CD4+ count-guided interruption of antiretroviral treatment.

BACKGROUND: Despite declines in morbidity and mortality with the use of combination antiretroviral therapy, its effectiveness is limited by adverse events, problems with adherence, and resistance of the human immunodeficiency virus (HIV). METHODS: We randomly assigned persons infected with HIV who had a CD4+ cell count of more than 350 per cubic millimeter to the continuous use of antiretroviral therapy (the viral suppression group) or the episodic use of antiretroviral therapy (the drug conservation group). Episodic use involved the deferral of therapy until the CD4+ count decreased to less than 250 per cubic millimeter and then the use of therapy until the CD4+ count increased to more than 350 per cubic millimeter. The primary end point was the development of an opportunistic disease or death from any cause. An important secondary end point was major cardiovascular, renal, or hepatic disease. RESULTS: A total of 5472 participants (2720 assigned to drug conservation and 2752 to viral suppression) were followed for an average of 16 months before the protocol was modified for the drug conservation group. At baseline, the median and nadir CD4+ counts were 597 per cubic millimeter and 250 per cubic millimeter, respectively, and 71.7% of participants had plasma HIV RNA levels of 400 copies or less per milliliter. Opportunistic disease or death from any cause occurred in 120 participants (3.3 events per 100 person-years) in the drug conservation group and 47 participants (1.3 per 100 person-years) in the viral suppression group (hazard ratio for the drug conservation group vs. the viral suppression group, 2.6; 95% confidence interval [CI], 1.9 to 3.7; P<0.001). Hazard ratios for death from any cause and for major cardiovascular, renal, and hepatic disease were 1.8 (95% CI, 1.2 to 2.9; P=0.007) and 1.7 (95% CI, 1.1 to 2.5; P=0.009), respectively. Adjustment for the latest CD4+ count and HIV RNA level (as time-updated covariates) reduced the hazard ratio for the primary end point from 2.6 to 1.5 (95% CI, 1.0 to 2.1). CONCLUSIONS: Episodic antiretroviral therapy guided by the CD4+ count, as used in our study, significantly increased the risk of opportunistic disease or death from any cause, as compared with continuous antiretroviral therapy, largely as a consequence of lowering the CD4+ cell count and increasing the viral load. Episodic antiretroviral therapy does not reduce the risk of adverse events that have been associated with antiretroviral therapy. (ClinicalTrials.gov number, NCT00027352 [ClinicalTrials.gov].).

Relative efficacy and toxicity of netilmicin and tobramycin in oncology patients.

We prospectively compared the efficacy and safety of netilmicin sulfate or tobramycin sulfate in conjunction with piperacillin sodium in 118 immunocompromised patients with presumed severe infections. The two treatment regimens were equally efficacious. Nephrotoxicity occurred in a similar proportion in patients treated with netilmicin and tobramycin (17% vs 11%). Ototoxicity occurred in four (9.5%) of 42 netilmicin and piperacillin and in 12 (22%) of 54 tobramycin and piperacillin-treated patients. Of those evaluated with posttherapy audiograms, three of four netilmicin and piperacillin-treated patients had auditory thresholds return to baseline compared with one of nine tobramycin and piperacillin-treated patients. The number of greater than or equal to 15-dB increases in auditory threshold as a proportion of total greater than or equal to 15-dB changes (increases and decreases) was significantly lower in netilmicin and piperacillin- vs tobramycin and piperacillin-treated patients (18 of 78 vs 67 of 115). We conclude that aminoglycoside-associated ototoxicity was less severe and more often reversible with netilmicin than with tobramycin.

Overall and cause-specific mortality in a cohort of homo-/bisexual men, injecting drug users, and female partners of HIV-infected men. Pulmonary Complications of Human Immunodeficiency Virus Infection Study Group.

OBJECTIVE: To study the overall and cause-specific HIV-related mortality in a cohort of HIV-seropositive subjects according to transmission category, race/ethnicity, sex and severity of immunosuppression. DESIGN: A cohort of 1129 HIV-seropositive homo-/bisexual men, injecting drug users, and female partners of HIV-infected men were enrolled at six centers in San Francisco, Los Angeles, Chicago, Newark, Detroit and New York between 1 November 1988 and 1 November 1989. Subjects were evaluated every 6 months at least until 31 March 1994. METHODS: The analyses of overall mortality for the subgroups of interest were performed with Kaplan-Meier plots and Cox proportional hazards models. Cause-specific analyses were performed on the primary cause of death using rates per 100 person-years of exposure. RESULTS AND CONCLUSIONS: Baseline severity of immunosuppression is the strongest predictor of mortality. There were no statistically significant differences in overall HIV-related mortality among transmission categories, race/ethnicity groups or sexes. There were differences, however, in cause-specific mortality among the different risk groups.

Quantitation of unintegrated HIV-1 DNA in asymptomatic patients in the presence or absence of antiretroviral therapy.

