Immunogenicity, reactogenicity, and safety of a second booster with BNT162b2 or full-dose mRNA-1273: A randomized VACCELERATE trial in adults aged ≥75 years (EU-COVAT-1-AGED Part B).

OBJECTIVES: To assess the safety and immunogenicity of a fourth vaccination (second booster) in individuals aged ≥75 years. METHODS: Participants were randomized to BNT162b2 (Comirnaty, 30 µg) or messenger RNA (mRNA)-1273 (Spikevax, 100 µg). The primary end point was the rate of two-fold antibody titer increase 14 days after vaccination, targeting the receptor binding domain (RBD) region of wild-type SARS-CoV-2. The secondary end points included changes in neutralizing activity against wild-type and 25 variants. Safety was assessed by monitoring solicited adverse events (AEs) for 7 days. RESULTS: A total of 269 participants (mean age 81 years, mRNA-1273 n = 135/BNT162b2 n = 134) were included. Two-fold anti-RBD immunoglobulin (Ig) G titer increase was achieved by 101 of 129 (78%) and 116 of 133 (87%) subjects in the BNT162b2 and the mRNA-1273 group, respectively (P = 0.054). A second booster of mRNA-1273 provided higher anti-RBD IgG geometric mean titer: 21.326 IU/mL (95% confidence interval: 18.235-24.940) vs BNT162b2: 15.181 IU/mL (95% confidence interval: 13.172-17.497). A higher neutralizing activity was noted for the mRNA-1273 group. The most frequent AE was pain at the injection site (51% in mRNA-1273 and 48% in BNT162b2). Participants in the mRNA-1273 group had less vaccine-related AEs (30% vs 39%). CONCLUSIONS: A second booster of either BNT162b2 or mRNA-1273 provided substantial IgG increase. Full-dose mRNA-1273 provided higher IgG levels and neutralizing capacity against SARS-CoV-2, with similar safety profile for subjects of advanced age.

Exploring patient-centered design solutions of a telehealth app for HIV - A qualitative study.

BACKGROUND: The Communication and Tracing App HIV (COMTRAC-HIV) project is developing a mobile health (mHealth) app for integrated care of HIV patients in Germany. The complexity of HIV treatment and continuous care necessitates the need for tailored mHealth solutions. This qualitative study explores design solutions and a prototype to enhance the app's functionality and effectiveness. METHODS: A total of eight HIV patients and pre-exposure prophylaxis (PrEP) users, recruited at the HIV Center Frankfurt, participated in focus groups and thinking-aloud tests (TA test). In the focus groups, design solutions were discussed for user-interface clarity, leading to the development of an interactive prototype, the usability of which was evaluated with a TA test. Data collection involved video/audio recordings. Qualitative analysis was conducted using a deductive category system, and focused on app design and usage in focus groups, and layout, navigation, interaction, terminology, comprehension, feedback, and level of satisfaction in TA tests. RESULTS: The app was commended for its simple, clear design, especially its medication reminders and health tracking features. Opinions on the symptom diary varied however, respondents noting it more suitable for HIV users than PrEP users. Privacy concerns suggest avoiding display of HIV-specific information. Suggested improvements include e.g. image uploads, drug interaction checks and prescription tracking. A total of 25 usability issues were identified in the TA test, with most found in the layout (n = 6), navigation (n = 5), interaction (n = 5), and terminology (n = 5) categories. Two examples are non-intuitive controls and illogical button placement. Despite these disadvantages, participants noted positive impressions (n = 5) in the satisfaction category. CONCLUSION: The study emphasizes the need for patient-centered design in mobile HIV care solutions, highlighting to the app's user-friendliness and potential to enhance care. Further research is necessary to refine the app's functionality and to align it with clinical and patients' privacy needs.

Care interruptions and mortality among adults in Europe and North America.

