Are you someone on HIV treatment, but depressed about not being suppressed? In other words, is your viral load not undetectable? Are you uncertain about whether something can or should be done about this predicament?
For starters, let’s review some background information and research. In plain English, if the virus is replicating while on treatment, it is mutating. Mutations are changes in the viral gene that allow it to continue reproducing itself and surviving. This occurs because the virus overcomes the presence of antiviral drugs in the bloodstream.
Several studies have been completed studying patients who are not undetectable with persistent or elevated viral loads. All have shown that these individuals are at risk for development of further increases in mutations to antivirals in the various drug classes.
As far back as 1998, Dr. Doug Richman reported on more than 1,000 blood samples taken randomly from the representative 132,500 patients who received care in the year 1996. This blood work was from study participants who were not undetectable or whose viral loads (HIV-RNA) were greater than 500 copies/mL in 1998.
Shockingly, 76% had resistance mutations for at least one of the drug classes and 48% of patients at that early year had already harbored resistance mutations to two drug classes. Additionally, 41% had resistance mutations to protease inhibitors, and 13% in 1998 had already developed triple class resistance mutations.
Thus, we can imagine what the statistics would look like today, with many more years of treatment and exposure to more medications by most patients. Let’s not forget about the many individuals now seroconverting or those getting infected with resistant virus at the starting gate.
Last year’s Conference on Retroviruses and Opportunistic Infections highlighted the SCOPE study investigating the changes in people on treatment with viral loads greater than 1,000 copies. They deferred regimen changes during the observation period of the study, with resistance testing every 120 days. At the end of one year, 44% had at least one new resistance mutation to one class; 23% to a nucleoside analogue, and 18% to a protease inhibitor. Thus, persistent viremia—that is, detectable virus—runs the risk of possibly limiting future treatment options. I should also mention that two other studies had similar results.
With these facts in mind, let’s discuss an example of managing a patient in this situation. Justin is a treatment-experienced guy who is failing his current antiretroviral regimen. He was on treatment for a few years now and his latest CD4 T-cell count is 290 cells/mm3, which has been relatively stable over the last year. His last visit with his doctor showed a viral load of 4,500 copies/mL, but this has been slowly increasing over the past few months. As a physician, it should be possible to construct a more effective treatment for Justin.
The doctor’s discussion with Justin would probably include answering questions about when to switch to the next treatment. Should Justin wait for his T-cell count to begin dropping? Should we wait until his viral load goes above 10,000? Should we wait until Justin starts feeling tired or sick, since currently he feels pretty well, although he is on testosterone injections at the clinic? Should we wait until he has better treatment options, since he has already failed Kaletra and also had a history of Viramune? Justin probably has mutations in several classes of drugs.
The answer to these questions should be NO! We don’t wait for patients to get sick, nor deteriorate. We try to be preemptive and offer patients more options and hope for the future.
Accordingly, there may be treatment options based on resistance testing, but other new drugs from newer classes can provide greater possibilities. Justin’s doctor may not know about the availability of MK-0518 (the Merck integrase inhibitor), or TMC-125, a second generation non-nuke. Educate him!
Nor may his doctor be involved in research that can grant possible access to Gilead’s integrase inhibitor, GS 9137. However, Prezista is a newer protease inhibitor shown to be effective for resistance to other PIs, and Fuzeon is an injectable fusion inhibitor. Both are readily available in your local drug store or AIDS Drug Assistance Program (ADAP) formulary. Other older agents may also show benefit, such as Ziagen and/or Viread.
Justin should have a resistance test to inform his options. A genotypic test examines the unique gene sequence of Justin’s virus, mapping out any expected resistance; a phenotype test provides clinical resistance information about which drugs Justin’s virus is susceptible to or effective.
The risk of waiting is that Justin will continue to develop more resistance and see his options diminish. Perhaps now, having been exposed to one protease inhibitor, he may not have accumulated overwhelming resistance mutations to PIs and may have several other PIs as options. Finally, newer treatments are under study and their availability provides patients with new hope and improved quality of life.
Daniel S. Berger, M.D., is Medical Director of Chicago’s largest private HIV treatment and research center, NorthStar Healthcare. Dr. Berger can be reached at DSBergerMD@aol.com or (773) 296–2400. |
