Creation of a long-acting nanoformulated dolutegravir

Monocytes were maintained in tissue culture for greater than 3 mo in media supplemented with rCSF-1. These cultures provided susceptible target cells for isolation and propagation of virus from PBMC of HIV- infected patients. HIV isolated into monocytes readily infected other rCSF-1-treated monocytes but only inefficiently infected PHA-stimulated lymphoblasts. Similarly, laboratory HIV strains passaged in T cell lines or virus isolated from patients' leukocytes into PHA-stimulated lymphoblasts inefficiently infected rCSF-1-treated monocytes. Persistent, low-level virion production was detected in macrophage culture fluids by reverse transcriptase activity or HIV antigen capture through 6-7 wk. Marked changes in cell morphology with cell death, syncytia, and giant cell formation were observed in monocyte cultures 2 wk after infection, but at 4-6 wk, all cells appeared morphologically normal. However, the frequency of infected cells in these cultures at 6 wk was 60-90% as quantified by in situ hybridization with HIV RNA probes or by immunofluorescence with AIDS patients' sera. Ultrastructural analysis by EM also showed a high frequency of infected cells; virtually all HIV budded into and accumulated within cytoplasmic vacuoles and virus particles were only infrequently associated with the plasma membrane. Retention of virus within macrophages and the macrophage tropism of HIV variants may explain mechanisms of both virus persistence and dissemination during disease.

This meta-analysis synthesizes eighty-four observational studies, conducted across twenty countries, to determine the mean proportion of people who reported ≥90% adherence to prescribed highly active antiretroviral therapy (HAART) and to identify the factors associated with high levels of adherence. Eight electronic databases were searched to locate all relevant studies available by January 2010, which were then coded for sample characteristics and adherence levels. The average rate of reporting ≥90% adherent HAART adherence is 62%. However, this proportion varies greatly across studies. In particular, a greater proportion of individuals maintaining ≥90% adherence to HAART is more likely in studies with higher proportions of men who have sex with men (MSM) and lower proportions of injection drug users (IDU), with participants in an earlier stage of infection, and in studies conducted in countries characterized by lower Human Development Index (HDI) scores.

Various drug delivery approaches can be used to maximize therapeutic efficacy and minimize side effects, by impacting absorption, distribution, metabolism, and elimination (ADME) of a drug compound. For those drugs with poor water solubility or low permeability, techniques such as amorphous solid dispersion, liposomes, and complexations have been used to improve their oral bioavailability. Modified release (MR) formulations have been widely used to improve patient compliance, as well as to reduce side effects, especially for those drugs with short half-lives or narrow therapeutic windows. More than ten drugs using sterile long-acting release (LAR) formulations with clear clinical benefit have been successfully marketed. Furthermore, drug delivery systems have been used in delaying drug clearance processes. Additionally, modifying the in vivo drug distribution using targeted delivery systems has significantly improved oncology treatments. All the drug delivery approaches have their advantages and limitations. For both brand and generic drugs, the achievement of consistent quality and therapeutic performance using drug delivery systems can also pose serious challenges in developing a drug for the market, which requires close collaboration among industry, academia, and regulatory agencies. With the advent of personalized medicines, there will be great opportunities and challenges in utilizing drug delivery systems to provide better products and services for patients.