Safety and efficacy of posaconazole in the long-term treatment of azole-refractory oropharyngeal and esophageal candidiasis in patients with HIV infection.

PURPOSE: To evaluate safety and efficacy of long-term posaconazole in HIV-infected patients with azole-refractory oropharyngeal candidiasis and/or esophageal candidiasis. METHOD: In this noncomparative, open-label study, participants received oral posaconazole 400 mg twice daily (bid) for 3 months. Enrolled patients (N = 100) included 60 from a previous 1-month acute study of posaconazole and 40 posaconazole-naïve participants. Participants with a clinical response could be followed untreated for up to 1 month afterwards. Participants who relapsed during follow-up, showed improvement at the end of 3 months of treatment (EOT), or were cured but likely to benefit from further therapy could continue on posaconazole 400 mg bid for up to 12 months. RESULTS: In the modified intent-to-treat population, clinical response (cure or improvement) occurred in 85.6% (77/90) at EOT. The results were similar in the previously treated participants and the posaconazole-naïve participants, 88.1% (52/59) and 80.6% (25/31), respectively. Posaconazole was well-tolerated, showing a similar safety profile during the 3-month study period and during suppressive therapy. The most frequently reported treatment-related adverse event was vomiting (4/100, 4%) during the early follow-up period (on or before day 105) and elevated hepatic enzymes (3/51, 6%) during the long-term follow-up (after day 105). CONCLUSION: Oral posaconazole 400 mg bid demonstrated long-term safety, tolerability, and efficacy, offering a long-term, suppressive treatment option for HIV-infected participants with azole-refractory mucosal candidiasis.

Clinical significance of eosinophilia in HIV-infected individuals.

PURPOSE: To assess the clinical significance of peripheral eosinophilia in HIV-infected individuals. METHODS: In a retrospective case-control study we compared 42 HIV-infected patients (cases) with peripheral eosinophilia (absolute eosinophil count > 500 cells/mm3) with 84 HIV-infected controls without eosinophilia. Cases were matched to controls by date, and by CD4 cell count. Data on clinical parameters possibly associated with eosinophilia were collected and compared among cases and controls. RESULTS: Eosinophilia was seen in patients with late-stage HIV disease (median CD4 cell count of 26 cells/mm3). Cases were more likely to be black (52% versus 18%, P = 0.0001), have pruritus (50% versus 20%, P = 0.002), and have a physician-documented rash (76% versus 52%, P = 0.02). Specific cutaneous diagnoses that were more prevalent in cases versus controls were eosinophilic folliculitis (24% versus 1% P = 0.0001), atopic dermatitis (14% versus 1%, P = 0.01), and prurigo nodularis (7% versus O, P = 0.07). Other parameters commonly associated with eosinophilia such as allergic reactions, parasitic infection, malignancy, and adrenal insufficiency were not found at higher incidence in cases. CONCLUSIONS: Eosinophilia in AIDS patients is associated with cutaneous disease, but not with other conditions commonly associated with eosinophilia including parasitic infections, allergic reactions, or malignancy. Extensive work up for asymptomatic eosinophilia in patients with AIDS and cutaneous disease is not warranted.

The importance of comorbidity in HIV-infected patients over 55: a retrospective case-control study.

