Publications

OBJECTIVE

To characterize HIV-infected patients with neurosymptomatic cerebrospinal fluid (CSF) 'escape', defined as detectable CSF HIV RNA in the setting of treatment-suppressed plasma levels or CSF RNA more than 1-log higher than plasma RNA.

DESIGN

Retrospective case series.

SETTING

Four urban medical centers in the United States and Europe.

PARTICIPANTS

Virologically controlled HIV-infected patients on antiretroviral therapy (ART) with progressive neurologic abnormalities who were determined to have CSF 'escape'. INTERVENTION Optimization of ART based upon drug susceptibility and presumed central nervous system exposure.

MAIN OUTCOME MEASURES

Levels of CSF HIV RNA and inflammatory markers, clinical signs and symptoms, and MRI findings.

RESULTS

Ten patients presented with new neurologic abnormalities, which included sensory, motor, and cognitive manifestations. Median CSF HIV RNA was 3900 copies/ml (range 134-9056), whereas median plasma HIV RNA was 62 copies/ml (range <50 to 380). Median CD4 T-cell count was 482 cells/μl (range 290-660). All patients had been controlled to less than 500 copies/ml for median 27.5 months (range 2-96) and five of 10 had been suppressed to less than 50 copies/ml for median 19.5 months (range 2-96). Patients had documentation of a stable ART regimen for median 21 months (range 9-60). All had CSF pleocytosis or elevated CSF protein; seven of eight had abnormalities on MRI; and six of seven harbored CSF resistance mutations. Following optimization of ART, eight of nine patients improved clinically.

CONCLUSION

The development of neurologic symptoms in patients on ART with low or undetectable plasma HIV levels may be an indication of CSF 'escape'. This study adds to a growing body of literature regarding this rare condition in well controlled HIV infection.

We sought to evaluate the association of urine calcium excretion (UCaE), which reflects systemic calcium absorption, with cardiovascular (CV) events and mortality in outpatients with prevalent coronary heart disease (CHD). Calcium supplementation is associated with vascular calcification and adverse CV outcomes in patients with end-stage renal disease. Recent studies have raised concern that this phenomenon may also extend to the general population. However, previous studies have assessed oral calcium intake, which correlates poorly with systemic calcium absorption. We measured UCaE from 24-hour urine collections provided by 903 outpatients who were recruited from 2000 to 2002. We used Cox proportional hazard models to evaluate the association of baseline UCaE with a primary end point of any CV event (myocardial infarction [MI], heart failure, stroke, or CV mortality). During a mean follow-up of 6 ± 3 years, 287 subjects (32%) had a CV event. After multivariate adjustment for demographics, traditional CV risk factors, and kidney function, there was no association between UCaE and the primary end point of any CV event (per 10-mg/day greater UCaE, hazard ratio 1.00, 95% confidence interval 0.98 to 1.02). Evaluation of individual CV outcomes revealed a lower rate of MI with higher UCaE (hazard ratio 0.97, 95% confidence interval 0.94 to 1.00). In conclusion, greater UCaE is not associated with higher overall CV event rates or mortality in outpatients with stable CHD. On the contrary, greater UCaE is associated with a modestly lower rate of MI. These findings suggest that greater systemic calcium absorption does not confer CV harm in outpatients with prevalent CHD.

Lichen sclerosus is a commonly misdiagnosed disease that is characterized by thinned, hypopigmented, crinkled skin that often forms a figure-eight shape around the vaginal and anal openings. We present a case of advanced lichen sclerosus in a 53-year-old female patient prescribed a nonsteroidal aromatase inhibitor after the excision of a breast cancer tumor. We present a diagnostic approach to lichen sclerosus by recognizing its common figure-eight pattern, and we review the known causes and treatment of lichen sclerosus. Research has shown that lichen sclerosus is more common in low estrogen states, and thus it is logical that aromatase inhibitors could increase a patient's risk for developing this disease. We therefore propose that all patients prescribed aromatase inhibitors undergo regular vulvo-vaginal exams to rule out lichen sclerosus and other hypoestrogen-related vulvo-vaginal problems.