Publications by authors named "Kwamena Sagoe"

36 Publications

Transmitted drug resistance mutations and subtype diversity amongst HIV-1 sero-positive voluntary blood donors in Accra, Ghana.

Virol J 2020 07 24;17(1):114. Epub 2020 Jul 24.

Department of Medical Microbiology, School of Medicine and Dentistry, University of Ghana, Accra, Ghana.

Background: Detection of HIV-1 transmitted drug resistance (TDR) and subtype diversity (SD) are public health strategies to assess current HIV-1 regimen and ensure effective therapeutic outcomes of antiretroviral therapy (ART) among HIV-1 patients. Globally, limited data exist on TDR and SD among blood donors. In this study, drug resistance mutations (DRMs) and SD amongst HIV-1 sero-positive blood donors in Accra, Ghana were characterized.

Methods: Purposive sampling method was used to collect 81 HIV sero-positive blood samples from the Southern Area Blood Center and confirmed by INNO-LIA as HIV-1 and/or HIV-2. Viral RNA was only extracted from plasma samples confirmed as HIV-1 positive. Complementary DNA (cDNA) was synthesized using the RNA as a template and subsequently amplified by nested PCR with specific primers. The expected products were verified, purified and sequenced. Neighbour-joining tree with the Kimura's 2-parameter distances was generated with the RT sequences using Molecular Evolutionary Genetic Analysis version 6.0 (MEGA 6.0).

Results: Out of the 81 plasma samples, 60 (74%) were confirmed as HIV-1 sero-positive by INNO-LIA HIVI/II Score kit with no HIV-2 and dual HIV-1/2 infections. The remaining samples, 21 (26%) were confirmed as HIV sero-negative. Of the 60 confirmed positive samples, (32) 53% and (28) 47% were successfully amplified in the RT and PR genes respectively. Nucleotide sequencing of amplified samples revealed the presence of major drug resistance mutations in two (2) samples; E138A in one sample and another with K65R. HIV-1 Subtypes including subtypes A, B, CRF02_AG and CRF09_cpx were found.

Conclusion: This study found major drug resistance mutations, E138A and K65R in the RT gene that confer high level resistance to most NNRTIs and NRTI respectively. CRF02_AG was most predominant, the recorded percentage of subtype B and the evolutionary relationship inferred by phylogenetic analysis may suggest possible subtype importation. However, a more prospective and detailed analysis is needed to establish this phenomenon. The data obtained would inform the selection of drugs for ART initiation to maximize therapeutic options in drug-naïve HIV-1 patients in Ghana.
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http://dx.doi.org/10.1186/s12985-020-01386-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378406PMC
July 2020

Identification of hepatitis B virus genotype A/E recombinants in Ghana.

Virus Genes 2019 Oct 25;55(5):707-712. Epub 2019 Jul 25.

Division of Digestive Disease, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Hepatitis B virus (HBV) exhibits a high degree of heterogeneity with at least 10 genotypes (A-J) identified to date. Intergenotypic recombination is relatively common. Previously, we investigated HBV drug resistance in HIV/HBV co-infected individuals in Ghana. After identifying multiple circulating genotypes and a novel D/E recombinant, we sought to determine if additional individuals were also infected with recombinant HBV. Partial genome sequences from three individuals were initially identified as genotype A4. Full-length HBV genomes were obtained using rolling circle amplification followed by PCR and shown to cluster with known A/E recombinant viruses. Similar recombination breakpoints were observed in these three individuals suggesting local spread of this novel recombinant HBV in Ghana.
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http://dx.doi.org/10.1007/s11262-019-01690-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6750976PMC
October 2019

Brief Report: Relationship Between ABCC4 SNPs and Hepatitis B Virus Suppression During Tenofovir-Containing Antiretroviral Therapy in Patients With HIV/HBV Coinfection.

J Acquir Immune Defic Syndr 2019 12;82(4):421-425

Department of Medicine, College of Medicine, University of Florida, Gainesville, FL.

Background: Incomplete hepatitis B virus (HBV) suppression during antiretroviral therapy (ART) in HIV and HBV coinfected patients is common, but underlying factors are not fully elucidated. We hypothesize that genetic factors that influence nucleoside analog pharmacokinetics will affect HBV treatment response.

Methods: HIV/HBV coinfected patients on tenofovir disoproxil fumarate/lamivudine (TDF/3TC)-containing ART were enrolled. Selected ABCC4 single nucleotide polymorphisms (SNPs) with known effects on nucleoside pharmacokinetics were genotyped using TaqMan assays. Relationship between ABCC4 SNPs and unsuppressed HBV DNA (HBV DNA ≥20 IU/mL) were examined.

Results: Of the 50 participants on TDF/3TC-containing ART for a median (range) of 1.5 (1-7.4) years, 20 (40%) had unsuppressed HBV DNA. Participants with unsuppressed compared with those with suppressed HBV DNA were more likely to have negative HBe antibody, lower body mass index, and lower CD4 count at enrollment. Carriers of ABCC4 rs11568695 (G3724A) variant allele were more likely than noncarriers to have unsuppressed HBV (61.1% vs. 29.0%, P = 0.038). Among 36 patients with suppressed HIV RNA (presumed good ART adherence), ABCC4 rs11568695 variant carriers were more likely than noncarriers to have unsuppressed HBV (58.8% vs. 20.0% P = 0.021). Logistic regression analysis that included genetic and nongenetic factors identified ABCC4 rs11568695 variant allele, body mass index, and male sex as predictors of unsuppressed HBV DNA.

Conclusions: We identified a novel association between ABCC4 rs11568695 SNP and poor HBV treatment response. If confirmed in further studies, ABCC4 genotyping could be used to identify individuals who may need intensified HBV therapy.
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http://dx.doi.org/10.1097/QAI.0000000000002136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817383PMC
December 2019

Drug resistance mutations and viral load in human immunodeficiency virus type 2 and dual HIV-1/HIV-2 infected patients in Ghana.

Medicine (Baltimore) 2019 Feb;98(6):e14313

Virology Department, Noguchi Memorial Institute for Medical Research, College of Health Sciences.

