Changing conditions and treatments in a dynamic cohort of ambulatory HIV patients: the HIV outpatient study (HOPS).

PURPOSE: Most HIV-infected persons are now treated as ambulatory patients. Obtaining continually updated data about these patients' changing conditions, therapies, and reimbursement is essential to health care provision and planning. The systematic tracking of patient medical and laboratory information in an ongoing commercial data collection program (The Health Research Network) allows clinicians to better understand health outcomes, practice patterns, and epidemiologic trends for their patients. METHODS: To evaluate trends in conditions and therapies of ambulatory HIV-infected patients, we analyzed such data electronically and prospectively collected in the HIV Outpatient Study (HOPS) from 1992 through 1996 from 1876 patients seen in 11,755 clinic visits to ten HIV clinical practices. RESULTS: Patients were as likely to be diagnosed with Mycobacterium avium complex ([MAC] 5.4 cases per 100 person-years) or wasting syndrome (7.8 cases per 100 person-years), as Pneumocystis carinii pneumonia ([PCP]; 7.6 cases per 100 person-years) or Kaposi sarcoma ([KS]; 6.9 cases per 100 person-years). A nested analysis showed that HIV-infected cigarette smokers were at substantially greater risk of pneumonia (relative hazard [RH] = 2.3), bronchitis (RH = 1.7) and hairy leukoplakia (RH = 1.9) than nonsmokers. By 1996, 35 (56%) of 62 patients with PCP, 9 (30%) of 30 patients with other pneumonias, 28 (90%) of 31 patients with KS, 35 (73%) of 48 patients with MAC, and 24 (63%) of 38 patients with cytomegalovirus retinitis were treated without hospitalization. CONCLUSIONS: The HOPS provides continually updated information on the changing characteristics, conditions, and therapy of ambulatory HIV-infected patients.

Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators.

BACKGROUND AND METHODS: National surveillance data show recent, marked reductions in morbidity and mortality associated with the acquired immunodeficiency syndrome (AIDS). To evaluate these declines, we analyzed data on 1255 patients, each of whom had at least one CD4+ count below 100 cells per cubic millimeter, who were seen at nine clinics specializing in the treatment of human immunodeficiency virus (HIV) infection in eight U.S. cities from January 1994 through June 1997. RESULTS: Mortality among the patients declined from 29.4 per 100 person-years in the first quarter of 1995 to 8.8 per 100 in the second quarter of 1997. There were reductions in mortality regardless of sex, race, age, and risk factors for transmission of HIV. The incidence of any of three major opportunistic infections (Pneumocystis carinii pneumonia, Mycobacterium avium complex disease, and cytomegalovirus retinitis) declined from 21.9 per 100 person-years in 1994 to 3.7 per 100 person-years by mid-1997. In a failure-rate model, increases in the intensity of antiretroviral therapy (classified as none, monotherapy, combination therapy without a protease inhibitor, and combination therapy with a protease inhibitor) were associated with stepwise reductions in morbidity and mortality. Combination antiretroviral therapy was associated with the most benefit; the inclusion of protease inhibitors in such regimens conferred additional benefit. Patients with private insurance were more often prescribed protease inhibitors and had lower mortality rates than those insured by Medicare or Medicaid. CONCLUSIONS: The recent declines in morbidity and mortality due to AIDS are attributable to the use of more intensive antiretroviral therapies.

Possible effectiveness of clarithromycin and rifabutin for cryptosporidiosis chemoprophylaxis in HIV disease. HIV Outpatient Study (HOPS) Investigators.

