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Galectins are a family of proteins with affinity for β-galactosides and their expression correlates with overall survival (OS) in several cancers. However, in breast cancer their prognostic potential is unclear. In this study we performed a meta-analysis to clarify the prognostic value of galectin expression in breast cancer and to identify sources of heterogeneity. For this purpose, we performed a search of related publications in PubMed, Central-Conchrane, Web of Science database, OVID-EMBASE, Scope and EBSCOhost until November 2021.Thirteen articles were included with a total of 2700 patients. High galectin expression was found not to correlate with OS in breast cancer (HR = 1.11, 95% CI 0.93-1.31). In the case of galectin-3, correlation with OS was observed when performing subgroup analysis by cellular localization (HR = 0.59, 95% CI 0.36-0.94 for cytoplasmic and HR = 1.82, 95% CI 1.00-3.29 for cytoplasmic plus nuclear). Galectin-7 correlates with DFS/PFS/DSS (HR = 2.43; 95% CI 1.36-4.31). Finally, galectin-3 correlates with some clinicopathological features such as lymph node metastasis, estrogen receptor expression and age. In conclusion, galectin-3 correlates with OS in breast cancer when cellular localization is considered while galectin-7 correlates with DFS/PFS/DSS. The cellular localization of galectins should be as fundamental aspect to be determined in future studies.

RESUMEN Introducción: Debido a la diferente epidemiología de la COVID-19 en diferentes regiones del planeta, es relevante conocer el impacto de variables sanitarias propias de cada país. Objetivo: Evaluar el rol del antecedente de vacunación con BCG y la historia reciente de Dengue entre los factores de riesgo para internación de pacientes con COVID-19. Métodos: Estudio observacional, de tipo transversal que, mediante entrevista estructurada, consignó variables sociodemográficas y clínicas en pacientes con diagnóstico de COVID-19 en cuatro instituciones de salud del Paraguay durante septiembre a diciembre de 2020. Modelos de regresión logística evaluaron factores asociados al desenlace. Resultados: Fueron incluidos 397 pacientes. La frecuencia de hospitalización fue mayor en individuos de sexo masculino, edad > 40 años, menor ingreso económico, obesidad, hipertensión arterial y diabetes mellitus. Hubo menos hospitalización entre el personal de salud y en quienes refirieron asma bronquial. El sexo masculino (ORa 3,72; IC95% 2,22-6,22), la hipertensión arterial (ORa 2,46; IC95% 1,30-4,64), el ingreso económico (ORa 1,98; IC95% 1,03-3,80), la labor hospitalaria (ORa 0,20; IC95% 0,11-0,37) y el asma bronquial (ORa 0,40; IC95% 0,20-0,82) se mostraron influyentes al análisis multivariado. En ciertos modelos estudiados por regresión logística aquellos que refirieron historia de vacunación con BCG se asociaron a menor frecuencia de internación hospitalaria. El antecedente de dengue sintomático no cupo entre las variables relevantes relativas al desenlace. Conclusiones: Entre varios modelos de predicción de severidad de la COVID-19, el antecedente de vacunación con BCG puede asociarse a las tasas de hospitalización con cierto impacto. ABSTRACT Introduction: Due to the different epidemiology of COVID-19 in different regions of the world, it is important to know the impact of health variables specific to each country. Objective: To evaluate the role of history of BCG vaccination and recent history of dengue among risk factors for hospitalization of patients with COVID-19. Methods: Observational, cross-sectional study that recorded sociodemographic and clinical variables by means of structured interview in patients diagnosed with COVID-19 in four health institutions in Paraguay (September to December 2020). Logistic regression models evaluated factors associated with outcome. Results: 397 patients were included. The frequency of hospitalization was higher in male patients, age > 40 years, lower income, obesity, hypertension and diabetes mellitus. There was less hospitalization among health personnel and in those who reported bronchial asthma. Male sex (ORa 3.72; 95%CI 2.22-6.22), arterial hypertension (ORa 2.46; 95%CI 1.30-4.64), income (ORa 1.98; 95%CI 1.03-3.80), healthcare worker (ORa 0.20; 95%CI 0.11-0.37) and bronchial asthma (ORa 0.40; 95%CI 0.20-0.82) were influential in the multivariate analysis. In certain models studied by logistic regression, those who reported a history of BCG vaccination were associated with a lower frequency of hospitalization. History of symptomatic dengue fever was not among the relevant variables related to outcome. Conclusions: Among several COVID-19 severity prediction models, BCG vaccination history may be associated with hospitalization rates.

