A characterization of the HIV population with limited/exhausted treatment options: a multicenter Belgian study.

OBJECTIVE: Describe the prevalence and characteristics of people living with HIV (PLWH) in Belgium with limited/exhausted treatment options. METHODS: A cross-sectional, multicenter study involving adult treatment-experienced individuals with limited/exhausted treatment options defined as having a multi-drug resistant HIV-1 or a history of multiple treatment changes. The primary outcome was to determine the prevalence of these individuals and classify them based on their two most recent consecutive HIV-1 viral loads (VLs): suppressed (2 VLs < 50 copies/mL), intermediate (≥1 VL between 50-200 copies/mL), or unsuppressed (2 VLs > 200 copies/mL). Secondary outcome was to characterize the participants included in this analysis. RESULTS: There were 119 individuals included (prevalence of 0.97%; 119 of 12 282 in care). The majority were aged > 50 years (88.2%), women represented 35.3%, and individuals were primarily White (54.7%). Median (IQR) CD4+ T-cell count was 635 (400-875) cells/µL and most (42%) were on a 3-drug ART regimen. Overall, 87.4% were classified as suppressed, 9.2% as intermediate, and 3.4% as unsuppressed. On multivariable analysis, CD4+ T-cell count < 200 cells/µL was associated with being classified as intermediate or unsuppressed (p = 0.004). CONCLUSION: In this analysis of PLWH in Belgium, individuals with limited/exhausted treatment options represented a small fraction. Most were on a 3-drug ART regimen, were virologically suppressed, and had a CD4+ T-cell count within normal range. A small proportion were not virologically suppressed while others, despite being suppressed, were on ≥ 4-drug ART regimens. As such, new therapeutic options are needed to achieve and maintain virologic suppression in such individuals while decreasing their pill burden.

Efficacy, durability, and tolerability of bictegravir/emtricitabine/tenofovir alafenamide for the treatment of HIV in a real-world setting in Belgium.

OBJECTIVES: Our objective was to evaluate the efficacy, durability, and tolerability of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in a real-world setting in Belgium. METHODS: This was a retrospective, multicentre cohort study involving adult treatment-naïve (TN) and treatment-experienced (TE) people living with HIV receiving BIC/FTC/TAF between 1 January 2019 and 30 September 2020. The primary outcome was rate of virological suppression (plasma HIV-1 viral load <50 copies/mL; on-treatment analysis) at weeks 24 and 48. The main secondary outcomes included loss of virological suppression (LVS; two consecutive viral loads of >200 copies/mL after being virologically suppressed) by week 48 and analysis of resistance-associated mutations at time of LVS; tolerability of BIC/FTC/TAF over the 48-week study period; and change in weight and proportion of participants reporting a >10% weight gain at week 48. RESULTS: Overall, 2001 participants were included. Through 48 weeks, overall rate of virological suppression was 93.5%, with similar results observed in the following subgroups: age ≥50 years (92.7%), women (92.8%), Black sub-Saharan African (91%), TN (94%), TE (93.2%), and non-suppressed at baseline (86.6%). LVS was observed in 0.7% (n = 14) of participants, with one participant developing resistance-associated mutations to nucleoside reverse transcriptase inhibitors (184 V) and integrase strand transfer inhibitors (263KR). Of the 131 (6.5%) treatment discontinuations, the most common reason was an adverse event (2.4%), with the most frequent being central nervous system/psychiatric (0.4%) and gastrointestinal (0.4%) toxicity. Median weight gain at week 48 was 2 kg (interquartile range -1 to 5), and a >10% weight increase was observed in 11.6% of participants. CONCLUSION: In this large real-world cohort, BIC/FTC/TAF showed excellent virological efficacy in a diverse population of patients with HIV. Rare occurrence of emergent drug resistance was observed, and treatment was well tolerated.

Efficacy, durability, and tolerability of dolutegravir/lamivudine and dolutegravir/rilpivirine for the treatment of HIV in a real-world setting in Belgium.

