Effectiveness, safety and discontinuation rates of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in people with HIV using real-world data: a systematic review and meta-analysis.

BACKGROUND: The use of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) is based on the results of robust clinical trials. OBJECTIVES: To assess the effectiveness and safety of BIC/FTC/TAF in treatment-naïve (TN) and treatment-experienced (TE) people with HIV using available real-world cohort studies. METHODS: Systematic review and meta-analysis of publications and communications identified via Boolean search in Medline, PubMed and Embase, and conference abstracts reporting retrospective real-world use of BIC/FTC/TAF, published until 31 January 2024. The primary endpoint was the proportion of TN and TE people with HIV with viral load (VL) < 50 copies/mL at 48 weeks while on treatment. RESULTS: Of the 38 identified publications and conference abstracts, for the present analysis we included 12 publications (comprising 792 TN and 6732 TE individuals). For the three publications including 507 TN participants reporting the primary outcome, VL suppression was 97% [95% confidence intervals (CI): 89-100]. For the nine publications including 4946 TE participants reporting the primary outcome, VL suppression was 95% (95% CI: 94-96), with suppression >93% in all studies. Total discontinuations at 48 weeks in TE individuals were 3% (95% CI: 2-5), 1% (95% CI: 0-2) due to side effects. A total of four publications with 151 TE individuals with previous presence of M184V substitution were identified, reporting a suppression rate at 48 weeks of 95% (95% CI: 88-100). CONCLUSIONS: Real-world studies demonstrate low discontinuation rates and high rates of virologic suppression in individuals treated with BIC/FTC/TAF, both TN and TE with and without previous detection of M184V substitution.

Rapid initiation of bictegravir/emtricitabine/tenofovir alafenamide as first-line therapy in HIV infection. A prospective study.

INTRODUCTION: Rapid initiation of ART after HIV diagnosis is recommended for individual and public health benefits. However, certain clinical and ART-related considerations hinder immediate initiation of therapy. METHODS: An open-label, single-arm, single-centre 48-week prospective clinical trial involving ART-naïve HIV-diagnosed adults who started bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) within a week from the first hospital visit, before the availability of baseline laboratory and genotype results. The primary aim was to determine the proportion of people with at least one condition that would hinder immediate initiation of any recommended ART regimen other than BIC/FTC/TAF. Clinicaltrials.gov: NCT04416906. RESULTS: We included 100 participants: 79% men, 64% from Latin America, median age 32 years. According to European AIDS Clinical Society (EACS) and US Department of Health and Human Services 2023 guidelines, 11% (95%CI 6; 19) of participants had at least one condition that made any ART different from BIC/FTC/TAF less appropriate for a rapid ART strategy. Seventy-nine percent of the people started BIC/FTC/TAF within the first 48 hours of their first hospital visit. There were 16 early discontinuations (11 lost to follow-up). By week 48, 92% (95%CI 86; 98) of the participants of the ITT population with observed data achieved viral suppression. Eight grade 3-4 adverse events (AEs), five serious AEs and six ART-related AEs were identified. Adherence remained high. CONCLUSIONS: BIC/FTC/TAF is an optimal treatment for rapid initiation of ART. However, additional strategies to improve retention in care must be implemented.

Efficacy and safety of raltegravir plus lamivudine maintenance therapy.

