Hepatitis B virus (HBV) viremia despite tenofovir disoproxil fumarate-containing antiretroviral therapy in persons with HBV/HIV coinfection.

BACKGROUND: The goal of treatment of hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection is suppression of both viruses; yet incomplete HBV suppression on tenofovir (TFV) disoproxil fumarate (TDF)-based antiretroviral therapy (ART) is common. This study investigated TFV resistance-associated mutations (RAMs) in individuals with HBV/HIV coinfection with viremia on TDF/lamivudine (3TC)-containing ART. METHODS: Samples from individuals with HBV DNA levels ≥20 IU/mL in a cross-sectional study of 138 persons with HBV/HIV coinfection in Ghana were analyzed in the present study. HBV was sequenced for RAM analysis. TFV-diphosphate (TFV-DP) concentration in peripheral blood mononuclear cells (PBMCs) was used to assess ART adherence level. RESULTS: Nine of 138 participants (6.5 %) had detectable HBV DNA levels ≥20 IU/mL while on ART. Seven of the nine participants had TFV-DP concentrations commensurate with 7 doses per week, and six had suppressed HIV RNA. Phylogenetic analysis revealed that eight sequences were HBV genotype E, with one genotype E/A recombinant. Ten previously-reported TFV RAMs were present in the study samples; eight were wild-type for HBV genotype E. The non-genotype-E-wild-type point mutations M267L and K333Q were found in two and one patients, respectively. No 3TC RAMs were found. CONCLUSION: HBV viremia despite high adherence to TDF/3TC-based ART may be associated with the presence of TFV RAMs. These findings highlight the need for enhanced resistance monitoring and further research to examine the clinical significance of reported TFV RAMs. Individuals with HBV/HIV coinfection and TFV resistance on TDF-based ART may need alternative treatment strategies.

Pharmacogenetic determinants of tenofovir diphosphate and lamivudine triphosphate concentrations in people with HIV/HBV coinfection.

The nucleos(t)ide analogs require phosphorylation to the pharmacologically active anabolites in cells. We investigated the hypothesis that single-nucleotide polymorphisms (SNPs) in genes that encode transporters and phosphodiesterase (PDE) enzymes involved in tenofovir (TFV), disoproxil fumarate (TDF), and lamivudine (3TC) disposition will be associated with concentrations of their phosphate anabolites and virologic response. Individuals with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfection receiving TDF/3TC-containing antiretroviral therapy were enrolled. Steady-state TFV diphosphate (TFV-DP) and 3TC triphosphate (3TC-TP) concentrations in peripheral blood mononuclear cells (PBMCs) and dried blood spot samples were quantified. The relationship between genetic variants and TFV-DP and 3TC-TP concentrations as well as with virologic response were examined using multivariable linear regression. Of the 136 participants (median age 43 years; 63% females), 6.6% had HBV non-suppression, and 7.4% had HIV non-suppression. The multidrug resistance protein 2 (encoded by ABCC2 rs2273697) SNP was associated with 3TC-TP concentrations in PBMCs. The human organic anion transporter-1 (encoded by SLC28A2) rs11854484 SNP was associated with HIV non-suppression, and when evaluated together with SNPs with marginal associations (ABCC2 rs717620 and PDE1C rs30561), participants with two or three variants compared to those with none of these variants had an adjusted odds ratio of 48.3 (confidence interval, 4.3-547.8) for HIV non-suppression. None of the SNPs were associated with HBV non-suppression. Our study identified ABCC2 SNP to be associated with 3TC-TP concentrations in PBMCs. Also, a combination of genetic variants of drug transporters and PDE was associated with HIV non-suppression.

Association of tenofovir diphosphate and lamivudine triphosphate concentrations with HIV and hepatitis B virus viral suppression.

