Search

We compared the efficacy of a 400-mg once-weekly dosage versus a 200-mg daily dosage of fluconazole for the prevention of deep fungal infections in a multicenter, randomized, double-blind trial of 636 human immunodeficiency virus-infected patients to determine if a less intensive fluconazole regimen could prevent these serious but relatively infrequent complications of AIDS. In the intent-to-treat analysis, a deep fungal infection developed in 17 subjects (5.5%) randomly assigned to daily fluconazole treatment and in 24 (7.7%) given weekly fluconazole during 74 weeks of follow-up (risk difference, 2.2%; 95% confidence interval [CI], -1.7% to 6.1%). Thrush occurred twice as frequently in the weekly versus daily fluconazole recipients (hazard ratio, 0.59; 95% CI, 0.40-0.89), and in a subset of patients evaluated, fluconazole resistance was infrequent. Fluconazole administered once weekly is effective in reducing deep fungal infections in patients with AIDS, but this dosage is less effective than the 200-mg-daily dosage in preventing thrush.

Infection due to the Mycobacterium avium complex (MAC) accounts for the most frequent AIDS-related opportunistic infections, but MAC infection is usually not the first AIDS-defining event that a patient infected with HIV experiences. The incidence increases linearly over time, at a rate of 20 to 25% per year, after a patient's first AIDS-defining event, and the incidence increases exponentially as the CD4+ cell count approaches zero. There is evidence that MAC may eventually infect most if not all HIV-infected patients who do not die from another HIV-related event. Since MAC infection contributes substantially to the morbidity and mortality of AIDS patients, prophylaxis appears to be mandatory. Rifabutin was the first drug which was shown to be effective in preventing MAC infection, and, recently, prophylaxis with clarithromycin was also found to prevent the disease. The optimal approach to prophylaxis still needs to be defined. Since a large majority of MAC infections occur in patients with CD4+ cell counts below 50/microliter, recommendations regarding the prophylaxis of patients with a history of an AIDS-defining opportunistic event and a CD4+ cell count between 50 and 200/microliter can be individualized, depending for example on how well the patient seems to be responding to antiretroviral treatment. Prophylaxis against MAC should be provided for any HIV-infected patient with a CD4+ cell count less than 50/microliter.

Acute psychosis was observed in two patients with AIDS who were treated with clarithromycin for disseminated Mycobacterium avium complex infection. The psychosis resolved when treatment with clarithromycin was discontinued and recurred when it was resumed. An adverse response to clarithromycin therapy is a rare but curable cause of acute psychosis in patients with AIDS.

Background: Published opinion has generally favored amphotericin B over fluconazole as initial therapy for acquired immunodeficiency syndrome-associated cryptococcosis, although data that support this recommendation are limited., Method: Retrospective review of 30 consecutive patients with acquired immunodeficiency syndrome-associated cryptococcosis seen at a single institution over a 1-year period and given fluconazole, 400 mg/d, as initial therapy., Results: No patient died within the first 30 days of therapy, and none of the 14 patients who died within 1 year had clinically detectable infection when last seen or at death. Pretreatment blood cultures were positive in 26 of 27 patients; cerebrospinal fluid cryptococcal antigen titer was greater than 1:1024 in 12 of 23 patients; and five of 30 patients presented with altered mental status. The median CD4 count at diagnosis was 0.042 x 10(9)/L (42/microL). Eight of 25 patients who were followed up for more than 30 days relapsed, as evidenced by a positive culture; all relapses were successfully treated with fluconazole, either by reinstitution of therapy or by increase of dosage., Conclusion: This experience supports the use of fluconazole as initial therapy for acquired immunodeficiency syndrome-associated cryptococcosis.

