Victor Gabriel

A controlled study of inhaled pentamidine for primary prevention of Pneumocystis carinii pneumonia

BACKGROUND Current recommendations for prophylaxis of Pneumocystis carinii pneumonia (PCP) are based on data from patients who have had at least one episode of PCP (secondary prevention). We designed a study to determine the efficacy and side effects of inhaled pentamidine in the primary prevention of PCP. METHODS Two hundred twenty-three patients sero-positive for human immunodeficiency virus (HIV) who had the acquired immunodeficiency syndrome (AIDS) but not PCP, who had advanced AIDS-related complex, or who had less than 0.2 x 10(9) CD4-positive lymphocytes per liter received either 300 mg of pentamidine isethionate or 300 mg of sodium isethionate every 28 days by inhaler. The proportion of patients surviving without PCP was analyzed with the log-rank test as a function of time spent in the trial, according to the intention to treat with either placebo or pentamidine. RESULTS The third of five planned interim analyses showed a significant difference in the occurrence of PCP, with 8 cases in pentamidine group and 23 in the placebo group (nominal P value = 0.0021). There were no deaths within 60 days of the diagnosis of PCP and no significant differences in survival between groups. Approximately 53 inhalations were needed to prevent one episode of pneumonia. Thirty-eight of 114 patients given pentamidine (33 percent) and 7 of 109 given placebo (6 percent) had moderate-to-severe coughing during inhalations (two-tailed P less than 0.00001), which caused 4 patients given pentamidine (3.5 percent) to discontinue taking it. CONCLUSIONS A dose of 300 mg of aerosolized pentamidine given every four weeks was well tolerated and 60 to 70 percent effective in preventing a first episode of PCP in patients with HIV infection.

A Controlled Study of Early Neurologic Abnormalities in Men with Asymptomatic Human Immunodeficiency Virus Infection

BACKGROUND Although neurologic complications are frequent in the acquired immunodeficiency syndrome, their incidence and progression in early human immunodeficiency virus (HIV) infection remain controversial. The goal of this study was to assess neurologic manifestations in asymptomatic carriers of HIV. METHODS We studied 29 HIV-seropositive homosexual men and 33 seronegative homosexual controls by means of neurologic and neuropsychological examinations, magnetic resonance imaging (MRI), and electrophysiologic tests (electroencephalography, multimodal evoked-potential tests, and otoneurologic tests). After six to nine months, the tests were repeated in 27 seropositive men and 30 controls. The investigators were blind to the serologic status of the subjects. RESULTS The seropositive subjects had a mean CD4+ lymphocyte count of 635 X 10(6) per liter. Neurologic and neuropsychological examination, MRI, and measurements of pattern visual evoked potentials did not show significant differences between the two groups. The latencies of the median-nerve somatosensory evoked potentials were slightly prolonged in the seropositive men. The initial electroencephalogram was judged abnormal in 8 of 27 of the seropositive subjects (30 percent) as compared with none of the controls, with a slowing of fundamental activity, anterior spread [corrected] of alpha rhythm, subnormal reactivity, and unusual anterior theta activities. These findings were confirmed by computerized spectral analysis. The second electroencephalogram was abnormal in 10 of 25 of the seropositive men (40 percent). The otoneurologic evaluation identified abnormalities in the central auditory or vestibulo-ocular pathways in 34 percent of the seropositive men (10 of 29), as compared with 6 percent of the controls (2 of 33), on the first examination and in 44 percent (12 of 27) and 7 percent (2 of 30), respectively, on the second examination. Altogether, electrophysiologic abnormalities were found in 67 percent of the seropositive men (18 of 27) and 10 percent of the controls (3 of 30) (P less than 0.00005). CONCLUSIONS In persons with asymptomatic HIV infection, electrophysiologic tests may be the most sensitive indicators of subclinical neurologic impairment. Electrophysiologic abnormalities are far more common in asymptomatic carriers of HIV than in controls and tend to progress over time.