OBJECTIVE: Concentrations of tenofovir diphosphate (TFV-DP) and lamivudine triphosphate (3TC-TP) in cells are correlates of medication adherence and antiviral activity. However, studies have yet to characterize the simultaneous relationship between TFV-DP and 3TC-TP concentrations with HIV and hepatitis B virus (HBV) suppression. METHODS: Individuals with HIV/HBV coinfection on tenofovir disoproxil fumarate (TDF)-containing antiretroviral therapy (ART) were enrolled. Peripheral blood mononuclear cells (PBMCs) and dried blood spots (DBS) samples were collected and steady-state TFV-DP and 3TC-TP concentrations quantified using validated methods. The relationship between patient factors, TFV-DP, and 3TC-TP concentrations in PBMCs and DBS with HBV and HIV viral suppression were examined. RESULTS: Of 138 participants on TDF-containing ART for a median duration (range) of 6 (0.75-15) years, the median age was 43 years and 64% were women. Overall, 128 (92.8%) and 129 (93.5%) had suppressed HIV and HBV viral loads, respectively. Of the 128 participants with suppressed HIV, 122 (95.3%) had suppressed HBV. Self-reported ART adherence, recent change to dolutegravir-based ART, TFV-DP, and 3TC-TP concentrations in PBMCs and DBS were associated with HIV RNA suppression, while HBe antigen positivity, HIV suppression, and TFV-DP concentrations in DBS were associated with HBV DNA suppression (including six persons with HBV nonsuppression and HIV suppression). CONCLUSION: Long-term TDF/3TC-conatining ART was highly efficacious in individuals with HIV/HBV coinfection. Higher TFV-DP concentrations were predictive of suppression for both viruses. Persistent HBV viremia on TDF/3TC-containg ART requires additional research, but may represent poor adherence and the need for adherence interventions or novel antivirals.

Hepatitis B and human immunodeficiency virus infections within correctional facilities in Ghana.

Previous studies have suggested high Immunodeficiency Virus (HIV) and hepatitis B virus (HBV) prevalence in prisons in Ghana. However, this study was part of a nationally representative bio-behavioural survey and determined the prevalence of HIV and HBV among prison inmates and identified factors associated with these infections. Both biomedical and behavioural data were collected from a total of 2,443 prison inmates from 19 prison stations during 2013 in Ghana; 12 male prisons and 7 female prisons selected across the country. The national HIV screening algorithm was used for HIV testing while two rapid detection tests were used to confirm HBV infections. HIV and HBV prevalence among prisoners in Ghana were approximately 2.34% and 12.38% respectively. Only 5 inmates, had co-infection with both viruses. The prevalence of HIV was significantly lower among male inmates (1.5%) compared to the female inmates (11.8%). Age, sex, and marital status, were significantly associated with both HIV and HBV infections. However, BMI category, IDU, and time spent in prison were associated with HIV infections. The educational level was significantly associated with HBV infections. After binary logistic regression, being female (AOR: 0.18, 95% CI: 0.07-0.45, p<0.001) and having a stay of 5 years or more (AOR: 0.07, 95% CI: 0.01-0.60, p = 0.016), increased the risk of having HIV infection. While, those with no formal education (AOR: 0.65, 95% CI: 0.45-0.95, p = 0.024) and are underweight (AOR: 0.51, 95% CI: 0.27-0.99, p = 0.046), were more likely to have HBV infection. Forced penetrative sex may be a problem in the prisons. The need to have and strengthen an integrated screening, treatment and vaccination plan for the prison is emphasized. The prison does not serve as an exceptionally high risk to the general population. The findings support a critical look at the issue of forced penetrative sex in the prisons.

Rubella virus IgM and IgG antibodies with avidity in pregnant women and outcomes at a tertiary facility in Ghana.