In an ongoing Mediterranean cohort, we compared age-related conditions between 208 HIV-infected persons and 104 matched controls. ≥3 comorbidities were found in 31.0% of HIV-infected patients and 8.7% of controls. Conditions significantly more frequent among the HIV-infected population were: lipid abnormalities, cancer, osteopenia/osteoporosis, liver disease, sexual dysfunction, hearing deficit, sleep disorders, falls, cognitive complaints, being single, living alone, and being elderly at risk. HIV-infected patients aged >70 years had a significantly higher number of cardiovascular risk factors (CVRF) and comorbidities than controls. HIV-infected persons who had never smoked had a higher prevalence of CVRFs, ≥3 comorbidities, liver disease, cancer, and cognitive complaints compared to controls. Factors associated with frailty were being a man who has sex with men, ≥3 CVRFs, nadir CD470 years. The multidisciplinary assessment also revealed concerning findings in social, cognitive, and functional variables among HIV-infected individuals, with a higher prevalence of elderly at risk than among controls.

Background:HIV infection is an increasingly complex chronic disease associated with numerous medical, psychological, and social problems. The life expectancy of affected patients has increased considerably. Medical apps could also play a role in prevention and management of comorbid conditions in the HIV-infected population. Objectives:To determine the usefulness of an app designed specifically for HIV-infected patients aged 60 years or older and to assess changes in patient satisfaction, adherence to treatment, and quality of health care. Methods:A randomized clinical trial was conducted, including 100 patients (50 per group): (1) an experimental group comprising patients using the app + routine medical care (app group) and (2) with routine medical care (control group). The usability of the app and patient satisfaction were evaluated in the app group at week 48. Quality of life, adherence to treatment, and clinical parameters were compared between both groups at 48 weeks, as well as the number of face-to-face visits. Results:We found that 52.2% and 73.8% of patients in the app group used the app at weeks 24 and 48, respectively. Patients used the app for a mean of 23.7 (+/- 2.84) days over the 48 weeks. The most visited screens were health counseling and medical records (24.8% and 22.2%, respectively). At week 48, 85.2% of patients thought that the app was useful and 91.4% would recommend the app to friends or relatives. The app was well valued by participants (4.79 [+/- 0.21] of 5.00) and 64.6% thought that the app improved their health care.

Advanced kidney disease is an emerging problem in people living with HIV despite sustained viral suppression.We performed a prospective cohort study to identify people living with HIV with advanced kidney disease according to the Kidney Disease Improving Global Outcomes criteria and to assess disease progression over a 48-week period following the offer of targeted multidisciplinary management.From our cohort of 3090 individuals, 55 (1.8%, 95% confidence interval [CI] 1.31-2.25) fulfilled the inclusion criteria. Most were male (83.6%), and the median (interquartile range [IQR]) age was 58 (53.25-66.75) years. Nadir CD4 T-cell count was 135.5 (IQR 43.5-262.75) cells/μl, current CD4 T-cell count was 574 (IQR 438.5-816) cells/μl, and 96% had maintained HIV viral suppression. The most frequent comorbidity was arterial hypertension (85.5%). Inadequate antiretroviral dose was detected in three individuals (5.5%), and drug-drug interactions were recorded in eight (14.5%), mainly involving the use of cobicistat (n = 5 [9%]). Four individuals (7%) required modification of their concomitant treatment. Seven (13%) had to start or resume follow-up with a nephrologist. Nine participants (16.4%) experienced an improvement in kidney disease stage, three individuals (5.5%) underwent renal transplantation, and one (2%) started haemodialysis.Our results show that a multidisciplinary approach, including a critical review of treatment and evaluation of specific requirements, could be useful for anticipating drug-drug interactions and toxicities and for reducing death and hospitalization in people living with HIV with advanced kidney disease.

Background The coronavirus disease (COVID-19) pandemic has caused an unprecedented worldwide public health crisis that requires new management approaches. COVIDApp is a mobile app that was adapted for the management of institutionalized individuals in long-term care facilities. Objective The aim of this paper is to report the implementation of this innovative tool for the management of long-term care facility residents as a high-risk population, specifically for early identification and self-isolation of suspected cases, remote monitoring of mild cases, and real-time monitoring of the progression of the infection. Methods COVIDApp was implemented in 196 care centers in collaboration with 64 primary care teams. The following parameters of COVID-19 were reported daily: signs/symptoms; diagnosis by reverse transcriptase–polymerase chain reaction; absence of symptoms for ≥14 days; total deaths; and number of health care workers isolated with suspected COVID-19. The number of at-risk centers was also described. Results Data were recorded from 10,347 institutionalized individuals and up to 4000 health care workers between April 1 and 30, 2020. A rapid increase in suspected cases was seen until day 6 but decreased during the last two weeks (from 1084 to 282 cases). The number of confirmed cases increased from 419 (day 6) to 1293 (day 22) and remained stable during the last week. Of the 10,347 institutionalized individuals, 5,090 (49,2%) remained asymptomatic for ≥14 days. A total of 854/10,347 deaths (8.3%) were reported; 383 of these deaths (44.8%) were suspected/confirmed cases. The number of isolated health care workers remained high over the 30 days, while the number of suspected cases decreased during the last 2 weeks. The number of high-risk long-term care facilities decreased from 19/196 (9.5%) to 3/196 (1.5%). Conclusions COVIDApp can help clinicians rapidly detect and remotely monitor suspected and confirmed cases of COVID-19 among institutionalized individuals, thus limiting the risk of spreading the virus. The platform shows the progression of infection in real time and can aid in designing new monitoring strategies.

