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Objective: To investigate the efficacy and safety of three regimens for primary prophylaxis of Pneumocystis carinii pneumonia (PCP) and toxoplasmic encephalitis (TE) and to evaluate their effect on survival in patients with HIV infection., Design: Randomized, open label, prospective trial., Setting: A single Infectious Diseases Department in Italy., Patients: HIV-infected patients (n = 197) with a CD4 count < 200 x 10(6)/l and without previous PCP or TE., Interventions: Patients were randomly assigned to receive (1) aerosolized pentamidine (AP; 300 mg monthly), (2) cotrimoxazole (CTX; 160 mg trimethoprim and 800 mg sulfamethoxazole every other day), or (3) dapsone-pyrimethamine (DP; 100 mg weekly dapsone and 25 mg biweekly pyrimethamine)., Main Outcome Measures: PCP, TE, death, and drug-limiting toxicity. Considering difference in PCP occurrence the trial was interrupted on June 1992. Observation was prolonged until June 1994 for TE and survival., Results: Intention-to-treat analysis yielded PCP rates of 10.2 per 100 person-years in the AP, 2.0 in the CTX, and 32.1 in the DP group [adjusted relative risk of DP versus CTX: 17.5; 95% confidence interval (CI), 2.2-139.6; P = 0.007]. TE rates in patients with positive Toxoplasma serology were 25.6 per 100 person-years in the AP, 8.9 in the CTX and 9.4 in the DP group. In 'on treatment' analysis, no episode of TE developed in the DP group, and rates were 34.7 per 100 person-years in the AP and 2.5 in the CTX group (AP versus CTX: P = 0.01; AP versus DP: P = 0.004). The adjusted risk of mortality for the DP group was 2.8 times that of the CTX group in the first part of the study (95% CI, 1.1-7.3; P = 0.037), and 1.8 times (95% CI, 1.1-2.9; P = 0.02) in the prolonged follow-up. No significant difference in the occurrence of serious adverse reactions was observed between the three treatment groups., Conclusions: Intermittent CTX was more effective than low-dose DP and showed a slight but not significant advantage on AP for primary PCP prophylaxis. DP was associated with a shorter survival. Both CTX and DP resulted in a significant reduction in the risk of TE.

Technetium-99m (99mTc) labelled polyclonal human immunoglobulin (HIG) is a new agent for the localization of active inflammatory diseases. The results obtained with HIG in 29 AIDS patients referred for suspected lung infections are reported (Table I). The patients also underwent Gallium-67 citrate scanning (GS), chest radiography (Rx), high-resolution thin-layer computed tomography (HRCT) and broncho-alveolar lavage (BAL). The study population was classified as follows: 12 patients (Table II) were studied before treatment for suspected Pneumocystis carinii pneumonia (PCP), 7 patients (Table III) had known PCP and were studied during medical therapy, and 10 patients (Table IV) had lung infections other than PCP. In all PCP patients studied before treatment, positive agreement was observed between HIG, Rx and HRCT findings. In 4 patients with final clinical diagnosis of no lung conditions, both nuclear and radiologic imaging were negative. 99mTc-HIG results in the PCP patients studied during therapy were consistent with clinical and radiologic improvement; there was disagreement with 67Ga findings in one case (no. 9). In lung infections other than PCP, HIG studies were often negative (always negative in mycobacteriosis), while they were positive in 3 pyogenic abscesses. In conclusion, as for PCP and abscesses, the results obtained with 99mTc-HIG are usually in agreement with GS findings, while HIG scans seem to be negative in mycobacterial infections. Moreover, HIG scintigraphy seems to be suitable for the evaluation of treatment results in PCP (this subject deserves further research). To assess respiratory impairment a semiquantitative index (ISQ) of 99mTc-HIG lung uptake is suggested, which showed a significant linear correlation with arterial pO2.

DNA amplification by the polymerase chain reaction (PCR) is a promising method for the detection of Pneumocystis carinii in immunosuppressed patients. The sensitivity and specificity of the PCR technique has been assessed in comparison with the immunofluorescence method (IF) on bronchoalveolar lavage fluid (BALF). Results correlated in 43 (78.8%) of 52 cases studied. P. carinii PCR gave positive results with BALF from all 32 patients found to have P. carinii pneumonia (PCP); IF gave positive results with 26 of them. PCR was more sensitive and as specific as IF. However, at the present time, we do not believe that it is clinically useful for detection of P. carinii in BALF samples. P. carinii DNA amplification by PCR should be reserved for testing IF-negative BALF samples from patients judged clinically to have PCP.

Fifty-five episodes of Pneumocystis carinii pneumonia (PCP) in AIDS patients were evaluated to assess clinical and laboratory risk factors predicting the probability of surviving the acute episode of PCP and the long-term survival after PCP. Age > 45 yrs, PaO2 < 50 mmHg, AaPO2 > 50 mmHg, and LDH > 800 IU/L correlated strongly with early mortality; patients who needed mechanical ventilation had a significantly lower PaO2 and serum albumin, and higher AaPO2 and LDH compared to the patients who did not. Neither age nor PaO2, AaPO2, LDH, albumin, days from onset, time for recovery, CD4+ cell count correlated with long-term survival of AIDS patients with PCP. Informations obtained at initial presentation of PCP may predict early outcome and influence therapeutic approach, improving chances for survival.

Scintigraphy with 99mTc labelled human polyclonal immunoglobulin was performed in 16 patients with ascertained or suspected AIDS-related infections. 99mTc-HIG lung scanning was compared, in 11 patients, with 67Ga scintigraphy, chest X-ray and high resolution lung CT. 67Ga and 99mTc-HIG were concordantly positive in five cases of BAL-ascertained Pneumocystis carinii pneumonia (PCP), while one of them was Rx and CT negative. X-ray, 67Ga and 99mTc were concordantly negative in 5 cases. 99mTc-HIG yielded negative results in two cases of Mycobacterium infection, both of which were 67Ga and Rx positive: Mycobacterium avium in diffuse lung involvement and Mycobacterium TBC in excavated infiltrate. 99mTc-HIG was also positive in other 3 AIDS patients: 1 case of intestinal cryptosporidiosis, 1 pulmonary abscess (Staphylococcus and Candida), and 1 sacral abscess; it was negative in 1 case of Kaposi sarcoma (also 201Tl negative). In conclusion, 99mTc-HIG scintigraphy in AIDS patients is feasible, and offers some practical advantages (continuous availability, fast response time, etc.). The initial results seem similar to those of 67Ga in lung scanning (and perhaps more specific for PCP).