CONTEXT: Cryptosporidium parvum infection, a common cause of diarrhea in persons infected with the human immunodeficiency virus (HIV), is difficult to treat or prevent. OBJECTIVE: To evaluate relative rates of cryptosporidiosis in HIV-infected patients who were either receiving or not receiving chemoprophylaxis or treatment for Mycobacterium avium complex. DESIGN: Analysis of prospectively collected data from HIV-infected patients' visits to their physicians since 1992. SETTING: Ten (8 private, 2 publicly funded) HIV clinics in 9 US cities. PATIENTS: A total of 1019 HIV-infected patients with CD4+ cell counts less than 0.075 x 10(9)/L. MAIN OUTCOME MEASURES: Incidence of clinical cryptosporidiosis during treatment with clarithromycin, rifabutin, and azithromycin. RESULTS: Five of the 312 patients reportedly taking clarithromycin developed cryptosporidiosis vs 30 of the 707 patients not taking clarithromycin (relative hazard [RH], 0.25 [95% confidence interval (CI), 0.10-0.67]; P=.004). Two of the 214 patients taking rifabutin developed cryptosporidiosis vs 33 of the 805 not taking rifabutin (RH, 0.15 [95% CI, 0.04-0.62]; P=.01). Prophylactic efficacy of either drug was 75% or greater. No protective effect was seen in the 54 patients reportedly taking azithromycin (RH, 1.48 [95% CI, 0.44-5.04]; P=.46). CONCLUSIONS: Clarithromycin and rifabutin were highly protective against development of cryptosporidiosis in immune-suppressed HIV-infected persons in this analysis; further study is warranted.

Oral famciclovir for suppression of recurrent genital herpes simplex virus infection in women. A multicenter, double-blind, placebo-controlled trial. Collaborative Famciclovir Genital Herpes Research Group.

OBJECTIVE: To evaluate the efficacy and safety of oral famciclovir in the suppression of genital herpes. METHODS: In this randomized, double-blind, placebo-controlled trial that was performed at 11 university and 9 private ambulatory care referral centers, 375 women who were 18 years of age or older and had a history of 6 or more episodes of genital herpes during 12 of the last 24 months in the absence of suppressive therapy were treated for 4 months with oral famciclovir, 125 mg once daily or twice daily, 250 mg once daily or twice daily, 500 mg once daily, or placebo. The primary outcome measures included the time to first clinically and virologically confirmed recurrences, and safety as measured by clinical laboratory tests and adverse experiences. RESULTS: The median time to first recurrence was 82 days in the placebo group, 114 days in those receiving famciclovir, 125 mg once daily, and more than 120 days in the other treatment groups. When compared with placebo recipients, the time to the first clinical recurrence was significantly prolonged in subjects who received famciclovir, 125 mg twice daily (hazard ratio, 1.8; 95% confidence interval, 1.0-3.0; P = .03), and in those who received famciclovir, 250 mg twice daily (hazard ratio, 3.6; 95% confidence interval, 1.9-6.9; P < .001). Treatment was well tolerated, and there was no evidence of emergence of resistance during or after suppressive famciclovir therapy. CONCLUSIONS: Oral famciclovir, 250 mg, given twice daily for 4 months is an effective, well-tolerated treatment for the suppression of genital herpes in women with frequent recurrences, but single daily doses produced less complete suppression of genital herpes.

Decreased exhaled nitric oxide in subjects with HIV infection.

BACKGROUND: Nitric oxide (NO) may be an important component of the host defence against infections. Endogenously produced NO is present in exhaled air and may be representative of respiratory tract production of NO. Since subjects infected with HIV are prone to develop respiratory infections, it was postulated that exhaled NO might be reduced in such individuals. METHODS: The exhaled concentration of NO (nl/l) and minute ventilation (l/min) were measured and exhaled NO release (nl/min/m2) calculated in 36 subjects infected with HIV (20 non-smokers, 16 smokers) and 31 non-smoking subjects with no active medical conditions. RESULTS: Exhaled NO from HIV positive individuals was less than from control subjects of similar age, height, and weight. Cigarette smoking did not account for the decreased exhaled NO in HIV positive individuals as both smoking and non-smoking HIV positive subjects had decreased exhaled NO compared with control subjects. CONCLUSION: Exhaled NO is decreased in subjects infected with the HIV. Since NO functions in host defence against bacterial, viral, and fungal infections, reduced exhaled NO may indicate a mechanism of impaired host defence in HIV infection.

Zidovudine alone or in combination with didanosine or zalcitabine in HIV-infected patients with the acquired immunodeficiency syndrome or fewer than 200 CD4 cells per cubic millimeter. Investigators for the Terry Beirn Community Programs for Clinical Research on AIDS.

