Heavy metals and inflammatory, oxidative/antioxidant and DNA damage biomarkers among people living with HIV/AIDS (PLWHA) in Niger Delta, Nigeria.

This study evaluated the association of heavy metals (HMs) and effect biomarkers (inflammation, oxidative stress/antioxidant capacity and DNA damage) among people living with HIV/AIDS (PHWHA) in Niger Delta area, Nigeria. Blood levels of lead (BPb), cadmium (BCd), copper (BCu), zinc (BZn), iron (BFe), C-reactive protein (CRP), Interleukin-6 (IL-6), Tumor necrosis factor-α (TNF-α), Interferon-γ (IFN-γ), Malondialdehyde (MDA), Glutathione (GSH) and 8-hydroxy-2-deoxyguanosine (8-OHdG) were determined in a total of 185 participants, 104 HIV-positive and 81 HIV-negative sampled in both Niger Delta and non-Niger Delta regions. BCd (p < 0.001) and BPb (p = 0.139) were higher in HIV-positive subjects compared to HIV-negative controls; on the contrary, BCu, BZn and BFe levels were lower (p < 0.001) in HIV-positive subjects compared to HIV-negative controls. The Niger Delta population had higher levels of heavy metals (p < 0.01) compared to non-Niger Delta residents. CRP and 8-OHdG were higher (p < 0.001) in HIV-positive than in HIV-negative subjects and in Niger-Delta than in non-Niger Delta residents. BCu had significant positive dose-response relationship with CRP (61.9%, p = 0.063) and GSH (1.64%, p = 0.035) levels in HIV-positive subjects, and negative response with MDA levels (26.6%, p < 0.001). Periodic assessment of HMs levels among PLWHA is recommended.

Toxic Metals and Non-Communicable Diseases in HIV Population: A Systematic Review.

Background and Objectives: HIV has been a serious global health concern since its discovery, with about 37.9 million people living with HIV worldwide as of 2018. Sub-Saharan Africa (SSA) accounts for 68% of the infection and contributed 74% of the 1.5 million deaths in 2013 despite having only 12% of the total world population residing in the region. This systematic review has attempted to determine the association between heavy metal toxicity and the occurrence of non-communicable diseases in the HIV/AIDS population. Materials and Methods: Three databases were systematically searched: PubMed, Scopus, and Google Scholar for studies written in English and published between 1 April 2000 and 12 April 2020. Studies were excluded if the main outcomes were not measured or did not meet the inclusion criteria. Results: All the six included studies are cross-sectional in design, and therefore were evaluated using the STROBE checklist. The data extraction was done using an extraction table; the ratio of female to male participants included in the study was 1.09:1. Qualitative analysis was used due to the heterogeneity in the heavy metal biomarkers and the outcome measured by the included studies. Two studies compared the concentration of heavy metals in HIV-positive and HIV-negative participants while one compared the levels between HAART-naïve and HAART-treated participants, and three determined the association between heavy metal toxicity and non-communicable diseases (liver fibrosis, anaemia, and reproductive parameters, respectively) in HIV-positive patients. Conclusions: Blood lead, cadmium, and mercury levels were higher in HIV-seropositive than -seronegative subjects, whereas serum zinc level was lower in HIV-seropositive than -seronegative subjects, but the causal association between heavy metals and non-communicable diseases in HIV subjects is largely unknown. Interdisciplinary research between nutrition, toxicology, and human health is envisaged for primary and secondary prevention and treatment.

An Individual Participant Data Population Pharmacokinetic Meta-analysis of Drug-Drug Interactions between Lumefantrine and Commonly Used Antiretroviral Treatment.

Treating malaria in HIV-coinfected individuals should consider potential drug-drug interactions. Artemether-lumefantrine is the most widely recommended treatment for uncomplicated malaria globally. Lumefantrine is metabolized by CYP3A4, an enzyme that commonly used antiretrovirals often induce or inhibit. A population pharmacokinetic meta-analysis was conducted using individual participant data from 10 studies with 6,100 lumefantrine concentrations from 793 nonpregnant adult participants (41% HIV-malaria-coinfected, 36% malaria-infected, 20% HIV-infected, and 3% healthy volunteers). Lumefantrine exposure increased 3.4-fold with coadministration of lopinavir-ritonavir-based antiretroviral therapy (ART), while it decreased by 47% with efavirenz-based ART and by 59% in the patients with rifampin-based antituberculosis treatment. Nevirapine- or dolutegravir-based ART and malaria or HIV infection were not associated with significant effects. Monte Carlo simulations showed that those on concomitant efavirenz or rifampin have 49% and 80% probability of day 7 concentrations <200 ng/ml, respectively, a threshold associated with an increased risk of treatment failure. The risk of achieving subtherapeutic concentrations increases with larger body weight. An extended 5-day and 6-day artemether-lumefantrine regimen is predicted to overcome these drug-drug interactions with efavirenz and rifampin, respectively.

