BioEd Online

Even the best drugs currently available cannot weed out HIV from all of its hiding places within the body, according to a new study of HIV patients in the United States. The discovery seems to confirm doctors' suspicions that once the virus gains a foothold, it can never be fully eradicated from the body.

After years of aggressive drug treatment, the virus still hides out in significant reservoirs, particularly in tissues surrounding the gut lining, the researchers report. Cells in these tissues, a part of the immune system called 'gut-associated lymphoid tissue', remain infected with the virus even though the patient may be leading an apparently healthy life.

Many HIV patients can manage their infection with a cocktail of drugs called antiretroviral therapies (ARTs). These can reduce their 'viral load' — the amount of virus circulating in the blood plasma — to undetectable levels.

But the new study shows that even in such 'non-infectious' patients the virus is still lurking in gut tissues, and still infecting other immune cells in the blood.

"It might not ever be possible to completely eradicate the virus from the body, even though people are doing well," says Anthony Fauci, director of the US National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, who led the research. He adds, however, that this doesn't mean that patients will be more likely than previously thought to pass on the virus to others.

Incurable

The finding underlines HIV's status as an 'incurable' infection, although in many cases doctors are able to stave off the onset of full-blown AIDS by giving patients sustained courses of drugs.

Indeed, so effective are current drugs that most say HIV should now be seen as a chronic disease requiring lifelong management, in the same way as diabetes or chronic hypertension. "It's not a death sentence," says Deenan Pillay of University College London, an expert on antiviral treatments.

Earlier this month, the Swiss National AIDS Commission broke with convention by declaring that HIV-positive patients who had had successful antiretroviral treatment could be declared 'non-infectious' through sex. Other health agencies still maintain that the only safe way to prevent HIV transmission is to practice safe sex, particularly by using a condom.

The new results show that even state-of-the-art drugs cannot stop HIV replicating in certain body tissues, Pillay says. "We have always known that current paradigms of treatment are not sufficient. If anything, this demonstrates that there's even further to go."

Fauci and his colleagues studied eight HIV patients, who had been taking ART drugs for several years, and in one case nearly a decade. All were in good health with low blood plasma levels of the virus. But when the researchers took biopsies of their gut lymphoid tissue, they found that HIV was still present, and levels of CD4+ cells — the cells targeted by the virus — were lower than normal.

The researchers also compared DNA from HIV found in the gut with DNA from HIV found in white blood cells , and found that they were very similar, indicating that the two tissues constantly re-infect one another as the virus replicates; the gut reservoir is not isolated from the rest of the body. The results are published in the Journal of Infectious Diseases¹.

Stamped down early

Pillay argues that HIV tests should be given to more patients who show the flu-like symptoms of early infection, in a bid to identify more people who have only just been exposed to the virus. Because the virus colonizes the gut tissues early in infection, rapid intervention may help to reduce the size of this viral reservoir. That could in turn make it easier to keep blood plasma viral loads low during the course of the disease.

Last year, Britain's chief medical officer Liam Donaldson wrote to doctors, urging them to test more widely for the virus. "There's a push to get wider testing, and I'm personally very much in favour of it," Pillay says.

Reducing viral reservoirs by early intervention could particularly help patients without access to top-of-the-range drug treatments, Pillay suggests.