Evaluation of cardiotoxicity and other adverse effects associated with concomitant administration of artemether/lumefantrine and atazanavir/ritonavir-based antiretroviral regimen in patients living with HIV.

The interplay of artemether-lumefantrine (AL) and atazanavir-ritonavir (ATVr) with Cytochrome P (CYP) 3A4 isoenzyme and QTc-interval may spawn clinically significant drug interactions when administered concomitantly. Cardiotoxicity and other adverse effects associated with interaction between AL and ATVr were evaluated in patients with HIV infection and malaria comorbidity. In a two-arm parallel study design, six doses of AL 80/480 mg were administered to 20 participants [control-arm (n = 10) and ATVr-arm (n = 10)], having uncomplicated Falciparum malaria, at intervals of 0, 8, 24, 36, 48 and 60 h respectively. Participants in the control arm took only AL while those in ATVr-arm took both AL and ATVr-based ART regimen. Electrocardiography, adverse events monitoring and blood tests were carried out for each of them at pre and post doses of AL. Data obtained were analyzed. QTc-interval was significantly increased in the ATVr-arm (0.4079 ± 0.008 to 0.4215 ± 0.007 s, p = 0.008) but not in the control-arm (0.4016 ± 0.018 to 0.4024 ± 0.014 s, p = 0.962). All values were, however, within normal range [0.36 - 0.44 / 0.46 s (male/female)]. General body weakness and chest pain were new adverse events reported, at post-dose of AL, in the ATVr-arm but not in the control-arm. There was no significant change (p > 0.05) in the plasma levels of creatinine, alanine aminotransferase, aspartate aminotransferase and hemoglobin at post-dose compared to pre-dose of AL in both arms of study. Concomitant administration of artemether-lumefantrine with atazanavir-ritonavir-based regimen is potentially cardiotoxic but not associated with clinically significant renal, blood nor liver toxicities. They must be used with caution.

Evaluation of the effects of atazanavir-ritonavir on the pharmacokinetics of lumefantrine in patients living with HIV in Lagos University Teaching Hospital, South-Western Nigeria.

PURPOSE: Atazanavir-ritonavir (ATVr)-based antiretroviral therapy and artemether-lumefantrine (AL) are commonly used drugs for the treatment of human immune deficiency virus (HIV) infection and malaria respectively. However, interaction of both drugs, with Cytochrome P 3A4 (CYP 3A4) isoenzyme, may spawn clinically significant pharmacokinetic interactions. This study evaluated the effects of atazanavir-ritonavir on the pharmacokinetics of lumefantrine. METHOD: In a case-control study, twenty participants having Plasmodium falciparum malaria were recruited and divided into two groups (ATVr-arm, n=10; and control-arm, n= 10). All the participants were administered six oral doses of AL 80-480 mg (Coartem). Thereafter, their blood samples were collected at different time intervals over seven days. The concentration of lumefantrine in each sample was quantified with high-performance liquid chromatography (HPLC) and used to determine its pharmacokinetic parameters which were compared between the test and control groups. RESULTS: ATVr increased the mean day 7 concentration of lumefantrine (ATVr 3847.09 ± 893.35 ng/mL, control 1374.53 ± 265.55 ng/mL, p = 0.016) and the area under its plasma concentration-time curve (ATVr 670529.57 ± 157172.93 ng.h/mL, control 447976.28 ± 80886.99 ng.h/mL, p = 0.224) by 179.88 % and 49.68 %, respectively, but decreased its mean maximum plasma drug concentration (Cmax) (ATVr 13725.70 ± 2658.44 ng/mL, control 15380.48 ± 2332.62 ng/mL, p = 0.645) by 10.76 %. CONCLUSION: ATVr increased drug exposure and day 7 plasma concentration of lumefantrine. AL is therefore considered effective for the treatment of malaria in patients taking ATVr-based regimen. However, the safety associated with the interaction requires further elucidation. TRIAL REGISTRATION: Clin ClinicalTrials.gov Identifier: NCT04531072, August 27, 2020. "Retrospectively registered".

Effect of nevirapine, efavirenz and lopinavir/ritonavir on the therapeutic concentration and toxicity of lumefantrine in people living with HIV at Lagos University Teaching Hospital, Nigeria.