PURPOSE: To study the impact of comorbidity on the course of HIV disease in older patients as compared to a matched cohort of younger patients. METHODS: In a retrospective case-control study, we compared 43 HIV-infected patients > 55 years old to a randomly selected cohort of 86 patients < 45 years old, matched by date of HIV diagnosis. We collected data on non-HIV-related morbidity (as assessed by the Charlson comorbidity index), initiator of HIV testing, HIV stage at time of HIV diagnosis (TOHD), AIDS defining diagnoses, AIDS-related illnesses (ARI), observed AIDS-free interval, survival, and frequency of HIV-related and unrelated hospitalizations. RESULTS: The older cohort was more likely to have had HIV testing initiated by a health care provider (36 of 36 versus 50 of 66, P = 0.003), and to have acquired HIV from a transfusion (5 of 43 versus 0 of 86, P = 0.001), had lower CD4 cell counts at TOHD (205 versus 429, P = 0.02), a shorter observed AIDS-free interval (24.0 versus 52.8 months, P = 0.0002) and a shorter survival (28.2 versus 58.9 months, P = 0.0002). The older cohort had more HIV-related (13.4 versus 9.2 per 100 patient-months, P = 0.024) and non-HIV-related hospitalizations (12.9 versus 8.1 per 100 patient-months, P = 0.0001). The comorbidity index was significantly higher in the older cohort (0.907 versus 0.198, P = 0.0001) and was a strong predictor of mortality, independent of age group (risk ratio = 1.38 per comorbidity point, P = 0.0003). CONCLUSIONS: Older HIV-infected patients presented with more advanced disease, which may have been due to lack of HIV awareness in this population. Older patients had a shorter observed AIDS-free interval and shorter survival. In addition, they had more HIV- and non-HIV-related comorbidity. The more rapid course and decreased survival in the elderly may be related to the increase in comorbidity.

Therapeutic developments in cytomegalovirus retinitis.

The incidence of cytomegalovirus (CMV) retinitis in AIDS has declined significantly due to the use of highly active antiretroviral therapy (HAART). However, patients with HIV, especially those failing HAART, may still suffer with CMV retinitis, which can lead to significant loss of vision and blindness. Ganciclovir has traditionally been considered the recommended treatment for CMV retinitis; however, due to side effects and the possibility of developing viral resistance, other agents may be preferred in certain situations. Foscarnet, which has similar efficacy to ganciclovir but a different side effect profile, is more difficult to administer and is less well-tolerated. Intravenous cidofovir, which may be more effective than either iv. ganciclovir or foscarnet, can also be used as a first line agent; however, it is associated with toxicity (renal and ocular) and thus needs careful use. Local therapy for CMV retinitis has been a significant advance. The intraocular ganciclovir implant has the highest efficacy of the approved agents and is well-tolerated. Fomivirsen, an oligonucleotide injected intravitreally, is a newly approved agent which offers alternative treatment. Intravitreal ganciclovir or foscarnet, although not approved, have been used successfully in some patients especially those with recurrent or refractory disease. The development of new anti-CMV agents has been stalled by the decreased incidence of the disease. Valganciclovir, a prodrug of ganciclovir, offers excellent oral bioavailability and is the closest to approval of all the new anti-CMV drugs. High ganciclovir blood levels are achieved without the complications associated with the requirement for long-term iv. access. The monoclonal antibody (mAb) MSL-109, did not offer a significant advantage when added to traditional anti-CMV therapy. Development plans of other agents such as cyclic HPMPC and lobucavir have been put on hold by their respective manufacturers. Adefovir is a nucleotide analogue that possesses anti-CMV activity, but is currently only being pursued for the treatment of hepatitis B virus. Other compounds possessing significant anti-CMV activity, including BAY 38-4766 and GW1263W94 are still in the early stages of development.

Polymerase chain reaction for detection of herpes simplex virus encephalitis.

A patient with herpes simplex virus encephalitis is described. The polymerase chain reaction (PCR) was used to confirm the diagnosis in cerebrospinal fluid. PCR allows the rapid diagnosis of many infectious organisms, such as HSV, in which prompt diagnosis is essential.

Granulocytopenia secondary to acute infection with the human immunodeficiency virus.

Acute infection with the human immunodeficiency virus (HIV) is often characterised by a mononucleosis-like syndrome. We describe a patient who presented with the typical febrile syndrome associated with acute HIV infection, who also had significant granulocytopenia. Although granulocytopenia is relatively common in the later stages of HIV infection, it has only been described once before in the acute stage. The mechanism may be immune mediated, although data are limited. Clinicians should be aware of acute HIV infection as a possible cause of granulocytopenia.

SPECT thallium-201 combined with Toxoplasma serology for the presumptive diagnosis of focal central nervous system mass lesions in patients with AIDS.

