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Costiniuk, Cecilia T.; Jenabian, Mohammad-Ali
Thanks to the success of modern antiretroviral therapy (ART), people living with HIV (PLWH) have life expectancies which approach that of persons in the general population. However, despite the ability of ART to suppress viral replication, PLWH have high levels of chronic systemic inflammation which drives the development of comorbidities such as cardiovascular disease, diabetes and non-AIDS associated malignancies. Historically, cannabis has played an important role in alleviating many symptoms experienced by persons with advanced HIV infection in the pre-ART era and continues to be used by many PLWH in the ART era, though for different reasons. Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) are the phytocannabinoids which have received most attention for their medicinal properties. Due to their ability to suppress lymphocyte proliferation and inflammatory cytokine production, there is interest in examining their therapeutic potential as immunomodulators. CB2 receptor activation has been shown in vitro to reduce CD4 T-cell infection by CXCR4-tropic HIV and to reduce HIV replication. Studies involving SIV-infected macaques have shown that Δ9-THC can reduce morbidity and mortality and has favourable effects on the gut mucosal immunity. Furthermore, Δ9-THC administration was associated with reduced lymph node fibrosis and diminished levels of SIV proviral DNA in spleens of rhesus macaques compared with placebo-treated macaques. In humans, cannabis use does not induce a reduction in peripheral CD4 T-cell count or loss of HIV virological control in cross-sectional studies. Rather, cannabis use in ART-treated PLWH was associated with decreased levels of T-cell activation, inflammatory monocytes and pro-inflammatory cytokines secretion, all of which are related to HIV disease progression and co-morbidities. Randomized clinical trials should provide further insights into the ability of cannabis and cannabinoid-based medicines to attenuate HIV-associated inflammation. In turn, these findings may provide a novel means to reduce morbidity and mortality in PLWH as adjunctive agents to ART.
Correspondence to Cecilia T. Costiniuk, Dr, Chronic Viral Illnesses Service, McGill University Health Centre, Montreal, Quebec Canada, Royal Victoria Hospital: Glen Site; 1001 boulevard Decarie, Montreal, Quebec, H4A 3J1. Tel: +14-843-2090; fax: +514-843-2092; e-mail: firstname.lastname@example.org
Received 6 August, 2019
Accepted 8 August, 2019
Copyright © 2019 Wolters Kluwer Health, Inc.
Management of partially-treated, community-acquired bacterial meningitis (PCBM) is commonly compromised by lack of microbiological diagnosis. We aimed to analyze the impact of FilmArray Meningitis-Encephalitis (FA-ME) PCR on the management of PCBM.
Comparison of treatment variables of PCBM cases between two periods, before (6.5 years, control group) and after (2 years, study group) the application of FA-ME PCR assay.
The total duration of antimicrobial treatment in the study group (n = 8) was significantly shorter than the control group (n = 23) (9.5 ± 3.7 days vs. 15.2 ± 5 days, p = 0.007). The percentage of narrow-spectrum regimens was significantly higher in the study group (78 ± 11% vs. 40 ± 9%, p = 0.03). There was a significant difference in implementation of antimicrobial chemoprophylaxis for close contacts (4/8 (50%) vs. 1/23 (4%), p = 0.01).
The use of FA-ME PCR provides significant benefits in the management of PCBM by shortening duration of antibiotic treatment, increasing the use of narrow-spectrum regimens, and allowing proper administration of antimicrobial chemoprophylaxis.
The study was approved and retrospectively registered by the Tel-Aviv Sourasky Medical Center (0378–17-TLV, 10/17/2017) and Rabin Medical Center (0270–18-RMC, 11/11/2018) Ethics committees and conforms to recognized standards.
Gynecomastia is known to occur in some men taking an efavirenz-based antiretroviral therapy (ART) regimen. However, the incidence and outcomes of gynecomastia are not known in Zimbabwe. We described the characteristics and outcomes of gynecomastia among male patients on an efavirenz-based ART regimen.
We conducted a retrospective cohort review of data of all male patients aged ≥18 years taking an efavirenz-based regimen at Newlands Clinic, Harare, Zimbabwe before 31 March 2017. The primary outcome was gynecomastia as defined by breast/nipple enlargement reported by patient and confirmed by clinical palpation. Routinely collected data on demographics, baseline CD4, body mass index, duration on efavirenz, clinical presentation and outcomes were extracted from the clinic database and analysed using STATA 12.1. We investigated for any associations with concomitant medicines using cox regression.
We analysed data for 1432 men with a median age of 40 years (IQR: 33–48). Half of the patients were in WHO stage 1 at ART commencement. Median body mass index and CD4 count at efavirenz commencement was 21 (IQR: 19–23) and 260 cells/mm3 (IQR: 126–412) respectively. The incidence of gynecomastia was 22/1000 person-years (IQR: 17.3–27.8). Over half of the cases (58%) were bilateral and 75% of all cases developed within two years of starting efavirenz. There were no significant associations with concomitant use of isoniazid (HR: 0.95, p = 0.87) or amlodipine (HR: 0.43, p = 0.24). Gynecomastia resolved in 83.5% of cases following withdrawal of efavirenz with a median time to resolution of 3 months (IQR: 2–9).