BACKGROUND: Decreasing medication burden with raltegravir plus lamivudine in virologically suppressed persons with HIV (PWH) maintained efficacy and was well tolerated at 24 weeks, but more comprehensive data over longer follow-up are required. METHODS: Prospective 48 week extension phase of the raltegravir plus lamivudine arm from a previous 24 week pilot randomized clinical trial in which virologically suppressed PWH were randomized 2:1 to switch to fixed-dose combination 150 mg lamivudine/300 mg raltegravir twice daily or to continue therapy. In this 48 week extension phase, raltegravir was dosed at 1200 mg/day and lamivudine 300 mg/day. Primary outcome was the proportion of PWH with treatment failure at Week 48. Secondary outcomes were changes in ultrasensitive plasma HIV RNA, HIV DNA in CD4 cells, serum IL-6, ultrasensitive C-reactive protein and sCD14, body composition, sleep quality, quality of life and adverse effects. RESULTS: Between May 2018 and June 2019, 33 PWH were enrolled. One participant experienced virological failure without resistance mutations and re-achieved sustained virological suppression without therapy discontinuation, and two others discontinued therapy due to adverse effects. Treatment failure was 9% (95% CI 2%-24%) and 3% (95% CI 0%-17%) in the ITT and on-treatment populations. There were significant changes between baseline and Week 48 in serum cytokines but not in other secondary outcomes. CONCLUSIONS: Switching to raltegravir and lamivudine in PWH with virological suppression maintains efficacy and is well tolerated. This maintenance regimen might be a cost-effective option for PWH at risk of drug-drug interactions or needing to avoid specific toxicities of certain antiretroviral drugs or their negative impact on comorbidities.

Epidemiological changes and outcomes of people living with HIV admitted to the intensive care unit: a 14-year retrospective study.

PURPOSES: Since 2016, the World Health Organization has recommended universal antiretroviral therapy (ART) for all people living with Human Immunodeficiency Virus (PLHIV). This recommendation may have influenced the characteristics and outcomes of PLHIV admitted to the Intensive Care Unit (ICU). This study aims to identify changes in the epidemiological and clinical characteristics of PLHIV admitted to the ICU, and their short- and medium-term outcomes before and after the implementation of universal ART (periods 2006-2015 and 2016-2019). METHODS: This retrospective, observational, single-center study included all adult PLHIV admitted to the ICU of a University Hospital in Barcelona from 2006 to 2019. RESULTS: The study included 502 admissions involving 428 patients, predominantly men (75%) with a median (P25-P75) age of 47.5 years (39.7-53.9). Ninety-one percent were diagnosed with HIV before admission, with 82% under ART and 60% admitted from the emergency department. In 2016-2019, there were more patients on ART pre-admission, reduced needs for invasive mechanical ventilation (IMV) and fewer in-ICU complications. ICU mortality was also lower (14% vs 7%). Predictors of in-ICU mortality included acquired immunodeficiency syndrome defining event (ADE)-related admissions, ICU complications, higher SOFA scores, IMV and renal replacement therapy (RRT) requirement. ART use during ICU admission was protective. Higher SOFA scores, admission from hospital wards, and more comorbidities predicted one-year mortality. CONCLUSIONS: The in-ICU mortality of critically ill PLHIV has decreased in recent years, likely due to changes in patient characteristics. Pre- and ICU admission features remain the primary predictors of short- and medium-term outcomes.

Tolerability of bictegravir/tenofovir alafenamide/emtricitabine versus dolutegravir/lamivudine as maintenance therapy in a real-life setting.

BACKGROUND: While both the burden of therapy and the individual drugs in bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) and dolutegravir/lamivudine differ, it is unclear whether their real-life tolerability may be also different. METHODS: Single-centre, clinical cohort analysis of all virologically suppressed persons with HIV (PWH) who were first prescribed bictegravir as BIC/TAF/FTC or dolutegravir as dolutegravir/lamivudine and had taken ≥1 dose of study medication. Major outcomes were discontinuations either for any reason or due to toxicity. Incidence was calculated as number of episodes per 100 person-years adjusted through propensity score analysis. RESULTS: Relative to persons treated with BIC/TAF/FTC (n = 1231), persons treated with dolutegravir/lamivudine (n = 821) were older and had more AIDS-defining conditions although better HIV control. After a median follow-up of 52 weeks, adjusted incidence rates for discontinuation were 6.68 (95% CI 5.18-8.19) and 8.44 (95% CI 6.29-10.60) episodes per 100 person-years for BIC/TAF/FTC and dolutegravir/lamivudine, respectively; adjusted incidence rate ratio for dolutegravir/lamivudine was 1.26 (95% CI 0.89-1.78) relative to BIC/TAF/FTC (P = 0.1847). Adjusted incidence rates for discontinuation due to toxicity were 3.88 (95% CI 2.70-5.06) and 4.62 (95% CI 3.05-6.19) episodes per 100 person-years for BIC/TAF/FTC and dolutegravir/lamivudine, respectively; adjusted incidence rate ratio for dolutegravir/lamivudine was 1.19 (95% CI 0.75-1.90) relative to BIC/TAF/FTC (P = 0. 4620). Adverse events leading to discontinuation were neuropsychiatric (n = 42; 2%), followed by gastrointestinal (n = 23; 1%), dermatological (n = 15; 1%) and weight increase (n = 15; 1%), without differences between regimens. CONCLUSIONS: Switching to BIC/TAF/FTC or dolutegravir/lamivudine showed no difference in the risks of overall or toxicity-related discontinuations or in the profile of adverse events leading to discontinuation.

