Going the Distance
by Liz Highleyman
The journey to long-term health starts with treatment
Whether you’re starting therapy for the first time or are a treatment veteran, your chances of gaining long-term benefits from ARV treatment are excellent. But this requires careful planning, including choosing HIV meds that have been proven to push viral loads to undetectable levels—and to keep them there for as long as possible.
When to Start
Treatment options for HIV-positive people have never been easier to take—or safer and more effective over the long run—than they are now, especially for those starting their first, or even their second, drug regimen.
In fact, modern-day ARV improvements over older first-line therapies that came about in the mid- to late-1990s have led many experts to recommend starting treatment earlier than was suggested in the past.
We’ve always known the importance of starting ARVs before the CD4 count falls below 200, when AIDS-related OIs and cancers become a risk. U.S. treatment guidelines now recommend starting treatment when CD4s fall to 350. However, research conducted during the past few years hints that starting even earlier might be best. Clinical trials testing this theory are now under way.
“Today, there’s much less focus on how long can we wait to start HIV treatment, and more on why not start now,” says Paul Volberding, MD, co-director of the Gladstone Institute of Virology and Immunology Center for AIDS Research at the University of California in San Francisco and one of the first doctors in the world to treat people with HIV/AIDS.
In addition to protecting you from AIDS-related problems, early treatment may also lower the risk of several conditions not usually tied to HIV infection—such as heart, liver and kidney disease, as well as a variety of cancers. The longer HIV goes untreated, the newest research indicates, the greater the risk of harm.
What to Use
With more than 20 meds to choose from, you and your health care provider must consider many factors when building a regimen, including your individual health history, treatment experience, dosing schedules, expected side effects and possible interactions with other medications you’re taking.
Of course, effectiveness is also a major factor. It’s important to use a combination of ARVs that’s potent as well as durable. This means you’ll want to consider meds that can quickly push your viral load to “undetectable” (less than 50 copies/mL using today’s viral load tests) and can keep it there. And while you play a big part in this—HIV meds are only effective if taken exactly as prescribed—some meds have been better studied than others in terms of their ability to go the distance.
Whereas many ARVs are studied in clinical trials lasting about a year, some have been evaluated—and compared with other HIV medications—in studies lasting several years. And while a lot can be said for medications that have been available in the “real world” for many years, there’s nothing quite like long-term clinical trial data to help determine the likelihood of long-term treatment success.
According to treatment guidelines from the U.S. Department of Health and Human Services (DHHS) for people starting HIV therapy for the first time, Sustiva (efavirenz), a non-nucleoside reverse transcriptase inhibitor (NNRTI), is listed as a “preferred” ARV. One of its first studies, comparing Sustiva plus Combivir (zidovudine and lamivudine) to a protease inhibitor (PI) called Crixivan (indinavir) plus Combivir, followed patients for more than three years (168 weeks). At that time point, 48 percent in the Sustiva group, compared with 29 percent in the Crixivan group, had undetectable viral loads.
Long-term clinical trial data also support Kaletra (lopinavir/ritonavir), a DHHS-preferred PI. One study followed 100 HIV-treatment newbies taking Kaletra plus Zerit (stavudine) and Epivir (lamivudine). After 312 weeks of treatment—almost six years—viral loads were still undetectable in 62 percent of the patients.
Long-term studies have also shown that not all nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) are equal in their effectiveness or possible side effects. (First-time treatment takers almost always use two NRTIs with an NNRTI or PI.) For example, a study conducted by Gilead Sciences—it was called Study 934—compared its Truvada (tenofovir and emtricitabine) to longtime dual-NRTI champion Combivir—both in combination with Sustiva. After 144 weeks, or nearly three years, 71 percent in the Truvada group maintained undetectable viral loads, compared with 58 percent in the Combivir group. Combivir was also more likely to cause several side effects than Truvada in this study.
Study 934, Dr. Gallant says, is one trial that moved doctors away from a particular group of NRTIs called thymidine analogues—zidovudine (found in Retrovir, Combivir and Trizivir) and Zerit—for initial HIV treatment. “We learned that while they’re effective, they have definite long-term side effects, including anemia, neuropathy and lipoatrophy [fat loss].”
A study comparing another popular two-in-one NRTI combination—Epzicom (abacavir and lamivudine)—with Truvada, for 96 weeks of treatment, has not yet produced its final follow-up results.
Are You Experienced?
If you started ARV treatment years ago and have tried many medications, you may have drug-resistant virus, which can chip away at your options. But even if you have lot of treatment experience under your belt, today’s potent meds can usually push viral load below 50 copies—“undetectable”—and keep the CD4 count above the danger zone.
But finding a regimen that can do this may be tricky. For example, if your HIV has become resistant to one drug in a particular class—such as the PIs or NNRTIs—it may limit your ability to use other members of this class.
Some people with HIV that’s resistant to several drugs may not be able to keep their viral load undetectable. But studies show that ARV therapy can still help maintain long-term health by lowering the amount of virus and reducing the damage it can do.
Two recently approved classes of ARVs that attack HIV in new and different ways—integrase inhibitors and CCR5 antagonists—offer new choices for treatment veterans with highly resistant virus.
“It’s critical that new meds be ‘protected’ by using them only in combination with other active drugs,” Gallant emphasizes. “Expert care is always important, but it’s especially important at this stage.”
HOW LONG CAN I LIVE WITH HIV?
Although there’s no easy answer to this common question, study estimates are highly optimistic.
According to a recent study by an international team of researchers, an HIV-positive 20-year-old starting treatment for the first time can expect to live to about age 69—just 11 years short of the average life expectancy for HIV-negative people.
“Having HIV could speed up the aging process and shorten your life span somewhat,” says Joel Gallant, MD, associate director of Johns Hopkins AIDS Service in Baltimore. “But I expect most of my patients to be doing great long after I’ve retired.”
Life expectancy for a person starting HIV treatment today is about 13 years longer than it was when combination therapy became the standard-of-care in 1996. This suggests that, as treatments continue to improve, as they have over the past 10 years, expected survival will likely continue to increase.
LAB TESTS FOR LONG-TERM SUCCESS
Lab tests are essential to lifelong wellness with HIV. Not only can they help you determine when to start treatment and which ARVs to use, but they can also help you and your health care providers figure out how you’re doing and ensure that you’re not experiencing any harm from your treatment.
CD4 cell count measures the number of disease-fighting white blood cells. This gives a snapshot of your immune system health and shows when to begin treatment.
But before starting a new regimen, you should take several tests to help decide which drugs are your best options. These include drug resistance tests; the HIV tropism test, which determines whether you can use the CCR5 entry inhibitor Selzentry (maraviroc); and the HLA B*5701 test, which figures out whether you’re at risk for a life-threatening allergy to abacavir—found in Ziagen, Epzicom and Trizivir—and should therefore avoid that drug.
Viral load tests measure HIV genetic material (RNA) in your blood and show whether your current regimen is working properly.
If not, drug resistance tests can show why treatment is failing and spell out which drugs you may want to switch to.
Tests for drug side effects show where you might experience problems. These include cholesterol tests, liver function tests and blood cell counts to detect fatigue-causing anemia.
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