Publications by authors named "Asgeir Johannessen"

38 Publications

Field performance of HBsAg rapid diagnostic tests in rural Ethiopia.

J Virol Methods 2021 03 31;289:114061. Epub 2020 Dec 31.

Regional Centre for Imported and Tropical Diseases, Oslo University Hospital Ullevål, Oslo, Norway; Department of Infectious Diseases, Vestfold Hospital Trust, Tønsberg, Norway.

Point-of-care rapid diagnostic tests (POC-RDTs) are widely used to screen and diagnose hepatitis B virus (HBV) infection and are often the only available diagnostic tools in resource-limited settings. The aim of this study was to evaluate the validity of three hepatitis B surface antigen (HBsAg) POC-RDTs (Healgen®, Advanced Quality™ and Determine™) in an area with high prevalence of HBV in eastern Ethiopia. Results were compared with a commercial enzyme linked immunosorbent assay (ELISA) as gold standard. Quantification of HBsAg was performed in false negative samples. A total of 511 subjects were screened, of whom 81 (15.9 %) were HBsAg-positive with the gold standard. All three POC-RDTs were positive in 65 of the 81 positive samples, yielding a sensitivity (95 % confidence interval) of 80.2 % (70.3-87.5) and a specificity of 99.8 % (98.7-100 for Healgen® and Determine™; 98.6-100 for Advanced Quality™). False negatives were observed in 16 patients associated with low levels of HBsAg (median 1.5 IU/mL). All three POC-RDTs had reasonably high sensitivity and excellent specificity, but false negative results were observed in patients with low titres of HBsAg. Thus, these POC-RDTs might be useful to identify patients in need of HBV treatment, but cannot be recommended as blood donor screening tests.
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http://dx.doi.org/10.1016/j.jviromet.2020.114061DOI Listing
March 2021

Validity of a point-of-care viral load test for hepatitis B in a low-income setting.

J Virol Methods 2021 03 29;289:114057. Epub 2020 Dec 29.

Regional Centre for Imported and Tropical Diseases, Oslo University Hospital Ullevål, PO Box 4956, Nydalen, 0424, Oslo, Norway; Department of Infectious Diseases, Vestfold Hospital Trust, PO Box 2168, 3103, Tønsberg, Norway. Electronic address:

The recent launch of the first point-of-care Xpert® hepatitis B virus (HBV) viral load kit from Cepheid could help to scale up treatment for chronic hepatitis B (CHB) in resource-limited settings. This study aimed to assess the performance of the Xpert kit under field conditions in Ethiopia. One-hundred-and-thirty CHB patients with viral loads ranging from <1 log to>7 log IU/mL were randomly sampled. The viral load was assessed with both the Xpert and the gold standard Abbott RealTime HBV Viral Load assay in each patient. There was a high correlation between the viral loads assessed by Xpert and Abbott (r = 0.948, p < 0.001). The Bland-Altman plot showed a small bias between the two assays, with an on average 0.23 log IU/mL higher viral load result of the Xpert kit; 4 samples differed by>1 log IU/mL. Using the treatment threshold of 2000 IU/mL in both tests, Xpert had a sensitivity of 94 %, specificity of 71 %, positive predictive value of 70 %, and negative predictive value of 95 %. In conclusion, the Xpert kit demonstrated good validity for the measurement of HBV viral load in a real-life setting.
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http://dx.doi.org/10.1016/j.jviromet.2020.114057DOI Listing
March 2021

Assessment of Noninvasive Markers of Liver Fibrosis in Patients With Chronic Hepatitis C in Ethiopia.

Clin Liver Dis (Hoboken) 2020 Oct 3;16(4):168-172. Epub 2020 Nov 3.

Centre for Imported and Tropical Diseases Oslo University Hospital Ullevål Oslo Norway.

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http://dx.doi.org/10.1002/cld.1040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609704PMC
October 2020

A novel score to select patients for treatment in chronic hepatitis B: Results from a large Ethiopian cohort.

J Hepatol 2019 10 2;71(4):840-841. Epub 2019 Aug 2.

Regional Centre for Imported and Tropical Diseases, Oslo University Hospital, Ullevål, Oslo, Norway; Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia.

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http://dx.doi.org/10.1016/j.jhep.2019.04.006DOI Listing
October 2019

Predictors of mortality in patients under treatment for chronic hepatitis B in Ethiopia: a prospective cohort study.

BMC Gastroenterol 2019 May 15;19(1):74. Epub 2019 May 15.

Centre for Imported and Tropical Diseases, Oslo University Hospital, Ullevål, Oslo, Norway.

Background: Antiviral treatment for chronic hepatitis B (CHB) is largely unavailable in sub-Saharan Africa; hence, little is known about the prognosis after initiating treatment in African CHB patients. In this study we aimed to assess predictors of mortality in one of the largest CHB cohorts in sub-Saharan Africa.

Methods: Two-hundred-and-seventy-six CHB patients who started treatment with tenofovir disoproxil fumarate at a public hospital in Ethiopia between March 18, 2015, and August 1, 2017, were included in this analysis. Patients were followed up until October 1, 2017, and deaths were ascertained through hospital records and telephone interview with relatives. Decompensated cirrhosis was defined as current or past evidence of ascites, either by clinical examination or by ultrasonography. Cox proportional hazard models were used to identify independent predictors of mortality.

Results: Thirty-five patients (12.7%) died during follow-up, 33 of whom had decompensated cirrhosis at recruitment. The median duration from start of treatment to death was 110 days (interquartile range 26-276). The estimated survival was 90.3, 88.2 and 86.3% at 6, 12 and 24 months of follow-up, respectively. Independent predictors of mortality were decompensated cirrhosis (adjusted hazard ratio [AHR] 23.68; 95% CI 3.23-173.48; p = 0.002), body mass index < 18.5 kg/m2 (AHR 3.65; 95% CI 1.73-7.72; p = 0.001) and older age (per 1-year increment; AHR 1.06; 95% CI 1.02-1.10; p = 0.007).

