Induction of ocular Behçet's disease remission after short-term treatment with infliximab: a case series of 11 patients with a follow-up from 4 to 16 years.

OBJECTIVES: Initial recommendations on anti-TNF treatment for Behçet's disease (BD) included an intravenous infliximab infusion for acute posterior uveitis to achieve a fast-onset response. We aimed to examine the long-term outcome of our patients with acute sight-threatening BD who received successful short-term treatment with infliximab. METHODS: We performed a retrospective longitudinal outcome study including consecutive patients who responded to one infliximab infusion (5mg/kg) for BD-associated acute posterior uveitis or panuveitis, followed, or not, by one or two additional infusions. RESULTS: Twelve patients (aged 51±14 years, mean±SD, 67% men) with bilateral (n=9) or unilateral (n=3) ocular attack (relapsing in 9 patients) achieved resolution of ocular inflammation within 4 weeks after the first infusion of infliximab, given as add-on to azathioprine (n=9) or to azathioprine/cyclosporine combination. Ten of 12 patients received a second infusion at 4 weeks and 9 of them received a third infusion at 8 weeks from baseline. Except from a patient who relapsed after 6 months and responded to infliximab re-treatment, 11 patients remain ocular relapse-free during follow-up, ranging from 4 to 16 years (10±4). Five patients (45%) discontinued azathioprine being in full BD remission and remain any drug-free at end of follow-up. CONCLUSIONS: Successful short-term infliximab treatment combined with conventional immunosuppressives for BD-associated sight-threatening uveitis may lead to remission for many years thereafter. This observation may suggest that infliximab as a first-line therapy should be promptly administered to every patient with ocular BD for rapid remission of ocular inflammation and preservation of visual acuity.

CMV-Related Anterior Uveitis in a Mediterranean European Population: Clinical Features, Prognosis, and Long-Term Treatment Outcomes.

PURPOSE: To describe the spectrum of clinical features of cytomegalovirus-related anterior uveitis (CMV-AU) along with potential comorbidities, to calculate complication rates, and to determine risk factors and biomarkers affecting prognosis in a cohort of a Southern European Mediterranean population. MATERIALS AND METHODS: It is a retrospective, multicenter case series of consecutive patients with persisting hypertensive AU, unresponsive to topical steroids therapy, and CMV-positive essays from two uveitis referral centers were collected and analyzed. RESULTS: Fifty-seven eyes of 53 patients with polymerase chain reaction-verified CMV-AU over a period of 8 years were included with a mean age of 48 ± 18. Four presentation patterns were identified: 26.3% as Posner-Schlossman-like, 31.6% as chronic AU, 19.3% as presumed herpetic uveitis, 12.3% as Fuchs uveitis syndrome-like, and 10.5% without specific initial classification. About 15.8% received oral valganciclovir, 22.8% received topical valganciclovir, and 61.4% received both, for a mean duration of treatment of 44 months. AU recurrences were observed in 23 eyes with a mean of 1.5 (±1.5) recurrences per year. The only finding significantly associated with recurrence was the presence of posterior synechiae (PS) (p = 0.034). Fewer keratic precipitates (KPs) were indicative for the need of longer treatment, and endotheliitis was strongly associated with the need for filtration surgery. CONCLUSION: In this immunocompetent southern European population, four distinct clinical presentation patterns were further confirmed, and possible biomarkers such as PS, KPs, and endotheliitis were newly reported to influence treatment outcomes. Large-scale studies could provide a more effective customized treatment protocol.

Association of lysyl oxidase-like 1 gene common sequence variants in Greek patients with pseudoexfoliation syndrome and pseudoexfoliation glaucoma.

