Publications by authors named "George A Yendewa"

18 Publications

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Dosing Colistimethate Every 8 h Results in Higher Plasma Concentrations of Active Colistin Than Every 12-Hourly Dosing without Increase in Nephrotoxicity: A Phase 1 Pharmacokinetics Trial in Healthy Adult Volunteers.

Antibiotics (Basel) 2022 Apr 6;11(4). Epub 2022 Apr 6.

Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.

Despite its use for decades, pharmacokinetic (PK) and safety studies on colistin are limited. We conducted a phase l, open-label trial to evaluate the safety and PK of multiple doses of intravenous (IV) and aerosolized colistimethate sodium (CMS) administered separately and in combination. In total, 31 healthy adults were enrolled into three cohorts of 9, 10, and 12 participants, respectively. Each cohort received increasing doses of CMS over three dosing periods as follows: Period 1 (IV only), 2.5 mg/kg every 12 h (q12h) to 3.3 mg/kg every 8 h (q8h); Period 2 (aerosolized only), 75 mg 2-4 doses, and Period 3 (combined IV aerosolized), in which was Periods 1 and 2 combined. Safety assessments, serum and lung concentrations of colistin analytes (colistin A, colistin B, CMS A, and CMS B), and kidney biomarkers were measured at specified time points. Increasing the CMS dose from 2.5 mg/kg q12h to q8h resulted in a 33% increase in serum colistin A concentrations from 3.9 μg/mL to 5.3 μg/mL-well above the accepted target of 2 μg/mL for 6 h after dosing, without evidence of nephrotoxicity. However, there was an increase in neurotoxicity, primarily perioral and lingual paresthesias, and self-limited ataxia. IV administration did not increase the lung concentrations of colistin.
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http://dx.doi.org/10.3390/antibiotics11040490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9029538PMC
April 2022

Multidrug-resistant tuberculosis in Sierra Leone.

Lancet Glob Health 2022 04;10(4):e459-e460

Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA; Division of Infectious Diseases and HIV Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

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http://dx.doi.org/10.1016/S2214-109X(22)00045-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8923690PMC
April 2022

Factors Associated with HBsAg Seropositivity among Pregnant Women Receiving Antenatal Care at 10 Community Health Centers in Freetown, Sierra Leone: A Cross-Sectional Study.

Pathogens 2022 Feb 12;11(2). Epub 2022 Feb 12.

Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.

Hepatitis B (HBV) is a major public health threat in Sierra Leone. Pregnant women are disproportionately impacted, yet little is known about the epidemiology of HBV in this group. We conducted a cross-sectional study of pregnant women aged ≥16 years receiving antenatal care across 10 community health centers in Freetown from July to September 2021 to assess the prevalence and associated factors of HBsAg seropositivity. Logistic regression was used to identify the predictors of HBsAg seropositivity. In total, 394 pregnant women were screened. The mean age was 24.4 ± 4.9 years, 78.2% were married, and 47.2% were in the second trimester. Only 1% had received the HBV vaccine. The prevalence of HBsAg was 7.9%, while HIV was 5.8% and HIV/HBV co-infection was 0.3%. Regarding high-risk practices, 76.6% reported female genital circumcision, 41.9% ear piercing, 29.0% endorsed multiple sexual partners, and 23.6% reported sexually transmitted infections. In the logistic regression analysis, having a husband/partner with HBV (adjusted odds ratio (aOR): 6.54; 95% CI: [1.72-24.86]; = 0.006) and residing in Central Freetown (aOR: 4.00; 95% CI: [1.46-11.00]; = 0.007) were independently associated with HBsAg seropositivity. Our findings support the scaling up of HBV services to target pregnant women and their partners for screening and vaccination to help reduce mother-to-child transmission rates in Sierra Leone.
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http://dx.doi.org/10.3390/pathogens11020243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8874792PMC
February 2022

Characterizing HIV-1 Genetic Subtypes and Drug Resistance Mutations among Children, Adolescents and Pregnant Women in Sierra Leone.

Genes (Basel) 2021 08 26;12(9). Epub 2021 Aug 26.

Group of Virology and Pathogenesis, Galicia Sur Health Research Institute (IIS Galicia Sur), Complexo Hospitalario Universitario de Vigo, SERGAS-UVigo, 36213 Vigo, Spain.

