Two new antiretrovirals from ViiV Healthcare look promising for HIV treatment based on early studies. Researchers evaluated oral versions of the third-generation integrase inhibitor VH-184 and the HIV capsid inhibitor VH-499 in small Phase IIa proof-of-concept trials that enrolled previously untreated people with HIV. Both drugs demonstrated potent antiviral activity when used alone for 10 days. The mean maximum changes in HIV RNA were −2.31 and −2.17 log copies using the highest tested doses of VH-184 and VH-499, respectively—comparable to viral load reductions seen in early studies of the second-generation integrase inhibitor dolutegravir. No one in the VH-184 study developed drug resistance, but one person taking the lowest dose of VH-499 had a mutation associated with reduced sensitivity to capsid inhibitors. Both novel drugs were safe and well tolerated with no serious adverse events. These results set the stage for ongoing trials of long-acting injectable formulations of VH-184 and VH-499. Ultimately, the goal is complete regimens that can be administered every six months or less.