48-Week effectiveness and tolerability of dolutegravir (DTG) + lamivudine (3TC) in antiretroviral-naïve adults living with HIV: A multicenter real-life cohort

Abstract

Background The main international guidelines indicate DTG/3TC therapy as one of the preferred regimens for people living with HIV (PLWH), due to its observed efficacy in randomized clinical trials. However, information in real-life cohorts is relatively scarce for first-line use. Methods A retrospective multicenter study of adult PLWH starting DTG+3TC as a first-line regimen before January 31st, 2020. Virological failure (VF) was defined as 2 consecutive HIV RNA viral load (VL) >50 copies/mL. Results 135 participants were included. Treatment was started without knowing baseline drug resistance testing (bDRT) results in 71.9% of cases, with baseline resistance mutations being later confirmed in 17 patients (12.6%), two of them with presence of M184V mutation. Effectiveness at week 48 was 85.2% (CI95%: 78.1–90.7%) (ITT missing = failure [M = F]) and 96.6% (CI 95%: 91.6–99.1%) (per-protocol analysis). Six patients (4.4%) discontinued treatment. One developed not confirmed VF after discontinuing treatment due to poor adherence; no resistance-associated mutations emerged. Three discontinued treatments due to central nervous system side effects (2.2%), and two due to a medical decision after determining the M184V mutation in bDRT. Finally, 14 (10.4%) were lost to follow-up, most of them due to the COVID-19 pandemic. Conclusions In a real-life multicenter cohort of ART-naïve PLWH, treatment initiation with DTG + 3TC showed high effectiveness and favorable safety results, comparable to those of randomized clinical trials, without treatment-emergent resistance being observed through week 48. Starting treatment before receiving the results of baseline drug resistance testing did not have an impact on the regimen’s effectiveness.

Dolutegravir Plus Lamivudine Dual-Drug Regimen in Treatment-Naive HIV-1—Infected Patients With High-Level Viral Load: Preliminary Data From the Real World

“…In our study, patients enrolled did not get the baseline drug resistance test results when they started treatment, but the results of high-frequency viral load monitoring showed that DTG + 3TC regimen was effective, and no patients had drug resistance mutations. This result is consistent with the results of a real-world study in Spain, 14 in which 135 naive patients did not get the baseline drug resistance test results at the beginning of treatment, and 85.2% of participants achieved HIV-1 RNA ,50 copies/mL at week 48, and no treatment-related drug resistance mutation occurred. This may be related to the low incidence of primary drug resistance in 3TC and the high resistance barrier of DTG.…”

Sustained Virologic Suppression With Dolutegravir/Lamivudine in a Test-and-Treat Setting Through 48 Weeks

“…A recent real-world study evaluated the efficacy of DTG/3TC in 135 ART-naive adults, 72% of whom initiated treatment without baseline drug resistance test results [ 13 ]. Similar to the STAT study, a high proportion of virologic suppression was seen by Week 48 (85%), with 2 (1.48%) treatment modifications due to M184V mutations (1 participant achieved HIV-1 RNA <50 copies/mL by Week 4 while still receiving DTG/3TC).…”

“…As has been previously reported [ 26 , 27 ], participants experienced weight gain after initiating DTG/3TC, with numerically higher gain occurring among those with higher baseline viral load and lower baseline CD4 + cell count, consistent with what might be expected for individuals who are returning to better health after ART initiation. Of note, STAT included a higher proportion of participants with viral load ≥100 000 copies/mL (39%) and CD4 + cell count <200 cells/mm 3 (28%) at baseline compared with other phase 3 treatment-naive studies (GEMINI, 20% and 8% [ 28 ]; REDOLA, 17% and 2% [ 13 ]; DIAMOND, 25% and 21% [ 23 ]; respectively), which may partly explain the somewhat greater weight gain observed in STAT [ 13 , 23 , 28 ]. Moreover, some studies have found that Black or African American individuals are at higher risk of weight gain compared with individuals of other races [ 27 , 29 ].…”

“…None of these 5 participants developed treatment-emergent INSTI substitutions. Similarly, in the GEMINI-1/GEMINI-2 and REDOLA studies, 3 of 1974 (0.15%) [ 12 ] and 2 of 135 (1.48%) [ 13 ] participants, respectively, were excluded from the study population for transmitted M184V resistance mutations. In Studies 1489 and 1490 evaluating bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), 3 of 1421 (0.21%) participants had baseline M184V or M184M/V mutations and were excluded [ 14 ].…”

Effectiveness and tolerability of dolutegravir/lamivudine for the treatment of HIV-1 infection in clinical practice

“…Several cohort studies have evaluated the use of dolutegravir/lamivudine in clinical practice worldwide, confirming the results of the previous clinical trials. 7–10 However, these studies have several shortcomings, especially regarding treatment-naive patients. Most of them involve a limited number of subjects and/or a single centre: this limits the power of the study to compare its effectiveness with other ARTs and the analysis of certain subgroups of interest, such as those with low CD4 cell counts or high plasma viral loads (VLs).…”