Human immunodeficiency virus (HIV) drug resistance (HIVDR) is widespread in sub-Saharan Africa. Children and pregnant women are particularly vulnerable, and laboratory testing capacity remains limited. We, therefore, used a cross-sectional design and convenience sampling to characterize HIV subtypes and resistance-associated mutations (RAMs) in these groups in Sierra Leone. In total, 96 children (age 2-9 years, 100% ART-experienced), 47 adolescents (age 10-18 years, 100% ART-experienced), and 54 pregnant women (>18 years, 72% ART-experienced) were enrolled. Median treatment durations were 36, 84, and 3 months, respectively, while the sequencing success rates were 45%, 70%, and 59%, respectively, among children, adolescents, and pregnant women. Overall, the predominant HIV-1 subtype was CRF02_AG (87.9%, 95/108), with minority variants constituting 12%. Among children and adolescents, the most common RAMs were M184V (76.6%, = 49/64), K103N (45.3%, = 29/64), Y181C/V/I (28.1%, = 18/64), T215F/Y (25.0%, = 16/64), and V108I (18.8%, = 12/64). Among pregnant women, the most frequent RAMs were K103N (20.6%, = 7/34), M184V (11.8%, = 4/34), Y181C/V/I (5.9%, = 2/34), P225H (8.8%, = 3/34), and K219N/E/Q/R (5.9%, = 2/34). Protease and integrase inhibitor-RAMs were relatively few or absent. Based on the genotype susceptibility score distributions, 73%, 88%, and 14% of children, adolescents, and pregnant women, respectively, were not susceptible to all three drug components of the WHO preferred first-line regimens per 2018 guidelines. These findings suggest that routine HIVDR surveillance and access to better ART choices may improve treatment outcomes in Sierra Leone.
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http://dx.doi.org/10.3390/genes12091314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469552PMC
August 2021

Impact of COVID-19 on Tuberculosis Case Detection and Treatment Outcomes in Sierra Leone.

Trop Med Infect Dis 2021 Aug 19;6(3). Epub 2021 Aug 19.

Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.

The COVID-19 pandemic has adversely affected tuberculosis (TB) care delivery in high burden countries. We therefore conducted a retrospective study to assess the impact of COVID-19 on TB case detection and treatment outcomes at the Chest Clinic at Connaught Hospital in Freetown, Sierra Leone. Overall, 2300 presumptive cases were tested during the first three quarters of 2020 (intra-COVID-19) versus 2636 in 2019 (baseline), representing a 12.7% decline. Testing declined by 25% in women, 20% in children and 81% in community-initiated referrals. Notwithstanding, laboratory-confirmed TB cases increased by 37.0% and treatment success rate was higher in 2020 (55.6% vs. 46.7%, = 0.002). Multivariate logistic regression analysis found that age < 55 years (aOR 1.74, 95% CI (1.80, 2.56); = 0.005), new diagnosis (aOR 1.69, 95% CI (1.16, 2.47); = 0.007), pulmonary TB (aOR 3.17, 95% CI (1.67, 6.04); < 0.001), HIV negative status (aOR 1.60, 95%CI (1.24, 2.06); < 0.001) and self-administration of anti-TB drugs through monthly dispensing versus directly observed therapy (DOT) (aOR 1.56, 95% CI (1.21, 2.03); = 0.001) independently predicted treatment success. These findings may have policy implications for DOTS in this setting and suggest that more resources are needed to reverse the negative impact of the COVID-19 pandemic on TB program activities in Sierra Leone.
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http://dx.doi.org/10.3390/tropicalmed6030154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8396336PMC
August 2021

Clinical Features and Outcomes of Coronavirus Disease 2019 Among People With Human Immunodeficiency Virus in the United States: A Multicenter Study From a Large Global Health Research Network (TriNetX).

Open Forum Infect Dis 2021 Jul 1;8(7):ofab272. Epub 2021 Jun 1.

Center for Clinical Research, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.

Background: Human immunodeficiency virus infection (HIV) is a presumed risk factor for severe coronavirus disease 2019 (COVID-19), yet little is known about COVID-19 outcomes in people with HIV (PWH).