Antiretroviral therapy (ART) and drug resistance studies worldwide have focused almost exclusively on human immunodeficiency virus type 1 (HIV-1). As a result, there is limited information on ART and drug resistance in HIV-2 patients. In Ghana, the HIV epidemic is characterized by the domination of HIV-1, with cocirculating HIV-2. We, therefore, sought to determine viral load and drug resistance mutations in HIV-2 patients to inform the clinical management of such individuals in Ghana.We used purposive sampling to collect blood from 16 consented patients, confirmed as HIV-2 or HIV-1/2 dual infections by serology. A 2-step real-time RT-PCR assay was used to determine plasma HIV-2 RNA viral loads. For drug resistance testing, nucleic acids were extracted from plasma and peripheral blood mononuclear cells. The reverse transcriptase and protease genes of HIV-2 were amplified, sequenced and analyzed for drug resistance mutations and HIV-2 group.HIV-2 viral load was detected in 9 of 16 patients. Six of these had quantifiable viral loads (range: 2.62-5.45 log IU/mL) while 3 had viral loads below the limit of quantification. Sequences were generated from 7 out of 16 samples. Five of these were classified as HIV-2 group B and 2 as HIV-2 group A. HIV-2 drug resistance mutations (M184V, K65R, Y115F) were identified in 1 patient.This study is the first to report HIV-2 viral load and drug resistance mutations in HIV-2 strains from Ghana. The results indicate the need for continuous monitoring of drug resistance among HIV-2- infected patients to improve their clinical management.
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http://dx.doi.org/10.1097/MD.0000000000014313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380870PMC
February 2019

Identification of Amino Acid Substitutions Within the VP7 Genes of G2 Rotavirus Strains in Ghana.

Pediatr Infect Dis J 2018 11;37(11):1172-1174

From the Department of Electron Microscopy and Histopathology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Accra, Ghana.

We used the dideoxynucleotide chain termination method to determine the strains of nine non-typeable rotavirus enzyme immunoassay-positive samples, which were identified as G2. We detected nucleotide changes in the primer-binding region and amino acid substitutions within the VP7 protein of the G2 rotavirus strains. Genotyping primers need to be updated regularly.
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http://dx.doi.org/10.1097/INF.0000000000002037DOI Listing
November 2018

Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana.

Virol J 2018 09 17;15(1):143. Epub 2018 Sep 17.

Department of Virology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Accra, Ghana.

Background: Antiretrovirals have been available in Ghana since 2003 for HIV-1 positive pregnant women for prevention of mother-to-child transmission (PMTCT). Suboptimal responses to treatment observed post-PMTCT interventions necessitated the need to investigate the profile of viral mutations generated. This study investigated HIV-1 drug resistance profiles in mothers in selected centres in Ghana on treatment with a history of prophylaxis.

Methods: Genotypic Drug Resistance Testing for HIV-1 was carried out. Subtyping was done by phylogenetic analysis and Stanford HIV Database programme was used for drug resistance analysis and interpretation. To compare the significance between the different groups and the emergence of drug resistance mutations, p values were used.

Results: Participants who had prophylaxis before treatment, those who had treatment without prophylaxis and those yet to initiate PMTCT showed 32% (8), 5% (3) and 15% (4) HIV-1 drug resistance associated mutations respectively. The differences were significant with p value < 0.05. Resistance Associated Mutations (RAMs) were seen in 14 participants (35%) to nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). The most common NRTI mutation found was M184 V; K103 N and A98G were the most common NNRTI mutations seen. Thymidine Analogue Mutations (TAMs) such as M41 L, K70R and T215Y were found in all the groups; the most common of the TAMs found were M41 L and T215Y. Majority of the subtypes were CRF02_AG (82%).

Conclusion: In Ghana initiation of uninterrupted treatment upon diagnosis, coupled with drug resistance testing, would produce a better treatment outcome for HIV-1 positive pregnant women.
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http://dx.doi.org/10.1186/s12985-018-1051-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6142311PMC
September 2018

Sustained impact of rotavirus vaccine introduction on rotavirus gastroenteritis hospitalizations in children <5 years of age, Ghana, 2009-2016.

Vaccine 2018 11 8;36(47):7131-7134. Epub 2018 May 8.

Centers for Disease Control and Prevention, Atlanta, GA, USA.

Introduction: Ghana introduced monovalent rotavirus vaccine in April 2012. We sought to determine the long-term impact of routine rotavirus vaccination on rotavirus gastroenteritis hospitalizations in Ghana during the first 4 years following rotavirus vaccine introduction.

Methods: Active sentinel surveillance for acute gastroenteritis hospitalizations among children <5 years of age was conducted at two sites from July 2009 through June 2016. Stool specimens were collected from enrolled children and tested by enzyme immunoassay. Changes in the proportion of all-cause gastroenteritis hospitalizations due to rotavirus pre- (July 2009-June 2012) and post-vaccine introduction (July 2012-June 2016) were compared using chi-square test.

Results: The proportion of acute gastroenteritis hospitalizations due to rotavirus among children <5 years of age significantly declined by 42% from a pre-vaccine median of 50% (343/684) to a post-vaccine median of 29% (118/396) (p < 0.001). The age distribution of rotavirus hospitalizations shifted toward older ages with 64% (759/1197) of rotavirus hospitalizations occurring in children <12 months of age pre-vaccine introduction to 47% (212/453) occurring in children <12 months of age post-vaccine introduction (p < 0.001).

Discussion: The decline in rotavirus hospitalizations following rotavirus vaccine introduction have been sustained over the first 4 years of the vaccination program in Ghana. Continued vaccination against rotavirus will ensure that this burden remains low.
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http://dx.doi.org/10.1016/j.vaccine.2018.02.058DOI Listing
November 2018

Human pegivirus (HPgV) infection in Ghanaians co-infected with human immunodeficiency virus (HIV) and hepatitis B virus (HBV).

Virus Genes 2018 Jun 17;54(3):361-367. Epub 2018 Mar 17.

Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Human pegivirus (HPgV) is a positive single-stranded RNA virus in the Flaviviridae family. Phylogenetic analysis reveals the presence of multiple HPgV genotypes with distinct geographic locations. HPgV is of interest because of its potential beneficial impact on HIV disease progression. Despite this, the effects of HPgV in the context of other viral infections, such as hepatitis B virus (HBV), are poorly understood, and data from resource-limited settings are scarce. Therefore, we conducted a cross-sectional analysis of HPgV in HIV/HBV co-infected patients in Ghana. Sera from 100 HIV/HBV co-infected individuals were evaluated for HPgV RNA, and the genotype determined by sequencing the 5' untranslated region. HPgV RNA was detected in 27 samples (27%). Of these, 26 were genotyped successfully with 23 belonging to HPgV genotype 1 and 3 belonging to HPgV genotype 2. The presence of HPgV RNA had no statistically significant impact on CD4 cell count or HBV DNA titers in the HIV/HBV co-infected patients. However, there was a trend towards decreased HBV DNA levels in HPgV RNA-positive patients with CD4 cell count < 200 (p = 0.0626). HPgV co-infection is common in Ghana. The effect of HPgV on HIV or HBV disease among HIV/HBV co-infected patients was minimal. However, decreased HBV DNA levels in HPgV RNA-positive patients with low CD4 cell counts highlight the need for prospective studies of HPgV in HIV and hepatitis co-infected patients, especially in those with advanced HIV disease, to study further the effects of HPgV on liver disease.
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http://dx.doi.org/10.1007/s11262-018-1555-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5953819PMC
June 2018

Rotavirus strain distribution in Ghana pre- and post- rotavirus vaccine introduction.