OBJECTIVE: Interruptions in care of people with HIV (PWH) on antiretroviral therapy (ART) are associated with adverse outcomes, but most studies have relied on composite outcomes. We investigated whether mortality risk following care interruptions differed from mortality risk after first starting ART. DESIGN: Collaboration of 18 European and North American HIV observational cohort studies of adults with HIV starting ART between 2004 and 2019. METHODS: Care interruptions were defined as gaps in contact of ≥365 days, with a subsequent return to care (distinct from loss to follow-up), or ≥270 days and ≥545 days in sensitivity analyses. Follow-up time was allocated to no/preinterruption or postinterruption follow-up groups. We used Cox regression to compare hazards of mortality between care interruption groups, adjusting for time-updated demographic and clinical characteristics and biomarkers upon ART initiation or re-initiation of care. RESULTS: Of 89 197 PWH, 83.4% were male and median age at ART start was 39 years [interquartile range (IQR): 31-48)]. 8654 PWH (9.7%) had ≥1 care interruption; 10 913 episodes of follow-up following a care interruption were included. There were 6104 deaths in 536 334 person-years, a crude mortality rate of 11.4 [95% confidence interval (CI): 11.1-11.7] per 1000 person-years. The adjusted mortality hazard ratio (HR) for the postinterruption group was 1.72 (95% CI: 1.57-1.88) compared with the no/preinterruption group. Results were robust to sensitivity analyses assuming ≥270-day (HR 1.49, 95% CI: 1.40-1.60) and ≥545-day (HR 1.67, 95% CI: 1.48-1.88) interruptions. CONCLUSIONS: Mortality was higher among PWH reinitiating care following an interruption, compared with when PWH initially start ART, indicating the importance of uninterrupted care.

Survival after cryptococcosis in Germany: A retrospective multicenter cohort study of patients diagnosed between 2004 and 2021.

Cryptococcosis is the most prevalent fungal infection of the central nervous system worldwide. We performed a retrospective multicenter cohort study to gain insights into the epidemiology of cryptococcosis in Germany. We describe the use of diagnostic tests, clinical management and patient outcome. We included 64 patients with underlying HIV infection (55%) or other predispositions. Molecular typing by MLST documented 20 individual sequence types among 42 typed isolates. A fatal outcome was documented in 14% of patients in the first two months after diagnosis.

Switching to dolutegravir plus rilpivirine versus maintaining current antiretroviral therapy regimen in virologically suppressed people with HIV-1 and the Lys103Asn (K103N) mutation: 48-week results from a randomised, open-label pilot clinical trial.

BACKGROUND: The combination of dolutegravir plus rilpivirine has been studied in people with virologically suppressed HIV with no previous history of treatment failure or resistance. We investigated the potential to maintain viral suppression with dolutegravir plus rilpivirine in people with Lys103Asn mutations whose HIV was previously managed with other treatment regimens. METHODS: In this open-label pilot trial at 32 clinical sites in seven European countries, virologically suppressed, HBsAg-negative adults aged 18 years or older with HIV-1 and Lys103Asn mutations were randomly assigned (2:1) to switch to 50 mg dolutegravir plus 25 mg rilpivirine (given as a single tablet) once daily or to continue their current antiretroviral therapy regimen (control group). After 48 weeks, participants in the control group also switched to dolutegravir plus rilpivirine. Randomisation was stratified by country, and a computer-generated randomisation list with permuted blocks within strata was used to assign participants to treatment groups. The primary endpoints were virological failure (ie, two consecutive measurements of 50 copies or more of HIV RNA per mL at least 2 weeks apart) and virological suppression (the proportion of participants with fewer than 50 copies of HIV RNA per mL) at week 48 (week 96 data will be reported separately). Analyses were done in the modified intention-to-treat population, which included all participants who received at least one dose of the study medication. This trial is registered with ClinicalTrials.gov, NCT05349838, and EudraCT, 2017-004040-38. FINDINGS: Between Nov 5, 2018, and Dec 9, 2020, 140 participants were enrolled and randomly assigned, 95 to the dolutegravir plus rilpivirine group and 45 to the control group. Virological failure was recorded in three participants (3·2%, 95% CI 0·7 to 9·0) in the the dolutegravir plus rilpivirine group and one (2·2%, 0·1 to 11·8) in the control group. The proportion of participants in whom virological suppression was maintained at week 48 was 88·4% (80·2 to 94·1) in the dolutegravir plus rilpivirine group versus 88·9% (75·9 to 96·3) in the control group (difference -0·5, -11·7 to 10·7). Significantly more adverse events were recorded in the dolutegravir plus rilpivirine group than in the control group (234 vs 72; p=0·0034), but the proportion of participants who reported at least one adverse event was similar between groups (76 [80%] of 95 vs 33 [73%] of 45; p=0·39). The frequency of serious adverse events was low and similar between groups. INTERPRETATION: Virological suppression was maintained at week 48 in most participants with Lys103Asn mutations when they switched from standard regimens to dolutegravir plus rilpivirine. The results of this pilot study, if maintained when the week 96 data are reported, support conduct of a large, well-powered trial of dolutegravir plus rilpivirine. FUNDING: ViiV Healthcare.

