Major cardiovascular events after COVID-19 in people with HIV.

OBJECTIVES: To assess the effect of COVID-19 on the postacute risk of cardiovascular events (CVEs) among people with HIV (PWH). METHODS: Population-based matched cohort, including all PWH ≥16 years in the Catalan PISCIS HIV cohort. We estimated the incidence rate of the first CVE after COVID-19, analysed it a composite outcome (2020-2022). We adjusted for baseline differences using inverse probability weighting and used competing risk analysis. RESULTS: We included 4199 PWH with and 14 004 PWH without COVID-19. The median follow-up was 243 days (interquartile range [IQR]: 93-455), 82% (14 941/18 203) were men, with a median age of 47 years. Overall, 211 PWH with COVID-19 and 621 without developed CVE, with an incidence rate of 70.2 and 56.8/1000 person-years, respectively. During COVID-19 infection, 7.6% (320/4199) required hospitalization and 0.6% (25/4199) intensive care unit admission, 97% (4079/4199) had CD4+T-cell ≥200 cells/µL, 90% (3791/4199) had HIV-RNA<50 copies/mL and 11.8% (496/4199) had previous CVE at baseline. The cumulative CVE incidence was higher among PWH after COVID-19 compared with PWH without COVID-19 during the first year (log-rank p=0.011). The multivariable analysis identified significantly increased CVE risk with age, heterosexual men, previous cardiovascular disease (CVD), and chronic kidney or liver disease. COVID-19 was associated with increased subsequent risk of CVE (adjusted hazard ratio 1.30 [95% CI, 1.09-1.55]), also when only including individuals without previous CVD (1.60 [95% CI, 1.11-2.29]) or nonhospitalized patients (1.34 [95% CI, 1.11-1.62]). DISCUSSION: COVID-19 was associated with a 30% increased risk of major CVE in PWH during the subsequent year, suggesting that COVID-19 should be considered an additional CVD risk in PWH in the short term.

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.

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.

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.

Changing Trends in the Global Consumption of Treatments Used in Hospitalized Patients for COVID-19: A Time Series Multicentre Study.

AIM: To analyze trends in the prescription of COVID-19 treatments for hospitalized patients during the pandemic. METHODS: Multicenter, ecological, time-series study of aggregate data for all adult patients with COVID-19 treated in five acute-care hospitals in Barcelona, Spain, between March 2020 and May 2021. Trends in the monthly prevalence of drugs used against COVID-19 were analyzed by the Mantel-Haenszel test. RESULTS: The participating hospitals admitted 22,277 patients with COVID-19 during the study period, reporting an overall mortality of 10.8%. In the first months of the pandemic, lopinavir/ritonavir and hydroxychloroquine were the most frequently used antivirals, but these fell into disuse and were replaced by remdesivir in July 2020. By contrast, the trend in tocilizumab use varied, first peaking in April and May 2020, declining until January 2021, and showing a discrete upward trend thereafter. Regarding corticosteroid use, we observed a notable upward trend in the use of dexamethasone 6 mg per day from July 2020. Finally, there was a high prevalence of antibiotics use, especially azithromycin, in the first three months, but this decreased thereafter. CONCLUSIONS: Treatment for patients hospitalized with COVID-19 evolved with the changing scientific evidence during the pandemic. Initially, multiple drugs were empirically used that subsequently could not demonstrate clinical benefit. In future pandemics, stakeholders should strive to promote the early implementation of adaptive randomized clinical trials.

Long-term impact of COVID-19 associated acute respiratory distress syndrome.

OBJECTIVES: To determine the health status, exercise capacity, and health related quality of life (HRQoL) of COVID-19 associated acute respiratory distress syndrome (ARDS) survivors, 8 months after diagnosis. METHODS: All eligible patients were interviewed and underwent a physical examination, chest X-ray, and 6 min walk test (6MWT). Scales to evaluate post-traumatic stress disorder, depression, anxiety, and HRQoL were applied. RESULTS: Of 1295 patients, 365 suffered ARDS and 166 survived to hospital discharge. Five died after discharge and 48 were lost to follow-up. Of the 113 remaining patients, 81% had persistent symptoms. More than 50% of patients completed less than 80% of the theoretical distance on the 6MWT, 50% had an abnormal X-ray and 93% of patients developed psychiatric disorders. Mean SF-36 scores were worse than in the general population. After multivariate regression analysis, female sex, non-Caucasian race, and Charlson index>2 were independent risk factors for a worse mental health component summary score on the SF-36, and age was associated with a better prognosis. Female sex and chronic obstructive pulmonary disease were independently associated with a worse physical component summary score. CONCLUSION: COVID-19 associated ARDS survivors have long-term consequences in health status, exercise capacity, and HRQoL. Strategies addressed to prevent these sequelae are needed.