Primary and secondary prophylaxis for Pneumocystis carinii related complications in HIV patients.

At the beginning of the acquired immune deficiency syndrome (AIDS) era, nearly 15 yrs ago, Pneumocystis carinii pneumonia (PCP) was the most common human immunodeficiency virus (HIV)-related complication. PCP represented about 60% of the initial case-defining events of AIDS patients [1]. Almost 80% of HIV and AIDS patients experienced at least one episode of PCP in the course of their HIV infection [2, 3]. Thanks to secondary prophylaxis, the number of relapses of PCP has recently declined. But PCP is still the most commonly reported AIDS-associated diagnosis amongst HIV-infected individuals in Western industrialized countries [4]. Mortality was high, as the disease was not recognized early enough in many cases and the benefits of systemic steroids were not known at that point of time [5, 6]. Increased risks for PCP are: a CD4+ count <200 cells·μL-1 at the time of AIDS diagnosis; male homosexuality/bisexuality; and the diagnosis of AIDS in northern Europe [7]. Of AIDS patients with a history of one or more episodes of PCP, 60% are likely to experience another relapse within one year if specific prophylaxis is not administered [8, 9]. A recent study suggested that some recurrent episodes of PCP are caused by reinfection rather than by reactivation of latent infection. This hypothesis is based on genetic heterogeneity of mitochondrial ribosomal ribonucleic acid (RNA) gene of Pneumocystis carinii hominis isolates from AIDS patients with recurrent episodes of PCP [10]. In 1990, LEOUNG et al. [9] published the first report proving the prophylactic efficacy of inhaled aerosolized pentamidine against PCP in 408 high-risk HIV patients. A dose of 300 mg aerosolized pentamidine administered once monthly by jet nebulizer was the most effective secondary prophylaxis. After 18 months, only 8 out of 139 participants receiving the 300 mg schedule had experienced a PCP relapse, as compared with 22 out of 135 subjects having been randomized to receive the low dose of 30 mg pentamidine every 2 weeks [9]. Another study investigated the preventive value of inhaled pentamidine in 223 HIV patients (<200 CD4+ cells·μL-1) or AIDS related complex = Centers for Disease Control (CDC) B3 in the current classification) without previous episode of PCP. Eight patients with primary prophylaxis versus 23 patients in the placebo group experienced a PCP (p=0.0021) [11]. On the basis of these two studies, the regular application of aerosolized pentamidine for primary and secondary prophylaxis against PCP had become a standard of management in HIV patients with less than 200 CD4+ cells·μL-1 or in AIDS patients with a previous episode of PCP. Administration of pentamidine by jet nebulizer and by ultrasonic nebulizer provides sufficient respirable particles [12]. Adverse events are rare and limited to transient unpleasant taste and cough. Smokers or patients with bronchial hyperreactivity may develop bronchospasm, which is usually prevented by prior administration of two puffs of a bronchodilator [13]. Long-term, unwanted effects or irreversible ventilatory dysfunctions are not known in patients regularly inhaling aerosolized pentamidine [14, 15]. Rash [16], pancreatitis [17], hypoglycaemia [17], diabetes [18], and renal insufficiency [19] have been described but occur much more commonly when pentamidine is administered intravenously. The association between the application of aerosolized pentamidine and the development of spontaneous pneumothorax is well-known [20]. Also, the financial aspects of aerosolized pentamidine cannot be overlooked; this prophylaxis being about five times more expensive than the administration of co-trimoxazole and about 10 times as expensive as dapsone. Additionally, there have been several reports describing extrapulmonary manifestations of Pneumocystis carinii. These are found in 0.5–3% of patients with PCP [21]. About 50% occur in HIV patients, despite regular inhalation of aerosolized pentamidine. Positive blood polymerase chain reactions (PCRs) for Pneumocystis carinii indicate haematogenous spread during acute pneumonia [22]. Almost all organs can be involved in disseminated Pneumocystis carinii infections in AIDS. Examples are mastoiditis [23], skin manifestations [24], hepatitis [25], splenitis [26], thyroiditis or the involvement of the bone marrow [27] with secondary pancytopenia. In this issue of the Journal, EWIG et al. [28] report an incidence of breakthrough PCP of 23% at 36 months in 95 HIV-infected patients with primary aerosolized pentamidine prophylaxis, similar to results published previously [29]. EWIG et al. [28] compared the clinical and radiographic presentation as well as the outcome of breakthrough PCP in those patients with "early" (≤12 months of inhalation time) and with "late" (>12 months of inhalation time) failure, and found no difference between these two groups. Presentation with upper lobe infections was also a radiographic pattern of late failures. EDELSTEIN and MCCABE [30] first described this atypical presentation in 1990 and, in contrast to EWIG et al. [28], they observed complicated courses, such as cavities and pneumothoraces. Lung cavitation in PCP may also occur without inhaled pentamidine prophylaxis [31]. EDITORIAL