Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association最新文献

Objective: To determine whether race is associated with health insurance coverage and health service use among gay and bisexual men in the Baltimore center of the Multicenter AIDS Cohort Study.

Methods: Data from eight semiannual study visits between 1991 and 1996 were used. Descriptive, stratified, and logistic regression analyses were conducted to determine whether race is associated with insurance coverage, medical, or dental service use, after controlling for socioeconomic variables.

Results: No difference was found between blacks' and whites' likelihood of having health insurance, private insurance, using inpatient, emergency department services, or antiretroviral medications. Whites were more likely to use outpatient services, particularly if CD4 cell counts were high, and were more likely to use dental services, although blacks were more likely to have dental insurance.

Conclusions: Further research must be conducted to examine cultural, social, and psychological factors that help explain why white gay men use more outpatient and dental services, when other service use is unrelated to race. Investigators should be precise when using race as a variable in health services and epidemiologic research, emphasizing when racial differences truly exist versus when the variable race is a surrogate for another factor.

Objective: To examine HIV risk behavior and HIV infection among new initiates into illicit drug injection in New York City.

Design and methods: Cross-sectional surveys of injecting drug users (IDUs) recruited from a large detoxification treatment program (n=2489) and a street store-front research site (n=2630) in New York City from 1990 through 1996. Interviews covering demographics, drug use history, and HIV risk behavior were administered; serum samples were collected for HIV testing. Subjects were categorized into two groups of newer injectors: very recent initiates (just began injecting through 3 years) and recent initiates (injecting 4-6 years); and long-term injectors (injecting > or = 7 years).

Results: 954 of 5119 (19%) of the study subjects were newer injectors, essentially all of whom had begun injecting after knowledge about AIDS was widespread among IDUs in the city. New injectors were more likely to be female and white than long-term injectors, and new injectors were more likely to have begun injecting at an older age (median age at first injection for very recent initiates, 27 years; median age at first injection for recent initiates, 25 years; compared with median age at first injection for long-term injectors, 17 years). The newer injectors generally matched the long-term injectors in frequencies of HIV risk behavior; no significant differences were found among these groups on four measures of injection risk behavior. HIV infection was substantial among the newer injectors: HIV prevalence was 11% among the very recent initiates and 18% among the recent initiates. Among the new injectors, African Americans, Hispanics, females, and men who engaged in male-male sex were more likely to be infected.

Conclusions: The new injectors appear to have adopted the reduced risk injection practices of long-term injectors in the city. HIV infection among new injectors, however, must still be considered a considerable public health problem in New York City.

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.

We performed a study to determine the duration of survival of HIV-1 in syringes typically used by injectors of illicit drugs (IDUs). We describe the effectiveness of a microculture assay in detecting viable virus in volumes of blood typical of those commonly found inside used syringes. Using this assay and modeling the worse-case situation for syringe sharing, we have recovered viable, proliferating HIV-1 from syringes that have been maintained at room temperature for periods in excess of 4 weeks. The percentage of syringes with viable virus varied with the volume of residual blood and the titer of HIV-1 in the blood. These experiments provide a scientific basis for needle exchange schemes, harm reduction, and other interventions among IDUs that support the nonsharing and removal of used syringes from circulation.

Objective: To assess the penetration of the HIV-1 protease inhibitor, nelfinavir, into cerebrospinal fluid (CSF).

Design: Nelfinavir, a commonly used HIV-1 protease inhibitor (PI), is highly effective for reducing plasma viral load. It is deployed clinically in combination with other antiretroviral agents, including nucleoside and nonnucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs). Despite its potency based on plasma HIV-1 RNA results, its effectiveness in reducing HIV-1 RNA levels (i.e., viral load) in the central nervous system (CNS) is less certain. We sampled the CSF as a surrogate for brain because this fluid also is separated from the blood by a barrier to free diffusion, the blood-CSF barrier (BCB), which shares properties with the blood-brain barrier (BBB). These studies of nelfinavir CSF pharmacokinetics exploited the multiple CSF samples derived from individual study subjects who were enrolled in studies the primary objective of which was to compare viral kinetics in CSF and blood in response to antiviral therapy.

Methods: Six study subjects, four with and two without AIDS dementia complex, underwent multiple lumbar punctures (LP). Intervals of CSF sampling after drug dosing were varied (from 0.48 hours to 10.3 hours after nelfinavir administration) to quantitate nelfinavir concentrations throughout the steady-state dosing interval. In four study subjects, CSF sampling was accompanied by assessment of nelfinavir levels in plasma before and after LP, whereas in the other two subjects, a single plasma sample was obtained before or after the LP. In total, 25 CSF samples were analyzed. Nelfinavir concentrations in CSF and plasma were determined using an high-performance liquid chromatography (HPLC) method with a limit of quantitation of 25 and 50 ng/ml, respectively.

