The Newest Class of Anti-HIV Therapies and
Their Effects on HIV Health Care Programs
June 25, 1996
HIV has proven an elusive and deadly adversary. For more than a decade, researchers and physicians have struggled to develop potent new treatments to fight HIV and AIDS. Despite their efforts, only a handful of drugs have been approved to treat HIV disease. Unfortunately, these drugs have proved to be of limited usefulness, succeeding only in slowing the inevitable progression to full-blown AIDS. Today, however, a new class of drugs is providing fresh hope in our battle against the epidemic: protease inhibitors.
Studies of protease inhibitors demonstrate that this new family of drugs is vastly more potent than the first group of drugs used to treat HIV, reverse transcriptase inhibitors (AZT, d4T, ddI, etc.). Data suggest that when used in combination with approved antivirals such as 3TC plus AZT or ddI, protease inhibitors can dramatically lower viral levels by as much as 99 percent in 60-to 90 percent of the individuals using the therapies. Though protease inhibitors alone do not represent a cure for HIV infection or AIDS, they do provide renewed hope for improved drug and treatment options for people with HIV and AIDS.
How Do Protease Inhibitors Work?
Much like reverse transcriptase inhibitors, protease inhibitors attack a viral
enzyme -- protease -- which plays a crucial role in HIV replication. This enzyme
serves as a biochemical scissor late in HIV replication by cutting longer chains
of proteins and enzymes in the host cell's nucleus into shorter pieces. Unlike
long chains, these shorter HIV proteins form new infectious HIV particles that
can infect neighboring cells.
Is There A Resistance Problem With Protease Inhibitors?
HIV's deadly ability to mutate and develop resistance to antiviral drugs
has proven the central barrier to our efforts to develop potent and lasting
therapies. Similar to all previous antiviral drugs, protease inhibitors can also
fall victim to HIV's uncanny ability to develop strains that are drug resistant.
However, at this time, the resistance is problematic only when the protease
drugs are administered in monotherapy.
Another devastating threat posed by protease monotherapy is the development of cross-resistance because resistance to one protease inhibitor often confers multi-drug resistance to several of the other protease inhibitors. However, with more carefully chosen treatment strategies in which protease inhibitors are used in combination with approved antivirals such as 3TC plus AZT or ddI, the size and duration of the antiviral effect is greatly enhanced. Since combination therapy requires HIV to mutate its genetic structure as many as eight times, it is hoped that the newly produced virus will be much less viable.
The threat of viral resistance and cross-resistance to protease inhibitors reiterates the importance of carefully delineated treatment plans. Without carefully chosen and rigorously followed strategies, the potent effects of protease inhibitors will be short-lived and quickly followed by multi-drug cross-resistance.
The Crisis in Access to HIV Drug Therapies
Unfortunately, a large number of people living with HIV and AIDS will be
unable to access what has become the new "standard of care." Because
HIV disease is inevitably impoverishing for the great majority of people who
become infected, over the last 15 years a fragile and intricate AIDS care
infrastructure has been built to ensure that impoverished and medically needy
people with AIDS have access to basic health care and life-saving drugs. Today,
the myriad programs that make up this AIDS care infrastructure are threatened by
pressures on federal and state health budgets. The rise in price for basic
antiviral therapy -- which now runs from $3,000 for antiviral monotherapy to up
to $13,000 for combination therapy -- is likely to accelerate this alarming
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This article was provided by AIDS Action Council.