Vaccine 2018 11 20;36(47):7238-7242. Epub 2018 Jan 20.

Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana. Electronic address:

Background: Ghana introduced the monovalent rotavirus vaccine (Rotarix) into its national paediatric vaccination programme in May2012. Vaccine introduction was initiated nationwide and achieved >85% coverage within a few months. Rotavirus strain distribution pre- and post-RV vaccine introduction is reported.

Methods: Stool samples were collected from diarrhoeic children <5 years of age hospitalized between 2009 and 2016 at sentinel sites across Ghana and analyzed for the presence of group A rotavirus by enzyme immunoassay. Rotavirus strains were characterized by RT-PCR and sequencing.

Results: A total of 1363 rotavirus EIA-positive samples were subjected to molecular characterization. These were made up of 823 (60.4%) and 540 (39.6%) samples from the pre- and post-vaccine periods respectively. Rotavirus VP7 genotypes G1, G2 and G3, and VP4 genotypes P[6] and P[8] constituted more than 65% of circulating G and P types in the pre-vaccine period. The common strains detected were G1P[8] (20%), G3P[6] (9.2%) and G2P[6] (4.9%). During the post-vaccine period, G12, G1 and G10 genotypes, constituted more than 65% of the VP7 genotypes whilst P[6] and P[8] made up more than 75% of the VP4 genotypes. The predominant circulating strains were G12P[8] (26%), G10P[6] (10%) G3P[6] (8.1%) and G1P[8] (8.0%). We also observed the emergence of the unusual rotavirus strain G9P[4] during this period.

Conclusion: Rotavirus G1P[8], the major strain in circulation during the pre-vaccination era, was replaced by G12P[8] as the most predominant strain after vaccine introduction. This strain replacement could be temporary and unrelated to vaccine introduction since an increase in G12 was observed in countries yet to introduce the rotavirus vaccine in West Africa. A continuous surveillance programme in the post-vaccine era is necessary for the monitoring of circulating rotavirus strains and the detection of unusual/emerging genotypes.
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http://dx.doi.org/10.1016/j.vaccine.2018.01.010DOI Listing
November 2018

Hepatitis B virus surface antigen and antibody markers in children at a major paediatric hospital after the pentavalent DTP-HBV-Hib vaccination.

Ghana Med J 2017 Mar;51(1):13-19

Clinical Virology Laboratory, School of Biomedical and Allied Health Sciences, University of Ghana, Accra, Ghana.

Objectives: The knowledge about outcomes of infant vaccination against HBV infections using the DPT-HepB-Hib vaccine in Ghana is limited. This study therefore investigated the levels of immunity to HBV among children who received the DPT-HepB-Hib vaccine and HBsAg carriage in non-responders. Correlates for non-response or poor response were also investigated.

Methods: Cross-sectional study. A major paediatric hospital in Accra. Four hundred and twenty four children between the ages of 5 to 32 months who had completed the full vaccination schedule for the DPT-HepB-Hib vaccine.

Results: Of the 424 children, 358 (84.4%) developed anti-HBs while 340 (80.2%) developed ≥10 mIU/ml anti-HBs (sero-protection) and 3 had HBsAg. A binary logistic regression analysis showed that younger children were associated with sero-conversion (p=.022) and sero-protection (p=.021). For anti-HBs titres ≥100 mIU/ml age was a weaker but significant contributor (p=.041), as compared to the number of vaccines from different manufacturers the child used (p=.028). The mean age of those who used a single type of vaccine was higher (14.75 ± 6.056 months; n=268) than those who used vaccines from two or more manufacturers (11.96 ± 4.645 months; n=156), p= <.001 (CI: -3.897 - 1.688), an indication that efforts to procure vaccine from same source when it was initially introduced are waning.

Conclusions: There is still a residual possibility of infection with HBV in spite of infant vaccination. In the light of possible loss of anamnestic response over time, there is the need to consider a birth dose for HBV vaccination for all neonates or booster dose for infants who may not have received the vaccine at birth. Using vaccines from a single manufacturer is recommended.

Funding: None declared.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5611951PMC
http://dx.doi.org/10.4314/gmj.v51i1.3DOI Listing
March 2017

Identification and comparative analysis of hepatitis B virus genotype D/E recombinants in Africa.

Virus Genes 2017 Aug 31;53(4):538-547. Epub 2017 May 31.

Division of Digestive Disease, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Globally, there are approximately 240 million people chronically infected with hepatitis B virus (HBV)-a major cause of hepatocellular carcinoma. Ten different HBV genotypes (A-J) have been identified with distinct geographic distributions. Novel variants generated by recombination between different HBV genotypes have been documented worldwide and represent an important element of genetic variability with possible clinical implications. Here, the complete genome sequence of an HBV genotype D/E recombinant from Ghana is reported. The full-length sequence was obtained using rolling circle amplification followed by PCR and sequenced using next-generation sequencing (NGS). A consensus sequence was extracted from the NGS data and underwent phylogenetic analysis to determine genotype, as well as the recombination pattern. Subsequently, the sequence was compared to recombinants described previously in Africa. Based on MCMC phylogenetic analysis, SimPlot recombination analyses, and intragroup genetic distance, the isolate 007N full-length genome is unique compared to other reported D/E recombinants in Africa.
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http://dx.doi.org/10.1007/s11262-017-1469-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5710801PMC
August 2017

Short-term treatment outcomes in human immunodeficiency virus type-1 and hepatitis B virus co-infections.

Ann Clin Microbiol Antimicrob 2016 Jun 2;15(1):38. Epub 2016 Jun 2.

Retrovirus Laboratory, Department of Pediatrics, Washington University Medical School, St. Louis, MO, USA.