OBJECTIVES: A paradigm shift from three-drug regimens to two-drug regimens (2DRs) is currently taking place in real-world clinical practice. This study aimed to describe the efficacy, durability, and tolerability of dolutegravir (DTG)/lamivudine (3TC) and DTG/rilpivirine (RPV) in a real-world setting. METHODS: This was a retrospective, observational, multicentre (ten centres in Belgium) study involving adult treatment-naïve and treatment-experienced people living with HIV on DTG/3TC or DTG/RPV between 1 January 2019 and 30 September 2020. The primary endpoint was rate of virological suppression (VS; plasma HIV-1 viral load [VL] <50 copies/ml) using an on-treatment analysis. Main secondary endpoints included the proportion of people that experienced loss of VS (LVS; defined as two consecutive HIV-1 VLs of >200 copies/ml after initially achieving VS) and a resistance analysis at the time of LVS; rate, incidence, and reasons for discontinuation of treatment (stopping treatment or changing any component of the 2DR); and change in weight, along with the proportion of people reporting a >10% weight gain. Ordinal logistic regression analysis examined associations between baseline variables and >10% on-treatment weight gain. RESULTS: Overall, 948 people were included, of whom 734 (77%) were on DTG/3TC and 214 (23%) were on DTG/RPV. Baseline characteristics included 54% aged ≥50 years, 31% female, 31% Black sub-Saharan African, 95% treatment-experienced, and 8% with HIV-1 VL ≥50 copies/ml. Through 48 weeks, the rate of VS for the overall cohort was 98.3% (99.1% with 3TC; 96.2% with RPV). LVS was observed in 0.5% (n = 5) of the overall population (n = 1 [3TC group], n = 4 [RPV group]). There were 40 treatment discontinuations (4.2%, n = 27 [3TC group]; n = 13 [RPV group]), corresponding to an incidence of 4.7 per 100 patient-years. The most common reason for discontinuation was an adverse event (1.4%), with neurotoxicity the most frequent (0.5%). Median on-treatment weight gain at week 48 was 1 kg (interquartile range [IQR] -1-3) overall, 1 kg (IQR -1-3) in the 3TC group, and 2 kg (IQR 0-4) in the RPV group. A >10% weight increase was observed in 6.3% of people. Regression analysis showed that being on a tenofovir disoproxil fumarate-based regimen prior to 2DR initiation was the only variable associated with a >10% increase in weight from baseline (odds ratio 3.48; 95% confidence interval 1.13-10.68; p = 0.038). CONCLUSION: In this real-world analysis, the 2DRs analysed were effective, durable, and safe for those who were treatment-naive and treatment-experienced. A slight increase in weight was associated with these regimens.

Clinical characteristics and outcomes of COVID-19 in people living with HIV in Belgium: A multicenter, retrospective cohort.

The aim of this study was to describe the clinical characteristics and outcomes of coronavirus disease 2019 (COVID-19) among people living with HIV (PLWH) in Belgium. We performed a retrospective multicenter cohort analysis of PLWH with either laboratory-confirmed, radiologically diagnosed, or clinically suspected COVID-19 between February 15, 2020 and May 31, 2020. The primary endpoint was outcome of COVID-19. Secondary endpoints included rate of hospitalization and length of hospital stay and rate of Intensive Care Unit (ICU) admission and mechanical ventilation. One hundred and one patients were included in this study. Patients were categorized as having either laboratory-confirmed (n = 65), radiologically-diagnosed (n = 3), or clinically suspected COVID-19 (n = 33). The median age was 51.3 years (interquartile range [IQR] 41.3-57.3) and 44% were female. Ninety-four percent of patients were virologically suppressed and 67% had a CD4+ cell count more than or equal to 500 cells/µl. Overall, 46% of patients required hospitalization and the median length of hospital stay was 6 days (IQR 3-15). Age more than or equal to 50 years, Black Sub-Saharan African patients, and being on an integrase strand transfer inhibitor-based regimen were associated with being hospitalized. ICU admission and mechanical ventilation was required for 15% and 10% of all patients respectively. Overall, 9% of patients died while 78 (77%) patients made a full recovery. HIV patients with COVID-19 experienced a high degree of hospitalization despite having elevated CD4+ cell counts and a high rate of virologic suppression. Matched case-control studies are warranted to measure the impact that HIV may have on patients with COVID-19.

Model informed dosing of hydroxycholoroquine in COVID-19 patients: Learnings from the recent experience, remaining uncertainties and gaps.