Clinical use and effectiveness of dolutegravir and lamivudine: a long-term, real-world, retrospective study.

BACKGROUND: The use of dolutegravir/lamivudine is based on solid clinical trials; however, real-world data remain limited. OBJECTIVES: To provide data on the clinical use and effectiveness of dolutegravir/lamivudine in persons with HIV in a real-world scenario. PATIENTS AND METHODS: Retrospective, single-centre and observational study. We included all adults starting dolutegravir/lamivudine since November 2014. We reported all demographic, virological and immunological variables at baseline and assessed effectiveness [on treatment (OT), modified ITT (mITT) and ITT in those persons who reached 6 and 12 month follow-ups (M6 and M12). RESULTS: Of the 1058 persons, 9 were treatment-naive; the final analysis included 1049 treatment-experienced people with HIV. Median (IQR) follow-up was 1 (0.3-1.6) years, with 81% and 63% persons reaching M6 and M12, respectively. The longest use of dolutegravir/lamivudine was 7.4 years. Per OT, mITT and ITT, HIV-RNA < 50 copies/mL was 97%, 92% and 81% (M6) and 98%, 90% and 80% (M12), respectively. Females [adjusted risk ratio, aRR (95% CI): 1.69 (1.19-2.40)]; immediate, previous PI-based regimen [aRR (95% CI): 1.67 (1.09-2.56)]; and viral load (VL) ≥ 50 copies/mL at dolutegravir/lamivudine initiation [aRR (95% CI): 3.36 (2.32-4.88)] were independently associated with lack of effectiveness at M12; other demographic, immunological and virological variables like previous M184V/I substitutions or virological failure, were unrelated. Of the total, 944 (90%) continued dolutegravir/lamivudine. The most frequent known reason for discontinuation was toxicity [48 (46%) cases]. CONCLUSIONS: In our real-world experience, virological suppression rates were high for treatment-experienced persons on dolutegravir/lamivudine; however, we identified subgroups with a higher risk of lack of effectiveness at M12, who may benefit from closer follow-ups.

Sex-based epidemiological and immunovirological characteristics of people living with HIV in current follow-up at a tertiary hospital: a comparative retrospective study, Catalonia, Spain, 1982 to 2020.

BackgroundEpidemiological and immunovirological features of people living with HIV (PLWH) can vary by sex.AimTo investigate, particularly according to sex, characteristics of PLWH who consulted a tertiary hospital in Barcelona, Spain, in 1982-2020.MethodsPLWH, still in active follow-up in 2020 were retrospectively analysed by sex, age at diagnosis, age at data extraction (December 2020), birth place, CD4+ cell counts, and virological failure.ResultsIn total, 5,377 PLWH (comprising 828 women; 15%) were included. HIV diagnoses in women appeared to decrease from the 1990s, representing 7.4% (61/828) of new diagnoses in 2015-2020. From 1997, proportions of new HIV diagnoses from patients born in Latin America seemed to increase; moreover, for women born outside of Spain, the median age at diagnosis appeared to become younger than for those born in Spain, with significant differences observed in 2005-2009 and 2010-2014 (31 vs 39 years (p = 0.001), and 32 vs 42 years (p < 0.001) respectively), but not in 2015-2020 (35 vs 42 years; p = 0.254). Among women, proportions of late diagnoses (CD4+ cells/mm3 < 350) were higher than men (significantly in 2015-2020: 62% (32/52) vs 46% (300/656); p = 0.030). Initially, virological failure rates were higher in women than men, but they were similar in 2015-2020 (12% (6/52) vs 8% (55/659); p = 0.431). Women ≥ 50 years old represented 68% (564/828) of women actively followed up in 2020.ConclusionsWomen still have higher rates of late HIV diagnoses than men. Among currently-followed-up women, ≥ 50 year-olds, who need age-adapted care represent a high percentage. Stratifying PLWH by sex matters for HIV prevention and control interventions.