Background: Co-infection of HIV with HBV is common in West Africa but little information is available on the effects of HBV on short-term therapy for HIV patients. A 28 day longitudinal study was conducted to examine short-term antiretroviral therapy (ART) outcomes in HIV infected individuals with HBV co-infection.

Methods: Plasma from 18 HIV infected individuals co-infected with HBV and matched controls with only HIV infection were obtained at initiation, and 7 and 28 days after ART. HIV-1 viral load changes were monitored. Clinical and demographic data were also obtained from patient folders, and HIV-1 drug resistance mutation and subtype analysis performed.

Results: The presence of HBV co-infection did not significantly affect HIV-1 viral load changes within 7 or 28 days. The CD4(+) counts on the other hand of patients significantly affected the magnitude of HIV-1 viral load decline after 7 days (ρ = -0.441, p = 0.040), while the pre-ART HIV-1 VL (ρ = 0.844, p = <0.001) and sex (U = 19.0, p = 0.020) also determined HIV-1 viral load outcomes after 28 days of ART. Even though the geometric sensitivity score of HIV-1 strains were influenced by the HIV-1 subtypes (U = 56.00; p = 0.036), it was not a confounder for ART outcomes.

Conclusions: There may be the need to consider the confounder effects of sex, pre-ART CD4(+), and pre-ART HIV-1 viral load in the discourse on HIV and HBV co-infection.
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http://dx.doi.org/10.1186/s12941-016-0152-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4890471PMC
June 2016

HBV genotypes and drug resistance mutations in antiretroviral treatment-naive and treatment-experienced HBV-HIV-coinfected patients.

Antivir Ther 2017 11;22(1):13-20. Epub 2016 May 11.

Warren Alpert Medical School of Brown University, Providence, RI, USA.

Background: The presence of HBV resistance mutations upon initiation or during antiretroviral therapy (ART) in HIV-coinfected patients is an important determinant of treatment response. The main objective of the study was to determine the prevalence of HBV resistance mutations in antiretroviral treatment-naive and treatment-experienced HBV-HIV-coinfected Ghanaian patients with detectable HBV viraemia.

Methods: HBV-HIV-coinfected patients who were ART-naive or had received at least 9 months of lamivudine (3TC)-containing ART were enrolled in a cross-sectional study. Demographic and clinical data were collected and HBV DNA quantified. Partial HBV sequences were amplified by PCR and sequenced bi-directionally to obtain a 2.1-2.2 kb fragment for phylogenetic analysis of HBV genotypes and evaluation of drug resistance mutations.

Results: Of the 100 HBV-HIV-coinfected study patients, 75 were successfully PCR-amplified, and 63 were successfully sequenced. Of these 63 patients, 27 (42.9%) were ART-experienced and 58 (92.1%) had HBV genotype E. No resistance mutations were observed in the 36 ART-naive patients, while 21 (77.8%) of 27 treatment-experienced patients had resistance mutations. All patients with resistance mutations had no tenofovir in their regimens, and 80% of them had HIV RNA <40 copies/ml. The 3TC resistance mutations rtL180M and rtM204V were observed in 10 (47.6%) of the 21 patients, while 5 patients (23.8%) had rtV173L, rtL180M and rtM204V mutations.

Conclusions: A high proportion of HBV-HIV-coinfected patients with detectable viraemia on 3TC-containing ART had resistance mutations despite good ART adherence as determined by HIV RNA suppression. This study emphasizes the need for dual therapy as part of a fully suppressive ART in all HBV-HIV-coinfected patients in Ghana.
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http://dx.doi.org/10.3851/IMP3055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5106338PMC
January 2018

Identification of OP354-like human rotavirus strains with subtype P[8]b in Ghanaian children with diarrhoea.

Virol J 2016 Apr 22;13:69. Epub 2016 Apr 22.

Department of Electron Microscopy and Histopathology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Accra, Ghana.

Background: Rotaviruses with the P[8] genotype have been associated with majority of infections. Recent improvements in molecular diagnostics have delineated the P[8] genotype into P[8]a and P[8]b subtypes. P[8]a is the previously known P[8] genotype which is common whilst P[8]b subtype also known as OP354-like strain is genetically distinct, rarely detected and reported from a few countries. In a previous study, the P-types could not be determined for 80 RVA-positive samples by conventional RT-PCR genotyping methods with the recommended pool of P-genotype specific primers used in the WHO Regional Rotavirus Reference Laboratory in Ghana. The present study employed sequence-dependent cDNA amplification method to genotype previously non-typeable P-types.

Methods: Viral RNAs were extracted and rotavirus VP4 genes amplified by one step RT-PCR using gene specific primers. PCR amplicons were purified, sequenced and sequences aligned with cognate gene sequences available in GenBank using the ClustalW algorithm. Phylogenetic analysis was performed using the Neighbour-Joining method in MEGA v6.06 software. Phylogenetic tree was statistically supported by bootstrapping with 1000 replicates, and distances calculated using the Kimura-2 parameter model.

Results: Of the 80 RVA-positive samples, 57 were successfully sequenced and characterized. Forty-eight of these were identified as P[8] strains of which 5 were characterized as the rare P[8]b subtype. Phylogenetic analysis of the VP8* fragment of the VP4 genes of these P[8]b strains revealed a close relationship with prototype OP354-like P[8]b strain and P[8]b strains of Russian and South African P[8]b origin.

Conclusion: The study highlights the importance of regularly updating the primers employed for molecular typing of rotaviruses.
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http://dx.doi.org/10.1186/s12985-016-0523-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4841057PMC
April 2016

Stroke Investigative Research and Education Network: Community Engagement and Outreach Within Phenomics Core.

Health Educ Behav 2016 04;43(1 Suppl):82S-92S

University of Ibadan, Ibadan, Nigeria.

Stroke is the leading cause of neurological hospital admissions in sub-Saharan Africa (SSA) and the second leading cause of death globally. The Stroke Investigative Research and Education Network seeks to comprehensively characterize the genomic, sociocultural, economic, and behavioral risk factors for stroke and to build effective teams for research to address and decrease the burden of stroke and other noncommunicable diseases in SSA. One of the first steps to address this goal is to effectively engage the communities that suffer the high burden of disease. The purpose of this article is to describe plans to elucidate information about knowledge, attitudes, beliefs, and practices about stroke and genomics from patients, caregivers, and local leaders, to recruit participation in research activities and dissemination of ongoing results, as well as to facilitate research uptake and impact within the broader communities of scientists, health professionals, policy makers, and others. We describe the (a) study sites and their communities; (b) plans for community advisory boards, focus groups, and surveys; (c) methods for data management in REDCap database; (d) analyses of qualitative data; (e) evaluation of community and public engagement across multiple sites and research teams in SSA and the United States; (f) use of RE-AIM for presentation of evaluation data; and (g) community indicators of success. This is the first of its kind public outreach engagement initiative to evaluate stroke and genomics in SSA, and has implications as a model for assessment in other high-stroke risk populations.
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http://dx.doi.org/10.1177/1090198116634082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4905563PMC
April 2016

Proportion and factors associated with Hepatitis B viremia in antiretroviral treatment naïve and experienced HIV co-infected Ghanaian patients.

