Evolving AIDS- and non-AIDS Mortality and Predictors in the PISCIS Cohort of People Living With HIV in Catalonia and the Balearic Islands (Spain), 1998-2020.

Background: Effective antiretroviral therapy (ART) has substantially reduced acquired immunodeficiency syndrome (AIDS)-related deaths, shifting the focus to non-AIDS conditions in people living with human immunodeficiency virus (HIV) (PLWH). We examined mortality trends and predictors of AIDS- and non-AIDS mortality in the Population HIV Cohort from Catalonia and Balearic Islands (PISCIS) cohort of PLWH from 1998 to 2020. Methods: We used a modified Coding Causes of Death in HIV protocol, which has been widely adopted by various HIV cohorts to classify mortality causes. We applied standardized mortality rates (SMR) to compare with the general population and used competing risks models to determine AIDS-related and non-AIDS-related mortality predictors. Results: Among 30 394 PLWH (81.5% male, median age at death 47.3), crude mortality was 14.2 per 1000 person-years. All-cause standardized mortality rates dropped from 9.6 (95% confidence interval [CI], 8.45-10.90) in 1998 through 2003 to 3.33 (95% CI, 3.14-3.53) in 2015 through 2020, P for trend = .0001. Major causes were AIDS, non-AIDS cancers, cardiovascular disease, AIDS-defining cancers, viral hepatitis, and nonhepatitis liver disease. Predictors for AIDS-related mortality included being aged ≥40 years, not being a man who have sex with men, history of AIDS-defining illnesses, CD4 < 200 cells/µL, ≥2 comorbidities, and nonreceipt of ART. Non-AIDS mortality increased with age, injection drug use, heterosexual men, socioeconomic deprivation, CD4 200 to 349 cells/µL, nonreceipt of ART, and comorbidities, but migrants had lower risk (adjusted hazard risk, 0.69 [95% CI, .57-.83]). Conclusions: Mortality rates among PLWH have significantly decreased over the past 2 decades, with a notable shift toward non-AIDS-related causes. Continuous monitoring and effective management of these non-AIDS conditions are essential to enhance overall health outcomes.

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.

HIV infection is associated with upregulated circulating levels of the inflammaging miR-21-5p.

BACKGROUND: HIV infection produces a chronic inflammation which leads to early aging of people living with HIV. Even though antiretroviral treatments (ART) have significantly increased HIV patient survival, an underlying chronic inflammation persists leading to HIV-related comorbidities. In this context, changes in microRNAs (miRNAs) expression may contribute to this inflammatory response. This study aims to detect differential expression of circulating miRNAs in treatment-naïve HIV-infected individuals compared to uninfected controls and evaluation of altered miRNAs after one year of ART. METHODS: Serum from patients and controls was collected at baseline and after 48-weeks on ART in HIV-treated patients. Circulating miRNAs were analysed using next generation sequencing. RESULTS: A total of 32 HIV patients and 10 controls were recruited. Of HIV+ individuals, 7 were long-term non-progressors (elite controllers), a group of HIV-infected individuals that spontaneously control the infection. Higher circulating levels of miR-21-5p, and lower levels of miR-6503-3p and miR-3135b were detected in HIV+ progressors. After one year of ART, these miRNAs remain altered. Moreover, miR-21-5p and miR-6503-3p were also altered in elite controllers compared to control group. In silico analyses showed that miR-21-5p target pathways are related to inflammation mechanisms and immune system. CONCLUSION: miR-21-5p circulating levels are involved in inflammation and oxidative stress mechanisms in HIV patients even after one year of ART or in elite controllers.

Switching to Dolutegravir/lamivudine or Bictegravir/Emtricitabine/Tenofovir alafenamide. A comparative real-world study.

BACKGROUND: This real-world study compared the safety and effectiveness of Dolutegravir/lamivudine (D/L) and Bictegravir/Emtricitabine/Tenefovir alafenamide (B/F/T) switch therapy regimens for people living with HIV (PLWH). METHODS: The retrospective study conducted from April 2019 to November 2022, included PLWH with < 50 copies/mL of HIV-RNA prior to recruitment who initiated either D/L or B/F/T switching therapy. The primary objective was to evaluate treatment discontinuation rates; safety and virologic outcomes were also evaluated. RESULTS: 690 PLWH were included, 358 in the D/L and 332 in the B/F/T, and a median follow-up of 728 and 1013 days, respectively. The discontinuation proportions were 8.7% (31 participants, incidence rate of 4.44 per 100 PYFU in the D/L group and 15.3% (51 participants, incidence rate of 6.25 per 100 PYFU) in the B/F/T group. The adjusted hazard ratio for B/F/T discontinuation compared to D/L was 1.20 (95% CI: 0.71;2.0; p = 0.494). Virologic failure (VL > 200 copies/mL in two consecutive measurements) occurred in 1.1% and 0.9% of patients in the D/L and B/F/T groups, respectively. Notably, one patient in D/L group with severe non-adherence and virologic failure developed resistance mutations. CONCLUSIONS: Switching to either B/T/F or D/L treatment for PLWH was effective and well tolerated in this real-world study. Treatment discontinuation rates did not significantly differ between the two regimens.

