Molecular detection of hepatitis B virus genotype E with immune escape mutations in chronic hepatitis B patients on long-term antiviral therapy in Jos, Nigeria.

Background: Previous studies in Nigeria have reported the presence of hepatitis B virus (HBV) genotype E and the availability of immune escape mutants. There is a paucity of data on chronic patients on long-term antiviral therapy for HBV infection. Objective: This study assessed HBV genotypes and drug resistance variants among patients with chronic HBV infection receiving tenofovir in Jos, Nigeria. Methods: This cross-sectional study consecutively enrolled 101 patients (51 with HIV/HBV co-infection and 50 with HBV infection only) on antiviral therapy from February 2018 to May 2019 at four hospitals in Jos, Nigeria. DNA quantification of HBV was performed on all samples; 30 samples with detectable viral load were selected for genotyping using Sanger sequencing by targeting the full-length sequences of reverse transcriptase gene of the HBV genome. Phylogenetic analysis was performed with reference sequences from GenBank. Escape mutant and drug resistance analysis were performed using HBV drug resistance interpretation and Geno2pheno. Results: Only 30 (29.7%) of the 101 study participants had detectable HBV DNA. Of these, six (20.0%) isolates were successfully amplified and sequenced. The identified genotype was E, including escape mutations L127R (16.7%) and G145A (16.7%). Conclusion: This study revealed exclusive dominance of genotype E in Nigeria. The S gene mutations G145A and L271R are known to be associated with modified antigenicity and impaired serologic assays, which may cause false negatives in the detection of anti-HBV surface antigen. The presence of mutants that are associated with vaccine immune escape may also have diagnostic and vaccine immune response implications.

Impact of pharmacist-led care on glycaemic control of patients with uncontrolled type 2 diabetes: a randomised controlled trial in Nigeria.

BACKGROUND: Diabetes mellitus is a chronic, degenerative disease, requiring a multi-dimensional, multi-professional care by healthcare providers and substantial self-care by the patients, to achieve treatment goals. OBJECTIVE: To evaluate the impact of pharmacist-led care on glycaemic control in patients with uncontrolled Type 2 Diabetes. METHODS: In a parallel group, single-blind randomised controlled study; type 2 diabetic patients, with greater than 7% glycated haemoglobin (A1C) were randomised into intervention and usual care groups and followed for six months. Glycated haemoglobin analyzer, lipid analyzer and blood pressure monitor/apparatus were used to measure patients' laboratory parameters at baseline and six months. Intervention group patients received pharmacist-structured care, made up of patient education and phone calls, in addition to usual care. In an intention to treat analysis, Mann-Whitney U test was used to compare median change at six months in the primary (A1C) and secondary outcome measures. Effect size was computed and proportion of patients that reached target laboratory parameters were compared in both arms. RESULTS: All enrolled participants (108) completed the study, 54 in each arm. Mean age was 51 (SD 11.75) and majority were females (68.5%). Participants in the intervention group had significant reduction in A1C of -0.75%, compared with an increase of 0.15% in the usual care group (p<0.001; eta-square= 0.144). The proportion of those that achieved target A1C of <7% at 6 months in the intervention and usual care group was 42.6% vs 20.8% (p=0.02). Furthermore, intervention patients were about 3 times more likely to have better glucose control; A1C<7% (aOR 2.72, 95% CI: 1.14-6.46) compared to usual care group, adjusted for sex, age, and duration of diabetes. CONCLUSIONS: Pharmacist-led care significantly improved glycaemic control in patients with uncontrolled T2DM.

Comparative incidence of adverse drug reaction during the first and subsequent year of antiretroviral therapy in a Nigerian HIV infected Cohort.

