As most of you are aware, the treatment of HIV requires multiple drugs. Since the mid-nineties, the rule has been to use three drugs to control HIV, but sometimes that wasn’t possible if the patient was resistant to drugs or had serious side-effects of drug-interactions.
In late 2017, the US approved the first two-drug combination, Juluca (dolutegravir + rilpivirine). Then, earlier this year, Dovato was approved (Dolutegravir + lamivudine). So we are seeing a continuing theme where less is more, as I have written about previously.
It was the use of triple-drug combinations with potent drugs in the mid to late 1990s that led us to control HIV infection in patients. Triple drug combinations suppressed the virus to undetectable levels but also made it more difficult for the virus to become resistant to the drugs.
On the downside, taking three drugs meant more pills to take and higher costs, at least until we combined them into single tablet products. More drugs could also mean more possible side-effects and more potential interactions with other drugs.
The question now is “How low can we go?”. Our drugs are very potent and for some combinations, two appear to work just as well as three. Newer combinations of two drugs may be cheaper than the same combinations with a third drug. Most importantly, if two drugs work as well as three and for extended periods of time, this is very good news.
People will be on therapy for many decades and some folk may have already been on therapy for well over two decades. Effective two-drug regimens mean that patients have more options! A person who gets infected in their mid 20’s could well be on therapy into their 70’s (until we find a cure). So the more treatment options, the better.
Islatravir is a new drug being developed by Merck Pharmaceuticals. It may be effective for HIV treatment as well as HIV prevention (used as Pre-Exposure Prophylaxis or PrEP). While it works similar to drugs like tenofovir (Viread), FTC (Emtriva), and abacavir (Ziagen), it has some unique actions that no other HIV drug has.
In short, Islatravir can very potently block HIV from making DNA in our cells, preventing it from replicating. It is more potent than any other HIV drug in use, meaning a very small dose is highly effective. Islatravir is slowly broken down in the body so that the patient may only have to take it once a week, possibly even less. There appears to be a low rate of side effects. All good news. But it doesn’t end there.
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Current studies are ongoing to determine if Islatravir can be used for PrEP. New forms of the delivering of the drug in the body are being explored that may allow dosing, get this…once a year! Imagine being protected against HIV for a whole year without having to take pills every day!
But remember, PrEP only protects from HIV and NOT Hepatitis, Gonorrhea, Chlamydia, syphilis or Human papillomavirus (HPV) infections. While most of these infections can be cured or prevented by vaccination, some are getting more and more difficult to treat as these infections become resistant to the drugs used to treat them (just as HIV can do).
Speaking of resistance, Islatravir appears to be able to work well against HIV virus that is resistant to other drugs in that class. This leads us to the results of the study that was presented this summer in Mexico City at the International AIDS Society (IAS) Conference.
In this study sponsored by Merck, Patients with new HIV infection were randomized to receive one of three doses of Islatravir, combined with the drug Doravirine and Tenofovir. Then after 24 weeks of viral suppression, the tenofovir was stopped and the patients remained on just two drugs: Islatravir (one of three doses) and Doravirine.
Doravirine is a new HIV drug that was approved earlier this year. It is related to efavirenz and rilpivirine. But it is like Islatravir in that it may work against HIV virus that is resistant to efavirenz or rilpivirine. The researchers found that after 48 weeks, two-drug therapy with just Islatravir and Doravirine was just as good as three-drug therapy with Islatravir, Doravirine, and Tenofovir. There were very few side-effects.
These results provide the basis for a larger trial (phase 3) to confirm the best dose of Islatravir with Doravirine. If this therapy continues to show success, we could be looking at the next two-drug combination. It could be a regimen that could be used by patients who just now starting therapy as well as patients who are experienced and may be resistant to other related drugs. Let’s keep our fingers crossed.
Dr. Crawford has over 25 years of experience in the treatment of HIV. While at Howard University School of Medicine, he worked in two HIV-specialty clinics at Howard University Hospital. He then did clinical research as a visiting scientist with the AIDS Clinical Trials Group (ACTG) at Johns Hopkins University School of Medicine. He served as the Assistant Chief of Public Health Research with the Military HIV Research Program where he managed research studies under the President’s Emergency Plan for AID Relief (PEPFAR) in four African countries.
He is currently working in the Division of AIDS in the National Institutes of Health. He has published research in the leading infectious diseases journals and serves on the Editorial Board of the journal AIDS. Any views and perspectives in his articles on blackdoctor.org are not representative of any agency or organization but a reflection of his personal views.
