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Our aim was to evaluate the effectiveness and safety of darunavir/cobicistat (DRV/c) monotherapy as an antiretroviral treatment simplification strategy in HIV-infected patients already on suppressive darunavir/ritonavir (DRV/r) monotherapy in routine clinical practice. We conducted a retrospective multicenter study including all adult patients switched from DRV/r monotherapy to DRV/c monotherapy while HIV-1 RNA was = 50 copies/mL or any change in the regimen after a single determination with HIV-1 RNA >= 50 copies/mL. Changes in renal function parameters and lipid profile were also evaluated. Factors associated with VF were analyzed using Cox regression. In this study, 173 subjects were included. The median (interquartile range) time of follow-up was 58 (50-67) weeks. Overall, 90% of patients remained free of TF during follow-up. Ten (6%) patients discontinued DRV/c monotherapy for nonvirological reasons and eight (5%) developed VF. No DRV-related mutations were identified in patients with VF. A decrease in triglyceride levels (p = .006) and estimated glomerular filtration rate (p = .005) were observed during follow-up. The presence of blips and CD4+ nadir

The NEUrocognitive (NEU) Screen is a practical tool proposed to screen for HIV-associated cognitive impairment in the clinical setting. This is a pencil-and-paper method that can be applied rapidly(

Integrase strand transfer inhibitors (INSTI) are a main component of the current antiretroviral regimens recommended for treatment of HIV infection. However, little is known about the impact of INSTI on neurocognition and neuroimaging. We developed a prospective observational trial to evaluate the effects of INSTI-based antiretroviral therapy on comprehensive brain outcomes (cognitive, functional, and imaging) according to the time since HIV-1 acquisition. We recruited men living with HIV who initiated antiretroviral therapy with INSTI < 3 months since the estimated date of HIV-1 acquisition (n = 12) and > 6 months since estimated date of HIV-1 acquisition (n = 15). We also recruited a group of matched seronegative individuals (n = 15). Assessments were performed at baseline (before initiation of therapy in HIV arms) and at weeks 4 and 48. Baseline cognitive functioning was comparable between the arms. At week 48, we did not find cognitive differences between starting therapy with INSTI earlier than 3 months or later than 6 months after acquisition of HIV-1 infection. Functional status was poorer in individuals diagnosed earlier. This effect recovered 48 weeks after initiation of therapy. Regarding brain imaging, we found that men living with HIV initiating antiretroviral therapy later experienced a greater decrease in medial orbitofrontal cortex over time, with expected negative repercussions for decision-making tasks. The study was supported by Fundació Lluita Contra la SIDA (FLS-ANT 2015-01). IMZ was supported by a P-FIS grant (FI17/00294) and CSM by a Miguel Servet contract (CPII16/00048) from the Instituto de Salud Carlos III. NPA was partially supported by grants MTM2015-64465-C2-1-R (MINECO/FEDER) and 2017 SGR 622 (GRBIO)

Collaborative work promoted by the GRBIO Research Group (https://grbio.upc.edu/en). -- Treball col·laboratiu del grup GRBIO desenvolupat perLupe Gómez, Yovaninna Alarcón-Soto, Mireia Besalú, Marta Bofill, Jordi Cortés, Daniel Fernández, Klaus Langohr, Núria Pérez, Alex SáncheziGuillermo Villacampa. https://grbio.upc.edu/en/grbio-divulga/grbio-divulga &nbsp

To determine the prevalence of potential prescribing issues (PPI) in HIV-infected subjects aged ≥65 years according to the Beers and STOPP/START criteria and antiretroviral drug-drug interactions (Liverpool website). Secondary objectives were to assess the concordance between Beers and STOPP/START criteria in our population, and to identify the drugs most frequently involved in PPI.Cross-sectional cohort study based on a systematic review of the electronic drug prescriptions confirmed by an interview of 91 HIV-infected patients aged ≥65 years. Discrepancies between prescription criteria were assessed using crosstabs and compared using the χThe mean age was 72.1 (5.6) years, 75.8% had ≥3 comorbidities and 59.3% polypharmacy. PPI were identified in 87.9%: 71.4% by STOPP/START and 45.1% by Beers. Comparing both criteria, 56.9% of PPI by STOPP/START were detected by Beers, while 92.5% of those detected by the Beers criteria were detected by STOPP/START (P.001). Amber/red flag interactions between antiretrovirals and comedications were found in 45.1%: 3 severe (red) in 2 patients (2.2%). The most frequent drugs involved in PPI were benzodiazepines (30%). Cobicistat was the drug most frequently involved in potential interactions (42.2%).The prevalence of PPI among older HIV-infected persons gives cause for concern, as it is almost 90%. Optimization strategies, including a critical review of the treatment plan, should be implemented in clinical routine by a multidisciplinary team, in particular in patients with multiple comorbidities and polypharmacy. The STOPP/START criteria seem to detect more PPI, mainly for European populations.

Our primary objective was to assess the independent association between liver fibrosis (LF) and abdominal fat accumulation (AFA) and fatty liver disease (FLD). We also aimed to determine the diagnostic accuracy of AFA and FLD for the prediction of cirrhosis measured using unenhanced low-dose computed tomography (CT). This is a cross-sectional study in stable human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients with active HCV replication. CT was used to quantify fat content in segments III and VI of the liver and AFA. Transient elastometry was used to stage LF. Multivariate logistic regression, receiver operating characteristic curve analysis, and linear mixed model analysis were applied. One hundred fifteen HIV/HCV-coinfected patients were included. Cirrhosis was detected in 20.8% (24 patients). There was a high correlation between anthropometric characteristics and radiological variables. The factors independently associated with cirrhosis were albumin concentration [odds ratio (OR), 0.69; 95% confidence interval (CI), 0.58-0.83; p < .0001] and visceral fat accumulation (OR, 1.02; 95% CI, 1.01-1.04; p = .0003). Multinomial analysis showed that visceral fat area (VFA) was the factor independently associated with stage F2 (OR, 1.02; 95% CI, 1.0-1.03; p < .005) and albumin concentration with stage F3 (OR, 0.75; 95% CI, 0.64-0.89; p < .001). VFA was the only radiological variable with an area under the curve >0.7 for the prediction of cirrhosis. There was no inter- or intraobserver variability in the measurement of AFA; however, high interobserver variability was recorded in the measurement of FLD. The association of VFA with cirrhosis, the high reproducibility of CT for the measurement of VFA, and the ability of VFA to predict cirrhosis make CT a suitable technique for identifying HIV/HCV-coinfected patients for closer surveillance.