BMC Infect Dis 2016 Jan 13;16:14. Epub 2016 Jan 13.

Warren Alpert Medical School of Brown University, Providence, RI, USA.

Background: The global burden of Hepatitis B virus (HBV) and HIV co-infection is enormous. The risk of developing cirrhosis and hepatocellular cancer is associated with HBV DNA levels. The main objective of the study was to determine proportion of Hepatitis B viremia in ART-naïve and ART-experienced co-infected Ghanaian patients and factors associated with HBV viremia after at least 36 weeks of lamivudine with or without tenofovir containing ART.

Methods: Hepatitis B and HIV co-infected patients who were ART-naïve or had received at least 9 months of lamivudine-containing ART were enrolled in a cross-sectional study at Korle-Bu Teaching Hospital. Demographic and clinical data were collected and samples obtained for Hepatitis B serology, liver function tests and HBV DNA. Factors associated with viremia were determined using univariate and multivariate logistic regression analysis.

Results: Of 3108 HIV-infected patients screened, 257 (8.3%) were HBsAg-positive, of which 235 enrolled. Overall, 152 (64.7%) were ART-experienced and 83 (35.3%) were ART-naïve. Eighty-nine-percent of ART-naïve and 42.1% of ART-experienced patients had HBV DNA > 20 IU/mL. In multivariate analysis of all patients, being ART-naïve (OR 10.1, 95% CI 4.6-21.9) and elevated ALT (OR 3.7, 95% CI 1.8-7.9) were associated with Hepatitis B viremia. In treatment experienced patients, elevated ALT (OR 4.8 CI 2.0-12.1) and male sex (OR 2.1, 95% CI 1.0-4.2) were associated with Hepatitis B viremia.

Conclusions: Majority of ART-naïve (89%) and 42% of ART-experienced patients had detectable hepatitis B viremia > 20 IU/mL. An abnormal serum ALT was significantly associated with hepatitis B viremia in HBV and HIV co-infected patients irrespective of treatment status. Baseline and on-treatment ALT may be a useful non-invasive predictor of Hepatitis B viremia in resource-constrained countries in sub-Saharan Africa where infection is endemic and viral load tests are not widely available.
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http://dx.doi.org/10.1186/s12879-016-1342-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710995PMC
January 2016

Phenotyping Stroke in Sub-Saharan Africa: Stroke Investigative Research and Education Network (SIREN) Phenomics Protocol.

Neuroepidemiology 2015 19;45(2):73-82. Epub 2015 Aug 19.

Korle-Bu Teaching Hospital, Accra, Ghana.

Background: As the second leading cause of death and the leading cause of adult-onset disability, stroke is a major public health concern particularly pertinent in Sub-Saharan Africa (SSA), where nearly 80% of all global stroke mortalities occur, and stroke burden is projected to increase in the coming decades. However, traditional and emerging risk factors for stroke in SSA have not been well characterized, thus limiting efforts at curbing its devastating toll. The Stroke Investigative Research and Education Network (SIREN) project is aimed at comprehensively evaluating the key environmental and genomic risk factors for stroke (and its subtypes) in SSA while simultaneously building capacities in phenomics, biobanking, genomics, biostatistics, and bioinformatics for brain research.

Methods: SIREN is a transnational, multicentre, hospital and community-based study involving 3,000 cases and 3,000 controls recruited from 8 sites in Ghana and Nigeria. Cases will be hospital-based patients with first stroke within 10 days of onset in whom neurovascular imaging will be performed. Etiological and topographical stroke subtypes will be documented for all cases. Controls will be hospital- and community-based participants, matched to cases on the basis of gender, ethnicity, and age (±5 years). Information will be collected on known and proposed emerging risk factors for stroke. STUDY SIGNIFICANCE: SIREN is the largest study of stroke in Africa to date. It is anticipated that it will shed light on the phenotypic characteristics and risk factors of stroke and ultimately provide evidence base for strategic interventions to curtail the burgeoning burden of stroke on the sub-continent.
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http://dx.doi.org/10.1159/000437372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604029PMC
July 2016

The burden of stroke in Africa: a glance at the present and a glimpse into the future.

Cardiovasc J Afr 2015 Mar-Apr;26(2 Suppl 1):S27-38

Medical University of South Carolina, USA.

Objective: Information on the current burden of stroke in Africa is limited. The aim of this review was to comprehensively examine the current and projected burden of stroke in Africa.

Methods: We systematically reviewed the available literature (PubMed and AJOL) from January 1960 and June 2014 on stroke in Africa. Percentage change in age-adjusted stroke incidence, mortality and disability-adjusted life years (DALYs) for African countries between 1990 and 2010 were calculated from the Global Burden of Diseases (GBD) model-derived figures.

Results: Community-based studies revealed an age-standardised annual stroke incidence rate of up to 316 per 100,000 population, and age-standardised prevalence rates of up to 981 per 100,000. Model-based estimates showed significant mean increases in age-standardised stroke incidence. The peculiar factors responsible for the substantial disparities in incidence velocity, ischaemic stroke proportion, mean age and case fatality compared to high-income countries remain unknown.

Conclusions: While the available study data and evidence are limited, the burden of stroke in Africa appears to be increasing.
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http://dx.doi.org/10.5830/CVJA-2015-038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4557491PMC
February 2016

Severe acute rotavirus gastroenteritis in children less than 5 years in southern Ghana: 2006-2011.

Pediatr Infect Dis J 2014 Jan;33 Suppl 1:S9-S13

From the *Department of Child Health, University of Ghana Medical School; †Korle Bu Teaching Hospital; ‡Department of Microbiology, University of Ghana Medical School, Accra, Ghana; §Africa Rotavirus Surveillance Network, WHO Regional Office for Africa, Djoue, Brazzaville, Republic of Congo; and ¶Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana.