AIDS-defining events among people living with HIV who have been under continuous antiretroviral therapy for more than one year, a German cohort study 1999-2018.

PURPOSE: This study examined the characteristics, incidence and prognostic factors of the first AIDS-defining condition developed after more than one year of continuous antiretroviral therapy (ART) among people living with HIV (PLHIV). METHODS: We used data from two multicentre observational cohorts of PLHIV in Germany between 1999 and 2018. Our outcome was the first AIDS-defining event that occurred during follow-up after more than one year of continuous ART. Descriptive analyses at ART initiation, at the time of the AIDS event and of the most frequently observed types of AIDS-defining illnesses were performed. We calculated the incidence rate (IR) per 1000 person-years (PY) and used a bootstrap stepwise selection procedure to identify predictors of the outcome. RESULTS: A total of 12,466 PLHIV were included in the analyses. 378 developed the outcome, constituting an overall IR of 5.6 (95% CI 5.1-6.2) AIDS events per 1000 PY. The majority of PLHIV was virally suppressed at the time of the event. Oesophageal candidiasis and wasting syndrome were the most frequently diagnosed AIDS-defining illnesses. We found a low CD4 count at ART initiation, a previous AIDS-defining condition and transmission through intravenous drug use to be meaningful prognostic factors of the outcome. CONCLUSION: The overall rate of AIDS-defining events among PLHIV under long-term ART was low, highlighting the importance of continuous treatment. PLHIV who started ART with indicators of impaired immune functioning were more susceptible to disease progression, suggesting that the public health response should continue to focus on early and sustained treatment for all PLHIV.

Next-generation study databases require FAIR, EHR-integrated, and scalable Electronic Data Capture for medical documentation and decision support.

Structured patient data play a key role in all types of clinical research. They are often collected in study databases for research purposes. In order to describe characteristics of a next-generation study database and assess the feasibility of its implementation a proof-of-concept study in a German university hospital was performed. Key characteristics identified include FAIR access to electronic case report forms (eCRF), regulatory compliant Electronic Data Capture (EDC), an EDC with electronic health record (EHR) integration, scalable EDC for medical documentation, patient generated data, and clinical decision support. In a local case study, we then successfully implemented a next-generation study database for 19 EDC systems (n = 2217 patients) that linked to i.s.h.med (Oracle Cerner) with the local EDC system called OpenEDC. Desiderata of next-generation study databases for patient data were identified from ongoing local clinical study projects in 11 clinical departments at Heidelberg University Hospital, Germany, a major tertiary referral hospital. We compiled and analyzed feature and functionality requests submitted to the OpenEDC team between May 2021 and July 2023. Next-generation study databases are technically and clinically feasible. Further research is needed to evaluate if our approach is feasible in a multi-center setting as well.

Pathogen spectrum of community acquired pneumonia in people living with HIV (PLWH) in the German CAPNETZ-Cohort.

