Dysregulated production of interleukin-8 in individuals infected with human immunodeficiency virus type 1 and Mycobacterium tuberculosis.
Interleukin-8 (IL-8) production in vivo was monitored in four study groups: normal blood donors, patients with pulmonary tuberculosis (TB), patients with human immunodeficiency virus type 1 (HIV-1) infection, and dually infected (HIV/TB) patients. We show that whereas there was evidence of detectable levels of cell-associated IL-8 (mRNA and protein) in peripheral cells of healthy individuals, this was largely lost in the disease states studied. Coupled with this finding was significantly increased circulating levels of IL-8 in HIV-1-infected individuals with or without concomitant pulmonary TB (P < 0.001). On the other hand, the capacity of peripheral mononuclear cells to produce IL-8 spontaneously ex vivo was enhanced in HIV-1 and TB patients (P < 0.05) and many of the HIV/TB group, but their corresponding capacities to respond to various stimuli, in particular phytohemagglutinin, were significantly diminished compared to those of normal donors (P < 0.05). Circulating levels of IL-8 in a group of HIV/TB patients were significantly positively correlated with the percentage of polymorphonuclear leukocytes (PMN) in the peripheral circulation (r = 0.65; P = 0.01), the proportions of IL-8 receptor A (IL-8RA)-expressing (r = 0.86; P < 0.01) and IL-8RB-expressing (r = 0.77; P < 0.01) PMN, and the capacity of PMN to migrate in response to IL-8 as chemoattractant (r = 0.68; P < 0. 01). IL-8RB fluorescence intensity, however, was negatively correlated with plasma IL-8 levels (r = -0.73; P < 0.01). Our results suggest that altered regulation of IL-8 in HIV-1 may have important implications for antimicrobial defenses and for normal immune processes. (+info)
Incidence and duration of hospitalizations among persons with AIDS: an event history approach.
OBJECTIVE: To analyze hospitalization patterns of persons with AIDS (PWAs) in a multi-state/multi-episode continuous time duration framework. DATA SOURCES: PWAs on Medicaid identified through a match between the state's AIDS Registry and Medicaid eligibility files; hospital admission and discharge dates identified through Medicaid claims. STUDY DESIGN: Using a Weibull event history framework, we model the hazard of transition between hospitalized and community spells, incorporating the competing risk of death in each of these states. Simulations are used to translate these parameters into readily interpretable estimates of length of stay, the probability that a hospitalization will end in death, and the probability that a nonhospitalized person will be hospitalized within 90 days. PRINCIPAL FINDINGS: In multivariate analyses, participation in a Medicaid waiver program offering case management and home care was associated with hospital stays 1.3 days shorter than for nonparticipants. African American race and Hispanic ethnicity were associated with hospital stays 1.2 days and 1.0 day longer than for non-Hispanic whites; African Americans also experienced more frequent hospital admissions. Residents of the high-HIV-prevalence area of the state had more frequent admissions and stays two days longer than those residing elsewhere in the state. Older PWAs experienced less frequent hospital admissions but longer stays, with hospitalizations of 55-year-olds lasting 8.25 days longer than those of 25-year-olds. CONCLUSIONS: Much socioeconomic and geographic variability exists both in the incidence and in the duration of hospitalization among persons with AIDS in New Jersey. Event history analysis provides a useful statistical framework for analysis of these variations, deals appropriately with data in which duration of observation varies from individual to individual, and permits the competing risk of death to be incorporated into the model. Transition models of this type have broad applicability in modeling the risk and duration of hospitalization in chronic illnesses. (+info)
Relative rates of AIDS among racial/ethnic groups by exposure categories.
The relative rates of acquired immunodeficiency syndrome (AIDS) were calculated among racial/ethnic populations using Centers for Disease Control and Prevention HIV (human immunodeficiency virus)/Surveillance reports assuming that racial/ethnic distributions reflect that of the US Census Data from 1990. For comparison, a rate of 1 was assigned to whites in each calculation. The overall relative rates were whites--1, African Americans--4.7, Hispanics--3, Asian/Pacific Islanders--0.4, and Native Americans--0.5. Acquired immunodeficiency syndrome surveillance data show higher rates of AIDS for African Americans and Hispanics compared with whites, Asians/Pacific Islanders, and Native Americans. The relative rates for African Americans and Hispanics compared with whites were highest for injecting drug users, heterosexual contact, and pediatric patients. These results led us to explore possible explanations for increased AIDS reporting in African Americans and Hispanics. We then explored available national datasets regarding those variables. The analyses indicate that variables such as access and receptivity to HIV prevention and treatment efforts, race/ethnicity, sexual behaviors, sexually transmitted diseases, socioeconomic status, and substance abuse interact in a complex fashion to influence HIV transmission and progression to AIDS in affected communities. (+info)
Outcome and predictors of failure of highly active antiretroviral therapy: one-year follow-up of a cohort of human immunodeficiency virus type 1-infected persons.