Background: Rotavirus is a major cause of acute gastroenteritis (AGE) globally. Local data on disease burden will guide recommendations for rotavirus vaccination and monitoring impact of the intervention.

Methods: Prospective surveillance for rotavirus gastroenteritis was conducted in 3 hospitals in southern Ghana during the period August 2006 to December 2011, as part of the African Rotavirus Surveillance Network. Clinical data and stool specimens were collected from children <5 years of age and hospitalized with AGE (defined as 3 or more watery stools for up to 7 days). Stool was tested for rotavirus by enzyme immunoassay and rotavirus genotype identified by reverse-transcriptase polymerase chain reaction.

Results: We tested 3044 stool samples from 3939 children. Rotavirus was detected in 45.6%, 51.3% and 48.5% of cases at the primary, secondary and tertiary care hospital, respectively. Both genders were equally affected; 75% (2954/3939) of the cohort were aged 3-18 months. Overall, rotavirus was detected in 49.4% (1504/3044) of cases, caused over 30% of AGE hospitalizations all year round and up to 70% of cases during peak seasons. Peak season occurred during cool dry months in 2008, 2010 and 2011 and the rainy season in 2009. Mortality from AGE occurred in 1.5% (45/3044) of cases and 48.9% (22/45) of these were rotavirus positive.

Conclusions: Rotavirus causes significant morbidity and mortality in young Ghanaian children. As Ghana introduced rotavirus vaccination in the national immunization program in 2012, continued surveillance is required to monitor the impact of this intervention.
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http://dx.doi.org/10.1097/INF.0000000000000045DOI Listing
January 2014

Effectiveness of first-line antiretroviral therapy and correlates of longitudinal changes in CD4 and viral load among HIV-infected children in Ghana.

BMC Infect Dis 2013 Oct 13;13:476. Epub 2013 Oct 13.

Departments of Pediatrics and Pharmacology, Yale School of Medicine, New Haven, CT, USA.

Background: Antiretroviral therapy (ART) scale-up in resource-limited countries, with limited capacity for CD4 and HIV viral load monitoring, presents a unique challenge. We determined the effectiveness of first-line ART in a real world pediatric HIV clinic and explored associations between readily obtainable patient data and the trajectories of change in CD4 count and HIV viral load.

Methods: We performed a longitudinal study of a cohort of HIV-infected children initiating ART at the Korle-Bu Teaching Hospital Pediatric HIV clinic in Accra, Ghana, aged 0-13 years from 2009-2012. CD4 and viral load testing were done every 4 to 6 months and genotypic resistance testing was performed for children failing therapy. A mixed linear modeling approach, combining fixed and random subject effects, was employed for data analysis.

Results: Ninety HIV-infected children aged 0 to 13 years initiating ART were enrolled. The effectiveness of first-line regimen among study participants was 83.3%, based on WHO criteria for virologic failure. Fifteen of the 90 (16.7%) children met the criteria for virologic treatment failure after at least 24 weeks on ART. Sixty-seven percent virologic failures harbored viruses with  ≥ 1 drug resistant mutations (DRMs); M184V/K103N was the predominant resistance pathway. Age at initiation of therapy, child's gender, having a parent as a primary care giver, severity of illness, and type of regimen were associated with treatment outcomes.

Conclusions: First-line ART regimens were effective and well tolerated. We identified predictors of the trajectories of change in CD4 and viral load to inform targeted laboratory monitoring of ART among HIV-infected children in resource-limited countries.
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http://dx.doi.org/10.1186/1471-2334-13-476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3852953PMC
October 2013

Rotavirus genotypes associated with childhood severe acute diarrhoea in southern Ghana: a cross-sectional study.

Virol J 2013 Sep 14;10:287. Epub 2013 Sep 14.

Department of Child Health, University of Ghana Medical School, College of Health Sciences, University of Ghana, Accra, Ghana.

Background: Rotavirus immunization has been effective in developed countries where genotype G1P[8] is the predominant rotavirus strain. Knowledge of circulating strains in a population before introduction of rotavirus immunization program will be useful in evaluating the effect of the intervention.

Methods: Rotavirus was identified by enzyme immuno-assay (EIA) on stool specimens of children (age 0-59 months) hospitalized with acute gastroenteritis from August 2007 to February 2011 in Accra, Ghana. Rotavirus positive specimens were further characterized by polyacrylamide gel electrophoresis (PAGE) and reverse-transcriptase polymerase chain reaction (RT-PCR).

Results: Of the 2277 acute gastroenteritis hospitalizations 1099 (48.2%) were rotavirus-positive by EIA. Of the 1099 cases 977 (89%) were PAGE positive. All EIA positive specimens were further subjected to RT-PCR and 876 (79.7%) had sufficient material for characterization. Of these 876 cases, 741 (84.6%) were assigned G genotype, 709 (80.9%) P genotype, and 624 (71.2%) both G and P genotypes. We identified 8 G genotypes (G1, G2, G3, G4, G8, G9, G10, G12) and 3 P genotypes (P[4], P[6], P[8]). G1 (50.9%), G2 (18.8%), G3 (12.8%), P[8] (36.1%) and P[6] (30.7%) were the most prevalent. The most prevalent genotype combination was G1P[8] (28%). Mixed G (7.3%) and P (24.2%) genotypes were not uncommon. There was year-by-year and seasonal variations for most genotypes.

Conclusion: There is great diversity of rotavirus strains in children with severe gastroenteritis in southern Ghana. Even though cross-protection with vaccine-induced immunity occurs, continued strain surveillance is recommended after the introduction of rotavirus vaccine in the national immunization program.
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http://dx.doi.org/10.1186/1743-422X-10-287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3848793PMC
September 2013

The effects of co-infection with human parvovirus B19 and Plasmodium falciparum on type and degree of anaemia in Ghanaian children.

Asian Pac J Trop Biomed 2013 Feb;3(2):129-39

Department of Microbiology, University of Ghana Medical School, Korle-Bu, Accra, Ghana ; Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Scotland, UK.

Objective: To determin the extent to which parvovirus B19 (B19V) and co-infection of B19V and malaria contribute to risk of anaemia in children.

Methods: B19V DNA and malaria parasites were screened for 234 children at the PML Children's Hospital in Accra. The role of B19V and co-infection with B19V and malaria in anaemia was evaluated by analysing full blood cell counts, malaria and B19V DNA results from these children.