BACKGROUND: We compared two combinations of nucleosides with zidovudine alone in patients with advanced human immunodeficiency virus (HIV) infection. METHODS: A total of 1102 patients with the acquired immunodeficiency syndrome or fewer than 200 CD4 cells per cubic millimeter were randomly assigned to receive zidovudine alone or zidovudine combined with either didanosine or zalcitabine. Disease progression, survival, toxic effects, and the CD4 cell response were assessed. RESULTS: After a median follow-up of 35 months, disease progression or death occurred in 62 percent of the 363 patients assigned to zidovudine plus didanosine, 63 percent of the 367 assigned to zidovudine plus zalcitabine, and 66 percent of the 372 assigned to zidovudine only (P=0.24). As compared with zidovudine therapy, treatment with zidovudine plus didanosine was associated with a relative risk of disease progression or death of 0.86 (95 percent confidence interval, 0.71 to 1.03), and treatment with zidovudine plus zalcitabine was associated with a relative risk of 0.92 (95 percent confidence interval, 0.76 to 1.10). Survival was similar in the three groups. In a subgroup analysis, combination therapy delayed disease progression or death in patients who had previously received zidovudine for 12 months or less. Therapy with zidovudine plus didanosine resulted in more gastrointestinal adverse effects, and treatment with zidovudine plus zalcitabine, more neuropathy. The mean increases in CD4 cell counts at two months were higher with combination therapy than with zidovudine alone. CONCLUSIONS: In patients with advanced HIV infection, combination therapy with zidovudine and either didanosine or zalcitabine is not superior to zidovudine therapy alone. However, these combinations may be more effective than zidovudine monotherapy in patients with little or no previous zidovudine treatment.

Predicting the effect of the Oregon Health Plan on Medicaid coverage for outpatients with HIV.

The Oregon Health Plan, which took effect in February 1994, extends Medicaid eligibility but limits coverage to conditions and treatments above a certain threshold on a prioritized list. Retrospective analysis was conducted on records of visits to two Oregon human immunodeficiency virus (HIV) outpatient clinics in 1991 and 1992 to determine Medicaid coverage if the plan had been operational. Of 1129 patients, 21.1% were Medicaid-eligible; an additional 56.5% would have been eligible under the Oregon plan. Only 5.0% to 6.8% of these patients' visits were for conditions listed below the plan's coverage threshold; almost none of these were for HIV-specific conditions.

The HIV wasting syndrome: a review.

The HIV wasting syndrome and other HIV-associated weight loss is a major problem in HIV-infected patients. The available data strongly suggest that wasting is associated with decreased survival. It may also further impair immune function. A variety of etiologies probably contribute to this wasting, including hypermetabolism, alterations in metabolism, lessened oral intake, malabsorption, cytokine effects, and endocrine dysfunction. The relative contributions of each of these etiologies to wasting probably varies considerably from patient to patient. Successful treatment calls for identification of possible etiologies of wasting in the individual patient with AIDS. Further treatment may include treating underlying conditions and controlling such symptoms as diarrhea, nausea, or fever. Nutritional support, including both parenteral and enteral nutrition, has shown some promise of efficacy, and a variety of drugs appears to be helpful. Future treatment to reverse wasting may include the use of several of these agents in combination. Currently, there is much that clinicians can do to evaluate and treat the HIV wasting syndrome, with significant potential benefits to their patients.

Endocrine function in the HIV wasting syndrome.

We compared endocrine function in patients with the HIV wasting syndrome with other HIV-positive patients without wasting to determine associations between endocrine dysfunction and wasting. Sixty-six HIV-seropositive patients were evaluated by thyroid, gonadal, and adrenal function tests. Fourteen of these patients met the clinical definition of wasting. Total and free testosterone levels were significantly lower in patients with wasting compared with patients without wasting with both similar and higher mean CD4 counts. Prolactin levels were significantly higher, and cortisol levels were higher with borderline significance in patients with wasting compared with patients with similar CD4 counts without wasting. These findings suggest that endocrine function in the HIV wasting syndrome differs from that of HIV-infected patients without wasting, which may have implications about the pathogenesis and treatment of the HIV wasting syndrome.

Micronutrient concentrations in the HIV wasting syndrome.