Conclusions: Decompensated cirrhosis, low body mass index and older age were independent predictors of mortality. Improved access to antiviral treatment and earlier initiation of therapy could improve the survival of African CHB patients.

Trial Registration: NCT02344498 ( ClinicalTrials.gov identifier). Registered 16 January 2015.
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http://dx.doi.org/10.1186/s12876-019-0993-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521482PMC
May 2019

The WHO guidelines for chronic hepatitis B fail to detect half of the patients in need of treatment in Ethiopia.

J Hepatol 2019 06 28;70(6):1065-1071. Epub 2019 Mar 28.

Regional Centre for Imported and Tropical Diseases, Oslo University Hospital, Ullevål, Oslo, Norway; Department of Infectious Diseases, Vestfold Hospital Trust, Tønsberg, Norway. Electronic address:

Background & Aims: In 2015, the World Health Organization (WHO) issued guidelines for the management of chronic hepatitis B (CHB) in low- and middle-income countries, but little is known about the applicability of the WHO treatment criteria in sub-Saharan Africa. The aim of this study was to evaluate the diagnostic performance of the WHO guidelines in a large CHB cohort in Ethiopia.

Methods: Treatment-naïve adults who attended a public CHB clinic in Addis Ababa were included in this analysis. All patients underwent a standardized evaluation at recruitment, including blood tests and transient elastography (Fibroscan®). A Fibroscan result >7.9 kPa was used to define significant fibrosis and >9.9 kPa to define cirrhosis. Treatment eligibility was assessed using the most recent guidelines from the European Association for the Study of the Liver (EASL) as the 'gold standard'.

Results: Out of 1,190 patients with CHB, 300 (25.2%) were eligible for treatment based on the EASL 2017 guidelines and 182 (15.3%) based on the WHO 2015 guidelines. The sensitivity and specificity of the WHO criteria were 49.0 and 96.1%, respectively. Most patients (94 of 182; 51.6%) who fulfilled the WHO criteria had decompensated cirrhosis and might have a dismal prognosis even with therapy. Only 41 of 115 patients (35.7%) with compensated cirrhosis, who are likely to benefit the most from therapy, were eligible for treatment based on the WHO criteria.

Conclusions: The WHO guidelines for CHB failed to detect half of the patients in need of treatment in Ethiopia, implying the need for a revision of the WHO treatment criteria.

Lay Summary: Antiviral therapy prevents disease progression and death in patients with chronic hepatitis B (CHB), but the identification of patients in need of treatment is a challenge in low- and middle-income countries. The World Health Organization (WHO) has suggested treatment eligibility criteria for use in such settings, but in our study the WHO criteria detected less than half of those in need of therapy in a large Ethiopian cohort of 1,190 patients with CHB. Our findings suggest that the WHO criteria might be unsuitable in sub-Saharan Africa.

Trial Registration Number: NCT02344498 (ClinicalTrials.gov identifier). Registered 16 January 2015.
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http://dx.doi.org/10.1016/j.jhep.2019.01.037DOI Listing
June 2019

Khat-related liver disease in sub-Saharan Africa: neglected, yet important.

Lancet Glob Health 2019 03;7(3):e310

Regional Advisory Unit for Imported and Tropical Diseases, Oslo University Hospital Ullevål, Oslo 0424, Norway; Department of Infectious Diseases, Vestfold Hospital Trust, Tønsberg, Norway.

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http://dx.doi.org/10.1016/S2214-109X(18)30527-8DOI Listing
March 2019

High Seroprevalence of Autoantibodies Typical of Autoimmune Liver Disease in Eastern Ethiopia: Is Chewing of Khat (Catha edulis) a Triggering Factor?

Can J Gastroenterol Hepatol 2018 23;2018:4980597. Epub 2018 Dec 23.

Regional Advisory Unit for Imported and Tropical Diseases, Oslo University Hospital Ullevål, Oslo, Norway.

Background: Recent studies have identified chewing of khat () as an independent risk factor for liver injury; however, the pathogenetic mechanism remains poorly understood. Case series have found markers of autoimmune hepatitis in patients with khat-related liver disease, suggesting that khat chewing might trigger an autoimmune response. The aims of the present study were (i) to assess the prevalence of autoantibodies typical for autoimmune liver diseases in a healthy population in Ethiopia and (ii) to explore the hypothesis that khat usage triggers autoimmunity.

Methods: Consenting adults (≥18 years) without known autoimmune disease or manifest liver disease were included. One-hundred-and-sixty-nine individuals with current khat use were compared to 104 individuals who never used khat. Seroprevalence of antinuclear (ANA), antismooth muscle (SMA), and antimitochondrial antibodies (AMA) were determined and compared between the groups using logistic regression models to adjust for age and sex.

Results: Overall, 2.6% of the study subjects were positive for ANA, 15.4% for SMA, and 25.6% for AMA. When comparing khat users to nonusers, ANA was detected in 4.1% vs. 0% (p=0.047), SMA in 16.0% vs. 14.4% (p=0.730), and AMA in 24.9% vs. 26.9% (p=0.704). ANA was excluded from multivariable analysis since there was no seropositive in the reference group. After adjusting for sex and age, no significant association between khat use and SMA or AMA was found.

Conclusions: No association between khat usage and the seropresence of SMA or AMA was found, weakening the hypothesis that khat-related liver injury is mediated through autoimmune mechanisms. However, the seroprevalences of AMA and SMA were strikingly high in this Ethiopian population compared to global estimates, suggesting that diagnostic algorithms for autoimmune liver diseases developed in Europe and North America might lead to misdiagnosis of patients on the African continent.
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http://dx.doi.org/10.1155/2018/4980597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6323432PMC
May 2019

Treatment of chronic hepatitis B in sub-Saharan Africa: 1-year results of a pilot program in Ethiopia.

BMC Med 2018 12 17;16(1):234. Epub 2018 Dec 17.

