Switching to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) plus darunavir/cobicistat in heavily antiretroviral-experienced, virologically suppressed HIV-infected adults receiving complex regimens.

OBJECTIVES: To evaluate the efficacy and safety of the two-pill regimen bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) plus darunavir/cobicistat as a switching strategy in heavily treatment-experienced people living with HIV (PLWH). METHODS: Multicentre, prospective, single-arm pilot clinical trial. Participants were virologically suppressed adults receiving a stable antiretroviral regimen of at least three pills from at least three drug families due to previous virological failures and/or toxicities with no documented resistance to integrase strand transfer inhibitors or darunavir (≥15 points, Stanford). Clinical and laboratory assessments were performed at 0, 4, 12, 24, 36 and 48 weeks. HIV-1 proviral DNA was amplified and sequenced by Illumina at baseline. Plasma bictegravir concentrations were determined in 22 patients using UHPLC-MS/MS. The primary study endpoint was viral load (VL)< 50 copies/mL at Week 48 (ITT). RESULTS: We enrolled 63 participants (92% men) with median baseline CD4 count of 515 cells/mm3 (IQR: 334.5-734.5), 24 years on ART (IQR: 15.9-27.8). The median number of pills was 4 (range: 3-10). At baseline, proviral DNA was amplified in 39 participants: 33/39 had resistance mutations. Three participants discontinued owing to toxicity. At 48 weeks, 95% had VL < 50 copies/mL by ITT and 100% by PP analysis. A modest increase was observed in the bictegravir plasma concentration, and a significant decrease in estimated glomerular filtration rate was observed only at Week 4, probably related to interaction with renal transporters. CONCLUSIONS: Our data suggest that BIC/FTC/TAF + darunavir/cobicistat is an effective, well-tolerated regimen that may improve convenience and, potentially, long-term success in stable heavily pre-treated PLWH.

Prevalence, progression, and management of advanced chronic kidney disease in a cohort of people living with HIV.

BACKGROUND: Advanced kidney disease is an emerging problem in people living with HIV despite sustained viral suppression. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Empowering Patients Through Virtual Care Delivery: Qualitative Study With Micropractice Clinic Patients and Health Care Providers.

BACKGROUND: Prior to the wider adoption of digital health technologies during the COVID-19 pandemic, applications of virtual care were largely limited to specialist visits and remote care using telehealth (phone or video) applications. Data sharing approaches using tethered patient portals were mostly built around hospitals and larger care systems. These portals offer opportunities for improved communication, but despite a belief that care has improved, they have so far shown few outcome improvements beyond medication adherence. Less is known about use of virtual care and related tools in the outpatient context and particularly in rural community contexts. OBJECTIVE: This study aims to reflect on the opportunities and barriers for sustainable virtual care through an example of a digitally enabled rural micropractice, which has provided 10%-15% virtual care since 2016 and 70% virtual care since March 2020. METHODS: Three focus groups, 1 with providers (physician and medical office manager) and 2 with a total of 8 patients from a rural micropractice in British Columbia, were conducted in November 2020 and December 2020. Virtual care delivery was explored through the topics of communication approach, mixing virtual and in-person care, the practice team's journey in developing these approaches, and provider and patient satisfaction with the care model. Interviews were transcribed, checked for accuracy against recordings, and thematically analyzed. RESULTS: Both patients and providers reported ease of communication and high satisfaction. Either could initiate communication, and patients found the ability to share health information asynchronously through the portal allowed time to reflect and prepare their thoughts. Patients were highly engaged and reported feeling empowered and true partners in their health care, although they noted limited care coordination with specialists. The mix of virtual and in-person visits was highly regarded by patients and providers, and patients reported feeling safe and cared for 24/7, although both expressed concern about work spilling into the provider's home life. The physician worried about missed diagnoses with virtual care. With respect to establishing the micropractice, solutions took about 5 years to optimize, with providers noting a learning curve requiring technical support for both themselves and their patients and a willingness to respond to patient feedback to identify the best solutions. Despite a mature virtual practice, patients reported deferred care due to COVID-19. CONCLUSIONS: The micropractice's hybrid care model encouraged patients to be true partners in their care and resulted in high patient engagement and satisfaction; yet, success may rely on the patient population being willing to engage and being comfortable with technology. Barriers lie in gaps in care coordination and provider fear that signs or symptoms more evident with an in-person exam could be missed. Even in this setting, deferral of care in light of COVID-19 was present, and opportunities to address care gaps should be sought.