OBJECTIVES: The objective of this study was to identify the pathogen spectrum of community acquired pneumonia in people living with HIV (PLWH), and to compare it with a matched HIV negative group in order to reassess therapeutic strategies for PLWH. METHODS: Seventy-three (n = 73) PLWH (median CD4 3-6 months before CAP: 515/µl; SD 309) with community acquired pneumonia (CAP) were matched with 218 HIV-negative CAP controls in a prospective study design. Pathogen identifications used blood culture, samples from the upper and lower respiratory tract (culture and multiplex PCR) and urinary pneumococcal and legionella antigen test. RESULTS: Although the vaccination rate among PLWH with CAP was significantly higher (pneumococcal vaccination: 27.4 vs. 8.3%, p < 0.001; influenza vaccination: 34.2 vs. 17.4%, p = 0.009), pneumococci were found most frequently as pathogen among both PLWH (n = 19/21.3%) and controls (n = 34/17.2%; p = 0.410), followed by Haemophilus influenzae (PLWH, n = 12/13.5%, vs. controls, n = 25 / 12.6%; p = 0.850). Staphylococcus aureus was found equally in 20.2 and 19.2% in PLWH and controls, but infection or colonization could not be distinguished. Mortality during 6-month follow-up was significantly higher for PLWH (5/73, or 6.8%) versus controls (3/218, or 1.4%), however with lower case numbers than previously reported. Typical HIV-associated pathogens such as Pneumocystis jirovecii were found only exceptionally. CONCLUSIONS: Our study underscores the persistent clinical burden of CAP for PLWH. From pathogen perspective, empirical antibiotic treatment for CAP in PLWH on antiretroviral therapy should cover pneumococci and Haemophilus influenzae and may be adopted from valid common recommendations.

Coinfections and antimicrobial treatment in a cohort of falciparum malaria in a non-endemic country: a 10-year experience.

INTRODUCTION: Falciparum malaria remains one of the deadliest infectious diseases worldwide. In Germany, it is mainly an imported infection among travellers. Rates of coinfection are often unknown, and a clinical rationale for the beneficial use of calculated antibiotic therapy in patients with malaria and suspected coinfection is lacking. METHODS: We conducted an analysis of all in-patients treated with falciparum malaria at a German infectious diseases centre in vicinity to one of Europe's major airports for 2010-2019. Logistic regression and time-to-event analysis were used to evaluate predictors for bacterial coinfection, the use of antibacterial substances, as well as their influence on clinical course. RESULTS: In total, 264 patients were included. Of those, 64% received an additional antibacterial therapy (n = 169). Twenty-nine patients (11.0%) were found to have suffered from a relevant bacterial coinfection, while only a small fraction had relevant bacteremia (n = 3, 1.4%). However, patients with severe malaria did not suffer from coinfections more frequently (p = 0.283). CRP levels were not a reliable predictor for a bacterial coinfection (OR 0.99, 95% CI 0.94-1.06, p = 0.850), while another clinical focus of infection was positively associated (OR 3.86, 95% CI 1.45-11.55, p = 0.010). CONCLUSION: Although bacterial coinfections were rare in patients with malaria at our centre, the risk does not seem negligible. These data point rather towards individual risk assessment in respective patients than to general empiric antibiotic use.

Differences in the Course of CD4 and CD8 Cells After Chemoradiotherapy in People Living with HIV with Anal Cancer.