Methods: We used the TriNetX database to compare COVID-19 outcomes of PWH and HIV-negative controls aged ≥18 years who sought care in 44 healthcare centers in the United States from January 1 to December 1, 2020. Outcomes of interest were rates of hospitalization (composite of inpatient non-intensive care [ICU] and ICU admissions), mechanical ventilation, severe disease (ICU admission or death), and 30-day mortality.

Results: Of 297 194 confirmed COVID-19 cases, 1638 (0.6%) were HIV-infected, with >83% on antiretroviral therapy (ART) and 48% virally suppressed. Overall, PWH were more commonly younger, male, African American or Hispanic, had more comorbidities, were more symptomatic, and had elevated procalcitonin and interleukin 6. Mortality at 30 days was comparable between the 2 groups (2.9% vs 2.3%,  = .123); however, PWH had higher rates hospitalization (16.5% vs 7.6%,  < .001), ICU admissions (4.2% vs 2.3%,  < .001), and mechanical ventilation (2.4% vs 1.6%,  < .005). Among PWH, hospitalization was independently associated with male gender, being African American, integrase inhibitor use, and low CD4 count; whereas severe disease was predicted by older age (adjusted odds ratio [aOR], 8.33; 95% confidence interval [CI], 1.06-50.00;  = .044) and CD4 <200 cells/mm (aOR, 8.33; 95% CI, 1.06-50.00;  = .044).

Conclusions: People with HIV had higher rates of poor COVID-19 outcomes but were not more at risk of death than their non-HIV-infected counterparts. Older age and low CD4 count predicted adverse outcomes.
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http://dx.doi.org/10.1093/ofid/ofab272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244788PMC
July 2021

Assessing eligibility for differentiated service delivery, HIV services utilization and virologic outcomes of adult HIV-infected patients in Sierra Leone: a pre-implementation analysis.

Glob Health Action 2021 01;14(1):1947566

Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.

Background: There are limited data to help guide implementation of differentiated HIV service delivery (DSD) in resource-limited settings in sub-Saharan Africa.

Objectives: This pre-implementation study sought to assess the proportion of patients eligible for DSD and HIV services utilization, as well as risk factor analysis of virologic failure in Sierra Leone.

Methods: We conducted a retrospective study of adult HIV-infected patients aged 18 years and older receiving care at the largest HIV treatment center in Sierra Leone 2019-2020. Multiple logistic regression was used to identify predictors of virologic failure.

Results: Of 586 unique patients reviewed, 210 (35.8%) qualified as 'stable' for antiretroviral therapy (ART) delivery. There was high utilization of certain HIV service programs (e.g. HIV status disclosure to partners (83%) and treatment 'buddy' program participation (62.8%)), while other service programs (e.g. partner testing and community HIV support group participation) had low utilization (<50%). Of 429 patients with available viral load, 277 (64.6%) were virologically suppressed. In the multivariate logistic regression analysis of risk factors of virologic failure, CD4 < 350 cells/mm (p = 0.009), atazanavir-based ART (p = 0.032), once monthly versus once two- or three-monthly ART dispensing (p = 0.028), history of ART switching (p = 0.02), poor adherence (p = 0.001) and not having received adherence support (p < 0.001) were independent predictors of virologic failure.

Conclusion: Approximately one in three HIV-infected patients on ART were eligible for DSD. We identified gaps in HIV care (i.e. low partner testing, treatment 'buddy', program participation and a substantially high rate of virologic failure) that need to be addressed in preparation for full implementation of DSD in Sierra Leone.
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http://dx.doi.org/10.1080/16549716.2021.1947566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381912PMC
January 2021

Prevalence of sero-markers and non-invasive assessment of liver cirrhosis in patients with Hepatitis B virus infection in Freetown, Sierra Leone: a cross-sectional study.

BMC Gastroenterol 2021 Aug 9;21(1):320. Epub 2021 Aug 9.

Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA.

Background: Hepatitis B virus (HBV) is a major global health problem. Although sub-Saharan Africa has a high proportion of the global burden of HBV, the epidemiology and clinical features of HBV in this region are poorly characterized, and access to diagnostic and treatment services remain limited.