Integrase resistance emergence with dolutegravir/lamivudine with prior HIV-1 suppression.

OBJECTIVES: Integrase resistance has not been reported with co-formulated dolutegravir/lamivudine in clinical trials or real-life cohorts. We aim to report, to the best of our knowledge, the first case of selection of the key integrase mutation R263K in a subject treated with this regimen started as a switch strategy with undetectable plasma HIV-1 viraemia. METHODS: Clinical case report. RESULTS: A patient with long-term suppressed HIV-1 viraemia (<50 copies/mL) with no known risk factors for virological failure and never exposed previously to an integrase inhibitor developed virological failure (consecutive plasma HIV-1 RNA 149 and 272 copies/mL) with 322 CD4 cells/mm3 despite good treatment adherence. He was receiving the anticonvulsant clobazam, considered to have a potential weak interaction with dolutegravir, unlikely to require a dose adjustment. Plasma HIV-1 genotypic deep sequencing (Vela System) revealed the emergence of R263K (79.6%) and S230N (99.4%) mutations in the integrase region (intermediate resistance to dolutegravir, score = 30 Stanford HIVDB 9.0). The reverse transcriptase and protease regions could not be amplified due to low viral loads. PBMC DNA deep sequencing performed some months later revealed mutations M184I (14.29%) and M230I (6.25%) in the reverse transcriptase and G163R (9.77%) and S230N (98.8%) in the integrase. R263K was only found at extremely low levels (0.07%). CONCLUSIONS: This case illustrates that integrase resistance can emerge in patients treated with co-formulated dolutegravir/lamivudine and raises awareness of the need to carefully consider and monitor drug-drug interactions, even when regarded as having a low potential, in subjects treated with dolutegravir/lamivudine.

Simplification from tenofovir disoproxil fumarate plus lamivudine or emtricitabine plus ritonavir-boosted protease inhibitor to ritonavir-boosted atazanavir plus lamivudine in virologically suppressed HIV-infected adults with osteopenia: a pilot study.

BACKGROUND: Tenofovir disoproxil fumarate, particularly when given with a ritonavir-boosted PI, reduces bone mineral density (BMD) and increases bone turnover markers (BTMs). Ritonavir-boosted atazanavir plus lamivudine is a feasible simplified option. We evaluated whether switching from a triple ritonavir-boosted PI plus tenofovir disoproxil fumarate to a two-drug regimen of lamivudine plus ritonavir-boosted atazanavir would improve BMD. METHODS: Single-arm pilot study. Virologically suppressed patients on tenofovir disoproxil fumarate plus lamivudine or emtricitabine plus ritonavir-boosted PI with low BMD, without previous resistance mutations and/or virological failure to study drugs were switched to 100/300 mg of ritonavir-boosted atazanavir plus 300 mg of lamivudine once daily. The primary endpoint was BMD change by DXA at Week 48. RESULTS: There were 31 patients, 4 (13%) female, and median age was 40 years. Seven participants (22.5%) had osteoporosis. At 48 weeks, mean (SD) changes in spine and hip BMD were +0.01 (0.03) (P = 0.0239) and +0.013 (0.03) g/cm2 (P = 0.0046), respectively. Mean (SD) T-score changes were +0.1 (0.23) (P = 0.0089) and +0.25 (0.76) (P = 0.0197), respectively. N-telopeptide and urine tenofovir disoproxil fumarate toxicity markers showed significant improvements. One participant withdrew from the study and two were lost to follow-up. There were no virological failures, or serious or grade 3-4 adverse events. CONCLUSIONS: Switching from a tenofovir disoproxil fumarate plus ritonavir-boosted PI triple therapy to a lamivudine plus ritonavir-boosted atazanavir two-drug regimen in virologically suppressed HIV-infected adults with low BMD was safe, increased low BMD and reduced plasma markers of bone turnover and urine markers of tenofovir disoproxil fumarate toxicity over 48 weeks.