Incidence of anal carcinoma (AC) in people living with HIV (PLWH) is increased compared to the general population. Adverse effects of chemoradiotherapy (CRT) on the immune system are associated with a significant detrimental prognosis on overall survival in patients receiving CRT for solid tumors. The aim of this study was to evaluate immunological factors, in particular the differences in recovery of CD4+ and CD8+ cell counts before and after CRT for AC in PLWH. Retrospective single-center chart review extraction to analyze immunological data collected from PLWH with AC; descriptive statistics were used. Thirty-six PLWH with histologically proven AC were included in the analysis. Absolute CD4 cell count 60 months after CRT was 67.2% of the value at the beginning of CRT, whereas the CD8 cell count reached 82.3%. These differences were statistically significant (p = .048), whereas CD4/CD8-ratio remained stable. The findings of the presented study regarding CD4+ and CD8+ cell recovery after CRT are congruent with results from prior studies in non-HIV infected patients. Although not reaching the level of prior CRT T cell numbers, the ability to generate CD8+ cells seems to be better recovered, while CD4+ regeneration is more impaired. These observations are best explained by faster recovery of CD8+ cells via thymic-independent pathways, which are not available for regeneration of CD4+ cells. Further studies with larger numbers of patients are required to analyze the specific CD4+ and CD8+ cell subsets.

Dynamics and durability of HIV-1 neutralization are determined by viral replication.

Human immunodeficiency virus type 1 (HIV-1)-neutralizing antibodies (nAbs) that prevent infection are the main goal of HIV vaccine discovery. But as no nAb-eliciting vaccines are yet available, only data from HIV-1 neutralizers-persons with HIV-1 who naturally develop broad and potent nAbs-can inform about the dynamics and durability of nAb responses in humans, knowledge which is crucial for the design of future HIV-1 vaccine regimens. To address this, we assessed HIV-1-neutralizing immunoglobulin G (IgG) from 2,354 persons with HIV-1 on or off antiretroviral therapy (ART). Infection with non-clade B viruses, CD4+ T cell counts <200 µl-1, being off ART and a longer time off ART were independent predictors of a more potent and broad neutralization. In longitudinal analyses, we found nAb half-lives of 9.3 and 16.9 years in individuals with no- or low-level viremia, respectively, and 4.0 years in persons who newly initiated ART. Finally, in a potent HIV-1 neutralizer, we identified lower fractions of serum nAbs and of nAb-encoding memory B cells after ART initiation, suggesting that a decreasing neutralizing serum activity after antigen withdrawal is due to lower levels of nAbs. These results collectively show that HIV-1-neutralizing responses can persist for several years, even at low antigen levels, suggesting that an HIV-1 vaccine may elicit a durable nAb response.

Enhancing HIV Patient Support Through Telehealth: Exploring Design Solutions.

In recent years, telemedicine has advanced significantly, offering new possibilities for improving healthcare and patient outcomes. This paper presents a telemedicine app for HIV patients, developed using a human-centered design approach. Designed to meet the diverse and specific needs of Pre-Exposure Prophylaxis (PrEP) users and Late Presenters (LP), the app is part of the COMTRAC-HIV Project at the University Hospital Frankfurt. Through interviews with HIV experts and healthcare professionals, initial design solutions were derived. The paper explores the app's design process, core functionalities, and future directions, aiming to provide comprehensive support for individuals living with HIV.

Interviews with HIV Experts for Development of a Mobile Health Application in HIV Care-A Qualitative Study.

The Communication and Tracing App HIV (COMTRAC-HIV) project aims to develop a mobile health application for integrated care of HIV patients due to the low availability of those apps in Germany. This study addressed organizational conditions and necessary app functionalities, especially for the care of late diagnosed individuals (late presenters) and those using pre-exposure prophylaxis. We followed a human-centered design approach and interviewed HIV experts in Germany to describe the context of use of the app. The interviews were paraphrased and analyzed with a qualitative content analysis. To define the context of use, user group profiles were defined and tasks derived, which will represent the functionalities of the app. A total of eight experts were included in the study. The results show that the app should include a symptom diary for entering symptoms, side effects, and their intensity. It offers chat/video call functionality for communication with an HIV expert, appointment organization, and sharing findings. The app should also provide medication overview and reminders for medications and appointments. This qualitative study is a first step towards the development of an app for HIV individuals in Germany. Further research includes involving patients in the initial app design and test design usability.

Trends in Cancer Incidence in Different Antiretroviral Treatment-Eras amongst People with HIV.