OBJECTIVE: To determine the utility of brain thallium-201 single photon emission computerized tomography (Tl-201 SPECT) combined with Toxoplasma serology for the diagnosis of focal CNS lesions in patients with AIDS. METHODS: Sixty-one consecutive HIV-infected patients with focal CNS lesion(s) on head computed tomography (CT) or MRI scan who underwent brain Tl-201 SPECT and serum Toxoplasma serology were evaluated, retrospectively. Thallium-201 uptake ratios were calculated by comparing lesion activity to contralateral scalp activity. Diagnoses were made by a combination of histology, serology, PCR, and empirical response to therapy. Toxoplasma serologies (IgG IFA) were compared in the patients with central nervous system (CNS) toxoplasmosis and those without CNS toxoplasmosis. RESULTS: Fifty-six patients were evaluable and a definitive diagnosis was made in 38 patients: toxoplasmosis (17), lymphoma (14), PML (three), Aspergillus (one), tuberculoma (one), Cryptococcus (one), varicella-zoster virus (one). Patients with lymphoma had significantly higher lesion/contralateral scalp ratios compared to patients without lymphoma: 1.03 vs. 0.67, P < 0.05. Using a cut-off of 0.90 for the lesion/scalp uptake ratios (based on analysis of ROC curves) the sensitivity and specificity for the diagnosis of lymphoma were 86% and 83%, respectively. Serum Toxoplasma IgG titres were significantly higher in patients diagnosed with toxoplasmosis compared to those with a diagnosis other than toxoplasmosis, 1:5444 vs. 1:15, P < 0.05. Only one patient with confirmed toxoplasmosis had a Toxoplasma serology < 1:256, while no patients without toxoplasmosis (including all lymphoma patients) had serologies > 1:256. CONCLUSIONS: In a series of HIV-infected patients, Tl-201 SPECT was able to accurately differentiate primary brain lymphoma from other causes of focal CNS lesions in most patients; however, both false positive and false negative results occurred. By combining Tl-201 SPECT with serum Toxoplasma IgG, diagnostic accuracy was improved.

Clinical manifestations of influenza in HIV-infected individuals.

Although influenza vaccination is recommended for individuals with HIV infection, there are no data indicating an increased incidence or severity of influenza in this population. We sought to describe the clinical manifestations and morbidity of influenza in HIV-infected patients. All cases of influenza occurring in HIV-infected individuals over 3 years at a large county hospital were reviewed. Forty-three cases of influenza were diagnosed. Most patients presented with typical signs and symptoms of influenza, including cough (90%), myalgias (64%), and fever (52%). Sore throat and headache occurred in less than half of patients. The mean CD4 cell count and HIV viral load in patients with influenza was 340 cells/mm(3) and 3.34 log copies/ml, respectively. No significant differences in CD4 counts or viral loads were noted in patients with pneumonia (n=7) compared with patients without pneumonia (n=36), P>0.5. Six patients were hospitalized. One patient each had encephalitis and renal failure, although the relationship to influenza was not clear. No new or unusual clinical manifestations were observed. The rate of pulmonary complications was similar to other studies in HIV-negative patients; however, the hospitalization rate was higher than commonly seen in HIV-negative individuals.

Protease inhibitor therapy is associated with markedly prolonged time to relapse and improved survival in AIDS patients with cytomegalovirus retinitis.

