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.

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.

Community-onset methicillin-resistant Staphylococcus aureus in an urban HIV clinic.

OBJECTIVES: To determine the proportion of skin/soft tissue infections (SSTIs) and to determine risks for MRSA infection caused by methicillin-resistant Staphylococcus aureus (MRSA) in HIV-infected out-patients. METHODS: We conducted a prospective study of SSTIs in HIV-infected out-patients. A questionnaire was used to record MRSA risk factors and treatment. In vitro testing for antibiotic susceptibility, inducible clindamycin resistance, panton-valentine leucocidin (PVL) toxin, and the staphylococcal chromosomal cassette mec (SCCmec) type was performed using standardized methods. Treatment outcomes included resolution of primary site of infection, nonresolution of infection and reinfection and were confirmed at clinic visit and/or telephone follow-up. RESULTS: Forty-one of 44 patients had an SSTI caused by MRSA. African-Americans comprised 21 of 41 MRSA patients. The median CD4 count of MRSA patients was 411 cells/microL. Four patients required hospitalization and three patients had secondary bacteraemia. Twenty-one of 41 MRSA patients had healthcare-associated (HCA) MRSA risk factors including a history of prior MRSA infection (n=9) and hospitalization within 6 months (n=11). Other prevalent MRSA risk factors included receipt of systemic antibiotics within 6 months (n=21) and previous incarceration (n=19). Twenty-two patients had a significant non-HIV-related comorbid illness. The majority of isolates were susceptible to trimethoprim-sulfamethoxazole, tetracycline, and clindamycin. Inducible clindamycin resistance was detected in 0 of 16 erythromycin-resistant, clindamycin-susceptible MRSA isolates. Twenty-one of 24 isolates tested positive for SCCmec type IV. Twenty-four of 24 isolates tested positive for the PVL gene. Antibiotic treatment was discordant (bacteria nonsusceptible to antibiotic used) in eight MRSA patients. The primary SSTI resolved in 37 of 40 MRSA patients. Recurrence of infection at a site other than the primary site was relatively common (11 patients). CONCLUSIONS: We found a high rate of MRSA causing SSTI in community-dwelling patients. The majority of isolates were positive for PVL and SCCmec IV, which is typical of community-associated MRSA isolates causing SSTIs in the general population. Inducible clindamycin resistance was not detected. Most patients had MRSA risk factors. The initial site of infection resolved in most cases but subsequent MRSA infection was relatively common.

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.

Long-term impact of highly active antiretroviral therapy on HIV-related health care costs.

CONTEXT: Highly active antiretroviral therapy (HAART) is associated with decreased opportunistic infections, hospitalization, and HIV-related health care costs over relatively short periods of time. We have previously demonstrated that decreases in total HIV cost are proportional to penetration of protease inhibitor therapy in our clinic. OBJECTIVE: To determine the effects of HAART on HIV health care use and costs over 44 months. SETTING: A comprehensive HIV service within a Veterans Affairs Medical Center. DESIGN: A cost-effectiveness analysis of HAART. MAIN OUTCOME MEASUREMENTS: The mean monthly number of hospital days, infectious diseases clinic visits, emergency room visits, non-HIV-related outpatient visits, inpatient costs, and antiretroviral treatment costs per patient were determined by dividing these during the period from January 1995 through June 1998 into four intervals. Viral load tests were available from October 1996. Cost-effectiveness of HAART was evaluated by determining the costs of achieving an undetectable viral load over time. RESULTS: Mean monthly hospitalization and associated inpatient costs decreased and remained low 2 years after the introduction of protease inhibitors (37 hospital days per 100 patients). Total cost decreased from $1905 per patient per month during the first quarter to $1090 per patient per month in the third quarter but increased to $1391 per patient per month in the fourth quarter. Antiretroviral treatment costs increased throughout the entire observation period from $79 per patient per month to $518 per patient per month. Hospitalization costs decreased from $1275 per patient per month in the first quarter to less than $500 per patient per month in each of the third and fourth quarters. The percentage of patients with a viral load <500 copies/mL increased from 21% in October 1996 to 47% in June of 1997 (p =.014). The cost of achieving an undetectable viral load decreased from $4438 per patient per month to $2669 per patient per month, but this trend did not reach statistical significance (p =.18). CONCLUSIONS: After an initial decrease, there was an increase in the total monthly cost of caring for HIV patients. Cost increases were primarily due to antiretroviral treatment costs, but these costs were offset by a marked decrease in inpatient-related costs. Increases in costs were not related to antiretroviral treatment failures as measured by the proportion of patients with low or undetectable viral loads. The cost of achieving an undetectable viral load remained stable despite increases in the cost of procuring antiretroviral agents.