Cardiovascular events in delayed presentation of HIV: the prospective PISCIS cohort study.

Objectives: People with HIV (PWH) have a higher cardiovascular risk than the general population. It remains unclear, however, whether the risk of cardiovascular disease (CVD) is higher in late HIV presenters (LP; CD4 ≤ 350 cells/µL at HIV diagnosis) compared to PWH diagnosed early. We aimed to assess the rates of incident cardiovascular events (CVEs) following ART initiation among LP compared to non-LP. Methods: From the prospective, multicentre PISCIS cohort, we included all adult people with HIV (PWH) initiating antiretroviral therapy (ART) between 2005 and 2019 without prior CVE. Additional data were extracted from public health registries. The primary outcome was the incidence of first CVE (ischemic heart disease, congestive heart failure, cerebrovascular, or peripheral vascular disease). The secondary outcome was all-cause mortality after the first CVE. We used Poisson regression. Results: We included 3,317 PWH [26 589.1 person/years (PY)]: 1761 LP and 1556 non-LP. Overall, 163 (4.9%) experienced a CVE [IR 6.1/1000PY (95%CI: 5.3-7.1)]: 105 (6.0%) LP vs. 58 (3.7%) non-LP. No differences were observed in the multivariate analysis adjusting for age, transmission mode, comorbidities, and calendar time, regardless of CD4 at ART initiation [aIRR 0.92 (0.62-1.36) and 0.84 (0.56-1.26) in LP with CD4 count <200 and 200- ≤ 350 cells/µL, respectively, compared to non-LP]. Overall mortality was 8.5% in LP versus 2.3% in non-LP (p < 0.001). Mortality after the CVE was 31/163 (19.0%), with no differences between groups [aMRR 1.24 (0.45-3.44)]. Women vs. MSM and individuals with chronic lung and liver disease experienced particularly high mortality after the CVE [aMRR 5.89 (1.35-25.60), 5.06 (1.61-15.91), and 3.49 (1.08-11.26), respectively]. Sensitivity analyses including only PWH surviving the first 2 years yielded similar results. Conclusion: CVD remains a common cause of morbidity and mortality among PWH. LP without prior CVD did not exhibit an increased long-term risk of CVE compared with non-LP. Identifying traditional cardiovascular risk factors is essential for CVD risk reduction in this population.

Development and Validation of a Risk Score for Predicting Non-Adherence to Antiretroviral Therapy.

Several patient-related factors that influence adherence to antiretroviral therapy (ART) have been described. However, studies that propose a practical and simple tool to predict nonadherence after ART initiation are still scarce. In this study, we develop and validate a score to predict the risk of nonadherence in people starting ART. The model/score was developed and validated using a cohort of people living with HIV starting ART at the Hospital del Mar, Barcelona, between 2012 and 2015 (derivation cohort) and between 2016 and 2018 (validation cohort),. Adherence was evaluated every 2 months using both pharmacy refills and patient self-reports. Nonadherence was defined as taking <90% of the prescribed dose and/or ART interruption for more than 1 week. Predictive factors for nonadherence were identified by logistic regression. Beta coefficients were used to develop a predictive score. Optimal cutoffs were identified using the bootstrapping methodology, and performance was evaluated with the C statistic. Our study is based on 574 patients: 349 in the derivation cohort and 225 in the validation cohort. A total of 104 patients (29.8%) of the derivation cohort were nonadherent. Nonadherence predictors were patient prejudgment; previous medical appointment failures; cultural and/or idiomatic barriers; heavy alcohol use; substance abuse; unstable housing; and severe mental illness. The cutoff point (receiver operating characteristic curve) for nonadherence was 26.3 (sensitivity 0.87 and specificity 0.86). The C statistic (95% confidence interval) was 0.91 (0.87-0.94). These results were consistent with those predicted by the score in the validation cohort. This easy-to-use, highly sensitive, and specific tool could be easily used to identify patients at highest risk for nonadherence, thus allowing resource optimization and achieving optimal treatment goals.

Changes in bone quality after switching from a TDF to a TAF based ART: A pilot randomized study.