OBJECTIVE: We measured micronutrient values in patients with the HIV wasting syndrome and in other HIV-seropositive patients to determine whether specific micronutrient deficiencies were associated with the wasting syndrome. METHODS: Serum from 47 HIV-seropositive patients was evaluated for concentrations of vitamin A, B6, B12, C, D, E, folate, the mineral zinc, carotene and glutathione. Comparisons were made between groups stratified by CD4 cell count and wasting/non-wasting status. RESULTS: Mean serum levels were significantly lower for vitamin A (P = 0.04), folate (P = 0.04) and carotene (P = 0.06) in patients with the HIV wasting syndrome than in non-wasting patients with comparable CD4 cell counts. Values of vitamins A, B6, C, D, carotene and glutathione were below the normal range in over 10% of HIV-seropositive patients in this study. CONCLUSION: Decreased micronutrient concentrations are common in HIV-infected patients and occur more frequently in patients with the wasting syndrome. Clinicians may wish to evaluate HIV-seropositive patients with wasting for individual micronutrient deficiencies, although they should note that particular deficiencies may be only part of the larger picture of malabsorption and undernutrition.

Beta-carotene in HIV infection.

beta-Carotene has been reported to have an immunostimulatory effect. Recent studies suggest that beta-carotene supplementation can increase CD4 counts in HIV-infected patients. Our double-blind, placebo-controlled clinical trial was designed to test the efficacy of beta-carotene in raising CD4 counts in HIV-infected patients. Twenty-one HIV-seropositive patients were randomized to receive either beta-carotene, 180 mg/day or placebo for 4 weeks, and then crossed over to receive the alternative treatment for the following 4 weeks. beta-Carotene resulted in a statistically significant increase in total WBC count (p = 0.01), % change in CD4 count (p = 0.02), and % change in CD4/CD8 ratios (p = 0.02) compared to placebo. The absolute CD4 count, absolute CD4/CD8 ratio, and total and B-lymphocytes all increased on carotene and fell during placebo, but these differences did not reach statistical significance. No toxicity was observed on either treatment. beta-Carotene appears to have an immunostimulatory effect in HIV-infected patients. Further studies are needed to demonstrate whether beta-carotene has a role as adjunct therapy in treatment of HIV-infected patients.

Occupational infectious disease exposures in EMS personnel.

Reports of occupationally transmitted hepatitis B virus (HBV) and human immunodeficiency virus (HIV) prompted the Portland Bureau of Fire Rescue and Emergency Services (PFB) to institute a comprehensive program for handling and tracking on-the-job infectious disease exposures. Data were collected for a 2-year period beginning January 1, 1988, and ending December 31, 1989, utilizing verbal and written exposure reports, prehospital care reports, and PFB statistical information. Two hundred and fifty-six (256) exposures were categorized. The overall incidence of reported exposure was 4.4/1,000 emergency medical service (EMS) calls. Of these exposures, 14 (5.5%) were needle sticks, 15 (5.9%) were eye splashes, 8 (3.1%) were mucous membrane exposures, 38 (14.8%) were exposure to nonintact skin, 120 (46.9%) were exposures to intact skin, and 61 (23.8%) involved respiratory exposure only. The incidence of exposure of nonintact skin or mucous membranes to blood or body fluids and needle sticks was 1.3/1,000 EMS calls. Forty-eight individuals (64% of those incurring needle sticks, or exposure of non-intact skin or mucous membranes to blood or body fluids) were treated and followed for signs of infection. Of this group, 11 individuals (26%) previously vaccinated against hepatitis B demonstrated inadequate HBsAb titers at the time of exposure. Requests for HIV and HBV information on source patients were made for needle sticks or exposure of nonintact skin or mucous membranes to blood or high-risk body fluids. Information on the source patient's HIV status was obtained for 57% of these requests.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of cefpimizole with cefotaxime and penicillin G for treatment of uncomplicated gonorrhea.