This is an openaccessarticledistributedunderthe termsof theCreativeCommonsAttributionLicense,whichpermitsunrestricted use, distribution, andreproductionin any medium,providedthe originalauthorand sourceare credited. Objective Optimization of antiretroviral therapy and anti-inflammatory treatments, such as statins, are among the strategies aimed at reducing metabolic disorders, inflammation and immune activation in people living with HIV (PLWH). We evaluated the potential benefit of combining both strategies. Design Forty-two PLWH aged =40 years receiving a protease inhibitor (PI)-based regimen were randomized (1:1) to switch from PI to Raltegravir (n = 20), or to remain on PI (n = 22). After 24 weeks, all patients received atorvastatin 20mg/day for 48 weeks. Methods We analyzed plasma inflammatory as well as T-cell maturation, activation, exhaustion and senescence markers at baseline, 24 and 72 weeks, Results Plasma inflammatory markers remained unchanged. Furthermore, no major changes on T-cell maturation subsets, immunoactivation, exhaustion or immunosenescence markers in both CD4 and CD8 T cell compartments were observed. Only a modest decrease in the frequency of CD38+ CD8 T cells and an increase in the frequency of CD28-CD57+ in both CD4 and CD8 T-cell compartments were noticed in the Raltegravir-switched group. Conclusions The study combined antiretroviral switch to Raltegravir and Statin-based anti-inflammatory strategies to reduce inflammation and chronic immune activation in PLWH. Although this combination was safe and well tolerated, it had minimal impact on inflammatory and immunological markers. Clinical Peer Reviewed Ativle signat per 10 autors/es: Eugènia Negredo, Montse Jiménez, Jordi Puig, Cora Loste, Núria Pérez-Álvarez, Victor Urrea, Patricia Echeverría, Anna Bonjoch, Bonaventura Clotet, Julià Blanco

Objectives Liver fibrosis (LF) is crucial for the individualized management of patients with hepatitis C virus (HCV). We evaluated the concordance between two noninvasive methods for staging LF, transient elastography (TE) and acoustic radiation force impulse (ARFI), in patients coinfected with human immunodeficiency virus and HCV. We propose an algorithm for optimal use of both techniques in routine clinical practice. Methods A total of 89 human immunodeficiency virus/HCV-coinfected patients underwent TE and ARFI on the same day. The kappa index was used to assess concordance between the techniques. An algorithm combining ARFI and TE was proposed based on the independent factors associated with a kappa index greater than or equal to 0.70, obtained from a multiple regression analysis. We performed a cost-effectiveness analysis. The study was approved by our institutional review board and all patients signed the informed consent. Results Concordance between TE and ARFI for F2, F3, and F4 was 0.55, 0.59, and 0.69, respectively. Ultrasound normal spleen size (odds ratio [OR], 0.20; 95% confidence interval [CI], 0.05–0.91) and high viral load (OR, 0.36; 95% CI, 0.17–0.77) reduced the probability of agreement between TE and ARFI, whereas ultrasound normal left liver lobe size (OR, 3.32; 95% CI, 1.21–9.10) increased this probability. The algorithm revealed that LF was adequately assessed in 74.16%, with 25.84% of patients misclassified. The incremental cost-effectiveness ratio of TE compared with ARFI to increase concordance by 1% was €8.86. Conclusions Concordance between TE and ARFI was moderate. In the algorithm we proposed, ARFI was cost-effective as a first technique for the staging of LF in the study population.

Background The effect of ART on endothelial cell function is incompletely characterized. Methods We performed a 24 week prospective, case-control and comparative pilot study of ART-naive HIV-infected patients who started a darunavir- or rilpivirine-based regimen, matched with non-HIV-infected volunteers, to compare changes at week 24 from baseline in levels of circulating endothelial cells (CECs), endothelial progenitor cells (EPCs) and circulating angiogenic cells, as well as changes in immune-activation markers. Results The study population comprised 24 HIV-infected patients and 24 non-infected volunteers. Both HIV groups completely suppressed viraemia. HIV-infected patients had higher levels of activation markers than the control group in CD8 T cells at baseline; these decreased after 24 weeks of treatment, but without reaching the levels of the control group. No statistical differences in immune activation were seen between the darunavir and rilpivirine groups. Levels of CECs were higher and levels of EPCs and circulating angiogenic cells were lower in HIV-infected patients than in the control group, although these parameters were similar between the darunavir group and the control group, but not the rilpivirine group, at week 24. An unfavourable association was observed between rilpivirine, age and increased number of CECs. Conclusions Restoration of circulating levels of EPCs and CECs in darunavir-treated patients was greater than in those treated with rilpivirine, suggesting ongoing endothelial repair mechanisms.

Background: Strong and broad antiviral T-cell responses targeting vulnerable sites of HIV-1 will likely be a critical component for any effective cure strategy. Methods: BCN01 trial was a phase I, open-label, non-randomized, multicenter study in HIV-1-positive individuals diagnosed and treated during early HIV-1 infection to evaluate two vaccination regimen arms, which differed in the time (8 versus 24 week)between the ChAdV63.HIVconsv prime and MVA.HIVconsv boost vaccinations. The primary outcome was safety. Secondary endpoints included frequencies of vaccine-induced IFN-γ+ CD8+ T cells, in vitro virus-inhibitory capacity, plasma HIV-1 RNA and total CD4+ T-cells associated HIV-1 DNA. (NCT01712425). Findings: No differences in safety, peak magnitude or durability of vaccine-induced responses were observed between long and short interval vaccination arms. Grade 1/2 local and systemic post-vaccination events occurred in 22/24 individuals and resolved within 3 days. Weak responses to conserved HIV-1 regions were detected in 50% of the individuals before cART initiation, representing median of less than 10% of their total HIV-1-specific T cells. All participants significantly elevated these subdominant T-cell responses, which after MVA.HIVconsv peaked at median (range)of 938 (73-6,805)IFN-γ SFU/106 PBMC, representing on average 58% of their total anti-HIV-1 T cells. The decay in the size of the HIV-1 reservoir was consistent with the first year of early cART initiation in both arms. Interpretation: Heterologous prime-boost vaccination with ChAdV63-MVA/HIVconsv was well-tolerated and refocused pre-cART T-cell responses towards more protective epitopes, in which immune escape is frequently associated with reduced HIV-1 replicative fitness and which are common to most global HIV-1 variants. Funding: HIVACAT Catalan research program for an HIV vaccine and Fundació Gloria Soler. Vaccine manufacture was jointly funded by the Medical Research Council (MRC)UK and the UK Department for International Development (DFID)under the MRC/DFID Concordat agreements (G0701669. Research in Context: Evidence Before this Study: T cells play an important role in the control of HIV infection and may be particularly useful for HIV-1 cure by killing cells with reactivated HIV-1. Evidence is emerging that not all T-cell responses are protective and mainly only those targeting conserved regions of HIV-1 proteins are effective, but typically immunologically subdominant, while those recognizing hypervariable, easy-to-escape immunodominant ‘decoys’ do not control viremia and do not protect from a loss of CD4 T cells. We pioneered a vaccine strategy focusing T-cell responses on the most conserved regions of the HIV-1 proteome using an immunogen designated HIVconsv. T cells elicited by the HIVconsv vaccines in HIV-uninfected UK and Kenyan adults inhibited in vitro replication of HIV-1 isolates from 4 major global clades A, B, C and D. Added Value of this Study: The present study demonstrated the concept that epitopes subdominant in natural infection, when taken out of the context of the whole HIV-1 proteome and presented to the immune system by a potent simian adenovirus prime-poxvirus MVA boost regimen, can induce strong responses in patients on antiretroviral treatment and efficiently refocus HIV-1-specific T-cells to the protective epitopes delivered by the vaccine. Implications of all the Available Evidence: Nearly all HIV-1 vaccine strategies currently emphasize induction of broadly neutralizing Abs. The HIVconsv vaccine is one of a very few approaches focussing exclusively on elicitation of T cells and, therefore, can complement antibody induction for better prevention and cure. Given the cross-clade reach on the HIVconsv immunogen design, if efficient, the HIVconsv vaccines could be deployed globally. Effective vaccines will likely be a necessary component in combination with other available preventive measures for halting the HIV-1/AIDS epidemic.

