Blepharoptosis and external ophthalmoplegia associated with long-term antiretroviral therapy.

BACKGROUND: Long-term antiretroviral therapy (ART) is associated with lipodystrophy, peripheral neuropathy, lactic acidosis, and myopathy. Blepharoptosis, without prior ART association, is usually caused by age-associated involutional ptosis, but it is also seen in mitochondrial myopathies with external ophthalmoplegia, cardiac conduction disturbances, and neurological impairments. METHODS: Patients presented over a 2-year period. Four patients underwent surgical blepharoptosis repair. RESULTS: Five human immunodeficiency virus type 1-infected patients (median age, 50 years; range, 46-53 years) who were receiving ART presented with severe blepharoptosis; 2 of these 5 also presented with external ophthalmoplegia. Findings included decreased palpebral fissure height (median, 6.5 mm; normal height, 9 mm), mildly impaired levator function (median, 10 mm; normal, >13 mm), and markedly decreased marginal reflex distance (median, 0.5 mm; normal, 4 mm). A greater advancement of the levator aponeurosis was required during surgical repair, a finding consistent more with myogenic than with involutional blepharoptosis. All patients had severe lipodystrophy, which preceded blepharoptosis by a median interval of 4.7 years (range, 2.8-5.7 years). Four patients also presented with peripheral neuropathy and metabolic abnormalities before the onset of blepharoptosis, and 3 had cardiac conduction disturbances. Patients received ART for a median of 7.8 years (range, 4.9-11.2 years), thymidine analogue-containing ART for a median of 7.1 years (range, 1.2-7.9 years), and protease inhibitor-containing ART for a median of 7.1 years (range, 4.9-8.9 years). CONCLUSIONS: We report the novel findings of blepharoptosis and external ophthalmoplegia in patients who are receiving ART. Ptosis was preceded by lipodystrophy with long-term use of both thymidine-analogue- and protease inhibitor-containing ART. The findings are most consistent with myogenic ptosis in a generalized mitochondrial myopathy syndrome. Clinicians should also be watchful for other potential myopathic ptosis-associated complications, including proximal weakness, dysphagia, deafness, and cardiac conduction disturbances.

Multicenter evaluation of the Bayer ADVIA Centaur HIV 1/O/2 enhanced (EHIV) assay.

BACKGROUND: It is important that serological assays detect antibodies to human immunodeficiency virus (HIV) in all infected individuals, including those infected with less prevalent, more diverse subtypes. METHODS: Performance of the ADVIA Centaur HIV 1/O/2 Enhanced (EHIV) Assay was tested on 1344 samples from HIV-positive subjects, 6061 samples from groups at low-risk for HIV infection, and 1042 samples from groups at high-risk for HIV-1 and HIV-2 infection. Results were compared with those of an FDA-approved predicate assay. RESULTS: The ADVIA Centaur EHIV Assay showed good precision with a diagnostic specificity of 99.9% and diagnostic sensitivity of 100%. HIV seroconversion was detected earlier in 6 panels, at the same time in 13 panels and later in only 1 of the panels when compared to the predicate assay, thereby narrowing the window period between infection and antibody detection. Of clinical significance, a blood donor sample that was indeterminate by HIV-1 Western blot and non-reactive by the predicate assay was repeatedly reactive in the ADVIA Centaur Assay and confirmed as positive by HIV-2 immunoblot. CONCLUSIONS: The ADVIA Centaur EHIV Assay is useful as an aid in the diagnosis of individuals infected with HIV-1 and/or HIV-2.

Clinical, microbiological, and immunological characteristics in HIV-infected subjects at risk for disseminated Mycobacterium avium complex disease: an AACTG study.

