It Is Safe to Discontinue Secondary Prophylaxis for PCP in HIV-Infected Patients Treated with HAART?

When a person has <200 CD4s and takes PCP prophylaxis, such as Bactrim, to prevent getting PCP that is called primary prophylaxis. When a person has experienced PCP and takes PCP prophylaxis to prevent recurrence, that is called secondary prophylaxis. Based on the results of several studies the recent PHS-DHHS Guidelines on OI prevention recommended discontinuation of prophylaxis for primary PCP with immune reconstitution (adequate increase in CD4s). However, they said there was not enough data to support discontinuation of secondary prophylaxis. The following studies are relatively short-term in follow-up, but suggest that if a person had a prior episode of PCP and their CD4s were now adequately higher, discontinuing PCP prophylaxis appears mostly safe. Although there still is a low risk of PCP recurring.

Several studies reported at Retrovirus address this question. The first study was reported by B Ledergerber and colleagues as a Late Breaker. It's an analysis of 246 patients (14% female) with prior definitive or presumptive PCP who stopped secondary prophylaxis for PCP. These patients were from 17,500 patients followed prospectively in 8 participating cohorts: EuroSida (Europe), ATHENA (The Netherlands), Swiss HIV Cohort Study ( Switzerland), Danish Cohort of Patients Discontinuing Prophylaxis (Denmark), Frankfurt HIV Cohort (Germany), Nice DMI-2 Cohort, ICONA (Italy), HSR Cohort (Italy).

The 246 patients had a definitive or presumptive diagnosis of PCP, had started secondary prophylaxis, had stopped secondary prophylaxis while on HAART (PI or NNRTI+ 2 nukes), and had a CD4 count of 200 or more at the time of stopping secondary (SP) prophylaxis. They discontinued SP after 15-32 months on SP, duration on HAART of 13-25 months, and CD4s were 277-371. The nadir (lowest) CD4 count before stopping SP was 24-69 cells. Follow-up has been for 5-13 months or 236 person years of follow-up. No one has experienced a recurrence of PCP. One patient experienced an AIDS-defing event (Wasting Syndrome) during follow-up. These results are encouraging but short-term. The risk of recurrence of PCP is still possible.

In a second study reported at Retrovirus, Koletar and colleagues presented preliminary data from ACTG 888 on patients with prior CD4s <100 and who had a previous case of PCP. A total of 269 patients were evaluated (144 with CD4+ counts < 100 cells [Group I] and 125 with prior PCP [Group II]). All had rises of CD4+ counts to > 200 cells/mm3 and all had prophylaxis discontinued. There has been a mean follow-up of 60 weeks in Group I and 38 weeks in Group II, and no cases of PCP in either group. Several patients resumed PCP prophylaxis after two consecutive CD4 tests <200.

Furrer and colleagues reported follow-up analysis from the Swiss StopCox Study.  This was a prospective multi-center study of the safety of discontinuation of primary prophylaxis in 396 patients with sustained (>12 weeks) CD4s >200, 14% CD4 percentage, CD4 nadir (lowest) of 105 cells (190 patients had CD4s <100). At discontinuation, the median CD4 count was 327 and the median viral load was 2 log (100 copies/ml). About 157 people had viral load >100 copies/ml.  About 46% of the patients in this study were seropositive for toxoplasma Gondii, and thus at risk. Follow-up was about 16 months. One patient was diagnosed with PCP. Their CD4 at diagnosis was 530 and viral load <50 copies/ml. No one was diagnosed with toxoplasma gondii.

Discontinuation is Not Risk Free. Fred Valentine from NYU Medical Center reported on two people who had substantially increased their CD4s, and reduced viral load to <50 copies/ml for >12 months. One patient who had biopsy proven PCP at >400 CD4s had no lymphocyte proliferative response to PCP antigens, even though his lymphocytes responded strongly to Candida, CMV, Mycobacterium, and Toxoplasma antigens. Lymphocytes from a second patient who developed CMV retinitis after his CD4s had increased to 190 did not respond to CMV antigens even though they responded to antigens from other opportunistic infections. It's possible these patients had completely lost specific immunity or CD4s in their "repertoire" to particular antigens. HIV replication may have depleted them. And CD4 increases were not able to regain this protection. Such an experience may be rare but possible.