Prior to the use of highly active antiretroviral therapy (HAART), cytomegalovirus retinitis (CMV-R) in AIDS patients was characterized by multiple relapses and decreased survival. Recent data suggest that CMV-R in patients treated with HAART may remain relapse-free for long periods. We performed a study of the effects of HIV protease inhibitors (PIs) on the incidence of relapse and time to death in AIDS patients with CMV-R treated with anti-CMV therapy. Medical records of all AIDS patients with CMV-R at Parkland Memorial Health and Hospital System treated with anti-CMV agents were reviewed for date of diagnosis of CMV-R, date of CMV-R relapse, type and duration of anti-CMV therapy, and duration of PI therapy. Relapse rates in subjects treated with PIs were compared with the relapse rates in those who were not treated with PIs. The primary endpoint was the time to relapse and death as determined by Kaplan-Meier analysis. Multivariate analysis was performed by Cox proportional hazard model. One hundred and nine cases of CMV-R were identified in 75 patients. Median follow-up time was 247 days (range 31-1818 days). There were 0.54 relapses per 1000 patient days in the group treated with PIs compared with 1.83 relapses per 1000 patient days in the non-PI treatment group (relative risk [RR]=0.29, P<0.01). Time to relapse was increased in the PI treatment group compared with the non-PI treatment group (endpoint not reached vs 182 days, P<0.001, log-rank). Similarly, the time to relapse or death was increased in the PI group compared with the non-PI group (543 days vs 103 days, P<0.001, log-rank). Multivariate analysis utilizing the Cox proportional hazards model demonstrated that only PI therapy but not anti-CMV therapy was associated with decreased risk of CMV-R relapse or death. Only 3 patients with an undetectable HIV viral load and one patient with a CD4 count >120 cells/microl had a relapse. We conclude that patients with CMV-R treated with HAART containing a PI have increased time to relapse and have prolonged survival.

Prosthetic hip infection related to a dental procedure despite antibiotic prophylaxis.

A 39-year-old man with systemic lupus erythematosus who was taking corticosteroids had a prosthetic hip infection with Streptococcus oralis after a dental procedure despite prophylaxis with erythromycin. The causative organism was resistant to erythromycin. For patients with prosthetic joints the literature does not support dental prophylaxis, which even if given appropriately, may fail to prevent infection. Some experts advocate giving antibiotic prophylaxis to patients at high risk, although data supporting this practice are limited. However, considering that most orthopedic surgeons and many dental clinicians provide antibiotic prophylaxis, alternatives to erythromycin such as a first-generation cephalosporin should be considered.

Neurocognitive effects of treatment interruption in stable HIV-positive patients in an observational cohort.

OBJECTIVE: Prior studies have shown improved neurocognition with initiation of antiretroviral treatment (ART) in HIV. We hypothesized that stopping ART would be associated with poorer neurocognitive function. METHODS: Neurocognitive function was assessed as part of ACTG 5170, a multicenter, prospective observational study of HIV-infected subjects who elected to discontinue ART. Eligible subjects had CD4 count >350 cells/mm(3), had HIV RNA viral load <55,000 cp/mL, and were on ART (>or=2 drugs) for >or=6 months. Subjects stopped ART at study entry and were followed for 96 weeks with a neurocognitive examination. RESULTS: A total of 167 subjects enrolled with a median nadir CD4 of 436 cells/mm(3) and 4.5 median years on ART. Significant improvements in mean neuropsychological scores of 0.22, 0.39, 0.53, and 0.74 were found at weeks 24, 48, 72, and 96 (all p < 0.001). In the 46 subjects who restarted ART prior to week 96, no significant changes in neurocognitive function were observed. CONCLUSION: Subjects with preserved immune function found that neurocognition improved significantly following antiretroviral treatment (ART) discontinuation. The balance between the neurocognitive cost of untreated HIV viremia and the possible toxicities of ART require consideration. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that discontinuing ART is associated with an improvement in 2 neuropsychological tests (Trail-Making Test A & B and the Wechsler Adult Intelligence Scale-Revised Digit Symbol subtest) for up to 96 weeks. Resuming ART was not associated with a decline in these scores for up to 45 weeks.

Human immunodeficiency virus infection in patients older than 50 years. A survey of primary care physicians' beliefs, practices, and knowledge.