Background: The impact of tenofovir disoproxil fumarate (TDF) antiretroviral (ART) regimens on bone health has been characterized mostly by bone mineral density (BMD), but recently also by bone quality (BQ). The aim of this pilot study is to assess the changes in BMD and BQ after switch from TDF to tenofovir alafenamide (TAF) ART. Methods: HIV individuals receiving TDF-based ART were randomized to switch to Bictegravir-TAF-Emtricitabine or to remain in the same regimen. At baseline and 24-weeks after randomization, participants underwent bone mineral density (BMD) by DXA and BQ assessment using bone microindentation, a validated technique that measures bone tissue quality expressed as bone material strength index (BMSi). A panel of plasma bone turnover biomarkers were measured by ELISA at the same time-points. Values are expressed as median [interquartile range] and non-parametric tests were used where appropriate. Results: A total of 24 HIV individuals were included in the study, 19 of which were men (80%). Median age at baseline was 43 years (IQR 38-54). Half of individuals were allocated in the TDF group while the other half changed to TAF treatment. No differences at baseline between both groups were detected in any parameter. Non-significant changes nor in lumbar or femoral BMD at week 24 was found in any regimen. In contrast, there was an increase in BMSi in the TAF arm at 24 weeks, and thus an improvement in BQ[81.6 (79-83) to 86 (80-88) (+5.1%);p=0.041], whereas the TDF arm remained stable from 82 (76-85) at baseline to 82 (73-83);p=0.812. Hence, at week 24 there were significant differences in BQ between arms (p=0.049). A reduction in bone formation markers was found at week 24 in both regimens: N-terminal propeptide of type-1 collagen decreased a 20% (-35 - -0.6); p=0.031 with TAF and -16% (-25 - -5); p=0.032 with TDF. Also a decrease in bone resorption marker C-telopeptide with TAF was detected [-10% (-19 - -5);p=0.028] but not with TDF (p=0.232), suggesting a less metabolically active bone after switching to TAF. Conclusion: A bone quality improvement was found after switching from a TDF to a TAF based ART independently of BMD, suggesting that the bone health benefits of TAF may extend beyond BMD. Future research should be directed to confirm these findings and to identify the underlying mechanisms of ART related bone toxicity.

Who is lost to follow-up in HIV care? Assessment of care retention over time and the impact of COVID-19. Longitudinal analysis of the PISCIS cohort.

INTRODUCTION: People living with HIV who are lost to follow-up have a greater risk of health deterioration, mortality, and community transmission. OBJECTIVE: Our aim was to analyse both how rates of loss to follow-up (LTFU) changed between 2006 and 2020 and how the COVID-19 pandemic affected these rates in the PISCIS cohort study of Catalonia and the Balearic Islands. METHODS: We analysed socio-demographic and clinical characteristics of LTFU yearly and with adjusted odds ratios to assess the impact of these determinants on LTFU in 2020 (the year of COVID-19). We used latent class analysis to categorize classes of LTFU based on their socio-demographic and clinical characteristics at each year. RESULTS: In total, 16.7% of the cohort were lost to follow-up at any time in the 15 years (n = 19 417). Of people living with HIV who were receiving follow-up, 81.5% were male and 19.5% were female; of those who were lost to follow-up, 79.6% and 20.4% were male and female, respectively (p < 0.001). Although rates of LTFU increased during COVID-19 (1.11% vs. 0.86%, p = 0.024), socio-demographic and clinical factors were similar. Eight classes of people living with HIV who were lost to follow-up were identified: six for men and two for women. Classes of men (n = 3) differed in terms of their country of birth, viral load (VL), and antiretroviral therapy (ART); classes of people who inject drugs (n = 2) differed in terms of VL, AIDS diagnosis, and ART. Changes in rates of LTFU included higher CD4 cell count and undetectable VL. CONCLUSIONS: The socio-demographic and clinical characteristics of people living with HIV changed over time. Although the circumstances of the COVID-19 pandemic increased the rates of LTFU, the characteristics of these people were similar. Epidemiological trends among people who were lost to follow-up can be used to prevent new losses of care and to reduce barriers to achieve Joint United Nations Programme on HIV/AIDS 95-95-95 targets.

An Abnormal Inflammatory Pattern Associated with Long-Term Non-Progression of HIV Infection Impacts Negatively on Bone Quality.

