Background: Patients who started combination antiretroviral therapy (cART) during primary HIV-1 infection (PHI) show a smaller HIV-1 reservoir size compared to patients who started cART during chronic infection. Thus, we hypothesized that a smaller HIV-1 reservoir size translates in sustained virological suppression after simplification of cART to dolutegravir monotherapy.
Methods: In this randomized, open-label, non-inferiority trial, we recruited patients >18 years with documented PHI who started cART < 180 days after estimated date of infection (EDI) and were fully suppressed for > 48 weeks. Exclusion criteria were previous virological failure or treatment interruption and major resistance associated mutations (RAM) to integrase inhibitors. We randomly assigned patients 2:1 to monotherapy with dolutegravir 50 mg once daily or to continuation of cART. Primary endpoint was virological response, defined as HIV-1 RNA < 50 cp/mL plasma at week 48, in the per-protocol-population, with a non-inferiority margin of 10% (NCT02551523).
Results: Between 11/2015-3/2017, we randomly assigned 101 patients (68 to dolutegravir monotherapy, 33 to continuation of cART). At week 48 in the per-protocol-population, 67/67 (100%) had virological response in the dolutegravir monotherapy group versus 31/31 (100%) in the cART group (difference 0%, 95%-CI [-1, 0.047)], showing non-inferiority at the prespecified level (Figure1). In the intention-to-treat population, 1 patient in the dolutegravir monotherapy group experienced viral failure at week 36 (viral load 382 cp/mL) and 2 patients in the cART group left the study before week 48 because they moved abroad. The patient who experienced viral failure was found to be chronically infected at the start of first cART and therefore violated entry criteria. Resistance test at time of viral failure revealed no RAMs and he was re-suppressed on cART. Overall, 14 severe adverse events occurred (dolutegravir monotherapy 10 [15%]; cART 4 [12%]), none related to study-drugs.
Conclusions: In our randomized simplification trial, monotherapy with once daily dolutegravir was effective, safe, and non-inferior to cART in patients with a documented PHI who initiated cART < 180 days after EDI and were virologically suppressed for at least 48 weeks. Our results suggest that future simplification studies should use a stratification according to time of infection at start of first cART.



[Figure 1: HIV-1 RNA <50 copies per mL plasma at week 48 for the per-protocol and intention-to-treat populations. Error bars are 95% CI.]