Patients living with HIV in malarial endemic regions may experience clinically significant drug interaction between antiretroviral and antimalarial drugs. Effects of nevirapine (NVP), efavirenz (EFV) and lopinavir/ritonavir (LPVr) on lumefantrine (LM) therapeutic concentrations and toxicity were evaluated. In a four-arm parallel study design, the blood samples of 40 participants, treated with artemether/lumefantrine (AL), were analysed. Lumefantrine Cmax was increased by 32% (p = 0.012) and 325% (p < 0.0001) in the NVP and LPVr arms respectively but decreased by 62% (p < 0.0001) in the EFV-arm. AUC of LM was, respectively, increased by 50% (p = 0.27) and 328% (p < 0.0001) in the NVP and LPVr arms but decreased in the EFV-arm by 30% (p = 0.019). Median day 7 LM concentration was less than 280 ng/mL in EFV-arm (239 ng/mL) but higher in control (290 ng/mL), NVP (369 ng/mL, p = 0.004) and LPVr (1331 ng/mL, p < 0.0001) arms. There were no clinically relevant toxicities nor adverse events in both control and test arms. Artemether/lumefantrine is safe and effective for treatment of malaria in PLWHA taking NVP and LPVr based ART regimen but not EFV-based regimen.

A prospective study of the effect of antihypertensive medications on the sexual functions of hypertensive adult male patients.

BACKGROUND: The potential for antihypertensive medications to produce deleterious adverse effects on sexual functions among hypertensive adult male patients has been widely reported, such adverse effects may limit drug adherence and compliance. AIM: The aim of this study was to assess the effect of antihypertensive medication use on sexual functions among hypertensive adult male patients. METHODOLOGY: The study was carried out at the outpatient clinic of a Nigerian University Teaching Hospital. A total of one hundred and fifty-nine recruited hypertensive adult male patients that were being managed at the center over a 3-month period between January 2017 and April 2017 participated in the study; provided they satisfied the inclusion and exclusion criteria for enrolment. RESULTS: The respondents were between 30 and 98 years of age, (mean of 59 ± 11.1 years). Blood pressure recorded was during their initial medical diagnosis for hypertension. Systolic blood pressure recorded was between 128 and 194 mmHg (mean of 162 ± 16.4 mmHg), while their diastolic blood pressure was between 78 and 120 mmHg (mean of 95 ± 10.7 mmHg). The highest occurrence of sexual dysfunctions was associated with calcium-channel blockers in 32 (20.1%) patients, followed by diuretics in 27 (17.0%) and, angiotensin-converting enzyme inhibitors in 20 (12.6%) patients. CONCLUSION: Calcium channel blockers caused the highest occurrence of sexual dysfunctions.

Clinically Significant Drug-Drug Interaction in a Large Antiretroviral Treatment Centre in Lagos, Nigeria.

Background: An important cause of treatment failure to antiretroviral therapy (ART) is the potential interaction between the antiretroviral (ARV) drugs and co-prescribed drugs used concomitantly for the treatment of opportunistic infections and co-morbid ailments in HIV-infected patients. Objectives: The study evaluated potential clinically significant drug interactions (CSDIs) occurring between recommended ART regimens and their co-prescribed non-antiretroviral drugs (CPD) Method: This study was carried out in a large HIV treatment centre (APIN clinic) in a Nigerian teaching hospital, in Lagos Nigeria, caring for over 20,000 registered patients. Electronic Medical Records (EMR) of 500 patients  who received treatment between 2005 and 2015, were selected using systematic random sampling, reviewed retrospectively, and evaluated for potential CSDIs using Liverpool HIV Pharmacology Database and other similar databases.                                                                                                                                          Results:  Majority of patients, 421 (84%) were at risk of CSDIs, of  which  410, (82%) were moderate and frequently involved co-trimoxazole + zidovudine (or stavudine) /lamivudine (386, 77.2%) and NNRTIs or PIs + artemisinin-based combination therapies (ACTs) [296, 59.2%]. Age (p=0.131), sex (p=0.316) and baseline CD4+ cell counts (p>0.05) were not significantly associated with CSDIs. The interactions, however, were significantly associated with the development of antiretroviral treatment failure (p <0.001) which occurred in nearly a third (139; 27.8%) of the patients. Conclusion: There is a high prevalence of CSDIs between ART and CPDs most of which were categorized as moderate.  Further studies are required to evaluate the pharmacokinetic and clinical relevance of these interactions.

Biochemical, hematological, and hormonal profile of rats orally administered methanol stem bark extract of Napoleona vogelii Hook and Planch (Lecythidaceae).

