A Review of the Toxicity and Phytochemistry of Medicinal Plant Species Used by Herbalists in Treating People Living With HIV/AIDS in Uganda

Introduction: Despite concerns about toxicity, potentially harmful effects and herb-drug interactions, the use of herbal medicines remains widely practiced by people living with HIV/AIDS (PLHIV) in Uganda. Objective: The objective of the paper was to comprehensively review the literature on the toxicity and chemical composition of commonly used medicinal plant species in treating PLHIV in Uganda. Methods: We reviewed relevant articles and books published over the last sixty years on ethnobotany, antiviral/anti-HIV activity, toxicity, phytochemistry of Vachellia hockii, Albizia coriaria, Bridelia micrantha, Cryptolepis sanguinolenta, Erythrina abyssinica, Gardenia ternifolia, Gymnosporia senegalensis, Psorospermum febrifugium, Securidaca longipendunculata, Warburgia ugandensis and Zanthoxylum chalybeum and their synonyms. We searched PubMed, Web of Science, Scopus, Science Direct and Google Scholar. Discussion: Most of the plant species reviewed apart from P. febrifugium, S. longipedunculata and C. sanguinolenta lacked detailed phytochemical analyses as well as the quantification and characterization of their constituents. Crude plant extracts were the most commonly used. However, purified/single component extracts from different plant parts were also used in some studies. The U87 human glioblastoma was the most commonly used cell line. Water, ethanol, methanol and DMSO were the commonest solvents used. In some instances, isolated purified compounds/extracts such as Cryptolepine and Psorospermin were used. Conclusion: Cytotoxicity varied with cell type, solvent and extract type used making it difficult for direct comparison of the plant species. Five of the eleven plant species namely, A. coriaria, C. sanguinolenta, G. ternifolia, P. febrifugium and Z. chalybeum had no cytotoxicity studies in animal models. For the remaining six plant species, the crude aqueous and ethanol extracts were mainly used in acute oral toxicity studies in mice. Herbalists reported only A. coriaria and W. ugandensis to cause toxic side effects in humans. However, selective cytotoxic plant extracts can potentially be beneficial as anticancer or anti-tumour drugs

Importance of Ethnicity, CYP2B6 and ABCB1 Genotype for Efavirenz Pharmacokinetics and Treatment Outcomes: A Parallel-group Prospective Cohort Study in two sub-Saharan Africa Populations.

We evaluated the importance of ethnicity and pharmacogenetic variations in determining efavirenz pharmacokinetics, auto-induction and immunological outcomes in two African populations. ART naïve HIV patients from Ethiopia (n = 285) and Tanzania (n = 209) were prospectively enrolled in parallel to start efavirenz based HAART. CD4+ cell counts were determined at baseline, 12, 24 and 48 weeks. Plasma and intracellular efavirenz and 8-hydroxyefvairenz concentrations were determined at week 4 and 16. Genotyping for common functional CYP2B6, CYP3A5, ABCB1, UGT2B7 and SLCO1B1 variant alleles were done. Patient country, CYP2B6*6 and ABCB1 c.4036A>G (rs3842A>G) genotype were significant predictors of plasma and intracellular efavirenz concentration. CYP2B6*6 and ABCB1 c.4036A>G (rs3842) genotype were significantly associated with higher plasma efavirenz concentration and their allele frequencies were significantly higher in Tanzanians than Ethiopians. Tanzanians displayed significantly higher efavirenz plasma concentration at week 4 (p<0.0002) and week 16 (p = 0.006) compared to Ethiopians. Efavirenz plasma concentrations remained significantly higher in Tanzanians even after controlling for the effect of CYP2B6*6 and ABCB1 c.4036A>G genotype. Within country analyses indicated a significant decrease in the mean plasma efavirenz concentration by week 16 compared to week 4 in Tanzanians (p = 0.006), whereas no significant differences in plasma concentration over time was observed in Ethiopians (p = 0.84). Intracellular efavirenz concentration and patient country were significant predictors of CD4 gain during HAART. We report substantial differences in efavirenz pharmacokinetics, extent of auto-induction and immunologic recovery between Ethiopian and Tanzanian HIV patients, partly but not solely, due to pharmacogenetic variations. The observed inter-ethnic variations in efavirenz plasma exposure may possibly result in varying clinical treatment outcome or adverse event profiles between populations

