PCP, or Pneumocystis carinii pneumonia, has always been closely associated with AIDS. From the beginning, PCP is the most common of the list of diseases that make up AIDS. Infected people who have never been tested for HIV are likely to come to an emergency room one day very short of breath and get a PCP diagnosis. Before effective antiviral treatment or PCP prophylaxis, 70-80% of all HIV-infected people in North American and Western Europe eventually got PCP, and often died from it.
The implementation of prophylaxis to prevent a first episode (primary prevention) or subsequent episode (secondary prevention) was the first drug therapy to substantially increase survival and improve quality of life for people with HIV/AIDS. We eventually learned that one tablet a day of trimethoprim-sulfamethoxazole (better known as Bactrim or Septra) was the best single means of PCP prophylaxis, and protected against toxoplasmosis as well as some bacterial respiratory tract infections. There are alternatives like dapsone or inhaled pentamidine for those who cannot tolerate Bactrim. The Public Health Service recommended that everyone whose t-cell (CD4) count dropped below 200 (and some folks whose counts were above that) take prophylaxisfor the rest of their lives.
That's the rub: for the rest of one's life. PCP prophylaxis is probably the cheapest and easiest of all our daily medications, but it is still one more pill, and carries the risk of drug resistance to some bacterial infections.
Are New T-Cells As Good As Your Original Ones? The desire to lessen one's daily pill count and compliance burden is one reason we have all been interested in the implications of rising CD4 counts with effective haart (highly active anti-retroviral or combination therapy). Most people on haart get a rise in t-cell counts to well above 200. Whether or not these newer t-cells are as protective against opportunistic infections as original t-cells, has been controversial. When people with AIDS, who required daily prophylaxis to PCP and other OIs, first began to respond to haart with rising CD4 counts, they still were vulnerable to OIs for a few months. As these t-cell gains were maintained for several months, however, the incidence of new OIs fell way off.
Laboratory scientists found evidence that paralleled this clinical observation. The first new t-cells created after HIV replication had been suppressed were simply clones of those that were still left in the person's damaged immune system. This means, they were exact duplicates of those t-cells (or memory cells) that still existed. If someone had already lost the ability to fight a particular OI, then the new clones would not restore it.
Scientists then found that later on, new "naïve" t-cells were created. Naïve, in this context, means that it is not pre-programmed to fight one, and only one, kind of opportunistic pathogen or cancer. Rather, it is available to learn to fight whatever comes along. As more of these new naïve cells are produced, then the immune system can resist or fight off OIs that it was formerly unable to.
Does It Work In Practice? Beyond observation and laboratory work, how can we determine if one's immune system is strong enough to stop prophylaxis? Well, a step toward this knowledge is a controlled clinical trial in a large and diverse group. Take a group of people on PCP prophylaxis whose t-cells have risen above 200. Stop prophylaxis and see if anyone gets PCP. At the same time, see if anyone gets toxoplasmosis brain disease.
Swiss investigators did just that. They reported their results in the April 29 issue of The New England Journal of Medicine this week. The study is based on the Swiss HIV Cohort, a study that includes most people with HIV in Switzerland. Everyone who had once been under 200 (and thus automatically started on PCP prophylaxis) and who had then risen to above 200 and at least 14%, and had maintained this rise for a minimum of 12 weeks, were eligible for this study. Of 396 individuals who met these criteria, 279 chose to participate.
They stopped taking PCP prophylaxis (whichever kind they were on) and were followed closely for at least nine months. The average age of the group was 37. Two-thirds were men and one-third were women. The exposure categories were about equally balanced among male-male sex, heterosexual sex, and drug injection. On average, the t-cell count when the study started was 325. On average, each participant's lowest t-cell count before starting haart was 111.
After about one year of observation, there have been no cases of PCP in the group. There have also been no cases of toxoplasmosis disease, whereas nearly half the group had evidence of prior exposure to toxo at study entry.
The investigators conclude that it is safe to stop PCP prophylaxis in those who meet their study's eligibility requirements: maintenance of t-cell counts above 200 and 14% for at least 12 weeks.
Comment: Though there are some necessary caveats, this is good news indeed. The caveats include the caution that we do not know whether those who enrolled in the Swiss study are completely representative of all people in comparable categories. The authors of this report did not characterize whether or not those who chose not to enroll differed in any potentially significant way from those who did participate.
The second caveat is that individuals differ. A controlled trial offers some of the best evidence we have for making decisions, but it is not foolproof. Though most people got PCP when their CD4 counts dipped below 200, still others got PCP at CD4 counts higher than 200. One should always evaluate one's individual risk profile with a knowledgeable clinician before deciding to stop this or any other medication.
Overall, this study offers one more welcome confirmation that damaged immune systems can be substantially-if not totally-rebuilt, and function competently once again, at least as long as effective antiviral therapy can be maintained. That is good news indeed.