BACKGROUND The coronavirus disease (COVID-19) pandemic has caused an unprecedented worldwide public health crisis that requires new management approaches. COVIDApp is a mobile app that was adapted for the management of institutionalized individuals in long-term care facilities. OBJECTIVE The aim of this paper is to report the implementation of this innovative tool for the management of long-term care facility residents as a high-risk population, specifically for early identification and self-isolation of suspected cases, remote monitoring of mild cases, and real-time monitoring of the progression of the infection. METHODS COVIDApp was implemented in 196 care centers in collaboration with 64 primary care teams. The following parameters of COVID-19 were reported daily: signs/symptoms; diagnosis by reverse transcriptase–polymerase chain reaction; absence of symptoms for ≥14 days; total deaths; and number of health care workers isolated with suspected COVID-19. The number of at-risk centers was also described. RESULTS Data were recorded from 10,347 institutionalized individuals and up to 4000 health care workers between April 1 and 30, 2020. A rapid increase in suspected cases was seen until day 6 but decreased during the last two weeks (from 1084 to 282 cases). The number of confirmed cases increased from 419 (day 6) to 1293 (day 22) and remained stable during the last week. Of the 10,347 institutionalized individuals, 5,090 (49,2%) remained asymptomatic for ≥14 days. A total of 854/10,347 deaths (8.3%) were reported; 383 of these deaths (44.8%) were suspected/confirmed cases. The number of isolated health care workers remained high over the 30 days, while the number of suspected cases decreased during the last 2 weeks. The number of high-risk long-term care facilities decreased from 19/196 (9.5%) to 3/196 (1.5%). CONCLUSIONS COVIDApp can help clinicians rapidly detect and remotely monitor suspected and confirmed cases of COVID-19 among institutionalized individuals, thus limiting the risk of spreading the virus. The platform shows the progression of infection in real time and can aid in designing new monitoring strategies.

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.

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

RESUMEN Introducción: La Brucelosis es una zoonosis común y en muchos países es un problema sanitario prevalente. En Paraguay no se ha encontrado evidencia de los conocimientos que tienen los trabajadores de hatos lecheros y las prácticas preventivas que utilizan. Objetivo: Evaluar el conocimiento, las prácticas de prevención y de bioseguridad sobre Brucelosis de los trabajadores expuestos a riesgo en hatos lecheros del departamento de Caaguazú, Paraguay. Materiales y métodos: Se realizó un estudio transversal, en una muestra representativa de establecimientos ganaderos del Departamento de Caaguazú. De mayo a junio de 2017 se entrevistó a 720 trabajadores de 360 hatos lecheros, utilizando un cuestionario estructurado, con preguntas cerradas. Se obtuvo información de los conocimientos, prácticas de prevención y bioseguridad sobre Brucelosis. Resultados: La mediana de edad de los trabajadores fue 34 años, 70% eran hombres. El 11,7% era analfabeto y 62,1% solo culminó la primaria. El 90% se desempeñaba como tambero/ordeñador. El 64% manifestó que no conocía la enfermedad, 73,6% ignoraba la forma en que se adquiere la enfermedad, 71,5% nunca recibió información acerca de la Brucelosis. El 73,3% no tenía conocimientos de las prácticas preventivas. Todos consumían subproductos lácteos sin pasteurizar, principalmente queso paraguay Conclusión: Existe desconocimiento de la enfermedad y la forma de transmisión. Las prácticas de riesgo son frecuentes. Es necesario implementar programas de educación y concienciación sobre la Brucelosis. ABSTRACT Background: Brucellosis is a common zoonosis and in many countries it is a prevalent health problem. In Paraguay, no evidence has been found of the knowledge that dairy herd workers have and the preventive practices they use. Objective: To evaluate the knowledge, prevention and biosecurity practices on Brucellosis of workers exposed to risk in dairy herds of Caaguazú. Materials and methods: A cross-sectional study was carried out in a representative sample of livestock establishments in the Department of Caaguazú. From May to June 2017, 720 workers from 360 dairy farms were interviewed, using a structured questionnaire with closed questions. Information on the knowledge, prevention and biosecurity practices on brucellosis was obtained. Result: The median age of the workers was 34 years, 70% were men. 11.7% were illiterate and 62.1% only completed the primary. 90% worked as a tambero/milker. Sixty-four percent said they did not know about the disease, 73.6% did not know how the disease was acquired, 71.5% never received information about brucellosis. 73.3% had no knowledge of preventive practices. All consumed unpasteurized dairy byproducts, mainly Paraguayan cheese Conclusion: There is a lack of knowledge of the disease and the way of transmission. Risk practices are frequent. It is necessary to implement education and awareness programs on brucellosis.

