Sustained HIV viral suppression with dolutegravir, tenofovir, and emtricitabine as initial therapy despite high-level transmitted multi-class resistance

Multi-class high-level transmitted HIV drug resistance is uncommon, and the selection of the optimal initial antiretroviral drug regimen may be challenging. We report a case of extensive transmitted multi-class resistance successfully treated with dolutegravir, tenofovir, and emtricitabine even though the baseline genotype demonstrated full susceptibility to only one drug class, the integrase strand transfer inhibitors. Our case highlights both the high resistance barrier of dolutegravir and the residual antiviral activity of nucleoside reverse transcriptase inhibitors despite extensive resistance on genotype.

Modern Solutions in the Treatment of HIV: From Antiretroviral Drug Therapy to Human Genome Editing

The human immunodeficiency virus (HIV) belongs to a group of anthroponotic viral diseases that cause HIV infection in the human body, apotheosely transforming into acquired immunodeficiency syndrome (AIDS). HIV infection, in people without adequate treatment, can lead to serious damage to the immune system (hereinafter referred to as IS), which leads to a sharp decrease in resistance to conditionally pathogenic microbes, as well as to the prevalence of oncological pathologies that may lead to death. Due to its simplicity, convenience, efficiency and cost-effectiveness, CRISPR/Cas has found application in a short period of time in a wide variety of fields of fundamental and applied medicine and biotechnology.

Facilitating primary care non-antiretroviral drug prescribing in people living with HIV: The ‘THINK ARV’ initiative

Objectives: Older people living with HIV (PLWH) have higher rates of multimorbidity, polypharmacy and an associated increased risk of potential drug–drug interactions (DDIs). We describe the development, implementation and evaluation of an intervention to increase community prescribers’ access to specialist prescribing advice. Methods: Phase One: a survey evaluating General Practitioners’ (GPs’) knowledge of, and confidence detecting DDIs affecting PLWH, was circulated to eight General Practices in one UK city. Phase Two: co-production was used to develop the THINK ARV intervention for prescribers in city-wide General Practices: a dedicated mobile phone and e-mail advice service staffed by HIV specialist pharmacists. Queries were audited for 6 months pre- and post-intervention. A user-satisfaction survey was emailed to enquirers. Results: Phase One: 42 GPs responded, of whom 62% requested further support identifying DDIs among PLWH. Phase Two: the number of queries received increased from 25 (6 months before ‘THINK ARV’ launch) to 63 in the following 6 months (152% increase). 94% of the queries were specifically about DDIs. Conclusions: Increasing community prescribers’ access to specialist telephone and e-mail advice resulted in increased awareness and detection of DDIs. Similar interventions could be embedded within different healthcare settings to optimise medicines and avoid potential patient harm.

Antiviral and antiretroviral drug shortages amidst COVID-19: How Africa is struggling

Antiviral drugs are of paramount importance in the accomplishment of the vision of zero new cases of COVID-19 globally, through sustainable retaliation against viral diseases. However, several challenges currently exist in Africa which include insufficient infrastructure, deteriorating health systems, and rising costs of healthcare delivery with concomitant rising inequity with regards to access to health services amid the COVID-19 pandemic. The pandemic itself has stimulated an increased use of phytotherapy in Africa as a result of essential drug shortages that have been attributed to a plethora of contributing factors such as travel restrictions, reduced per capita income as well as increased expenditure on transport. As a result, the paucity of antiviral along with antiretroviral drugs used to combat COVID-19 as well as several other endemic viral diseases in Africa has created a worrisome state. This article therefore discusses and aims to underscore the causes, effects, and implications of antiviral and antiretroviral shortages amid COVID-19 in Africa.

Evidence that C/EBP-β LAP Increases Fat Metabolism and Protects Against Diet-Induced Obesity in Response to mTOR Inhibition

Aging and obesity are common risk factors for numerous chronic pathologies, and the compounding effects of old age and increased adiposity pose a serious threat to public health. Starting from the assumption that aging and obesity may have shared underpinnings, we investigated the antiobesogenic potential of a successful longevity intervention, the mTORC1 inhibitor rapamycin. We find that rapamycin prevents diet-induced obesity in mice and increases the activity of C/EBP-β LAP, a transcription factor that regulates the metabolic shift to lipid catabolism observed in response to calorie restriction. Independent activation of C/EBP-β LAP with the antiretroviral drug adefovir dipivoxil recapitulates the anti-obesogenic effects of rapamycin without reducing signaling through mTORC1 and increases markers of fat catabolism in the liver. Our findings support a model that C/EBP-β LAP acts downstream of mTORC1 signaling to regulate fat metabolism and identifies a novel drug that may be exploited to treat obesity and decrease the incidence of age-related disease.