PURPOSE: Three common sequence variants in the lysyl oxidase-like 1 (LOXL1) gene were recently associated with pseudoexfoliation (PEX) and pseudoexfoliation glaucoma (PEXG) in populations from various parts of the world. In this study, the genetic association of these variants was investigated in Greek patients with PEX and PEXG. METHODS: The three LOXL1 single nucleotide polymorphisms (SNPs), one intronic (rs2165241) and two nonsynonymous coding SNPs (rs1048661: R141L and rs3825942: G153D), were genotyped in a total of 48 unrelated patients with PEX, 35 patients with PEXG, and 52 healthy subjects who had normal findings in repeated ophthalmic examinations. A genetic association study was performed. RESULTS: Between the two coding SNPs, R141L did not show an association with PEX (p=0.297 for allele G, p=0.339 for genotype GG), whereas allele G of G153D showed a significant association (odds ratio [OR]=3.52, 95% confidence interval [CI]=1.735-7.166, p=3.24×10(-4) for allele G, p=0.004 for genotype GG). Likewise, for the intronic SNP of rs2165241, genotype TT (p=0.005) and its corresponding allele T (OR=2.99, 95% CI=1.625-5.527, p=3.53×10(-4)) showed a significant association with PEX. The allele G of G153D showed a significant association with PEXG (OR=3.74, 95% CI=1.670-8.387, p=0.001). The combined haplotype GGT, consisting of all three risk alleles, was associated with PEX (p=0.037), conferring a 1.8-fold of increased risk to the disease (OR=1.799, 95% CI=1.04-3.13). Furthermore, the haplotype GGT presented in 39.8% of the patients with PEX and 26.9% of the controls. CONCLUSIONS: Certain genetic variants in LOXL1 confer risk for PEX in Greek populations, confirming in part findings in patients from Northern Europe.

Pediatric Non-Infectious Uveitis: Long-Term Outcomes and Complications.

PURPOSE: To describe the long-term prevalence of ocular complications and visual prognosis in patients with pediatric uveitis. METHODS: Demographics, etiology and location of uveitis, type of complications, treatment and visual outcomes were recorded in 296 children at first examination and at 1-, 2-, 3-, 5- and 10-year time points. RESULTS: Αnterior uveitis represented 53.4% of cases, followed by intermediate (28.0%), posterior uveitis (11.1%) and panuveitis (7.4%). The leading diagnoses were idiopathic uveitis (31.1%), juvenile idiopathic arthritis (27.0%) and pars planitis (22.6%). Posterior synechiae was the most frequent complication of anterior uveitis and panuveitis, cystoid macular edema and disc edema of intermediate and posterior uveitis respectively. Posterior uveitis and panuveitis had more severe final vision loss (23.1% and 20% respectively). CONCLUSIONS: This study provides clinical characteristics and main complications in a longitudinal long-term follow-up of a large non-infectious pediatric uveitis Greek population. Early diagnosis and close monitoring remain of fundamental importance.

A single infliximab infusion vs corticosteroids for acute panuveitis attacks in Behçet's disease: a comparative 4-week study.

OBJECTIVE: To compare a single infusion of the anti-TNF antibody infliximab vs CSs for acute panuveitis attacks in Behçet's disease (BD). METHODS: A prospective, observational study of patients with panuveitis, who received either an infliximab infusion (5 mg/kg, 19 eyes) or high-dose methylprednisolone intravenously (1 g/day for 3 days, 8 eyes), or intra-vitreal triamcinolone acetonide (4 mg, 8 eyes) at attack's onset. Baseline maintenance therapy remained unchanged during the following 30 days. Visual acuity, anterior chamber cells, vitreous cells and inflammation of the posterior eye segment were assessed at baseline and at Days 1, 7, 14 and 29 (±1) post-treatment. RESULTS: While no significant differences were noted between i.v. and intra-vitreal CSs, infliximab was faster than CSs in decreasing total ocular inflammation scores and fundus inflammation scores (P = 0.01 and P < 0.0001 for treatment × time(2) interaction, respectively, using generalized estimating equation analysis). Independently of time, infliximab was superior to CSs in clearing retinal vasculitis (P < 0.003), as well as in resolution of retinitis (P = 0.008) and cystoid macular oedema (P < 0.007). Moreover, a faster regression of cystoid macular oedema was observed with infliximab compared with CSs (P < 0.03). The beneficial effects of the three treatment modalities on visual acuity were comparable from baseline to the end of follow-up. No side effects were noted with infliximab or methylprednisolone, whereas intra-vitreal triamcinolone acetonide caused ocular hypertension in four of the eight eyes, requiring surgical intervention in two. CONCLUSION: A single infusion of infliximab should always be considered, even as an adjunct therapy, for the control of acute panuveitis attacks in BD.

Efficacy and safety of latanoprost in eyes with uveitic glaucoma.