Introduction. Long-term non-progressors (LTNPs) are HIV-infected individuals (HIV+) whose viral replication is controlled. However, these individuals experience complications associated with HIV, among them, bone remodeling impairment. This study aims to perform a comprehensive bone health assessment and its association with the inflammatory status of HIV+ LTNPs. A cross-sectional study was conducted comparing bone strength components (bone mineral density and bone tissue quality) between age-, sex-, and comorbidities-matched groups of HIV+ LTNPs, HIV+ progressors, and HIV-negative individuals. A panel of bone turnover and inflammatory biomarkers was measured in fasting plasma using ELISA. Bone tissue quality was assessed by bone microindentation, a technique that directly measures the bone resistance to fracture and yields a dimensionless quantifiable parameter called bone material strength (BMSi). Thirty patients were included: ten LTNPs, ten HIV+ progressors, and ten HIV-negative individuals. LTNPs showed an abnormal pattern of immune activation that was represented by significantly lower levels of anti-inflammatory cytokine IL-10 (p = 0.03), pro-inflammatory cytokine IL-8 (p = 0.01), and TNF-α (p < 0.001) with respect to the other groups. Regarding bone health, LTNPs presented lower BMSi, and thus, worse bone tissue quality than HIV-negative individuals (83 (78−85) vs. 90 (89−93), respectively; p = 0.003), and also lower BMSi than HIV+ progressors (83 (78−85) vs. 86 (85−89), respectively; p = 0.022). A trend was found of lower BMSi in HIV+ progressors with respect to the HIV-negative individuals (86 (85−89) vs. 90 (89−93), respectively; p = 0.083). No differences were detected in bone mineral density between groups. In conclusion, LTNPs showed a different inflammatory profile, along with worse bone tissue quality, when compared to HIV+ progressors and HIV-negative individuals. This may contribute to increasing evidence that HIV infection itself has a deleterious effect on bone tissue, likely through a persistent altered inflammation status.

Comparison of Hospitalized Coronavirus Disease 2019 and Influenza Patients Requiring Supplemental Oxygen in a Cohort Study: Clinical Impact and Resource Consumption.

BACKGROUND: To compare clinical characteristics, outcomes, and resource consumption of patients with coronavirus disease 2019 (COVID-19) and seasonal influenza requiring supplemental oxygen. METHODS: Retrospective cohort study conducted at a tertiary-care hospital. Patients admitted because of seasonal influenza between 2017 and 2019, or with COVID-19 between March and May 2020 requiring supplemental oxygen were compared. Primary outcome: 30-day mortality. Secondary outcomes: 90-day mortality and hospitalization costs. Attempted sample size to detect an 11% difference in mortality was 187 patients per group. RESULTS: COVID-19 cases were younger (median years of age, 67; interquartile range [IQR] 54-78 vs 76 [IQR 64-83]; P < .001) and more frequently overweight, whereas influenza cases had more hypertension, immunosuppression, and chronic heart, respiratory, and renal disease. Compared with influenza, COVID-19 cases had more pneumonia (98% vs 60%, <.001), higher Modified Early Warning Score (MEWS) and CURB-65 (confusion, blood urea nitrogen, respiratory rate, systolic blood pressure, and age >65 years) scores and were more likely to show worse progression on the World Health Organization ordinal scale (33% vs 4%; P < .001). The 30-day mortality rate was higher for COVID-19 than for influenza: 15% vs 5% (P = .001). The median age of nonsurviving cases was 81 (IQR 74-88) and 77.5 (IQR 65-84) (P = .385), respectively. COVID-19 was independently associated with 30-day (hazard ratio [HR], 4.6; 95% confidence interval [CI], 2-10.4) and 90-day (HR, 5.2; 95% CI, 2.4-11.4) mortality. Sensitivity and subgroup analyses, including a subgroup considering only patients with pneumonia, did not show different trends. Regarding resource consumption, COVID-19 patients had longer hospital stays and higher critical care, pharmacy, and complementary test costs. CONCLUSIONS: Although influenza patients were older and had more comorbidities, COVID-19 cases requiring supplemental oxygen on admission had worse clinical and economic outcomes.

Factors associated to neurocognitive impairment in older adults living with HIV.

OBJECTIVE: The HIV infection is a chronic disease that causes neurocognitive impairment (NI) and has been related with early development of frailty. We aimed to study the main risk factors for neurocognitive disorders and frailty in HIV older adults. MATERIALS AND METHODS: Cross-sectional study with 40 HIV individuals older than 65 years under antiretroviral therapy in Hospital del Mar (Barcelona) recruited between November 2019 and October 2020. Data has been obtained through clinical scores and a blood sample to evaluate NI and frailty and has been analyzed with non-parametric tests and a multivariate logistic regression model. RESULTS: Among the 40 patients admitted for the study, 14 (35%) had positive screening for NI. We found that HIV individuals with nadir CD4+ T-cell count lower than 350 cells/mm3 had 39.7 more risk for NI (95% CI 2.49-632.10; p = 0.009). Those with a lower education level had 22.78 more risk for neurocognitive disorders (95% CI 2.13-242.71; p = 0.01) and suffering any comorbidity with a punctuation ≥ 1 in the Charlson Comorbidity index had an increased risk of 18.26 of developing NI and frailty (95% CI 1.30-256.33; p = 0.031), among them diabetes was significantly more frequent in NI. CONCLUSION: We observed that the main risk factors for a positive NI screening in HIV older adults were low education level, a nadir CD4+ T-cell count < 350 cells/mm3 and the presence of any comorbidity, highlighting diabetes among them.

Osteoarticular Cryptococcosis Successfully Treated with High-Dose Liposomal Amphotericin B Followed by Oral Fluconazole.

