Battling Drug-Resistant HIV Strains in Newly Infected Patients

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Nov. 16, 1999 (Atlanta) -- Swiss researchers are shedding some light on an emerging concern: drug-resistant strains of HIV -- the virus that causes AIDS -- in recently infected patients. Some types of HIV are showing resistance to protease inhibitors -- among the most effective anti-HIV drugs. The researchers' findings are published in a recent issue of The Lancet.

Highly active antiretroviral therapy (HAART) -- also called HIV/AIDS drug "cocktail" therapy -- is credited with lowering the rates of HIV-related disease and death in developed countries such as the U.S. HAART includes protease inhibitors as well as the older reverse-transcriptase inhibitors (for example, zidovudine, or AZT).

Resistance of HIV-1 -- the most common form of HIV in the U.S. and other developed countries -- to antiretroviral drugs is the main cause of HIV treatment failure. The primary causes of the development of drug-resistant HIV strains include 1) insufficient treatment to suppress the infection and 2) patient failure to follow the treatment regimen as directed.

Previous studies had calculated the rate of HIV resistance to zidovudine at 5-15%, but no previous studies had been done to calculate the rate of resistance to protease inhibitors.

"We analyzed 82 patients with primary HIV-1 in the Geneva area, from January 1996 to July 1998, and we found 10% of patients [had] mutations associated with resistance to reverse-transcriptase inhibitor [RTI] therapy," researcher Sabine Yerly, MSc, tells WebMD. "We thought we'd find some [resistance,] but we didn't expect to find such a high prevalence of transmission of resistance -- 10% is a very high percentage." Yerly is a research associate in the laboratory of senior researcher Luc Perrin, MD, at the Geneva University Hospital.

"What is also alarming for us is [that] we found 4% of patients with a resistance to protease inhibitors," says Yerly. "Protease inhibitors in Switzerland [became] available in 1995. These patients were infected between 1996 and 1998, and it means that in 2 years we [have seen] this resistance develop."

"I don't think this is terribly surprising; it is too bad, but it is something I think everybody anticipated might happen," Charles Carpenter, MD, tells WebMD. "I would guess that the likelihood of resistance is very similar in the big cities on the East Coast [of the U.S.] as it is in Geneva. Perrin is a first-rate investigator, and his lab is very good; I think the data are solid." Carpenter, a professor of medicine at Brown University, reviewed the study for WebMD.

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Yerly's research group analyzed data from 82 patients with HIV-1 infection -- more than three-quarters of them men -- who were referred to the Geneva AIDS Center between January 1996 and July 1998. None had been treated with anti-HIV drugs at the time the study began, with blood-sample testing. All patients had been infected within 3 months prior to sample collection.

Genetic testing of all patients for reverse-transcriptase inhibitor resistance showed mutations associated with zidovudine resistance in seven patients; two patients had mutations associated with resistance to lamivudine and nevirapine.

Genetic mutations associated with resistance to protease inhibitors were detected in three patients, of whom two also had reverse-transcriptase inhibitor-resistant mutations. Decreased sensitivity to three or four protease inhibitors was seen in three patients, including one patient who had 12 mutations associated with resistance to multiple reverse-transcriptase inhibitors and protease inhibitors.

The researchers recommend pretreatment resistance testing in all recently infected individuals in order to start each patient on the anti-HIV/antiretroviral treatment most likely to be effective. "Resistance testing is important, especially in the case of primary infection ... to be sure to give the best treatment, because the first treatment is the best chance for the patient," says Yerly.

"I would certainly agree with that," says Carpenter. "You would like to check and therefore treat with a regimen that is going to knock the virus levels in [the patient's] blood down to undetectable levels -- that will make transmission far less likely. If you have a resistant virus, and the antiviral agents that you give are not effective in lowering the level in the blood, then the likelihood of [transmitting] resistance, if the patient has any unsafe behavior, is greater.

"That is what I think most of us would want to do -- in those few cases where we see patients that early in the disease -- but we usually don't see them until after that early period, by which time they often have several different strains of resistant virus," says Carpenter.

Carpenter is not overly optimistic that drug-resistant HIV can be contained. "We have not been able to do that very well with other [organisms] -- resistant Staphylococcus, for instance," he says. Despite this, resistance testing may be the only option currently available. "The alternative to knowing what agents the virus is resistant to," he says, "is treating ineffectively, and the patient gets sicker and care becomes much more expensive."

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