BACKGROUND: To compare the efficacy and safety of latanoprost against a fixed combination of dorzolamide and timolol in eyes with elevated intraocular pressure (IOP) or glaucoma and anterior or intermediate uveitis. METHODS: Fifty-eight patients with anterior or intermediate uveitis and elevated IOP or glaucoma presented or followed up in the Ocular Inflammation and Immunology Service of General Hospital of Athens were randomly assigned to receive treatment either with latanoprost (30) or with dorzolamide/timolol (28). The main outcome measures were inflammatory relapses and IOP response to treatment. RESULTS: Ten patients (34%) in the latanoprost group and sixteen patients (57%) in the dorzolamide/timolol group experienced relapses of anterior uveitis (p = 0.93). There was no statistical difference between the two groups in respect of inflammatory relapses (p = 0.21). Twenty-one patients were followed up before starting latanoprost. The number of recurrences of anterior uveitis per patient per year before treatment with latanoprost was 0.82 +/- 1.2. The rate of relapses per patient per year after starting latanoprost was 0.39 +/-0.7 for these patients (p = 0.038). After 1 year of treatment, intraocular pressure was dropped from 27.8 +/- 8.4 mmHg to 18.6 +/- 5.3 mmHg (p < 0.001) in the latanoprost group and from 28.2 +/-8.1 mmHg to 22.6 +/-10.1 mmHg (p < 0.001) in the dorzolamide/timolol group. Four patients during treatment with latanoprost and five patients during treatment with dorzolamide/timolol developed macular edema. CONCLUSION: Latanoprost is safe and equally effective to a fixed combination of dorzolamide and timolol in the treatment of uveitic glaucoma.

Biologic Treatment Options for Retinal Neovascularization in Behçet's Disease.

PURPOSE: Relapsing ocular inflammation occurs in about 70% of patients with Behçet's disease (BD) and can lead to permanent loss of vision. Neovascularization of the optic disc (NVD) or elsewhere in the retina (NVE) is a relatively uncommon but severe complication that lacks standardized treatment. METHODS: We report on the therapeutic use of anti-TNF monoclonal antibodies for BD-associated NVD and NVE in one pediatric patient (subcutaneous adalimumab) and one young man (intravenous infliximab). Also, we review the previously published experience on biologic therapeutic options, namely anti-TNF agents and interferon-alpha in a total of three and eight patients, respectively. RESULTS: A fast-onset therapeutic effect was observed in both patients leading to complete regression of neovascularizations. CONCLUSIONS: Both options may lead to regression of neovascularization, thus preventing loss of vision, but comparative studies need to determine the optimal treatment for this sight-threatening complication of BD.

Course of macular edema in uveitis under medical treatment.

OBJECTIVE: To describe the response of uveitic macular edema to various treatment methods using optical coherence tomography (OCT). METHODS: This is a prospective study of consecutive uveitis patients with macular edema in at least one eye. The patients received medical treatment. Best corrected Snellen Visual Acuity (BCVA) and tomographic features of the macula, including macular thickness measurement, were obtained at one, three, six, and 12 months after commencing treatment. RESULTS: Eighty-one eyes of 58 patients were analyzed. Complete resolution of macular edema occurred in 38 eyes (47%). The average BCVA was 20/34 logarithm of minimum angle of resolution (-logMAR, 0.2 +/- 0.3) upon study entry and 20/27 (-logMAR, 0.13 +/- 0.29) upon study completion. The difference was statistically significant (p = 0.04). The corresponding mean retinal thickness at the central fovea was 319 +/- 150 microm at the beginning of the study compared to 241 +/- 125 microm at 12 months (p < 0.001). A weak but statistically significant correlation between the reduction of macular thickness and the improvement of BCVA (r = 0.3, p = 0.01) was found. Thirteen of the 43 eyes (30%) with persistent macular edema had a more than 15% reduction of macular thickness compared to baseline, whereas 10 eyes (23, 3%) had a more than 15% increase in macular thickness. Statistical analysis indicated that the presence of an epiretinal membrane and an OCT pattern of diffuse macular edema was a significant factor associated with medical treatment failure. CONCLUSION: This study demonstrates the overall favorable visual prognosis of uveitic macular edema under medical treatment. The presence of an epiretinal membrane is an important factor associated with medical treatment failure.

Brief Report: Drug-Free Long-Term Remission in Severe Behçet's Disease Following Withdrawal of Successful Anti-Tumor Necrosis Factor Treatment.