Objectives Given the need for easily managed treatment of osteoporosis in HIV-infected patients, we evaluated the efficacy and tolerability of two doses of zoledronate, by comparing three groups of patients: those with annual administration, those with biennial administration (one dose in 2 years) and a control group with no administration of zoledronate. Methods We randomized (2:1) 31 patients on antiretroviral therapy with low bone mineral density (BMD) to zoledronate (5 mg administered intravenously; 21 patients) plus diet counselling and to a control group (diet counselling; 10 patients). At week 48, patients treated with zoledronate were randomized again to receive a second dose (two-dose group; n = 12) or to continue with diet counselling only (single-dose group; n = 9). Changes in lumbar spine and hip BMD and bone turnover markers were compared. Results The median percentage change from baseline to week 96 in L1−L4 BMD was −1.74% [interquartile range (IQR) −2.56, 3.60%], 7.90% (IQR 4.20, 16.57%) and 5.22% (IQR 2.02, 7.28%) in the control, two-dose and single-dose groups, respectively (P

Background Osteoporotic fractures still remain very infrequent and physicians rarely evaluate bone health. We wanted to assess the magnitude of this problem in the near future by determining the risk and likelihood of progression to osteoporosis. Methods We estimated the risk of progression to osteopenia/osteoporosis among HIV-infected patients with at least 2 DXA scans (3726 scans from 875 patients). Time-non-homogeneous bidirectional multistate models based on three states (normal bone mineral density, osteopenia and osteoporosis) were used to model the progression of bone mineral density as a function of age and to study the association between the risk of bone loss and antiretroviral use. Results The HRs associated with age (>45 versus ≤45 years) were: (i) from normal bone mineral density to osteopenia, 0.71 (95% CI 0.45-1.11) for men and 1.06 (95% CI 0.55-2.05) for women; and (ii) from osteopenia to osteoporosis, 0.83 (95% CI 0.51-1.35) for men and 0.99 (95% CI 0.38-2.56) for women. The transition probabilities from osteopenia to osteoporosis over 10 years among men aged 30 and 50 years were 14.9% (95% CI 10.5%-20.4%) and 19% (95% CI 14.3%-24.3%), respectively; and for women, 6.9% (95% CI 3.1%-14.4%) and 30.1% (95% CI 19.8%-41.8%), respectively. An increased osteoporosis risk was observed for PIs and PIs + tenofovir disoproxil fumarate; darunavir was associated with a higher risk of osteoporosis among men (HR 3.9; 95% CI 2-7.5) and women (HR 4.5; 95% CI 1.4-14.7); and atazanavir was associated with a higher risk of osteoporosis among women (HR 4.2; 95% CI 1.3-14). Conclusions Our results highlight the importance of monitoring bone mineral density given the high probability of progression to osteopenia/osteoporosis, especially in women. In the future, changes in antiretrovirals other than tenofovir, such as PIs, should be recommended to reduce the risk of fracture.

The most relevant endpoint in therapeutic HIV vaccination is the assessment of time to viral rebound or duration of sustained control of low-level viremia upon cART treatment cessation. Structured treatment interruptions (STI) are however not without risk to the patient and reliable predictors of viral rebound/control after therapeutic HIV-1 vaccination are urgently needed to ensure patient safety and guide therapeutic vaccine development. Here, we integrated immunological and virological parameters together with viral rebound dynamics after STI in a phase I therapeutic vaccine trial of a polyvalent MVA-B vaccine candidate to define predictors of viral control. Clinical parameters, proviral DNA, host HLA genetics and measures of humoral and cellular immunity were evaluated. A sieve effect analysis was conducted comparing pre-treatment viral sequences to breakthrough viruses after STI. Our results show that a reduced proviral HIV-1 DNA at study entry was independently associated with two virological parameters, delayed HIV-1 RNA rebound (p = 0.029) and lower peak viremia after treatment cessation (p = 0.019). Reduced peak viremia was also positively correlated with a decreased number of HLA class I allele associated polymorphisms in Gag sequences in the rebounding virus population (p = 0.012). Our findings suggest that proviral DNA levels and the number of HLA-associated Gag polymorphisms may have an impact on the clinical outcome of STI. Incorporation of these parameters in future therapeutic vaccine trials may guide refined immunogen design and help conduct safer STI approaches.

We model the evolution of bone mineral density measurements in a cohort of HIV-infected persons by DXA scans. We define the minimum T-score (MTS) from the DXA measures at four different sites and propose a disease progression model for the transitions between three different health states: normal, osteopenia, and osteoporosis. A linear mixed model for the MTS is fitted, the estimated ages at osteopenia and osteoporosis onset are imputed, and the transition probabilities between the states are estimated.

Prevalence of kidney disease ( KD) is increasing among human immunodeficiency virus (HIV)-infected population. Different factors have been related, varying on different published series. The objectives were to study prevalence of KD in those patients, its evolution, and associated risk factors. An observational cohort study of 1596 HIV-positive patients with cross-sectional data collection in 2008 and 2010 was conducted. We obtained clinical and laboratory markers, and registered previous or current treatment with tenofovir (TDF) and indinavir (IDV). The sample was divided according to estimated glomerular filtration rate (eGFR) by modification of diet in renal disease (MDRD) equation. Group 1: eGFR 60mL/min/1.73m(2). Among the patients, 76.4% were men, mean age (SD) 45 +/- 9 years, time since diagnose of HIV 14 +/- 7 years, and 47.2% of the patients received previous treatment with TDF and 39.1% with IDV. In 2008, eGFR

Background Nyaditum resae® (NR) is a galenic preparation of heat-killed Mycobacterium manresensis, a new species of the fortuitum complex, that is found in drinkable water, and that has demonstrated to protect against the development of active TB in a murine experimental model that develop human-like lesions. Methods Double-blind, randomized, placebo-controlled Clinical Trial (51 volunteers included). Two different doses of NR and a placebo were tested, the randomization was stratified by Latent Tuberculosis Infection (LTBI)-positive (n = 21) and LTBI-negative subjects (n = 30). Each subject received 14 drinkable daily doses for 2 weeks. Results All patients completed the study. The 46.3% of the overall reported adverse events (AE) were considered related to the investigational treatment. None of them were severe (94% were mild and 6% moderate). No statistical differences were found when comparing the median number of AE between the placebo group and both treatment groups. The most common AE reported were gastrointestinal events, most frequently mild abdominal pain and increase in stool frequency. Regarding the immunogenic response, both LTBI-negative and LTBI-positive volunteers treated with NR experienced a global increase on the Treg response, showed both in the population of CD25+CD39-, mainly effector Treg cells, or CD25+CD39+ memory PPD-specific Treg cells. Conclusion This clinical trial demonstrates an excellent tolerability profile of NR linked to a significant increase in the population of specific effector and memory Tregs in the groups treated with NR in both LTBI-positive and negative subjects. NR shows a promising profile to be used to reduce the risk of active TB.