Centre for Imported and Tropical Diseases, Oslo University Hospital, Ullevål, PO Box 4956 Nydalen, 0424, Oslo, Norway.

Background: The World Health Organization has set an ambitious goal of eliminating viral hepatitis as a major public health threat by 2030. However, in sub-Saharan Africa, antiviral treatment of chronic hepatitis B (CHB) is virtually unavailable. Herein, we present the 1-year results of a pilot CHB treatment program in Ethiopia.

Methods: At a public hospital in Addis Ababa, CHB patients were treated with tenofovir disoproxil fumarate based on simplified eligibility criteria. Baseline assessment included liver function tests, viral markers, and transient elastography (Fibroscan). Changes in laboratory markers were analyzed using Wilcoxon signed-rank tests. Adherence to therapy was measured by pharmacy refill data.

Results: Out of 1303 patients, 328 (25.2%) fulfilled the treatment criteria and 254 (19.5%) had started tenofovir disoproxil fumarate therapy prior to September 1, 2016. Of the patients who started therapy, 30 (11.8%) died within the first year of follow-up (28 of whom had decompensated cirrhosis), 9 (3.5%) self-stopped treatment, 7 (2.8%) were lost to follow-up, and 4 (1.6%) were transferred out. In patients who completed 12 months of treatment, the median Fibroscan value declined from 12.8 to 10.4 kPa (p < 0.001), 172 of 202 (85.1%) patients with available pharmacy refill data had taken ≥ 95% of their tablets, and 161 of 189 (85.2%) patients with viral load results had suppressed viremia. Virologic failure (≥ 69 IU/mL) at 12 months was associated with high baseline HBV viral load (> 1,000,000 IU/mL; adjusted OR 2.41; 95% CI 1.04-5.55) and suboptimal adherence (< 95%; adjusted OR 3.43, 95% CI 1.33-8.88).

Conclusions: This pilot program demonstrated that antiviral therapy of CHB can be realized in Ethiopia with good clinical and virologic response. Early mortality was high in patients with decompensated cirrhosis, underscoring the need for earlier detection of hepatitis B virus infection and timely initiation of treatment, prior to the development of irreversible complications, in sub-Saharan Africa.

Trial Registration: NCT02344498 (ClinicalTrials.gov identifier). Registered 16 January 2015.
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http://dx.doi.org/10.1186/s12916-018-1229-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6296040PMC
December 2018

Are Risk Factors for Coronary Artery Disease Different in Persons With and Without Obesity?

Metab Syndr Relat Disord 2018 10 8;16(8):440-445. Epub 2018 Aug 8.

4 Department of Nutrition and Food Technology, Faculty of Agriculture, University of Jordan , Amman, Jordan .

Background: Although obesity is an independent risk factor for coronary artery disease (CAD), observational studies have found that persons with obesity have a better prognosis in established CAD compared with those with a normal body weight, suggesting that the underlying risk factors might differ between the two groups. In this study, we studied risk factors for CAD in persons with and without obesity in a Middle Eastern setting where obesity is endemic.

Methods: Five hundred and fifty-six patients referred for elective coronary catheterization at Prince Hamza Hospital, Amman were included in a cross-sectional study. Patients with CAD (n = 353; 63.5%) were compared to patients with a normal coronary angiography (n = 203; 36.5%). Associations between CAD and baseline variables were assessed in multivariate logistic regression models.

Results: In persons with obesity, male sex [adjusted odds ratio (AOR) = 2.62, 95% confidence interval (CI): 1.37-4.99], increasing age (45-54 years: AOR = 5.00, 95% CI: 2.01-12.48; 55-64 years: AOR = 3.77, 95% CI: 1.39-10.23; ≥65 years: AOR = 13.87, 95% CI: 4.62-41.63), diabetes mellitus (AOR = 2.79, 95% CI: 1.49-5.22), and smoking (AOR = 2.25, 95% CI: 1.12-4.50) were strong and significant predictors of CAD. The same risk factors were identified in persons without obesity, but in addition, waist circumference (per 1 cm increment: AOR = 1.04, 95% CI: 1.01-1.07) was a significant predictor of CAD in this group.

Conclusions: Sex, age, diabetes mellitus, and smoking predicted CAD in all patients. Waist circumference only predicted CAD in persons without obesity, suggesting that normal-weight central obesity might be an important risk factor in this setting.
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http://dx.doi.org/10.1089/met.2017.0152DOI Listing
October 2018

Elevated fasting blood glucose, but not obesity, is associated with coronary artery disease in patients undergoing elective coronary angiography in a referral hospital in Jordan.

Ann Saudi Med 2018 Mar-Apr;38(2):111-117

Dr. Abdel-Ellah Al-Shudifat, Faculty of Medicine, Department of Internal Medicine,, The Hashemite University,, Zarqa, Jordan, T: +962 796004849, ORCID: http://orcid.org/0000-0003-4829.0978.

Background: Obesity and its metabolic complications are endemic in the Middle East, but the cardiovascular consequences are not well defined in local studies.

Objective: To assess the association between fasting blood glucose (FBG), obesity and coronary artery disease (CAD) in Jordan.

Design: A cross-sectional, hospital-based study.

Setting: A referral hospital in Amman, Jordan.

Patients And Methods: Patients with complete anthropomorphic data who were referred for elective coronary angiography were included in the analysis. Associations between CAD, FBG and obesity were assessed in multivariate logistic regression models, adjusting for known risk factors.

Main Outcome Measure: The presence of CAD.

Sample Size: 434 subjects.

Results: Only those who underwent coronary angiography and had complete anthropometric data were included in the study: 291 (67.1%) had CAD and 143 (32.9%) had a normal coronary angiogram.The mean body mass index, waist circumference and FBG of the study participants was 30.0 kg/m2, 106.0 cm and 8.8 mmol/L, respectively. The mean FBG was significantly higher in patients with CAD compared to those without CAD (9.5 vs. 7.3 mmol/L, P less than .001). Waist circumference was significantly higher in women with CAD compared to women without CAD (111.0 vs. 105.9 cm, P=.036), but no significant difference was observed in men. In a multivariate analysis, FBG was a strong and significant predictor of CAD; however, none of the measures of obesity were significantly associated with CAD. The findings were robust in a sensitivity analysis that excluded patients with known diabetes mellitus.