OBJECTIVES Cobicistat seems to have a low rate of adverse events compared with ritonavir. METHODS This restrospective observational study to evaluated changes in lipid parameters and the percentage of subjects with dyslipidemia in virologically suppressed HIV-infected patients who were receiving a regimen containing darunavir/ritonavir and were then switched from ritonavir to cobicistat, carried out from December 2015 to May 2016, included 299 HIV-1-infected patients who were on stable antiretroviral treatment including darunavir/ritonavir (monotherapy, bitherapy or triple therapy for at least 6 months) and were then switched from ritonavir to cobicistat. Lipid parameters, as well as plasma HIV-1 RNA and CD4 cell counts, were recorded at baseline just before the switch, and 24 weeks after the switch. Patients were stratified according to the presence of hypercholesterolaemia [baseline total cholesterol > 200 mg/dL and/or low-density lipoprotein (LDL) cholesterol > 130 mg/dL] or hypertriglyceridaemia (baseline triglyceride levels > 200 mg/dL). RESULTS Two hundred and ninety-nine patients were enrolled in the study. Fifty-two per cent of the total study population showed dyslipidaemia at baseline. All patients maintained HIV-1 RNA ≤ 50 HIV-1 RNA copies/mL at week 24. No statistically significant changes were seen in CD4 T-cell count from baseline to week 24 [654 (298) to 643 (313) cells/μL; P = 0.173]. When patients were stratified according to the presence of hypercholesterolaemia at baseline (n = 124), significant changes were observed in total cholesterol (P

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 Information and communication technologies are key to improving health and ensuring a quality, modern, and sustainable health system. They could prove particularly useful in the care of patients with chronic conditions such as diabetes, obesity, cardiovascular disease, and HIV infection. It could also play a role in the prevention of comorbid conditions OBJECTIVE To determine the usefulness of an app designed specifically for HIV-infected patients aged 60 years or older by evaluating its usability. To assess changes in patient satisfaction with the app, adherence to treatment, and quality of health care in HIV-infected patients who use the app METHODS Randomized clinical trial, including 2 groups: 1) an experimental group comprising patients using the app + routine medical care and 2) a control group. The usability of the app and patient satisfaction were evaluated in the app group at weeks 24 and 48. Quality of life, adherence to treatment, and clinical parameters were compared in both groups at 48 weeks RESULTS The study population comprised 100 patients (50 per group). Men accounted for 73%, median age was 65 (IQR, 63-69) years, 46% were men who have sex with men, and the median time with HIV infection was 21 (IQR 16-25) years. We found that 52.2% and 73.8% of patients in the app group used the app at weeks 24 and 48. Patients visited the app on a mean of 23.7 (±2.84) days over the 48 weeks. The total number of sessions was 6,177, and the mean session time was 6 minutes and 51 (±34.72) seconds.The most visualized screens were health counseling and medical records (laboratory results) (24.8% and 22.2%, respectively). Patients aged 60 to 65 years were the age group that most actively used the app compared with those aged over 65 years (P=.029). At week 48, 85.2% of patients thought that the app was useful, and 91.4% would recommend the app to friends or relatives. The app was well valued by participants (4.79 [±0.21] out of 5.00), and 64.6% thought that the app improved their health care. The number of face-to-face visits to the HIV unit during the study was 4.29 (±1.43) for the app group and 5.33 (±1.72) for the control group (P=.03). There were no significant differences in patient quality of life, adherence, or inter- and intragroup clinical parameters. CONCLUSIONS Our study shows the low usability of the app in HIV-infected patients, mainly among those aged over 65 years. Patients reported that the main use for the app was to receive health counseling and medical data (laboratory results). It is therefore necessary to promote knowledge of the app and motivate patients in this age group to use it.

Background Previous studies suggest that nonnucleoside reverse-transcriptase inhibitors (NNRTIs) cause faster virologic suppression, while ritonavir-boosted protease inhibitors (PI/r) recover more CD4 cells. However, individual trials have not been powered to compare clinical outcomes. Methods We searched databases to identify randomized trials that compared NNRTI- vs PI/r-based initial therapy. A metaanalysis calculated risk ratios (RRs) or mean differences (MDs), as appropriate. Primary outcome was death or progression to AIDS. Secondary outcomes were death, progression to AIDS, and treatment discontinuation. We calculated RR of virologic suppression and MD for an increase in CD4 cells at week 48. Results We included 29 trials with 9047 participants. Death or progression to AIDS occurred in 226 participants in the NNRTI arm and in 221 in the PI/r arm (RR, 1.03; 95% confidence interval, .87-1.22; 12 trials; n = 3825), death in 205 participants in the NNRTI arm vs 198 in the PI/r arm (1.04; 0.86-1.25; 22 trials; n = 8311), and progression to AIDS in 140 participants in the NNRTI arm vs 144 in the PI/r arm (1.00; 0.80-1.25; 13 trials; n = 4740). Overall treatment discontinuation (1.12; 0.93-1.35; 24 trials; n = 8249) and from toxicity (1.21; 0.87-1.68; 21 trials; n = 6195) were comparable, but discontinuation due to virologic failure was more common with NNRTI (1.58; 0.91-2.74; 17 trials; n = 5371). At week 48, there was no difference between NNRTI and PI/r in virologic suppression (RR, 1.03; 0.98-1.09) or CD4(+) recovery (MD, -4.7 cells; -14.2 to 4.8). Conclusions We found no difference in clinical and viro-immunologic outcomes between NNRTI- and PI/r-based therapy.