Methods: We conducted a retrospective study of HBV-infected children and adults of all age groups who were evaluated at public and private health facilities in Freetown, Sierra Leone between January 2017 and January 2019. We assessed their clinical presentation, HBV sero-markers, stages of liver disease, prevalence of cirrhosis by non-invasive tools, and the proportion of treatment eligible patients using the criteria recommended by the World Health Organization's 2015 treatment guidelines for HBV. Logistic regression was used to identify predictors of liver cirrhosis.

Results: 163 HBV patients included in the study, with mean age 32.6 years and 65.0% (106) being males. Most (84.0%) were asymptomatic at presentation. The majority (69.9%) were classified as having HBeAg-negative chronic infection (or inactive HBsAg carrier phase), 24.5% were in the HBeAg-negative immune active phase, 3.1% had HBeAg positive hepatitis, and 2.5% were HBsAg negative. The median Aspartate aminotransferase to Platelet Ratio (APRI) and Fibrosis-4 (FIB-4) scores were 0.37 and 0.80, respectively. The prevalence of cirrhosis was 7.6% and 6.2%, estimated by the APRI and FIB-4 scores, respectively. About 20.0% of patients were eligible for treatment with antiviral agents. Based on APRI scores, the presence of any symptom [adjusted odds ratio (aOR) 20.0, 95% confidence interval (CI) (4.1-85.9); p < 0.001], elevated direct bilirubin [aOR 12.1, 95% CI (1.9-63.0); p = 0.003], and elevated total bilirubin [aOR 16.1, 95% CI (3.2-80.8); p = 0.001] were independent predictors of cirrhosis.

Conclusion: Although most patients with HBV infection were asymptomatic, the prevalence of liver cirrhosis and proportion of patients requiring antiviral treatment were substantial. This small study from a hyperendemic setting in Sierra Leone suggests that routine population-based screening may increase early detection and linkage of HBV patients to care before development of complications. Larger studies are needed to confirm our findings.
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http://dx.doi.org/10.1186/s12876-021-01892-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353767PMC
August 2021

Prevalence of hepatitis B surface antigen and serological markers of other endemic infections in HIV-infected children, adolescents and pregnant women in Sierra Leone: A cross-sectional study.

Int J Infect Dis 2021 Jan 28;102:45-52. Epub 2020 Sep 28.

Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA; Division of Infectious Diseases and HIV Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.

Objective: To assess the prevalence of serological markers of HBV and endemic acute and chronic infections (HAV, HCV, CMV, HTLV-1/2 and syphilis) in HIV-infected children, adolescents and pregnant women in Sierra Leone.

Method: We conducted a cross-sectional study at the national children's and women's hospitals in Freetown. Logistic regression was used to assess predictors of HBsAg positivity.

Results: 183 HIV-infected participants were enrolled, comprising children (n = 88), adolescents (n = 47) and pregnant women (n = 48). All participants (100%) were CMV IgG-positive, while 56.8%, 93.6% and 100% of children, adolescents and pregnant women, respectively, were HAV IgG-positive. The prevalence of HCV, HTLV-1/2 and syphilis were <4%. HBV markers were distributed as follows-children: HBsAg (2.3%), HBeAg (0%), anti-HBc (5.7%); adolescents: HBsAg (17.0%), HBeAg (6.4%), anti-HBc (27.7%); and pregnant women: HBsAg (18.8%), HBeAg (4.2%), anti-HBc (77.1%). Age >10 years, i.e., being born pre-2009 before implementation of routine hepatitis B immunization (aOR 5.05 [1.18-21.28]; p = 0.029) and CD4 count <350 cells/mm (aOR 3.97 [1.07-14.71]; p = 0.039) predicted HBsAg positivity.

Conclusion: A high burden of chronic HBV and other endemic infections was observed among HIV-infected patients born pre-2009 before implementation of routine HBV immunization in Sierra Leone, warranting targeted screening and immunization of this high-risk population.
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http://dx.doi.org/10.1016/j.ijid.2020.09.1459DOI Listing
January 2021

Diagnosis and treatment outcomes of adult tuberculosis in an urban setting with high HIV prevalence in Sierra Leone: A retrospective study.

Int J Infect Dis 2020 Jul 24;96:112-118. Epub 2020 Apr 24.

Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA; Division of Infectious Diseases and HIV Medicine, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA; Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.

Objective: To assess the diagnosis, treatment outcomes, and predictors of mortality in adult tuberculosis (TB) patients in an urban setting with a high HIV prevalence.

Methods: A retrospective study was conducted of adult TB patients aged ≥15 years who were treated at Connaught Hospital in Freetown, Sierra Leone from January through December 2017. Multivariate logistic regression was used to identify predictors of mortality.

Results: Of 1127 TB cases notified in 2017, 1105 (98%) were tested for HIV, yielding a TB/HIV co-infection rate of 32.0%. Only HIV-tested cases (n=1105) were included in the final analysis. The majority were male (69.3%), aged 25-34 years (29.2%), and had pulmonary TB (96.3%). Treatment outcomes were as follows: 29.0% cured, 29.0% completed, 0.5% treatment failure, 24.2% lost to follow-up, 12.8% transferred/not evaluated, and 4.5% died. The majority of deaths (80.0%, 40/50) occurred within 2 months of TB treatment initiation. Age 65 years or older (adjusted odds ratio 3.48, 95% confidence interval 1.15-10.56; p=0.027) and HIV-positive status (adjusted odds ratio 3.50, 95% confidence interval 1.72-7.12; p=0.001) were independent predictors of mortality.

Conclusions: Suboptimal TB treatment outcomes were observed in Sierra Leone in 2017. More local and international action is warranted to help achieve the 2035 global TB elimination targets.
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http://dx.doi.org/10.1016/j.ijid.2020.04.038DOI Listing
July 2020

Causes of hospitalization and predictors of HIV-associated mortality at the main referral hospital in Sierra Leone: a prospective study.

BMC Public Health 2019 Oct 21;19(1):1320. Epub 2019 Oct 21.

Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA.

Background: HIV infection is a growing public health problem in Sierra Leone and the wider West Africa region. The countrywide HIV prevalence was estimated at 1.7% (67,000 people), with less than 30% receiving life-saving ART in 2016. Thus, HIV-infected patients tend to present to health facilities late, with high mortality risk.

Methods: We conducted a prospective study of HIV inpatients aged ≥15 years at Connaught Hospital in Freetown-the main referral hospital in Sierra Leone-from July through September 2017, to assess associated factors and predictors of HIV-related mortality.

Results: One hundred seventy-three HIV inpatients were included, accounting for 14.2% (173/1221) of all hospital admissions during the study period. The majority were female (59.5%, 70/173), median age was 34 years, with 51.4% (89/173) of them diagnosed with HIV infection for the first time during the current hospitalization. The most common admitting diagnoses were anemia (48%, 84/173), tuberculosis (24.3%, 42/173), pneumonia (17.3%, 30/173) and diarrheal illness (15.0%, 26/173). CD4 count was obtained in 64.7% (112/173) of patients, with median value of 87 cells/μL (IQR 25-266), and was further staged as severe immunosuppression: CD4 < 100 cells/μL (50%, 56/112); AIDS: CD4 < 200 cells/μL (69.6%, 78/112); and late-stage HIV disease: CD4 < 350 cells/μL (83%, 93/112). Fifty-two patients (30.1%, 52/173) died during hospitalization, 23% (12/52) of them within the first week. The leading causes of death were anemia (23.1%, 12/52), pneumonia (19.2%, 10/52), diarrheal illness (15.4%, 8/52) and tuberculosis (13.6%, 7/52). Neurological symptoms, i.e., loss of consciousness (p = 0.04) and focal limb weakness (p = 0.04); alcohol use (p = 0.01); jaundice (p = 0.02); cerebral toxoplasmosis (p = 0.01); and tuberculosis (p = 0.04) were significantly associated with mortality; however, only jaundice (AOR 0.11, 95% CI [0.02-0.65]; p = 0.01) emerged as an independent predictor of mortality.