Safety of honey consumed in Enugu State, Nigeria: a public health risk assessment of lead and polycyclic aromatic hydrocarbons

Background: Information about lead (Pb) and polycyclic aromatic hydrocarbons (PAHs) concentrations in honey and their dietary intake is very important in human health risk assessment. Currently, there are paucity of data on the risk assessment and concentrations of lead and PAHs in honey in Nigeria. Objective: This study has determined the potential human health risk of lead and PAHs associated with the consumption of honey in Enugu state, Nigeria. Materials and methods: Lead and US EPA 16 priority PAHs in honey harvested from rural and urban communities in March 2016 were determined using Atomic Absorption Spectrometer and Gas Chromatograph respectively. Carcinogenic and non-carcinogenic risk assessments were carried. Results: The mean concentration of Pb in honey ranged from 0.005 mg/kg ­ 0.08 mg/kg. The mean concentrations of 16 PAHs in honey ranged from 4.71E-03 ­ 2.72 mg/kg. The dietary intake of the PAHs for adults and children ranged from 0.0021 ­ 0.0259 mg/kg/day and 0.0011 ­ 0.0129 mg/kg/day respectively. The levels of BaPeq and their margin of exposure MOE suggest non-significant health risk. The incremental life cancer risk ILCR of Pb were within safe range of <1E-04. Conclusion: Consumption of honey from Enugu State, Nigeria may not pose a significant health risk_

HIV-positive nigerian adults harbor significantly higher serum lumefantrine levels than HIV-negative individuals seven days after treatment for Plasmodium falciparum infection.

Management of coinfection with malaria and HIV is a major challenge to public health in developing countries, and yet potential drug-drug interactions between antimalarial and antiviral regimens have not been adequately investigated in people with both infections. Each of the constituent components of artemether-lumefantrine, the first-line regimen for malaria treatment in Nigeria, and nevirapine, a major component of highly active antiretroviral therapy, are drugs metabolized by the cytochrome P450 3A4 isoenzyme system, which is also known to be induced by nevirapine. We examined potential interactions between lumefantrine and nevirapine in 68 HIV-positive adults, all of whom were diagnosed with asymptomatic Plasmodium falciparum infections by microscopy. Post hoc PCR analysis confirmed the presence of P. falciparum in only a minority of participants. Day 7 capillary blood levels of lumefantrine were significantly higher in HIV-positive participants than in 99 HIV-negative controls (P = 0.0011). Associations between day 7 levels of lumefantrine and risk of persistent parasitemia could not be evaluated due to inadequate power. Further investigations of the impact of nevirapine on in vivo malaria treatment outcomes in HIV-infected patients are thus needed.

Potential deleterious effects of paracetamol dose regime used in Nigeria versus that of the United States of America.

Paracetamol, also known as acetaminophen (N-acetyl-para-aminophenol, APAP) is the world's most used over-the-counter analgesic-antipyretic drug. Despite its good safety profile, acetaminophen can cause severe hepatotoxicity in overdose, and poisoning from paracetamol has become a major public health concern. Paracetamol is now the major cause of acute liver failure in the United States and Europe. This systematic review aims at examining the likelihood of paracetamol use in Nigeria causing more liver toxicity vis-à-vis the reduced maximum recommended daily adult dose of 3 g for the 500 mg tablet. Online searches were conducted in the databases of PubMed, Google Scholar and MEDLINE for publications using terms like "paracetamol toxicity," "acetaminophen and liver toxicity," "paracetamol and liver diseases in Nigeria," and other variants. Further search of related references in PubMed was carried out, and synthesis of all studies included in this review finalized. There were 94 studies that met the inclusion criteria. Evaluation of hepatic disorder was predicated mostly on a constellation of clinical features and limited clinical laboratory investigations. Determination of blood paracetamol concentration was rarely reported, thus excluding paracetamol poisoning as one of the likely causes of liver disorders in Nigeria. In Nigeria and elsewhere, several factors are known to increase paracetamol's predisposition to liver injury. They include: the over-the-counter status of paracetamol, use of fixed-dose combinations of paracetamol with other drugs, malnutrition, dose miscalculations, and chronic alcohol consumption. The tendency to exceed the new paracetamol maximum daily dose of 3 g in Nigeria may increase its risk for hepatotoxicity than observed in the United States of America known for emphasizing lower dose of the drug. In addition to recommending the new maximal daily paracetamol dose allowance, the historical maximum daily adult dose of 4 g should be de-emphasized in Nigeria.

Antimalarial drug resistance markers in human immunodeficiency virus (HIV)-positive and HIV-negative adults with asymptomatic malaria infections in Port Harcourt, Nigeria.

BACKGROUND: In Nigeria, indiscriminate use of antimalarial drugs may contribute to the threat of drug resistance, but this has not been evaluated among people living with human immunodeficiency virus (HIV). METHODS: HIV-positive adults attending a university hospital HIV clinic and HIV-negative adult volunteers from the university hospital community with a positive blood film were treated with artemether-lumefantrine. Parasite DNA from before and after treatment was polymerase chain reaction amplified to identify molecular markers of drug susceptibility. RESULTS: The pfcrt76T genotype was prevalent among both HIV-positive and HIV-negative participants (78.6% and 68.2%, respectively). Three new mutations in the pfmdr1 gene-F73S, S97L and G165R-and the uncommon pfdhps S436F variant were detected, whereas pfdhps K540E and pfdhfr I164L were absent. The A437G allele of pfdhps predominated (62/66 [94%]). The I431 V mutation was found in 19 of 66 pretreatment pfdhps sequences (28.8%). The pfmdr1 86N allele was significantly more common at day 3 post-treatment than at baseline (odds ratio 8.77 [95% confidence interval 1.21 to 380]). CONCLUSIONS: We found evidence of continued chloroquine use among HIV-positive individuals. Selection for the pfmdr1 86N after artemether-lumefantrine treatment was observed, indicating a possible threat to antimalarial efficacy in the study area. The complexity of pfdhps haplotypes emphasises the need for careful monitoring of anti-folate susceptibility in Nigeria.