translation agency

AIDS Treatment Data Network
(ATDN) Combining drugs better than taking AZT alone

November 1, 1995
Treatment Review No. 20; November 1995

The most commonly prescribed anti-HIV treatment is the drug AZT (brand name Retrovir), although there are other readily available anti-HIV drugs including ddI (Videx), ddC (Hivid) and d4T (Zerit). In addition, the anti-HIV drug 3TC (lamivudine) has been given to over 30,000 people nationwide through a special Expanded Access program. Recently completed studies clearly show that taking AZT in combination with another anti-HIV drug such as ddI or ddC is better than taking AZT alone.

The DELTA Study - This DELTA study included over 3,000 people. The participants had T cell counts between 50 and 350. The medications given were either AZT alone, AZT with ddI or AZT with ddC. The DELTA study was divided into two groups, DELTA 1 and DELTA 2. About two thirds of the total participants in the DELTA study had never taken AZT before and made up the DELTA 1 group. In this group, combinations of AZT with ddI and AZT with ddC were much more effective than AZT taken alone at preventing new symptoms and death. The death rate in DELTA 1 in people taking the drug combinations was reduced by 38% (over a third) compared to people taking AZT alone. Participants in the DELTA 2 group had been taking AZT before. In this group, there were no significant differences between people taking AZT alone and people taking the drug combinations. In both DELTA 1 and DELTA 2 groups, combination therapy was shown to be no more likely to cause serious side effects than taking AZT alone. In France, the results of the DELTA study have led the government to recommend that prescriptions for combination therapy be accepted at all hospitals.

The ACTG 175 Study - The second combination therapy study (ACTG 175) was done in the U.S. and included 2,467 people with T cell counts between 200 and 500. People were followed by the researchers for an average of three years. The people in this study were randomly assigned to one of four different treatments. One group took AZT alone. The second group took AZT with ddI. The third group took AZT with ddC. The fourth group took ddI alone. When the researchers looked at the study results overall, they found that both AZT with ddI and ddI alone were better than AZT alone at preventing an AIDS diagnosis or death. Unlike the DELTA study, the benefits of AZT with ddI or ddI alone were most clearly seen in people that had already been taking AZT. Because no one in the DELTA study took ddI alone, ACTG 175 leaves some unanswered questions about the benefits of ddI taken alone. The study did clearly show that taking a combination is better than taking AZT alone. A little less than half the people in ACTG 175 had never taken AZT before. There were not enough cases of people progressing to AIDS in this group to give a clear idea of what drug or combination of drugs works best for people who are starting anti-HIV therapy. The results of the DELTA study give a much clearer answer to this question. In the ACTG 175 study, AZT with ddI caused slightly more side effects than either AZT alone, ddI alone or AZT with ddC.

The Two Studies Together - Many researchers and doctors feel that the results of the DELTA study give the best, most reliable proof of the benefits of combination therapy verus monotherapy. The reason for this is that very few people in the DELTA study dropped out or stopped taking their medications before the study finished. About half the people that started the ACTG 175 study had dropped out or stopped taking their medications before the study finished, which means that the results may not be as reliable as those from DELTA. The DELTA study clearly showed that people that haven't taken any anti-HIV therapies do better starting with combination therapy. In ACTG 175, people that had been taking AZT before did better taking AZT with ddI or taking ddI alone. Neither study was designed to find out when people should start anti-HIV therapy. However, it's encouraging that people in the DELTA study, who had T cells between 50 and 350, all seemed to benefit from combination therapy even if they already had symptoms or an AIDS diagnosis.

3TC and AZT - More information from studies of AZT used in combination with 3TC is about to be released. It shows that increases in T cells and decreases in the amount of HIV in the blood have now lasted for up to two years in people in the study. 3TC is expected to be approved for prescription in the U.S. before the end of 1995. Federal reviewers (the FDA) are deciding for what uses the drug combination should be approved. 3TC is currently available through an expanded access program for people with less than 300 T cells. Doctors can call Glaxo-Wellcome at (800) 248-9757 for more information.