Conclusions: Elevated FBG, but not obesity, predicted CAD in a Middle Eastern population. Improved prevention, detection and management of type 2 diabetes should be a priority in this setting.

Limitations: The cross-sectional design cannot control for temporal changes in risk factors and/or reverse causation.

Conflict Of Interest: None.
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http://dx.doi.org/10.5144/0256-4947.2018.111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6074363PMC
September 2018

Unexplained chronic liver disease in Ethiopia: a cross-sectional study.

BMC Gastroenterol 2018 Feb 13;18(1):27. Epub 2018 Feb 13.

Regional Centre for Imported and Tropical Diseases, Oslo University Hospital Ullevål, Oslo, Norway.

Background: Hepatitis B virus (HBV) infection is assumed to be the major cause of chronic liver disease (CLD) in sub-Saharan Africa. The contribution of other aetiological causes of CLD is less well documented and hence opportunities to modulate other potential risk factors are being lost. The aims of this study were to explore the aetiological spectrum of CLD in eastern Ethiopia and to identify plausible underlying risk factors for its development.

Methods: A cross-sectional study was undertaken between April 2015 and April 2016 in two public hospitals in Harar, eastern Ethiopia. The study population comprised of consenting adults with clinical and radiological evidence of chronic liver disease. The baseline evaluation included: (i) a semi-structured interview designed to obtain information about the ingestion of alcohol, herbal medicines and local recreational drugs such as khat (Catha edulis); (ii) clinical examination; (iii) extensive laboratory testing; and, (iv) abdominal ultrasonography.

Results: One-hundred-and-fifty patients with CLD (men 72.0%; median age 30 [interquartile range 25-40] years) were included. CLD was attributed to chronic HBV infection in 55 (36.7%) individuals; other aetiological agents were identified in a further 12 (8.0%). No aetiological factors were identified in the remaining 83 (55.3%) patients. The overall prevalence of daily khat use was 78.0%, while alcohol abuse, defined as > 20 g/day in women and > 30 g/day in men, was rare (2.0%). Histological features of toxic liver injury were observed in a subset of patients with unexplained liver injury who underwent liver biopsy.

Conclusion: The aetiology of CLD in eastern Ethiopia is largely unexplained. The widespread use of khat in the region, together with histopathological findings indicating toxic liver injury, suggests an association which warrants further investigation.
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http://dx.doi.org/10.1186/s12876-018-0755-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5812015PMC
February 2018

Khat chewing increases the risk for developing chronic liver disease: A hospital-based case-control study.

Hepatology 2018 07 15;68(1):248-257. Epub 2018 May 15.

Regional Centre for Imported and Tropical Diseases, Oslo University Hospital, Oslo, Norway.

The chewing of the leaves of Catha edulis (khat) has been implicated in the development of liver disease, but no controlled observations have been undertaken. The objective of the present study was to determine whether khat chewing is associated with development of chronic liver disease (CLD). A case-control study was conducted at two public hospitals in Harar, Ethiopia, between April 2015 and April 2016. A consecutive sample of 150 adult hospital attendees with CLD were included as cases, and 300 adult hospital attendees without clinical or laboratory evidence of CLD were included as controls. Khat consumption was quantified in "khat years"; 1 khat year was defined as daily use of 200 g of fresh khat for 1 year. A logistic regression model was used to control for confounders. There was a significant association between chewing khat and the risk for developing CLD (crude odds ratio, 2.64; 95% confidence interval [CI], 1.56-4.58). In men, this risk, following adjustment for age, alcohol use, and chronic hepatitis B/C infection, increased with increasing khat exposure; thus, compared to never users the adjusted odds ratios were for low khat exposure 3.58 (95% CI 1.05-12.21), moderate khat exposure 5.90 (95% CI 1.79-19.44), and high khat exposure 13.03 (95% CI 3.61-47.02). The findings were robust in a post hoc sensitivity analysis in which individuals with identifiable risk factors for CLD were excluded.

Conclusion: A significant association was observed between chewing khat and the risk for developing CLD, and in men the association was strong and dose-dependent, suggesting a causal relationship; as the prevalence of khat chewing is increasing worldwide, these findings have major public health implications. (Hepatology 2018;68:248-257).
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http://dx.doi.org/10.1002/hep.29809DOI Listing
July 2018

Response to Non-invasive fibrosis markers for chronic hepatitis B in sub-Saharan Africa.

Liver Int 2017 11;37(11):1739

Centre for Imported and Tropical Diseases, Oslo University Hospital, Ullevål, Oslo, Norway.

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http://dx.doi.org/10.1111/liv.13425DOI Listing
November 2017

Hepatitis delta virus infection in a large cohort of chronic hepatitis B patients in Ethiopia.

Liver Int 2018 06 20;38(6):1000-1009. Epub 2017 Oct 20.

Centre for Imported and Tropical Diseases, Oslo University Hospital, Ullevål, Oslo, Norway.

Background & Aims: Hepatitis D virus (HDV) infection is associated with a more severe outcome in patients with chronic hepatitis B (CHB); however, little is known about the presence of HDV in sub-Saharan Africa. We aimed to determine the prevalence of HDV infection, as well as its clinical, biological and virological characteristics, in a large CHB cohort in Ethiopia.

Methods: In total, 1267 HIV-negative CHB patients at St. Paul's Hospital Millennium Medical College in Addis Ababa were screened for anti-HDV antibodies using ELISA assays. Confirmed positive samples were further tested for HDV RNA using a consensus commercial real-time RT-PCR assay. HDV genotypes were also determined for RNA-positive samples by nucleotide sequencing followed by phylogenetic analyses. Demographical, clinical and biological data from patients were recorded and compared based on HDV RNA results.