BACKGROUND: Congenital rubella syndrome (CRS) is a recognised cause of childhood deafness and blindness caused by the transplacental transmission of rubella virus during pregnancy. Women in the reproductive age group, and by extension their unborn babies may therefore be at increased risk. The prevalence of Rubella virus specific IgM and IgG antibodies, including IgG avidity, was determined in pregnant women attending the antenatal clinic at a Teaching Hospital in Ghana. METHODS: One hundred and forty-five women in their second and third trimesters of pregnancy from the outpatient clinic were recruited over a period of 2 months after written informed consent was obtained. Study participants completed a questionnaire and venous blood drawn for IgM, IgG, and avidity testing using SERION ELISA (SERION® Immunologics, Würzburg, Germany). Babies of mothers with positive or indeterminate IgM and low avidity IgG antibodies were offered specialist cardiological, ophthalmological or hearing assessment during follow up. RESULTS: One hundred and twenty-eight (88.3%) had only IgG antibodies, 5 (3.4%) had IgM and IgG antibodies, while 12 (8.3%) had no antibodies. No patient had IgM antibodies alone. Ten women (6.9%) had indeterminate levels of IgM antibodies. Majority of the women had high avidity IgG antibodies, while 5 (3.4%) had low avidity antibodies. No patient had IgM with low avidity antibodies. There was no statistical association between socio-demographic factors and the presence of IgM, IgG (low or high avidity) antibodies. Of all the children followed, none had the clinical definition of CRS. CONCLUSIONS: Consistent with the World Health Organization elimination strategy for measles and rubella viruses, non-immune women in the reproductive age group should be vaccinated. The immunization programme should be expanded to include teenagers and adults. Though Congenital Rubella Syndrome was not detected, the risk still remains.

Pharmacokinetics of Efavirenz 600 mg Once Daily During Pregnancy and Post Partum in Ghanaian Women Living With HIV.

PURPOSE: The updated World Health Organization guidelines recommend efavirenz (EFV) 400 mg as the preferred alternate first-line antiretroviral therapy to dolutegravir, with EFV 600 mg recommended only in special situations. We examined the pharmacokinetic (PK) properties of EFV 600 mg/d during pregnancy and post partum to inform EFV dosing decisions in pregnant women. METHODS: Ghanaian pregnant women with HIV infection initiating tenofovir disoproxil fumarate 300 mg/lamivudine 300 mg/EFV 600 mg fixed-dose combination tablet once daily were enrolled. Efavirenz concentrations were measured at 4 weeks of antiretroviral therapy initiation during pregnancy and 6 weeks post partum using validated LC-MS/MS assays. Efavirenz PK parameters were calculated using noncompartmental analysis, and within-group parameters between the 2 periods were compared. FINDINGS: Of 25 enrolled women, 19 completed PK sampling during pregnancy and post partum. The Cmax, Cmin, AUC0-24h, and CL/F for EFV during pregnancy were similar to values at 6 weeks post partum. The pregnancy/postpartum geometric mean ratios for EFV Cmax, Cmin, AUC0-24, and CL/F were 1.10 (95% CI, 0.93-1.31), 0.88 (95% CI, 0.67-1.17), 0.84 (95% CI, 0.71-0.98), and 1.20 (95% CI, 1.02-1.40), respectively. Viral load suppression (HIV RNA <200 copies/mL) was achieved in 16 of 17 participants (94%) by the time of delivery. There was 1 maternal-to-child transmission. IMPLICATIONS: We found that the PK parameters of EFV 600 mg once daily during pregnancy were similar to those in the postpartum period. Our findings suggest that EFV dose adjustment during pregnancy is not necessary in our study population.

Hepatitis B infection outcome is associated with novel human leukocyte antigen variants in Ghanaian cohort.

IMPACT STATEMENT: Genetic association studies can determine the effect size of gene loci on disease outcomes. In the arena of HBV infections, HLA alleles that associate with HBV outcomes can be used in clinical management decisions. This potential translational utility can shape the future management of HBV infections by identifying at-risk individuals and tailoring medical interventions accordingly. This precision medicine motif is currently only a nascent idea. However, it has stakes that may well override the current "wait and see" approach of clinical management of HBV infections. Here, we have identified HLA alleles associated with HBV outcome in a Ghanaian cohort. Our findings support the motif that HLA alleles associate with HBV outcome along geo-ethnic lines. This buttresses the need for further population pivoted studies. In the long term, our findings add to efforts towards the development of an HLA molecular-based algorithm for predicting HBV infection outcomes.

Potential of Cocoa Pod Husk Pectin-Based Modified Release Capsules as a Carrier for Chronodelivery of Hydrocortisone in Sprague-Dawley Rats.