Background. Sarcopenia is a geriatric syndrome that leads to a loss of functionality and mortality. Methods. We assessed the prevalence of sarcopenia in HIV-infected patients attended in our HIV Unit who had at least two DXA scans from 2000 to 2016 (1,720 DXA scans from 860 individuals). Sarcopenia was determinate according to appendicular skeletal muscle mass index (ASM) calculated as the ratio between skeletal muscle mass index (SMI) by DXA and height2 (kg/m2). We stratified patients by gender and age (50 years) and according to the interval between DXAs (≤3, 3-7, 7-10, >10 years). The statistical analysis was performed using SPSS version 19. Results. Median (IQR) age was 52 (47; 57) years, and 76% were male. The median (IQR) time with HIV infection was 8 (3; 15) years. The prevalence of sarcopenia was 25.7% (95% CI, 22.8-28.7), more prevalent in those aged >50 years (27.8%). Stratifying by gender, 43% of women aged >50 years presented sarcopenia compared with 8.8% of men. The frequency of sarcopenia increased from 37.6% to 49.4% when interval between DXA was 7-10 years (n=109), significantly higher in women than in men (p=0.016). In addition to the traditional risk factors, time with HIV infection was associated with sarcopenia [RR 1.780 (95% CI, 1.314-2.411), p=0.001]. Conclusion. The prevalence and progression of sarcopenia in HIV-infected patients were high, mainly among women. Further studies are necessary to assess the best approaches to prevent this condition and its consequences.

Long-term results ( > 5 years) for synthetic substances used to repair facial lipoatrophy have not been published. We performed a cross-sectional study to evaluate the 10-year safety of polyacrylamide hydrogel (Aquamid) among the 751 patients from our unit who received facial infiltrations at least 10 years ago. Epidemiological and clinical data such as complications and patient satisfaction were collected. We also identified those patients who presented a facial infection at any time after infiltration. A total of 104 patients had received Aquamid at least 10 years ago. Before infiltrations, 24.0%, 41.3%, and 34.7% presented very severe, severe, and moderate facial lipoatrophy, respectively. After a mean (SD) of 10.3 (0.5) years since the infiltrations, 19.2%, 47.7%, and 31.7% of patients reported moderate, mild, and no signs of facial lipoatrophy. The values reported by physicians for the same categories were 1.9%, 10.6%, and 87.5%. Indurations were detected in 6.7% of patients and nodules in 3.8%. Five patients (4.8%) had a local infection. A further 15 patients with a shorter follow-up (less than 10 years) presented local infections (overall incidence considering the 751 patients who received infiltrations of Aquamid, 2.7%); the product had to be withdrawn in three cases. The majority of patients were highly satisfied (74.8%) or satisfied (23.4%) with the cosmetic results; among patients with severe or very severe lipoatrophy at baseline, 31.4% were satisfied and 65.7% were highly satisfied. Infiltrations with polyacrylamide hydrogel (Aquamid) are a safe strategy for the treatment of facial lipoatrophy in the long term. The rate of severe complications was low, and patient satisfaction with the cosmetic results was high. However, facial infections may appear in the long term. Therefore, HIV-infected patients who received synthetic substances should be carefully monitored over time.

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

Several studies have reported associations between lipid parameters and clinical progression of HIV infection. We performed a cross-sectional study including 468 antiretroviral-treated HIV-infected patients to investigate the impact of 13 polymorphisms of 9 genes affecting lipid metabolism and CD4 and CD8-T cell levels. Polymorphisms were identified in genes selected for their role in the development of atherogenic dyslipidemia, defined as triglycerides P1.7 mmol/L and high-density lipoprotein cholesterol (HDLc)

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.

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.

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.

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.