BACKGROUND: Skeletal involvement of Cryptococcus neoformans is infrequent and usually associated with disseminated cryptococcosis or underlying predisposing conditions. We present an atypical case of osteoarticular cryptococcosis in an immunocompetent patient. CASE PRESENTATION: We herein report a case of bone and soft tissue cryptococcal infection in a 42-year-old male from Pakistan with well-controlled diabetes without other associated immunodeficiencies treated with antifungal therapy without surgical debridement. Furthermore, the patient developed toxidermia due to fluconazole use, so a fluconazole desensitization was performed. Therapeutic management also included the performance of therapeutic drug monitoring of fluconazole plasma concentrations. CONCLUSION: To our knowledge, this is the first case of osteoarticular cryptococcosis treated with this treatment regimen. This strategy may be of interest to try to reduce hospital stay and associated complications.

Documento de consenso para mejorar la adherencia a la farmacoterapia en pacientes con infección por el virus de la inmunodeficiencia humana en tratamiento antirretroviral / Consensus document on enhancing medication adherence in patients with the human immunodeficiency virus receiving antiretroviral therapy

La adherencia al tratamiento en el paciente con infección por el virus de la inmunodeficiencia humana sigue siendo foco de atención de profesionales sanitarios e investigadores. Sin embargo, el perfil del paciente y el arsenal terapéutico disponible han cambiado enormemente en la última década. La adherencia inadecuada, no solo al tratamiento antirretroviral sino también a otros fármacos prescritos, sigue siendo la principal causa de fracaso terapéutico. Existen diversos factores asociados a la mala adherencia y otros que facilitan la misma, de ahí la importancia de identificar y manejar las situaciones que puedan dificultar la adherencia e intentar corregirlas. Asimismo, se debe reevaluar periódicamente la adherencia durante el seguimiento del tratamiento antirretroviral y del resto de los fármacos prescritos. En la actualidad no existe un método único para medir la adherencia de forma fiable. Por ello se hace necesario utilizar varios métodos combinados de fácil realización. Adicionalmente, una buena relación entre el personal sanitario y los pacientes facilita la obtención de una adecuada información sobre la adherencia. Las intervenciones para mejorar la adherencia deben ser multidisciplinares, individualizadas y ajustadas a los nuevos patrones de transmisión de la infección, y es fundamental incluir el control de la adherencia a otros fármacos prescritos al paciente con el virus de la inmunodeficiencia humana. El presente documento actualiza las recomendaciones publicadas en 2008 tras una revisión de la literatura científica, lo que ha permitido emitir unas recomendaciones consensuadas para la mejora de la adherencia al tratamiento. El objetivo principal es ayudar a todos los profesionales sanitarios dedicados al control clínico y terapéutico de los pacientes con el virus de la inmunodeficiencia humana (médicos, farmacéuticos, enfermeras, psicólogos y trabajadores sociales) a mejorar la adherencia a toda la farmacoterapia que tengan prescrita

Adherence to treatment in patients living with HIV remains the focus of attention of health professionals and researchers. However, patient pro-files and the available therapeutic arsenal have changed greatly over the last decade. Inadequate adherence not only to antiretroviral therapy but also to other prescribed drugs remains the main cause of therapeutic failure. There are several factors associated with poor adherence and others that facilitate it, hence the importance of identifying, managing and correcting situations that may hinder adherence. Likewise, adherence should be periodically reassessed during the follow-up of ART and other prescribed drugs. It has so far proved impossible to find a single method capable of providing a reliable measurement of adherence. That is why it is necessary to use a combination of multiple easy-to-implement methods. Additionally a good relationship with the patient facilitates the conveyance of adequate information on adherence. It is currently considered that interventions to improve adherence should be multidisciplinary, individualized and adjusted to the new patterns of infection transmission, and that controlling adherence to other drugs prescribed to patients with HIV should be part of such interventions. This document provides an update on the recommendations published in 2008 based on a review of the scientific literature. The main goal is to help healthcare professionals dedicated to the clinical and therapeutic management of HIV patients (doctors, pharmacists, nurses, psychologists and social workers) improve adherence of such patients to all the drugs prescribed to them as treatment for their HIV infection

Consensus document on enhancing medication adherence in patients with the human immunodeficiency virus receiving antiretroviral therapy.