Objectives Maximizing ART efficiency is of growing interest. This study assessed the efficacy, safety, pharmacokinetics and economics of a darunavir dose-reduction strategy. Methods This was a multicentre, randomized, open-label clinical trial in HIV-infected patients with plasma HIV-1 RNA 50 copies/mL or discontinuation of study treatment by week 48. The study was registered at https://www.clinicaltrialsregister.eu (trial number 2011-006272-39). Results Fifty participants were allocated to each arm. The mean (SD) CD4+ T cell count at baseline was 562 (303) cells/mm3 and HIV-1 RNA had been Conclusions The efficacy of a darunavir daily dose of 600 mg seemed to be similar to the efficacy of the standard 800 mg dose in virologically suppressed HIV-infected patients on triple ART. This strategy can potentially translate to substantial savings in the cost of care of HIV-infected patients.

Background: Data on the efficacy of simplifying therapy using darunavir/ritonavir and lopinavir/ritonavir monotherapy in clinical practice remain limited.; Methods: A retrospective single-centre study including patients initiating darunavir/ritonavir or lopinavir/ritonavir monotherapy with a plasma HIV-1 viral load (pVL) 50 copies/mL or as any change in the regimen after a single determination with a pVL >50 copies/mL) during the follow-up. We also evaluated the percentage of patients remaining free of treatment failure (TF; defined as VF or the early discontinuation of monotherapy for any reason) and compared the effectiveness of the two regimens. Effectiveness was evaluated using cumulative survival analysis (at Weeks 48 and 96). Factors associated with VF and TF were analysed using Cox regression.; Results: A total of 522 patients were included (309 receiving lopinavir/ritonavir and 213 receiving darunavir/ritonavir). The median follow-up was 64.3 (30.5-143.0) weeks. The percentage of patients free of VF and TF was 94% (95% CI 91%-96%) and 79% (95% CI 75%-82%) at 48 weeks, respectively, and 86% (95% CI 81%-89%) and 62% (95% CI 57%-67%) at 96 weeks, respectively. The risk of VF was similar for the two regimens (HR = 1.0, 95% CI 0.6-1.8; P = 0.962). Lopinavir/ritonavir monotherapy was associated with a 1.5-fold greater risk of TF (95% CI 1.1-2.1; P = 0.012) and a 2.3-fold greater risk of discontinuation of therapy due to adverse events (95% CI 1.3-3.9; P = 0.003).; Conclusions: The virological efficacy of darunavir/ritonavir and lopinavir/ritonavir monotherapy is high in clinical practice. Treatment discontinuation due to safety issues is more frequent with lopinavir/ritonavir. This study was supported in part by grants from Lluita contra la SIDA Foundation (Barcelona, Spain), the Spanish AIDS Network ‘Red Temática Cooperativa de Investigación en SIDA’ (RIS, RD06/0006), NEAT (European AIDS Treatment Network), Ministerio de Economía y Competitividad of Spain (MTM2012-38067-C02-01) and GRBIO (Grup de Recerca en Bioestadística i Bioinformàtica; 2014 SGR 464). The funders had no role in study design, data collection and analysis, the decision to publish or drafting of the manuscript.

OBJECTIVE Practical screening methods are necessary to detect neurocognitive impairment (NCI) in HIV-infected patients. We aimed to find a brief and feasible paper-based tool to facilitate the diagnosis of an HIV-associated neurocognitive disorder. METHODS A total of 106 HIV-infected outpatients with variable clinical characteristics were recruited in a multicenter investigation. NCI was diagnosed using a standardized neuropsychological tests battery (7 areas, 21 measures, ∼2 hours). Multiple score combinations were compared to find a paper-based method that took ≤10 minutes to apply. The presence of NCI was considered the gold standard for comparisons, and the sensitivity and specificity were calculated. RESULTS Subjects were mostly middle-aged (median, 44 years) men (87%) on antiretroviral treatment. NCI was detected in 51 individuals (48%) and was associated with lower nadir CD4 count (P < 0.001), receiving antiretroviral therapy (P = 0.004), fewer years of education (P = 0.009), and presence of comorbidities (P < 0.001). The score combination that showed the highest sensitivity (74.5%) and specificity (81.8%) detecting NCI included 3 measures of attention/working memory, executive functioning, and verbal fluency (part A of Trail Making Test, part B of Trail Making Test, and Controlled Oral Word Association Test scores). A broader paper-based selection of measures covering 7 areas indicated a sensitivity of 100% and a specificity of 96.3% (7 measures, ∼35 minutes). CONCLUSIONS The combination of the 3 measures presented in this study seems to be a rapid and feasible screening mean for NCI in HIV-infected patients. This approach, combined with screening for potential comorbidities and daily functioning interference, could help in the initial stages of a HIV-associated neurocognitive disorder diagnosis and in settings with limited access to neuropsychological resources.

Objetivo Este estudio modela el tiempo hasta la respuesta y el tiempo hasta la fase avanzada o crisis blastica en pacientes con leucemia mieloide cronica (LMC) recien diagnosticada y tratada con dasatinib 100 mg o imatinib 400 mg.

Kidney injury (defined as the presence of albuminuria, proteinuria, glycosuria [without hyperglycemia], hematuria, and/or renal hypophosphatemia) is an emerging problem in human immunodeficiency virus (HIV)-infected patients, although few data are available on the role of protease inhibitors (PIs) in this condition. To determine the time to kidney injury in a cohort of HIV-infected patients receiving a PI-containing regimen. We report the results of a subanalysis of a published cross-sectional study. The subanalysis included only patients receiving PI-containing regimens for more than 6 months (377 of the overall 970 patients). We determined associated factors and constructed receiver operating characteristic curves to estimate time to kidney injury depending on the PI used. The percentage of patients with kidney injury was 27.7% for darunavir, 27.9% for lopinavir, and 30% for atazanavir. Time to kidney injury was as follows: 229 days for atazanavir/ritonavir (area under the curve [AUC], 0.639; sensitivity, 0.89; specificity, 0.41); 332 days for atazanavir/ritonavir plus tenofovir (AUC, 0.603; sensitivity, 0.75; and specificity, 0.29); 318 days for nonboosted atazanavir (AUC, 0.581; sensitivity, 0.89; and specificity, 0.29); 478 days for lopinavir/ritonavir (AUC, 0.566; sensitivity, 0.864; and specificity, 0.44); 1339 days for lopinavir/ritonavir plus tenofovir (AUC, 0.667; sensitivity, 0.86; and specificity, 0.77); 283 days for darunavir/ritonavir (AUC, 0.523; sensitivity, 0.80; and specificity, 0.261); and 286 days for darunavir/ritonavir plus tenofovir (AUC, 0.446; sensitivity, 0.789; and specificity, 0.245). The use of lopinavir/ritonavir without tenofovir was a protective factor (odds ratio = 1.772; 95% CI, 1.070-2.93; P = 0.026). For all PIs, the percentage of patients with kidney injury exceeded 27%, irrespective of tenofovir use. The longest time to kidney injury was recorded with lopinavir/ritonavir. These results demonstrate the need for renal monitoring, including urine samples, in patients receiving a PI-based regimen, even when tenofovir is not used concomitantly.