The objective of this work was to determine the amount of unintegrated human immunodeficiency virus (HIV) DNA (HIV uDNA) in asymptomatic individuals in the presence or absence of antiretroviral therapy. Twenty-one healthy seropositive individuals with no history of any opportunistic infection or previous use of nucleoside antiretrovirals, and 9 similarly asymptomatic individuals who had initiated nucleoside antiretroviral therapy within the last 24 months were studied. All patients had CD4 lymphocyte counts above 400/microliters. All subjects administered antiretrovirals received 400-600 mg of zidovudine daily for 2-24 months. Two individuals additionally received 400 mg of dideoxyinosine (ddI) daily for 4 and 5 months. Patient peripheral blood mononuclear cells (PBMCs) were examined for integrated and unintegrated HIV DNA by a quantitative PCR assay. In addition, CD4 counts were measured, and free and immune complex dissociated p24 antigen was detected in plasma by ELISA. The mean percentage of HIV uDNA in asymptomatic individuals not on therapy was 59%, with 95% confidence limits from 50 to 69%. In contrast, patients on therapy had a mean of only 13% HIV uDNA, with confidence limits from 2 to 25% (p < 0.001). These findings indicate that a significant amount of HIV DNA in infected, healthy patients not on therapy is in the unintegrated form, and that the amount of HIV uDNA in asymptomatic patients on nucleoside therapy is much less. The amount of HIV uDNA in PBMCs deserves further study as a new marker of the efficacy of antiretroviral therapy.

Infection surveillance in cardiac transplantation.

Infections are a major cause of morbidity and mortality in cardiac transplantation. There is little information describing screening and prospective surveillance of heart recipients. We describe a surveillance program that was used for 35 patients, which screens and follows recipients through serologic, virologic, and immunologic parameters. Pretransplantation surveillance identified four (11.4%) patients whose skin tests with purified protein derivative (PPD) were positive, one patient with giardiasis, and seven (20%) recipients who were susceptible to cytomegalovirus (CMV). Twelve (34.3%) patients had CMV infections, only one of which was primary and involved a seropositive donor. The low rate of primary infection (14%) may result from our use of CMV-negative blood products. Seven (20%) recipients who were seronegative for toxoplasmosis received seropositive hearts, and disseminated toxoplasmosis developed in one of them. Eight (22.8%) patients had asymptomatic significant increases in Epstein-Barr virus antibody titers, without evidence of lymphoma. Fifteen (42.8%) recipients had at least one herpes simplex virus reactivation. Preventive, diagnostic, and early therapeutic interventions should occur as a result of infection surveillance, thus leading to a reduced risk of infection during the period after cardiac transplantation.

Medical management of osteomyelitis: considerations for home antibiotic chemotherapy.

Osteomyelitis can result from hematogenous seeding or contiguous infection, especially in association with impaired vascularity. Appropriate antibiotic therapy requires identification of the pathogen or pathogens and confirmation that the pathogens are susceptible to the antibiotic selected. Because of the long duration of parenteral antibiotic therapy required, treatment of osteomyelitis is expensive when patients are kept in the hospital for this reason alone. The development of long-half-life antibiotics that can be administered intramuscularly once a day and that are well tolerated has made outpatient parenteral therapy possible for many such patients. Cefonicid is a long-acting second-generation cephalosporin with activity against many of the microorganisms involved in osteomyelitis. Clinical studies have shown that cefonicid is effective and safe when used in an outpatient treatment program. Such programs have realized considerable savings over the cost of inpatient therapy.

Optimistic explanatory style and dispositional optimism in HIV-infected men.

OBJECTIVE: This study examined associations of two types of optimism (Peterson and Seligman's optimistic explanatory style and Scheier and Carver's dispositional optimism) with each other as well as with symptoms and immune status among human immunodeficiency virus (HIV)-infected men. METHOD: We related both types of optimism to HIV symptoms and to CD4 counts in a cross-sectional study of 78 men, and to change in CD4 counts in a 2-year prospective study of a subsample of these men. RESULTS: Analyses controlled for age, education, employment status, duration since diagnosis, and azidothymidine (AZT) use. The two types of optimism were only minimally related to each other (r=.25). Cross-sectionally, higher levels of both types of optimism were associated with having fewer HIV symptoms, but a more optimistic explanatory style was related to having poorer immune status (lower CD4). Prospectively, an optimistic explanatory style was a substantial predictor of greater decline in CD4 counts after 2 years, after controlling for baseline CD4. Dispositional optimism was unrelated to CD4 counts. Neither health behaviors nor coping strategies mediated these relationships, and the relationships of optimistic explanatory style (and to a lesser extent, dispositional optimism) were independent of negative affectivity. CONCLUSIONS: These optimism measures tap different types of optimism, and although both are related to better subjective health in HIV-infected men, an optimistic explanatory style predicts greater decline in immune status over time. This latter relationship may be related to the unique stress and life experiences associated with having HIV.

