The pharmacokinetics, pharmacodynamics, and clinical role of fixed dose combination of tenofovir disoproxil fumarate, lamivudine and reduced dose efavirenz (TLE-400) in treating HIV-1 infection

Abstract

Co-formulated fixed dose combination (FDC) of antiretroviral drugs tenofovir disoproxil fumarate, lamivudine, and reduced dose efavirenz [TDF 300 mg/3TC 300mg/EFV400 mg (TLE-400)] is a single daily tablet recently approved for the treatment of HIV-1 infection. Areas covered: An overview of the pharmacokinetics, pharmacodynamics and role of TLE-400 in the treatment of HIV-1 infection based on the publications from Medline and Pubmed as of February, 2018. Expert opinion: Although TLE-400 has not been formally evaluated in a clinical trial as a new formulation, previous studies have evaluated its components individually and in different doses as other FDCs have shown favorable efficacy and safety results to support continuing its approval and indication in the management of HIV-1 infection. Due to the lower dose of EFV, TLE-400 has a lower rate of toxicity and higher tolerability compared to its predecessor, the TLE-600, which contained a higher 600 mg dose of EFV. Given its low cost and ease of administration, TLE-400 is a promising alternative first line FDC in the management of HIV-1.

Fixed dose drug combinations – are they pharmacoeconomically sound? Findings and implications especially for lower- and middle-income countries

“…Potential advantages for FDCs compared with prescribing the components separately or where there are concerns with monotherapy alone include: (i) improved response rates where there is an inadequate response to monotherapy through for instance different mechanisms of action of the medicines in the combination, (ii) the combination of the medicines in the FDC achieves the desired effect more rapidly, (iii) the proposed FDC reduces toxicity with one medicine potentially counteracting the adverse reactions of another and (iv) the potential for combining doses that are subtherapeutic when used as monotherapy because of issues such as safety as seen for instance with combination medicines for patients infected with human immunodeficiency virus (HIV), with these benefits often translating into lower costs of care [3,15,25,[32][33][34][35][36].…”

Efficacy and safety of a single‐tablet regimen containing tenofovir disoproxil fumarate 300 mg, lamivudine 300 mg and efavirenz 400 mg as a switch strategy in virologically suppressed HIV‐1‐infected subjects on nonnucleoside reverse transcriptase inhibitor‐containing first‐line antiretroviral therapy in Pune, India

“…In the light of the data from these two trials and demonstrations of the safety and efficacy of EFV400 in pregnancy [27] and in HIV/tuberculosis coinfection [28], WHO recommended TLE400 STR as an alternate first‐line ART regimen for LMICs in July 2019 [29]. However, a clinical trial to evaluate the efficacy and safety of TLE400 STR in Indian PWH has not been conducted, despite the availability of TLE400 STR in the country since July 2017 [25,26,30,31]. This represents a major knowledge gap that needs to be addressed before the introduction of TLE400 STR in the Indian National ART Program.…”