Osteonecrosis in HIV: a case-control study.

BACKGROUND: Osteonecrosis (avascular necrosis) has been infrequently reported in HIV-infected patients. It is not known whether HIV itself is an independent risk factor for osteonecrosis. METHODS: We identified 25 patients with osteonecrosis from 1984 to 1999 from a large county teaching hospital and two large practices in Dallas County that specialize in HIV-disease related therapy. A retrospective chart review was performed to evaluate potential risk factors for osteonecrosis. Each case was matched with two controls for HIV positive status and date of osteonecrosis diagnosis. RESULTS: In the study, 22 of 25 (88%) case patients had at least one osteonecrosis risk factor compared with 24 of 50 (48%) controls, p =.003. The most common osteonecrosis risk factors were hyperlipidemia (32%), alcoholism (28%), pancreatitis (16%), corticosteroids (12%), and hypercoaguability (12%). Of the cases, 12% were idiopathic. Multiple joints were involved in 72% of cases. Four of the case patients compared with none of the controls received megesterol acetate before the diagnosis of osteonecrosis, p =.01. No significant differences were found between cases and controls with respect to liver function tests, testosterone levels, triglyceride levels, cholesterol levels, or CD4 cell counts. Saquinavir was independently associated with osteonecrosis, p <.05. However, no differences in overall use of protease inhibitors among cases and controls were noted: 79% versus 76%, respectively. CONCLUSIONS: The increased incidence of osteonecrosis in HIV/AIDS may be due to an increased frequency of risk factors previously associated with osteonecrosis such as hyperlipidemia, corticosteroid use, alcohol abuse, and hypercoaguability. Use of protease inhibitors was not independently associated with osteonecrosis.

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.

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.

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.

Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. Study 006 Team.

BACKGROUND: Efavirenz is a nonnucleoside reverse-transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1). We compared two regimens containing efavirenz, one with a protease inhibitor and the other with two nucleoside reverse-transcriptase inhibitors, with a standard three-drug regimen. METHODS: The study subjects were 450 patients who had not previously been treated with lamivudine or any nonnucleoside reverse-transcriptase inhibitor or protease inhibitor. In this open-label study, patients were randomly assigned to one of three regimens: efavirenz (600 mg daily) plus zidovudine (300 mg twice daily) and lamivudine (150 mg twice daily); the protease inhibitor indinavir (800 mg every eight hours) plus zidovudine and lamivudine; or efavirenz plus indinavir (1000 mg every eight hours). RESULTS: Suppression of plasma HIV-1 RNA to undetectable levels was achieved in more patients in the group given efavirenz plus nucleoside reverse-transcriptase inhibitors than in the group given indinavir plus nucleoside reverse-transcriptase inhibitors (70 percent vs. 48 percent, P<0.001). The efficacy of the regimen of efavirenz plus indinavir was similar (53 percent) to that of the regimen of indinavir, zidovudine, and lamivudine. CD4 cell counts increased significantly with all combinations (range of increases, 180 to 201 cells per cubic millimeter). More patients discontinued treatment because of adverse events in the group given indinavir and two nucleoside reverse-transcriptase inhibitors than in the group given efavirenz and two nucleoside reverse-transcriptase inhibitors (43 percent vs. 27 percent, P=0.005). CONCLUSIONS: As antiretroviral therapy in HIV-1-infected adults, the combination of efavirenz, zidovudine, and lamivudine has greater antiviral activity and is better tolerated than the combination of indinavir, zidovudine, and lamivudine.