The clinical, microbiologic, and immunologic parameters in HIV-infected subjects first presenting with disseminated Mycobacterium avium complex (DMAC) were determined. Four HIV-positive groups not yet on DMAC treatment were enrolled: 19 subjects with CD4 lymphocyte counts < or =50/microl thought to have DMAC on clinical grounds; 18 subjects newly found to have a positive blood culture for MAC; 25 asymptomatic controls (CD4 cell counts < or =50); and 25 asymptomatic controls (CD4 counts 100-250/microl). Outcome measures include comparisons between groups for clinical characteristics; results of cultures from blood, marrow, and gastrointestinal and respiratory tracts; immunological markers from staining of marrow and flow cytometry of circulating lymphocytes; and cytokine production of PBMCs. Only 21% of the 19 patients entered on suspicion of having DMAC grew MAC from blood or marrow. Neither clinical presentation nor laboratory tests differentiated those culture-positive from those culture-negative patients. However, prior PCP or multiple other opportunistic infections were more common in the DMAC group. MAC was isolated from 82% of marrow and 50% of blood specimens from the DMAC group. Respiratory or gastrointestinal colonization was present in 36% of DMAC subjects, but only 5% of non-DMAC subjects with CD4 counts <50 cells/microl. CD8+ cells were more frequent in bone marrow, and CD4 cells recognizing MAC antigen were more frequent in blood from DMAC subjects vs. controls. Results suggest an early stage of tissue dissemination preceding persistent bacteremia, and mucosal entry without persistence of colonization. MAC-specific T cell responses apparently develop and persist during DMAC, but are dysfunctional or too infrequent to prevent persistence.

Regional body fat distribution in HIV-infected patients with lipodystrophy.

BACKGROUND: Objective criteria for the assessment of patients with lipodystrophy syndrome in human immunodeficiency virus infection (LDHIV) have not emerged. METHODS: We compared regional body fat changes in 13 men with severe LDHIV on protease inhibitor-inclusive antiretroviral therapy with 13 control HIV-infected men using anthropometry, dual-energy X-ray absorptiometry (DEXA), and whole-body magnetic resonance imaging (MRI). RESULTS: LDHIV patients, compared with control subjects, had thinner gluteal, suprailiac, and triceps skinfolds (p < .01) and increased waist circumference (98 +/- 5 cm vs 86 +/- 9 cm, respectively; p = .0008). DEXA studies revealed reduced lower extremity fat (12 +/- 5% vs 22 +/- 9%; p = .0006), increased head and neck fat (18 +/- 3% vs 16 +/- 1%; p = .01), and increased proportion of total body fat in the trunk (65 +/- 7% vs 53 +/- 8%; p = .0005). MRI analysis revealed reduced thigh fat (12 +/- 5% vs 22 +/- 12%; p = .01), increased dorsocervical fat depth (47 +/- 24 mm vs 19 +/- 7 mm; p = .0009), and nearly significant increase in intra-abdominal fat (218 +/- 90 cm2 vs 157 +/- 70 cm2; p = .057). Interestingly, control subjects showed a positive relationship between intra-abdominal and dorsocervical fat (r= .57, p = .04), but the LDHIV patients showed a negative relationship (r= -.55, p = .05), suggesting a novel split phenotype among LDHIV patients of either dorsocervical or intra-abdominal fat accumulation. CONCLUSIONS: We conclude that MRI provides the best tools for definition of LDHIV syndrome and reveals variable phenotypes among LDHIV patients.

T cells containing T cell receptor excision circles are inversely related to HIV replication and are selectively and rapidly released into circulation with antiretroviral treatment.

OBJECTIVE: To examine baseline predictors of T-cell receptor rearrangement excision circle (TREC) levels and their changes during treatment with combined antiretroviral therapy. METHODS: Peripheral blood and lymph node lymphocytes were examined for the presence of TREC by real-time polymerase chain reaction and circulating lymphocyte phenotypes were examined by flow cytometry. Correlates for CD4 and CD8 cell TREC levels at baseline were identified among CD4 and CD8 immunophenotypes, viral load and patient demographics; the significance of TREC changes after initiation of antiretroviral therapy was assessed. RESULTS: Circulating TREC levels correlated inversely with age, with HIV RNA levels, with activation markers on circulating T cells and with naive CD4 but not CD8 cell frequencies. With initiation of antiretroviral therapy, TREC and naive T cell frequencies increased in peripheral blood during the first 2 weeks of treatment and these changes correlated negatively with TREC frequencies in lymph node aspirates, particularly among CD8 T cells. CONCLUSIONS: These findings suggest that recent thymic emigrants are sequestered in lymphoid tissue during uncontrolled HIV replication and are selectively released into circulation rapidly after initiation of antiretroviral therapies.