Real-life experience with bictegravir/emtricitabine/tenofovir alafenamide in a large reference clinical centre.

BACKGROUND: The use of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) is mainly based on robust, pivotal clinical trials. OBJECTIVES: To provide data on clinical use of BIC/FTC/TAF in real life. PATIENTS AND METHODS: This was an observational, retrospective and single-centre study. We included all adult, treatment-naive (TN) and treatment-experienced (TE) people living with HIV (PLWH) starting BIC/FTC/TAF from 8 June 2018. We evaluated effectiveness [on treatment (OT), modified intention-to-treat (mITT) and intention-to-treat (ITT)], tolerability and safety in those patients who reached 6 months of follow-up (M6). RESULTS: We included 1584 PLWH [213 TN (13%) and 1371 TE (87%)]. The median (IQR) follow-up was 16 (7-21) months, with 81% and 53% of PLWH reaching M6 and M12, respectively. By OT, mITT and ITT, HIV-RNA <50 copies/mL was 77%, 70% and 62% at M6 and 92%, 77% and 63% at M12 for TN PLWH and 94%, 89% and 83% at M6 and 93%, 85% and 78% at M12 for TE PLWH, respectively. In PLWH carrying an M184V/I substitution, OT RNA <50 copies/mL was 89.5% at M6. The median CD4 cell count increased from 329 to 511/µL in TN PLWH and from 630 to 683/µL in TE PLWH at M6. Of the total, 1148 (88%) PLWH continued on BIC/FTC/TAF at M6. The most frequent known reason for discontinuation was toxicity [42 (69%) cases]; only 7 cases were considered virological failures (0.6% of the total OT cohort at M6), with no emerging resistance substitutions. CONCLUSIONS: In real life, BIC/FTC/TAF showed high rates of virological suppression and also in PLWH carrying lamivudine/emtricitabine resistance substitutions. The tolerability and safety of BIC/FTC/TAF were good, with high persistence observed for patients on this regimen at M6.

Chemsex Practices in PrEP: Beyond Addiction and Risk Toward a Healthy Sex Life-Baseline Experiences from a Hospital-Based PrEP Program in Barcelona, Spain.

Pre-exposure prophylaxis (PrEP) is a biomedical intervention that has demonstrated efficacy in HIV prevention in individuals at high-risk, among them chemsex users. Out of 190 PrEP users followed at Hospital Clinic of Barcelona until October 2020, 89% reported drug use, and 63% disclosed that they had engaged in chemsex practices, initiated in 64% of cases within the past year. Twenty-one percent used 3 or more drugs simultaneously, being GHB/GBL, nitrites, sildenafil, and methamphetamine the most prevalent combination. Eight percent reported slamming. Forty-one percent described having had negative experiences and 8% did not remember the last time they had sober sex. Methamphetamine, mephedrone, GHB/GBL, and having had open relationships, group sex, double penetration, and fisting were significantly more prevalent. Forty-nine percent admitted being worried about chemsex use, and 18% said they needed help. A comprehensive, interdisciplinary approach is mandatory to enable the attainment of a healthy approach to one's sex life.