BACKGROUND: Despite close to two decades of antiretroviral therapy (ART) in Nigeria, data on late on-onset ART-associated adverse drug reactions (ADRs) are sparse. OBJECTIVES: To describe early and late-onset ADRs and compare their incidence in an outpatient HIV positive Cohort on ART. METHOD: We described the incidence of clinical ADRs identified and documented in an outpatient clinic cohort of HIV-positive patients treated between June 2004 and December 2015 at a tertiary health facility in Nigeria. Incidence rates of ADRs during the first and subsequent years of ART were compared. RESULTS: of the 13,983 patients' data analyzed, 9317 were females (66%), and those in the age bracket of 25 to 45 years made up 78% of the studied population. During 52,411 person-years (py) of ART, 1485 incident ADRs were recorded; Incidence rate (IR) 28.3 (95% confidence interval [CI] 26.9:29.8) ADRs per 1000 person-years (py) of ART. The IR of ADRs was about two times higher in the first year of ART compared to subsequent years of treatment; crude incidence rate ratio (IRR) 1.77 (95% CI 1.59:1.97). Anemia, hypersensitivity reactions, and nervous system disorders had 7, 23, and 5 times higher incidence, respectively, in the first year of therapy, compared to subsequent years. CONCLUSION: The first year of ART is the period of highest risk of ADRs. Individual and programmatic treatment success in resource-limited settings requires strategies for early identification and management of ADR during the period of greatest risk of ADRs.

Long Term Exposure to Tenofovir Disoproxil Fumarate-Containing Antiretroviral Therapy Is Associated with Renal Impairment in an African Cohort of HIV-Infected Adults.

OBJECTIVES AND METHOD: There are growing concerns of tenofovir disoproxil fumarate (TDF)-associated renal toxicity. We evaluated the effect of long-term TDF exposure on renal function in a cohort of HIV-1-infected Nigerians between 2006 and 2015. Multivariate logistic regression was used to identify predictors of renal impairment at different time over 144 weeks of antiretroviral therapy (ART). RESULTS: Data of 4897 patients, median age 42 years (interquartile range: 36-49), and 61% females were analyzed. The prevalence of renal impairment increased from 10% at week 24 to 45% at 144 weeks in TDF-exposed participants compared to an increase from 8% at 24 weeks to 14% at 144 weeks in TDF-unexposed participants. Tenofovir disoproxil fumarate exposure predicted the risk of renal impairment at 144 weeks of ART (odds ratio: 2.36; 95% confidence interval: 1.28-4.34). CONCLUSION: Long-term exposure to TDF-based ART significantly increases the likelihood of renal impairment. The continued use of TDF-based regimen in our setting should be reviewed. We recommend the urgent introduction of tenofovir alafenamide-based regimen in the HIV treatment guidelines of Nigeria and other resource-limited countries.

Antiretroviral Therapy-associated Adverse Drug Reactions and their Effects on Virologic Failure- A Retrospective Cohort Study in Nigeria.

BACKGROUND: Adverse drug reactions (ADRs) associated with antiretroviral therapy (ART) can rapidly reverse the gains of ART resulting in poor health outcomes. We need an improved understanding of specific ART-related ADRs that influence virologic outcomes. OBJECTIVE: To investigate the frequency of clinical ADRs and assess their effect on virologic failure in patients on ART. METHOD: We described the prevalence of major clinical ADRs, and the association between specific ADRs and virologic failure in a clinic cohort of HIV-1 infected Nigerians aged ≥18 years, on firstline ART between June 2004 and February 2012. Multivariable logistic regression was run to identify predictors of virologic failure at 24 and 72 weeks of ART. RESULTS: Data of 12,115 patients with a median age of 34 (interquartile range: 29-41) years, and predominantly females (67%) were evaluated. Overall, 957 (7.9%) patients experienced at least one ADR during a median follow-up period of 4 years (interquartile range: 1-7). The three most prevalent ADRs were lipodystrophy (2.6%), anemia (1.9%), and skin rash (0.7%). Virologic failure rate was 36% and 34% at 24 and 72 weeks of ART, respectively. Anemia independently predicted the odds of virologic failure at 72 weeks of ART (adjusted odds ratio, 1.74; 95% CI: 1.2-2.51); adjusted for sex, age, pre-treatment CD4+ cell count, antiretroviral regimen, and medication refill adherence. CONCLUSION: Antiretroviral therapy-associated anemia increases the likelihood of late virologic failure. We recommend routine monitoring of hemoglobin levels and prompt management of anemia in all patients on ART as a strategy to improve virologic success rates.

