Ask Dr. Jeff
Question: A friend of mine was diagnosed with HIV when he came down with pneumocystis pneumonia (PCP) one year ago. At the time, his viral load was 200,000 with a 200 CD4 count. His doctor put him on Combivir, Norvir, and Bactrim. His current viral load is below the limit of detection, with a 360 CD4 count. His doctor wants to eliminate AZT and Norvir from his regimen and change to Zerit, Epivir, and Sustiva. The rationale is that the doctor wants to save the other drugs for a backup plan if his numbers should drop in the future. Another observation in support of the change was the fact that he has had PCP in the past. A number of his friends are concerned about the wisdom of switching a drug regimen that is currently doing the job and is well tolerated, to the point where he is able to work full time. His numbers and health just do not fit the usual protocol for making a change in medication.
Answer: You ask a very important question for which there is no one correct answer. However, there are several important factors to consider when switching from a regimen that is working, i.e. keeping the viral load below 50. First, by definition your friend had fairly advanced HIV disease, evidenced by a high viral load, relatively low CD4 cell counts and a major opportunistic infection, PCP. He has done well on a three-drug regimen containing a protease inhibitor (PI). So, the question is really "Why mess with success?"
First, there are some long-term complications that appear to occur more often in people on PIs. These are lipodystrophy, insulin resistance (high blood sugar), and high blood lipids (high cholesterol and/or triglycerides). So the considerations are these: Does your friend have any of these problems? Are his cholesterol and triglycerides levels high? Any elevated glucose? Any fat loss or accumulation problems? If the answer to any of these is Yes, he would potentially benefit from switching to a non-PI regimen. While all the facts are still not in on whether this will be an effective strategy, studies presented at the Retrovirus Conference in February showed that most people with good viral suppression on a PI-containing regimen continue to have good suppression when switched to an NNRTI-based regimen, so it appears safe to switch.
Will an NNRTI-based regimen be better in preventing lipodystrophy? We do not know. In this issue of the STEP Perspective, we review data from the First Lipodystrophy Conference held this June that suggests that d4T (Zerit) may be associated with lipodystrophy, along with PIs. However, in my experience, most people show some signs of abnormal blood lipids or lipodystrophy within the first year of therapy. So, if your friend has been on a PI-containing regimen for more than a year without these problems, then I think his chances of developing them in the future are lower than someone just beginning a PI-containing regimen.
Another consideration is drug tolerance. Norvir, in doses used as a single PI, is generally associated with a high incidence of gastrointestinal (digestive) problems. However, your friend is tolerating it well, so there is no need to change for that reason. Overall, Sustiva is very well tolerated, but many people have some significant problems with abnormal dreams and inhibited thought processes the first few weeks, as reported by the DuPont 006 trial. However, for most people, these problems resolve within a few weeks.
Next, many providers are reluctant to start someone with advanced disease on a non-PI containing regimen. However, the data from DuPont's 006 trial showed that people with viral loads above 100,000 did better with Sustiva (an NNRTI), AZT, and 3TC, compared to a regimen of Crixivan (a PI), AZT, and 3TC.
The AIDS Clinical Trials Group (ACTG) has a major ongoing study (ACTG 384) that compares a PI to an NNRTI-based three-drug regimen; it also compares AZT to d4T as the first nucleoside analog. Over 800 people are currently enrolled in that trial, but there are no results yet available.
The ACTG also has another trial (ACTG 388) for people with viral loads over 80,000, or CD4 cells below 200. It compares a regimen with a PI plus two nucleoside analogs to regimens with two PIs, a PI plus an NNRTI, and a PI plus two nucleosides. This trial has enrolled over 500 people, but again, no data is yet available.
The final consideration is whether you can switch and preserve treatment options in the future. You can. With either a PI or an NNRTI-based regimen, you can switch to the other class if the current drug regimen fails to suppress HIV replication. There is no cross resistance between the PI and NNRTI classes of drugs, only cross resistance within those classes of drugs. Also, since only one mutation is required to develop resistance to NNRTIs (the K103 N mutation), while multiple mutations are required to become resistant to PIs, some providers prefer the PI regimen in people with advanced HIV disease. Regarding AZT versus d4T, there is no data to show that using one first is better than using the other first. As noted above, ACTG 384 is studying this question.
So, as you can see, there is no correct answer. However, in general, I think that if a regimen is working, unless there are serious problems, it is best not to change, particularly in someone with advanced disease.
Answer: A surgeon who refuses to operate on you because you are HIV-positive is in violation of the American with Disabilities Act (ADA), unless there is a valid medical reason, other than your HIV-status, for refusing to do the operation. The U.S. Supreme Court, in Bragdon v. Abbott et al., on June 25, 1998, ruled that a dentist cannot refuse to provide dental care to an HIV-positive person. One of the major issues was whether an HIV-positive person was covered by the protections of the Americans with Disabilities Act, and the court ruled that they are. Also, courts have rejected the argument that healthcare providers can refuse to provide HIV care because of their risk of being infected. In the past, some surgeons argued that the risks of elective surgery on people who are HIV-positive were too high, due to fears of infections or wound healing problems. However, the data shows that in general the risks are very low and should not be a basis for refusal to operate on HIV-positive people.
While you may not want to force someone to provide care they do not want to provide, you might be able to sue and collect damages. However, ADA cases are generally very expensive to litigate. I would suggest you try to get written documentation from your surgeon stating the reason for his/her refusal to operate on you. I would also suggest you call the major medical centers or medical schools in your area for a surgical referral. Also, you could ask the major HIV providers in your area for names of surgeons they have worked with who are comfortable operating on people who are HIV-positive. In general, most general surgeons have been very good at providing care to HIV-positive people, unlike some members in the dental profession. (I say this not only because I am a former general surgeon.)
This article was provided by Seattle Treatment Education Project. It is a part of the publication STEP Perspective.