The incidence of gynecomastia among patients taking efavirenz-based ART was low with most cases developing early on during treatment. Most cases resolved completely after withdrawing efavirenz.
Despite rapid scale up of antiretroviral therapy (ART), Tuberculosis (TB) remains the commonest opportunistic infection and cause of death among HIV infected individuals in resource limited settings like India. Incidence of TB in individuals on ART in private healthcare sector in India is infrequently studied.
This retrospective cohort study conducted between 1st March 2009 and 1st March 2017 aimed to evaluate rate of incident TB in individuals initiated on ART at 3 private sector ART clinics in Pune, India. Individuals more than 12 years of age with ART duration of atleast 6 months were included. Patients were classified as having prevalent TB if they had a TB episode within the year prior to ART initiation or if they developed TB within 6 months of starting ART. Individuals who were diagnosed with TB after 6 months of starting ART were classified as incident TB cases. A recurrent episode of TB after treatment completion or cure of prevalent TB was also regarded as incident TB. Patients were classified as definitive TB if Mycobacterium tuberculosis was grown in culture from a biological sample or a positive rapid molecular test. Patients were classified as probable TB if there was radiologic evidence of TB in absence of confirmatory culture or PCR.
1904 patients with a median duration of follow up on ART of 57 (IQR = 32.0, 84.0) months were included. Of these, 182 developed incident TB (22% definitive TB, 38% recurrent cases). TB incidence at 6–12 months, 13–24 months, 25–60 months and > 60 months of ART was 24.32, 5.46, 2.54 and 0.75 cases per 100 person years respectively. Current time updated CD4 count
Montgomery, Elizabeth T.; Roberts, Sarah T.; Nel, Annalene; Malherbe, Mariette; Torjesen, Kristine; Bunge, Katherine; Singh, Devika; Baeten, Jared M.; Marrazzo, Jeanne; Chirenje, Z. Michael; Kabwigu, Samuel; Beigi, Richard; Riddler, Sharon A.; Gafoor, Zakir; Reddy, Krishnaveni; Mansoor, Leila E.; Nair, Lulu; Woeber, Kusbashini; Moodley, Jothi; Jeenarain, Nitesha; Siva, Samantha; Naidoo, Logashvari; Govender, Vaneshree; Palanee-Phillips, Thesla
Assessment of safety is an integral part of real-time monitoring in clinical trials. In HIV prevention research, safety of investigational products and trial participation has been expanded to include monitoring for “social harms” (SH), generally defined as negative consequences of trial participation that may manifest in social, psychological, or physical ways. Further research on SH within HIV prevention research is needed to understand the potential safety risks for women and advance the implementation of prevention methods in real-world contexts.
Secondary analysis of quantitative data from three randomized, double-blind, placebo-controlled trials of microbicide candidates in sub-Saharan Africa was conducted. Additionally, we assessed data from two prospective cohort studies that included participants who became HIV-positive or pregnant during parent trials.
SH reporting was low across the largest and most recent microbicide studies. SH incidence per 100 person-years ranged from 1.10 (95% CI: 0.78–1.52) to 3.25 (95% CI: 2.83–3.74) in the phased trials. Reporting differed by dosing mechanism (e.g. vaginal gel, oral tablet, ring) and study, most likely as a function of measurement differences. SH were most frequently associated with male partners, rather than, for example, experiences of stigma in the community.
Measurement and screening for SH is an important component of conducting ethical research of novel HIV prevention methods. To date SH incidence reported in microbicide trials has been relatively low (
Vancomycin resistant enterococci (VRE) infections are of increasing concern in many hospitalized patients. Patients with cirrhosis are at added risk of infection with VRE, with associated increased risk for complications from infections. The goals of this study were to:  identify risk factors for VRE amongst cirrhotic patients before liver transplantation, and  evaluate risk of morbidity and mortality at 30-days and one-year after VRE infection.
Chart review of 533 cirrhotic patients hospitalized at a tertiary medical center was performed. Patients infected with VRE (n = 65) were separately compared to patients infected with gram-negative organisms (n = 80) and uninfected patients (n = 306).
In multivariable logistic regression analyses, female gender (OR 3.73(95% CI1.64,8.49)), severity of liver disease measured by higher Child Pugh scores (OR 0.37(95%CI 0.16,0.84)), presence of ascites (OR 9.43(95% CI 3.22,27.65) and any type of dialysis (OR 3.31,95% CI (1.21,9.04), oral antibiotic prophylaxis for spontaneous bacterial peritonitis and rifaximin use were statistically significantly associated with VRE infection (OR 2.37 (95%CI 1.27, 4.42)). VRE-infected patients had significantly longer mean ICU and total hospital stays (both p
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