Single-Tablet Regimens in the Treatment of HIV-1 Infection
Finally, at the population level, the potential benefits of STRs must be balanced with the increased costs compared with that of generic ART regimens with multiple pills. For example, a mathematical simulation model based on 2009 U.S. data suggested that switching all patients in the U.S. from the branded STR EFV/TDF/FTC to a triple regimen of generic EFV, 3TC, and branded TDF would have saved almost $1 billion per year with only a small decrement in virologic efficacy.53 More costeffectiveness analyses are needed, especially for the developing world, to inform strategies for the use of STRs to improve outcomes in the most costeffective way globally.
When to Use STRS?
For initial ART in treatment-naïve patients, 3 of the available STRs are listed as recommended regimens by the HHS guidelines: EVG/c/TDF/FTC, DTG/ABC/3TC, or EVG/c/TAF/FTC.7 In choosing an initial regimen, a number of factors must be considered, including baseline HIV-1 resistance, drug-drug interactions, medical comorbidities, food restrictions, patient preference and convenience, and cost. Patients with drug-resistant HIV-1 or significant renal impairment are less ideal candidates for STRs for initial therapy. Otherwise, the determination typically depends on which of the NRTI backbone drugs, TDF or TAF vs ABC, is most appropriate. Clinicians may favor TDF-containing or TAFcontaining regimens in patients with HBV coinfection, clinically significant CV disease, or patients with the HLA-B*5701 genetic polymorphism.
Conversely, clinicians may favor ABC-containing or TAF-containing regimens in patients at high risk or with preexisting metabolic bone disease or more mild renal impairment. Drug-drug and drug-supplement interactions must be carefully considered in all cases. Although listed as alternative regimens, the other available STRs—EFV/TDF/FTC or RPV/TDF/FTC—may still be the preferred regimen in select individual patients.
In patients already on ART, a switch to a STR may be considered in the following scenarios, with the caveat that most of the clinical trials evaluating switch therapy have been in patients who were virologically suppressed for 6 months on their prior regimens:
- Improve tolerability. In the STRATEGY-NNRTI trial, patients on a stable EFV-containing regimen experienced significant improvements in neuropsychiatric AEs after switching to EVG/c/TDF/FTC.35
- Virologically suppressed patients with multiple comorbidities. Difficulty managing dyslipidemia or high CV risk might necessitate a switch from a PI-containing regimen. From the results of the SPIRIT trial54 and the STRATEGY-PI trial,34 these patients could be switched safely to RPV/TDF/FTC or EVG/c/TDF/FTC, respectively.
- Management of virologic failure. This may be beneficial provided that drug resistance has not compromised the components of the regimen.
Conclusion
The potency and once-daily dosing of EFV-based regimens ushered in the era of STRs. The list of STRs has now expanded with the introduction of an RPV-based STR and, lately, 3 different INSTI-based STRs. In the current HHS guidelines, only the INSTI-based STRs are included in the recommended list, mostly because of poor tolerability of EFV/TDF/FTC and lower efficacy of RPV/TDF/FTC in patients with high baseline viremia. In general, the safety profile of STRs has been improving with newer iterations. Their main advantages are convenience, simplicity and improvements in adherence, and possibly reductions in medication errors. Due to these advantages, the percentage of patients on STRs is likely to continue rising. Further expansions of the ART armamentarium may include the development of boosted PI-based STRs as well as novel delivery strategies, such as long-acting injectable regimens.55 In the meantime, clinicians should develop a greater familiarity with the use of the currently available STRs.