Despite cancer being a leading comorbidity amongst individuals with HIV, there are limited data assessing cancer trends across different antiretroviral therapy (ART)-eras. We calculated age-standardised cancer incidence rates (IRs) from 2006-2021 in two international cohort collaborations (D:A:D and RESPOND). Poisson regression was used to assess temporal trends, adjusted for potential confounders. Amongst 64,937 individuals (31% ART-naïve at baseline) and 490,376 total person-years of follow-up (PYFU), there were 3763 incident cancers (IR 7.7/1000 PYFU [95% CI 7.4, 7.9]): 950 AIDS-defining cancers (ADCs), 2813 non-ADCs, 1677 infection-related cancers, 1372 smoking-related cancers, and 719 BMI-related cancers (groups were not mutually exclusive). Age-standardised IRs for overall cancer remained fairly constant over time (8.22/1000 PYFU [7.52, 8.97] in 2006-2007, 7.54 [6.59, 8.59] in 2020-2021). The incidence of ADCs (3.23 [2.79, 3.72], 0.99 [0.67, 1.42]) and infection-related cancers (4.83 [4.2, 5.41], 2.43 [1.90, 3.05]) decreased over time, whilst the incidence of non-ADCs (4.99 [4.44, 5.58], 6.55 [5.67, 7.53]), smoking-related cancers (2.38 [2.01, 2.79], 3.25 [2.63-3.96]), and BMI-related cancers (1.07 [0.83, 1.37], 1.88 [1.42, 2.44]) increased. Trends were similar after adjusting for demographics, comorbidities, HIV-related factors, and ART use. These results highlight the need for better prevention strategies to reduce the incidence of NADCs, smoking-, and BMI-related cancers.

Time discrepancy for tuberculosis-negative microscopy and culture - the diagnostic gap remains: systematic analysis from a large tertiary care tuberculosis-clinic, Germany 2013-2017.

OBJECTIVES: Patients with open pulmonary tuberculosis (opTB) are subject to strict isolation rules. Sputum smear microscopy is used to determine infectivity, but sensitivity is lower than for culture. This study aimed to investigate the clinical relevance of this mismatch in contemporary settings. METHODS: Differential results between microscopy and culture were determined at the time of microscopic sputum conversion, from all patients with opTB between 01/2013 and 12/2017. In addition, data on HIV, multi/extensive drug-resistant TB status, time to smear- and cultural-negativity conversion were analyzed; and a Kaplan-Meier curve was developed. RESULTS: Of 118 patients with opTB, 58 had demographic data available for microbiological and clinical follow-up analysis; among these, 26 (44.8%) had still at least one positive culture result. Median time from opTB-treatment initiation to full microscopic sputum- or culture conversion, was 16.5 days (range 2-105), and 20 days (1-105), respectively (median difference: +3.5 days). Sixteen days after de-isolation, >90% had converted culturally. HIV- or multi/extensive drug-resistant TB status did not impact conversion time. CONCLUSION: When patients with opTB were de-isolated after 3 negative sputum smear microscopy tests, a substantial part still revealed cultural growth of Mycobacterium tuberculosis complex, but it remains unclear, whether smear-negative and culturally-positive individuals on therapy are really infective. Thus, the clinical relevance of this finding warrants further investigation.

Motile microfilaria captured by fluorescent microscopy and the unmasking of eosinophilia following treatment.

A 24-year-old patient from Cameroon presented to our hospital because of a foreign structure in her left eye. To our knowledge, for the first time, fluorescent microscopy revealed motile microfilariae, and the diagnosis of loiasis was established. Despite substantial microfilaremia, eosinophilia only unmasked after the initiation of antiparasitic therapy.

Expanding epidemic of recently acquired HCV in HIV-coinfected patients over a period of 10 years.