Pharmacogenetic & Pharmacokinetic Biomarker for Efavirenz Based ARV and Rifampicin Based Anti-TB Drug Induced Liver Injury in TB-HIV Infected Patients

BACKGROUND: Implication of pharmacogenetic variations and efavirenz pharmacokinetics in concomitant efavirenz based antiviral therapy and anti-tubercular drug induced liver injury (DILI) has not been yet studied. We performed a prospective case-control association study to identify the incidence, pharmacogenetic, pharmacokinetic and biochemical predictors for anti-tubercular and antiretroviral drugs induced liver injury (DILI) in HIV and tuberculosis (TB) co-infected patients. METHODS AND FINDINGS: Newly diagnosed treatment naïve TB-HIV co-infected patients (n = 353) were enrolled to receive efavirenz based ART and rifampicin based anti-TB therapy, and assessed clinically and biochemically for DILI up to 56 weeks. Quantification of plasma efavirenz and 8-hydroxyefaviernz levels and genotyping for NAT2, CYP2B6, CYP3A5, ABCB1, UGT2B7 and SLCO1B1 genes were done. The incidence of DILI and identification of predictors was evaluated using survival analysis and the Cox Proportional Hazards Model. The incidence of DILI was 30.0%, or 14.5 per 1000 person-week, and that of severe was 18.4%, or 7.49 per 1000 person-week. A statistically significant association of DILI with being of the female sex (p = 0.001), higher plasma efavirenz level (p = 0.009), efavirenz/8-hydroxyefavirenz ratio (p = 0.036), baseline AST (p = 0.022), ALT (p = 0.014), lower hemoglobin (p = 0.008), and serum albumin (p = 0.007), NAT2 slow-acetylator genotype (p = 0.039) and ABCB1 3435TT genotype (p = 0.001). CONCLUSION: We report high incidence of anti-tubercular and antiretroviral DILI in Ethiopian patients. Between patient variability in systemic efavirenz exposure and pharmacogenetic variations in NAT2, CYP2B6 and ABCB1 genes determines susceptibility to DILI in TB-HIV co-infected patients. Close monitoring of plasma efavirenz level and liver enzymes during early therapy and/or genotyping practice in HIV clinics is recommended for early identification of patients at risk of DILI

Ar Diffusion in Muscovite: 2D in situ Imaging and Numerical Modeling of Coupled Lattice and Defect Mediated Diffusion

International audienc

Poor immunological recovery among severely immunosuppressed antiretroviral therapy-na&iuml;ve Ugandans

Sarah Nanzigu,1,2 Ronald Kiguba,1 Joseph Kabanda,3 Jackson K Mukonzo,1 Paul Waako,1 Cissy Kityo,4 Fred Makumbi31Department of Pharmacology and Therapeutics, Makerere University College of Health Sciences, Kampala, Uganda; 2Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden; 3Institute of Public Health, Makerere University College of Health Sciences, Kampala, Uganda; 4Joint Clinic Research Centre, Kampala, UgandaIntroduction: CD4 T lymphocytes remain the surrogate measure for monitoring HIV progress in resource-limited settings. The absolute CD4 cell counts form the basis for antiretroviral therapy (ART) initiation and monitoring among HIV-infected adults. However, the rate of CD4 cell change differs among patients, and the factors responsible are inadequately documented.Objective: This study investigated the relationship between HIV severity and ART outcomes among ART-na&iuml;ve Ugandans, with the primary outcome of complete immunological recovery among patients of different baseline CD4 counts.Methods: Patients&#39; records at two HIV/ART sites &ndash; the Joint Clinic Research Centre (JCRC) in the Kampala region and Mbarara Hospital in Western Uganda &ndash; were reviewed. Records of 426 patients &ndash; 68.3% female and 63.2% from JCRC &ndash; who initiated ART between 2002 and 2007 were included. HIV severity was based on baseline CD4 cell counts, with low counts considered as severe immunosuppression, while attaining 418 CD4 cells/&micro;L signified complete immunological recovery. Incidence rates of complete immunological recovery were calculated for, and compared between baseline CD4 cell categories: <50 with &ge;50, <100 with &ge;100, <200 with &ge;200, and &ge;200 with &ge;250 cells/&micro;L.Results: The incidence of complete immunological recovery was 158 during 791.9 person-years of observation, and patients with baseline CD4 &ge; 200 cells/&micro;L reached the end point of immunological recovery 1.89 times faster than the patients with baseline CD4 < 200 cells/&micro;L. CD4 cell change also differed by time, sex, and site, with a faster increase observed during the first year of treatment. CD4 cell increase was faster among females, and among patients from Mbarara.Conclusion: Initiating ART at an advanced HIV stage was the main reason for poor immunological recovery among Ugandans. Earlier ART initiation might lead to better immunological responses.Keywords: baseline CD4 cells, HIV severity, immunological recovery, ART outcome, AR

