Virologic Efficacy of Recycling Tenofovir and Lamivudine/Emtricitabine in Second-Line Antiretroviral Treatment with Dolutegravir: A Non-Inferiority-Matched Cohort Study in Senegal

Background: The World Health Organization (WHO) now recommends dolutegravir (DTG)-based regimens as the preferred option for first-line and second-line antiretroviral therapy (ART) for all people living with HIV (pwHIV). However, exposure to tenofovir (TDF) in first-line antiretroviral therapy (ART) could compromise its efficacy (K65r mutation). Our study aimed to assess whether recycling TDF and lamivudine or emtricitabine (XTC) with DTG as second line ART is non-inferior to optimized nucleotide reverse transcriptase inhibitor (NRTI)-based regimens. Methods: This multicenter noninferiority-matched cohort study included pwHIV (> 18 years) who switched to second-line ART between october 2013-october 2023 in six HIV clinics in Senegal. The test group consisted of pwHIV on TDF + XTC +DTG with ≥ 2 years of TDF exposure in the first-line regimen, while those receiving other second-line ART with no history of prior TDF exposure composed the control group. We used propensity score matching analysis to balance the two groups. The primary outcome was viral load (VL) suppression (VL < 400 copies/mL) at week 48. Noninferiority was considered when the lower limit of the one-sided 95% confidence interval (95% CI) of the difference in VL suppression rates between groups was > -12%. Results: Overall, 254 out of 907 pwHIV who were switched to second-line ART during our study period, were included in the matching process. Ultimately, 126 participants (63 pairs) were enrolled with optimal standard mean differences (SMDs). Of the 126 participants included, 86 (68.3%) were female, and the median age was 38 years (interquartile range [IQR]: 27-46 years). Seventy-two (64.3%) participants had a CD4 count < 200 cells/mm3, and 33 (26.2%) were classified as WHO stage 4. At the week 48, 58 pwHIV in the test group (92.1%) and 51 in the test group (81.0%) had VL < 400 copies (difference: 11.10% 95% CI [1.23-20.97]), which met the noninferiority criterion. Conclusions: DTG-based regimen with recycled TDF was noninferior to alternative second-line regimens at the 48-week endpoint. However, further studies are needed to evaluate its efficacy over extended periods.