Adherence to treatment in patients living with HIV remains the focus of attention of health professionals and researchers. However, patient profiles and the  available therapeutic arsenal have changed greatly over the last decade.  Inadequate adherence not only to antiretroviral therapy but also to other  prescribed drugs remains the main cause of therapeutic failure. There are  several factors associated with poor adherence and others that facilitate it,  hence the importance of identifying, managing and correcting situations that  may hinder adherence. Likewise, adherence should be periodically reassessed  during the follow-up of ART and other prescribed drugs. It has so far proved  impossible to find a single method capable of providing a reliable measurement  of adherence. That is why it is necessary to use a combination of multiple easy- to-implement methods. Additionally, a good relationship with the patient  facilitates the conveyance of adequate information on adherence. It is currently  considered that interventions to improve adherence should be multidisciplinary,  individualized and adjusted to the new patterns of infection transmission, and  that controlling adherence to other drugs prescribed to patients with HIV should  be part of such interventions. This document provides an update on the  recommendations published in 2008 based on a review of the scientific  literature. The main goal is to help healthcare professionals dedicated to the  clinical and therapeutic management of HIV patients (doctors, pharmacists,  nurses, psychologists and social workers) improve adherence of such patients to  all the drugs prescribed to them as treatment for their HIV infection.

La adherencia al tratamiento en el paciente con infección por el virus de la  inmunodeficiencia humana sigue siendo foco de atención de profesionales sanitarios e investigadores. Sin embargo, el perfil del paciente y el  arsenal terapéutico disponible han cambiado enormemente en la última década.  La adherencia inadecuada, no solo al tratamiento antirretroviral sino también a otros fármacos prescritos, sigue siendo la principal causa de fracaso  terapéutico. Existen diversos factores asociados a la mala adherencia y otros  que facilitan la misma, de ahí la importancia de identificar y manejar las  situaciones que puedan dificultar la adherencia e intentar corregirlas. Asimismo, se debe reevaluar periódicamente la adherencia durante el  seguimiento del tratamiento antirretroviral y del resto de los fármacos  prescritos. En la actualidad no existe un método único para medir la adherencia  de forma fiable. Por ello se hace necesario utilizar varios métodos combinados de fácil realización. Adicionalmente, una buena relación entre el  personal sanitario y los pacientes facilita la obtención de una adecuada  información sobre la adherencia. Las intervenciones para mejorar la adherencia  deben ser multidisciplinares, individualizadas y ajustadas a los nuevos patrones  de transmisión de la infección, y es fundamental incluir el control de la adherencia a otros fármacos prescritos al paciente con el virus de la  inmunodeficiencia humana. El presente documento actualiza las  recomendaciones publicadas en 2008 tras una revisión de la literatura científica,  lo que ha permitido emitir unas recomendaciones consensuadas para la mejora  de la adherencia al tratamiento. El objetivo principal es ayudar a todos los  profesionales sanitarios dedicados al control clínico y terapéutico de los  pacientes con el virus de la inmunodeficiencia humana (médicos, farmacéuticos,  enfermeras, psicólogos y trabajadores sociales) a mejorar la adherencia a toda  la farmacoterapia que tengan prescrita.

Bone density, microarchitecture and tissue quality after 1 year of treatment with dolutegravir/abacavir/lamivudine.

BACKGROUND: Bone mineral density (BMD) decreases with ART initiation with a tenofovir disoproxil fumarate-containing regimen, although bone tissue quality increases. The impact of dolutegravir (DTG)/abacavir (ABC)/lamivudine (3TC)-based ART initiation on bone health parameters is not clear. OBJECTIVES: To study the impact of DTG/ABC/3TC-based therapy on bone health parameters in ART-naive individuals with HIV after 48 weeks of treatment. METHODS: An observational, prospective and analytical study of treatment-naive patients with HIV undergoing a DTG/ABC/3TC-based regimen at 48 week follow-up. Changes in bone strength parameters (BMD, bone microarchitecture and bone tissue quality) were assessed with non-parametric methods. RESULTS: Sixteen HIV-infected ART-naive patients starting DTG/ABC/3TC were included. BMD in the lumbar spine showed a significant decrease of -2.25% (P = 0.007) and -4.1% in the femoral neck (P = 0.007). Bone microarchitecture, as measured by trabecular bone score, also decreased significantly by -2.5% (P = 0.03). In contrast, bone quality [bone material strength index (BMi)], as measured by microindentation, significantly increased with respect to baseline after 48 weeks of treatment, showing better bone properties of +6.53% (P < 0.001). No significant changes were found in bone turnover markers. In addition, a positive significant correlation between the CD4/CD8 cell count ratio at baseline and changes in BMSi after 48 weeks of treatment was observed (Spearman's rho = 0.4974; P = 0.04). CONCLUSIONS: After a 48 week treatment with DTG/ABC/3TC-based ART, BMD and trabecular bone score decreased while bone tissue quality, as measured by microindentation, improved significantly. The state of the immune system at ART initiation is related to bone quality recovery. An overarching approach to assess bone toxicity in ART-treated patients is needed.

"It made me more confident that I have it under control": Patient and provider perspectives on moving to a two-drug ART regimen in the United States and Spain.