A Review of the Toxicity and Phytochemistry of Medicinal Plant Species Used by Herbalists in Treating People Living With HIV/AIDS in Uganda

Introduction: Despite concerns about toxicity, potentially harmful effects and herb-drug interactions, the use of herbal medicines remains widely practiced by people living with HIV/AIDS (PLHIV) in Uganda. Objective: The objective of the paper was to comprehensively review the literature on the toxicity and chemical composition of commonly used medicinal plant species in treating PLHIV in Uganda. Methods: We reviewed relevant articles and books published over the last sixty years on ethnobotany, antiviral/anti-HIV activity, toxicity, phytochemistry of Vachellia hockii, Albizia coriaria, Bridelia micrantha, Cryptolepis sanguinolenta, Erythrina abyssinica, Gardenia ternifolia, Gymnosporia senegalensis, Psorospermum febrifugium, Securidaca longipendunculata, Warburgia ugandensis and Zanthoxylum chalybeum and their synonyms. We searched PubMed, Web of Science, Scopus, Science Direct and Google Scholar. Discussion: Most of the plant species reviewed apart from P. febrifugium, S. longipedunculata and C. sanguinolenta lacked detailed phytochemical analyses as well as the quantification and characterization of their constituents. Crude plant extracts were the most commonly used. However, purified/single component extracts from different plant parts were also used in some studies. The U87 human glioblastoma was the most commonly used cell line. Water, ethanol, methanol and DMSO were the commonest solvents used. In some instances, isolated purified compounds/extracts such as Cryptolepine and Psorospermin were used. Conclusion: Cytotoxicity varied with cell type, solvent and extract type used making it difficult for direct comparison of the plant species. Five of the eleven plant species namely, A. coriaria, C. sanguinolenta, G. ternifolia, P. febrifugium and Z. chalybeum had no cytotoxicity studies in animal models. For the remaining six plant species, the crude aqueous and ethanol extracts were mainly used in acute oral toxicity studies in mice. Herbalists reported only A. coriaria and W. ugandensis to cause toxic side effects in humans. However, selective cytotoxic plant extracts can potentially be beneficial as anticancer or anti-tumour drugs

A Review of the Toxicity and Phytochemistry of Medicinal Plant Species Used by Herbalists in Treating People Living With HIV/AIDS in Uganda

Introduction: Despite concerns about toxicity, potentially harmful effects and herb-drug interactions, the use of herbal medicines remains widely practiced by people living with HIV/AIDS (PLHIV) in Uganda. Objective: The objective of the paper was to comprehensively review the literature on the toxicity and chemical composition of commonly used medicinal plant species in treating PLHIV in Uganda. Methods: We reviewed relevant articles and books published over the last sixty years on ethnobotany, antiviral/anti-HIV activity, toxicity, phytochemistry of Vachellia hockii, Albizia coriaria, Bridelia micrantha, Cryptolepis sanguinolenta, Erythrina abyssinica, Gardenia ternifolia, Gymnosporia senegalensis, Psorospermum febrifugium, Securidaca longipendunculata, Warburgia ugandensis and Zanthoxylum chalybeum and their synonyms. We searched PubMed, Web of Science, Scopus, Science Direct and Google Scholar. Discussion: Most of the plant species reviewed apart from P. febrifugium, S. longipedunculata and C. sanguinolenta lacked detailed phytochemical analyses as well as the quantification and characterization of their constituents. Crude plant extracts were the most commonly used. However, purified/single component extracts from different plant parts were also used in some studies. The U87 human glioblastoma was the most commonly used cell line. Water, ethanol, methanol and DMSO were the commonest solvents used. In some instances, isolated purified compounds/extracts such as Cryptolepine and Psorospermin were used. Conclusion: Cytotoxicity varied with cell type, solvent and extract type used making it difficult for direct comparison of the plant species. Five of the eleven plant species namely, A. coriaria, C. sanguinolenta, G. ternifolia, P. febrifugium and Z. chalybeum had no cytotoxicity studies in animal models. For the remaining six plant species, the crude aqueous and ethanol extracts were mainly used in acute oral toxicity studies in mice. Herbalists reported only A. coriaria and W. ugandensis to cause toxic side effects in humans. However, selective cytotoxic plant extracts can potentially be beneficial as anticancer or anti-tumour drugs

