Comparable viral decay with initial dolutegravir plus lamivudine versus dolutegravir-based triple therapy

Abstract

Objectives To expand understanding of the virological potency of initial dolutegravir plus lamivudine dual therapy (dolutegravir/lamivudine), we compared the viral decay seen in the pilot ACTG A5353 study with the decay observed with dolutegravir plus two NRTIs in the SPRING-1 and SINGLE studies, while also exploring the impact of baseline viral load (VL). Methods Change in VL from baseline was calculated for timepoints shared by A5353 (n = 120, including 37 participants with pretreatment VL >100000 copies/mL), SPRING-1 (n = 51) and SINGLE (n = 417). The 95% CIs of change from baseline were determined for each observed week, using the mean log10-transformed VL, and compared between the dolutegravir/lamivudine and triple therapy groups using the Wilcoxon Rank Sum test for non-inferiority (δ = 0.5). To assess the impact of baseline VL on viral decay, we examined a bi-exponential non-linear mixed-effect model. Results The mean VL change from baseline to week 24 was −2.9 log10 copies/mL for dolutegravir/lamivudine versus −3.0 log10 copies/mL for dolutegravir-based three-drug therapy (P < 0.001). In the decay model, baseline VL >100000 copies/mL was associated with a slower initial decay rate (d1). A faster initial decay rate was seen with dolutegravir/lamivudine, which was partially offset when baseline VL was >100000 copies/mL as indicated by a significant interaction between baseline VL and drug therapy group. The secondary decay rate (d2) was not significantly different from zero, with no significant associations. Conclusions Viral decay with dolutegravir/lamivudine was comparable to viral decay with dolutegravir-based triple therapy, even in individuals with higher pretreatment VL (>100000 copies/mL).

Changes in Serum Inflammatory Markers in Antiretroviral Therapy–Naive HIV-Infected Patients Starting Dolutegravir/Lamivudine or Dolutegravir/Lamivudine/Abacavir

“…However, a major concern of dual therapy is a possible incomplete viral suppression (mostly in viral reservoirs), leading to an increasing residual viremia and a higher inflammatory activity. 4,5 Integrase strand transfer inhibitors (INSTIs) prevent HIV integrase from incorporating proviral HIV-DNA into the human host cell DNA, so it has been speculated that INSTIs could reduce viral reservoirs and decrease immune inflammation more than other antiretroviral classes. However, conflicting results have been published regarding a potential anti-inflammatory role of INSTIs.…”

“…However, a major concern of dual therapy is a possible incomplete viral suppression (mostly in viral reservoirs), leading to an increasing residual viremia and a higher inflammatory activity. 4,5…”

Dolutegravir Plus Lamivudine Two-Drug Regimen: Safety, Efficacy and Diagnostic Considerations for Its Use in Real-Life Clinical Practice—A Refined Approach in the COVID-19 Era

“…In GEMINI-1 and -2, the median time to reach TND viral load (VL) values with DTG+3TC was comparable to that observed with DTG+emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) arms (8-weeks, median), with no apparent role for higher VL or lower CD4 cell count at BL ( Table 3 ) [ 7 , 12 , 13 , 14 ], thus dispelling any doubts that this type of “simplified” therapy could slow down viral decay. Rather, the 117 patients with BL VL >100,000 copies/mL treated with DTG+3TC achieved TND VL values in a median (IQR) time of 16 (16–24) weeks, apparently even shorter than that observed in the 132 receiving DTG+TDF/FTC (median (IQR) = 24 (24–36) weeks) [ 9 ] ( Table 3 ).…”