Incidence and predictors of tenofovir disoproxil fumarate-induced renal impairment in HIV infected Nigerian patients.

INTRODUCTION: The use of tenofovir disoproxil fumarate (TDF) in the treatment of HIV infection has been associated with renal dysfunction. In Nigeria, data on the incidence and risk factors of TDF nephrotoxicity is sparse. We determined the cumulative incidence of and risk factors for TDF-induced renal impairment in HIV-infected individuals accessing care at the antiretroviral therapy (ART) clinic of Jos University Teaching Hospital, Nigeria. METHODS: This retrospective cohort analysis included patients aged ≥16 years that initiated ART between January 2008 and December 2011. Renal impairment, defined as glomerular filtration rate GFR <60 mL/min/1.73 sqm using the Modification of Diet in Renal Disease (MDRD) equation was assessed at baseline and at 48 weeks on ART. Logistic regression was performed to determine factors associated with incident renal impairment. RESULTS: The mean age was 39±9 years, and 67.1% were female. The cumulative incidence of renal impairment among the TDF-exposed and TDF-unexposed groups was 4.6% and 2.3% respectively (p<0.001). TDF exposure was significantly associated with renal impairment [OR=2.0, 95%CI=(1.48-2.89), p<0.001] in bivariate analysis. In multivariate analysis, older age (aOR=1.06, 95%CI=(1.05-1.08), p<0.001), TDF exposure [aOR=1.85, 95%CI=(1.31-2.60), p<0.001] and co-morbidities [aOR=2.71, 95%CI=(1.72-4.25), p<0.001] were significantly associated with renal impairment. CONCLUSION: TDF exposure, aging and comorbidities were predictors of renal toxicity among HIV positive patients. Regular monitoring of renal function in such high-risk individuals is recommended.

Changes in the haematological parameters of HIV-1 infected children at 6 and 12 months of antiretroviral therapy in a large clinic cohort, North-Central Nigeria.

BACKGROUND: Prior to commencing antiretroviral therapy (ART), haematological abnormalities are a common occurrence in individuals diagnosed with human immunodeficiency virus (HIV). In the course of receiving ART, these abnormalities usually improve. We determined the prevalence of haematological abnormalities in children diagnosed with HIV-1 and the changes in haematological parameters that occur after 6 and 12 months of being on ART. METHODS: A cross-sectional study of HIV-1 infected children aged 2 months to 15 years, between July 2005 and March 2013, at the paediatric HIV clinic of the Jos University Teaching Hospital, Jos. Median values of repeated measures were compared using the Wilcoxon signed-rank sum test. RESULTS: The prevalence of anaemia, thrombocytopenia and leukopenia among the 941 children studied, prior to ART was 6.4%, 7.0% and 8.6%. Median (IQR) haemoglobin (Hb) levels increased from 10 g/dL (9-11 g/dL) at baseline to 11 g/dL (10-12 g/dL) and 11 g/dL (10-12 g/dL) at 6 and 12 months of ART (P<0.001 and P<0.001), respectively, a 10% increase in both cases. Also, platelet count increased from a median of 327×103/µL (243-426×103/µL) at baseline to 333×103/µL (266-408×103/µL) at 6 months and 339×103/µL (267-420×103/µL) at 12 months, representing a 1.8% and 3.7% increase, respectively. The median total white blood cell count decreased from 7.4×103/µL (5.3-9.9×103/µL) at baseline to 5.9×103/µL (4.6-8.0×103/µL) and 5.8×103/µL (4.5-7.5×103/µL) at 6 and 12 months of ART (P<0.001 and P<0.001), a 20.3% and 21.6% decrease, respectively. CONCLUSION: During the 12 months of ART, children in our cohort had significant improvements in haematological parameters such as haemoglobin levels and platelet counts, which would suggest an early positive response to ART.

