Idiopathic CD4+ T lymphocytopenia disclosed by the onset of empyema thoracis.
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A 56-year-old man was admitted to our hospital in December 1996 due to empyema thoracis. A laboratory examination revealed lymphocytopenia and CD4+ T lymphocytopenia (<300 cells/ microl). No evidence for a human immunodeficiency virus (HIV) infection was found. No malignant, hematological or autoimmune disease was detected. We thus diagnosed this case as being idiopathic CD4+ T lymphocytopenia (ICL). During his hospital treatment, he was affected with cytomegaloviral retinitis and cured by therapy. His subsequent treatment went well without a recurrence of severe infection although a low CD4+ T lymphocyte count continued after the recovery from empyema thoracis. (+info)
Cytomegalovirus (CMV) retinitis activity is accurately reflected by the presence and level of CMV DNA in aqueous humor and vitreous.
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To evaluate the potential of ocular and systemic specimens to provide markers of active cytomegalovirus (CMV) retinitis, we examined the relationship between virologic and clinical aspects of CMV infections in AIDS patients with CMV retinitis. CMV polymerase chain reaction (PCR) analysis of 74 aqueous humor and vitreous specimens indicated that ocular specimens can provide accurate markers to differentiate active and inactive CMV retinitis (aqueous or vitreous PCR, P<.001). Moreover, these markers were superior to extraocular measures, including plasma PCR (P=.08) and blood and urine CMV cultures (P=.05). A direct correlation was identified between the quantity of CMV DNA in aqueous humor or vitreous specimens and the corresponding surface area of active CMV retinitis (r2=.69 and.44, respectively). Thus, qualitative and quantitative PCR-based analyses of aqueous humor can provide valuable markers of CMV retinitis activity. Such assays could provide rapid and reliable tools to assist in management of patients with CMV retinitis in whom the view of the retina is obscured. (+info)
Phase I study of combination therapy with intravenous cidofovir and oral ganciclovir for cytomegalovirus retinitis in patients with AIDS.
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Ganciclovir and cidofovir, two antiviral agents used in the treatment of cytomegalovirus (CMV) retinitis, have a synergistic effect inhibiting CMV replication in vitro. In a phase I study, seven patients with AIDS-related CMV retinitis were treated with cidofovir (5 mg/kg intravenously every 2 weeks) combined with ganciclovir (1 g orally three times a day). During a median of 5.5 months (range, 1-12 months) of combined therapy, only one patient had retinitis progression, and only two of 28 blood cultures (specimens of which were obtained on a monthly basis) yielded CMV. Dose-limiting adverse ocular effects (anterior uveitis [two patients] and hypotony [two patients]) occurred in three of seven patients. The results suggest that combination therapy with intravenous cidofovir and oral ganciclovir (a regimen that does not require indwelling central venous catheter access) might enhance clinical efficacy. Less frequent administration of cidofovir in combination with oral ganciclovir should be prospectively studied to determine if the incidence of treatment-associated toxicity might be reduced. (+info)
Oral ganciclovir for patients with cytomegalovirus retinitis treated with a ganciclovir implant. Roche Ganciclovir Study Group.
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BACKGROUND: The intraocular ganciclovir implant is effective for local treatment of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome (AIDS), but it does not treat or prevent other systemic manifestations of cytomegalovirus infection. METHODS: Three hundred seventy-seven patients with AIDS and unilateral cytomegalovirus retinitis were randomly assigned to one of three treatments: a ganciclovir implant plus oral ganciclovir (4.5 g daily), a ganciclovir implant plus oral placebo, or intravenous ganciclovir alone. The primary outcome measure was the development of new cytomegalovirus disease, either contralateral retinitis or biopsy-proved extraocular disease. RESULTS: The incidence of new cytomegalovirus disease at six months was 44.3 percent in the group assigned to the ganciclovir implant plus placebo, as compared with 24.3 percent in the group assigned to the ganciclovir implant plus oral ganciclovir (P=0.002) and 19.6 percent in the group assigned to intravenous ganciclovir alone (P<0.001). As compared with placebo, oral ganciclovir reduced the overall risk of new cytomegalovirus disease by 37.6 percent over the one-year period of the study (P=0.02). However, in the subgroup of 103 patients who took protease inhibitors, the rates of new cytomegalovirus disease were low and of similar magnitude, regardless of treatment assignment. Progression of retinitis in the eye that initially received an implant was delayed by the addition of oral ganciclovir, as compared with placebo (P=0.03). Treatment with oral or intravenous ganciclovir reduced the risk of Kaposi's sarcoma by 75 percent (P=0.008) and 93 percent (P<0.001), respectively, as compared with placebo. CONCLUSIONS: In patients with AIDS and cytomegalovirus retinitis, oral ganciclovir in conjunction with a ganciclovir implant reduces the incidence of new cytomegalovirus disease and delays progression of the retinitis. Treatment with oral or intravenous ganciclovir also reduces the risk of Kaposi's sarcoma. (+info)
Cystoid macular oedema and cytomegalovirus retinitis in patients with HIV disease treated with highly active antiretroviral therapy.