Ultrasound-Based Assessment of Preperitoneal Fat as a Surrogate Marker of Cardiovascular Risk: Comparative Study Between People Living with HIV and Controls.

Optimal management of cardiovascular disease should start with the identification of subjects at subclinical stages. However, available tools are not always accurate or affordable. We assess the usefulness of ultrasound-guided measurement of abdominal fat layers as a surrogate marker of cardiovascular risk. We performed a cross-sectional, case-control, exploratory, pilot study in 10 people living with HIV (PLWH) and 10 HIV-uninfected subjects (control group) matched for age, sex, and body mass index. All participants were men 45-60 years of age, with no active disease or previous abdominal surgery; the PLWH group had been virologically suppressed for ≥2 years under stable antiretroviral therapy. The thickness of abdominal superficial and deep subcutaneous fat, preperitoneal fat, omental (periaortic) fat, and retroperitoneal (perirenal) fat was compared between both groups. Correlations between fat layers and traditional markers of cardiovascular risk were assessed. The thickness of most layers was always higher among PLWH. The differences were statistically significant for the preperitoneal fat layer (p = .04). The presence of atherosclerotic plaque was correlated with the preperitoneal fat layer in the PLWH group (odds ratio = 1.49, p = .02), and metabolic syndrome was correlated with superficial subcutaneous fat, although this was low (odds ratio = 0.54, p = .02). In the control group, several associations were found between carotid intima media thickness and abdominal fat layers. All abdominal fat layers were thicker in the PLWH group, especially preperitoneal fat, and several associations were found between specific fat layers and traditional cardiovascular risk markers. Our results suggest that the thickness of abdominal fat layers, assessed by ultrasound, could be a marker of cardiovascular risk. However, further studies with larger populations are required to confirm these findings.

Accentuated aging associated with HIV in a Mediterranean setting occurs mainly in persons aged>70 years: a comparative cohort study (Over50 cohort).

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.

Remote Health Monitoring in the Workplace for Early Detection of COVID-19 Cases during the COVID-19 Pandemic Using a Mobile Health Application: COVIDApp.

Background: COVIDApp is a platform created for management of COVID-19 in the workplace. Methods: COVIDApp was designed and implemented for the follow-up of 253 workers from seven companies in Catalonia. The assessment was based on two actions: first, the early detection and management of close contacts and potential cases of COVID-19, and second, the rapid remote activation of protocols. The main objectives of this strategy were to minimize the risk of transmission of COVID-19 infection in the work area through a new real-time communication channel and to avoid unnecessary sick leave. The parameters reported daily by workers were close contact with COVID cases and signs and/or symptoms of COVID-19. Results: Data were recorded between 1 May and 30 November 2020. A total of 765 alerts were activated by 76 workers: 127 green alarms (16.6%), 301 orange alarms (39.3%), and 337 red alarms (44.1%). Of all the red alarms activated, 274 (81.3%) were activated for symptoms potentially associated with COVID-19, and 63 (18.7%) for reporting close contact with COVID-19 cases. Only eight workers (3.1%) presented symptoms associated with COVID-19 infection. All of these workers underwent RT-PCR tests, which yielded negative results for SARS-CoV2. Three workers were considered to have had a risk contact with COVID-19 cases; only 1 (0.4%) asymptomatic worker had a positive RT-PCR test result, requiring the activation of protocols, isolation, and contact tracing. Conclusions: COVIDApp contributes to the early detection and rapid activation of protocols in the workplace, thus limiting the risk of spreading the virus and reducing the economic impact caused by COVID-19 in the productive sector. The platform shows the progression of infection in real time and can help design new strategies.