AIMS: In the absence of a commonly agreed dosing protocol based on pharmacokinetic (PK) considerations, the dose and treatment duration for hydroxychloroquine (HCQ) in COVID-19 disease currently vary across national guidelines and clinical study protocols. We have used a model-based approach to explore the relative impact of alternative dosing regimens proposed in different dosing protocols for hydroxychloroquine in COVID-19. METHODS: We compared different PK exposures using Monte Carlo simulations based on a previously published population pharmacokinetic model in patients with rheumatoid arthritis, externally validated using both independent data in lupus erythematous patients and recent data in French COVID-19 patients. Clinical efficacy and safety information from COVID-19 patients treated with HCQ were used to contextualize and assess the actual clinical value of the model predictions. RESULTS: Literature and observed clinical data confirm the variability in clinical responses in COVID-19 when treated with the same fixed doses. Confounding factors were identified that should be taken into account for dose recommendation. For 80% of patients, doses higher than 800 mg day on day 1 followed by 600 mg daily on following days might not be needed for being cured. Limited adverse drug reactions have been reported so far for this dosing regimen, most often confounded by co-medications, comorbidities or underlying COVID-19 disease effects. CONCLUSION: Our results were clear, indicating the unmet need for characterization of target PK exposures to inform HCQ dosing optimization in COVID-19. Dosing optimization for HCQ in COVID-19 is still an unmet need. Efforts in this sense are a prerequisite for best benefit/risk balance.

Population Pharmacokinetics of Hydroxychloroquine in COVID-19 Patients: Implications for Dose Optimization.

BACKGROUND AND OBJECTIVE: In the absence of characterization on pharmacokinetics and reference concentrations for hydroxychloroquine in COVID-19 patients, the dose and treatment duration for hydrochloroquine are currently empirical, mainly based on in vitro data, and may vary across national guidelines and clinical study protocols. The aim of this paper is to describe the pharmacokinetics of hydroxychloroquine in COVID-19 patients, considered to be a key step toward its dosing optimization. METHODS: We have developed a population pharmacokinetic model for hydroxychloroquine in COVID-19 patients using prospectively collected pharmacokinetic data from patients either enrolled in a clinical trial or treated with hydroxychloroquine as part of standard of care in two tertiary Belgian hospitals. RESULTS: The final population pharmacokinetic model was a one-compartment model with first-order absorption and elimination. The estimated parameter values were 9.3/h, 860.8 L, and 15.7 L/h for the absorption rate constant, the central compartment volume, and the clearance, respectively. The bioavailability factor was fixed to 0.74 based on previously published models. Model validations by bootstraps, prediction corrected visual predictive checks, and normalized prediction distribution errors gave satisfactory results. Simulations were performed to compare the exposure obtained with alternative dosing regimens. CONCLUSION: The developed models provide useful insight for the dosing optimization of hydroxychloroquine in COVID-19 patients. The present results should be used in conjunction with exposure-efficacy and exposure-safety data to inform optimal dosing of hydroxychloroquine in COVID-19.

Microbiological profile and antimicrobial resistance among diabetic foot infections in Lebanon.

