Pneumocystis carinii pneumonia after cessation of secondary prophylaxis in a patient on highly active antiretroviral therapy with a CD4 cell count greater than 200/mm3.

Abstract

Recently published data suggest that HIV-infected individuals receiving highly active antiretroviral therapy (HAART) who maintain a CD4 cell count greater than 200/mm3 for a 3 month period and virological suppression to less than 5000 copies/ml can safely discontinue secondary prophylaxis against Pneumocystis carinii pneumonia (PCP) [1,2]. We describe a 61-year-old man who developed PCP after the cessation of trimethoprim–sulfamethoxazole as secondary prophylaxis. The patient was diagnosed with HIV infection in 1990. His treatment, CD4 cell counts and viral loads are summarized in Fig. 1. In 1993, he developed microbiologically confirmed PCP when his CD4 cell count was 270/mm3 (18.5%). After treatment, he remained on trimethoprim–sulfamethoxazole prophylaxis. After the initiation of nevirapine his CD4 cell count increased from a nadir of 150/mm3 to a peak of 420/mm3. Subsequently, his CD4 cell count decreased by 42 cells/mm3 per year (utilizing linear regression of multiple CD4 cell counts measured after 3 months of therapy) [3]. His viral load was often undetectable, and never exceeded 1500 copies/ml. His trimethoprim–sulfamethoxazole prophylaxis was ceased when his CD4 cell count had been greater than 300/mm3 for over 12 months.Fig. 1.: Changes in the patient's CD4 cell count (•) and HIV viral load (▪) after antiviral therapy with zidovudine, didanosine and nevirapine. Sulfamethoxazole–trimethoprim (bactrim) prophylaxis is shown. Two episodes of P. carinii pneumonia are shown with black arrows.Twelve months after the cessation of secondary prophylaxis, the patient was diagnosed with microbiologically confirmed PCP. His CD4 cell count was 360/mm3 (16.4%) with a viral load of 800 copies/ml. He responded to standard therapy with trimethoprim–sulfamethoxazole and remains on prophylaxis with this agent. To our knowledge, at the time of writing, this is the first reported case of PCP after the cessation of secondary prophylaxis with trimethoprim–sulfamethoxazole in a patient with a CD4 cell count greater than 200/mm3 and low viral loads while on HAART. In considering the possible reasons for the recurrence of PCP in this patient, it is of note that his first episode of PCP occurred when his CD4 cell count was 270/mm3, a well described but uncommon event. Interestingly, this patient failed to demonstrate a steady biphasic increase in total CD4 cell count, the latter phase believed to be associated with an increase in naive CD4 T cells [4]. These atypical changes and indeed relative decline in CD4 cells may be indicative of inadequate immunological regeneration in our patient. We suggest caution be exercised when ceasing secondary prophylaxis in individuals in whom a first episode of PCP occurs at CD4 cell counts greater than 200/mm3. Advances in methods to quantify the regeneration of pathogen-specific T cell responses to PCP (as has been demonstrated with cytomegalovirus [5]) may be useful in refining future treatment decisions in this setting. Lyn-li Lim Alan C. Street Sharon R. Lewin