A Specific Mobile Health Application for Older HIV-Infected Patients: Usability and Patient's Satisfaction.

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.

Potential prescribing issues among older HIV-infected subjects in a Mediterranean cohort: Does the current prevalence give cause for concern?

AIMS: 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. METHODS: 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 χ2 test or Fisher exact test. RESULTS: The 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%). CONCLUSION: 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.

A randomized pilot trial to evaluate the benefit of the concomitant use of atorvastatin and Raltegravir on immunological markers in protease-inhibitor-treated subjects living with HIV.

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 TRIALS REGISTRATION: NCT02577042.

COVIDApp as an Innovative Strategy for the Management and Follow-Up of COVID-19 Cases in Long-Term Care Facilities in Catalonia: Implementation Study.

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.

Arterial oxygen saturation and heart rate in term newborn in the first hour after birth. / Saturación arterial de oxígeno y frecuencia cardíaca en recién nacidos de término sanos durante la primera hora post nacimiento.

INTRODUCTION: The pulse oximeter has been useful in the cardiorespiratory evaluation of the newborn. OBJECTIVE: To assess arterial oxygen saturation (SpO2) and heart rate (HR) in newborns in the first 60 minutes after birth. PATIENTS AND METHOD: Prospective observational study in healthy term newborns, delivered vaginally or by cesarean section, with maternal bonding, carried out at sea level. A continuous post- ductal SpO2 and HR record were obtained from minute 1 to 10 after birth, and then at 15, 30 and 60 minutes. The SpO2 and HR were measured with a Nellcor pulse oximeter. The software Stata v.14 was used for the statistical analysis. RESULTS: 324 healthy term newborns that met the inclusion criteria were included, of which 160 born vaginally and 164 by cesarean section. The SpO2 increased progres sively from minute 1 (58.7%) to minute 10 (94.5%). Newborns delivered vaginally had a significantly higher SpO2 until minute 10 after birth than those born by cesarean section (p < 0.001). In newborns delivered vaginally, HR was significantly higher in the first two minutes after birth, and then from minute 10 to 60 (p < 0.003). There were no differences by gender in SpO2 and HR. CONCLUSION: In term newborns, the SpO2 increases progressively, being higher in the first 10 minutes in those born vaginally. In newborns delivered vaginally, a higher HR was also observed in the first and last minutes evaluated.

Saturación arterial de oxígeno y frecuencia cardíaca en recién nacidos de término sanos durante la primera hora post nacimiento / Arterial oxygen saturation and heart rate in term newborn in the first hour after birth

INTRODUCCIÓN: El oxímetro de pulso ha sido útil en la evaluación cardiorrespiratoria del neonato. OBJETIVO: Evaluar la saturación arterial de oxígeno (SpO2) y frecuencia cardíaca (FC) en recién nacidos (RN) en los pri meros 60 minutos después del nacimiento. PACIENTES Y MÉTODO: Estudio observacional prospectivo en RN de término sanos, nacidos por vía vaginal o cesárea, con apego materno, efectuado a nivel del mar. Se obtuvo registro continuo de SpO2 post-ductal y de FC desde el minuto 1 al 10 post-natal, y luego a los 15, 30 y 60 minutos. La SpO2 y FC se midieron con un oxímetro de pulso Nellcor. Para el análisis estadístico se utilizó programa Stata v.14. RESULTADOS: Se enrolaron 324 RNT sanos, que cum plieron criterios de inclusión, de los cuales 160 nacieron por vía vaginal y 164 por cesárea. La SpO2 aumentó progresivamente desde el minuto 1 (58,7%) hasta el minuto 10 (94,5%). Los RN por vía vaginal presentaron una SpO2 significativamente mayor hasta el minuto 10 post-natal respecto a los nacidos por cesárea (p < 0,001). En los neonatos nacidos por vía vaginal, la FC fue significativamente mayor en los 2 primeros minutos post-natales, y luego desde el minuto 10 al 60 (p < 0,003). No se encontraron diferencias por género en SpO2 y FC. CONCLUSIÓN: En RNT la SpO2 post-natal aumenta progresivamente, siendo mayor en los primeros 10 minutos en los nacidos por vía vaginal. En los RN por vía vaginal se observó también una FC mayor en los primeros y últimos minutos evaluados.

