Studies Find D4T Plus 3TC Effective Against HIV
Sequence Of Combination Therapy Deemed Important
January 24, 1997
-- Results of two studies presented here at the Fourth Conference on Retroviruses and Opportunistic Infections show that the previously untested combination of d4T (stavudine) plus 3TC (lamivudine) is effective against HIV. One study demonstrated that d4T plus 3TC was effective as initial therapy, but less effective if used after AZT plus 3TC. Investigators in the other study found that adding 3TC to ongoing treatment with d4T significantly reduced HIV in some patients to undetectable levels.
These studies have given us three important pieces of information, stated Kevin Robert Frost, director of amfAR's Community Based Clinical Trials Network (CBCT). First, we have evidence that confirms the growing concern that the order in which we use combinations of drugs will affect therapeutic options in the future. Second, effective control of HIV may be possible if new agents are added to ongoing, stable therapy. Finally, the data suggest that two-drug combinations may adequately control HIV for some individuals.
In an effort to control HIV, physicians and patients are frequently turning to combinations such as d4T plus 3TC and others that have not been tested in clinical trials, Frost continued. We now have more definitive data that tell us what are good choices to make.
The study designated as the retrospective study showed a statistically significant 84% drop in people for whom d4T plus 3TC was the first HIV treatment. That drop was less than 50% if 3TC plus AZT had previously been used, said amfAR researcher Calvin Cohen, MD, research director of the Community Research Initiative of New England, who chaired both studies. At present, we believe that we want to see a drop of at least 68%, or we will try to find another treatment.
"The other study, designated the 'bDNA study', showed that adding 3TC to ongoing treatment with d4T and certain other drugs significantly reduced HIV, and that, in some people, HIV fell below the levels that could be detected using a very sensitive assay. These results open the intriguing question of whether we can offer potentially less toxic two-drug regimens to some patients," added Dr. Cohen, who presented results of both studies today.
A very sensitive test, which can detect as little as 500 copies of HIV per mL of the patient's blood, was used in the bDNA study to measure changes in HIV over time, making it possible to track the effect a drug is having even when the amount of virus is quite low.
The bDNA study is an ongoing observational, non-randomized open label study of HIV levels in the blood of persons who added 3TC to ongoing therapy with another drug or drugs of the same class (known as nucleoside analogues) but other than AZT. Other trials have tested the addition of AZT to ongoing combination therapy, but it was not known whether adding 3TC to other drugs would produce the incremental drop in HIV seen with AZT.
For the whole study population, HIV was 76% lower 12 weeks after 3TC was added to their previous regimen. However, adding 3TC was not equally effective for all types of baseline therapy. While at week 12, the drop for those who added 3TC to ongoing d4T therapy was 90%; for those who began the study taking ddI (didanosine) alone the drop was 52%; and, for ddI plus AZT the drop was 56%.
The retrospective study examined the anti-HIV effect of starting d4T plus 3TC combination therapy in 330 individuals who either began this combination as initial therapy or who had a wide range of prior treatment. (Forty-nine of the patients were followed for six months.) The driving force behind the study was a need to gather information quickly on a combination widely used clinically, but for which experimental data had not previously been collected.
For the 35 patients who had not been treated with any anti-HIV agents for more than two months before receiving d4T/3TC, viral load decreased by 84%. However, in patients previously treated with AZT and 3TC, the average decrease was only 50%, a drop that was not statistically significant -- a drop of less than 68% is judged to not be of great benefit.
The results of these studies suggest that d4T and 3TC have little potential for enhanced toxicity based on their use as single agents. Both studies looked at possible effects of HIV disease history on treatment outcome, and found that d4T and 3TC worked equally well regardless of a patient's initial viral load, prior opportunistic disease history, or baseline CD4 cell counts. The lack of such an effect suggests that these parameters will not enter into treatment decisions.
These studies were sponsored by the American Foundation for AIDS Research (amfAR) and conducted through its Community Based Clinical Trials (CBCT) Program. amfAR is the nation's leading nonprofit organization dedicated to the support of AIDS research (both basic biomedical research and clinical research), education for AIDS prevention, and sound AIDS-related public policy. Since 1985, amfAR has invested nearly $83 million in grants to 1,700 projects. amfAR mobilizes the goodwill, energy, and generosity of caring people everywhere to end the AIDS epidemic. The CBCT Program of amfAR seeks to enhance the length and quality of life of people living with HIV through the efficient conduct of high-quality clinical research in the community setting. Funding for these studies was provided through an unrestricted educational grant from Bristol-Myers Squibb Immunology.
For more information, contact Kevin Frost, director of amfAR's Community Based Clinical Trials Network at 212-682-7440, extension 133.
This article was provided by amfAR, The Foundation for AIDS Research. Visit amfAR's website to find out more about their activities and publications.