RESUMEN: La PrEP es una intervención biomédica eficaz en la prevención del VIH en personas con alto riesgo, entre ellas las personas que practican chemsex. De los 190 usuarios de PrEP seguidos en el Hospital Clínic de Barcelona hasta octubre de 2020, el 89% refirió utilizar drogas y el 63% en contexto de chemsex, iniciando el consumo el 64% durante el último año. El 21% refería policonsumo, siendo GHB/GBL, nitritos, sildenafilo y metanfetamina la combinación más prevalente. El 8% reportó slamming. El 41% describió haber tenido experiencias negativas y el 8% no recordaba la última vez que tuvo sexo sobrio. Metanfetamina, mefedrona, GHB/GBL y haber tenido relaciones abiertas, sexo en grupo, doble penetración y fisting fueron significativamente más frecuentes. El 49% refirió estar preocupado por la práctica de chemsex y el 18% necesitar ayuda. Un abordaje integral e interdisciplinar mejoraría el acompañamiento global de la sexualidad en estas personas.

Impact of SARS-CoV-2 viral load and duration of symptoms before hospital admission on the mortality of hospitalized COVID-19 patients.

PURPOSE: Assess the impact of viral load estimated by cycle threshold (Ct) of reverse transcription real time-polymerase chain reaction (rRT-PCR) and the days from symptoms onset on mortality in hospitalized patients with COVID19. METHODS: Retrospective observational study of 782 patients with a positive rRT-PCR from a nasopharyngeal swab was performed within the first 24 h from admission. Demographic data, clinical manifestations and laboratory parameters were collected. Uni- and multivariate analyses were performed to identify factors associated with mortality at 60 days. RESULTS: Ct was divided into three groups and the mortality rate decreased from 27.3 to 20.7% and 9.8% for Ct values of ≤ 20, 21-25 and > 25, respectively (P = 0.0001). The multivariate analysis identified as predictors of mortality, a Ct value < 20 (OR 3.13, CI 95% 1.38-7.10), between 21-25 (OR 2.47, CI 95% 1.32-4.64) with respect to a Ct value > 25. Days from symptoms onset is a variable associated with mortality as well (DSOA) ≤ 6 (OR 1.86, CI 95% 1.00-3.46), among other factors. Patients requiring hospital admission within 6 DSOA with a Ct value ≤ 25 had the highest mortality rate (28%). CONCLUSIONS: The inclusion of Ct values and DSOA in the characterization of study populations could be a useful tool to evaluate the efficacy of antivirals.

Barriers and facilitators to cervical cancer screening among under-screened women in Cuenca, Ecuador: the perspectives of women and health professionals.

BACKGROUND: Cervical cancer screening is a cost-effective method responsible for reducing cervical cancer-related mortality by 70% in countries that have achieved high coverage through nationwide screening strategies. However, there are disparities in access to screening. In Ecuador, although cervical cancer is the second most common cancer in women, only 58.4% of women of reproductive age have ever been screened for cervical cancer. METHODOLOGY: A qualitative study was performed to understand the current barriers to screening and to identify strategies that could increase uptake in Azuay province, Ecuador. Seven focus group discussions (FGDs) were conducted with under-screened women and health professionals (HPs). The FGDs were recorded and transcribed. Content analysis was done using the socio-ecological framework to categorize and analyse the data. RESULTS: Overall, 28 women and 27 HPs participated in the study. The two groups perceived different barriers to cervical cancer screening. The HPs considered barriers to be mainly at the policy level (lack of a structured screening plan; lack of health promotion) and the individual level (lack of risk perception; personal beliefs). The women identified barriers mainly at organizational level, such as long waiting times, lack of access to health centres, and inadequate patient-physician communication. Both groups mentioned facilitators at policy level, such as national campaigns promoting cervical cancer screening, and at community and individual level, including health literacy and women's empowerment. CONCLUSIONS: The women considered access to health services the main barrier to screening, while the HPs identified a lack of investment in screening programmes and cultural patterns at the community level as major obstacles. To take an integrated approach to cervical cancer prevention, the perspectives of both groups should be taken into account. Additionally, new strategies and technologies, such as self-administered human papillomavirus (HPV) testing and community participation, should be implemented to increase access to cervical cancer screening.

Factors associated with the use and composition of two-drug regimens in a large single-centre HIV cohort.

