HIV and Hep C Advances at CROI
New HIV drugs and treatment strategies look promising, especially for people with resistant virus, and hepatitis C treatment has entered a new era, researchers reported at the Conference on Retroviruses and Opportunistic Infections this month in Atlanta.
As the pace of antiretroviral drug development has slowed, CROI - now in its 20th year - has largely shifted its focus toward treatment access, biomedical prevention, and related conditions such as cardiovascular disease and hepatitis C.
There is also growing interest in research that might one day lead to a functional cure for HIV, as demonstrated by the biggest news out of Atlanta: a toddler in Mississippi who appears free of active virus after starting antiretroviral therapy within two days of birth.
As antiretroviral drugs have become more effective, less toxic, and easier to use, there is now more emphasis on the "cascade of care" - the shrinking proportion of people with HIV at each successive stage from testing to starting antiretroviral therapy to staying on treatment and maintaining an undetectable viral load.
Looking at new HIV drugs presented at CROI, first out of the pipeline is likely to be dolutegravir, ViiV Healthcare’s next-generation integrase inhibitor, which was submitted for Food and Drug Administration approval late last year. New data from the SAILING study show that dolutegravir worked better than raltegravir (Isentress) - the sole approved drug in this class - for treatment-experienced people with resistant HIV currently on failing therapy.
Andrew Zolopa from Stanford presented findings from a study comparing Gilead Science’s widely used TDF version of tenofovir (Viread, also in the Truvada, Atripla, Complera, and Stribild coformulations) to a new version known as TAF. TAF reaches higher concentrations in cells than TDF, meaning it can be used at much lower doses. People taking TAF in a new four-in-one pill similar to Stribild had equivalent viral suppression and CD4 T-cell gains, but less evidence of kidney dysfunction and bone loss.
Joseph Gathe from Therapeutic Concepts in Houston reported good results with Tobira Therapeutics’ dual-action cenicriviroc, which blocks both the CCR5 co-receptor - one of the two gateways HIV uses to enter cells - and the CCR2 co-receptor, which plays a role in inflammation. Further back in the pipeline, Merck researchers presented promising early data on MK-1439, its next-generation NNRTI.
Are NRTIs necessary?
People with highly resistant HIV - especially those who started treatment with less effective therapy early in the epidemic - may take multiple drugs in an effort to suppress the virus and make it less "fit." But each additional medication adds cost and side effects, leading Karen Tashima from Brown University and colleagues to ask whether fewer might be better.
The ACTG OPTIONS trial enrolled 360 participants on failing regimens with resistance to nucleoside/nucleotide analogs and NNRTIs. They had been on treatment for 12 years on average and had a median CD4 count of only 200. Investigators put together optimized regimens, choosing among 20 combinations of potent modern drugs. Patients were then randomly assigned to either add nucleosides/nucleotides or go nuke-free.
Omitting nucleoside/nucleotides worked just as well as traditional regimens, with more than two-thirds of patients taking either nuke-free or nuke-containing combinations achieving viral suppression within one year. People in both groups had similar rates of side effect, but there were significantly fewer deaths among the nuke-avoiders.
This study is a "game-changer," said Zolopa. "Many of us are recycling nukes, but it looks quite convincing that we don’t have to do this."
Direct-acting antiviral drugs that target the hepatitis C virus lifecycle - working much like HIV therapy - have ushered in a new era of treatment. But the two drugs approved so far, Merck’s boceprevir (Victrelis) and Vertex’s telaprevir (Incivek), must still be used with pegylated interferon and ribavirin, and many patients and providers are waiting for more tolerable therapy.
Researchers at CROI presented promising data on several interferon-free combinations studied in HIV-negative people. The latest findings from Gilead’s ELECTRON trial showed that a 12-week triple combination of the once-daily HCV polymerase inhibitor sofosbuvir (GS-7977), NS5A inhibitor ledipasvir (GS-5885), and ribavirin cured 100 percent of hard-to-treat HCV genotype 1 patients, including prior null responders. Gilead is currently testing a fixed-dose coformulation of sofosbuvir and ledipasvir without ribavirin, which can cause anemia.