Background: Disseminated Mycobacterium avium complex infection eventually develops in most patients with the acquired immunodeficiency syndrome (AIDS). This infection results in substantial morbidity and reduces survival by about six months., Methods: We conducted two randomized, double-blind, multicenter trials of daily prophylactic treatment with either rifabutin (300 mg) or placebo. All the patients had AIDS and CD4 cell counts < or = 200 per cubic millimeter. The primary end point was M. avium complex bacteremia as assessed monthly by blood culture. The secondary end points were signs and symptoms associated with disseminated M. avium complex infection, adverse events, hospitalization, and survival., Results: In the first trial, M. avium complex bacteremia developed in 51 of 298 patients (17 percent) assigned to placebo and 24 of 292 patients (8 percent) assigned to rifabutin (P < 0.001). In the second trial, bacteremia developed in 51 of 282 patients in the placebo group (18 percent) and 24 of 274 patients in the rifabutin group (9 percent) (P = 0.002). Rifabutin significantly delayed fatigue, fever, decline in the Karnofsky performance score (by > or = 20 percent), decline in the hemoglobin level (by more than 10 percent), elevation in alkaline phosphatase, and hospitalization. The incidence of adverse events was similar with rifabutin and placebo. Overall survival did not differ significantly between the two groups, although there were fewer deaths with rifabutin (33) than with placebo (47) during the double-blind phase (P = 0.086). The distribution of minimal inhibitory concentrations of rifabutin among the isolates of M. avium complex did not differ significantly between the treatment groups., Conclusions: Rifabutin, given prophylactically, reduces the frequency of disseminated M. avium complex infection in patients with AIDS and CD4 counts < or = 200 per cubic millimeter.

Background: An experimental sustained release intraocular device has been designed to deliver ganciclovir over a long period of time. As part of an efficacy trial, the ganciclovir intraocular device was used to treat cytomegalovirus (CMV) retinitis in patients with acquired immune deficiency syndrome (AIDS)., Methods: All patients had active CMV retinitis that had progressed despite intravenous ganciclovir therapy. The ganciclovir intraocular device was inserted into the vitreous cavity by making an inferotemporal full-thickness circumferential sclerotomy and anchored to the incision. Intravenous therapy was then discontinued and patients were followed up at 2-week intervals until death. Seven eyes from five patients were obtained 2 to 10 hours postmortem and submitted for histopathologic examination. Light and electron microscopic studies were performed and correlated to the clinical outcome. Follow-up period after device placement ranged from 16 to 82 days (median, 70 days)., Results: All seven eyes showed clinical stabilization of the CMV retinitis. Light microscopy showed varying degrees of retinal atrophy with areas of gliosis. In addition, we observed syncytial megalic cells containing Cowdrey type A inclusions affecting all layers of the retina. Concurrent choroidal infections with Pneumocystis carinii (1) and Mycobacterium avium (2) also were seen. Electron microscopy showed virus particles located mostly at the junction of uninvolved and "healed" retinitis. No evidence of retinal toxic effects or inflammation at the site of ganciclovir intraocular device implant was noted., Conclusion: The ganciclovir intraocular device appeared to be effective in controlling the progression of CMV retinitis. The clinical and pathologic results are similar to those observed in the eyes of patients with intravenously administered ganciclovir. The lack of toxic effects and sustained levels of intravitreal ganciclovir may provide an improved therapeutic method of local treatment of CMV retinitis.

An experimental intravitreal sustained-release device containing ganciclovir was used to treat 22 patients with acquired immunodeficiency syndrome-associated cytomegalovirus retinitis. Fourteen eyes were excluded (five not involved and nine with macular scarring and/or severe debility). Thirty eyes received the ganciclovir intraocular device implant and were prospectively followed up from 16 to 419 days (median, 125 days). Twenty-seven (90%) of 30 eyes showed stabilization of the retinitis. Nine (33%) of 27 eyes showed reactivation of the retinitis once the device was empty of ganciclovir; seven received a replacement device, with subsequent stabilization of the retinitis. Postoperative complications included vitreous hemorrhage (n = 1), endophthalmitis (n = 1), and progressive retinitis (n = 2). Late retinal detachment was seen in three eyes (11%) at 35 to 140 days. Survival analysis of all 30 eyes revealed the mean time to progression of retinitis to be 19 weeks (133 days). The ganciclovir intraocular device offers a promising alternative for the treatment of cytomegalovirus retinitis associated with acquired immunodeficiency syndrome.