To assess primary care physicians' attitudes, knowledge, and practices with respect to the human immunodeficiency virus (HIV) in older patients, a prospective survey of a representative cohort of primary care physicians was conducted in Dallas County, Texas, a large metropolitan area. Three hundred thirty primary care physicians participated in the survey. Questions were asked regarding physician demographics, practice characteristics, and knowledge and practices with respect to HIV and the acquired immunodeficiency syndrome (AIDS) in patients older than 50 years. The responses of the following groups were compared: family practitioners vs internists, physicians younger than 40 years vs those aged 40 years and older, those who saw 5 or less vs more than 5 patients with HIV or AIDS per year, and those in private vs nonprivate practice. Most respondents (85.5%) reported having seen 10 or fewer patients with HIV or AIDS in the previous year. Most physicians (69.7%) reported that patients older than 50 years rarely or never asked questions concerning HIV or AIDS. Most physicians rarely or never discussed HIV or AIDS with patients older than 50 years (60.8%) and rarely or never discussed risk factor reduction (67.5%). Physicians were more likely to rarely or never ask patients older than 50 years compared with those younger than 30 years about HIV risk factors (40.0% vs 6.8%, P < .001). Physicians incorrectly rank ordered the most prevalent risk factors in patients older than 50 years. The correct order is (1) male-male sex, (2) intravenous drug use, (3) blood transfusion, and (4) heterosexual sex. Physicians aged 40 years and older were more likely to correctly identify the most prevalent risk factor (P = .03). Family practitioners were more likely to rarely or never ask older patients about risk factors for HIV (54.9% vs 28.9%, P = .007). Primary care physicians have inadequate knowledge concerning HIV and AIDS risk factors in older patients and insufficiently discuss HIV and AIDS with older patients. Physicians should counsel patients of all ages about HIV and AIDS.

Catheter-related bacteremia due to Mycobacterium smegmatis.

Rapidly growing mycobacteria have occasionally been reported to cause catheter-related infections. We report a case of a central venous catheter-related bacteremia, caused by Mycobacterium smegmatis, in a patient with cancer. Cultures of the catheter tip and blood cultures grew M smegmatis and Enterococcus faecalis. The patient responded to catheter removal and a 3-month course of antibiotics (doxycycline and ciprofloxacin). Based on our experience and the reported experience with other rapidly growing mycobacteria, M smegmatis catheter-related bacteremia should be treated with catheter removal and a course of appropriate antibiotics, based on in vitro susceptibility testing.

Nontunneled central venous catheters in patients with AIDS are associated with a low infection rate.

Patients with AIDS frequently require long-term central venous access devices for intravenous (IV) therapy. We reviewed the medical records of all HIV-infected patients at a single large urban hospital who had a central venous catheter (CVC) placed during a 1-year period to assess the overall complication rate, infection rate, and the microbiology of infectious complications. One hundred fifty-six catheters were inserted in 87 patients for 11,041 catheter days. These catheters (142 of 156) were primarily nontunneled, nonimplantable CVCs (NT-CVCs), and analyses were limited to these. Of these catheters, 79% were primarily used to treat disease caused by cytomegalovirus (CMV). The complication rate for the NT-CVCs was 5.1/1000 catheter days with a mean time to any complication of 106 days. The total infection rate of the NT-CVCs was 2.8/1000 catheter days, and the serious infection rate (bacteremia) for the NT-CVCs was 1.4/1000 catheter days. The mean time to a serious infection was 407 days. None of the following parameters was associated with an increased infection rate: HIV risk factor, indication for catheter, medications received via catheter, number of catheter ports, anatomic site of catheter insertion, or the presence of neutropenia. NT-CVCs were associated with low complication and infection rates that were comparable with historical rates seen in AIDS patients with tunneled and totally implantable central venous access devices. NT-CVCs may be a safe, cost-effective alternative to other central venous access devices in patients with HIV/AIDS.

Peripherally inserted central catheters in patients with AIDS are associated with a low infection rate.

We reviewed the medical records of all human immunodeficiency virus (HIV)-infected patients who had a peripherally inserted central catheter (PICC) placed during a 1-year period. Ninety-seven PICCs were inserted in 66 patients for 8337 catheter-days. Eighty of 97 catheters were used primarily to treat cytomegalovirus disease. The mean time to any complication was 150 days. The total complication rate was 6.1 per 1000 catheter-days. The total infection rate was 1. 3 per 1000 catheter-days, and the serious infection rate was 0.8 per 1000 catheter-days. The mean time to a serious infection was 310 days. The noninfectious complication rate was 4.6 per 1000 catheter-days. PICCs were associated with a low infection rate and a moderate mechanical complication rate, which compare favorably with historical rates seen in AIDS patients with other types of central venous access devices. PICCs are a reasonable alternative to other central venous access devices in patients with HIV or AIDS.

