The present study was conducted to describe our single-center experience of HIV-infected patients when switching from the ARVs to the fixed-dose single-tablet EVG/COBI/FTC/TAF regimen. The main reasons for switching therapy were ADRs, inconvenience, and poor therapeutic effect. After switching, the reported ADRs decreased, blood lipids levels increased, blood glucose levels decreased, and proteinuria decreased. The viral inhibition rate increased from 90% before switching to 99% after switching and patient satisfaction increased when using the single-dose combined tablet.
ART for managing HIV infection requires triple therapy, including two nucleotide reverse transcriptase inhibitors (NRTIs) and another core drug, such as a Non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor. Good adherence with the drug regimen is a crucial prerequisite for successful antiretroviral treatment, and adherence is significantly influenced by the pill burden. Single-tablet regimens contain multiple antiretroviral drugs with different mechanisms of action. Such combined pills reduce the pill burden, improving drug adherence and quality of life. Moreover, as more single-tablet regimens are being covered by the National Medical Insurance of China, patient acceptance of these regimens has gradually increased due to significant price reductions, which has also improved adherence to therapeutic protocols.
Integrase inhibitors such as elvitegravir have revealed their potential for viral inhibition in pre-market clinical trials, with increased short- and long-term drug safety and tolerance. They are, thus, recommended by major public health agencies as first-line therapeutic options [5, 12–20]. However, since participants in clinical trials are selected based on strict inclusion and exclusion criteria, the results obtained from these clinical trials cannot fully represent the general population of potential patients. The present study was based on the clinical data of patients switching from drugs recommended by the National Free Antiretroviral Treatment Program to fixed-dose single-tablet EVG/COBI/FTC/TAF therapy, and results from the present study provides clinicians with useful information with respect to the efficacy and safety of a specific fixed-dose single-tablet ART regimen to treat HIV infection.
TDF + 3TC + EFV and AZT/3TC + EFV are the first-line drugs used in the National Free Antiretroviral Treatment Program, and their efficacy have been established by past clinical studies. However, they also have many adverse effects [21, 22]. Side effects of these regimens include neurological abnormalities, gastrointestinal reactions, skin rash, liver function aberrations, and untoward changes to renal function [21, 22]. These adverse effects may be the main reason causing patients to switch to a single-tablet regimen. In addition, the significant reduction in pill burden is another important reason for switching.
The present study showed that after 6 months of treatment, EVG/COBI/FTC/TAF as a single-tablet regimen showed a 99% (99/100) viral suppression rate in a real-world setting, which is significantly higher viral suppression rate than before switching. Nevertheless, there is a paucity of studies on combined EVG/COBI/FTC/TAF treatment regimens in China. In one previous study, other treatment regimens (such as LPV/r-based and EFV-based regimens) achieved 93.8% and 87.8% viral suppression (HIV RNA level of < 40 RNA copies/mL), respectively, at 6 months in previously untreated Chinese patients [23]. In addition to the specific clinical and therapeutic reasons for the different regimens used, different study populations and different definitions of viral suppression also might contribute to observed differences in results.
In this study, no significant decline in liver and renal function was found in patients treated with EVG/COBI/FTC/TAF, suggesting the superior tolerance of EVG/COBI/FTC/TAF in a real-world setting. The present study observed no significant uric acid changes after switching from ART drugs used in the National Free Antiretroviral Treatment Program to EVG/COBI/FTC/TAF therapy. In the single-dose regimen, TAF is a tenofovir prodrug that can effectively reduce the circulating plasma concentration of tenofovir, resulting in fewer off-target adverse effects, such as proximal tubulopathy and Fanconi syndrome [24].
In a phase III clinical study of EVG/COBI/FTC/TAF use in ART naïve patients, blood lipid levels were increased significantly, mainly in the first year, and there were no significant continuous increases in lipid levels in the second and third years of treatment [25]. Increased blood lipids were also observed in one retrospective study [26]. The increased blood lipids observed in previous studies are consistent with the results of the present study.
Fasting glucose concentrations have been observed to be higher among PLWH [27], and this may be attributable to several factors. One study found that abnormally elevated levels of blood glucose were significantly decreased after the switch of the therapy, which may have been related to the long-term use of TDF in 205 of 246 patients before the switch [28]. Even in the absence of protease inhibitor treatment, HIV may directly influence the function of pancreatic beta cells and insulin secretion, which may induce insulin resistance [29, 30]. Polsky et al., have observed that HIV infection and antiretroviral treatment increased the risk of hyperglycemia, regardless of the treatment used [31]. The present study found that blood glucose concentrations were decreased at 24 weeks after switching to EVG/COBI/FTC/TAF, suggesting the enhanced benefit of this treatment regimen for PLWH.
Our study observed that the main ADRs before switching were nervous system-related ADRs including dizziness (43.3%) and excessive dreams (21.2%), possibly associated with EFV use. The incidence of neurological adverse effects was significantly reduced after switching to EVG/COBI/FTC/TAF. One 48-week phase III clinical trial observed that patients treated with the EVG/COBI/FTC/TDF regimen experience less dizziness compared to those receiving EFV/FTC/TDF [32]. As FTC and 3TC may be considered to be therapeutically interchangeable [33], switching to EVG/COBI/FTC/TAF might contribute to the reduced incidence of ADRs. The HIV-TSQ showed that patient satisfaction increased significantly after the switch to EVG/COBI/FTC/TAF because of the reduced ADRs and pill burden.
This study had limitations. This was a single center study, and the sample size was relatively small. In addition, patients were followed-up for 24 weeks only, which is a relatively short period, considering that these patients will have to take lifelong ART. Due to the COVID-19 epidemic, participants had only one efficacy follow-up at 24 weeks. The requisition of immune function laboratory indices in the study was low, and the self-control analysis could not be performed, which may have led to a degree of measurement bias.