Two experimental drugs aimed at controlling viral loads among HIV-positive people who have developed drug resistance show promise

Two experimental antiretroviral drugs, called TMC278 and elvitegravir, show promise in controlling the viral loads of HIV-positive people who have developed resistance to available drugs, researchers said Wednesday at the 14th Annual Conference on Retroviruses and Opportunistic Infections in Los Angeles, the Los Angeles Times reports (Chong, Los Angeles Times, 3/1).

An estimated 40,000 HIV-positive people in the U.S. have developed resistance to available antiretrovirals and rely on a complex and changing combination of available drugs (Kaiser Daily HIV/AIDS Report, 2/28). One drug, developed by Johnson & Johnson subsidiary Tibotec and called TMC278, is a variation of a drug class called nucleoside reverse transcriptase inhibitors. The other antiretroviral, developed by Gilead and called elvitegravir, is an integrase inhibitor, which works by blocking an HIV enzyme called integrase, the Times reports (Los Angeles Times, 3/1). Integrase is one of the three enzymes necessary for HIV to replicate in the body, and integrase inhibitors would stop HIV from inserting its genes into uninfected DNA. The other two enzymes necessary for viral replication -- reverse transcriptase and protease -- already are targeted by a variety of antiretrovirals (Kaiser Daily HIV/AIDS Report, 2/28).

Studies

• TMC278: Anton Pozniak of London's Chelsea and Westminster Hospital on Wednesday at the conference reported on a study funded by J & J that compared three different doses of TMC278 with a regimen containing Bristol-Myers Squibb's Sustiva, Reuters reports (Reuters, 2/28). The drug combinations were administered during 48 weeks to 368 HIV-positive people who had not previously received antiretrovirals, the Times reports (Los Angeles Times, 3/1). The Phase II study found that 77% to 81% of participants who received TMC278 experienced a decrease in viral loads to undetectable levels, compared with 80% of participants on a standard dose of Sustiva. According to Pozniak, serious adverse events occurred in about 10% of both TMC278 and Sustiva participants. Nervous system disorders affected 33% of those who received TMC278, compared with 53% of those who received Sustiva, Pozniak said. J & J will test a 75-mg dose of the drug in a Phase III trial, according to Pozniak (Reuters, 2/28).

• Elvitegravir: Andrew Zolopa of Stanford University reported on a study that involved 278 HIV-positive people who already were receiving standard antiretrovirals, the Times reports. For the study, one group received a 50-mg dose of elvitegravir, a second group received a 125-mg dose and a third group received a protease inhibitor. The study found the group that received a 50-mg dose showed some signs of benefiting from the drug. The participants who received the 125-mg dose had a 98% reduction in viral loads after 24 weeks, compared with a 94% reduction in viral loads recorded in the third group, the study found. According to Zolopa, although elvitegravir appeared effective, viral loads tended to rebound slightly after a few weeks. Testing will continue on the drug, which likely will not be available before 2009, Gilead officials said.

Reaction
Daniel Kuritzkes, director of AIDS research at Brigham and Women's Hospital who was not involved in the studies, said he was excited by the possibility of new antiretrovirals that could target HIV through a variety of methods. "We have every expectation we can suppress the virus in the vast majority of patients," Kuritzkes said, adding that more methods mean there is a reduced chance that HIV will mutate into a resistant strain (Los Angeles Times, 3/1). "It's a brand new day," Stephen Smith, director of the department of infectious diseases at Saint Michael's Medical Center, said. He added, "This means that no one in the developed world should be walking around anymore with any detectable levels of virus in their blood" (MacPherson, Newark Star-Ledger, 3/1).