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Being Alive

Combination Antiviral Therapy: Where Is the Proof?


Being Alive 1995 Feb 5: 4

Last month, in my report of the top ten HIV/AIDS stories of 1994, I once again reported on my long held belief that "two drugs generally work better than one." One Newsletter reader challenged this statement by pointing out that there is no proof that someone on combination therapy lives longer and progresses more slowly than someone on only one antiviral. While it is true that no survival benefit has been definitively established, there seems to me enough evidence to date to suggest that combination therapy is a reasonable alternative to monotherapy and just may provide greater efficacy.

The early studies of combination antivirals were all done in the test tube. These in vitro studies showed that a combination of drugs was indeed more powerful in slowing HIV replication than was a single antiviral. In 1992, data from an in vivo study, ACTG 106, were released. This large study looked at six different combinations of AZT and ddC, and did show a T-cell advantage in people who were taking both drugs. Unfortunately, there was no long-term follow up, and so we do not have survival data. One of the big unanswered questions about HIV therapy is whether increased T-cell counts translate to longer survival. Intuitively we think so, but we have to date no proof.

In 1993, researchers presented the data from ACTG 155. This study was the first to look at clinical endpoints in combination therapy. For those in the study with a CD4 count less than 150, there was no difference in outcome whether on combination therapy or monotherapy. For those with a CD4 count between 150 and 300, there was a non-statistically significant difference in improved survival for those on combination therapy. Some would argue that this non-statistically significant difference points to a possible trend and that with people whose CD4 count was above 300, we might indeed establish that combination therapy offers a survival benefit. Unfortunately, we do not have such data from ACTG 155.

A more recent ACTG study, ACTG 229, demonstrated that a three drug combination provided greater viral suppression and higher T-cell rise than did monotherapy. Again, we do not have follow up data to determine long term benefit.

So where is the proof that combination antiviral therapy is ultimately more efficacious than monotherapy? For some, the studies that show increased T-cells and decreased viral load are enough. For others, since no survival advantage has been definitely established, the proof is lacking. As with so much of this disease, one needs to review the available data and make reasonable choices. In that light, it seems to me that we can say that two drugs, all else being equal, generally work better than one.


Information in this article was accurate in February 5, 1995. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.