Diabetic Foot Infection (DFI) is a challenging complication of diabetes mellitus with a high burden in the Middle East where there is a marked increase in diabetes prevalence and complications. Early detection of DFI and the infectious organisms could result in the early initiation of appropriate antibiotic therapy and improved outcomes. DFI microbiological profiles differ between countries. In our region, Western guidelines are used when initiating treatment for DFI in the absence of local guidance. The purpose of our study was to determine the microbiologic profile and antimicrobial susceptibility of the DFI admissions at a large tertiary referral centre in Beirut and review other reported series in Lebanon and our region. This is a retrospective observational study of patients with DFI admitted to the American University of Beirut Medical Centre from January 2008 to June 2017. The bacteriologic isolation and antimicrobial susceptibility tests were performed according to standard microbiological methods. Between 2008 and 2017, 319 diabetic patients with DFU were admitted to AUBMC, and deep-tissue cultures were taken for 179 patients. From 179 deep tissue cultures, 314 bacterial isolates were obtained. Fifty-four percent of patients had the polymicrobial infection. Aerobic gram-negative rods (GNR) were more prevalent than gram-positive cocci (GPC) (55%, 39%, respectively). The most common isolate was Escherichia coli (15%) followed by Enterococcus (14%) and Pseudomonas aeruginosa (11%). Staphylococcus aureus isolates accounted for 9% with 50% of them being methicillin-resistant (MRSA). Among Enterobacteriaceae, 37% of isolates were fluoroquinolone-resistant, 25% were ESBL producers, and 2% were carbapenem-resistant. Antibiotic resistance was significantly associated with prior usage of antibiotics. Anaerobes were isolated in 1% and Candida species in 5% of isolates. The sensitivity, specificity, PPV, and NPV of swab culture recovery of pathogens compared with deep tissue culture were (76%, 72%, 76%, 72%) and (94%, 81%, 91%, 86%) for gram-positive and gram-negative organisms, respectively. The microbiological profile of DFI in Lebanon is comparable to other countries in the MENA region with big differences compared with the West. Therefore, it is imperative to develop local guidelines for antimicrobial treatment. The high prevalence of GNR in DFI and the high fluoroquinolone resistance should be taken into consideration when choosing empiric antibiotics. Empiric treatment for MRSA or Pseudomonas does not appear necessary except for patients with specific risk factors.

Effectiveness of dolutegravir-based antiretroviral therapy in a real-world setting in a Belgian cohort of 4101 HIV patients.

OBJECTIVE: To describe the treatment outcomes of patients receiving dolutegravir (DTG) in a 'real-world setting' in Belgium. DESIGN: Retrospective, observational, multicenter cohort. METHODS: Inclusion criteria: HIV-1 patients at least 18 years old having received DTG as part of their combined antiretroviral therapy (cART) between 1 April 2014 and 1 December 2017. Primary endpoint: rate of virologic suppression, defined as plasma HIV-1 viral load less than 50 copies/ml, at weeks 24, 48, and 96. Secondary endpoints: durability, expressed as probability of experiencing loss of virologic suppression by week 96 (defined as two consecutive HIV-1 viral load measurements of at least 200 copies/ml after having initially achieved virologic suppression); immunological response at weeks 24, 48, and 96; incidence of and reasons for DTG discontinuation; and change in weight at week 96. RESULTS: Four thousand, one hundred and one patients were included. Through 96 weeks, virologic suppression rate was 96% (on-treatment analysis), probability of experiencing loss of virologic suppression was 7%, and mean increase in CD4 cell count was 100 cells/µl (SD 220). There were 785 (19.1%) discontinuations of DTG (8.9 discontinuations per 100 patient-years). The most common cause of discontinuation was an adverse drug reaction (ADR; 9.5%) with neuropsychiatric toxicity being the most prevalent (5.2%; 2.4 discontinuations per 100 patient-years). By week 96, the median change in weight for the study population was +2.0 kg (IQR -1 to 5). CONCLUSION: In this large cohort, DTG showed excellent virologic efficacy and was generally well tolerated. Whether DTG results in undesirable weight gain or rather statistically significant results, remains a debate.

Clinical Management of Argentine Hemorrhagic Fever using Ribavirin and Favipiravir, Belgium, 2020.

We report a case of Argentine hemorrhagic fever diagnosed in a woman in Belgium who traveled from a disease-endemic area. Patient management included supportive care and combination therapy with ribavirin and favipiravir. Of 137 potential contacts, including friends, relatives, and healthcare and laboratory workers, none showed development of clinical symptoms of this disease.

Bilateral Carotid Patch Infection Occurring 12 years Following Endarterectomy.