Results: Most patients (n = 748, 59.0%) were men, and the median age was 31 years (interquartile range 26-40). Anti-HDV antibodies were detected in 19 individuals (1.5%), 12 of whom were HDV RNA-positive with a viral load ranging from <2 to >8 log 10 IU/mL. All strains were genotype 1. HDV RNA-positive patients were more likely to have significant liver fibrosis (63.6% vs 24.7%, P = .007) and cirrhosis (45.5% vs 16.4%, P = .024).

Conclusions: HDV infection is rare in Ethiopia but is associated with more advanced liver fibrosis.
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http://dx.doi.org/10.1111/liv.13607DOI Listing
June 2018

Risk factors for coronary artery disease in patients undergoing elective coronary angiography in Jordan.

BMC Cardiovasc Disord 2017 07 11;17(1):183. Epub 2017 Jul 11.

Faculty of Agriculture, The University of Jordan, Amman, Jordan.

Background: Unhealthy lifestyle factors such as smoking, obesity, inactivity and type 2 diabetes are endemic in the Middle East. The public health consequences might be detrimental; however, local studies on risk factors for coronary artery disease (CAD) are scarce.

Methods: Patients referred for coronary angiography at a tertiary hospital in Amman, Jordan, between January and December 2015, were included in this study. Risk factors for CAD were assessed in a multivariate logistic regression model, and presented as odds ratio (OR) with 95% confidence interval (CI).

Results: Among 557 participants, 356 (63.9%) had CAD and 201 (36.1%) had a normal cardiogram. The majority (n = 395, 70.9%) were male, and median age was 55 years (interquartile range 47-64). Two-hundred-and-fifteen (38.6%) individuals reported previous diabetes, and 287 (51.5%) were current or previous smokers. In multivariate analysis, male gender (OR 3.7, 95% CI 2.3-6.0), age (45-54 years: OR 4.8, 95% CI 2.7-8.5; 55-64 years: OR 6.0, 95% CI 3.2-11.4; ≥65 years: OR 15.7, 95% CI 7.8-31.3), previous diabetes (OR 2.6, 95% CI 1.7-4.1) and current/previous smoking (OR 2.1, 95% CI 1.3-3.4) were significant predictors of CAD.

Conclusions: Age, gender, diabetes and smoking were strong and significant risk factors for CAD in Jordan. Public health interventions to reduce the prevalence of smoking and diabetes are urgently needed.
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http://dx.doi.org/10.1186/s12872-017-0620-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5504622PMC
July 2017

Early experiences from one of the first treatment programs for chronic hepatitis B in sub-Saharan Africa.

BMC Infect Dis 2017 06 19;17(1):438. Epub 2017 Jun 19.

Centre for Imported and Tropical Diseases, Oslo University Hospital, Ullevål, Box 4956 Nydalen, 0424, Oslo, PO, Norway.

Background: Treatment for chronic hepatitis B (CHB) is virtually absent in sub-Saharan Africa. Here we present early experiences from a pilot program for treatment of CHB in Ethiopia.

Methods: Adults (≥18 years) with CHB were included in a cohort study at St. Paul's Hospital Millennium Medical College, Addis Ababa, from February 2015. The baseline assessment included liver function tests, viral markers and transient elastography (Fibroscan 402, Echosense, France). Logistic regression models were used to identify predictors of fibrosis. Tenofovir disoproxil fumarate (TDF) was initiated based on the European Association for the Study of the Liver (EASL) criteria, with some modifications. The initial 300 patients underwent a more comprehensive evaluation and are presented here.

Results: One-hundred-and-thirty-eight patients (46.0%) were women and median age was 30 years (interquartile range 26-40). Co-infections were rare: four patients (1.3%) were anti-HCV positive, 11 (3.7%) were anti-HDV positive, whereas 5 (1.7%) had HIV-infection. The majority were hepatitis B e-antigen (HBeAg) negative (n = 262; 90.7%) and had a normal (≤40 U/L) alanine aminotransferase (ALT) (n = 245; 83.1%). Of 268 patients with a valid Fibroscan result, 79 (29.5%) had significant fibrosis (>7.9 kPa). Independent predictors of fibrosis were male sex, age > 35 years and viral load >20,000 IU/ml. In total, 74 patients (24.7%) started TDF therapy, of whom 46 (62.2%) had cirrhosis.

Conclusions: The majority were HBeAg negative and had normal ALT. However, one quarter of the patients were in need of antiviral treatment, underscoring the need to scale up CHB treatment on the African continent.

Trial Registration: NCT02344498 ( ClinicalTrials.gov identifier). Registered 16 January 2015.
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http://dx.doi.org/10.1186/s12879-017-2549-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5477340PMC
June 2017

Diabetes Risk Score in a Young Student Population in Jordan: A Cross-Sectional Study.

J Diabetes Res 2017 29;2017:8290710. Epub 2017 Apr 29.

Faculty of Medicine, Hashemite University, Zarqa, Jordan.

. The Middle East is the home to the most obese population in the world, and type 2 diabetes mellitus is endemic in the region. However, little is known about risk factors for diabetes in the younger age groups. . The Finnish Diabetes Risk Score (FINDRISC) is a simple, validated tool to identify persons at risk of diabetes. We investigated students at Hashemite University in Jordan with FINDRISC and measured fasting plasma glucose in those who were categorized in the high-risk group. . Overall, 1821 students (881 [48.4%] female) were included in the study. Risk factors for diabetes were common: 422 (23.2%) were overweight or obese and 497 (27.3%) had central obesity. Using the FINDRISC score, 94 (5.2%) students were at moderate risk and 32 (1.8%) at high risk of diabetes. The mean FINDRISC score was significantly higher in men than women (5.9 versus 5.4; = 0.002). Twenty-eight students in the high-risk group had a subsequent plasma glucose measurement, and 8 (29%) of them fulfilled the diagnostic criteria for diabetes. . Risk factors for diabetes were common in a young student population in Jordan, suggesting that preventive measures should be initiated early in adulthood to turn the diabetes epidemic in the region.
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http://dx.doi.org/10.1155/2017/8290710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5429959PMC
January 2018

Are non-invasive fibrosis markers for chronic hepatitis B reliable in sub-Saharan Africa?