Protease inhibitor-based therapy is associated with decreased HIV-related health care costs in men treated at a Veterans Administration hospital.

BACKGROUND: Protease inhibitor (PI) therapy for HIV infection is associated with decreased rates of opportunistic infections and death. Statistical models predict that decreased complications will be associated with decreased hospitalization costs. A recent report suggested that the decrease in the HIV hospitalization costs were offset by increases in demand for outpatient services. We performed a study of hospital use and HIV-associated health care costs in our center to determine the following: whether PI therapy is associated with decreased inpatient use; whether PI therapy is associated with decreased outpatient use and costs; whether decreased HIV health care costs are associated with increased use of nucleoside analogues. METHODS: The Dallas Veteran Affairs Medical Center provides comprehensive inpatient and outpatient HIV care and thus can evaluate the relation between inpatient and outpatient costs. The mean monthly number of hospital days, Infectious Diseases clinic visits, emergency department visits, other outpatient clinic visits, inpatient costs, outpatient costs, and PI costs were determined from January 1, 1995 through July 31, 1997. This time period was then divided into three intervals. Comparisons of PI use and HIV-related health care costs were during the three intervals was performed using analysis of variance (ANOVA). Significant differences between the baseline characteristics were further analyzed through multiple linear regression. RESULTS: A decrease in hospital days, and all outpatient visits including emergency visits, and HIV clinic visits was determined. No difference was found in the rate of use of other outpatient services. The per patient costs of HIV care decreased from a monthly average of $1905 U.S. in the first interval to $1122 U.S. in the last interval (p < .01). Linear regression demonstrated an inverse relation between PI use and total HIV costs (B=-0.67, p=.00, adjusted R2=0.52) but no relation between nucleoside use, stage of disease or financial class. CONCLUSIONS: PI therapy is associated with decreased hospital days and use of outpatient services. Total patient costs decreased, but a concomitant rise in outpatient costs took place. This increase was primarily a result of increased costs of acquiring PI. Increases in the number of nucleoside agents prescribed were not associated with decreased costs.

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.

A retrospective study of the addition of ciprofloxacin to clarithromycin and ethambutol in the treatment of disseminated Mycobacterium avium complex infection.

Disseminated Mycobacterium avium complex (DMAC) infection is associated with increased morbidity and mortality in HIV-infected individuals. The combination antibiotic regimens containing clarithromycin can decrease symptoms and improve survival in patients with DMAC, however, optimal therapy remains to be defined. Quinolones have been widely used in the treatment of DMAC but their utility has not been established. A retrospective cohort study of DMAC infection was established in a metropolitan hospital providing comprehensive care to over 3000 HIV-infected individuals. Medical records of patients with DMAC diagnosed at the Parkland Memorial Hospital from 1991 to 1994 were reviewed for therapeutic regimens for DMAC, concomitant therapy for HIV and Pneumocystis carinii prophylaxis and date of death. Subjects were included if they were treated with clarithromycin and ethambutol. Cases were defined as those patients who received more than 30 days of ciprofloxacin as therapy for DMAC in addition to the other drugs that they received. The primary endpoint was the time to death from the data of DMAC diagnosis. Covariates effecting survival were analysed through the Cox proportional hazards model. Eighty-nine subjects with DMAC who were treated with clarithromycin and ethambutol were identified. Fifty-eight received ciprofloxacin in addition to clarithromycin and ethambutol. The time to death was significantly better in those subjects who were treated with ciprofloxacin than those who were not (489 days vs 281 days, P=0.01). The sole significant predictor of improved survival on Cox proportional hazards model was ciprofloxacin therapy. Subjects treated with combination of clarithromycin, ethambutol and ciprofloxacin had improved survival over those treated with clarithromycin and ethambutol alone.

