In September 2015, the World Health Organization (WHO) launched evidence-based guidelines by recommending that any person at substantial HIV risk should be offered oral pre-exposure prophylaxis (PrEP) containing tenofovir disoproxil fumarate (TDF) as an additional prevention choice. Since 2017, PrEP medicines have also been listed in the WHO's Essential Medicines List, including TDF/emtricitabine (FTC) and TDF in combination with lamivudine (3TC). A descriptive policy review and analysis of countries adopting WHO's 2015 recommendation on oral PrEP was conducted. As of June 2018, we identified 35 countries that had some type of policy on oral PrEP, and an additional five countries where a specific policy on PrEP is currently pending. A total of 19 high-income countries (HICs) and 21 low- and middle-income countries (LMICs) have adopted or have a pending policy. Most countries that have adopted or pending PrEP are in the European (42.9%) or African (30.0%) region. TDF/FTC is the most commonly recommended PrEP drug in the guidelines reviewed, although seven countries, namely in sub-Saharan Africa (6/7), are also recommending the use of TDF/3TC for PrEP. In sum, by the end of 2018, at least 40 countries (20.6%) are anticipated to have adopted WHO's oral PrEP recommendation. Nonetheless, policy uptake does not reflect broader programmatic coverage of PrEP services, which remain limited across all settings, irrespective of income status. Enhancing global partnerships is needed to support and track ongoing policy adoption and to ensure that policy is translated into meaningful implementation of PrEP services.

Clinicians sometimes use switching strategies based on regimens such as RAL + ABC/3TC or RPV + ABC/3TC in order to resolve tolerability or safety issues associated with conventional recommended first-line strategies. Despite the low genetic barrier of these regimens, high safety and efficacy rates have been reported in retrospective studies.

2',3'-dideoxyguanosine (DoG) has been demonstrated to inhibit duck hepatitis B virus (DHBV) replication in vivo in a duck model of HBV infection. In the current study, the in vitro antiviral effects of DoG on human and animal hepadnaviruses were investigated. Our results showed that DoG effectively inhibited HBV, DHBV, and woodchuck hepatitis virus (WHV) replication in hepatocyte-derived cells in a dose-dependent manner, with 50% effective concentrations (EC50) of 0.3 ± 0.05, 6.82 ± 0.25, and 23.0 ± 1.5 μmol/L, respectively. Similar to other hepadnaviral DNA polymerase inhibitors, DoG did not alter the levels of intracellular viral RNA but induced the accumulation of a less-than-full-length viral RNA species, which was recently demonstrated to be generated by RNase H cleavage of pgRNA. Furthermore, using a transient transfection assay, DoG showed similar antiviral activity against HBV wild-type, 3TC-resistant rtA181V, and adefovir-resistant rtN236T mutants. Our results suggest that DoG has potential as a nucleoside analogue drug with anti-HBV activity.

No single-tablet antiretroviral (ARV) regimens (STRs) are approved for patients with human immunodeficiency virus (HIV) and end-stage renal disease (ESRD) on hemodialysis (HD). Based on known pharmacokinetic (PK) properties, abacavir (ABC)/lamivudine (3TC)/dolutegravir (DTG) STR may represent a promising option. This case series presents the safety and efficacy of ABC/3TC/DTG STR in patients with HIV and ESRD on HD. Patients were included if they were HIV-positive, maintained on intermittent HD for ESRD, switched to an ARV regimen containing ABC/3TC/DTG, and had at least one set of virologic data before and after the switch. Average age (±standard deviation) was 59 (±8) years. The majority of patients were cis-gender male and non-Hispanic Black. Only one demonstrated clinically significant resistance at baseline. All were on multiple-tablet regimens prior to the switch. Five patients (83%) achieved undetectable HIV-RNA after the switch while only four patients (46%) were undetectable immediately prior. No decline in immune function was noted. ABC/3TC/DTG STR was well tolerated. Only one patient self-reported an adverse event (nausea), which resolved without drug discontinuation. Based on these data, it appears that ABC/3TC/DTG may be a safe and effective ARV-STR option for patients with HIV and ESRD on HD. A larger trial including a PK analysis is needed to confirm these findings.

Nucleoside reverse transcriptase inhibitors (NRTI) such as zidovudine (AZT) are constituents of HIV-1 therapy and prevention of mother to child transmission. Prolonged thymidine analogues exposure has been associated with mitochondrial toxicities to heart, liver, and skeletal muscle. We hypothesized that the thymidine analogue AZT might interfere with autophagy in myocytes, a lysosomal degradation pathway implicated in regulation of mitochondrial recycling, cell survival and the pathogenesis of myodegenerative diseases. The impact of AZT and lamivudine (3TC) on C2C12 myocyte autophagy was studied using various methods based on LC3-GFP overexpression or LC3 staining in combination with western blotting, flow cytometry and confocal and electron microscopy. Lysosomal and mitochondrial functions were studied using appropriate staining for lysosomal mass, acidity, cathepsin activity as well as mitochondrial mass and membrane potential in combination with flow cytometry and confocal microscopy. AZT, but not 3TC, exerted a significant dose and time-dependent inhibitory effect on late stages of autophagosome maturation, which was reversible upon mTOR inhibition. Inhibition of late autophagy at therapeutic drug concentrations led to dysfunctional mitochondria accumulation with membrane hyperpolarization and increased ROS generation, and ultimately compromised cell viability. These AZT effects could be readily replicated by pharmacological and genetic inhibition of myocyte autophagy and most importantly rescued by pharmacological stimulation of autophago-lysosomal biogenesis. Our data suggest that the thymidine analogue AZT inhibits autophagy in myocytes, which in turn leads to accumulation of dysfunctional mitochondria with increased ROS generation and compromised cell viability. This novel mechanism could contribute to our understanding of the long-term side effects of antiviral agents.