Liver Int 2017 10 23;37(10):1461-1467. Epub 2017 Mar 23.

Centre for Imported and Tropical Diseases, Oslo University Hospital, Ullevål, Oslo, Norway.

Background: In the absence of liver biopsy, the World Health Organization recommends non-invasive tests, such as aspartate aminotransferase to platelet ratio index and FIB-4, to assess liver fibrosis in patients with chronic hepatitis B. However, these tests are not well validated in sub-Saharan Africa. Recently, a new marker, gamma-glutamyl transpeptidase to platelet ratio, was found to be more accurate in an African setting, but this needs confirmation in other cohorts.

Methods: A treatment program for chronic hepatitis B was initiated in Addis Ababa, Ethiopia, in 2015. Non-invasive tests were compared with transient elastography (Fibroscan 402, Echosense, France) using the following thresholds: no fibrosis (≤7.9 kPa), significant fibrosis (>7.9 kPa) and cirrhosis (>11.7 kPa). The diagnostic accuracy was estimated by calculating the area under the receiver operating characteristics curve.

Results: Of 582 treatment-naïve patients, 141 (24.2%) had significant fibrosis and 90 (15.5%) had cirrhosis. The area under the receiver operating characteristics curve of aspartate aminotransferase to platelet ratio index, FIB-4 and gamma-glutamyl transpeptidase to platelet ratio was high both to diagnose significant fibrosis (0.79 [95% CI 0.75-0.84], 0.79 [95% CI 0.75-0.84], 0.80 [95% CI 0.75-0.85]) and cirrhosis (0.86 [95% CI 0.81-0.91], 0.86 [95% CI 0.81-0.91], 0.87 [95% CI 0.82-0.91]). The specificity was high for all tests (94%-100%); however, the sensitivity was poor both to detect fibrosis (10%-45%) and cirrhosis (10%-36%).

Conclusions: Aspartate aminotransferase to platelet ratio index, FIB-4 and gamma-glutamyl transpeptidase to platelet ratio had good diagnostic properties to detect liver fibrosis and cirrhosis in patients with chronic hepatitis B in East Africa. However, the sensitivity was low, and only 10% of patients with cirrhosis were detected using aspartate aminotransferase to platelet ratio index at the World Health Organization recommended threshold.
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http://dx.doi.org/10.1111/liv.13393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637891PMC
October 2017

Dry Blood Spots a Reliable Method for Measurement of Hepatitis B Viral Load in Resource-Limited Settings.

PLoS One 2016 7;11(11):e0166201. Epub 2016 Nov 7.

Centre for Imported and Tropical Diseases, Oslo University Hospital, Ullevål, Oslo, Norway.

Background & Aims: Hepatitis B virus (HBV) quantification is essential in the management of chronic hepatitis B, both to determine treatment eligibility and in the monitoring of treatment effect. This test, however, is rarely available in resource-limited settings due to high costs and stringent requirements for shipment and storage of plasma. Dried Blood Spots (DBS) can be a convenient alternative to plasma, but its use for HBV monitoring has not been investigated under real-life conditions in Africa.

Methods: The performance of DBS in HBV quantification was investigated using a modified commercial test (Abbott RealTime HBV assay). Paired DBS and plasma samples were collected from an HBV positive cohort in Addis Ababa, Ethiopia. DBS were stored at ambient temperature for 4-39 days before shipment to the laboratory.

Results: Twenty-six paired samples were selected covering the total range of quantification, from 2.14 log IU/ml to >7 log IU/ml. HBV was detected in 21 of 21 (100%) DBS from patients with a corresponding plasma viral load above 2.70 log IU/ml. The mean difference between plasma and DBS was 0.59 log IU/ml, and the correlation was strong (R2 = 0.92). In stability studies there was no significant change in DBS viral load after storage at room temperature for up to 12 weeks.

Conclusions: This study suggests that DBS can be a feasible and reliable alternative to plasma for quantification of HBV in resource-limited settings. DBS can expand access to antiviral treatment for patients in low- and middle-income countries.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0166201PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5098817PMC
June 2017

Is aspartate aminotransferase-to-platelet ratio index a reliable tool in human immunodeficiency virus patients in Africa?

Liver Int 2015 Aug 16;35(8):2059. Epub 2015 Feb 16.

Department of Hepatology, Imperial College London, St Mary's Hospital, London, UK.

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http://dx.doi.org/10.1111/liv.12793DOI Listing
August 2015

Antiretroviral treatment failure predicts mortality in rural Tanzania.

Int J STD AIDS 2015 Aug 13;26(9):633-9. Epub 2014 Aug 13.

Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway Vestre Viken HF, Drammen Hospital, Drammen, Norway

Virological monitoring of HIV-infected patients on antiretroviral treatment (ART) is rarely available in resource-limited settings and many patients experience unrecognized virological failure. We studied the long-term consequences of virological failure in rural Tanzania. Previously, virological efficacy was measured in a cohort treated with ART. In the present study, patients with virological failure (VF; HIV-RNA >400 copies/ml) were followed up and compared to those with virological response (VR; HIV-RNA <400 copies/ml) with regard to mortality, CD4 change and subsequent virological outcome. Fifty-six patients with VF had a median CD4 count of 358 cells/µl (interquartile range [IQR] 223-635) and a median HIV-RNA of 13,573 copies/ml (IQR 2326-129,736). Median CD4 count for those with VR was 499 cells/µl (IQR 290-636). During a median follow-up time of 39 months (IQR 18-42), 8 of 56 patients (14.3%) with VF died, compared to 1 of 63 patients (1.6%) with VR (p = 0.009). All registered deaths were HIV-related. Of 55 patients with subsequent HIV-RNA measurements, only 12 of 30 (40%) patients with VF achieved virological suppression, compared to 20 of 25 (80%) patients with VR (p = 0.003). Virological failure predicted death and subsequent virological failure in patients on ART in a resource-limited setting.
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http://dx.doi.org/10.1177/0956462414548460DOI Listing
August 2015

HIV-1 drug mutations in children from northern Tanzania.