Results: The prevalence of B19V, malaria and co-infection with B19V and malaria was 4.7%, 41.9% and 2.6%, respectively. Malaria posed a greater risk in the development of mild anaemia compared to severe anaemia (OR=5.28 vrs 3.15) whereas B19V posed a higher risk in the development of severe anaemia compared to mild anaemia (OR=4.07 vrs 1.00) from a non-anaemic child. Persons with co-infection with B19V and malaria had 2.23 times the risk (95% CI=0.40-12.54) of developing severe anaemia should they already have a mild anaemia. The degree of anaemia was about three times affected by co-infection (Pillai's trace=0.551, P=0.001) as was affected by malaria alone (Pillai's trace=0.185, P=0.001). B19V alone did not significantly affect the development of anaemia in a non-anaemic child. Microcytic anaemia was associated with B19V and co-infection with B19V and malaria more than normocytic normochromic anaemia.

Conclusions: B19V was associated with malaria in cases of severe anaemia. The association posed a significant risk for exacerbation of anaemia in mild anaemic children. B19V and co-infection with B19V and malaria may be associated with microcytic anaemia rather than normocytic normochromic anaemia as seen in cases of B19V infection among persons with red cell abnormalities.
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http://dx.doi.org/10.1016/S2221-1691(13)60037-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3627173PMC
February 2013

Prevalence of severe acute rotavirus gastroenteritis and intussusceptions in Ghanaian children under 5 years of age.

J Infect Dev Ctries 2012 Feb 13;6(2):148-55. Epub 2012 Feb 13.

Department of Child Health, University of Ghana Medical School, Accra, Ghana.

Introduction: Vaccination is the most effective preventive strategy against rotavirus disease. Regional differences in prevalent rotavirus genotypes may affect vaccine efficacy. Pre-vaccine surveillance for burden of rotavirus disease, prevalent rotavirus genotypes, and association between rotavirus disease and intussusceptions helps in monitoring the impact of vaccination.

Methodology: A prospective study was conducted from January 2008 to December 2009 in children younger than five years hospitalized for longer than 24 hours with acute gastroenteritis. Data on confirmed cases of intussusception were collected retrospectively. Stools were tested by enzyme immunoassay, reverse-transcriptase polymerase chain reaction and nucleotide sequencing. 

Results: Acute gastroenteritis (AGE) caused 13.1% (2,147/16,348) of hospitalizations among children under five years. Stools were tested for 50.2% (1077/2147) of AGE cases. Of these, 49% (528/1077) were rotavirus positive. Rotavirus gastroenteritis, non-rotavirus gastroenteritis, and intussusceptions were most prevalent in children under 15 months [80.3%, 74% and 91% respectively]. Rotavirus was detected from more than 60% of acute gastroenteritis cases during peak months. The prevalence of intussusception showed no seasonal pattern. The peak ages of six to twelve months for acute gastroenteritis and five to eight months for intussusception overlapped. G1, G2 and mixed G/P genotypes were common in the isolated rotaviruses.

Conclusion: Rotavirus gastroenteritis causes significant morbidity in children younger than five years of age in Ghana. Although the peak age of rotavirus gastroenteritis and intussusceptions overlapped, there was no seasonal correlation between them. The high prevalence of mixed G/P genotypes in Ghanaian children may affect the effectiveness of vaccination.
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http://dx.doi.org/10.3855/jidc.1667DOI Listing
February 2012

Prevalence and impact of hepatitis B and C virus co-infections in antiretroviral treatment naïve patients with HIV infection at a major treatment center in Ghana.

J Med Virol 2012 Jan;84(1):6-10

Clinical Virology Laboratory, Department of Microbiology, University of Ghana Medical School, Accra, Ghana.

Data on the effects of the presence of hepatitis B virus (HBV) and hepatitis C virus (HCV) in patients co-infected with these viruses and HIV in West Africa are conflicting and little information is available in Ghana. A cohort of 138 treatment naïve individuals infected with HIV was screened for HBV and HCV serologic markers; HBsAg positive patients were tested for HBeAg, anti-HBe, and anti-HBc IgM. The viral load of HIV-1 in the plasma was determined in 81 patients. Eighteen of the 138 patients (13%) and 5 (3.6%) had HBsAg and anti-HCV, respectively. None of the patients had anti-HBc IgM, but 10 (55.6%) and 8 (44.4%) of the 18 patients who were HBsAg positive had HBeAg and anti-HBe, respectively. In patients with measurement of CD4(+) undertaken within 1 month (n = 83), CD4(+) count was significantly lower in patients with HBeAg (median [IQR], 81 [22-144]) as compared to those with anti-HBe (median [IQR], 210 [197-222]) (P = 0.002, CI: -96.46 to 51.21). However, those with HIV mono-infection had similar CD4(+) counts (median [IQR], 57 [14-159]) compared to those with HBeAg (P = 1.0, CI: -71.75 to 73.66). Similar results were obtained if CD4(+) count was measured within 2 months prior to initiation of HAART (n = 119). Generally, HBV and anti-HCV did not affect CD4(+) and viral loads of HIV-1 in plasma but patients with HIV and HBV co-infection who had HBeAg had more severe immune suppression as compared to those with anti-HBe. This may have implication for initiating HAART in HBV endemic areas.
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http://dx.doi.org/10.1002/jmv.22262DOI Listing
January 2012

Misclassification of recent HIV-1 seroconversion in sub-Saharan Africa using the sensitive/less sensitive technique.

Virol J 2011 Apr 17;8:176. Epub 2011 Apr 17.

Clinical Virology Laboratory, Department of Microbiology, University of Ghana Medical School, Accra, Ghana.

Background: In resource-limited settings where HIV-1 is endemic, there is a need for simple, inexpensive but effective rapid methods for detecting recent infections and estimating incidence for the purposes of surveillance and management. We sort to determine possible reasons for reported misclassifications of recent HIV-1 seroconversion as determined with the S/LS assay in sub-Saharan Africa.

Findings: We used the modified Determine HIV-1/2 sensitive/less sensitive method for determining recent HIV-1 seroconversion to determine recent infections among ELISA repeat HIV-1 positive samples from blood donors. Furthermore, HIV-1 seropositivity was confirmed using a line immunoassay and the results used to validate the performance of the modified Determine HIV-1/2 S/LS assay. The results confirmed reported misclassifications of recent HIV-1 seroconversion in sub-Saharan Africa. It was noted that, lack of confirmation of HIV-1 seropositivity in suspected cases of HIV-1 contributed to misclassifications.