Antituberculosis drugs and hepatotoxicity among hospitalized patients in Jos, Nigeria.

BACKGROUND: Tuberculosis (TB) could be fatal if left untreated, however, adverse effects of anti-TB medications (anti-TBs) themselves may limit treatment. We determined the incidence and clinical characteristics of hepatotoxicity in hospitalized patients receiving first-line anti-TB treatment. METHODS: A retrospective cohort study of patients aged ⩾18years seen at the medical wards of the Jos University Teaching Hospital from January 2013 to June 2013 was carried out. Data were retrieved for 110 patients who were prescribed anti-TBs. Their demographic and clinical characteristics were described, and the incidence of symptomatic hepatotoxicity determined. The incidence of hepatotoxicity by strict American Thoracic Society criteria (symptomatic hepatotoxicity plus alanine transaminase in IU/L levels >3×upper limit of normal) was also determined. RESULTS: Twenty patients developed symptomatic hepatotoxicity, giving an incidence of 18.2%. Furthermore, 18 (16.4%) patients had hepatotoxicity according to the American Thoracic Society criteria. Those with symptomatic hepatotoxicity unexpectedly had lower baseline alanine transaminase interquartile range (IQR) (35 [16-63] vs. 67 [4-226]; p=.04) and bilirubin (µmol/L): total IQR (15.3 [10.2-74.8] vs. 20.4 [20.4-20.4]; p=.01) and conjugated IQR (7.6 [5.1-34.8] vs. 10.2 [10.2-10.2]; p=.004). However, there were no significant differences in age, sex, body mass index, and duration of anti-TB treatment, human immunodeficiency virus infection status, antiretroviral therapy status, alcohol consumption, and the presence of hepatitis B surface antigen or hepatitis C virus antibody. CONCLUSION: Hepatotoxicity due to first-line anti-TBs, whether based on clinical features alone or backed by liver chemistry, is common among hospitalized patients in our environment. Studies to determine the predictors of hepatotoxicity to guide clinical interventions aimed at the prevention or timely identification of cases are needed.

Prevalence of and risk factors for pulmonary tuberculosis among newly diagnosed HIV-1 infected Nigerian children.

INTRODUCTION: Studies on the prevalence of and risk factors for tuberculosis (TB) among newly diagnosed human immunodeficiency virus (HIV)-infected children in sub-Saharan Africa are scarce and in Nigeria there is paucity of reported data. We determined the prevalence of and risk factors for pulmonary TB (PTB) in newly diagnosed (treatment-naïve) HIV-1 infected children at the pediatric HIV clinic of the Jos University Teaching Hospital (JUTH) in Nigeria. METHODS: We performed a retrospective analysis of 876 children, aged 2 months - 13 years, diagnosed with HIV-1 infection between July 2005 and December 2012, of which 286 were diagnosed with PTB at presentation after TB screening. The study site was the AIDS Prevention Initiative in Nigeria (APIN)-supported Pediatric HIV clinic at JUTH, Jos. A multivariate forward logistic regression modelling was used to identify risk factors for PTB-HIV co-infection. RESULTS: The prevalence of PTB-HIV co-infection was 32% (286/876). Severe immunosuppression (SI) and World Health Organization (WHO) HIV clinical stage 3/4 were identified as independent risk factors for PTB-HIV co-infection in HIV infected children. The odds of PTB-HIV co-infection was increased two-fold in HIV-infected children with WHO clinical stage 3/4 compared to those with stage 1/2 (adjusted odds ratio (AOR) 1.76 [1.31-2.37], p<0.001) and 1.5-fold in children with SI compared to those without SI (AOR 1.52 [1.12-2.06], p=0.007). CONCLUSION: In our setting, the burden of PTB was high among newly diagnosed HIV-infected children, and late WHO HIV clinical stage and severe immunosuppression were associated with PTB-HIV co-infection. Therefore there is a clear need to improve strategies for early diagnosis of both HIV and PTB to optimize clinical outcomes.

