HIV Cure

In an article I wrote earlier this year, I shared some optimism from the medical and scientific community about the possibility of a cure for HIV.

Research continues, but new studies indicate there are still some significant challenges to reach a cure.  If a cure for HIV is discovered, it may not be effective for everyone.  If the successes continue and we reach our goal, we’re still years away from any cure being widely available. But even though we can’t cure HIV yet, we can certainly treat it. Current estimates suggest that a substantial percentage of those infected may be able to live close to a normal lifespan.  Yet patients may develop resistance to their HIV medications and need to change therapy.  Some drugs may cause toxicities which restrict their use in patients at risk. Also, patients may have other diseases or may be taking other drugs that are incompatible with certain HIV medicines.  The bottom line is that we need new drugs. As we approach World AIDS Day 2013 on December 2^nd, we have much to celebrate with some new treatments that are either available now or may soon be available.  Let me introduce you to some of them.

Teaching an old dog new tricks.

Yes, you can teach an old dog new tricks. Tenofovir (Viread, in combination, Truvada) has been around for over ten years (that’s a long time in the HIV medicine world). It is a strong drug against HIV and has been used safely in tens of thousands of patients.  It can also be used for HIV prevention in PreP (pre-exposure prophylaxis). In some circumstances however, it can cause damage to the kidney and some patients may experience loss of bone, similar to osteoporosis.  It is easy for your medical provider to monitor for these effects.  If detected, these problems will usually go away after your provider stops the medicine. A new form of this drug is available.  It is tenofovir alafenamide. It is essentially tenofovir that has learned a few new tricks.  Some minor changes to the drug makes it get into the tissues easier and suppress the virus while less of the drug circulates to potentially cause side effects. In clinical studies, tenofovir alafenamide has been shown to be even safer than tenofovir and causing fewer effect on the kidney and bone.

New Kids on the block

The integrase inhibitors are the most powerful class of HIV medicines we have today.  They are so potent  at suppressing HIV that they can drop the levels of virus to undetectable within just a few days, when combined with other active HIV medicines. They act by preventing the virus from combining its genes with our genes.  This process where HIV inserts its genes into our DNA is called integration.  This step is absolutely required for HIV to reproduce itself and these drugs block this step. Raltegravir (Isentress) has been available for several years now and has been used safely in many patients. Now we have two new drugs available that work the same way as raltegravir.

Elvitegravir is available as a combination of several drugs combined into one pill, like Atripla (efavirenz, tenofovir and emtricitibine). This combination also includes tenofovir and emtricitibine.  Another new drug called cobicistat is also part of the combination.  It has no affect on HIV. It is included in the combination to keep the concentration of elvitegravir high in the bloodstream and tissues, and this allows elvitegravir to be taken just once a day. It works similar to ritonavir, which keeps levels of protease inhibitor drugs high and improves the dosing. This new four drug combination of Elvitegravir, cobicistat, tenofovir and emtricitabine is called, Stribild (I wonder how they come up with the names of these products?),  and is sometimes referred to as “the quad pill” since it contains four drugs.

More recently, another integrase inhibitor has been approved. This drug dolutegravir (Tivicay).  It is also dosed once a day.  In some cases if a patient develops resistance to raltegravir, the first integrase inhibitor, they may be able to successfully switch to dolutegravir.

When we started using combination therapy to treat HIV infection in the mid 1990’s, were finally able to totally suppress the virus from replicating.  This came at a price where these early drug combinations required the patient to take many pills up to three times a days. It sometimes became difficult for patients to stay controlled when they had to take so many pills multiple times a day. A major achievement was developing combinations that only needed to be taken once a day, and then to combine combinations into a single pill.  It doesn’t get any better than that.  Or does it?

A number of HIV drugs are being developed that may only have to be taken once a month, or even less! The drug rilpivirine (Edurant) is in the same class as Efavirennz (Sustiva, Atripla) and Etravirine (Intellence).  It is dosed once a day and is formulated a combination pill with rilpivirine, tenofovir and emtricitibine (called Complera).  But once a day just didn’t seem to be good enough.  A preparation of rilpivirine is being developed that would be injected into the muscle once a month! The preparation is developed so that it is slowly released from the tissue to maintain steady-blood levels for an entire month.

The company Glaxo Smith Kline is developing a new integrase inhibitor (GSK744LAP) that is long-acting and can probably be dosed monthly as well. It is important that long-acting drugs from different classes be developed because combination therapy is required. It also defeats the purpose of convenience if one drug in the regimen can be taken once a month and the other drugs in the regimen have to be taken everyday.

In addition to their use in HIV-infected individuals.  These long-acting drugs may have use in PreP, to prevent HIV infection.  People who are not infected may not be as attentive to taking the medicines  daily since they don’t have the infection.  These long-acting drugs may be better at prevention.

An investigational drug that “Tag-Teams” the HIV virus

Cenicriviroc is an investigational drug that in showing a lot of promise in clinical studies.    This drug is unique in having two effects that can be important in treating HIV infection.  First Cenicrivroc works by the same mechanism as the drug Mariviroc (Selzentry), by blocking a key target that HIV uses to infect blood cells. It is in the class of entry inhibitors, since it blocks HIV’s entry and infection of cells.  This is clearly the most effective and important action of the drug.  But in addition, it can suppress inflammation.  This inflammation from HIV infection can actually drive the disease process and may be responsible for complications from HIV infection, such as heart disease (see my articles from   the blackdoctor.org archives on HIV and inflammation). It will be interesting to see the effect of this drug (if it gets approved) on reducing the long-term complications of HIV infection, like heart disease and some cancers.

Always remember, HIV medicines only work when they’re taken properly.  If the virus becomes resistant to the medicine, it no longer works. Resistance to one drug in your regimen may also effect other drugs in the class even if you are not taking those drugs.  Keep as many treatment options available by taking your currently prescribed medicines as directed and notifying your health providers whenever you have problems or questions.