Rates and Correlates of Short Term Virologic Response among Treatment-Naïve HIV-Infected Children Initiating Antiretroviral Therapy in Ethiopia: A Multi-Center Prospective Cohort Study

There is limited data on virologic outcome and its correlates among HIV-infected children in resource-limited settings. We investigated rate and correlates of virologic outcome among treatment naïve HIV-infected Ethiopian children initiating cART, and were followed prospectively at baseline, 8, 12, 24 and 48 weeks using plasma viral load, clinical examination, laboratory tests and pretreatment HIV drug resistance (PDR) screening. Virologic outcome was assessed using two endpoints–virological suppression defined as having “undetectable” plasma viral load < 150 RNA copies/mL, and rebound defined as viral load ≥150 copies/mL after achieving suppression. Cox Proportional Hazards Regression was employed to assess correlates of outcome. At the end of follow up, virologic outcome was measured for 110 participants. Overall, 94(85.5%) achieved virological suppression, of which 36(38.3%) experienced virologic rebound. At 48 weeks, 9(8.2%) children developed WHO-defined virological treatment failure. Taking tenofovir-containing regimen (Hazard Ratio (HR) 3.1-[95% confidence interval (95%CI) 1.0–9.6], p = 0.049) and absence of pretreatment HIV drug resistance (HR 11.7-[95%CI 1.3–104.2], p = 0.028) were independently associated with earlier virologic suppression. In conclusion, PDR and cART regimen type correlate with rate of virologic suppression which was prominent during the first year of cART initiation. However, the impact of viral rebound in 38.3% of the children needs evaluation.Medicine, Faculty ofOther UBCNon UBCReviewedFacultyResearche

Output from the CIHR Canadian HIV Trials Network international postdoctoral fellowship for capacity building in HIV clinical trials

CITATION: Mbuagbaw, L., et al. 2018. Output from the CIHR Canadian HIV Trials Network international postdoctoral fellowship for capacity building in HIV clinical trials. HIV/AIDS - Research and Palliative Care, 10:151-155, doi:10.2147/HIV.S150107.The original publication is available at https://www.dovepress.comENGLISH ABSTRACT: As a response to the human immunodeficiency virus (HIV) epidemic and part of Canadian Institutes for Health Research’s mandate to support international health research capacity building, the Canadian Institutes for Health Research Canadian HIV Trial Network (CTN) developed an international postdoctoral fellowship award under the CTN’s Postdoctoral Fellowship Awards Program to support and train young HIV researchers in resource-limited settings. Since 2010, the fellowship has been awarded to eight fellows in Cameroon, China, Lesotho, South Africa, Uganda and Zambia. These fellows have conducted research on a wide variety of topics and have built a strong network of collaboration and scientific productivity, with 40 peer-reviewed publications produced by six fellows during their fellowships. They delivered two workshops at international conferences and have continued to secure funding for their research, using the fellowship as a stepping stone. The CTN has been successful in building local HIV research capacity and forming a strong network of like-minded junior low- and middle-income country researchers with high levels of research productivity. They have developed into mentors, supervisors and faculty members, who, in turn, build local capacity. The sustainability of this international fellowship award relies on the recognition of its strengths and the involvement of other stakeholders for additional resources.https://www.dovepress.com/output-from-the-cihr-canadian-hiv-trials-network-international-postdoc-peer-reviewed-article-HIV#Publisher's versio