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HIV: When to treat and why

June 11, 2009

Doctors typically wait until HIV wreaks havoc on an individual’s immune system before prescribing HIV-fighting antiretrovirals. The drugs are costly and potent. So deferring treatment not only saves money, it also reduces an infected individual’s lifetime exposure.  

New results from Haiti, however, show that earlier treatment can improve survival and reduce the risk of tuberculosis. This latest study, along with several other recently published investigations, has resparked the long-standing debate over when to treat and why.

To Treat or Not to Treat? Good Question!

The pendulum of when to prescribe antiretrovirals has swung back and forth over the past decade or so. Originally, physicians adopted a “hit early, hit hard” strategy. But concerns about the toxicity of the drugs and their high costs drove them to reconsider. Furthermore, they reasoned that the longer they delay treatment, the longer they could delay the evolution of drug resistance, given that resistance doesn’t develop until a patient has begun therapy.

The current standard in the developed world is to withhold treatment until the patient has symptoms, or until his CD4 count — a measure of immune function — drops to 350 (a healthy, uninfected individual’s CD4 count typically falls between 500 and 1,500). In the developing world, the treatment threshold is even lower, a CD4 count of around 200. But today it looks as though the pendulum may be swinging back toward earlier treatment. 

Gold Standard

What makes the Haiti study special is that it is the first randomized controlled trial to show the benefits of early treatment. These studies are the gold standard in medicine.

The study, which began in 2005, randomly assigned 816 HIV-infected adults who had CD4 counts between 200 and 350 to an early or a late treatment group. Those in the early treatment group received therapy 2 weeks after enrollment. Those assigned to the late treatment group received therapy when they developed AIDS, or when their CD4 counts dropped to 200 — the current standard of care. 

As of May 28, only six participants in the early treatment had group died compared to 23 participants in the late treatment group. In fact, the survival benefit of early treatment was so overwhelming, the data safety and monitoring board (an independent committee that oversees all clinical trials) recommended that the trial be stopped early so that all participants could receive treatment. 

Upon reviewing the data, the board also found that half as many people in the early treatment group developed tuberculosis compared with the late treatment group. 

That’s good news for people infected with HIV, but it may also be good news for those who aren’t infected. 

Ounce of Prevention?

Earlier antiretroviral treatment could not only improve survival, it could also prevent new infections. It works like this: People who are infected with HIV have viral particles floating around in their blood, semen and vaginal secretions. Studies have shown that the higher an individual’s viral load, the more likely he is to transmit the virus. Antiretrovirals stop (or at least slow) viral replication, thereby lowering viral load. So people taking the drugs should, theoretically, be less infectious. In fact, Swiss experts have gone so far as to say that infected individuals taking antiretrovirals can’t transmit HIV via sex as long as their viral loads have been suppressed for at least six months, they adhere to their drug regimen, and neither partner has any other STDs. If they are right, it stands to reason that the earlier infected individuals receive antiretrovirals, the less time they have to transmit the disease.

A randomized controlled trial to test this hypothesis is already underway in South Africa. But the results likely won’t be available for two or three years. 

Even if the study shows that antiretrovirals do prevent new infections, getting treatment requires that an individual know his status . . . and that presents its own special set of challenges.

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