Accurate radiographic evaluation of mandibular fractures.

Proper radiographic evaluation is essential to confirm the presence and location of a mandibular fracture. The panoramic view of the mandible is considered to be a very accurate technique and has been heavily relied on by many clinicians as the initial or sole means of diagnosing mandibular fractures. Three cases of mandibular fractures are presented in which a panoramic view failed to demonstrate fractures of the mandible that were obvious on plain film radiographs. Diagnosis and treatment planning should not be based on the information obtained from a single roentgenogram such as a panoramic view. The combination of the mandibular series with the panoramic view provides increased diagnostic information that should enable accurate diagnosis of fractures in all areas of the mandible.

Prosthodontic restoration with dental implants and an intraoral cranial bone onlay graft: a case report.

In 1988, a 54-year-old edentulous patient received a cranial bone onlay graft with the immediate placement of five dental implants. Treatment procedures and early results of restoration are described.

Immediate permanent reconstruction of a mandibular continuity defect with use of a prosthesis of chromium-cobalt alloy.

A report of ten-year follow-up examinations of a patient who had a hemimandibulectomy with disarticulation because of fibrous dysplasia and immediate permanent reconstruction of the mandible with a Vitallium custom-cast prosthesis is presented. Careful preoperative planning, operative technique, and postoperative follow-up examinations are essential for successful maintenance of the prosthesis. Autogenic bone grafts are, in general, superior to alloplasts in permanent reconstruction of defects in mandibular continuity after resection. However, there are indications for alloplastic reconstruction when the condyle is disarticulated with the resection.

Evaluation and treatment of mandibular and midface fractures.

The classification of mandibular and midface fractures is discussed. Signs and symptoms of fractures are presented and the radiographic examinations described. The latest treatment modalities, including the use of skeletal fixation with titanium plates, are also discussed.

Effect of IL-2 on hepatitis C virus RNA levels in patients co-infected with human immunodeficiency virus receiving HAART.

The effect of interleukin-2 (IL-2) on the plasma levels of hepatitis C RNA (HCV-RNA) has varied in published reports. We measured the impact of IL-2 on plasma HCV RNA levels in 54 human immunodeficiency virus (HIV)/HCV coinfected patients enrolled in a randomized trial of 512 participants designed to compare the virologic and immunologic effects of cycled IL-2 plus antiretroviral therapy (ART) vs ART alone in the treatment of HIV in patients with CD4 cell counts > or =300 cells/mm(3). The mean decreases in average HCV RNA levels (copies/mL, log (10)) were 0.28 log in the IL-2 group (n = 26) and 0.04 log in the ART alone group (n = 28) at 12 months (P = 0.18). The changes in HCV RNA level were not associated with baseline or nadir CD4 cell counts, baseline aspartate aminotransferanse, CD4 cell response to IL-2, or changes in plasma HIV RNA values. Compared with those participants who only had HIV, the HIV/HCV co-infected patients did not have a significantly different CD4 cell response to IL-2 therapy. Intermittent IL-2 therapy does not produce a significant sustained decrease in plasma HCV RNA levels among patients co-infected with HIV/HCV who are on highly active ART.

Patient characteristics and costs associated with dyslipidaemia and related conditions in HIV-infected patients: a retrospective cohort study.

BACKGROUND: Metabolic abnormalities are common in HIV-infected individuals and, although multifactorial in origin, have been strongly associated with antiretroviral therapy. METHODS: Using automated claims and clinical databases, combined with medical record data, we evaluated the burden of dyslipidaemia (DYS) and associated metabolic abnormalities among a cohort of 900 HIV-infected patients aged 18 years and older who received their care from a large multispecialty medical group between 1 January 1996 and 30 June 2002. A Cox proportional hazards model for DYS was developed. Resource use was compiled and subsequently costed with stratification to account for variable length of follow-up. RESULTS: Mean follow-up time was 3.3 years. DYS was present in 54% of the cohort and 3.4% experienced a cardiovascular (CV) event. Both unadjusted and adjusted results found patients with dyslipidaemia and cardiovascular events significantly more likely to have received protease inhibitor (PI) treatment for longer periods of time. In the Cox proportional hazards model the following factors were significantly associated with an increased risk for DYS: older age, white race, PI use and male sex. Diagnoses of hypertension, hepatitis C virus infection, depression or opportunistic infections were all negatively associated with a DYS diagnosis. When controlled for length of follow up, patients with DYS (and no CV-related events) incurred greater median and mean total average costs than patients without DYS or CV-related events. For patients with more than 2 years of follow up, these total cost differences were statistically significant (P<0.05). CONCLUSIONS: These findings indicate that DYS is common among patients with HIV infection and is associated with increased use of medical resources.