The potential of cocoa pod husk (CPH) pectin-based modified release (MR) capsules as a carrier for chronodelivery of hydrocortisone in Sprague-Dawley rats was assessed. Extemporaneously formulated CPH pectin-based hydrocortisone (10 mg) capsules crosslinked with calcium chloride (Formulation A) or zinc (Formulation B) and a commercial immediate release hydrocortisone formulation were administered orally to Sprague-Dawley rats and the pharmacokinetic parameters were evaluated using noncompartmental analysis. Formulation A had a 2 h lag phase followed by an increase in serum drug concentration in the treated rats. Peak concentrations (Cmax) of 21.799 ± 1.993 ng/ml and 20.844 ± 2.661 ng/ml were achieved after 6 ± 0.23 h and 6 ± 0.35 h (Tmax), respectively, for capsules A and B. The immediate release formulation had a peak concentration of 15.322 ± 0.313 ng/ml within 1 ± 0.2 h. The relative bioavailability of the CPH pectin-based capsules A and B was 213% and 274%, respectively. Formulations A and B had half-lives more than three times that of the immediate release formulation. The MR capsules exhibited a higher exposure, greater bioavailability, and versatility in release of cortisol than the commercial immediate release formulation. Additionally, the MR capsules exhibited an extended drug release with overnight cortisol rise and early morning cortisol peak and hold promise in the management of adrenal insufficiency.

Impact of exercise intensity on oxidative stress and selected metabolic markers in young adults in Ghana.

OBJECTIVE: This study aimed to evaluate the effect of different levels of exercise on markers of oxidative stress and selected metabolic parameters in Ghanaian young adults. RESULTS: Significant increases in a marker of oxidative stress malondialdehyde and antioxidants such as superoxide dismutase and uric acid were observed in the exercisers compared with the inactive group (p < 0.05). Total cholesterol and high density lipoprotein levels were significantly different (p < 0.05) between the two groups. Positive associations between exercise intensity, antioxidant concentration and malondialdehyde were observed within the exercise group for vigorous exercise with regards to uric acid, superoxide dismutase and malondialdehyde (r = 0.512, p = 0.004; r = 0.810, p = 0.001; r = 0.715, p = 0.001) respectively and moderate exercise vs malondialdehyde (r = 0.841, p = 0.001) compared to the inactive group. Exercise participants performed more vigorous exercise (p < 0.001), moderate exercise (p < 0.001) and more walking (p < 0.001) compared with the inactive group while the inactive group exhibited more sitting (p < 0.001). The study provides a first report on the risk associated with increase in oxidative stress and the importance of walking as a health promotion intervention among young Ghanaian adults.

Biobanking in a Challenging African Environment: Unique Experience from the SIREN Project.

Africa was previously insufficiently represented in the emerging discipline of biobanking despite commendable early efforts. However, with the Human, Heredity, and Health in Africa (H3Africa) initiative, biorepository science has been bolstered, regional biobanks are springing up, and awareness about biobanks is growing on the continent. The Stroke Investigative Research and Educational Network (SIREN) project is a transnational, multicenter, hospital and community-based study involving over 3000 cases and 3000 controls recruited from 16 sites in Ghana and Nigeria. SIREN aims to explore and unravel the genetic and environmental factors that interact to produce the peculiar phenotypic and clinical characteristics of stroke as seen in people of African ancestry and facilitate the development of new diagnostics, therapeutics, and preventative strategies. The aim of this article is to describe our experience with the development of the procedure for collection, processing, storage, and shipment of biological samples (blood, serum, plasma, buffy coat, red cell concentrates, and DNA) and brain imaging across coordinating and participating sites within the SIREN Project. The SIREN network was initiated in 2014 with support and funding from the H3Africa Initiative. The SIREN Biobank currently has 3015 brain images, 92,950 blood fractions (serum, plasma, red cell concentrates, and buffy coat) accrued from 8450 recruited subjects, and quantified and aliquoted good-quality DNA extracts from 6150 study subjects. This represents an invaluable resource for future research with expanding genomic and trans-omic technologies. This will facilitate the involvement of indigenous African samples in cutting-edge stroke genomics and trans-omics research. It is, however, critical to effectively engage African stroke patients and community members who have contributed precious biological materials to the SIREN Biobank to generate appropriate evidence base for dealing with ethical, legal, and social issues of privacy, autonomy, identifiability, biorights, governance issues, and public understanding of stroke biobanking in the context of unique African culture, language, and belief systems.

