Claudie Marche

Treatment of central nervous system toxoplasmosis with pyrimethamine/sulfadiazine combination in 35 patients with the acquired immunodeficiency syndrome. Efficacy of long-term continuous therapy.

Thirty-five patients with the acquired immunodeficiency syndrome (AIDS) and central nervous system toxoplasmosis, seen over a 30-month period, were treated with the combination pyrimethamine/sulfadiazine. All patients had clinical and computed tomographic scan findings consistent with active neurotoxoplasmosis. Mean duration of total therapy was six months. During the first two months of therapy, four patients died of acute neurotoxoplasmosis and 31 showed improvement. Of the 24 patients evaluable for long-term therapy, 14 (58 percent) achieved complete resolution and 10 had late clinical (n = 7) and/or computed tomographic scan (n = 6) sequelae. Six patients experienced 10 relapses, which occurred within six weeks of treatment discontinuation in seven of 10. Reintroduction of the combination led to complete resolution of the relapse in eight cases. These clinical results were correlated with brain anatomic findings in the 15 autopsied cases. Side effects, noted in 25 of 35, were mainly hematologic toxicity (n = 21) and cutaneous rash (n = 12). However, the combination had to be definitively stopped in only two cases and sulfadiazine alone had to be withdrawn in eight other cases. These data suggest that pyrimethamine/sulfadiazine is highly efficacious in neurotoxoplasmosis and that life-long therapy is needed to prevent relapses in patients with AIDS.

PREVENTION OF PNEUMOCYSTIS CARINII PNEUMONIA RELAPSE BY PENTAMIDINE AEROSOL IN ZIDOVUDINE-TREATED AIDS PATIENTS

To examine the efficacy and tolerance of pentamidine aerosol in the prevention of Pneumocystis carinii pneumonia (PCP) relapse in patients with the acquired immunodeficiency syndrome (AIDS) being treated with zidovudine, 51 patients who had had an episode of PCP in the previous 5 months were enrolled in a randomised controlled study. 25 patients (group I) received pentamidine mesylate aerosol (4 mg/kg every 2 weeks for the first month then monthly) and zidovudine, and 26 patients (group II) zidovudine alone. 3 group I patients withdrew from pentamidine therapy prematurely and were excluded from the analysis of efficacy. Relapses of PCP occurred in 2 out of 22 (9%) group I patients and in 16 out of 26 (61%) group II patients after a mean follow-up of 10 and 8.7 months, respectively. The two groups differed significantly (p less than 0.0001) in proportions without relapse. They did not differ in proportions surviving. Bronchial intolerance was common (47%); no systemic side-effects of pentamidine were observed. Pentamidine aerosol thus seems to be effective in preventing PCP relapses in AIDS patients on zidovudine. The early termination of the trial prevented assessment of the long-term efficacy and safety of pentamidine given by aerosol.

Presence of HIV-1 in human parenchymal and non-parenchymal liver cells in vivo

The infection of liver cells by HIV-1 was investigated in vivo. Liver biopsies from 13 anti-HIV-1 antibody-positive patients were studied and HIV-1 DNA was revealed by polymerase chain reaction (PCR) in eight. In situ hybridization demonstrated the presence of HIV-1 RNA in all eight PCR-positive liver specimens. Mononuclear inflammatory cells in the portal tracts and Kupffer cells were labeled by a HIV-1 35S-RNA probe in all cases and by an anti-p24 monoclonal antibody, in seven cases. In addition, hepatocytes also clearly scored positive for HIV-1 RNA in three cases. These results demonstrate the infection of both parenchymal and non-parenchymal liver cells by HIV-1 in vivo and therefore show that HIV-1 can infect an epithelial CD4-negative cell type.

Cytomegalovirus colitis in Hiv-1-infected patients: a prospective research in 55 patients

Objective:To determine criteria for the diagnosis of cytomegalovirus (CMV) colitis and to analyse stages of the course and prognosis of CMV colonic involvement in HIV-1-infected patients. Design:Prospective search for CMV colonic involvement with systematic biopsies to search for CMV intranuclear inclusion bodies and for CMV culture. The evolution of CMV colonic involvement was estimated using further coloscopies and autopsy. Setting:Infectious diseases department in a tertiary referral teaching hospital in Paris, France. Participants:Fifty-five consecutive patients with HIV-1 infection, who had not previously received anti-CMV drugs, and who had at least one coloscopy performed. Results:According to initial coloscopy, colitis, either ulcerative or inflammatory, was found in nine (16%) out of the 55 patients, CMV intranuclear inclusions were present in the colon of four (7%) patients, and colonic cultures were positive for CMV in 15 (27%) patients. The results of the initial coloscopy showed a positive correlation between endoscopic colitis (either ulcerative or inflammatory), CMV inclusions and positive CMV culture from colonic biopsies. The absence of endoscopic ulcerative lesions had a 98% (49 out of 50) negative predictive value for recording CMV inclusions in the colon (95% confidence interval, 89–100). CMV inclusions were recorded in three out of five ulcerative colitis. Male homosexuality, HIV-1 infection stages IVB, C1, D or E, according to the Centers for Disease Control and Prevention classification, CD4 lymphocyte count <200×106/l and CMV viraemia also correlated positively with CMV colonic involvement. During the observation period (mean, 7.3 months), the estimated incidence of CMV colitis according to coloscopic studies was 13%. Deterioration in condition was the most frequent spontaneous evolution of CMV colonic infection, whereas anti-CMV treatment resulted in an improvement. Ulcerative lesions occurred earlier in patients with colonic CMV inclusions or positive colonic CMV culture than in patients without CMV colonic involvement at the initial coloscopy. CMV colitis occurred late in the course of HIV-1 infection, on average 4 months before death. The presence of CMV inclusions was an indicator of poor prognosis with earlier occurrence of CMV viraemia and retinitis and no survival after 9 months. Conclusions:These results confirm that the colon is a target organ for CMV in HIV-1-infected patients. Coloscopy should be used to diagnose CMV colitis, because of the close correlation between endoscopic and histological data (i.e., intranuclear inclusions). This combination allows us to propose an evolutive staging of CMV colonic involvement and provide stratification criteria to assess the efficacy of anti-CMV drugs.