Non-invasive in vivo diffuse optical characterization of human bone opens a new possibility of diagnosing bone related pathologies. We present an in vivo characterization performed on seventeen healthy subjects at six different superficial bone locations: radius distal, radius proximal, ulna distal, ulna proximal, trochanter and calcaneus. A tailored diffuse optical protocol for high penetration depth combined with the rather superficial nature of considered tissues ensured the effective probing of the bone tissue. Measurements were performed using a broadband system for Time-Resolved Diffuse Optical Spectroscopy (TRS) to assess mean absorption and reduced scattering spectra in the 600–1200 nm range and Diffuse Correlation Spectroscopy (DCS) to monitor microvascular blood flow. Significant variations among tissue constituents were found between different locations; with radius distal rich of collagen, suggesting it as a prominent location for bone related measurements, and calcaneus bone having highest blood flow among the body locations being considered. By using TRS and DCS together, we are able to probe the perfusion and oxygen consumption of the tissue without any contrast agents. Therefore, we predict that these methods will be able to evaluate the impairment of the oxygen metabolism of the bone at the point-of-care.

Background. Prospective studies about the reversibility of tenofovir disoproxil fumarate- (TDF-) related renal impairment remain scarce.Methods. This is an observational prospective study including all patients that presented at our HIV Unit who interrupted TDF owing to nephrotoxicity. We assessed the evolution of renal parameters after discontinuation of this drug.Results. We included 59 patients, who were followed up for 72 weeks. Most were male (41, 69.5%), median (IQR) age was 53 (44; 58) years, and median time receiving TDF-containing regimens was 55.4 (28; 87.7) months. Most patients were receiving PI-based treatments (67%). At the final visit, most of the subjects showed complete recovery (35, 59.3%) or improvement (13 subjects, 22%). Significant improvements were observed in creatinine levels (from 84.9 [73.8; 97.5] to 78 [69.6; 91] μmol/L,p=0.013), estimated glomerular filtration rate (eGFR, CKD EPI equation, from 87.7 [67; 99] to 89.9 [73.6; 99.3] mL/min/1.73 m2,p=0.017), and number of patients with eGFR 2(from 9 [15.3%] to 1 [1.7%],p=0.031). A trend toward significance was observed in abnormal urine proteinuria/creatinine ratio (from 22 [37%] to 8 [13.6%],p=0.057).Conclusions. Our results corroborate the high frequency of complete or partial renal recovery in patients receiving TDF-containing regimens who discontinued therapy owing to nephrotoxicity.

Background: Hypovitaminosis D is highly prevalent among HIV-infected patients. Since hypovitaminosis D is a secondary cause of low bone mineral density (BMD), we assessed its prevalence and associated factors in HIV-infected patients with osteopenia/osteoporosis, compared with HIV-infected patients with normal BMD. Materials & methods: Serum 25-hydroxy vitamin D (25[OH]D) concentration were collected from 149 HIV-infected subjects with low BMD and 36 with normal BMD from April to October, 2010. Regression analyses were fitted to predict the probability of hypovitaminosis D in all patients. Results: Of the 149 patients with low BMD (51.8 ± 8 years old, 76.5% men), 83% had vitamin D insufficiency (

We assessed the progress of renal damage after discontinuation of tenofovir (TDF) in patients who started therapy with normal renal parameters. Normal local reference values were as follows: estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease equation (MDRD), ⩾60mL/min/1.73m(2); creatinine, ⩽1.20mg/dL; serum phosphate: ⩾2.69mg/dL; proteinuria:30mg/dL, and glycosuria:20mg/dL in nondiabetic patients. A logistic regression analysis was used to evaluate factors related to normalization of renal function. We included 183 patients; 85% were male, and median (IQR) age was 44 (40-50)years. Time on TDF was 39 (22-63)months. After 22 (13-49.5)months from TDF discontinuation, renal parameters returned to normal values in 59% of patients, improved (without reaching normal values) in 9.8%, and did not improve in 31%. Median time until normalization was 4 (2-15.75)months, and time to maximum improvement in patients whose values did not return to normal was 14 (8.75-27.75)months. Follow-up was12months in 30% of the patients who did not improve. The only factors significantly associated with normalization of renal parameters were nadir CD4 T-cell count (p=0.034; OR=1.002, per 1 cell of increase) and CD4 T-cell count at the end of therapy with TDF (p=0.030; OR=1.033, per 1 cell of increase). Reversibility of renal damage was prompt and complete in 59% of patients receiving TDF-containing regimens and was associated with a higher nadir and current CD4+ T-cell count, suggesting a role of preserved cellular immunity in renal recovery in this population.

Objective: The ability of a prolonged antiretroviral treatment interruption to reverse mitochondrial toxicity was evaluated in a sub-study of TIBET, a prospective trial examining antiretroviral treatment interruption guided by CD4+ cell count. Patients and Methods: The study population was composed of patients from the TIBET study who had been followed for ≥96 weeks and whose peripheral blood mononuclear cells (PBMCs) had been collected at baseline and throughout the study period. Of the 201 patients included in the TIBET study, 38 were selected for the mitochondrial sub-study; 18 patients discontinued antiretroviral therapy for ≥96 weeks and 20 maintained therapy. Mitochondrial DNA (mtDNA) and RNA (mtRNA) were measured in PBMCs using real-time polymerase chain reaction, and mitochondrial function relative to mitochondrial content was assessed using the cytochrome c oxidase and citrate synthase ratio (COX/CS). Results: Whereas mtDNA content showed a similar progressive decrease throughout the study period in both arms, the mtRNA amount remained stable in both groups and the COX/CS ratio improved significantly in patients who interrupted therapy. Conclusions: Mitochondrial function improved during a prolonged antiretroviral treatment interruption despite a decrease in mtDNA levels in PBMCs, probably because of the existence of a mitochondrial transcriptional and translational upregulation mechanism or the reversion of mitochondrial toxicity by a mechanism that is independent of DNA polymerase gamma. The reduction in virus-related mitochondrial damage should be considered another relevant benefit of antiretroviral therapy.