J Antimicrob Chemother 2014 Jul 11;69(7):1928-32. Epub 2014 Apr 11.

Botswana Harvard HIV Research Laboratory, Gaborone, Botswana.

Objectives: In resource-limited settings, it is a challenge to get quality clinical specimens due to poor infrastructure for their collection, transportation, processing and storage. Using dried blood spots (DBS) might be an alternative to plasma for HIV-1 drug resistance testing in this setting. The objectives of this study were to determine mutations associated with antiretroviral resistance among children <18 months old born to HIV-1-infected mothers enrolled in prevention of mother-to-child transmission services in northern Tanzania.

Patients And Methods: Kilimanjaro Christian Medical Center (KCMC) Clinical Laboratory is the zonal centre for early infant diagnosis using DBS in northern Tanzania. DBS were collected from January 2011 to December 2012. Mothers were kept on triple therapy and single-dose nevirapine before pregnancy and during labour, respectively. Infants were given single-dose nevirapine and most of them were breastfed. Genotypic resistance was determined in those with a viral load of >400 copies/mL.

Results: Genotypic resistance mutations were detected in 13 of 46 children (28%). HIV-1 genotypes were A1 (n = 27), C (n = 10), A/D (n = 4), D (n = 3) and CRF10_CD (n = 2). The median age was 12 weeks (IQR 6-28). The mean log10 viral load was 3.87 copies/mL (SD 0.995). All major mutations were detected in the reverse transcriptase gene and none in the protease gene region. The most frequent mutations were Y181C (n = 8) and K103N (n = 4), conferring resistance to non-nucleoside reverse transcriptase inhibitors.

Conclusions: One-third of infants newly diagnosed with HIV in northern Tanzania harboured major drug resistance mutations to currently used antiretroviral regimens. These mutations were detected from DBS collected from the field and stored at room temperature. Surveillance of drug resistance among this population in resource-limited settings is warranted.
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http://dx.doi.org/10.1093/jac/dku087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4054989PMC
July 2014

Cytomegalovirus viremia in dried blood spots is associated with an increased risk of death in HIV-infected patients: a cohort study from rural Tanzania.

Int J Infect Dis 2012 Dec 30;16(12):e879-85. Epub 2012 Sep 30.

Department of Infectious Diseases, Oslo University Hospital, POB 4956 Nydalen, N-0424 Oslo, Norway.

Objectives: The objectives of the study were to assess the utility of dried blood spots (DBS) for the detection of cytomegalovirus (CMV) antibody and viremia in a resource-poor setting, to study the prevalence of CMV antibody and viremia in HIV-infected patients with access to antiretroviral therapy (ART) in Tanzania, and to relate CMV viremia to outcome.

Methods: DBS were prepared from 168 ART-naïve patients at baseline. Demographic, clinical, and laboratory data were obtained from patient records. CMV antibody was analyzed by chemiluminescent microparticle immunoassay and viremia by quantitative PCR.

Results: All patients were CMV-seropositive. At baseline 38 (22.6%) had detectable CMV viremia and 14 (8.3%) had a CMV viral load ≥ 200 copies/ml. In 135 patients available for follow-up, CMV ≥ 200 copies/ml was an independent risk factor for death with a hazard ratio of 5.0 (95% confidence interval 2.1-11.9) after adjusting for confounders. Symptoms compatible with CMV disease were common with viremia ≥ 200 copies/ml and CD4+ T cell counts <100 cells/mm(3), but confirmatory diagnostic procedures were unavailable.

Conclusions: DBS are suitable for the detection of CMV antibody and viremia in HIV patients in resource-poor areas. CMV viremia was frequent and associated with an increased risk of death. Improved diagnosis and treatment of CMV may improve the prognosis for HIV-infected patients in developing countries and should be addressed in future studies.
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http://dx.doi.org/10.1016/j.ijid.2012.08.003DOI Listing
December 2012

Antiretroviral treatment reverses HIV-associated anemia in rural Tanzania.

BMC Infect Dis 2011 Jul 11;11:190. Epub 2011 Jul 11.

Department of Infectious Diseases, Oslo University Hospital, Ulleval, Oslo, Norway.

Background: HIV-associated anemia is common and associated with poor prognosis. However, its response to antiretroviral treatment (ART) in rural Africa is poorly understood.

Methods: HIV-infected adults (≥15 years) who enrolled in HIV care at Haydom Lutheran Hospital in northern Tanzania were included in the study. The effect of ART (zidovudine/stavudine + lamivudine + efavirenz/nevirapine) on HIV-associated anemia was studied in a subset of patients who were anemic at the time they started ART and had a follow-up hemoglobin measurement 12 months later. Pregnant women were excluded from the study, as were women who had given birth within the past 6 weeks. Anemia was defined as hemoglobin <12 g/dL in women and <13 g/dL in men. We applied paired sample T-tests to compare hemoglobin levels before and one year after ART initiation, and logistic regression models to identify predictors of persistent anemia.

Results: At enrollment, mean hemoglobin was 10.3 g/dL, and 649 of 838 patients (77.4%) were anemic. Of the anemic patients, 254 (39.1%) had microcytosis and hypochromia. Among 102 patients who were anemic at ART initiation and had a follow-up hemoglobin measurement after 12 months, the mean hemoglobin increased by 2.5 g/dL (P < 0.001); however, 39 patients (38.2%) were still anemic after 12 months of ART. Independent predictors of persistent anemia were mean cell volume in the lower quartile (<76.0 fL; Odds Ratio [OR] 4.34; 95% confidence interval [CI] 1.22-15.5) and a zidovudine-containing initial regimen (OR 2.91; 95% CI 1.03-8.19).