Altered immunoglobulins (A and G) in Ghanaian patients with type 2 diabetes.

OBJECTIVES: Elevated immunoglobulin levels have been strongly linked to the development and progression of inflammatory disorders such as type 2 diabetes and obesity. This study aimed to evaluate circulating immunoglobulin levels and to identify other metabolic factors that influence humoral immune response among Ghanaian subjects with type 2 diabetes. METHODS: A comparative cross-sectional study conducted at the National Diabetes Management and Research Center, Accra. Eighty persons with type 2 diabetes were age-matched with 78 controls. Immunoglobulin A, immunoglobulin G and immunoglobulin M; interleukin 6; fasting blood glucose; glycated hemoglobin; and lipid parameter concentrations were measured. Blood pressure, anthropometry and body composition indices were also assessed. RESULTS: Median immunoglobulin A and immunoglobulin G (g/L) levels were higher in the case group compared with controls (0.89 vs 0.74, p = 0.043; 7.58 vs 7.29, p < 0.001). Immunoglobulin G, immunoglobulin A and interleukin 6 levels in the case cohort, respectively, associated weakly with fasting blood glucose (r = 0.252, p = 0.001; r = 0.170, p = 0.031; r = 0.296, p = 0.001). There were positive correlations within the control group for immunoglobulin A versus interleukin 6 (r = 0.366, p = 0.001) and within the case group for glycated hemoglobin versus interleukin 6 (r = 0.190, p = 0.020). CONCLUSION: Our data suggest that humoral immune response is altered in subjects with type 2 diabetes and that serum immunoglobulin levels could serve as useful biomarkers in the investigation and management of diabetes mellitus.

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

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.

Decline in severe diarrhea hospitalizations after the introduction of rotavirus vaccination in Ghana: a prevalence study.

BACKGROUND: Almost all diarrhea deaths in young children occur in developing countries. Immunization against rotavirus, the leading cause of childhood severe dehydrating acute diarrhea may reduce the burden of severe diarrhea in developing countries. Ghana introduced rotavirus and pneumococcal vaccination in the national expanded program on immunization in May 2012. METHODS: Review of all-cause diarrheal hospitalization data for children aged 59 months and younger at 2 pediatric referral hospitals in southern Ghana from 2008 to 2014. The proportion of acute diarrhea (defined as 3 or more watery, non-bloody stools within 24 hours that has lasted for less than 7 days) cases caused by rotavirus was determined. Temporal trend and age group distribution of all-cause diarrhea and rotavirus gastroenteritis before and after introduction of the new vaccines were compared. RESULTS: Of the 5847 children hospitalized with all-cause diarrhea during the 74 months (January 2008 - February 2014), 3963 (67.8%) children were recruited for rotavirus surveillance and stool specimens were tested for rotavirus in 3160/3963 (79.7%). Median monthly hospitalization for all-cause diarrhea reduced from 84 [interquartile range (IQR) 62 - 105] during the 52 months pre-vaccination introduction to 46 (IQR 42 - 57) in the 22 months after implementation of vaccination. Significant decline in all-cause diarrhea hospitalization occurred in children aged 0 - 11 months: 56.3% (2711/4817) vs. 47.2% 486/1030 [p = 0.0001, 95% confidence interval (CI) 0.77 - 0.88] and there was significant reduction of rotavirus gastroenteritis hospitalization: 49.7% (1246/2505) vs. 27.8% (182/655) [p = 0.0001, 95% CI 0.32 - 0.47] before and after vaccine introduction respectively. CONCLUSIONS: Implementation of rotavirus vaccination program may have resulted in significant reduction of severe diarrhea hospitalization even though this observational study could not exclude the effect of other confounding factors. Continued surveillance is recommended to monitor the progress of this program.