OBJECTIVES: We aimed to assess the clinical characteristics associated with the use of two-drug regimens (2DRs) and the factors associated with specific antiretrovirals in 2DRs in a large single-centre HIV cohort. METHODS: Retrospective analysis of demographics, HIV characteristics and AIDS events, antiretroviral prescription, virological failure and genotypic resistance testing, and laboratory results from all adult people with HIV (PWH) prospectively followed at the Hospital Clinic of Barcelona who were receiving a 3DR or a 2DR in January 2020. We assessed factors associated with the probability of receiving 2DRs relative to three-drug regimens (3DRs) using a logistic regression model, controlling for age, sex and year of HIV diagnosis. The same methodology was applied to identify factors associated with the prescription of integrase inhibitor-based regimens or PI-based regimens among PWH receiving 2DRs. RESULTS: There were 3432 (88%) PWH receiving 3DRs and 463 (12%) receiving 2DRs. In the final adjusted model, ≥2 previous virological failures, previous resistance mutations, previous AIDS diagnosis, longer time on current regimen, higher total cholesterol or triglycerides and lower baseline haemoglobin were independent factors associated with 2DRs. The majority of 2DRs included an integrase inhibitor or/and a PI. We identified independent factors associated with the inclusion of integrase inhibitors (lower HDL cholesterol) or PIs (prior AIDS, prior genotypic resistance mutations and lower CD4/CD8 ratio) in the 2DR. CONCLUSIONS: In this large single-centre HIV cohort, a worse cardiometabolic status or more archived resistance were key factors associated with inclusion of integrase inhibitors or PIs, respectively, in 2DRs.

Impact of remdesivir according to the pre-admission symptom duration in patients with COVID-19.

BACKGROUND: The use of remdesivir has demonstrated a significant reduction in the time to recovery in patients with COVID-19. However, the impact on mortality is still controversial. Therefore, it is necessary to evaluate whether there is a specific subgroup of patients in whom an active antiviral therapy also reduces the mortality. METHODS: Patients admitted for >48 h in our hospital for a SARS-CoV-2 confirmed or suspected infection from February 2020 to February 2021 were retrospectively analysed. The primary outcome of the study was mortality at 30 days. Univariate and multivariate analyses were performed to identify predictors of mortality. RESULTS: In total, 2607 patients (438 receiving remdesivir and 2169 not) were included with a median (IQR) age of 65 (54-77) years and 58% were male. Four hundred and seventy-six were admitted to the ICU (18.3%) and 264 required invasive mechanical ventilation (10.1%). The global 30 day mortality rate was 10.7%. Pre-admission symptom duration of 4-6 days and ≤3 days was associated with a 1.5- and 2.5-fold increase in the mortality rate, respectively, in comparison with >6 days and treatment with remdesivir was independently associated with a lower mortality rate (OR = 0.382, 95% CI = 0.218-0.671). The analysis showed that the major difference was among patients with shorter pre-admission symptom duration (<6 days). CONCLUSIONS: Patients with ≤3 days and 4-6 days from symptom onset to admission are associated with a 2.5- and 1.5-fold higher risk of death, respectively. Remdesivir was associated with 62% reduced odds of death versus standard-of-care and its survival benefit increased with shorter duration of symptoms.

Liver transplant recipients have an increased risk of developing colorectal adenomas: Results from a retrospective study.

BACKGROUND: Liver transplant recipients have an increased incidence of malignancies, but it is unclear whether they have a higher risk of colorectal cancer. AIM: To investigate whether liver transplant recipients have an increased risk of developing colorectal adenomas (a surrogate marker of colorectal cancer risk). PATIENTS AND METHODS: One hundred thirty-nine liver transplant recipients (excluding primary sclerosing cholangitis) who underwent a colonoscopy and polypectomy before and after transplantation, and 367 nontransplanted patients who underwent a colonoscopy for colorectal cancer screening and a second colonoscopy later were retrospectively studied. The risks of incident colorectal adenomas and high-risk adenomas (advanced or multiple adenomas or carcinomas) were compared between both cohorts. RESULTS: Incident colorectal adenomas were found in 40.3% of the transplanted patients and 30.0% of the nontransplanted patients (15.1% and 5.5%, respectively, had high-risk adenomas). After adjusting for age, sex, presence of adenomas in the baseline endoscopy, and interval between colonoscopies, transplant recipients showed a higher risk of developing colorectal adenomas (OR: 1.61; 95% CI: 1.05-2.47; p = .03) and high-risk adenomas (OR: 2.87; 95% CI: 1.46-5.65; p = .002). CONCLUSIONS: Our results suggest that liver transplant recipients have an increased risk of developing colorectal adenomas and lesions with high risk of colorectal cancer.