Conclusions: Most patients had anemia at enrollment, of whom nearly 40% had microcytosis and hypochromia suggestive of iron deficiency. The mean hemoglobin increased significantly in patients who received ART, but one third were still anemic 12 months after ART initiation indicating that additional interventions to treat HIV-associated anemia in rural Africa might be warranted, particularly in patients with microcytosis and those treated with zidovudine.
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http://dx.doi.org/10.1186/1471-2334-11-190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145581PMC
July 2011

HIV-1 drug resistance testing from dried blood spots collected in rural Tanzania using the ViroSeq HIV-1 Genotyping System.

J Antimicrob Chemother 2011 Feb 25;66(2):260-4. Epub 2010 Nov 25.

Department of Infectious Diseases, Oslo University Hospital, Ulleval, Oslo, Norway.

Objectives: To assess whether the commercial ViroSeq HIV-1 Genotyping System (Abbott Molecular, Des Plains, IL, USA) can be used in conjunction with dried blood spots (DBS) for clinical monitoring of drug resistance in patients who fail antiretroviral treatment (ART) in rural Tanzania.

Patients And Methods: Patients at Haydom Lutheran Hospital with confirmed treatment failure (viral load >1000 copies/mL) of a first-line ART regimen were selected for resistance testing. DBS were stored with desiccant at -20 °C for a median of 126 days (range 0-203) and shipped at ambient temperature for 20 days. After manual extraction of nucleic acids, the ViroSeq kit was used for amplification and sequencing. DBS-derived genotypes were compared with those of a plasma-based assay.

Results: Seventeen of 36 (47%) DBS specimens were successfully genotyped. Only 2 of 16 (13%) DBS with a viral load <10,000 copies/mL could be amplified, compared with 15 of 20 (75%) DBS with a viral load >10,000 copies/mL (P = 0.001). In samples that yielded a sequence, all 23 clinically significant reverse transcriptase (RT) mutations in plasma were also detected in DBS. One RT mutation was found in DBS only. In the protease region, 77 polymorphisms were found in plasma, of which 70 (91%) were also detected in DBS. Sixteen of 17 (94%) patients had identical resistance profiles to antiretroviral drugs in plasma and DBS.

Conclusions: The ViroSeq kit performed well in patients with a high viral load, but failed to genotype most DBS with a viral load <10,000 copies/mL. In DBS that yielded a genotype, there was high concordance with a plasma-based assay.
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http://dx.doi.org/10.1093/jac/dkq433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3019084PMC
February 2011

[A step in the right direction].

Tidsskr Nor Laegeforen 2010 Nov;130(22):2223

Leger uten grenser og Infeksjonsmedisinsk avdeling, Oslo universitetssykehus, Ullevål, 0407 Oslo, Norway.

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http://dx.doi.org/10.4045/tidsskr.10.1100DOI Listing
November 2010

Dried blood spots in HIV monitoring: applications in resource-limited settings.

Bioanalysis 2010 Nov;2(11):1893-908

Department of Infectious Diseases, Oslo University Hospital, Ulleval, Oslo, Norway.

By the end of 2008, 4 million people were receiving antiretroviral treatment for HIV/AIDS in low- and middle-income countries. In industrialized countries, monitoring of treatment with viral load measurements and drug resistance testing is the standard of care to ensure early detection of treatment failure and a prompt switch to a fully active second-line regimen, before drug-resistant mutations accumulate. These tests, however, require highly specialized laboratories and stringent procedures for storage and shipment of plasma, and are rarely available in resource-limited settings. Therefore, treatment failure in such settings is usually not detected until patients develop severe immunodeficiency, at which stage widespread resistance is likely. Dried blood spots (DBS) are easy to collect and store, and can be a convenient alternative to plasma in settings with limited laboratory capacity. This review provides an overview of possible applications of DBS technologies in the monitoring of HIV treatment, with the main focus on viral load quantification and drug resistance testing.
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http://dx.doi.org/10.4155/bio.10.120DOI Listing
November 2010

HIV type-1 drug resistance testing on dried blood spots is feasible and reliable in patients who fail antiretroviral therapy in rural Tanzania.

Antivir Ther 2010 ;15(7):1003-9

Department of Infectious Diseases, Oslo University Hospital, Ullevål, Oslo, Norway.

Background: HIV type-1 (HIV-1) drug resistance testing is rarely available in resource-limited settings because of high costs and stringent requirements for storage and transport of plasma. Dried blood spots (DBS) can be a convenient alternative to plasma, but the use of DBS needs validation under field conditions. We assessed the performance of DBS in genotypic resistance testing of patients who failed first-line antiretroviral therapy (ART) in rural Tanzania.

Methods: A total of 36 ART-experienced patients with viral loads >1,000 copies/ml (median 15,180 copies/ml [range 1,350-3,683,000]) and with various HIV-1 subtypes were selected for resistance testing. DBS were stored with desiccant at ambient temperature for a median of 29 days (range 8-89). Samples were amplified using an in-house reverse transcriptase-nested PCR method and sequenced using the ViroSeq™ assay (Abbott Molecular, Des Plaines, IL, USA). DBS-derived genotypes were compared with genotypes from plasma.

Results: Overall, 34 of 36 (94%) DBS specimens were successfully genotyped. In the protease region, of 142 polymorphisms found in plasma, 132 (93%) were also detected in DBS. In the reverse transcriptase region, of 57 clinically relevant mutations present in plasma, 51 (89%) were also detected in DBS. A total of 30 of 34 (88%) patients had identical resistance profiles to antiretroviral drugs in plasma and DBS.

Conclusions: Genotyping was successful in the vast majority of DBS specimens stored at ambient temperature for up to 3 months, and there was high concordance between mutations found in DBS and plasma. Our study suggests that DBS can be a feasible and reliable tool to monitor HIV-1 drug resistance in patients on ART in resource-limited settings.
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http://dx.doi.org/10.3851/IMP1660DOI Listing
February 2011