Conclusion: HIV-infected patients account for a substantial proportion of admissions at Connaught Hospital, with a high morbidity and in-hospital mortality burden. These findings necessitate the implementation of specific measures to enhance early HIV diagnosis and expand treatment access to all HIV-infected patients in Sierra Leone.
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http://dx.doi.org/10.1186/s12889-019-7614-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805411PMC
October 2019

A two-part phase 1 study to establish and compare the safety and local tolerability of two nasal formulations of XF-73 for decolonisation of Staphylococcus aureus: A previously investigated 0.5mg/g viscosified gel formulation versus a modified formulation.

J Glob Antimicrob Resist 2020 06 7;21:171-180. Epub 2019 Oct 7.

Department of Medicine and Division of Infectious Diseases and HIV Medicine, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH, USA.

Objectives: Successful decolonisation of nasal Staphylococcus aureus (SA) carriage by mupirocin is limited by increasing drug resistance. This randomised, open-label, phase 1 study compared the safety and local tolerability of two nasal formulations of XF-73, a novel porphyrinic antibacterial with rapid intrinsic activity against SA.

Methods: The study was performed in 60 healthy adults. In Part 1, eight non-SA carriers were randomised to groups of four subjects each and were treated with XF-73 concentrations of 0.5mg/g 2% gel or 2.0mg/g 2% gel. In Part 2, 52 persistent SA carriers were randomised to groups of 13 subjects each and were treated with XF-73 concentrations of 0.5mg/g 2% gel, 2.0mg/g 2% gel, 0.5mg/g 4% gel or 4% viscosified placebo gel. Plasma pharmacokinetic and pharmacodynamic studies were performed. Antistaphylococcal activity was assessed as the presence/absence of SA and by quantification of colonisation using a semiquantitative scale (SA score).

Results: 56 subjects (8/8 from Part 1 and 48/52 from Part 2) completed the study, with 47/60 comprising the pharmacokinetic population and 48/60 the pharmacodynamic population. There was no measurable systemic absorption of XF-73. XF-73 treatment was associated with rapid reduction in SA score in all subjects. The most common treatment-emergent adverse events (TEAEs) were rhinorrhoea and nasal dryness (15.5% each in Parts 1 and 2). TEAEs were mild and resolved spontaneously.

Conclusion: XF-73 was well tolerated with minimal side effects at doses of 0.5mg/g 2% gel and 2.0mg/g 2% gel. These findings support further development of XF-73.
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http://dx.doi.org/10.1016/j.jgar.2019.09.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136135PMC
June 2020

Prevalence of drug resistance mutations among ART-naive and -experienced HIV-infected patients in Sierra Leone.

J Antimicrob Chemother 2019 07;74(7):2024-2029

Group of Virology and Pathogenesis, Galicia Sur Health Research Institute (IIS Galicia Sur)-Complexo Hospitalario Universitario de Vigo, SERGAS-UVigo, Vigo, Spain.

Objectives: The aim of this study was to assess the prevalence of HIV drug resistance (HIVDR) in HIV-infected ART-naive and -experienced patients in Sierra Leone.

Patients And Methods: We conducted a cross-sectional study of HIV-positive adults aged ≥18 years at Connaught Hospital in Freetown, Sierra Leone in November 2017. Sequencing was performed in the reverse transcriptase, protease and integrase regions, and interpreted using the Stanford HIVDR database and WHO 2009 mutation list.

Results: Two hundred and fifteen HIV-infected patients were included (64 ART naive and 151 ART experienced). The majority (66%) were female, the median age was 36 years and the median ART exposure was 48 months. The majority (83%) were infected with HIV-1 subtype CRF02_AG. In the ART-naive group, the pretreatment drug resistance (PDR) prevalence was 36.7% (14.2% to NRTIs and 22.4% to NNRTIs). The most prevalent PDR mutations were K103N (14.3%), M184V (8.2%) and Y181C (4.1%). In the ART-experienced group, 64.4% harboured resistance-associated mutations (RAMs) and the overall prevalence of RAMs to NRTIs and NNRTIs was 85.2% (52/61) and 96.7% (59/61), respectively. The most prevalent RAMs were K103N (40.7%), M184V (28.8%), D67N (15.3%) and T215I/F/Y (15.3%). Based on the genotypic susceptibility score estimates, 22.4% of ART-naive patients and 56% of ART-experienced patients were not susceptible to first-line ART used in Sierra Leone.