Efficacy of Elbasvir/Grazoprevir in Early Chronic G1/G4 Hepatitis C infection in HIV/HCV co-infected patients with mild fibrosis.

BACKGROUND: Acute hepatitis C virus (AHC) infection is increasingly common among HIV+ men who have sex with men (MSM). Until 2017, the guidelines recommended therapy with pegylated-interferon plus ribavirin with a mild sustained virological response (SVR). This prompted many patients to reject that treatment, at that time, waiting to be treated with better and safer options with new Direct-Acting-Antivirals (DAA). OBJECTIVES: Assess the efficacy and safety of Elbasvir/Grazoprevir to treat recent chronic hepatitis C infection, genotype 1 or 4, in HIV+ MSM patients. METHODS: Prospective, open-labeled, two center, pilot study. SVR is analyzed for treatment with Elbasvir/Grazoprevir (8 weeks in GT1b or 12 in GT1a or GT4) in patients with a recent chronic HCV infection, defined as HCV infection lasting less than 4 years and mild liver fibrosis (liver stiffness <8kPa). RESULTS: Forty-eight patients were included (May 2017-March 2018): 2 GT1b, 24 GT1a and 22 GT4. HCV-RNA>800000UI in 63% and medium liver stiffness 4.9kPa. The SVR was 98%, one patient failed due to poor adherence. 67% of patients had adverse effects, but only 16% treatment related. The most frequent side effects were gastrointestinal (19%), related with the central nervous system (18%), respiratory (16%) and systemic symptoms (15%). During one year of follow-up post-therapy, 4 AHC and 18 patients with sexually transmitted diseases (STD) were diagnosed. CONCLUSIONS: Treatment with Elbasvir/Grazoprevir in this scenario is highly effective and safe. Patients with risky sexual practices must remain linked to the medical care system to detect new STD and HCV reinfection.

Treatment of graft-versus-host disease with mesenchymal cells as a complication of a liver transplantation.

We present the case of a liver transplant (LT) recipient donor who developed graft versus host disease (GVHD). The main features were cutaneous rash, diarrhea and pancytopenia. Mesenchymal cells were administered as part of the treatment. This is the first case of a patient with GVHD after LT reported to date. Despite the treatment, there was no improvement in aplasia or gastrointestinal symptoms and the patient died due to a disseminated infection.

Pneumocystis jirovecii pneumonia in a patient with pustular psoriasis with an IL-36RN deficiency treated with infliximab: Case report and review of the literature.

Pneumocystis jirovecii pneumonia (PCP) is a relatively rare complication in non-HIV patients receiving immunosuppressive treatment. Since the introduction of tumour necrosis factor-α inhibitors cases of this complication have increased. We report the case of a 54-year-old, HIV-negative patient, who presented to our department with a long history of pustular psoriasis with poor response to traditional treatments. During the last admission he developed a severe flare that was unresponsive to cyclosporine, therefore infliximab was initiated. After the third dose he developed PCP that required admission to the intensive care unit, with a positive response to i.v. administration of trimethoprim/sulfamethoxazole. During follow up a mutation in the IL36RN gene compatible with an IL-36RN deficiency was found and anakinra was started, with rapid improvement of his psoriasis. PCP is a severe complication in patients receiving immunosuppressive therapy and is probably underreported by dermatologists. There are no clinical guidelines for PCP prophylaxis in dermatological patients who will receive immunosuppressive or biological treatments. We believe that it is necessary to report the cases of PCP to assess the real impact of this complication and develop appropriate prophylaxis guidelines.