OBJECTIVE: To test the hypothesis that remission of Behçet's disease (BD) in patients with severe vital organ involvement is maintained after withdrawal of successful anti-tumor necrosis factor (anti-TNF) treatment. METHODS: This single-center, retrospective, longitudinal outcomes study focused on consecutive patients with disease refractory to treatment with conventional immunosuppressant agents who responded to add-on long-term anti-TNF treatment that was subsequently discontinued. The end point was the proportion of patients remaining in complete remission for at least 3 years after withdrawal of anti-TNF treatment. RESULTS: In our BD cohort comprising 87 patients, 29 were eligible for analysis. All of these patients had disease that was refractory to conventional immunosuppressive therapy and had received successful anti-TNF treatment for a median of 2 years (interquartile range [IQR] 1.1-2.0) before treatment discontinuation. Of these patients, 12 (41%) achieved the study end point. The remaining 17 patients experienced a relapse within 1 year (IQR 0.6-1.5) after discontinuation. Re-treatment with anti-TNF was safe and effective in 14 (82%) of 17 patients; so far, 4 of these patients also achieved the study end point. Overall, 16 patients have remained in complete remission (median 6.5 years [IQR 5.5-8]). Ten of these patients are in drug-free remission (treated with anti-TNF agents, mainly for sight-threatening disease), and 6 are in azathioprine-maintained remission (treated with anti-TNF agents for ocular, intestinal, or central nervous system involvement). Notably, patients in drug-free remission were significantly younger and had a significantly shorter duration of BD when anti-TNF treatment was initiated compared to patients receiving azathioprine maintenance treatment. CONCLUSION: Drug-free, long-term remission after withdrawal of successful anti-TNF treatment is feasible in patients with severe BD. Because an anti-TNF agent-induced "cure" cannot be differentiated from spontaneous remission by natural history, prospective studies should examine whether anti-TNF agents should be used as first-line treatment for the induction of remission in every patient with vital organ involvement.

Intravenous pulse methylprednisolone therapy for acute treatment of serpiginous choroiditis.

PURPOSE: To evaluate the safety and efficacy of high-dose intravenous steroid therapy (HDIST) for the acute treatment of vision-threatening serpiginous choroiditis. METHODS: Retrospective review of the records of five patients with serpiginous choroiditis who were treated with HDIST (1 g methylprednisolone for three days) in addition to their standard immunosuppressive treatment. The visual acuities and improvement of ocular signs after HDIST were evaluated. RESULTS: Twelve episodes of macula-threatening choroiditis in five patients with serpiginous choroiditis were treated during a seven-year period. All patients responded to HDIST with evidence of a decrease in intraocular inflammation immediately after and complete restoration of visual acuity within 10 days of commencing treatment. In one patient, medical intervention was required because of gastric distress. During the follow-up, three out of five patients experienced new attacks and two patients developed subretinal neovascularization. CONCLUSION: HDIST is effective in controlling severe vision-threatening serpiginous choroiditis and in improving visual function in a short period of time. However, the effect of this treatment in long-term disease control is uncertain.

Regression of neovascular age-related macular degeneration following infliximab therapy.

PURPOSE: To describe the effects of the antitumor necrosis factor (TNF) monoclonal antibody Infliximab systemic therapy on choroidal neovacularisation (CNV) secondary to age-related macular degeneration (AMD). DESIGN: Prospective, noncomparative series of three patients. METHODS: A subretinal membrane secondary to AMD was documented by fluoroangiography at baseline in three elderly patients scheduled to receive Infliximab therapy for inflammatory arthritis (infusions of 5 mg/kg at weeks 0, 2, 6, and every 8 weeks thereafter). Follow-up was performed at three months post-baseline, as well as during 18 months of continuing treatment in the first patient. RESULTS: CNV regressed partially at three months and resolved at six months in the first patient. Best-corrected visual acuity (BCVA) increased from 0.05 to 0.2; this effect was sustained at 18 months. Regression of subretinal membrane and increase of BCVA was also documented in the other patients. No ocular or extra-ocular side effects were noted. CONCLUSIONS: These findings suggest a plausible pathogenetic role of TNF in CNV secondary to AMD. Additional patients should be studied to confirm the promising clinical results.

The role of fundus autofluorescence imaging in the study of the course of posterior uveitis disorders.