Conclusions: A high prevalence of circulating NRTI- and NNRTI-resistant variants was observed in ART-naive and -experienced HIV-1-infected patients in Sierra Leone. This necessitates the implementation of HIVDR surveillance programmes to inform national ART guidelines for the treatment and monitoring of HIV-infected patients in Sierra Leone.
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http://dx.doi.org/10.1093/jac/dkz134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587425PMC
July 2019

Seroprevalence of Hepatitis B, Hepatitis C, and Human T-Cell Lymphotropic Virus Infections in HIV-Infected Patients in Sierra Leone.

Am J Trop Med Hyg 2019 06;100(6):1521-1524

Division of Infectious Diseases and HIV Medicine, University Hospitals Cleveland Medical Center, Cleveland, Ohio.

HIV coinfection with hepatitis B virus (HBV), hepatitis C virus (HCV), and human T-cell lymphotropic viruses 1 and 2 (HTLV-1 and HTLV-2) is common because of shared transmission routes. There is no published data on the prevalence of these infections in people living with HIV in Sierra Leone. We conducted a cross-sectional study of 211 HIV-positive patients aged ≥ 18 years in Freetown, Sierra Leone, in November 2017. Plasma samples were analyzed using the chemiluminescent microparticle immunoassay (Architect System, Abbott ARCHITECT Analyzer, Abbott Park, IL. The majority were female (63.5%), with median age 36 years (interquartile range [IQR]: 32-44) and median CD4 count of 396 cells/µL (IQR: 214-534). Sixty patients (28.4%) were newly diagnosed and antiretroviral therapy (ART) naive; 151 patients (71.6%) were ART experienced. The prevalence of the hepatitis B surface antigen (HBsAg), total anti-hepatitis B core antibody, and anti-HCV was 21.7%, 82.9%, and 4.3%, respectively. No cases of HTLV-1 or HTLV-2 were detected. Male gender ( = 0.004) and CD4 < 350 cells/µL ( = 0.017) were associated with the HBsAg positive status.
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http://dx.doi.org/10.4269/ajtmh.18-1001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6553887PMC
June 2019

New insights from IeDEA and COHERE on global trends in CD4 counts at ART initiation

Authors:
George A Yendewa

AIDS Rev 2018 ;20(3):174-175

Division of Infectious Diseases and HIV Medicine Case Western Reserve University School of Medicine Cleveland, Ohio, USA.

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February 2019

High Prevalence of Late-Stage Disease in Newly Diagnosed Human Immunodeficiency Virus Patients in Sierra Leone.

Open Forum Infect Dis 2018 Sep 23;5(9):ofy208. Epub 2018 Aug 23.

Department of Medicine, Case Western Reserve University, Cleveland, Ohio.

A high prevalence of late-stage disease (75.4%) and severe immunosuppression (23.3%) was observed in 155 newly diagnosed human immunodeficiency virus patients in Freetown, Sierra Leone during August to November 2017. Within the late-stage diagnosis group, a significantly high proportion of patients reported fever (84.2% vs 65.2%; = .01), weight loss (82.2% vs 63.5%; = .01), and malaise (89.7% vs 71.7%; = .05). Fever was identified as the only independent predictor of late-stage disease in this study.
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http://dx.doi.org/10.1093/ofid/ofy208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6121223PMC
September 2018

HIV/AIDS in Sierra Leone: Characterizing the Hidden Epidemic.

AIDS Rev 2018 Apr-Jun;20(2):104-113

Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.

Sierra Leone is a low-income West African country that has dealt with waves of economic, political, and public health challenges in its recent past, including a decade-long brutal civil war and the Ebola epidemic of 2014-2016. The HIV/AIDS epidemic, which has raged on in the country since 1987, has long been characterized as stable. The latest UNAIDS report estimates a countrywide HIV prevalence rate of 1.7% in 2016 among adults aged 15-49 years. However, there are indications that the epidemic may be in fact escalating and unless arrested urgently, has the potential to deteriorate into a major public health emergency. Although there are high levels of HIV awareness among adults (over 94%), uptake in voluntary HIV testing has remained low (<30%), and under one-third (29%) of the country's 60,000 people living with HIV/AIDS were on antiretroviral therapy in 2015. This review attempts to address the paucity of scientific information on the subject by presenting the historical and epidemiological background to the HIV/AIDS epidemic in Sierra Leone. Other aspects of the HIV/AIDS epidemic in Sierra Leone are examined, including routine HIV screening and diagnosis, linkage to and retention in HIV care, clinical characteristics and molecular epidemiology, treatment coverage, and prevention strategies. Finally, we identify four key areas of challenge that are hampering current efforts attempting to bring the epidemic under control, and perspective is offered on the way forward.
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http://dx.doi.org/10.24875/AIDSRev.M18000022DOI Listing
October 2018