Respiratory syncytial virus genotypes circulating in urban Ghana: February to November 2006.

INTRODUCTION: Respiratory syncytial virus (RSV) is the major cause of acute lower respiratory tract infection (ALRI) in young children. RSV strains have been divided into 2 major antigenic groups (A and B), which are further divided into several genotypes, but very little is known about its circulating genotypes in Ghana. This study characterized RSV genotypes detected in children with ALRI in Accra between February and November 2006. METHODS: Nasopharyngeal aspirates (NPA) were obtained from children diagnosed with ALRI between February and November 2006. The NPA were screened for RSV using a nested multiplex reverse transcriptase polymerase chain reaction (RT-PCR) method for genotyping RSV. Viral RNA was extracted from the NPA using guanidinium isothiocyanate method and purified with an RNAID commercial kit. Care-givers gave their consent prior to specimen collection. Administered questionnaires captured information on patient demographic and clinical history. RESULTS: A total of 53 children were enrolled in the study with a male to female ratio of 3:1. Of the 53 NPA analyzed, 60.4% (32/53) were positive for RSV. Subsequent genotypic analysis showed that 72% (23/32) of the 60.4% RSV infections were RSV B only and 28% (9/32) were co-infections of both RSV A and B. Children between the ages of 2 - 12 months were the most affected age group per an RSV infection rate of 37.5% (12/32). No significant difference was detected in the recovery rate of ALRI (98.1%) and RSV (96.9%) positive patients from the infection. One patient died resulting in a mortality rate of 3.1%. Bronchopneumonia (20 out of 32 cases) was the major diagnosis on admission. RSV infection was seasonal dependent, described by 2 peaks in October and April-May. CONCLUSION: Both RSV A and RSV B genotypes co-circulated during the study period with RSV B predominating. RSV may possibly be the main pathogen of lower respiratory tract illness during epidemics in the wet seasons. Genotyping by the multiplex RT-PCR is one of the first attempts at molecular diagnosis of RSV infection in Ghana.

Microbial carriage of cockroaches at a tertiary care hospital in ghana.

Cockroaches are common in the environment of many hospitals in Ghana; however, little is known about their public health risks. To evaluate potential risks, we investigated the external and internal microbial flora of 61 cockroaches from a tertiary hospital in Ghana and evaluated the antibiotic resistance profiles of the common bacterial species. Standard methods were used in all the microbiological investigations and antibiotic susceptibility testing. A rotavirus carriage rate of 19.7% was observed among the cockroaches. Four types of intestinal parasites were carried externally by the cockroaches, and the most prevalent was Hookworm (4.9%). Eight nosocomial bacteria were isolated from the cockroaches, and the most prevalent was Klebsiella pneumoniae, which occurred internally in 29.5% of the cockroaches and 26.2% externally. Multiple drug resistance among common bacteria isolated from the cockroaches ranged from 13.8% (Escherichia coli) to 41.1% (Klebsiella pneumoniae). Cockroaches constitute an important reservoir for pathogenic microorganisms, and may be important vectors of multiple resistant nosocomial pathogens in the studied hospital.

Interindividual variability in pharmacokinetics of generic nucleoside reverse transcriptase inhibitors in TB/HIV-coinfected Ghanaian patients: UGT2B7*1c is associated with faster zidovudine clearance and glucuronidation.