Anaerobic pericarditis: case report and review.

Purulent pericarditis is uncommon and is rarely caused by anaerobic bacteria. We describe a 58-year-old man with purulent pericarditis secondary to infection with Bacteroides fragilis; the most likely source for the B. fragilis infection was subsequently found to be a ruptured appendix. His pericarditis eventually resolved after drainage of purulent fluid and treatment with antibiotics directed against B. fragilis. We also review 29 cases of anaerobic pericarditis previously reported in the English-language literature (we excluded those cases due to actinomyces). In 17 cases only anaerobic bacteria were isolated, while in 13 anaerobes were isolated with a mixture of facultative and/or aerobic bacteria. The cases were secondary to a contiguous focus of infection or occurred via hematogenous seeding. Treatment of both anaerobic pericarditis and purulent pericarditis due to aerobic bacteria entails adequate drainage and appropriate antibiotic therapy, and in all cases there should be a search for the source of the organism infecting the pericardium.

Disseminated sporotrichosis with extensive cutaneous involvement in a patient with AIDS.

Sporotrichosis most commonly presents as a localized, lymphocutaneous infection that follows trauma, such as an injury from a rose thorn. In patients infected with HIV, it may be widespread and disseminated. We describe a patient with AIDS who developed disseminated sporotrichosis, a rare opportunistic fungal infection that may affect these patients. The condition remained undiagnosed because of failure to recognize characteristic histopathologic findings and failure of clinicians to interface closely with the microbiology laboratory. The condition was difficult to treat, requiring systemic administration of amphotericin. While localized sporotrichosis is an innocuous disorder that responds well to therapy, in immunocompromised hosts, it is potentially life-threatening and may require prolonged therapy with potentially toxic medications such as amphotericin B. It is important that clinicians be aware of the presentation of this unusual opportunistic infection and that they maintain close communication with pathology and clinical microbiology laboratories to ensure that proper stains and cultures are performed to avoid potential misdiagnosis.

Sulfonamide-induced reactions in desensitized patients with AIDS--the role of covalent protein haptenation by sulfamethoxazole.

BACKGROUND: Adverse reactions to sulfonamides cause significant morbidity in patients with AIDS. We have demonstrated previously a approximately 40 kd sulfamethoxazole (SMX)-substituted protein in the serum of some individuals treated with SMX. OBJECTIVE: The purpose of this study was to examine patients with AIDS who had undergone SMX desensitization because of a prior history of SMX allergy for the presence of SMX-haptenated serum proteins and to determine whether these proteins, SMX-specific IgG antibodies, or both predict the development of subsequent clinical reactivity. METHODS: Four patients with no history of allergy and in whom SMX prophylaxis was initiated and eight patients with AIDS who had undergone SMX desensitization because of prior allergy were evaluated. SMX-conjugated serum proteins were identified with an immunoblotting assay, and SMX-specific IgG antibodies were identified by ELISA inhibition. RESULTS: One of the four patients receiving SMX prophylactic treatment demonstrated SMX-protein haptenation, none had detectable SMX-specific IgG antibodies, and none developed an SMX-associated reaction during the time in which they were followed. Of the eight patients who underwent SMX desensitization, six (75%) demonstrated SMX-protein haptenation, and three of these six (50%) subsequently developed SMX-induced cutaneous reactions. Only one of these six patients had detectable SMX-specific IgG antibodies. The two individuals who did not demonstrate SMX-protein haptenation have not developed a clinical reaction. CONCLUSION: These preliminary data suggest that SMX haptenation, but not SMX-specific antibodies, may be important in the development of clinical sensitivity in patients with AIDS who have undergone SMX desensitization.