BACKGROUND: Two-drug regimens (2DR) to treat HIV infection have the potential to reduce long-term toxicity and increase therapeutic options for people living with HIV (PLHIV). Prior phase III trials, SWORD-1 and SWORD-2, as well as GEMINI-1 and GEMINI-2, have demonstrated that a dolutegravir-based 2DR is as effective as three- or four-drug regimens among virologically suppressed patients. Limited information exists, however, on patient and provider experiences with 2DR to inform roll-out and integration into routine clinical care. METHODS: We conducted 39 in-depth interviews with PLHIV currently on 2DR in the context of routine care and 8 of their clinical care providers in the United States (U.S.) and Spain. Participants included 33 male and 6 female PLHIV and 8 providers. Interview topics explored perceptions of and experiences with 2DR compared to prior anti-retroviral regimens (ARVs), side effects, patient satisfaction, and clinical performance. Interviews were audio-recorded, transcribed and analyzed using thematic content analysis. RESULTS: Participants viewed 2DR as a significant and positive advance, in terms of its ability to effectively treat HIV with reduced toxicity and essentially no reported side effects. Patients noted the central role providers played in the decision to switch to a 2DR regimen and, among U.S. participants, the importance of insurance coverage making this preferred option feasible. Patients and providers agreed that a 2DR regimen would be appropriate for any PLHIV regardless of whether they were treatment naïve or had significant experience with ARVs. CONCLUSIONS: Participants' experiences with a 2DR regimen were positive with no participants, reporting side effects and all reporting continued viral suppression. Providers valued the reduced toxicity offered by 2DR and served as the primary gateway to a transition to 2DR for patients in both settings. This study provides a foundation for further research on the transition to 2DR regimens in other populations and contexts including low- and middle-income settings.

Correlation between blood telomere length and CD4+ CD8+ T-cell subsets changes 96 weeks after initiation of antiretroviral therapy in HIV-1-positive individuals.

In 31 participants who started first-line antiretroviral therapy in the NEAT 001/ANRS 143 clinical trial, we found after 96 weeks a statistically significant increase in blood telomere length (TL) of 0.04 (T/S Ratio) (p = 0.03). This increase was positively correlated with both the change in the percentage of CD4+ T-cells and with the decrease of CD38+ molecules on Central Memory CD8+ and negatively correlated with the change in the percentage of CD4+ Effector Memory cells. Increase in TL could be an expression of immune reconstitution and the associated decrease in immune activation. We acknowledge for the low statistical power due to the small sample size and the potential for false positive results due to multiple testing. Hence, further studies are needed to confirm these observations.

Risk Factors for Mortality among Patients with Pseudomonas aeruginosa Bloodstream Infections: What Is the Influence of XDR Phenotype on Outcomes?

This study aimed to assess the impact of extensively drug-resistant (XDR) phenotype on mortality in Pseudomonas aeruginosa bacteremia. A retrospective cohort study was performed in a tertiary hospital from January 2000 to December 2018. All consecutive prospectively recorded P. aeruginosa bacteremia in adult patients were assessed. In this study, 382 patients were included, of which 122 (31.9%) due to XDR P. aeruginosa. Independent factors associated with 14-day mortality were as follows: high-risk source of bacteremia (hazard ratio (HR) 3.07, 95% confidence interval (CI), 1.73-5.46), septic shock (HR 1.75, 95% CI, 1.12-2.75), and higher Pitt scores (one-point increments; HR 1.25, 95% CI, 1.12-1.38). Otherwise, the appropriateness of definitive antibiotic therapy was a protective factor (HR 0.39, 95% CI, 0.24-0.62). The same variables were also associated with 30-day mortality. XDR phenotype was not associated with 14- or 30-day mortality. In a subanalysis considering only high-risk source cases, combined antimicrobial therapy was independently associated with 14-day favorable outcome (HR 0.56, 95% CI, 0.33-0.93). In conclusion, XDR phenotype was not associated with poor prognosis in patients with P. aeruginosa bacteremia in our cohort. However, source of infection, clinical severity, and inappropriate definitive antibiotic therapy were risk factors for mortality. Combined antimicrobial therapy should be considered for high-risk sources.

Factors associated with the number of drugs in darunavir/cobicistat regimens.