The aim of this study was to determine and compare changes in arterial oxygen saturation (SpOThis was a prospective observational study in healthy term infants. SpOA total of 216 healthy term infants were divided into three different groups: 136 (63%) born by vaginal delivery, 56 (26%) born by cesarean section with bonding, and 24 (11%) born by cesarean section without bonding. No difference in SpOIn healthy term newborns, maternal bonding in infants born by cesarean section did not have effects on SpO

Introduction: HIV-infected patients treated with Highly Active Antiretroviral Therapy (HAART) may be predisposed to hypertriglyceridemia, which gives rise to a highly atherogenic lipid profile known as atherogenic dyslipidemia (AD). We propose that genetic variability leaves some HIV-infected patients more predisposed to AD than others [1,2]. Methods: This was a cross-sectional, observational study conducted in 468 antiretroviral-treated HIV-infected patients attending at the outpatient clinic of a tertiary hospital over a 6-month period, who were classified as normolipidemic (n 173) or presenting with AD (triglycerides: 1.7 mmol/L and HDLc B1.02 [men] or 1.28 mmol/L [women]) (n 148). Polymorphisms were identified in the APOA5, APOC3, LPL, CETP, HL, MTP, APOE, LRP5 and VLDLR genes. Results: Atherogenic dyslipidemia was detected in 31% of patients, most of whom were men (77%). This group was also older and had higher levels of remnant lipoprotein cholesterol (RLPc) than normolipidemic patients. The polymorphisms rs328 in LPL, rs708272 in CETP and rs1800588 in HL were 10 40% significantly more frequent in normolipidemic patients. At least 1 of these polymorphisms was detected in 90% of normolipidemic patients; in AD patients, the percentage decreased to 75% (p 0.003). This effect was dependent on both the allele and the dose of HAART and independent of the regimen administered. The protective combination showed a trend towards higher HDLc (1.13 [0.40] vs 1.24 [0.23] mmol/L), lower triglycerides (2.23 [2.34] vs 1.89 [1.24] mmol/L) and lower RLPc (16.41 [11.42] vs 12.99 [11.69] mmol/L). Conclusion: Polymorphisms in LPL, CETP and HL protect HIV-infected patients from developing AD in a dose-dependent manner.

Although some clinical trials have studied the impact of treatments on bone mineral density (BMD), scarce data are available about the impact of protease inhibitor (PI) monotherapies on BMD. The aim of this study was to evaluate changes in BMD in patients after one, two, or three years of a PI monotherapy. This study included 46 HIV-infected patients who switched from a conventional triple antiretroviral strategy to a monotherapy with lopinavir/ritonavir (LPV/r) or darunavir/ritonavir (DRV/r) for one (one-year group, n=16), two (two-year group, n=20), and three (three-year group, n=10) years. BMD was assessed by dual-energy X-ray absorptiometry (DXA). The median percentage of change in total femur BMD was 0.20% after one, 0.79% after two, and -0.31% after three years. The change in lumbar spine was -0.08%, -0.14%, and 0.50% % after the same years. No significant differences were found when patients were classified regarding the type of PI and whether or not had previously received PI or tenofovir. However, patients who interrupted tenofovir or those who started with DRV/r had a higher BMD increment. Patients who had taken non-nucleoside reverse transcriptase inhibitors previously decreased BMD when started PIs. Monotherapy treatment with ritonavir-boosted protease inhibitors (both LPV/r and DRV/r) during one, two, or three years leads to the stabilization of BMD in HIV-infected patients with long-term virological suppression. Larger studies are necessary to compare the effect of starting or withdrawing PIs on BMD.

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.

Introduction : Polymorphisms in some host genes have a significant impact on susceptibility to HIV-1 infection and rate of disease progression [1,2]. The purpose of the current sub-study was to find out the relationship between polymorphisms in genes involved in the lipid metabolism and the CD4/CD8 T-cell counts. Methods : Sub-study of a cross-sectional, observational study conducted in 468 patients with HIV infection attended at the outpatient clinic to investigate individual genetic predisposition to atherogenic dyslipidemia (AD). All patients were genetically characterized and all polymorphisms were in Hardy–Weinberg equilibrium. Thirteen polymorphisms were selected from nine genes: APOA5 (rs662799 and rs3135506); APOC3 (rs5128 and rs4520); LPL (rs328 and rs268); CETP (rs708272); HL (rs1800588); MTP (rs1800591); APOE (rs7412 and rs429358); LRP5 (rs7116604); and VLDLR (rs1454626). Lipid and lipoprotein parameters, CD4 and CD8 T-cell counts and plasma HIV-RNA were determinate. The statistical analysis was performed using SPSS statistical software version 19 (SPSS Inc., Chicago, IL, USA). Results : We studied 468 HIV-infected patients (men, 77%), with a mean (SD) age of 45.9 (19.7) years. The mean CD4 T-cell count and nadir CD4 was 547 (459) and 193 (159) cells/µL, respectively; 78.7% of participants were virologically suppressed. Patients carrying rs3135506 in the APOA5 gene presented a 9% increase in circulating TG levels ( p =0.002) and 10% decrease in HDLc levels ( p =0.005). Such association of APOA5 towards dyslipidemia was accompanied by a 21% decrease of the CD4 T-cell count ( p =0.024) and a 19% increase in CD8 T-cell count ( p =0.002) in carriers of the rare allele in the APOA5 rs662799 polymorphism adjusted by age and gender. Patients carrying the rare allele in rs5128 (APOC3) had a 16% decrease in circulating CD4 T cells ( p =0.029); patients carrying rs1800591 (MTP) had a 29% decrease in CD4 T cells and 14% decrease in CD8 T cells ( p =0.018 and p =0.008, respectively); patients carrying the rare allele rs1800588 in HL had a 11% increase in CD4 T cells ( p =0.043); and carriers of the rs145626 in the VLDLR gene had 10% decrease in CD4 circulating T cells ( p =0.013). Conclusion : Variants in genes involved in the development of AD may also influence the immunological host–virus equilibrium in chronically HIV-infected subjects [2,3]. (Published: 2 November 2014) Citation : Abstracts of the HIV Drug Therapy Glasgow Congress 2014 Echeverria P et al. Journal of the International AIDS Society 2014, 17(Suppl 3) :19555 http://www.jiasociety.org/index.php/jias/article/view/19555 | http://dx.doi.org/10.7448/IAS.17.4.19555