One hundred sixteen patients (92 men and 24 women) with suspected uncomplicated gonorrhea were randomized in a double-blind manner to receive intramuscular treatment with 1.0 g of cefpimizole, 1.0 g of cefotaxime, or 4.8 x 10(6) units of aqueous procaine penicillin G (APPG) with 1 g of oral probenecid. Seventeen percent were nonassessable (cultures negative, co-existing syphilis, etc.). Infection sites in 96 assessable patients were urethra (78), cervix (17), pharynx (two), and rectum (two). Of 52 patients treated with cefpimizole, 46 (88%) were bacteriologically cured, as compared with 100% (24 of 24) treated with APPG (P = 0.18) and 90% (18 of 20) treated with cefotaxime (P greater than 0.20). On a weight basis the in-vitro activity of cefpimizole against Neisseria gonorrhoeae was similar to that of APPG. Pain at the injection site was reported by 52% of patients treated with cefpimizole as compared with 27% of those given cefotaxime (P = 0.008) and 17% of those given APPG (P = 0.002). No major organ toxicity was found with cefpimizole, cefotaxime, or APPG. Thus, for acute uncomplicated gonorrhea cefpimizole is similar in efficacy to cefotaxime and APPG but has a higher frequency of pain at the injection site.

Nephrotoxicity of the constituents of the gentamicin complex.

Commercial gentamicin C is a mixture of gentamicin C1, C1a, and C2. The nephrotoxicity of each of these constituents was compared with that of the gentamicin complex. After seven days the mean creatinine level in serum was 0.8 mg/dl in rats given C2 and 0.5 mg/dl in rats given C1, C1a, or the gentamicin complex (P less than .001). Toxicity attributable to C1a was not detected until day 14, and only minimal toxicity was noted in C1-treated rats after 21 days. Nephrotoxicity caused by the gentamicin complex was similar to that caused by C2. By a new high-pressure liquid chromatographic method, the renal concentration of C1, C1a, and C2 was quantified in rats given the gentamicin complex. The results indicated an early, preferential renal accumulation of C2. Subsequently, the C2 content of 12 commercial lots of gentamicin C was measured. The C2 concentration ranged from 12.4 to 20.1 mg/ml. In short, experimental nephrotoxicity from gentamicin C is largely the result of the C2 constituent, and the concentration of this constituent in commercial preparations of gentamicin varies by as much as 7.7 mg/dl.

The influence of aminoglycoside antibiotics on the in vitro function of rat liver ribosomes.

There are few studies of the influence of aminoglycoside antibiotics on the ribosomes of higher eukaryotic organisms. To this end, cytoplasmic ribosomes were prepared from rat liver. In vitro, poly(U)-directed ribosome protein synthesis was studied in the presence and absence of selected aminoglycosides. Misreading of poly(U) was also assessed. Consistent with earlier studies using different sources of ribosomes, paromomycin inhibited cell-free protein synthesis and caused poly(U) misreading. In contrast to the findings of other studies in cell-free ribosomes of eukaryotic organisms, netilmicin, tobramycin, and neomycin were most active in inhibiting protein synthesis, and gentamicin C2 and neomycin caused appreciable misreading. Thus the previous suggestion that a paromamine fragment (found in paromomycin) might be a structural requirement for in vitro inhibition of protein synthesis and misreading is not substantiated by the results in rat liver ribosomes. Commercial gentamicin C is a mixture of gentamicins C1, C1a, and C2. Despite nearly identical chemical structures, the three constituents displayed greatly different propensities for inducing poly(U) misreading. C2 was the most active, followed by C1a. In summary, selected aminoglycoside antibiotics caused inhibition and mistranslation of poly(U) messenger in an in vitro ribosome system prepared from rat liver. These effects were not limited to paromamine-containing aminoglycoside antibiotics. Gentamicin C2 caused much more poly(U) misreading than the other two constituents of the gentamicin C complex.

Mixed invasive infection with Alternaria species and Curvularia species.

Alternaria and Curvularia species were isolated from the nasal septum of a neutropenic patient and tissue invasion was documented histologically. The patient recovered without the use of systemic antifungal agents following surgical excision of the nasal septum and spontaneous resolution of neutropenia.

Disappearance of a hyperfunctioning thyroid nodule following TSH stimulation.

Following stimulation with exogenous TSH, a patient with a large hyperfunctioning autonomous thyroid nodule developed transient hyperthyroidism and decreased radioiodine uptake, and subsequently the nodule disappeared.