analysis was significantly lower among patients starting an STR treatment than those starting an MTR (adjusted mean: €12,096.00 vs €16,106.00, P=0.0001). CONCLUSION: STR was associated with a lower annual cost per patient than MTR, thus can be considered a cost-saving strategy in the treatment of HIV patients. This analysis is an important tool for policy makers and health care professionals to make short- and long-term cost projections and thus assess the impact of these on available budgets.

Optimal dietary calcium intake in HIV treated patients: no femoral osteoporosis but higher cardiovascular risk.

BACKGROUND & AIMS: We performed a cross-sectional study on adult HIV-infected patients, on HAART, without calcium or vitamin D supplementation to evaluate if the cardiovascular risk or the presence of osteoporosis may be predictive factors of an optimal daily calcium intake (DCI>1000 mg/day). METHODS: Patients underwent a dual-energy X-ray absorptiometry, measured biochemical parameters and compiled a validated questionnaire for the assessment of DCI. Osteoporosis (OP) was defined according to the WHO classification at either the vertebral spine or femoral neck. Cardiovascular risk was assessed by the 10-year Framingham cardiovascular risk score. RESULTS: 200 HIV-infected patients evaluated: 171 (86%) males with a median age of 48.1 (42.3-53.8) years and 10.6 (4.3-13.6) years of HAART exposure. DCI was 889 (589-1308) mg/day and 79 (40%) patients had an optimal DCI. Framingham risk>20% was found in 13 (6.7%) patients and femoral OP was diagnosed in 12 (6%) pts. By multivariate analysis, optimal DCI was more likely in patients with a Framingham risk>20% [OR = 5.547, 95% CI:1.337, p = 0.025] and less likely in patients with femoral osteoporosis [OR = 0.159, 95% CI: 0.018-0.790, p = 0.047]. CONCLUSIONS: We found that an optimal dietary calcium intake was more likely in patients with high cardiovascular risk and no femoral osteoporosis.

Boosted or unboosted atazanavir as a simplification of lopinavir/ritonavir-containing regimens.

UNLABELLED: Switches from lopinavir/ritonavir (LPV/r) to either atazanavir/ritonavir (ATV/r) or unboosted ATV (ATV) are increasingly common in clinical practice, but data on outcome comparison between these two simplification strategies are very limited. METHODS: Multicenter, observational, retrospective study. Data were collected from five Italian clinics. The objective of the study was to investigate the outcome of LPV/r simplification with ATV/r or ATV and to identify factors predicting virological rebound. Patients who switched from LPV/r to ATV/r or ATV with an HIV-RNA value<50 copies/mL at the time of switch and with at least one follow-up visit were included. We evaluated 468 patients (74.1% males), followed for a median (Q1-Q3) of 547 (305-788) days: 380 (81%) and 88 (19%) switched to ATV/r and to ATV, respectively. Virological rebound was detected in 78/468 (16.7%, 95% CI: 13.6 -20.3) patients [16/88 (18.2%, 95% CI: 11.4 -27.6) switched to ATV and 62/380 (16.3%, 95% CI: 12.9 -20.4) to ATV/r (p=0.638)]. Virological rebound was more frequent in patients who started LPV/r with HIV-RNA >30000 copies/mL (28% vs 6%, p=0.014). Replacing lopinavir/r with ATV or ATV/r yielded similar rates of virological rebound. Viral load at the initiation of lopinavir/r may be useful in driving the choice between ATV/r and ATV.

Clinical, virologic, and immunologic outcomes in lymphoma survivors and in cancer-free, HIV-1-infected patients: a matched cohort study.

BACKGROUND: The objective of this study was to compare immunologic, virologic, and clinical outcomes between living human immunodeficiency virus (HIV)-infected individuals who had a diagnosis of lymphoma versus outcomes in a control group of cancer-free, HIV-infected patients. METHODS: In this matched cohort study, patients in the case group were survivors of incident lymphomas that occurred between 1997 and June 2010. Controls were living, cancer-free, HIV-infected patients who were matched to cases at a 4:1 ratio by age, sex, nadir CD4 cell count, and year of HIV diagnosis. The date of lymphoma diagnosis served as the baseline in cases and in the corresponding controls. RESULTS: In total, 62 patients (cases) who had lymphoma (20 with Hodgkin disease [HD] and 42 with non-Hodgkin lymphoma [NHL]) were compared with 211 controls. The overall median follow-up was 4.8 years (interquartile range, 2.0-7.9 years). The CD4 cell count at baseline was 278 cells/mm³ (interquartile range, 122-419 cells/mm³) in cases versus 421 cells/mm³ (interquartile range, 222-574 cells/mm³) in controls (P = .003). At the last available visit, the CD4 cell count was 412 cells/mm³ (range, 269-694 cells/mm³) in cases versus 518 cells/mm³ (interquartile range, 350-661 cells/mm³) in controls (P = .087). The proportion of patients who achieved virologic success increased from 30% at baseline to 74% at the last available visit in cases (P = .008) and from 51% to 81% in controls (P = .0286). Patients with HD reached higher CD4 cell counts at their last visit than patients with NHL (589 cells/mm³ [range, 400-841 cells/mm³] vs 332 cells/mm³ [interquartile range, 220-530 cells/mm³], respectively; P = .003). Virologic success was similar between patients with HD and patients with NHL at the last visit. Forty cases (65%) and 76 controls (36%) experienced at least 1 clinical event after baseline (P < .0001); cases were associated with a shorter time to occurrence of the first clinical event compared with controls (P < .0001). CONCLUSIONS: HIV-infected lymphoma survivors experienced more clinical events than controls, especially during the first year of follow-up, but they reached similar long-term immunologic and virologic outcomes.