Abstract Body

The WHO has recommended a rapid transition from non-nucleoside reverse transcriptase inhibitors (NNRTI)-based to dolutegravir (DTG)-based ART regimens due to a rise in HIV drug resistance to NNRTIs. However, there is a paucity of data to inform transition of individuals not virologically suppressed on NNRTI-based to DTG-based regimens while maintaining the NRTI backbone.

We conducted a 144 week, randomized, open-label, phase 3 noninferiority trial in Zambia where we randomized adults on tenofovir disoproxil fumarate (TDF), lamivudine (3TC) plus efavirenz (EFV) or nevirapine (NVP). In Arm A, adults with viral load (VL) <1,000 copies/mL were randomized to TDF, 3TC, DTG (TLD) or tenofovir alafenamide (TAF), emtricitabine (FTC), DTG (TAFED). In Arm B, those with VL ?1000 copies/mL were randomized to TLD, TAFED, or the standard-of-care (SOC) second line protease inhibitor (PI/r)-based regimen lopinavir/ritonavir (LPV/r) or atazanavir/r (ATV/r), zidovudine (ZDV), 3TC. Primary end point was VL <1,000 copies /mL (viral suppression (VS)) at week 48, assessed using the FDA snapshot algorithm (intent-to-treat (ITT) population). Noninferiority was tested with a margin of 10 percentage points. We herein report the primary (week 48) efficacy data.

Of 1201 randomized adults, 100% were black, 61% female, with a median age of 40 years. At week 48, in Arm A, 88% TLD-treated adults maintained VS compared to 87% for TAFED [difference, -0.5%, 95% CI -6.9 – 5.9]. In Arm B, 82% TLD-treated adults achieved VS, compared to 87% for TAFED and 76% for 3TC/ZDV/PI/r. Noninferiority of switching to both DTG-based arms was achieved compared to the SOC boosted PI regimen [TLD versus ZDV/3TC/PI/r difference, 6.2% [-0.7 – 13.0]; TAFED versus ZDV/3TC/PI/r difference, 11.7% [5.3 – 18.0]. Consistent results were shown in other analyses (Table 1). Weight gain was greater among females receiving TAFED (mean increase, +4.8kg in TAFED, +2.8kg in TLD, +2.4kg in ZDV/3TC/PI/r groups) but was similar among males (mean increase, +2.9kg in TAFED, +2.6kg in the TLD, +2.7kg in ZDV/3TC/PI/r groups).

In the VISEND trial, HIV-positive adults with virologic failure to TDF/3TC/NNRTI, had favorable outcomes when switched to DTG with either TAF/FTC or TDF/3TC compared to those switched to SOC boosted-PI ART. Women receiving DTG, however, due to significant weight gain, may be at heightened risk for non-communicable diseases and/or metabolic complications hence longer-term follow up is needed.