BACKGROUND: To evaluate the correlation of fundus autofluorescence (FAF) with indocyanine green angiography (ICGA) in patients with various posterior uveitis disorders. METHODS: Interventional case series including 23 eyes of 15 patients with diagnosis of a specific type of retinochoroiditis, such as acute posterior multifocal placoid pigment epitheliopathy (APMPPE), serpiginous-like choroiditis, multifocal choroiditis (MFC), Harada disease, and syphilitic retinochoroiditis. Also, some cases with undefined retinochoroiditis were included. FAF and ICGA were performed and correlated at baseline and during follow-up after treatment. RESULTS: In ICGA, early hypofluorescence was found to be the hallmark of acute choroidal inflammation, resolving in later stages and remaining in the late phase in areas with retinal pigment epithelium (RPE) damage. Poorly defined hyperautofluorescent areas correlated with acute choroidal lesions. Hypoautofluorescent delineation suggested the initiation of RPE healing processes, correlating well with the late phase of ICGA and delineating the RPE damage. Early hyperautofluorescence with late hypofluorescence in ICGA indicated the presence of primary RPE involvement. CONCLUSION: FAF contributes to the interpretation of RPE disease and may be a useful tool for the follow-up of progressive inflammatory disorders. Comparative evaluation of FAF and ICGA allows a characterization of the sequence of inflammatory events and the level of tissue affected.

Macular hole closure after peribulbar steroid injection.

PURPOSE: To report the closure of a macular hole after a peribulbar corticosteroid injection in a patient with anterior uveitis associated with human leukocyte antigen B*27. DESIGN: Interventional case report.The patient was evaluated by comprehensive ophthalmic check-up and optical coherence tomography. RESULTS: A healthy 50-year-old woman presented to our service with active human leukocyte antigen B*27-associated anterior uveitis, macular hole in the right eye and macular edema in the left eye. Visual acuity was 20/200 in both eyes. Peribulbar injections of triamcinolone acetonide were administered in both eyes. Three months later, visual acuity improved to 20/50 in both eyes, and the uveitis was in complete remission. Optical coherence tomography verified that the macular hole in the right eye was closed. CONCLUSIONS: Inflammation and macular edema might be contributing factors in macular hole formation in patients with uveitis. This case indicates that treatment of inflammation and macular edema might lead to macular hole closure in similar cases.

Infliximab for chronic cystoid macular edema associated with uveitis.

PURPOSE: To assess the efficacy of the anti-TNF monoclonal antibody infliximab in uveitis patients without clinically evident ocular inflammation and impaired visual acuity because of chronic cystoid macular edema (CME). DESIGN: Prospective, noncomparative, interventional case series. METHODS: Patients with refractory CME (14 eyes, mean duration of 14 months), associated with intermediate uveitis (n = 6), Adamantiades-Behcet disease (n = 2), adult-type vascular pseudotumor (n = 1), and HLAB27+-related uveitis (n = 1) received an intravenous infliximab infusion (5 mg/kg); five patients were retreated after 1 month. RESULTS: Macular thickness, measured by ocular coherence tomography, was reduced from 428 +/- 138 microm to 219 +/- 51 microm at 2 months postbaseline (P = .0001), while visual acuity increased from 0.41 +/- 0.18 to 0.83 +/- 0.17 (P < .00001). Anatomic and functional improvement was sustained at 6 months in all. No ocular or extra-ocular side effects were noted. CONCLUSION: These promising results suggest that TNF may play an important pathogenetic role in chronic CME, thus, a controlled trial is warranted.

Human mast cell subtypes in conjunctiva of patients with atopic keratoconjunctivitis, ocular cicatricial pemphigoid and Stevens-Johnson syndrome.

PURPOSE: Investigate mast cell (MC(S)) subtypes in atopic keratoconjunctivitis (AKC), ocular cicatrical pemphigoid (OCP), and Stevens-Johnson Syndrome (SJS). METHODS: MC(S) subtypes were determined by immunohistochemistry of conjunctiva (obtained from 34 patients--9 AKC, 9 OCP, 9 SJS and 7 normal) using monoclonal antibodies directed against chymase (MC(C)) and tryptase (MC(T)). Double staining was used to distinguish MC(S) as positive for both chymase and tryptase (MC(TC)). RESULTS: The number of MC(S) was significantly increased in AKC, OCP and SJS patients, compared to normal subjects. MC( C) were especially high in AKC, and moderately high in OCP. MC(T ) and MC(TC) were similar in each disease group. CONCLUSIONS: While the AKC findings were not surprising, the result in OCP and SJS suggests that MC(S) play an underappreciated role in the inflammatory process of these disorders. Disparate proportions of MC(S) subtypes in these diseases may imply differential functions of MC(S) in these disorders.