Conclusions: It was concluded that, with confirmation of HIV-1 seropositivity, the modified Determine HIV-1/2 S/LS assay will be a rapid and cost effective method for determining HIV-1 recent infections and estimating incidence in resource-limited settings. The need for detailed studies to validate simple methods for determining recent HIV-1 infections is emphasized.
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http://dx.doi.org/10.1186/1743-422X-8-176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3083366PMC
April 2011

Viral decay rates are similar in HIV-infected patients with and without TB coinfection during treatment with an Efavirenz-based regimen.

Clin Infect Dis 2011 Feb 20;52(4):547-50. Epub 2011 Jan 20.

University of Ghana Medical School, Ghana.

Viral decay rates during efavirenz-based therapy were compared between human immunodeficiency virus (HIV)-infected patients without tuberculosis (n = 40) and those with tuberculosis coinfection who were receiving concurrent antituberculous therapy (n = 34). Phase I and II viral decay rates were similar in the 2 groups (P > .05). Overall, concurrent antituberculous therapy did not reduce the efficacy of the HIV treatment.
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http://dx.doi.org/10.1093/cid/ciq196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3060905PMC
February 2011

Paradoxically elevated efavirenz concentrations in HIV/tuberculosis-coinfected patients with CYP2B6 516TT genotype on rifampin-containing antituberculous therapy.

AIDS 2011 Jan;25(3):388-90

The Miriam Hospital, Providence, Rhode Island 02906, USA.

Some individuals have higher efavirenz plasma concentrations during rifampin-containing tuberculosis (TB) therapy, contrary to the expected induction effect of rifampin. Among HIV-infected patients without (n = 38) and with TB on rifampin-containing therapy (n = 18), we tested the hypothesis that drug-gene interaction may explain the highly variable drug interactions. Two-way analysis of variance revealed a significant interaction between CYP2B6 516G→T polymorphism and rifampin-containing therapy, suggesting that efavirenz dose adjustment may need to be individualized on the basis of the patient's genotype.
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http://dx.doi.org/10.1097/QAD.0b013e3283427e05DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6170200PMC
January 2011

CYP2B6, CYP2A6 and UGT2B7 genetic polymorphisms are predictors of efavirenz mid-dose concentration in HIV-infected patients.

AIDS 2009 Oct;23(16):2101-6

Warren Alpert Medical School of Brown University, Rhode Island, USA.

Objective: UDP-glucuronosyltransferase (UGT) 2B7 was recently identified as the main enzyme mediating efavirenz N-glucuronidation. In this study, we determined whether selected UGT2B7 polymorphisms could be used to enhance the prediction of efavirenz plasma concentrations from CYP2B6 and CYP2A6 genotypes.

Methods: Mid-dose efavirenz plasma concentrations were determined in 94 HIV-infected Ghanaian patients at 2-8 weeks of antiretroviral therapy. CYP2B6 and CYP2A6 genotypes had been previously reported. UGT2B7 exon 2 single-nucleotide polymorphisms (SNPs) c.735A>G (UGT2B7*1c; rs28365062) and c.802C>T (H268Y; UGT2B7*2; rs7439366) were determined by direct sequencing with UGT2B7*1a defined as the reference allele. Relationships between efavirenz plasma concentrations, demographic variables and genotypes were evaluated by univariate and multivariate statistical approaches.

Results: The mean (+/-SD) mid-dose efavirenz plasma concentration was 3218 (+/-3905) ng/ml with coefficient of variation of 121%. Independent predictors of efavirenz concentration included CYP2B6 c.516TT genotype (4030 ng/ml increase; 95% confidence interval 2882-5505 ng/ml, P < 0.001), UGT2B7*1a carrier status (475 ng/ml increase; 95% confidence interval 138-899 ng/ml, P = 0.004) and CYP2A6*9 and/or *17 carrier status (372 ng/ml increase; 95% confidence interval 74-742 ng/ml, P = 0.013). Overall, CYP2B6 c.516TT genotype, UGT2B7*1a carrier status and CYP2A6*9 or *17 carrier status accounted for 45.2, 10.1 and 8.6% of the total variance, respectively.

Conclusion: Our findings demonstrate independent effects of CYP2A6 and UGT2B7 genetic variation on efavirenz disposition beyond that of the CYP2B6 polymorphisms. The development and testing of a pharmacogenetic algorithm for estimating the appropriate dose of efavirenz should incorporate genotypic data from both the oxidative and glucuronidation pathways.
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http://dx.doi.org/10.1097/QAD.0b013e3283319908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2875867PMC
October 2009

Web interface-supported transmission risk assessment and cost-effectiveness analysis of postdonation screening: a global model applied to Ghana, Thailand, and the Netherlands.

Transfusion 2009 Dec 25;49(12):2729-42. Epub 2009 Aug 25.

Unit of PharmacoEpidemiology and PharmacoEconomics, Department of Pharmacy, University of Groningen, Groningen, The Netherlands.

Background: The goal of our research was to actively involve decision makers in the economic assessment of screening strategies in their region. This study attempted to accomplish this by providing an easy-to-use Web interface at http://www.bloodsafety.info that allows decision makers to adapt this model to local conditions.

Study Design And Methods: The cost-effectiveness was compared of 1) adding antigen screening to antibody screening for hepatitis C virus (HCV) and human immunodeficiency virus (HIV); 2) adding nucleic acid amplification testing (NAT) on hepatitis B virus (HBV), HCV, and HIV in minipool (pool of 6 [MP6] and 24 [MP24]) to antibody screening and hepatitis B surface antigen (HBsAg) screening; and 3) individual-donation NAT on HBV, HCV, and HIV to antibody screening and HBsAg screening for Ghana, Thailand, and the Netherlands.

Results: The combination of HCV antibody-antigen combination (combo) and HIV combo added to antibody screening in Ghana and Thailand was cost-effective according to the WHO criteria. MP24-NAT screening in Ghana was also cost-effective. MP24-NAT on HBV, HCV, and HIV was not cost-effective compared to the other screening strategies evaluated for the Netherlands. Large regional differences in cost-effectiveness were found for Thailand.

Conclusion: The young transfusion recipient population of Ghana in combination with a high risk of viral transmission yields better cost-effectiveness for additional tests. The advanced age of the transfused population of the Netherlands and a small risk of viral transmission gives poor cost-effectiveness for more sensitive screening techniques. It was demonstrated that a global health economic model combined with a Web interface can provide easy access to risk assessment and cost-effectiveness analysis.
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http://dx.doi.org/10.1111/j.1537-2995.2009.02351.xDOI Listing
December 2009