Because interruptions of antiretroviral treatment may entail clinical risks for human immunodeficiency virus (HIV)-infected individuals, we investigated their impact on neurocognitive functioning. Cross-sectional study was carried out, comparing HIV-infected persons who had interrupted antiretroviral therapy in the past (interruption group, IG) with persons who had never discontinued therapy (noninterruption group, NIG). Interruption was defined as the discontinuation of highly active antiretroviral therapy (HAART) for more than 15 days after previous treatment of at least 15 days. All the participants were on therapy. Demographic, clinical, and neurocognitive variables were assessed. The primary end point was the percentage of people with neurocognitive impairment. The score in different neurocognitive domains was a secondary end point. A total of 83 subjects participated in the study (IG: n = 27; NIG: n = 56). Demographic and clinical characteristics were balanced between the groups, except for years since HIV diagnosis (IG, 13.8; NIG, 10.2 [P = .003]). The percentage of people with neurocognitive impairment was significantly higher in the IG group (IG, 59.25%; NIG, 33.92% [P = 0.02]). As for scores in neurocognitive domains, individuals in the IG showed worse neurocognitive functioning, and significant differences in attention/working memory and information processing speed were found. The adjusted analysis supported the unadjusted analysis. In this study, a higher prevalence of neurocognitive impairment was detected in HIV-infected persons who had interrupted antiretroviral therapy in the past. Additionally, neurocognitive functioning was observed to be more impaired in the same individuals. Further studies should examine the potential negative effects of antiretroviral therapy interruptions on neurocognitive functioning.

BACKGROUND: Although antiretroviral therapy improves immune response, some human immunodeficiency virus-infected patients present unsatisfactory CD4 T cell recovery despite achieving viral suppression, resulting in increased morbidity and mortality. METHODS: Cross-sectional, case-control study to characterize the mechanism and to identify predictive factors of poor immune response. We included 230 patients who were receiving highly active antiretroviral therapy and who had a viral load 2 years; 95 were "discordant" (case patients; CD4 T cell count always

Background Although efavirenz and lopinavir/ritonavir(r) are both recommended antiretroviral agents in antiretroviral-naive HIV-infected patients, there are few randomized comparisons of their efficacy and tolerability. Methods A multicenter and randomized study was performed including 126 antiretroviral-naive patients, randomly assigned to efavirenz + Kivexa ® ( n = 63) or lopinavir/r + Kivexa ® ( n = 63). Efficacy endpoints were the percentage of patients with HIV-RNA ≤50 copies/mL at week 48 and CD4 recovery. Safety was assessed by comparing toxicity and discontinuations. Statistical analyses were performed on an intention-to-treat (ITT) basis (Missing = Failure). Results At week 48, 56.7% of patients in the efavirenz and 63.2% in the lopinavir/r groups showed HIV-1 RNA P = 0.770) (intention-to-treat analysis; Missing = Failure). Only 1 (1.53%) patient from each group experienced virological failure. CD4 values increased in both groups (298 cells in the efavirenz group, P = 0.001; 249 cells in the lopinavir/r group, P = 0.002; P = 0.126 between groups). HDL-cholesterol only increased in the efavirenz group (from 39 ± 12 mg/dL to 49 ± 11; P = 0.001). Discontinuations were more frequent in the lopinavir/r group (36.5% versus 28.5%; P = 0.193), but more patients with efavirenz interrupted due to toxicity (11.1% versus 6.3%); most of them were attributed to hypersensitivity reaction. Conclusions Similar virological efficacy was observed for efavirenz and lopinavir/r, when administered with Kivexa ® in antiretroviral-naive patients, while immunological improvement was slightly superior for efavirenz. The higher rate of discontinuation due to toxicity in the efavirenz group was related to a higher incidence of hypersensitivity reaction. Nowadays, the use of the new formulation of lopinavir/r and the HLA-B*5701 genotype test before starting abacavir should improve the safety profiles of these regimens.

We designed a multicenter cross-sectional study to describe the epidemiological characteristics of the HIV-1-infected population aged 70 years or more in our setting. 179 individuals from eight university hospitals in Barcelona, Spain, were included, representing 1.5% of HIV-1 infected subjects followed during 2008. Most subjects were male (76%) and had acquired HIV infection through sexual intercourse (87%); 69% had been diagnosed with HIV-1 after their sixties. The CD4 cell counts at HIV-1 diagnosis were200 cells/mm(3) in 52% of individuals, whereas this was only seen in 34% of subjects from a published cohort including younger HIV- infected adults from the same setting [1]. Most of our patients were on HAART, had undetectable HIV-1 viremia and the most recent median CD4 cell counts wereor= 350 cells/mm(3). 154 subjects had at least one comorbid condition, including dyslipidemia (54%), hypertension (36%), hyperglycemia or diabetes (30%), cardiovascular disease (23%), chronic renal failure (18%), history of neoplasia (17%) and cognitive impairment (11%). Lipodystrophy was reported in 58% of individuals. Rates of hypercholesterolemia, diabetes and cancer were higher than those reported in unselected local population (28%, 17% and 7%, respectively). The study participants were taking an average of 2.97 drugs (range 1-10) other than antiretrovirals. In conclusion, the elder population infected with HIV-1 is likely being diagnosed late and at lower CD4+ counts and is frequently affected by comorbidities and co-medication. Based on our findings, we suggest some recommendations regarding the management of this growing population.

Background. Nucleoside reverse-transcriptase inhibitor (NRTI)-related mitochondrial toxicity has been suggested as a key factor in the induction of antiretroviral-related lipoatrophy. This study aimed to evaluate in vivo the effects of NRTI withdrawal on mitochondrial parameters and body fat distribution. Methods. A multicenter, prospective, randomized trial assessed the efficacy and tolerability of switching to lopinavir-ritonavir plus nevirapine (nevirapine group; n = 34), compared with lopinavir-ritonavir plus 2 NRTIs (control group; n = 33) in a group of human immunodeficiency virus-infected adults with virological suppression. A subset of 35 individuals (20 from the nevirapine group and 15 from the control group) were evaluated for changes in the mitochondrial DNA (mtDNA) to nuclear DNA ratio and cytochrome c oxidase (COX) activity after NRTI withdrawal. Dual-energy X-ray absorptiometry (DEXA) scans were used to objectively quantify fat redistribution over time. Results. The nevirapine group experienced a progressive increase in mtDNA content (a 40% increase at week 48; P = .039 for comparison between groups) and in the COX activity (26% and 32% at weeks 24 and 48, respectively; P = .01 and P = .09 for comparison between groups, respectively). There were no statistically significant between-group differences in DEXA scans at week 48, although a higher fat increase in extremities was observed in the nevirapine group. No virologic failures occurred in either treatment arm. Conclusions. Switching to a nucleoside-sparing regimen of nevirapine and lopinavir-ritonavir maintained full antiviral efficacy and led to an improvement in mitochondrial parameters, which suggests a reversion of nucleoside-associated mitochondrial toxicity. Although DEXA scans performed during the study only revealed slight changes in fat redistribution, a longer follow-up period may show a positive correlation between reduced mitochondrial toxicity and a clinical improvement of lipodystrophy.

A central goal in molecular evolution is to understand how genetic interactions between protein mutations shape protein function and fitness. While intergenic epistasis has been extensively explored in eukaryotes, bacteria, and viruses, intragenic epistatic interactions have been insufficiently studied. Here, we employ a model system in which lambda phage fitness correlates with the enzymatic activity of human immunodeficiency virus type 1 (HIV-1) protease to systematically determine the epistatic interactions between intragenic pairs of deleterious protein substitutions. We generated 114 genotypes of the HIV-1 protease, each carrying pairs of nucleotide substitution mutations whose separated and combined deleterious effects on fitness were then determined. A high proportion (39%) of pairs displayed lethality. Several pairs exhibited significant interactions for fitness, including positive and negative epistasis. Significant negative epistatic interactions predominated (15%) over positive interactions (2%). However, the average ± SD epistatic effect, ē = 0.0025 ± 0.1334, was not significantly different from zero ( p = 0.8368). Notably, epistatic interactions, regardless of epistatic direction, tend to be more frequent in the context of less deleterious mutations. In the present study, the high frequencies of lethality and negative epistasis indicate that the HIV-1 protease is highly sensitive to the effects of deleterious mutations. Therefore, proteins may not be as robust to mutational change as is usually expected.

