Ibalizumab. Another newer agent “worth mentioning,” according to Dr. Spach, is ibalizumab. This monoclonal antibody has a unique mechanism of action. It is 1 of only 2 drugs used for HIV treatment that targets human receptors (all of the others work by inhibiting either an HIV enzyme or binding to the HIV virus itself). Ibalizumab targets the D2 region of the CD4 receptor. It is an injectable (intravenous) compound administered with an initial loading dose and then every 2 weeks thereafter. Dr. Spach reported that the data surrounding ibalizumab show that it is effective as an add-on medication in more advanced resistant settings. Also, it provides an option for people who can't take oral drugs, such as those who have had major surgery or trauma.
Remaining questions
Dr. Spach explained that 1 of the questions that remains is whether to prescribe ARV therapy for patients who are viremic controllers (those who inherently control HIV through their own immunologic response to a level < 200 copies) or elite controllers (those whose own immunologic response controls the virus to a level < 50 copies, which is in the undetectable range). Both of these groups still have a higher risk for hospitalization and for HIV-related inflammatory conditions such as heart disease, according to Dr. Spach. Current thinking among most experts is to initiate and maintain therapy as long as it is tolerated well.
3 drugs to 2? Another question that remains is whether to switch patients who are doing well on 3-drug maintenance therapy to 2-drug maintenance therapy. According to Dr Spach, studies involving the combination dolutegravir/rilpivirine indicate that patients who have suppressed HIV RNA levels for at least 6 months on a 3-drug maintenance regimen do well after switching to the 2-drug combination dolutegravir/rilpivirine, as long as they do not have baseline resistance to either dolutegravir or rilpivirine. But he questioned the need for the change if the individual is tolerating a 3-drug regimen well, saying that given the safety of current regimens, the only broader motivating force may be cost savings. For now, he said, if patients are without complaints or tolerability issues on 3 drugs, leave them alone.
INSTIs and weight gain. The last issue is weight gain with the use of INSTIs. Preliminary data suggest disproportionate weight gain with these drugs (on the order of about 6 kg over a year and half, which may be 2-3 kg greater than that which occurs with PI-based and NNRTI-based regimens). At this point, experts do not recommend avoiding these agents, mainly because of the tremendous benefits that have been observed with INSTIs. Dr. Spach concluded, "Although we will continue to use INSTIs widely in clinical practice, there may be a subset of individuals taking an INSTI who have pronounced weight gain and may need to switch to another regimen that does not contain an INSTI.”