Ready for HIV Dual Therapy? - New Data from International HIV/AIDS Society 2017.

AIDS Rev 2017 Oct-Dec;19(3):167-172

Case Western Reserve University School of Medicine, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.

The introduction of combination antiretroviral therapy (ART) in the 1990s has fundamentally transformed the landscape of HIV medicine, greatly improved disease morbidity and mortality, and reduced transmission rates across all demographic groups. Central to this success was the idea that to achieve best disease outcomes and minimize the development of drug resistance, at least three antiretroviral agents should be used for HIV treatment. This therapeutic strategy is a core tenet of HIV medicine, backed by incontrovertible scientific evidence, and made easy to deploy by the high compliance levels with once-daily coformulations, which have generally been well tolerated. However, there has been increasing support for a paradigm shift toward dual therapy in recent years, particularly during the maintenance therapy phase of treatment. This concept advocates that once virologic suppression has been achieved with at least three antiretroviral drugs during the treatment initiation phase, a switch to a two-drug regimen should be possible. The results of Phase III of the SWORD trials (Llibre et al., Abstract 44LB) and LAMIDOL trial (Joly et al., Abstract 458) presented at the 2017. Conference on Retroviruses and Opportunistic Infections earlier this year seemed to lend support this hypothesis. More new evidence was recently presented at the 2107 International HIV/AIDS Society (IAS) meeting in Paris that adds to the growing body of evidence in favor of a two-drug regimen approach in maintenance therapy. The LATTE-2 study (Eron et al., Abstract 5628) was of major interest because of the exciting new therapeutic options that long-acting injectable antiretroviral agents may bring in the near future. However, more than that, the findings of comparable response between a traditional three-drug oral regimen and a novel injectable two-drug regimen at 96 weeks were quite noteworthy. In this Phase II, multicenter open-label study of 286 HIV-infected ARTnaïve patients, once-daily oral cabotegravir/abacavir/lamivudine achieved virologic suppression in 84% of study participants. In comparison, 87% in the injectable cabotegravir/rilpivirine once every 4-weekly group and 94% in injectable cabotegravir/rilpivirine once every 8-weekly group remained suppressed at 96 weeks. Crucially, no drug resistance mutations were seen in study participants who remained on their regimen. While the idea of a two-drug regimen has been entertained for maintenance therapy, there may be little willingness to push this further into the area of antiretroviral treatment initiation, for the justifiable concerns that exist around the emergence of drug resistance. Despite this, new data presented at the IAS 2017 showed that the idea is not without merit. In a proof of concept, the ACTG A5353 single-arm pilot study of 120 treatment naïve HIV-infected participants with high viral load (VL ≥1000 and >500,000 copies/mL), showed that once-daily dolutegravir/lamivudine had virologic efficacy of 90% at 24 weeks, with 96% of the as-treated study population achieving VL >50 copies/mL (Taiwo et al., Abstract MOAB0107LB). The regimen was well tolerated, with no reported drug resistance mutations while on treatment. There are many real-world advantages to a two-drug regimen approach, among them lower costs (crucial in resource-limited settings where affordability may be a limiting factor), fewer adverse effects or drug toxicities, and possibly improved compliance. These are all important considerations, given that improved mortality now means patients are going to stay on ART treatment for much longer than previously seen. But how the two-drug regimen approach will hold up against firmly held norms and tradition is far from clear, and it is almost certain that the understandable nervousness that surrounds this idea will continue to last. Until the case for the two-drug regimen approach is made more convincingly in ongoing and future trials, the "three or more" rule will reign, not only as the orthodoxy but also as the cornerstone of good clinical practice.
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June 2018
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