Idiopathic retinal vasculitis, arteriolar macroaneurysms and neuroretinitis: clinical course and treatment.

BACKGROUND: The purpose of the study is to describe the clinical course and treatment of idiopathic retinitis, vasculitis, aneurysms and neuroretinitis. The study utilized non-randomized, retrospective and interventional case series. The eight eyes of six patients were analysed. Testing included wide fluorescein angiography, indocyanine green angiography and systemic evaluation. Treatment involved observation, panretinal laser photocoagulation (PRP) for peripheral retinal ischemia, grid laser for macular oedema and focal laser on the macroaneurysms. The main outcome measures were initial visual acuity (VA), initial stage at diagnosis, clinical course, surgical intervention, final VA, final stage and complications of disease. RESULTS: Five out of eight eyes with retinal ischemia in more than two quadrants that were treated with PRP and grid laser for macular oedema maintained excellent VA and demonstrated no progression of retinal ischemia during follow-up. The two eyes which exhibited retinal ischemia in less than two quadrants and macular oedema were treated with grid laser and focal laser on the macroaneurysms, but did not undergo PRP. VA improved by two lines of the Snellen chart, and there was no progression of retinal ischemia during the 3 and 4 years of follow-up. One eye with neither retinal ischemia nor macular oedema was not treated, and the clinical picture remained stable during the follow-up. CONCLUSION: Early PRP may be considered in the presence of angiographic evidence of peripheral retinal non-perfusion. However, treatment could be withheld until the patient develops retinal ischemia in more than two quadrants.

Twelve months of follow-up after intravitreal injection of ranibizumab for the treatment of idiopathic parafoveal telangiectasia.

AIMS: To report the anatomic and functional outcomes of intravitreal ranibizumab in idiopathic parafoveal telangiectasia (IPT). MATERIAL AND METHODS: Four eyes of three patients were included in this interventional case series. One patient (two eyes) had bilateral IPT (type 2) and two patients (two eyes) had unilateral (type 1) IPT. Retreatment was scheduled in case of leakage persistence in combination with visual acuity (VA) deterioration. Fluorescein angiography and optical coherence tomography were performed together with a full ophthalmic examination at baseline, 1, 3, 6, 9, and 12 months after injection. RESULTS: One intravitreal injection of ranibizumab was performed in all four eyes. Complete cessation of leakage was documented postintervention in three eyes and partial cessation in one eye, followed by improvement of best corrected VA in one of them. In all eyes, structural changes of the photoreceptor layer were detected in tomography and were responsible for visual loss, which was in most cases, refractory to the applied therapy. CONCLUSION: Use of ranibizumab might be efficient in eliminating leakage activity in the macular region in patients with IPT. Nevertheless, improvement in VA was infrequent. Preexisting early photoreceptor alteration in IPT might render such patients unable to improve VA.

Human herpes virus-6 as a cause of recurrent posterior uveitis in a HIV-positive patient.

PURPOSE: To report a case of bilateral recurrent posterior uveitis caused by human herpes virus-6 (HHV-6) in a human immunodeficiency virus-positive individual. METHODS: Comprehensive ophthalmic examination, including imaging with optical coherence tomography, fluorescein and indocyanine green angiography, and adequate laboratory tests were performed. A human immunodeficiency virus-positive patient without any AIDS defining condition, with a history of recurrent bilateral posterior uveitis referred to us with the diagnosis of retinal detachment. RESULTS: Vitreous polymerase chain reaction detected an aberrant band for herpes viruses, which proved to be human herpes virus-6 by repeated polymerase chain reactions. Serum antibodies titer was positive for human herpes virus-6. The patient responded well to antiviral therapy with valacyclovir. CONCLUSION: This is the first case of human herpes virus-6-related bilateral posterior uveitis in a human immunodeficiency virus-positive individual without clinical manifestations of AIDS.