To report long-term data on safety and effectiveness of antiretroviral regimens, including nevirapine. HIV-1-infected patients who received nevirapine-based approaches for at least 4 years were identified in the databases of five centers and included in a retrospective cohort study. Data collected included plasma HIV-RNA (viral load) and CD4+ T-cell counts, lipid and liver function tests, at baseline, 2-year and > 4-year time points. Hepatitis C virus (HCV) coinfection, adverse events, and reasons for using nevirapine were also recorded. Two hundred and twenty-nine patients (139 males/90 females) were included. The mean age was 37 years (range 20-59). Most patients (n = 124; 54%) were former intravenous drug users. One hundred and thirty-five of the patients (59%) were coinfected with HCV. Median time on nevirapine was 72.6 months. The main reasons for nevirapine use included: second- or third-line therapy (39%), simplification of therapy (29%), first-line therapy (18%) and efavirenz intolerance (9%). LDL cholesterol and triglycerides decreased during the >4-year follow-up (135 mg/dl to 109 mg/dl, p = 0.04; and 216 mg/dl to 153 mg/dl, p

We evaluated the prevalence of menstrual disorders in HIV-1-infected women and explored the association between such disorders and adherence to antiretroviral therapy, sexual functioning, and depressive symptoms in a group of HIV-1-infected women aged younger than 46 years and on antiretroviral therapy. Participants were included in a cross-sectional survey between June 2005 and December 2006. Women provided information about their menstrual cycle and adherence in a single visit and responded to the Greene Climacteric Scale, the Massachusetts General Hospital Sexual Functioning Questionnaire and the Beck Depression Inventory. Women with and without menstrual disorders were compared using parametric and nonparametric tests. A multivariate stepwise logistic regression model was developed. The participants were 107 Caucasian women with a median (interquartile range [IQR]) age of 39 years (IQR, 36-42 years) and a median CD4 cell count of 483 cells/mm(3) (IQR, 332-679 cells/mm(3)). The viral load was below 50 copies per milliliter in 76.6% of the women. Sixty-four percent of the women had acquired HIV-1 infection through sexual intercourse. Menstrual disorders, observed in 32% of participants, were more frequent in women with detectable viral loads (p = 0.018). Women with menstrual disorders reported worse adherence (p = 0.005) and more sexual dysfunction (p0.05). Sixty-nine percent of the women who attributed their menstrual disorders to the use of antiretrovirals had inadequate adherence. Depressive symptoms were not observed. Vasomotor symptoms (p = 0.004), having a detectable viral load (p = 0.03) and adherence less than 95% (p = 0.02) were predictors of menstrual disorder. A third of the HIV-1-infected women assessed had menstrual disorders that impacted negatively on adherence to therapy and sexual function. The subjective attribution of these irregularities to antiretrovirals seems to affect medication intake, possibly favoring negative clinical consequences.

Resilience is a predictor of emotional well-being and psychological adjustment in people living with HIV infection. We report the results of a cross-sectional study in which we evaluated resilience and its association with perception of ageing, coping strategies, quality of life, and emotional status in a group of long-term diagnosed HIV-infected patients. The analysis included 151 consecutive participants (57.6% men). Resilience was moderately high to high in 65 (43%) participants, moderately low to moderate in 57 (37.7%), and very low in 29 (19.2%). Univariate and multivariate analyses were performed. Two factors of perception of ageing (good cognitive self-concept and good subjective perception of social relationships), the use of positive reframing as a coping strategy and better emotional status remained associated with high resilience. Our findings suggest that successful ageing is possible in people living with HIV infection. Resilience seems to play a key role in the ageing process.

Background Tenofovir is involved in accelerated bone mineral density (BMD) loss. Methods We recently published a hip BMD improvement at week 48 [+2.1% (95% CI: −0.6, 4.7) (P = 0.043)] in HIV-infected patients with osteopenia/osteoporosis randomized to switch from tenofovir to abacavir (n = 26), although without reaching statistical significance compared with those who maintained tenofovir (n = 28). Here, we present changes at week 48 in bone markers [C-terminal telopeptide of collagen type 1 (CTX), osteocalcin and procollagen type 1 N propeptide (P1NP)] as well as in circulating levels of three proteins involved in bone regulation [osteoprotegerin, receptor activator for NF-κB ligand (RANKL) and sclerostin, a selective regulator of bone formation through the Wnt pathway] in 44 of these patients. χ2 or Fisher and Student t-tests were performed according to the distribution of the variables. Results Bone markers decreased only in the abacavir group [mean (SD) CTX changed from 0.543 (0.495) to 0.301 (0.306) ng/mL; mean (SD) osteocalcin changed from 23.72 (22.20) to 13.95 (12.40) ng/mL; and mean (SD) P1NP changed from 54.68 (54.52) to 28.65 (27.48) ng/mL (P Conclusions The switch from tenofovir to abacavir seems to induce a positive effect on bone tissue, since bone turnover markers decreased. In addition, circulating sclerostin levels increased, a change associated with improved bone properties.

Lipodystrophy is one of the foremost concerns among the HIV-positive population, and is often associated with psychosocial disorders. We evaluated the clinical efficacy of facial infiltrations with autologous fat, polylactic acid, and polyacrylamide gel using clinical inspection and facial photographs (ordinal scale). Additionally, we assessed the safety of the infiltration techniques and determined changes in patient satisfaction, emotional status, and quality of life. Evaluations were made at 48- and 96-week follow-up visits. This paper presents the 48- week follow-up results. The current analysis includes 138 patients: 8, 25, and 105 in the fat, polylactic acid, and polyacrylamide gel groups, respectively. At baseline, almost 50% of the patients (67/138) presented grades 3 and 4 lipoatrophy, but at week 48 only 7.5% (7/93) remained in these advanced grades (no patients from the polyacrylamide group). A new round of infiltrations at week 48 was necessary in 35% (33/93) of patients (88%, 84%, and 8% in the fat, polylactic, and polyacrylamide groups, respectively). No serious adverse events were detected with any of the substances. Patient satisfaction and quality of life improved significantly in all three groups. Infiltrations with autologous fat, polylactic acid, or polyacrylamide gel appear to be an effective and safe alternative to repair facial lipoatrophy, at least up to 48 weeks, significantly improving patient quality of life. Similar results were observed for all degrees of severity and between genders. Polyacrylamide gel provided the longest lasting benefits.

