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

Early switching of tenofovir disoproxil fumarate (TDF) in HIV-infected patients with TDF-induced nephrotoxicity: a prospective study

Background: Tenofovir disoproxil fumarate (TDF) can induce proximal renal tubulopathy (PRT) and necessitate changes in treatment regimen. This prospective study aimed to compare tubular function recovery following early switching versus late switching of TDF in human immunodeficiency virus (HIV)-infected patients with TDF-induced PRT. Methods: For this prospective study, conducted during 2017–2019, we enrolled HIV-1-infected, virologically suppressed adults undergoing TDF-containing combination antiretroviral therapy. Patients were separated into a late-switching group (LSG) and an early-switching group (ESG). The LSG included patients having an estimated glomerular filtration rate (eGFR) decrease ≥25% from the pretreatment level or Fanconi syndrome. The ESG included patients having ≥2 of the following indicators of PRT: fractional excretion of phosphate (FEUP) ≥10%, low tubular maximum reabsorption of phosphate (TmP)/GFR, or uricosuria; fractional uric acid excretion ≥10%; urine protein–creatinine index (UPCI) ≥500 mg/g creatinine, normoglycemic glycosuria, or decrease in eGFR of 15%–24%. Recovery of proximal tubular function at 6 and 12 months after TDF discontinuation was assessed. Complete recovery was defined as normalization of all abnormal tubular markers. Results: Thirty-three HIV-infected patients were enrolled (70% male). Except for tubular function markers, baseline characteristics were not significantly different between the two groups. The proportion of patients having complete recovery was significantly higher in the ESG (p = 0.007, log-rank test). FEUP improved significantly in the ESG after TDF discontinuation; improvements of eGFR and UPCI were greater in the LSG. An eGFR change of 10% from baseline was the only independent predictor of failure to achieve complete recovery after switching. After median follow-up of 2.25 years post-trial, sustained recovery of eGFR within 5% of pre-TDF eGFR was achieved only in the ESG. Conclusions: Early-switching of TDF in HIV patients with PRT may allow complete recovery of proximal renal tubular function

Telepharmacy during home isolation: drug-related problems and pharmaceutical care in COVID-19 patients receiving antiviral therapy in Thailand

Abstract Background Home isolation has been proposed for coronavirus disease 2019 (COVID-19) patients with mild symptoms to avoid hospital overcrowding. This study aimed to describe the drug-related problems (DRPs) and the pharmaceutical care of home-isolating COVID-19 patients in Thailand. Methods Our cross-sectional study was undertaken from July 1 to September 30, 2021, at the King Chulalongkorn Memorial Hospital, Thailand. Patients who were ≥ 18 years old, were diagnosed with mild COVID-19 by real-time polymerase chain reaction (RT-PCR), and were able to isolate at home while receiving an antiviral agent and standard symptomatic treatment were enrolled. Infectious disease pharmacists provided a telepharmacy service on days 1 and 3 after the COVID-19 diagnosis. Results A total of 197 patients met the study criteria. Their median age was 45 years, and their most common underlying disease was hypertension (44.29%). All patients exhibited excellent anti-COVID-19 drug adherence. We identified 125 DRPs, including adverse reactions (68%), and the unnecessary use of products (62.40%). Moreover, 91 patients (46.19%) reported the use of supplements or herbs, with vitamin C being the main supplement (37.36%). Pharmacists provided 36 recommendations and received 33 questions from COVID-19 patients. Conclusions Our study demonstrates that telepharmacy is an essential service for detecting and preventing DRPs in home-isolating COVID-19 patients

Long-term immunogenicity in previously vaccinated healthcare workers with inactivated virus vaccine after SARS-CoV-2 infection or booster vaccination

Immunity against SARS-CoV-2 infection in vaccinated individuals varies based on the vaccine type, duration after vaccination or infection, and SARS-CoV-2 variant type. We conducted a prospective observational study to evaluate the immunogenicity of a booster vaccination with AZD1222 after two doses of CoronaVac (booster group) compared to individuals who had SARS-CoV-2 infection after receiving two doses of CoronaVac (infection group). We used a surrogate virus neutralization test (sVNT) to evaluate immunity against wild-type and Omicron variant (BA.1) at 3 and 6 months after infection or booster dose. Of the 89 participants, 41 were in the infection group, and 48 were in the booster group. At 3 months post-infection or booster vaccination, the median (IQR) sVNT against wild-type was 97.87 % (97.57–97.93 %) and 97.65 % (95.38–98.00 %), p = 0.66, respectively, while the sVNT against Omicron was 18.8 % (0–47.10 %) and 24.46 (11.69–35.47 %), p = 0.72 respectively. At 6 months, the median (IQR) sVNT against wild-type was 97.68 % (95.86–97.92 %) in the infection group, higher than 94.7 % (95.38–98.00 %) in the booster group (p = 0.03). Results showed no significant difference in immunity against wild-type and Omicron at 3 months between the two groups. However, the infection group exhibited better immunity than the booster group at 6 months