Changes in Liver Function Enzymes of HIV/AIDS Patients Treated with Antiretroviral Drugs (ARVS) in Specialist Hospital, Sokoto, Nigeria

This study assessed the effect of Human Immunodeficiency Virus and Antiretroviral Drugs (ARVs) on liver enzyme markers (Aspartate aminotransferase, Alanine aminotransferase and Alkaline phosphatase) and CD4 T-cells. A total of Seventy Five (75) individuals were enrolled into the study, which comprised Twenty Five (25) HIV negative (control), Twenty Five (25) HIV positive non-treated with ARVs and Twenty Five (25) HIV positive treated with antiretroviral drugs (ARVs). Females were found to be the majority of HIV infected patients and most patients were at the middle age of 20-39 years. AST and ALT were assessed according to the Reitman and Frankel’s (1957) method, while ALP was based on King Armstrong’s (1980) method and CD4 T-cells using a method assayed of Cassens et al., (2004). The result show a significant increase (p<0.05) in AST and ALT levels of HIV positive non treated group compared to HIV negative group (control). AST and ALT levels of HIV positive treated with ARVs is significantly higher in comparison to HIV positive non-treated group. But the ALP activity was significantly lower (p<0.05) in HIV positive treated group compared to non-treated group. Infection by HIV increases the activities of the three enzymes, which may be due to liver cells apoptosis caused by HIV infection, intact immune response to HIV replication which subsequently leads to hepatocellular necrosis and inflammation. But at the commencement of antiretroviral therapy the activities of the three afore-mentioned enzymes decreases which may be as result of decrease in the negative effect of the virus to the liver enzymes by ARVs. For clinical significance, it is necessary to investigate the activities of liver enzymes in HIV positive patients in order to monitor the diagnosis and advanced infection of the liver cells by HIV.Keywords: Aspartate aminotransferase, Alanine aminotransferase, Alkaline phosphatase, Human immunodeficiency virus and antiretroviral drug

Influence of ARVs on Some Biochemical Changes in Liver Non Enzymatic Markers of HIV Positive Patients Attending Specialist Hospital Sokoto, Nigeria

Both HIV infection and antiretroviral drugs (ARVs) are associated with abnormalities of liver function, revealed by both enzymatic and non-enzymatic markers. This study evaluated the effect of HIV infection and antiretroviral drugs on the liver non enzymatic marker (total and direct bilirubin, total protein and albumin level) of HIV positive patients (pre-highly active antiretroviral therapy and those on therapies) attending the voluntary counselling and testing units in the state. Seventy five subjects were enrolled into the study, which constituted 25 HIV negative individuals (control group), 25 HIV positive patient not on antiretroviral therapy and 25 on the therapy. Bilirubin, albumin, total protein and CD4 cell count were determined using standard methods. Significantly (p<0.05) higher level of total bilirubin, direct bilirubin and total protein in the HIV positive non-treated with ARVs was observed compared to the control group. At the initiation of antiretroviral therapy the levels of the three parameters were lower, though statistically not significant except for total protein. Albumin level and CD4 cell count were significantly (p<0.05) lower in the non-treated group compared to the control subjects. But at the initiation of therapy the serum levels of Albumin and CD4 count was significantly (p<0.05) higher except for albumin level. HIV infection lowers the level of liver non enzymatic markers, which increase at the initiation of antiretroviral therapy.Keywords: Bilirubin, Albumin, Total protein and CD4 cel

Drug dosing during pregnancy—opportunities for physiologically based pharmacokinetic models

Drugs can have harmful effects on the embryo or the fetus at any point during pregnancy. Not all the damaging effects of intrauterine exposure to drugs are obvious at birth, some may only manifest later in life. Thus, drugs should be prescribed in pregnancy only if the expected benefit to the mother is thought to be greater than the risk to the fetus. Dosing of drugs during pregnancy is often empirically determined and based upon evidence from studies of non-pregnant subjects, which may lead to suboptimal dosing, particularly during the third trimester. This review collates examples of drugs with known recommendations for dose adjustment during pregnancy, in addition to providing an example of the potential use of PBPK models in dose adjustment recommendation during pregnancy within the context of drug-drug interactions. For many drugs, such as antidepressants and antiretroviral drugs, dose adjustment has been recommended based on pharmacokinetic studies demonstrating a reduction in drug concentrations. However, there is relatively limited (and sometimes inconsistent) information regarding the clinical impact of these pharmacokinetic changes during pregnancy and the effect of subsequent dose adjustments. Examples of using pregnancy PBPK models to predict feto-maternal drug exposures and their applications to facilitate and guide dose assessment throughout gestation are discussed

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials

Background Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX). Methods In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung–Knapp–Sidik–Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care