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

Introduction Peak bone mass (PBM) is the amount of bone present at the end of skeletal maturation. It is an important determinant of osteoporotic fracture risk. Data on the PBM in the HIV-infected population are lacking. Design and methods We performed a multicenter (6 centers in Spain), case-control study to assess PBM using dual-energy x-ray absorptiometry. We studied HIV-infected patients aged 20-30 years and compared them with age- and gender-matched non-HIV-infected controls. We also assessed the predictive factors for a low PBM. Results We included 307 subjects: 232 HIV-infected patients and 75 non-HIV-infected controls. Bone mineral density was similar in both groups although differences were seen in the total femur T-score (-0.15SD versus +0.50SD, respectively, P = 0.018). The percentage of osteopenia and osteoporosis was higher in the HIV-infected patients (56.5% and 10.7%, respectively) than in the controls (50.7% and 4%, respectively; P = 0.019). Osteoporosis was more frequent in HIV-infected men than in control men and HIV-infected women (12.2% versus 5.5% and 4.8%, P = 0.033). Protease inhibitors and nadir CD4 T-cells were negatively associated with PBM, whereas fat and lean mass were positively associated with PBM. Conclusions Bone mineral density was similar between HIV-infected patients aged 20-30 years than in age- and gender-matched controls. However, lower femoral T-scores and higher rate of osteopenia and osteoporosis were seen in HIV-infected men. Therapy with protease inhibitors, nadir CD4 counts, and fat and lean mass were predictive factors of PBM. Given that these patients will be living with HIV infection for many years, every effort should be made to modify risk factors.

BACKGROUND Immune hyperactivation in immunodiscordant patients can induce residual HIV replication and limit CD4 T cell recovery. We assessed the impact of raltegravir intensification on CD4 T cell recovery and viral persistence. METHODS We performed a randomized, controlled, pilot trial. Patients with CD4 T cell counts

Background Switching from PIs to dolutegravir in virologically suppressed HIV-infected individuals has not been assessed. Objectives The principal aim was to assess the evolution of bone mineral density (BMD) when switching from a ritonavir-boosted PI to dolutegravir in HIV-infected patients with osteopenia or osteoporosis. The secondary objective was to assess the antiviral efficacy and safety of the switch therapy. Methods This randomized, multicentre study assessed changes in BMD, bone turnover markers, and antiviral efficacy and safety in 73 virologically suppressed patients with osteopenia/osteoporosis taking a ritonavir-boosted PI plus abacavir/lamivudine who were randomized to switch from PI to dolutegravir (DOLU group, n = 37) or continue with a PI (PI group, n = 36). Clinical Trials: NCT02577042. Results One and three patients from the DOLU and PI groups, respectively, withdrew prematurely (unrelated to treatment). At 48 weeks, 97.3% versus 91.7%, respectively, maintained viral suppression (snapshot analysis, ITT, M = F). No significant differences were seen between the groups in percentage change from baseline to week 48 in femoral ( P = 0.56) and lumbar spine ( P = 0.29) BMD, although lumbar spine BMD improved by 1.43% (-1.36; 2.92) in the DOLU group [0.12% (-2.83; 2.89) in the PI group]. Bone marker values did not vary significantly. At week 48, triglycerides were lower ( P < 0.001) and HDL cholesterol higher ( P = 0.027) in the DOLU group. Conclusions Dolutegravir + Kivexa ® was safe and well-tolerated in virologically suppressed patients receiving a PI-based regimen. The lipid profile was better, albeit without significant changes in BMD, probably because of the short follow-up.