Background & Aims: Ongoing transmission of HCV infections is associated with risk factors such as drug injection, needlestick injuries, and men who have sex with men (MSM). Ways of transmission, the course of acute infection, changes of virologic features, and incidence over time are not well known. Methods: Over a period of 10 years, n = 161 patients with recently acquired HCV infection (RAHC) (median follow-up 6.8 years) were prospectively enrolled. NS5B sequencing was performed to re-evaluate the HCV genotype (GT) and for phylogenetic analyses. Results: Patients with RAHC were mainly male (92.5%), MSM (90.1%), and HIV-coinfected (86.3%). Transmission risk factors for MSM and non-MSM were sexual risk behaviour (100 and 6.3%, respectively), injection drug use (9.7 and 37.5%, respectively), and nasal drug use (15.2 and 0%, respectively). Spontaneous and interferon- or direct-acting antiviral-based clearance rates were 13.6, 84.3 and 93.4%, respectively. Mean RAHC declined from 19.8 in the first to 13.2 in the past five study years. Although the majority of infections was caused by HCV GT1a, the frequency of HCV GT4d and slightly HCV GT3a increased over time. No relevant clustering of HCV isolates was observed in non-MSM. However, 45% of HCV GT1a and 100% of HCV GT4d MSM cases clustered with MSM isolates from other countries. Travel-associated infections were supported by personal data in an MSM subgroup. No international clustering was detected in MSM with HCV GT1b or HCV GT3a. Conclusions: RAHCs were mainly diagnosed in HIV-coinfected MSM patients and were associated with sexual risk behaviour. Spontaneous clearance rates were low, and phylogenetic clusters were observed in the majority of patients. Impact and Implications: We evaluated the occurrence and transmission of recently acquired HCV infections (RAHCs) over a period of 10 years. Our data demonstrate that the presence of RAHC was mainly found in HIV-coinfected MSM, with internationally connected transmission networks being observed in the majority of patients. Spontaneous clearance rates were low, and reinfection rates increased mainly driven by a small subset of MSM patients with high-risk behaviour.

Incidence of Hypertension and Blood Pressure Changes in Persons With Human Immunodeficiency Virus at High Risk for Cardiovascular Disease Switching From Boosted Protease Inhibitors to Dolutegravir: A Post-hoc Analysis of the 96-week Randomised NEAT-022 Trial.

BACKGROUND: Integrase inhibitors have been recently linked to a higher risk for hypertension. In NEAT022 randomized trial, virologically suppressed persons with human immunodeficiency virus (HIV, PWH) with high cardiovascular risk switched from protease inhibitors to dolutegravir either immediately (DTG-I) or after 48 weeks (DTG-D). METHODS: Primary endpoint was incident hypertension at 48 weeks. Secondary endpoints were changes in systolic (SBP) and diastolic (DBP) blood pressure; adverse events and discontinuations associated with high blood pressure; and factors associated with incident hypertension. RESULTS: At baseline, 191 (46.4%) participants had hypertension and 24 persons without hypertension were receiving antihypertensive medications for other reasons. In the 197 PWH (n = 98, DTG-I arm; n = 99, DTG-D arm) without hypertension or antihypertensive agents at baseline, incidence rates per 100 person-years were 40.3 and 36.3 (DTG-I) and 34.7 and 52.0 (DTG-D) at 48 (P = .5755) and 96 (P = .2347) weeks. SBP or DBP changes did not differed between arms. DBP (mean, 95% confidence interval) significantly increased in both DTG-I (+2.78 mmHg [1.07-4.50], P = .0016) and DTG-D (+2.29 mmHg [0.35-4.23], P = .0211) arms in the first 48 weeks of exposure to dolutegravir. Four (3 under dolutegravir, 1 under protease inhibitors) participants discontinued study drugs due to adverse events associated with high blood pressure. Classical factors, but not treatment arm, were independently associated with incident hypertension. CONCLUSIONS: PWH at high risk for cardiovascular disease showed high rates of hypertension at baseline and after 96 weeks. Switching to dolutegravir did not negatively impact on the incidence of hypertension or blood pressure changes relative to continuing protease inhibitors.