BACKGROUND: Carotid endarterectomy (CEA) is the most commonly used invasive procedure for treatment of carotid stenosis. Different methods are used to close the arteriotomy including primary closure and patch repair with a graft. Prosthetic patch infection is a rare but serious complication of patch closure, and we will present a unique case of carotid patch infection (CPI) 12 years after implantation. CASE: Patient is 76-year-old male ex-smoker with history of bilateral CEA with Dacron patch closure 12 years prior to presentation. He had a left neck draining sinus one year prior to presentation that was treated by patch excision and ICA ligation. He presented to us one year later with a right neck draining sinus tract, reaching the carotid sheath on CT scan. Surgery was done under EEG and NIRS oximetry with shunting. Excision of the patch with the involved ICA was done. CCA to distal ICA bypass was done by a reversed GSV graft. Intraoperative cultures of the patch grew Staphylococcus species coagulase negative, so the patient was discharged on antibiotics for one month. The patient had early postoperative swallowing difficulty that resolved over six weeks but no other complications. Patient was followed-up every three months and he was doing well on one-year follow-up. DISCUSSION: Carotid patch infection is a well-documented complication of CEA with a prevalence between 0.27% and 1%. It most commonly presents as a pseudoaneurysm, draining sinus or neck swelling. The highest incidence is during the first year after the operation, and especially within the first three months postop due to contamination or wound infections; however, late presentations such as our case are rare. Bacterial cultures are positive in around 80% of the cases, growing mostly gram-positive cocci. Other organisms include Pseudomonas and Enterobacter. Management of CPI is challenging; difficulties include distal ICA control, friable arteries and adhesions to cranial nerves. Debridement with ligation of the vessel stump is an option, but may not be tolerated. Best outcomes are obtained with autogenous revascularization after debridement as was done in our case on the right side. Newer endovascular techniques may provide alternatives in urgent or high-risk situations, especially as staged procedures. This case is unique in its bilaterality and the longest time till presentation in the literature.

Three versus five lumbar paravertebral injections for inguinal hernia repair in the elderly: a randomized double-blind clinical trial.

PURPOSE: The objective of the study was to compare three nerve stimulator-guided paravertebral injections versus five injections for elderly patients undergoing inguinal hernia repair in terms of the amount of intraoperative fentanyl and propofol consumption and conversion to general anesthesia. The secondary objective was postoperative pain. METHODS: A prospective, randomized, double-blind clinical trial was performed. 200 elderly patients undergoing unilateral herniorrhaphy were randomized into two groups. Group III received three PVB injections from T12 to L2 and placebo at T11 and L3. Group V received five PVB injections from T11 to L3. RESULTS: The mean intraoperative fentanyl and propofol consumption were significantly lower in group V (4.9 ± 7.2 µg versus 20.0 ± 12.9 µg and 5.7 ± 11.6 mg versus 34.6 ± 22.9 mg, respectively, p value < 0.0001). Five patients (5.0%) in group III had failed block and were converted to general anesthesia (p value = 0.024). Group V had significantly lower pain scores compared to group III during the first three postoperative days (p value < 0.0001). CONCLUSION: The five PVB injection technique is more suitable as a sole anesthetic technique for elderly patients undergoing herniorrhaphy, since it required less intraoperative supplemental analgesia and provided lower postoperative pain scores compared to the three PVB injection technique. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02537860.

Risk Factors, Clinical Presentation, and Outcome of Acinetobacter baumannii Bacteremia.

Infections caused by Acinetobacter baumannii (AB), an increasingly prevalent nosocomial pathogen, have been associated with high morbidity and mortality. We conducted this study to analyze the clinical features, outcomes, and factors influencing the survival of patients with AB bacteremia. We retrospectively examined the medical records of all patients developing AB bacteremia during their hospital stay at a tertiary care hospital in Beirut between 2010 and 2015. Ninety episodes of AB bacteremia were documented in eighty-five patients. Univariate analysis showed that prior exposure to high dose steroids, diabetes mellitus, mechanical ventilation, prior use of colistin and tigecycline, presence of septic shock, and critical care unit stay were associated with a poor outcome. High dose steroids and presence of septic shock were significant on multivariate analysis. Crude mortality rate was 63.5%. 70.3% of the deaths were attributed to the bacteremia. On acquisition, 39 patients had septicemia. Despite high index of suspicion and initiation of colistin and/or tigecycline in 18/39 patients, a grim outcome could not be averted and 37 patients died within 2.16 days. Seven patients had transient benign bacteremia; three of which were treated with removal of the line. The remaining four did not receive any antibiotics due to withdrawal of care and died within 26.25 days of acquiring the bacteremia, with no signs of persistent infection on follow up. A prolonged hospital stay is frequently associated with loss of functionality, and steroid and antibiotic exposure. These factors seem to impact the mortality of AB bacteremia, a disease with high mortality rate and limited therapeutic options.