FAILURE OF PROPHYLAXIS AGAINST PCP IN PATIENTS WITH HIV-INFECTION

Since the end of the 1980s, primary anti-Pneumocystis carinii pneumoni a (PCP) prophylaxis has become a fundamental part of the global AIDS c ontrol strategy in industrialized countries. The widespread adoption o f anti-PCP chemoprophylaxis has been a key element in prolonging the s urvival of patients with AIDS. There is general agreement on the need to begin chemoprophylaxis when individual CD4(+) cell counts drop belo w the value of 200/mu L. However, PCP still develops in up to 27% of s usceptible HIV-infected patients despite regular prophylaxis intake. F ailure of chemoprophylaxis may depend on different factors. The choice of the regimen and the patient's compliance to it have been the first variables to be identified, whereas the importance of the residual ce llular immune function as complementary protective mechanism against P CP has emerged in subsequent clinical studies. Albeit of limited gener al concern, issues such as P. carinii drug resistance and defective dr ug absorption may play some role in prophylaxis failure in selected pa tients. Regarding the epidemiology of primary and recurrent episodes o f PCP, recent studies based on genetic fingerprinting techniques revea led that interhuman transmission of the organism could be more relevan t than so far expected, thus raising some concern of the possibility o f nosocomial spread among susceptible individuals. The downgrading ten dency of immune competence in HIV infection and the related increasing risk of developing PCP make it possible to envisage a two-step chemop rophylactic strategy, with the most effective compound, cotrimoxazole, to be reserved for the last and most risky disease stage, when immune response no longer provides any support for preventing the developmen t of PCP.