Kids’ Doc in Jos

In the HIV/AIDS treatment community, we’ve heard it over and over. Adherence is everything. The key to a long-term suppression of the virus is to keep it from multiplying, because multiplying means mutating, and mutating means developing resistance to the drugs. So a large part of our effort must be directed toward doing everything we can to ensure that our patients are able and determined to take every dose. The situation is so critical that missing one or two doses during one month can spell drug failure and ultimately death for the patient. See the story, “The Monkeys’ New Houses,” that I wrote for AIDS Is Real and It’s In Our Church.

If you’ve ever had to take medicines for even a week or two, you probably found that it’s easy to forget a dose or two. Maybe you’re held up at work and don’t have the drug with you. Maybe you are feeling too sick, or the drugstore is closed until the next day. In most situations, doctors are probably very happy if patients get 80-90% of their doses. Not so with HIV/AIDS.

Paul (not his real name) is three-and-a-half years old. He was one of the first children in our antiretroviral (ARV) program, which he entered nearly 18 months ago. He did very well, making a remarkable turnaround. His CD4 count (a measure of the strength of the immune system) went from a terrible 16 to an almost normal 700 after 8 months. Now, though, he’s once again quite ill, and his latest CD4 count is again less than 20. What went wrong? [Chart above: Paul’s growth chart showing rise and fall of CD4 and weight (height too, but that’s surely due to measurement error).

Well, we don’t have the resources to determine just what went wrong. Very few centers in Africa do have the ability to count the virus in the blood (viral load) or to determine to which drugs a patient’s virus is resistant or not. So we have to go by the most likely scenario. If the next paragraphs are too technical for you, just skip to “The Bottom Line” below.

Paul’s mother died last summer, quite suddenly and unexpectedly. In the turmoil surrounding that tragedy, Paul went for at least a week without taking his antiretroviral drugs. The first event was that two of his three drugs (zidovudine and lamivudine) quickly disappeared from his body after a day or two. Next, the virus started multiplying, though at a low rate because it was still held in check by the third drug, nevirapine, which stays in the body for days to weeks. Almost every new HIV virus particle is different from its “parent” because the copying process is so error-prone, and there were perhaps ten to a hundred million new viruses being made in Paul’s body each day.

HIV only needs a single mutation to make it completely resistant to nevirapine and related drugs. Very likely the mutation arose during that one-week gap in Paul’s treatment. Being unaffected by the nevirapine and in the absence of the other two drugs, it would quickly reach high levels of multiplication and begin destroying the immune system again.

If we had known this at the time, not just worried about it, and if we had had an alternate class of drug available, we might have stopped the downward slide. We didn’t. Next Paul started taking all three drugs again, but unknown to us, only two of them were still effective. That meant the virus kept multiplying at a low level, slowly accumulating mutations that made the zidovudine less effective, and at some point (probably) aquiring another single mutation, the infamous M184V, that made his lamivudine next to useless as well. Now, with much more freedom to multiply, the virus could even more quickly accumulate mutations against zidovudine.

All of this happened silently. Finally, with the virus probably near its original levels, Paul became sick again and his CD4 count fell back to near zero. The damage is done, though, because resistance cannot be undone. On top of everything else, it looks as if Paul has had a recurrence or new case of tuberculosis, though other lung diseases are possible.

Second line, what second line?

(Feel free to skip to The Bottom Line). So, now what? We need at least two new drugs to which the virus is (hopefully) sensitive. Our current choices of drugs are: zidovudine, stavudine, didanosine, lamivudine, tenofovir+zalcitabine, nevirapine, efavirenz, and Kaletra (lopinavir/ritonavir).

Lamivudine, zalcitabine, nevirapine and efavirenz have failed (zalcitabine with lamivudine and efavirenz with nevirapine). Zidovudine and stavudine (more-or-less equivalent drugs) are compromised. Didanosine and tenofovir (?) are possibilities, but cannot be given together, and in any case we would have a hard time getting the right dose of tenofovir since we don’t have it in liquid form. Kaletra is the only remaining drug, and a very good candidate, but the anti-TB drug rifampin is incompatible (causing the body to get rid of Kaletra too quickly).

The Bottom Line

It’s likely that when Paul missed a single week of treatment this led, silently at first, to the failure of all three of the drugs we were using for him. Plus he may have tuberculosis (TB) which is very difficult to diagnose accurately here. We’re in a pickle. To do proper second line treatment, we need to have at least two new drugs, preferably three, to which Paul’s virus is still sensitive. We do not have three drugs. Without resistance testing we have to play the odds, as we do on the question of whether to treat him for TB. If we do treat for TB, that eliminates the most promising second-line drug choice during the 6-9 months of TB treatment.

We’ll have to make a decision this week. I’d love to hear comments or advice.

This entry was posted on Sunday, March 12th, 2006 at 10:11 pm and is filed under Mike's jottings, My patients. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.