Seasonal Variation of Antiretroviral Drug Exposure during the Year: The Experience of 10 Years of Therapeutic Drug Monitoring

Although studies show an annual trend for immunosuppressive drugs, particularly during different seasons, no data are available for antiretroviral drugs exposures in different periods of the year. For this reason, the aim of this study was to investigate an association between seasonality and antiretroviral drugs plasma concentrations. Antiretroviral drugs exposures were measured with liquid chromatography validated methods. A total of 4148 human samples were analysed. Lopinavir, etravirine and maraviroc levels showed seasonal fluctuation. In detail, maraviroc and etravirine concentrations decreased further in summer than in winter. In contrast, lopinavir concentrations had an opposite trend, increasing more in summer than in winter. The etravirine efficacy cut-off value of 300 ng/mL seems to be affected by seasonality: 77.1% and 22.9% of samples achieved this therapeutic target, respectively, in winter and summer, whereas 30% in winter and 70% in summer did not reach this value. Finally, age over 50 years and summer remained in the final multivariate regression model as predictors of the etravirine efficacy cut-off. This study highlights the seasonal variation in antiretroviral drugs plasma concentrations during the year, leading to a better understanding of inter-individual variability in drug exposures. Studies are required in order to confirm these data, clarifying which aspects may be involved.

Acute myocardial infarction associated with abacavir and tenofovir based antiretroviral drug combinations in the United States

Introduction Although individual antiretroviral drugs have been shown to be associated with elevated cardiovascular disease (CVD) risk, data are limited on the role of antiretroviral drug combinations. Therefore, we sought to investigate CVD risk associated with antiretroviral drug combinations. Methods Using an administrative health-plan dataset, risk of acute myocardial infarction (AMI) associated with current exposure to antiretroviral drug combinations was assessed among persons living with HIV receiving antiretroviral therapy (ART) across the U.S. from October 2009 through December 2014. To account for confounding-by-indication and for factors simultaneously acting as causal mediators and confounders, we applied inverse probability of treatment weighted marginal structural models to longitudinal data of patients. Results Over 114,417 person-years (n = 73,071 persons) of ART exposure, 602 cases of AMI occurred at an event rate of 5.26 (95% CI: 4.86, 5.70)/1000 person-years. Of the 14 antiretroviral drug combinations studied, persons taking abacavir-lamivudine-darunavir had the highest incidence rate (IR: 11/1000; 95% CI: 7.4–16.0) of AMI. Risk (HR; 95% CI) of AMI was elevated for current exposure to abacavir-lamivudine-darunavir (1.91; 1.27–2.88), abacavir-lamivudine-atazanavir (1.58; 1.08–2.31), and tenofovir-emtricitabine-raltegravir (1.35; 1.07–1.71). Tenofovir-emtricitabine-efavirenz was associated with reduced risk (0.65; 0.54–0.78). Abacavir-lamivudine-darunavir was associated with increased risk of AMI beyond that expected of abacavir alone, likely attributable to darunavir co-administration. We did not find an elevated risk of AMI when abacavir-lamivudine was combined with efavirenz or raltegravir. Conclusion The antiretroviral drug combinations abacavir-lamivudine-darunavir, abacavir-lamivudine-atazanavir and tenofovir-emtricitabine-raltegravir were found to be associated with elevated risk of AMI, while tenofovir-emtricitabine-efavirenz was associated with a lower risk. The AMI risk associated with abacavir-lamivudine-darunavir was greater than what was previously described for abacavir, which could suggest an added risk from darunavir. The results should be confirmed in additional studies.

Evaluation of Anti-Retroviral Drugs Effects on Liver Function Tests of HIV Infected Individuals

The Human Immunodeficiency Virus (HIV) continues to be a major global public health issue, having claimed more than 35 million lives so far. Antiretroviral therapy, the drug used to treat HIV patients, had been reported to have an adverse effect on patients’ livers. Therefore, this research aims to assess the parameters for measuring liver injury of HIV patients undergoing antiretroviral therapy in Owo and to determine the patients' vulnerability to liver injury. The study sample was divided into five groups comprising Control groups and groups with 6 months, 1 year, 3 years and 5 years’ periods of administration of an antiretroviral drug. Serum was separated from their blood and values of ALT, ALP and BILT were determined. The results of profiling the patients based on values ALT, ALP and BILT indicated that 73%, 71% and 59% of the patients are within the reference range of the parameters, respectively. Further analysis of the percentage of patients likely to have liver diseases indicated that only 3.2% are prone to liver injury. The results of the One-way Analysis of Variance of the mean values of the groups on ALT, ALP and BILT indicated differences in mean values of the groups. It is suggested that a longitudinal study should be carried out to determine the effect of seasonal variation in the value of the studied parameters. It is also suggested that a wider interval of the period for the groups should be used in the future to determine whether there will be a relationship between the period of administration of the drug and the parameters.