INTRODUCTION: The pulse oximeter has been useful in the cardiorespiratory evaluation of the newborn. OBJECTIVE: To assess arterial oxygen saturation (SpO2) and heart rate (HR) in newborns in the first 60 minutes after birth. PATIENTS AND METHOD: Prospective observational study in healthy term newborns, delivered vaginally or by cesarean section, with maternal bonding, carried out at sea level. A continuous post ductal SpO2 and HR record were obtained from minute 1 to 10 after birth, and then at 15, 30 and 60 minutes. The SpO2 and HR were measured with a Nellcor pulse oximeter. The software Stata v.14 was used for the statistical analysis. RESULTS: 324 healthy term newborns that met the inclusion criteria were included, of which 160 born vaginally and 164 by cesarean section. The SpO2 increased progres sively from minute 1 (58.7%) to minute 10 (94.5%). Newborns delivered vaginally had a significantly higher SpO2 until minute 10 after birth than those born by cesarean section (p < 0.001). In newborns delivered vaginally, HR was significantly higher in the first two minutes after birth, and then from minute 10 to 60 (p < 0.003). There were no differences by gender in SpO2 and HR. CONCLUSION: In term newborns, the SpO2 increases progressively, being higher in the first 10 minutes in those born vaginally. In newborns delivered vaginally, a higher HR was also observed in the first and last minutes evaluated.

High Prevalence of Sarcopenia in HIV-Infected Individuals.

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 (<40, 41-50, and >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.

High risk and probability of progression to osteoporosis at 10 years in HIV-infected individuals: the role of PIs.

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.

Switching from a ritonavir-boosted PI to dolutegravir as an alternative strategy in virologically suppressed HIV-infected individuals.

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.

Impact of protease inhibitors on the evolution of urinary markers: Subanalyses from an observational cross-sectional study.

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.

Arterial oxygen saturation and heart rate after birth in newborns with and without maternal bonding.

BACKGROUND: The aim of this study was to determine and compare changes in arterial oxygen saturation (SpO2 ) and heart rate (HR) in healthy term infants with and without maternal bonding. METHOD: This was a prospective observational study in healthy term infants. SpO2 and HR were recorded from 1 to 10 min after birth. After this, SpO2 and HR were registered at 15, 30 and 60 min and then at 12 and 24 h after birth. SpO2 and HR were measured with a pulse oximeter. RESULTS: A 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 SpO2 was found in babies born by cesarean section with or without maternal bonding. In neonates delivered vaginally, SpO2 was significantly higher during the first 10 min after birth than in neonates born by cesarean section with bonding (P < 0.05). Compared with infants born by cesarean section without bonding, this tendency was not significant. In general, HR was similar across groups, although, for infants born by cesarean section, neonates who received bonding had lower HR from 6 to 8 min (P < 0.05). CONCLUSIONS: In healthy term newborns, maternal bonding in infants born by cesarean section did not have effects on SpO2 . Some differences were observed in HR between infants born by cesarean section with and without bonding.

Nonnucleoside Reverse-transcriptase Inhibitor- vs Ritonavir-boosted Protease Inhibitor-based Regimens for Initial Treatment of HIV Infection: A Systematic Review and Metaanalysis of Randomized Trials.

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.

Prospective Study to Assess Progression of Renal Markers after Interruption of Tenofovir due to Nephrotoxicity.

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 <60 mL/min/1.73 m2 (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.