Results: Plasma concentrations before and after LP averaged 2420+/-1365 ng/ml and 2528+/-1132 ng/ml, respectively. Nelfinavir was not detected in any of the CSF samples and levels >25 ng/ml were not present in the CSF. Thus, standard therapy with nelfinavir does not result in CSF drug concentrations at or exceeding the IC95 level for most HIV-1 isolates. However, study subjects with high CSF viral loads experienced a marked reduction in the context of the combination-drug regimen including nelfinavir with two subjects showing a comparable CSF response with that in plasma.

Conclusions: Nelfinavir does not appreciably penetrate into the CSF. The clinical importance of this observation is not certain, in that in four study subjects who initiated nelfinavir in combination with other antiretroviral therapy, a comparable degree of viral suppression was obtained in both the CSF and the blood when sampled 4 weeks or later after initiating therapy.

Objective: To evaluate the association of ganciclovir (GCV) and foscarnet (PFA) therapy with the outcome of previously diagnosed Kaposi's sarcoma (KS) after initiating antiviral therapy for cytomegalovirus (CMV) end-organ disease.

Design: Retrospective study.

Methods: KS progression was defined as a clinically obvious increase in size of baseline cutaneous or mucosal lesions, a new diagnosis of visceral KS, or initiation of a new systemic antineoplastic regimen or radiation therapy to treat KS. Multivariate analyses of risk of KS progression were calculated for prior duration of KS before initiating CMV treatment, treatment with PFA or GCV, number of weeks treated with PFA or GCV, absolute CD4 lymphocyte count at time of CMV-related disease diagnosis, diagnosis of KS prior to 1991, visceral KS, prior systemic chemotherapy, and prior radiation therapy.

Results: Among 66 patients who received > or = 14 days PFA (N=20) or only GCV (N=46), median time to progression of KS was 211 days (95% confidence interval [CI], 46-578) for patients who received PFA versus 22 days (95% CI, 15-41) for those who received only GCV (p < .001). In the stepwise multivariate analysis, only prior visceral KS (rate ratio [RR]=2.80; 95% CI, 1.07-7.35) and foscarnet therapy (RR = 0.24; 95% CI, 0.11-0.53) were significantly associated with risk of KS progression.

Conclusion: PFA may be an effective therapy for AIDS-related KS; prospective trials are indicated.

Hydroxylamine derivatives of sulfamethoxazole may be the reactive metabolites that cause adverse reactions to trimethoprim-sulfamethoxazole (TMP-SMX). The increased frequency of reactions observed in HIV-positive individuals is hypothesized to be due to systemic glutathione deficiency and a decreased ability to scavenge these metabolites. Two hundred and thirty-eight patients were randomized to receive or not receive N-acetylcysteine (3 g of the 20% liquid solution) 1 hour before each dose of TMP-SMX (trimethoprim 80 mg, sulfamethoxazole 400 mg) twice daily, which was initiated as primary Pneumocystis carinii pneumonia prophylaxis. Forty-five patients had to discontinue TMP-SMX within 2 months because of fever, rash, or pruritus including 25 of 102 patients (25%) who were receiving TMP-SMX alone and 20 of 96 patients (21%) who were randomized to TMP-SMX and N-acetylcysteine. The difference between treatment groups is 4% (95% confidence interval [CI]: -16%, +9%). No independent association was found with the hypersensitivity reaction and age, gender, race, HIV risk factor, prior AIDS, concurrent use of fluconazole, or baseline CD4. N-acetylcysteine at a dose of 3 g twice daily could not be shown to prevent TMP-SMX hypersensitivity reactions in patients with HIV infection.

The association of maternal and perinatal factors with mother-infant transmission of HIV-1 was examined in a prospective multicenter cohort of singleton live births to 508 HIV-1-infected women with children of known HIV-1 infection status (91 [18%] HIV-1-infected, 417 [82%] uninfected). From multivariate logistic regression, independent predictors of HIV-1 transmission included maternal CD4 percentage (CD4%) (odds ratio [OR] per 10% increase in CD4% = 0.70; p = .003), ruptured membranes <24 hours (OR = 3.15; p = .02), and maternal bleeding (OR = 2.90; p = .03), whereas maternal zidovudine (ZDV) use was marginally associated (OR = 0.60; p = .08). The associations of maternal urinary cytomegalovirus (CMV) shedding, oropharyngeal Epstein-Barr virus (EBV) shedding, and serology profiles during pregnancy with HIV-1 transmission were examined in the subset of mothers in whom the CMV and EBV measurements were available. Maternal EBV seropositivity, CMV shedding, and CMV seropositivity were 100% (279 of 279), 7% (16 of 229), and 92% (270 of 274), respectively. These rates did not differ between transmitting and nontransmitting mothers. In univariate analyses, maternal EBV shedding was higher among transmitting than nontransmitting mothers (40 of 49 [82%] compared with 154 of 226 [68%]; p = .06) and was independently associated with transmission in multivariate logistic analyses adjusting for CD4%, ruptured membranes, and ZDV use, with an OR of 2.45 (95% confidence interval (CI), 1.03-5.84; p = .04). This permits the conclusion that EBV shedding is associated with maternal-infant HIV-1 transmission, independent of CD4%.