Combined antiretroviral treatments have significantly improved the morbidity and mortality related to HIV infection, thus transforming HIV infection into a chronic disease; however, the efficacy of antiretroviral treatments is highly dependent on the ability of infected individuals to adhere to life-long drug combination therapies. A major milestone in HIV treatment is the marketing of the long-acting intramuscular antiretroviral drugs cabotegravir and rilpivirine, allowing for infrequent drug administration, with the potential to improve adherence to therapy and treatment satisfaction. Intramuscular administration of cabotegravir and rilpivirine leads to differences in pharmacokinetics and drug-drug interaction (DDI) profiles compared with oral administration. A notable difference is the long elimination half-life with intramuscular administration, which reaches 5.6-11.5 weeks for cabotegravir and 13-28 weeks for rilpivirine, compared with 41 and 45 h, respectively, with their oral administration. Cabotegravir and rilpivirine have a low potential to cause DDIs, however these drugs can be victims of DDIs. Cabotegravir is mainly metabolized by UGT1A1, and rilpivirine is mainly metabolized by CYP3A4, therefore these agents are susceptible to DDIs with inhibitors, and particularly inducers of drug-metabolizing enzymes. Intramuscular administration of cabotegravir and rilpivirine has the advantage of eliminating DDIs occurring at the gastrointestinal level, however interactions can still occur at the hepatic level. This review provides insight on the intramuscular administration of drugs and summarizes the pharmacology of long-acting cabotegravir and rilpivirine. Particular emphasis is placed on DDI profiles after oral and intramuscular administration of these antiretroviral drugs.

Background In the Ethiopian dairy farming system, prevalence of zoonotic diseases such as bovine tuberculosis (bTB) is high in the cattle population. This, combined with some risky milk and meat consumption habits, such as raw milk and uninspected raw meat consumption, poses a considerable risk of zoonotic disease transmission. A survey was conducted to investigate milk and meat consumption patterns, and the level of exposure to urban and peri-urban dairy-keeping households for risks of zoonotic disease transmission. Methods Data on milk and meat consumption behaviours and other socioeconomic and demographic variables were collected from 480 urban and peri-urban dairy farms randomly surveyed in major towns in Ethiopia (Mekele, Hawassa, and Gondar towns, Addis Ababa city, as well as five Oromia towns around Addis Ababa). Determinants of raw milk consumption associated with a number of demographic and socio-economic factors were analysed using a generalised ordered logistic model. Results The results indicated that about 20% the population consumed raw milk and their awareness about pasteurisation and its benefits were low. Location, gender of the household head, previous bTB testing of cattle on the farm, knowledge of zoonotic risks associated with raw milk consumption, household size, and per-capita milk consumption were found to be important determinants of the frequency of raw milk consumption. About 60% of the respondents were exposed to the risk of zoonotic diseases through their habit of frequently consuming raw meat. This was despite that over 90% of the respondents were aware of possible zoonotic risks of raw meat consumption. The determinants of raw meat consumption behaviours were associated with location, gender and age of the household head, household size, meat type preference, per-capita meat consumption, knowledge about disease transmission risks, and training on zoonoses. Conclusion Creating awareness about the risk factors for zoonotic transmission of diseases through training and media campaigns, improving meat hygiene through better abattoir services, and inducing behavioural change around meat sourcing, raw meat and raw milk consumption, are all crucial to the successful prevention and control of the spread of zoonotic diseases, including bTB.

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As global health services respond to the coronavirus pandemic, many prescribers are turning to experimental drugs. This review aims to assess the risk of drug–drug interactions in the severely ill COVID-19 patient. Experimental therapies were identified by searching ClinicalTrials.gov for ‘COVID-19’, ‘2019-nCoV’, ‘2019 novel coronavirus’ and ‘SARS-CoV-2’. The last search was performed on 30 June 2020. Herbal medicines, blood-derived products and in vitro studies were excluded. We identified comorbidities by searching PubMed for the MeSH terms ‘COVID-19’, ‘Comorbidity’ and ‘Epidemiological Factors’. Potential drug–drug interactions were evaluated according to known pharmacokinetics, overlapping toxicities and QT risk. Drug–drug interactions were graded GREEN and YELLOW: no clinically significant interaction; AMBER: caution; RED: serious risk. A total of 2378 records were retrieved from ClinicalTrials.gov, which yielded 249 drugs that met inclusion criteria. Thirteen primary compounds were screened against 512 comedications. A full database of these interactions is available at www.covid19-druginteractions.org. Experimental therapies for COVID-19 present a risk of drug–drug interactions, with lopinavir/ritonavir (10% RED, 41% AMBER; mainly a perpetrator of pharmacokinetic interactions but also risk of QT prolongation particularly when given with concomitant drugs that can prolong QT), chloroquine and hydroxychloroquine (both 7% RED and 27% AMBER, victims of some interactions due to metabolic profile but also perpetrators of QT prolongation) posing the greatest risk. With management, these risks can be mitigated. We have published a drug–drug interaction resource to facilitate medication review for the critically ill patient.

In a recent issue of Br J Clin Pharmacol Smith et al1 published an outstanding commentary titled 'Dosing will be a key success factor in repurposing antivirals for Covid-19'. They highlighted that the success in our repurposing efforts will be dependent on 'getting the dose right' for drugs which have been developed for different indications and stressed some of the unique challenges of treating this particular disease. They pointed the reader to lopinavir/ritonavir (LPV/r) as an example of a repurposed antiviral and the limited experience of this drug regimen (and other treatments) in the elderly population with comorbiditiesie those most at risk from Covid-19. It is on the issue of comorbidities, polypharmacy and drug-drug interactions (DDIs) that we wish to comment.COVID-19 treatment in patients with comorbidities: Awareness of drug-drug interactions.

Within the community-orientated primary care module for training family physicians at the Kamuzu University of Health Sciences in Malawi, a relationship was formed between Nkhoma Mission Hospital’s Family Medicine Department and the Diamphwe Community Health Centre (HC) to strengthen the continuity of healthcare and capacity team building. The initial focus was on improving the management of hypertension and diabetes in terms of diagnosis, tracking of the patients in a registry and timely referral to secondary care facilities The relationship has received positive support from Diamphwe healthcare workers, which then improved the management of non-communicable diseases and patient care at Diamphwe. It has also shown how family medicine physicians can improve HC capacity through support and mentorship.

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A series of Focus Group Discussions were held with farmers, veterinarians and human health workers in two sites in Ethiopia, as part of the Ethiopia Control of Bovine Tuberculosis Strategies Project's efforts to devise and test the acceptability and feasibility of various control strategies for Bovine Tuberculosis (bTB). Group members were asked to give their responses to a range of strategies collected from global efforts to control the disease in cattle and humans in the context of intensification of the dairy industry, as well as those suggested by researchers within the project. Key findings from the study include the observation that a number of strategies utilised routinely to control bTB elsewhere in the world, including 'Test and Slaughter' and 'Test and Segregation' are likely to be impractical in low-resource settings where infrastructure may be unreliable and space both between and on individual farms is limited. It also became clear that farmers called upon to implement biosecurity measures should be supplied with locally-specific information and instructions in order to effectively control and prevent the spread of disease. Additionally, this research supports the need for investment in animal health system strengthening in Ethiopia and other similar settings, in order to enable animal health workers, including veterinarians, to devote time to disease surveillance and farmer sensitisation. Similarly, investment in milk pasteurisation processes and public education on these processes should be prioritised in order to increase their acceptability and feasibility among both producers and consumers.