Treatment for Cerebral Toxoplasmosis Protects against Pneumocystis carinii Pneumonia in Patients with AIDS

OBJECTIVE To determine whether long-term maintenance treatment for toxoplasmosis protects against Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN Cohort study. SETTING Switzerland. PATIENTS A total of 453 patients with human immunodeficiency virus (HIV) entered the Swiss HIV Cohort Study. Ninety-nine patients with cerebral toxoplasmosis but no previous or simultaneous P. carinii pneumonia were compared with 240 patients with AIDS and other severe opportunistic infections (Centers for Disease Control [CDC] stage IVC1 infection other than toxoplasmosis and P. carinii pneumonia) as well as with 114 patients receiving inhaled pentamidine in a study of primary pneumocystis prophylaxis in patients infected with HIV. MEASUREMENTS Life-table analysis for P. carinii-free survival. MAIN RESULTS Six of 99 (6%) patients with toxoplasmosis, 50 of 240 (21%) patients with other severe opportunistic infections, and 8 of 114 (6%) patients receiving inhaled pentamidine developed P. carinii pneumonia. Life-table analysis showed that the incidence of pneumonia was substantially lower in patients with toxoplasmosis compared with that in patients with other severe opportunistic infections and was similar to the incidence in patients receiving pentamidine as prophylaxis. Analysis of the medication records from patients with toxoplasmosis showed that pyrimethamine and sulfonamides were administered 50% of the time; pyrimethamine and clindamycin, 25% of the time; and pyrimethamine alone, 9.9% of the time but that only one of the six patients with toxoplasmosis who developed P. carinii pneumonia received pyrimethamine and sulfonamides in the month before diagnosis. CONCLUSION Patients with cerebral toxoplasmosis have a low risk for subsequently developing P. carinii pneumonia. This decreased risk is probably the result of chronic suppressive treatment with pyrimethamine and sulfonamides.

Behavioural changes in intravenous drug users in Geneva: rise and fall of HIV infection, 1980-1989

In the early 1980s, more than 90% of intravenous drug users (IVDUs) shared needles and syringes in Geneva. The prevalence of antibodies to HIV in the sera of outpatient IVDUs increased from 6% in 1981 to 38% in 1983; it was, however, still only 37% in 1988. IVDUs starting methadone maintenance in 1987-1989 had a seroprevalence rate of 22%. In 1989 the percentage of IVDUs exchanging syringes and needles fell to only 5% of seropositive addicts. Only one seroconversion was observed in 1094 patient-months of observation in 1988-1989, which was probably due to sexual contact. The evidence suggests that, in the IDVUs studied, transmission of HIV has diminished since the early 1980s.

Reasons for failure of prevention of Toxoplasma encephalitis. Swiss HIV Cohort Study

Objective:To study whether absence of prophylaxis is a risk factor for cerebral toxoplasmosis, and to determine the reasons for absence of prophylaxis among AIDS patients diagnosed with Toxoplasma encephalitis (TE). Design:Retrospective chart review and matched case–control study. Patients:Patients (104 first episodes and 26 relapses of TE) were registered in the Swiss HIV Cohort Study from three centres from July 1992 to December 1994; 91 matched controls were included for 52 patients with a first episode, and 17 matched controls for 17 patients with relapse of TE. Results:Prophylaxis was prescribed to 17 patients (16%) with a first episode and 19 patients (73%) with a relapse of TE. Reasons for the absence of prophylaxis included patient refusal (25%), non-proposal by physicians (17%), and drug intolerance (17%). Reduced absorption due to non-compliance, diarrhoea or vomiting was identified among 12 patients with a first episode and 14 patients with a relapse of TE. Absence of prescription of prophylaxis was associated with a 10-fold increased risk of a first episode of TE (odds ratio, 9.8; 95% confidence interval, 2.7–35.4) in the matched case–control study. Conclusions:TE continues to occur among patients not receiving prophylaxis. At least one-half of the cases may be prevented with better motivation of physicians and increased compliance of patients.