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BACKGROUND: Although cystoid macular oedema (CMO) is a rare cause of visual loss in AIDS related cytomegalovirus (CMV) retinitis, nine cases are reported of CMO occurring in HIV infected patients with a prior diagnosis of CMV who were receiving highly active antiretroviral therapy (HAART). METHODS: Medical and ophthalmological records of nine AIDS patients with inactive CMV retinitis were retrospectively analysed. Ophthalmic examination data, laboratory findings, and the systemic antiviral treatment were studied. Ophthalmic examination included visual acuity, anterior chamber flare measured with the laser flare cell meter (LCFM), vitreous haze quantification according to the Nussenblatt grading system, and fluorescein angiography. RESULTS: Nine HIV infected patients, eight men and one woman, mean age 39 years (range 29-53 years) presented with inactive CMV retinitis and CMO. On fluorescein angiography, CMO was present only in eyes (14 eyes) with signs of previous CMV retinitis. CMV retinitis was inactive in all of them. Visual acuity ranged from 20/200 to 20/30. In 10 eyes with CMV retinitis, anterior chamber flare measured with the LCFM ranged from 18.5 to 82 photons/ms (mean 35.42 ph/ms). A significant vitreous inflammation (1.5+) was observed in eight eyes. All patients had been treated with anti-CMV drugs for a mean period of 18 months (range 12-36 months). All nine patients received HAART with a combination of two nucleotide analogue reverse transcriptase inhibitors and one protease inhibitor for a mean period of 14 months (range 9-18 months). The HIV viral load was below detectable levels (< 200 copies/ml) in eight patients and low (3215 copies/ml) in one. At the time of CMO, the median CD4+ lymphocyte count was 232 cells x 10(6)/l (range 99-639). CONCLUSION: In AIDS patients, the usual absence of intraocular inflammation in eyes affected by CMV retinitis has been tentatively explained by the profound cellular immunodeficiency. In these patients, treated with HAART, CD4+ counts were increased for several months (mean 14 months). In their eyes, CMV retinitis was associated with significant ocular inflammation and CMO. These findings could be related to the restoration of immune competence after HAART as recently shown. (+info)
IL-10 in HIV infection: increasing serum IL-10 levels with disease progression--down-regulatory effect of potent anti-retroviral therapy.
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To examine the potential pathogenic role of IL-10 in HIV infection, we measured serum IL-10 levels in 51 HIV-infected patients and 23 healthy controls both on cross-sectional and longitudinal testing. All clinical groups (Centers for Disease Control (CDC) categories) of HIV-infected patients had significantly higher circulating IL-10 levels than controls, with the highest levels among the AIDS patients, particularly in patients with ongoing Mycobacterium avium complex (MAC) infection. Among 32 HIV-infected patients followed with longitudinal testing (median observation time 39 months), patients with disease progression had increasing IL-10 levels in serum, in contrast to non-progressing patients where levels were stable. While both IL-10 and tumour necrosis factor-alpha (TNF-alpha) increased in patients with disease progression, the IL-10/TNF-alpha ratio decreased in these patients, suggesting imbalance between these two cytokines. Finally, we found that highly active anti-retroviral therapy (HAART) induced a significant, gradual decrease in IL-10 levels but without normalization. These findings suggest a pathogenic role for IL-10 in HIV infection, and may suggest a possible role for immunomodulating therapy which down-regulates IL-10 activity in addition to concomitant potent anti-retroviral therapy in HIV-infected patients. (+info)
Treatment of immune recovery vitritis with local steroids.
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AIMS: To report a series of patients requiring treatment for falling visual acuity associated with immune recovery vitritis, a recently described syndrome of a predominantly vitreous inflammatory reaction in patients with AIDS and cytomegalovirus (CMV) retinitis. METHODS: The medical records of all patients requiring treatment for falling visual acuity associated with immune recovery vitritis were reviewed between March 1996 and March 1998. RESULTS: Nine eyes in seven patients required treatment for falling visual acuity. All patients had inactive CMV retinitis and had received highly active antiretroviral treatment including a protease inhibitor. Vitreous inflammation developed at a mean of 5.5 months (range 1-14) after starting a protease inhibitor. The onset of inflammation correlated with a mean rise in CD4(+) lymphocyte levels of 83 x 10(6)/l (range 30-128). The visual acuity fell by a mean of 2.8 Snellen lines (range 1-4) before treatment, and rose by a mean of 1.9 Snellen lines (range 0-4) after treatment with orbital floor steroids. The mean time interval between treatment with orbital floor steroids and improvement in visual acuity was 3.5 weeks (range 1-8). Following treatment the visual acuity improved or remained stable in all nine eyes, eight eyes returning to within one line of their preinflammation Snellen visual acuity. No eyes developed reactivation or progression of CMV retinitis after treatment, and none developed any other pathology. CONCLUSIONS: Orbital floor steroids appear to be have a useful role in the treatment of persistent immune recovery vitritis where the visual acuity is compromised. (+info)
Cytomegalovirus (CMV) resistance in patients with CMV retinitis and AIDS treated with oral or intravenous ganciclovir.
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Treatment of cytomegalovirus (CMV) retinitis with oral ganciclovir results in relatively low plasma concentrations of drug, which theoretically could cause more frequent viral resistance compared with intravenous (iv) ganciclovir. By use of a plaque-reduction assay to quantify phenotypic sensitivity to ganciclovir, virus isolates were studied from patients with CMV retinitis participating in four clinical trials of oral ganciclovir. Before treatment, 69% of patients were culture-positive but just 1.1% of patients yielded a resistant CMV, defined as a median inhibitory concentration (IC50) >6 microM. On treatment, the first resistant isolate was recovered at 50 days. Overall, 3.1% of patients receiving iv ganciclovir and 6. 5% of those taking oral ganciclovir shed resistant CMV (median ganciclovir exposures of 75 and 165 days, respectively). Since IC50s for clinical isolates increased proportionately with treatment duration, it is likely that viral resistance would be more frequent with longer treatment. (+info)