There are limited data on the pharmacokinetics of generic nucleoside reverse transcriptase inhibitors (NRTIs) in native African populations, in whom they are commonly used. The authors characterized the pharmacokinetics of lamivudine (n = 27), zidovudine (n = 16), and stavudine (n = 11) in human immunodeficiency virus (HIV)/tuberculosis (TB)-coinfected Ghanaians and evaluated associations between zidovudine metabolism and UDP-glucuronosyltransferase (UGT) 2B7 polymorphisms. Lamivudine, zidovudine, and stavudine apparent oral clearance (CL/F) values (mean +/- SD [% coefficient of variation [CV]) were 7.3 +/- 2.8 (39%), 31.9 +/- 33.6 (106%), and 16.4 +/- 5.8 (35%) mL/min/kg, respectively, whereas half-life values were 4.2 +/- 1.9 (46%), 8.1 +/- 7.9 (98%), and 1.5 +/- 1.0 (65%) hours, respectively. Zidovudine CL/F was 196% higher (P = .004) in UGT2B7*1c (c.735A>G) carriers versus noncarriers. This was confirmed using human liver bank samples (n = 52), which showed 48% higher (P = .020) zidovudine glucuronidation and 33% higher (P = .015) UGT2B7 protein in UGT2B7*1c carriers versus noncarriers. In conclusion, generic NRTI pharmacokinetics in HIV/TB-coinfected Ghanaians are similar to other populations, whereas the UGT2B7*1c polymorphism may explain in part relatively high interindividual variability in zidovudine clearance.

Pharmacokinetics of efavirenz when co-administered with rifampin in TB/HIV co-infected patients: pharmacogenetic effect of CYP2B6 variation.

The goal of this study was to determine the effect of CYP2B6 genetic variation on the steady-state pharmacokinetics of efavirenz (600 mg/d) in TB/HIV co-infected patients receiving concomitant rifampin, a potent CYP inducer. In the 26 patients studied, CYP2B6 c.516GG, GT, and TT genotype frequencies were 0.27, 0.50, and 0.23, respectively. Mean plasma efavirenz area under the curve was significantly higher in patients with CYP2B6 c.516TT than in those with GT (107 vs 27.6 microg x h/mL, P< .0001) or GG genotype (107 vs 23.0 microg x h/mL, P< .0001). Apparent oral clearance (CL/F) was significantly lower in patients with CYP2B6 c.516TT than in those with GT genotype (2.1 vs 8.4 mL/min/kg, P<0.0001) and GG genotype (2.1 vs 9.9 mL/min/kg, P< .0001). No differences in efavirenz exposure or CL/F existed between patients with CYP2B6 c.516GT and GG genotypes. Our results indicate that CYP2B6 c.516TT genotype can be used to identify efavirenz poor metabolizers in patients co-treated with rifampin.

Seroprevalence of HHV-8, CMV, and EBV among the general population in Ghana, West Africa.

BACKGROUND: Human herpesvirus 8 (HHV-8), cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are prevalent in Africa, but less common elsewhere and the modes of transmission are still subject to debate. Generally, they rarely cause disease in the immunocompetent host but are highly oncogenic when associated with immunosuppression. Although the high prevalence of HHV-8, CMV and EBV has been well documented in Africa, such data are sparse from Ghana. METHODS: Serum samples from 3275 HIV-seronegative healthy blood donors and 250 HIV-AIDS patients were tested for antibodies specific for HHV-8, CMV and EBV by IgG ELISA assays. Differences in seropositivity rates by gender and age were evaluated using the Chi-square test with Yates correction. RESULTS: Of the 3275 HIV-seronegative healthy blood donors tested, 2573 (78.6%) were males and 702 (21.4%) were females, with ages ranging from 18 to 65 years (median 32.6; mean 31.2; mode 30). Of the 250 HIV-AIDS patients tested, 140 (56%) were males and 110 (44%) were females, with ages ranging from 17 to 64 years (median 30.8; mean 30.3; mode 28). Among the HIV-seronegative healthy blood donors, overall seroprevalence of HHV-8, CMV and EBV was 23.7%, 77.6% and 20.0%, respectively. Among the HIV-AIDS patients, overall seroprevalence of HHV-8, CMV and EBV was 65.6%, 59.2% and 87.2%, respectively. The seroprevalence of HHV-8 (p < 0.005) and EBV (p < 0.001) was statistically significantly higher in HIV-AIDS patients compared to HIV-seronegative healthy blood donors. There was no statistically significant difference (p = 0.24) between CMV seroprevalence in HIV-AIDS patients and HIV-seronegative healthy blood donors. Age and gender were not independent determinants (p > 0.05) for all three infections among HIV-seronegative healthy blood donors and HIV-AIDS patients in Ghana. CONCLUSION: The results presented herein indicate that HHV-8, CMV and EBV infections are hyperendemic in both HIV-seronegative and HIV-seropositive Ghanaians, and suggest primarily a horizontal route of transmission of these three viral infections in Ghana.