The outcome and predictors of virologic treatment failure of highly active antiretroviral therapy (HAART) were determined for 271 human immunodeficiency virus (HIV)-infected protease inhibitor-naive persons. During a follow-up of 48 weeks after the initiation of HAART, 6.3% of patients experienced at least one new AIDS-defining event, and 3.0% died. Virologic treatment failure occurred in 40% (indinavir, 27%; ritonavir, 30%; saquinavir, 59%; ritonavir plus saquinavir, 32%; chi2, P=.001). Risk factors for treatment failure were baseline plasma HIV-1 RNA (odds ratio [OR], 1.70 per log10 copies increase in plasma HIV-1 RNA), baseline CD4 cell count (OR, 1. 35 per 100 CD4 cells/mm3 decrease), and use of saquinavir versus other protease inhibitors (OR, 3.21). During the first year of treatment, 53% of all patients changed (part of) their original HAART regimen at least once. This was significantly more frequent for regimens containing saquinavir (62%; 27% for virologic failure) or ritonavir (64%; 55% for intolerance) as single protease inhibitor. (+info)
Characterization of viral dynamics in human immunodeficiency virus type 1-infected patients treated with combination antiretroviral therapy: relationships to host factors, cellular restoration, and virologic end points.
Biphasic plasma viral decays were modeled in 48 patients treated with ritonavir, zidovudine, and lamivudine. Estimated first- and second-phase decay rates were d1 as 0.47/day and d2 as 0.04/day. Interpatient differences in both decay rates were significant. The d1 was directly correlated with baseline CD4+, CD4+CD28+, and CD8+CD28+ T lymphocyte counts (P<.05) and inversely correlated with baseline virus load (P=.044) and the magnitude of CD4+ and CD8+ T lymphocyte recovery (P<.01). The d2 was directly correlated with baseline percentage of CD8+ T lymphocytes (P=.023), the CD8+CD38+ cell number (P=.024), and the level of IgG that binds to human immunodeficiency virus (HIV) type 1 gp120 (P=.02). Viral decay rates were not predictive of treatment failure or durability of viral suppression. These exploratory findings are consistent with a model in which immunologic factors contribute to elimination of HIV-infected cells and suggest a dynamic interplay between regulation of HIV expression and lymphocyte activation and recovery. (+info)
Proliferative responses to human immunodeficiency virus type 1 (HIV-1) gp120 peptides in HIV-1-infected individuals immunized with HIV-1 rgp120 or rgp160 compared with nonimmunized and uninfected controls.
The proliferative responses to a series of peptides constituting the human immunodeficiency virus type 1 (HIV-1) gp120 sequence were evaluated in 19 HIV-1-infected rgp160 vaccine recipients, 17 HIV-1-infected rgp120 vaccine recipients, 15 HIV-1-infected placebo recipients, and 18 HIV-1-uninfected controls. Many regions of the gp120 molecule were found to contribute proliferative epitopes, although there were clearly regions of relative dominance and silence. Vaccine recipients tended to have broader, more robust, and more frequent peptide recognition than the placebo recipients. Despite the considerable variability in the pattern of peptide recognition among individuals, there was a striking similarity between the rgp160 and rgp120 vaccinee groups as a whole. Low-risk HIV-1-uninfected individuals may react to a few peptides within the gp120 sequence as well, despite a lack of significant response to the whole gp120 protein. (+info)
No evidence for an effect of the CCR5 delta32/+ and CCR2b 64I/+ mutations on human immunodeficiency virus (HIV)-1 disease progression among HIV-1-infected injecting drug users.
The relationship between CCR5 and CCR2b genotypes and human immunodeficiency virus (HIV)-1 disease progression was studied among the 108 seroconverters of the Amsterdam cohort of injecting drug users (IDUs). In contrast to earlier studies among homosexual men, no effect on disease progression of the CCR5 Delta32/+ and the CCR2b 64I/+ genotypes was found, when progression to AIDS, death, or a CD4 cell count <200/microL was compared by a Cox proportional hazards model. Furthermore, CD4 cell decline (by a regression model for repeated measurements) and virus load in the first 3 years after seroconversion did not differ between the CCR5 and CCR2b wild type and heterozygous genotypes. A nested matched case-control study also revealed no significant effect of the CCR5 and CCR2b mutations. Immunologic differences between IDUs and homosexual men may account for the observed lack of effect. Alternatively, difference in transmission route or characteristics of the HIV-1 variants that circulate in IDUs could also explain this phenomenon. (+info)
A randomized trial of high- versus low-dose subcutaneous interleukin-2 outpatient therapy for early human immunodeficiency virus type 1 infection.
Forty-nine outpatients infected with human immunodeficiency virus with baseline CD4 cell counts >/=500/mm3, who were on stable antiretroviral therapy, were randomized to receive 5-day cycles of either low-dose (1.5 million IU [MIU] twice a day) or high-dose (7.5 MIU twice a day) subcutaneous (sc) interleukin (IL)-2 every 4 or every 8 weeks. High-dose recipients experienced mean slopes of +116.1 cells/month and +2.7 %/month in CD4 cells and percents, respectively, whereas low-dose recipients displayed mean slopes of +26.7 and +1.3% in the same parameters. At month 6, high-dose recipients achieved a 94.8% increase in mean CD4 cells over baseline compared with a 19.0% increase in low-dose recipients. While high-dose recipients encountered more constitutional side effects, these were generally not dose-limiting. High-dose scIL-2 therapy in outpatients with early HIV-1 infection was well tolerated and induced dramatic, sustained rises in CD4 cells. (+info)