Rationale and clinical utility of the darunavir–cobicistat combination in the treatment of HIV/AIDS

Opass Putcharoen,1 Tanya Do,2 Anchalee Avihingsanon,2 Kiat Ruxrungtham1,2 1Department of Medicine, Faculty of Medicine, Chulalongkorn University, 2The HIV Netherlands Australia Thailand (HIV-NAT) Research Collaboration, The Thai Red Cross AIDS Research Center, Bangkok, Thailand Abstract: This article is to provide an update overview of cobicistat (COBI)-boosted darunavir in response to its recent approval by the US Food and Drug Administration, and inclusion as an alternative first-line regime in the 2015 treatment guidelines in the US. COBI is a relatively new non-antiretroviral cytochrome P450 3A inhibitor or pharmacoenhancer. The rationale behind COBI development was to provide an alternative to ritonavir (RTV) as a protease inhibitor pharmacoenhancer, due to associated adverse events with short- and long-term RTV use, such as gastrointestinal intolerability, drug–drug interactions, insulin resistance, lipodystrophy, and hyperlipidemia. Although in vitro studies suggest that COBI may result in a lower incidence of undesired drug–drug interactions and lipid-associated disorders than RTV, not all Phase III studies have well addressed these issues, and the data are limited. However, Phase III studies have demonstrated tolerability, noninferiority, and bioequivalence of COBI compared to RTV. Two main advantages of COBI over RTV-containing regimes have been noted as follows: 1) COBI has no anti-HIV activity; therefore, resistance to COBI as a booster in addition to protease inhibitor resistance is of little concern, allowing for COBI-containing regimes in future. 2) COBI’s solubility and dissolution rate allow for co-formulated/fixed-dose combination products. Nonetheless, prior to initiating COBI-containing treatment regimens, the following should be considered: 1) COBI may increase serum creatinine levels and reduce estimated glomerular filtration rate (GFR) without affecting actual GFR; 2) potential drug–drug interaction data are insufficient, warranting caution when initiating COBI in conjunction with concomitant medication or in individuals with multiple comorbidities; 3) food plays a pivotal role in boosting darunavir exposure, warranting caution and patient education on the importance of taking COBI-containing regimens with appropriate amounts of food; and 4) data on the success of COBI-containing regimens in treatment-experienced patients are limited. Keywords: first-line regime, pharmacoenhancer, adverse events, ritonavir, drug–drug interactions, tolerability&nbsp

A qualitative assessment of barriers and facilitators to antiretroviral adherence in Thai patients.

OBJECTIVES: Excellent adherence to combination antiretroviral therapy can suppress HIV replication and produce life expectancies nearing those of individuals without HIV infection. This qualitative study sought to identify the barriers and facilitators to good antiretroviral medication adherence in Thai patients living with HIV. METHODS: Semi-structured interviews were conducted with a convenience sample (n=21) of patients attending routine clinic visits at Srinagarind Hospital in Khon Kaen, or HIV-NAT, the Thai Red Cross AIDS Research Centre in Bangkok. RESULTS: Median informant age was 43 years (range 27-60 years) and 43% were female. We identified key facilitators and barriers to adherence among HIV-infected Thai patients along three major themes (patient-related, health system-related and medication-related). Stigma was a primary concern for most informants, operating throughout Thai society to induce feelings of shame for Thai people living with HIV. Determination to stay healthy and incorporate taking cART into their daily routine were key components of good adherence. Supportive and trusting relationships, particularly with the clinic team, empowered patients to maintain good medication adherence. CONCLUSIONS: Changing public perceptions about HIV, and training of HIV clinic staff on the importance of trusting and supportive provider-patient relationships in promoting good health outcomes, will help Thailand achieve its aim of having zero new HIV infections, zero discrimination and zero AIDS-related deaths by 2030

Investigational protease inhibitors as antiretroviral therapies

INTRODUCTION: Highly Active Antiretroviral Therapy (HAART) has tremendously improved the life expectancy of the HIV-infected population over the past three decades. Protease inhibitors have been one of the major classes of drugs in HAART regimens that are effective in treating HIV. However, the emergence of resistance and cross-resistance against protease inhibitors encourages researchers to develop new PIs with broad-spectrum activity, as well as novel means of enhancing the efficacy of existing PIs. AREAS COVERED: In this article we discuss recent advances in HIV protease inhibitor (PI) development, focusing on both investigational and experimental agents. We also include a section on pharmacokinetic booster drugs for improved bioavailability of protease inhibitors. Further, we discuss novel drug delivery systems using a variety of nanocarriers for the delivery of PIs across the blood-brain barrier to treat the HIV in the brain. EXPERT OPINION: We discuss our opinion on the promises and challenges on the development of novel investigational and experimental PIs that are less toxic and more effective in combating drug-resistance. Further, we discuss the future of novel nanocarriers that have been developed to deliver PIs to the brain cells. Although these are promising findings, many challenges need to be overcome prior to making them a viable option

Rapid design and fielding of four diagnostic technologies in Sierra Leone, Thailand, Peru, and Australia: Successes and challenges faced introducing these biosensors

Febrile illnesses are among the most common reasons for visits to hospitals and clinics worldwide. Since fevers can arise from a wide range of diseases, identifying the causative pathogen is essential not only for effective personal treatment but also for early detection of outbreaks. The Defense Threat Reduction Agency (DTRA) tasked a coalition of commercial, academic, and government researchers with moving diagnostic technology concepts from ideation to field use as rapidly as possible using scientifically sound evaluations. DTRA's 24 Month Challenge program examined >30 technologies before fielding four technologies on four continents. >10,000 in field test results were recorded. Here we discuss our tiered evaluation system to assess candidate technologies developed by commercial partners and the process of field testing those technologies at various front-line clinics in Sierra Leone, Thailand, Peru, and Australia. We discuss successes and challenges for introducing two multiplexed lateral flow immunoassay (LFI) tests that detect malaria, dengue fever, melioidosis, and the plague. Additionally we discuss the use of a LFI reader that assisted the interpretation of the assay, communicated results to a data cloud, and greatly facilitated reach-back support. Lastly, we discuss the concurrent field testing of a multiplexed PCR assay on the FilmArray platform, which had an assay pouch specially designed for the 24 Month Challenge. Either standard-of-care or gold-standard testing were run alongside our fielded technologies to benchmark their performance