G-CSF association with prolonged survival in HIV-infected patients with disseminated Mycobacterium avium complex infection.

Clarithromycin can ameliorate symptoms and improve survival in disseminated Mycobacterium avium complex (DMAC) infection. Optimal combinations of this drug with other agents remain unknown. Granulocyte colony stimulating factor (G-CSF) is a cytokine that can improve phagocytosis of M. avium complex in vitro. We aim to determine if G-CSF administration is associated with improved survival in patients with DMAC in a retrospective, cohort study. Case records from 1991 to 1995 of 91 patients with DMAC at Parkland Memorial Hospital were reviewed for date of initial DMAC diagnosis, baseline CD4 count, race, sex, antiretroviral use, G-CSF use, therapy for DMAC (clarithromycin, ethambutol, ciprofloxacin and rifabutin) and date of death. Of 91 cases identified, 25 were treated with G-CSF and 66 never received this drug. Baseline characteristics were similar in each group including CD4 count (40 cells/mm3 vs 33 cells/mm3, P=0.68), clarithromycin use (18 patients vs 52 patients, P=0.90), and antiretroviral use (20 patients vs 42 patients, P=0.21). Subjects treated with G-CSF lived longer than those who did not receive this drug (355 days vs 211 days, P<0.01). In the subgroup treated with clarithromycin, G-CSF was also associated with increased survival (377 days vs 252 days, P<0.01). Cox proportional hazards model showed a decreased risk of death in patients treated with G-CSF (RH=0.22, P<0.01), clarithromycin (RH=0.13, P<0.01) and ethambutol (RH=0.51, P=0.02). Ciprofloxacin and rifabutin use did not influence survival. These data support the use of clarithromycin and ethambutol in the treatment of DMAC. Addition of G-CSF to a regimen of clarithromycin and ethambutol may increase survival in DMAC and should be studied prospectively.

Granulocyte colony-stimulating factor use is associated with decreased bacteremia and increased survival in neutropenic HIV-infected patients.

BACKGROUND: Neutropenia occurs in up to 17% of human immunodeficiency virus (HIV)-infected individuals. Although granulocyte colony-stimulating factor (G-CSF) can reverse HIV-related neutropenia, it is not established that this therapy can reduce bacterial infections and affect survival. METHODS: A retrospective cohort study of 152 neutropenic, HIV-infected patients was performed to determine the therapeutic utility of G-CSF. Medical records of 71 patients who received G-CSF and 81 patients who never received G-CSF, during the years of 1991 to 1994 at Parkland Memorial Hospital, were reviewed for the incidence of bacteremia, G-CSF use, antiretroviral therapy (AR), Pneumocystis carinii pneumonia prophylaxis (PCPP), and opportunistic infections (OI). RESULTS: The two patient groups had similar baseline characteristics including CD4 count (37 cells/mm3 versus 40 cells/ mm3, P=0.7). Univariate analysis revealed and trend toward decreased rates of all bacteremias in the G-CSF-treated group compared with the controls (0.54 bacteremias/100 patient months versus 2.2 bacteremias/100 patient months, P=0.064) and a marked decrease in the rates of gram-negative rod bacteremias in the G-CSF-treated group compared with the untreated group (0.09 gram-negative rod bacteremias/100 patient months versus 1.7 gram-negative rod bacteremias/100 patient months, P=0.002). In a multivariate analysis, significant decreased risk for bacteremia was found with G-CSF use (odds ratio [OR]=0.15, P=0.02). Survival was longer in patients treated with G-CSF than in the untreated group (median: 397 days versus 165 days). Multivariate analysis using Cox Proportional Hazards Model showed decreased risk of death in patients treated with G-CSF, ARs, PCPP. CONCLUSIONS: We conclude that G-CSF use is associated with decreased bacteremias and is associated with prolonged survival in neutropenic, HIV-infected patients.

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.

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.