To identify a new circulating recombinant form (CRF) of HIV-1 comprising two circulating subtypes in the southern region in Brazil, subtypes B and C.A total of 152 HIV-positive patients followed at two hospitals in southern Brazil had their viral pol genes isolated by reverse transcriptase-polymerase chain reaction (PCR) from plasma. PCR products were sequenced and phylogenetically analysed using HIV-1 subtype reference sequences. Six full-length subtype C viruses from Brazil previously described as 'pure' strains were included in the analysis. Sequences suggestive of recombination were analysed by boot scanning and phylogenetic analyses of separate fragments. The common ancestry of recombinant strains was evaluated by similarity plot and informative site analyses.: HIV-1 subtypes commonly found in Brazil (B, C and F1) were observed. Sixty-two viruses were initially assigned as subtype C, but 15 viruses clustered in a separate internal clade. Pol from two full-length genomes of subtype C viruses grouped together with those samples. Boot scanning analysis showed that all 17 viruses had the same recombinant structure, with a 240 base pair fragment of subtype B in the middle of the reverse transcriptase pol region. Subtype B assignment of this fragment was confirmed by phylogenetic analyses using different methods of tree inference and cluster robustness tests. Mosaics were shown to have a common ancestry.As CRF_BC represents 11% of the HIV-1 viruses circulating in the southern region of the country, which borders several south American countries, the assessment of its spread is of pivotal importance to the HIV/AIDS epidemic in Brazil and Latin America.

Using a multicenter, cross-sectional, observation study, the long-term safety, metabolic profile, and viral efficacy of nevirapine (NVP)-based approaches in HIV-1-infected patients treated for at least 2 years were assessed. For 4 months, all consecutive HIV-1-infected patients who had been receiving an NVP-containing regimen for at least 2 years were recruited. A total of 613 patients were included with a median follow-up period of 43 months (IQR: 31-51). At baseline, 24.5% (150 patients) were treatment naive, 41.5% (254 patients) switched for simplification purposes, and 34% (209 patients) were failing HAART. Increases by five times or more in AST/ALT values were observed in fewer than 2% of patients. Only 5.7% of all adverse events reported during the investigation were attributable to NVP. The percentage of patients with normal HDL cholesterol levels rose from 17.7% at baseline to 35.4% at the last visit. At the latest time point available for analysis, 76% of naive and 74% of those who had switched had HIV-1 RNA loads of50 copies/ml, while 59% of salvage patients achieved this level of viral suppression. Factors associated with viral suppression at the latest visit were adequate adherence (OR: 2.58, 95% CI: 0.85-7.78, p0.001), first-line treatment (OR: 3.02, 95% CI: 1.52-6.00, p = 0.002), and baseline CD4 cells400 cells/microl (OR: 2.34, 95% CI: 1.22-4.47, p = 0.010). Exposure to nevirapine for up to 4 years is safe. Liver toxicity is infrequent and generally mild. HDL cholesterol levels consistently increase over time and viral suppression is maintained.

BACKGROUND: Tenofovir has been associated with a decrease in bone mineral density (BMD). However, data on changes in BMD after discontinuing tenofovir are lacking. METHODS: We performed a two-centre randomized pilot study in virologically suppressed HIV-infected patients receiving tenofovir with osteopenia/osteoporosis (OsteoTDF study, ClinicalTrials.gov number NCT 01153217). Fifty-four patients were randomly assigned to switch from tenofovir to abacavir (n = 26) or to continue with tenofovir (n = 28). Changes in lumbar and total hip BMD were evaluated at Week 48 from baseline. RESULTS: Five patients discontinued the study (three from the tenofovir group and two from the abacavir group). No significant differences were detected between the groups at Week 48 (P = 0.229 for total hip and P = 0.312 for lumbar spine). However, hip BMD improved by 2.1% (95% CI -0.6 to 4.7) (P = 0.043) in the abacavir group and 0.7% (95% CI -0.9 to 2.4) (P = 0.372) in the tenofovir group. Lumbar spine BMD varied by -0.7% (95% CI -3.8 to 3.3) (P ≤ 0.001) in the abacavir group and -1.2% (95% CI -3.8 to 0.4) (P < 0.001) in the tenofovir group. CONCLUSIONS: Switching from tenofovir to abacavir led to a slight improvement in femoral BMD although no differences were detected between groups. Larger studies are necessary before firm recommendations can be made on the discontinuation of tenofovir in patients with a low BMD.

Renal disorders are an emerging problem in HIV-infected patients. We performed a cross-sectional study of the first 1000 HIV-infected patients attended at our HIV unit who agreed to participate. We determined the frequency of renal alterations and its related risk factors. Summary statistics and logistic regression were applied. The study sample comprised 970 patients with complete data. Most were white (94%) and men (76%). Median (IQR) age was 48 (42–53) years. Hypertension was diagnosed in 19%, dyslipidemia in 27%, and diabetes mellitus in 3%. According to the Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) equation, 29 patients (3%) had an eGFR < 60 ml/min/1.73m2; 18 of them (62%) presented altered albumin/creatinine and protein/creatinine (UPC or UAC) ratios. Of the patients with eGFR> 60mL/min, it was present in 293 (30%), 38 of whom (7.1%) had UPC> 300mg/g. Increased risk of renal abnormalities was correlated with hypertension (OR, 1.821 [95%CI, 1.292;2.564]; p = 0.001), age (OR, 1.015 [95%CI, 1.001;1.030], per one year; p = 0.040), and use of tenofovir disoproxil fumarate (TDF) plus protease inhibitor (PI), (OR, 1.401 [95%CI, 1.078;1.821]; p = 0.012). Current CD4 cell count was a protective factor (OR, 0.9995 [95%CI, 0.9991;0.9999], per one cell; p = 0.035). A considerable proportion of patients presented altered UPC or UAC ratios, despite having an eGFR > 60mL/min. CD4 cell count was a protective factor; age, hypertension, and use of TDF plus PIs were risk factors for renal abnormalities. Based on our results, screen of renal abnormalities should be considered in all HIV-infected patients to detect these alterations early.

Background Etravirine (ETR) was approved for patients with virological failure and antiretroviral resistance mutations. It has also shown antiviral efficacy in antiretroviral-naïve patients. However, data on the switching from protease inhibitors (PI) to ETR are lacking. Methods HIV-1-infected patients with suppressed viral load (VL) during a PI-containing regimen (>12 months) and no previous virological failure were randomized to switch from the PI to ETR (400 mg/day, dissolved in water) (ETR group, n = 22) or to continue with the same regimen (control group, n = 21). Percentage of patients with VL≤50 copies/mL were assessed at week 48, as well as changes in CD4 T-cell counts and metabolic profile. Results We included 43 patients [72.9% male, 46.3 (42.2; 50.6) years]. Two patients receiving ETR (grade-1 diarrhea and voluntary discontinuation) and another in the control group (simplification) discontinued therapy early. No patients presented virological failure (two consecutive VL>50 copies/mL); treatment was successful in 95.2% of the control group and 90.9% of the ETR group (intention-to-treat analysis, missing = failure) (p = 0.58). CD4+ T-cell counts did not significantly vary [+49 cells/µL in the ETR group (p = 0.25) and −4 cells/µL in the control group (p = 0.71)]. The ETR group showed significant reductions in cholesterol (p