Background: The high antiviral potency and low toxicity of saquinavir/ritonavir (SQV/r) prompted us to assess a viable strategy in chronic virologically suppressed HIV-infected patients. Methods: A randomized, multicenter pilot trial. Patients taking triple HAART with (VL < 50 copies/mL) and no history of virological failure with a protease inhibitor (PI) or PI-related resistance were assigned in a 2:1 ratio to receive SQV 1000 mg/ritonavir 100 mg BID (SQV/r group) or to continue with their habitual treatment (control group). Comparisons were performed using the Mann-Whitney test for medians, the t test or ANOVA for means, and the χ2 or Fishers exact test for proportions. Results: 28 patients were randomized: 17 to the SQV/r group and 11 to the control group. Only 1 patient from the SQV/r group experienced virological failure at week 48. A similar mean increase was observed in CD4+ T-cell counts in both groups at week 48. Three patients (17.6%) from the SQV/r group prematurely interrupted the study for reasons other than virological failure. HDL cholesterol increased significantly at week 48 in the SQV/r group (from 41±11 mg/dL to 56±35, P=.026); patients in the control group showed a decrease in LDL cholesterol (from 129±37 mg/dL to 107±17, P=.028). The median (IQR) trough plasma concentrations of SQV were 760 ng/mL (379.5-1332.25 ng/mL). Three patients had saquinavir concentrations lower than 100 ng/mL. Conclusion: SQV/r as monotherapy has proven to be a valid, safe, and economical option for virologically suppressed HIV-infected patients, especially in those who experience intolerance or toxicity with nucleoside analogs.

Introduction : HIV-infected patients treated with Highly Active Antiretroviral Therapy (HAART) may be predisposed to hypertriglyceridemia, which gives rise to a highly atherogenic lipid profile known as atherogenic dyslipidemia (AD). We propose that genetic variability leaves some HIV-infected patients more predisposed to AD than others [1,2]. Methods : This was a cross-sectional, observational study conducted in 468 antiretroviral-treated HIV-infected patients attending at the outpatient clinic of a tertiary hospital over a 6-month period, who were classified as normolipidemic (n=173) or presenting with AD (triglycerides: 1.7 mmol/L and HDLc < 1.02 [men] or 1.28 mmol/L [women]) (n=148). Polymorphisms were identified in the APOA5, APOC3, LPL, CETP, HL, MTP, APOE, LRP5 and VLDLR genes. Results : Atherogenic dyslipidemia was detected in 31% of patients, most of whom were men (77%). This group was also older and had higher levels of remnant lipoprotein cholesterol (RLPc) than normolipidemic patients. The polymorphisms rs328 in LPL, rs708272 in CETP and rs1800588 in HL were 10–40% significantly more frequent in normolipidemic patients. At least 1 of these polymorphisms was detected in 90% of normolipidemic patients; in AD patients, the percentage decreased to 75% (p=0.003). This effect was dependent on both the allele and the dose of HAART and independent of the regimen administered. The protective combination showed a trend towards higher HDLc (1.13 [0.40] vs 1.24 [0.23] mmol/L), lower triglycerides (2.23 [2.34] vs 1.89 [1.24] mmol/L) and lower RLPc (16.41 [11.42] vs 12.99 [11.69] mmol/L). Conclusion : Polymorphisms in LPL, CETP and HL protect HIV-infected patients from developing AD in a dose-dependent manner [3]. (Published: 2 November 2014) Citation : Abstracts of the HIV Drug Therapy Glasgow Congress 2014 Echeverria P et al. Journal of the International AIDS Society 2014, 17(Suppl 3) :19557 http://www.jiasociety.org/index.php/jias/article/view/19557 | http://dx.doi.org/10.7448/IAS.17.4.19557

Address: 1Hospital Clinic Universitari, Barcelona, Spain, 2Hospital de Bellvitge, Barcelona, Spain, 3Hospital de Sant Pau, Barcelona, Spain, 4Fundacio IrsiCaixa, Barcelona, Spain, 5Hospital Vall d'Hebron, Barcelona, Spain, 6Hospital General Universitario de Elche, Elche, Spain, 7Hospital del Mar, Barcelona, Spain, 8Hospital Gregorio Maranon, Madrid, Spain, 9Hospital Principe de Asturias, Madrid, Spain, 10Hospital Clinico San Carlos, Madrid, Spain and 11Hospital Clinic Universitari, Barcelona, Spain * Corresponding author

Methods This is a cross-sectional study to evaluate the bone mineral density (BMD) in HIV-infected patients from a HIV unit of a Spanish university hospital. All patients with at least one evaluation of BMD of total body, lumbar spine and femoral neck measured by dual-energy X-ray absorptiometry (DEXA) were included in the analysis. The MannWhitney U test was used to compare two populations (normal and abnormal bone mineralization), and the Kruskal Wallis test to compare normal, osteopenia and osteoporosis populations (based on the World Health Organization criteria). A uniand multivariant logistic regression were used to analyse the association between HIV disease status, demographics and antiretroviral treatments with the frequency of bone abnormalities.