BACKGROUND: Darunavir/cobicistat can be used as mono, dual, triple or more than triple therapy. OBJECTIVES: To assess factors associated with the number of drugs in darunavir/cobicistat regimens. METHODS: A nationwide retrospective cohort study of consecutive HIV-infected patients initiating darunavir/cobicistat in Spain from July 2015 to May 2017. Baseline characteristics, efficacy and safety at 48 weeks were compared according to the number of drugs used. RESULTS: There were 761 patients (75% men, 98% were antiretroviral-experienced, 32% had prior AIDS, 84% had HIV RNA <50 copies/mL and 88% had ≥200 CD4 cells/mm3) who initiated darunavir/cobicistat as mono (n=308, 40%), dual (n=173, 23%), triple (n=253, 33%) or four-drug (n=27, 4%) therapy. Relative to monotherapy, triple therapy was more common in men aged <50 years, with prior AIDS and darunavir plus ritonavir use, and with CD4 cells <200/mm3 and with detectable viral load at initiation of darunavir/cobicistat; dual therapy was more common with previous intravenous drug use, detectable viral load at initiation of darunavir/cobicistat and no prior darunavir plus ritonavir; and four-drug therapy was more common with prior AIDS and detectable viral load at initiation of darunavir/cobicistat. Monotherapy and dual therapy showed a trend to better virological responses than triple therapy. CD4 responses and adverse effects did not differ among regimens. DISCUSSION: Darunavir/cobicistat use in Spain has been tailored according to clinical characteristics of HIV-infected patients. Monotherapy and dual therapy have been common and preferentially addressed to older patients with a better HIV status, suggesting that health issues other than HIV infection may have been strong determinants of its prescription.

Predictive factors of renal impairment in HIV-infected patients on antiretroviral therapy: Results from the VACH longitudinal cohort study / Factores predictivos de insuficiencia renal en pacientes infectados por el VIH que reciben tratamiento antirretroviral: resultados del estudio de cohortes longitudinal VACH

BACKGROUND: The use of combination antiretroviral therapy has led to dramatic improvements in the life expectancy of HIV-infected persons. As result, the HIV population is aging and increasingly facing illnesses typically seen in the elderly, such as chronic kidney disease (CKD). METHODS: A retrospective longitudinal study was conducted using data from years 2010 and 2014 in all HIV-infected persons enrolled at the Spanish VACH cohort. We analyzed the prevalence and the predictive factors for developing CKD (estimated glomerular filtration rate, eGFR< 60 mL/min/1.73 m2). RESULTS: The CKD prevalence at baseline was 456/8968, 5.1% [4.6-5.6%]. Of 8512 HIV-positive individuals examined without CKD at baseline (73.7% male, median age 44 years-old), 2.15% developed CKD (eGFR < 60 mL/min/1.73m2). The odds ratios [95%CI] for the independent predictive factors identified were gender (male) 0.54 [0.39-0.75], age (per year) 1.08 [1.07-1.10], AIDS diagnosis 1.40 [1.03-1.91], protease inhibitor-based regimens 1.49 [1.10-2.02], hypertension 1.37 [0.94-1.99], diabetes 1.84 [1.33-2.55] and history of cardiovascular events 1.66 [0.96-2.86]. CONCLUSION: The prevalence and risk factors for CKD and its progression are high in the VACH cohort. Thus, preventive measures such as control of hypertension, diabetes and obesity, as well as efforts for avoiding exposure to nephrotoxic drugs, including some antiretrovirals, are warranted in this aging HIV population

ANTECEDENTES: El uso de tratamiento antirretroviral combinado ha dado lugar a mejoras sustanciales en la esperanza de vida de las personas infectadas por el virus de la inmunodeficiencia humana (VIH). Como resultado, la población con VIH está envejeciendo y haciendo frente cada vez más a enfermedades normalmente observadas en las personas de edad avanzada, como la nefropatía crónica (NC). MÉTODOS: Se ha realizado un estudio longitudinal retrospectivo usando datos de los años 2010 y 2014 en todas las personas infectadas por el VIH incluidas en la cohorte VACH española. Se ha analizado la prevalencia y los factores predisponentes para el desarrollo de NC (filtración glomerular estimada [FGe]:< 60 ml/min/1,73m2). RESULTADOS: La prevalencia de NC al inicio fue de 456/8.968; 5,1% (4,6-5,6%). De las 8.512 personas infectadas por el VIH evaluadas sin NC al inicio (73,7 varones, mediana de edad: 44 años), el 2,15% desarrolló NC (FGe < 60 ml/min/1,73m2). Los cocientes de posibilidades (IC del 95%) de los factores predictivos independientes identificados fueron 0,54 (0,39-0,75) para el sexo (varón); 1,08 (1,07-1,10) para la edad (por año); 1,40 (1,03-1,91) para el diagnóstico de sida; 1,49 (1,10-2,02) para los tratamientos basados en inhibidores de la proteasa; 1,37 (0,94-1,99) para la hipertensión; 1,84 (1,33-2,55) para la diabetes y 1,66 (0,96-2,86) para los antecedentes de acontecimientos cardiovasculares. CONCLUSIÓN: La prevalencia y los factores de riesgo para la NC y su progresión son elevados en la cohorte VACH. Por lo tanto, está justificada la aplicación de medidas preventivas (como el control de la hipertensión, la diabetes y la obesidad), así como la aplicación de esfuerzos para evitar la exposición a fármacos nefrotóxicos (incluidos algunos antirretrovirales) en esta población con VIH que envejece