Napoleona vogelii is used in traditional medicine for the management of stomach aches, ulcer, and cancers. This study was conducted to investigate the subchronic toxicological effect of methanol stem bark extract of N. vogelii on biochemical, hematological, and hormonal profile of male and female rats. Forty rats of both sexes were randomly divided into four groups of 10 rats each and were administered 100, 200, and 400 mg/kg of the extract p.o. for 90 d. Ten milliliter per kilogram of distilled water p.o. was administered to control rats. On hematological assessment, mean corpuscular hemoglobin concentration was significantly (p < 0.01) increased at 400 mg/kg compared to control. Biochemical assessment showed a significant increase (p < 0.05) in levels of alanine aminotransferase and aspartate aminotransferase at 200 and 400 mg/kg, respectively, compared to control. Hormonal assessment of male rats revealed a significantly (p < 0.0001) reduced level of testosterone at all treatment doses compared to control while estradiol was significantly (p < 0.05) reduced at 100 mg/kg, but significantly (p < 0.0001) increased at 200 and 400 mg/kg respectively compared to control in female rats. Findings from this study demonstrate that N. vogelli is relatively safe on oral acute exposure but may possess the potential to cause hepatic dysfunction and infertility in male rats by perturbations of the hypothalamic-pituitary axis while conversely enhancing fertility in female rats on subchronic administration.

Antimalaria action of antiretroviral drugs on Plasmodium berghei in mice.

Malaria parasitemia enhances replication of human immunodeficiency virus. Antiretroviral drugs that possess antiplasmodial activity may reverse such an effect. Activity of the antiretroviral drugs lamivudine (L), zidovudine (Z), nevirapine (N), and stavudine (S) against Plasmodium berghei inoculated into 70 adult albino mice was investigated. Eight groups of five animals each were treated with different drugs as either curative or prophylactic regimens. These regimens were also given to four groups as L/Z/N or L/S/N. Z therapy alone and L/Z/N eliminated malaria parasites as follows: curative and prophylactic Z groups, mean ± SEM = 62,132.87 ± 22,816.1 parasites/µL and 62,474.85 ± 14,639.1 parasites/µL, respectively on day 4 and 0 parasites/µL on day 26; curative L/Z/N group, 31,583.53 ± 6,361.67 parasites/µL, and 0 parasites/µL (days 4 and 18, respectively); prophylactic L/Z/N group, 41,138.1 ± 3,528.03 parasites/µL, and 0 parasites/µL (days 4, and 20 respectively). Peters four-day suppressive values were 67-82.2%. Zidovudine or L/Z/N therapy may modify the epidemiology of malaria and therefore the pandemic of human immunodeficiency virus infection.

Pharmacovigilance amongst doctors in private hospitals in Lagos West Senatorial District, Nigeria.

Appropriate practice of pharmacovigilance in Nigeria will require total involvement of the private medical practitioners considering their number and closeness to the community. Thus, the understanding and attitude of Doctors practicing in the private sectors, towards Pharmacovigilance, was investigated. A consecutive sampling was used to distribute two hundred and seventy questionnaires to consenting doctors in the private hospitals of the Lagos West Senatorial District. The response rate was 93% and the results showed that majority of the respondents, 208 (82.9%), have heard about pharmacovigilance and a large percentage (79.3%) defined pharmacovigilance correctly. However, most of the respondents, 141 (56.2%), did not know how to report ADRs and where to obtain the ADR forms (71.7%). Only 14 (5.6%) of the respondents reported ADRs in the last one month. However, the majority of the respondents (89.6%) were willing to practice pharmacovigilance if they are trained. There were significant associations (p < 0.05) between previous areas of practice of the respondents; the respondents' academic qualifications; years of experience and reporting of ADRs. The NPC has already been organizing series' of trainings for doctors on pharmacovigilance, however, more periodic trainings should be organized for doctors especially those practicing in private hospitals. The curriculum of medical schools should be reviewed for its pharmacovigilance content.

Knowledge, treatment seeking and preventive practices in respect of malaria among patients with HIV attending Lagos University Teaching Hospital, Nigeria.

The synergistic interaction between Human Immunodeficiency virus (HIV) disease and malaria makes it mandatory for patients with HIV to respond appropriately in preventing and treating malaria. Such response will help to control the two diseases. This study assessed the knowledge of 495 patients attending the HIV clinic, in Lagos University Teaching Hospital, Nigeria. Their treatment seeking, preventive practices with regards to malaria, as well as the impact of socio-demographic / socioeconomic status were assessed. Out of these patients, 245 (49.5%) used insecticide treated bed nets; this practice was not influenced by sociodemographic or socioeconomic factors. However, knowledge of the cause, knowledge of prevention of malaria, appropriate use of antimalarial drugs and seeking treatment from the right source increased with increasing level of education (P < 0.05). A greater proportion of the patients, 321 (64.9%) utilized hospitals, pharmacy outlets or health centres when they perceived an attack of malaria. Educational intervention may result in these patients seeking treatment from the right place when an attack of malaria fever is perceived.