Battling Drug-Resistant HIV Strains in Newly Infected Patients
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."