Pattern of drug therapy problems and interventions in ambulatory patients receiving antiretroviral therapy in Nigeria.

OBJECTIVES: We describe the frequency and types of drug therapy problems (DTPs), and interventions carried out to resolve them, among a cohort of HIV-infected patients on ART in Jos, Nigeria. METHODS: A prospective pharmacists' intervention study was conducted between January and August 2012 at the outpatient HIV clinic of the Jos University Teaching Hospital (JUTH). Pharmacists identified DTPs and made recommendations to resolve them. The main outcome measures were number of DTPs encountered, interventions proposed and acceptance rate of recommendations. RESULTS: A total of 42,416 prescriptions were dispensed to 9339 patients during the eight months study. A total of 420 interventions (Intervention rate of 1 per 100 prescriptions) were made to resolve DTPs in 401 (4.3%) patients with a mean age of 41 (SD=10) years, and made up of 73% females. DTPs encountered were drug omission (n=89, 21.2%), unnecessary drug (n=55, 13.1%) and wrong drug indication (n=55, 13.1%). Recommendations offered included; Addition of another drug to the therapy (n=87, 20.7%), rectification of incomplete prescriptions (n=85, 20.2%), change of drug or dosage (n=67, 16.0%), and discontinuation of the offending drug (n=59, 14.0%). A total of 389 (93%) out of 420 of the recommendations were accepted. In all, 50.4% (212) of the problematic prescriptions were changed and dispensed, 22.2% (89) were clarified and dispensed, while wrong identities were corrected in 11.7% (49). However, 7.5% (30) prescriptions were dispensed as prescribed, 5.2% (21) were not dispensed, and 3% (12) were unresolved. CONCLUSION: Our findings suggest that pharmacists-initiated interventions can ameliorate DTPs in patients receiving ART given the high intervention acceptance rate recorded. The implication of this finding is that pharmacists with requisite training in HIV pharmacotherapy are an excellent resource in detecting and minimizing the effect of antiretroviral drug-related errors.

Pharmaceutical care outcomes in an outpatient human immunodeficiency virus treatment center in Jos, Nigeria.

RATIONALE: Pharmacotherapy for patients infected with human immunodeficiency virus (HIV) is complex and increases the potential for drug therapy problems (DTPs). We described the frequency and type of DTPs in a Nigerian cohort of HIV infected patients on antiretroviral therapy (ART), as well as the changes in HIV clinical outcomes after pharmacists' intervention. METHODS: A prospective 1-year descriptive study was conducted from July 2010 to June 2011, at the adult HIV clinic of Jos University Teaching Hospital, Nigeria. DTPs and the associated pharmacist-initiated interventions were documented. Chi-square and Wilcoxon signed ranks test was used as appropriate, to compare the main outcome measures of pre- and post-intervention levels of viral load and CD+ cell count. RESULTS: A total of 64,839 prescriptions were dispensed to 9320 patients. Interventions were documented for 85 unique patients (incidence of 1.31 interventions/1000 prescriptions), of which 62 (73%) and 3 (3.5%) were on first- and second-line ART, respectively, while 20 (23.5%) were yet to commence ART. Reasons for pharmacist intervention included failure to initiate therapy for HIV or hepatitis B infection; therapeutic failure (25.9%); and drug toxicity (24.7%). After intervention, the percentage of patients with HIV ribonucleic acid level <400 copies/mL rose from 29.4% to 67.1% (P < 0.001), while median (interquartile range) CD4+ cell count increased from 200 (123-351) to 361 (221-470) cells/mm(3) (P < 0.001). CONCLUSION: Pharmacist intervention resulted in clinically significant improvements in patients HIV virological and immunological outcomes. This highlights an important role for the pharmacist in the treatment and care of HIV-infected patients, in a multidisciplinary team.