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

Abstract

Objectives As per National AIDS Control Organization (NACO) estimates, there are 2.1 million people living with HIV (PWH) in India, of whom 1.2 million are on first‐line antiretroviral therapy (ART). This study explored the use of a single‐tablet regimen containing tenofovir disoproxil fumarate 300 mg + lamivudine 300 mg + efavirenz 400 mg (TLE400 STR) as a first‐line switch strategy in PWH in Pune, India. Methods This retrospective cohort study was conducted in private sector ART clinics in three tertiary‐level hospitals in Pune, India. PWH > 12 years of age (n = 502) who initiated first‐line ART (predominantly TLE600 STR), completed ≥ 6 months of follow‐up and achieved virological suppression [plasma viral load (VL) < 1000 HIV‐1 RNA copies/mL] were identified and switched to TLE400 STR. The virological and immunological efficacy of TLE400 STR at 6 and 12 months of follow‐up were noted. Grade 3/4 adverse events (especially efavirenz‐related neuropsychiatric adverse events) leading to regimen discontinuation were also noted. Results Of 502 PWH who switched to TLE400 STR, complete virological suppression (VL < 20 copies/mL) was maintained in more than 97% of patients at follow‐up. TLE400 STR was successful in maintaining CD4 counts within the range observed at the start of the regimen. Grade 3/4 adverse events leading to TLE400 STR discontinuation were seen in 11 (2.2%) patients. Virological failure (VL > 1000 copies/mL) and treatment regimen failure were seen in six (1.2%) and 49 (9.8%) subjects, respectively. Conclusions TLE400 STR exhibits excellent efficacy and safety as a switch strategy and should be introduced in the Indian National ART Program, especially for PWH who are virologically suppressed on TLE600 STR.

Efficacy and safety of 400 mg efavirenz versus standard 600 mg dose when taken with tenofovir and lamivudine combination in Indian adult patients with HIV-1 infection: An open-label, interventional, randomized, non-inferiority trial

“…A recent study conducted in Pune, India to explore the combination of TLE 400 single dose regimen as a first line switch strategy found that TLE 400 exhibits good efficacy and safety specially for patients who are virologically suppressed on TLE 600. [21] The current study further supports the effectiveness of TLE 400 compared to TLE 600.…”

“…These findings were in accordance with the previously reported non-inferiority clinical trials. [17,21–23]…”

“…These findings were in accordance with the previously reported non-inferiority clinical trials. [17,[21][22][23] The limitation of the study is it's an open label study with both the investigator and the patient being aware of the treatment received. However, this was overcome by using laboratory parameter as the primary efficacy endpoint and the clinical laboratory was blinded to the treatment assigned.…”

Safety of low dose efavirenz regimen in Indian adults with HIV-1 infection: Insights from a phase 4 interventional randomised trial

“…Similar trends were seen in ENCORE1 trial and other published studies evaluating the safety of lower dose efavirenz. [ 16 , 20 , 23 ] In the ENCORE1 trial, reduced drug-related discontinuations were reported in the efavirenz 400 mg group as compared to 600 mg group (6 patients, 2% to 18 patients, 6%). [ 16 ] An Indian study comparing TLE600 and TLE400 as switch strategy also reported that only 11 patients (2.2%) patients discontinued the TLE400 regimen group.…”

“…[ 16 ] An Indian study comparing TLE600 and TLE400 as switch strategy also reported that only 11 patients (2.2%) patients discontinued the TLE400 regimen group. [ 23 ] Another study conducted in the Netherlands evaluated the relationship between dose reduction of efavirenz and discontinuations indicating a positive correlation wherein dose reduction prevents toxicity-induced discontinuations in patients with high efavirenz plasma concentrations without reducing the virological efficacy. [ 24 ] The CNS symptoms and psychiatric adverse effects affect almost half of the individuals taking EFV and can often impede adherence and lead to treatment discontinuation.…”