Correlates of HIV, HBV, HCV and syphilis infections among prison inmates and officers in Ghana: A national multicenter study.

BACKGROUND: Prisons are known to be high-risk environments for the spread of bloodborne and sexually transmitted infections. Prison officers are considered to have an intermittent exposure potential to bloodborne infectious diseases on the job, however there has been no studies on the prevalence of these infections in prison officers in Ghana. METHODS: A national multicenter cross-sectional study was undertaken on correlates of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and syphilis infections in sample of prison inmates and officers from eight of ten regional central prisons in Ghana. A total of 1366 inmates and 445 officers were enrolled between May 2004 and December 2005. Subjects completed personal risk-factor questionnaire and provided blood specimens for unlinked anonymous testing for presence of antibodies to HIV, HCV and Treponema pallidum; and surface antigen of HBV (HBsAg). These data were analyzed using both univariate and multivariate techniques. RESULTS: Almost 18% (1336) of 7652 eligible inmates and 21% (445) of 2139 eligible officers in eight study prisons took part. Median ages of inmates and officers were 36.5 years (range 16-84) and 38.1 years (range 25-59), respectively. Among inmates, HIV seroprevalence was 5.9%, syphilis seroprevalence was 16.5%, and 25.5% had HBsAg. Among officers tested, HIV seroprevalence was 4.9%, HCV seroprevalence was 18.7%, syphilis seroprevalence was 7.9%, and 11.7% had HBsAg. Independent determinants for HIV, HBV and syphilis infections among inmates were age between 17-46, being unmarried, being illiterate, female gender, being incarcerated for longer than median time served of 36 months, history of homosexuality, history of intravenous drug use, history of sharing syringes and drug paraphernalia, history of participation in paid sexual activity, and history of sexually transmitted diseases. Independent determinants for HIV, HBV, HCV and syphilis infections among officers were age between 25-46, fale gender, being unmarried, being employed in prison service for longer than median duration of employment of 10 years, and history of sexually transmitted diseases. CONCLUSION: The comparably higher prevalence of HIV, HBV, HCV and syphilis in prison inmates and officers in Ghana suggests probable occupational related transmission. The implementation of infection control practices and risk reduction programs targeted at prison inmates and officers in Ghana is urgently required to address this substantial exposure risk.

Variability of the human immunodeficiency virus type 1 polymerase gene from treatment naïve patients in Accra, Ghana.

BACKGROUND: Little is known about the HIV-1 drug resistance mutations in Ghana. OBJECTIVES: To determine the background protease (PR) and reverse transcriptase (RT) mutations of HIV-1 from treatment naïve patients in Ghana. STUDY DESIGN: Twenty-five plasma samples randomly selected were analyzed for drug resistance mutations. The molecular phylogeny and recombinant patterns of the polymerase gene of HIV-1 were also analysed. RESULTS: No major drug-resistance mutations were seen in protease or reverse transcriptase genes. The L10I, L10V, V11I and E35G minor mutations were seen in four patients, while the V179E was observed in a patient with subtype G. An insertion of lysine was found at codon 36 of the protease gene of one patient. The predominant subtype was the CRF02_AG strain (n=22), but 3 (13.6%) of these were recombinants with HIV-1 subtype K and/or A1. Two patients harboured unclassified/complex strains with D/CRF01_AE and G/CRFAG_02 subtypes for the PR and RT, respectively, using the Stanford Database. Viral loads (VL) ranged from 2290 to >1,500,000c/ml (mean=339,065c/ml). CONCLUSIONS: Treatment naïve patients in Ghana before scale-up may have minor but not major PR mutations and high viral loads. The clinical effects of minor mutations/polymorphisms in the PR and RT genes and recombinants need to be investigated.