摘要:

Antiviral agents are the primary therapy for patients infected with HIV-1. However, supportive therapies are often necessary in addition to antiviral drugs because of the devastating wasting process associated with HIV-1 infection and AIDS. Oxandrolone, an anabolic steroid, is used in promoting weight gain and, most important lean body mass (LBM), in patients with HIV-1 disease. We investigated whether oxandrolone interferes with the antiviral activity of zidovudine (ZDV), dideoxyinosine (ddI), and dideoxycytidine (ddC) on HIV-1 replication in peripheral blood lymphocytes and macrophage-monocytes. The nucleoside analogues had nanomolar 50% inhibitory concentrations (IC50) in peripheral lymphocytes. Combinations of nucleoside analogues and oxandrolone did not result in increased IC50values. Oxandrolone used alone exhibited micromolar IC50values in peripheral blood lymphocytes. Lack of interference was consistent for nucleoside concentrations up to 5 μM and for oxandrolone concentrations up to 100 μM in several combinations of drugs, viral strains, and peripheral lymphocytes and macrophages. We conclude that oxandrolone can be used for the promotion of weight gain in patients with AIDS-related wasting without interference with the antiviral effects of ZDV, ddI, or ddC.

ISSN:1077-9450    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Clinical trial endpoints based on magnitude of reduction in HIV-1 RNA levels provide an important complement to endpoints based on percentage of patients achieving complete virologic suppression. However, interpretation of magnitude of reduction can be biased by measurement limitations of virologic assays, particularly lower and upper limits of quantification. Using data from two AIDS Clinical Trials Group (ACTG) studies, widely used crude methods of analyzing HIV-1 RNA reductions were compared with methods that take into account censoring of HIV-1 RNA measurements. Such methods include Kaplan-Meier and censored regression analyses. It was found that standard crude methods of analysis consistently underestimated treatment effects. In some cases, the bias induced by crude methods masked statistically significant differences between treatment arms. Although statistically significant, adjustment for baseline HIV-1 RNA levels had little effect on estimated treatment differences. Furthermore, convenient parametric analyses performed as well as more complex nonparametric analyses. It is concluded that conveniently implemented censored data analyses should be conducted in preference to widely used crude analyses of magnitude of HIV-1 RNA reduction. To obtain complete information about virologic response to antiretroviral therapy, such analyses of magnitude of virologic response should be used to complement analyses of the percentage of patients having complete virologic suppression.

ISSN:1077-9450    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objective:Recent studies have documented alterations in body fat distribution that have been associated with protease inhibitor therapy. We compared body composition, including measurements of fat distribution, in 96 HIV-infected subjects studied since January 1996 (current HIV), subjects seen prior to January 1996 (previous HIV), and healthy controls.Design:Retrospective cross-sectional studies of subjects matched by gender, race, age, and height.Methods:Body weight, height, body cell mass by whole-body counting of40K plus fat, fat-free mass, and body fat distribution by anthropometry were measured.Results:Current HIV men weighed more (p= .025) and had more body cell mass than previous HIV men, but less than controls (p< .001). In women, the between group differences in fat were greater than the differences in body cell mass. Current and previous HIV study subjects had lower indices of subcutaneous and higher indices of visceral fat than controls. In current HIV subjects, body fat distribution was significantly associated with log plasma HIV RNA content but not with antiretroviral or protease inhibitor usage, nor with CD4+lymphocyte counts. In 7 of 9 current HIV subjects studied, 24-hour urinary free cortisol excretion was abnormally high.Conclusions:Alterations in body fat distribution are a characteristic feature in HIV infection. The occurrence of increased visceral fat content and decreased subcutaneous fat content preceded the era of combination antiretroviral therapy. The alteration in fat distribution may be affected by plasma HIV RNA content rather than antiretroviral or protease-inhibitor therapy. The body composition alterations might be associated with endogenous hypercortisolism.

ISSN:1077-9450    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objective:To study the stability of cutaneous anergy in women with or at risk for HIV infection.Design:Prospective multicenter cohort studyMethods:Interviews, CD4+lymphocyte counts, and intradermal skin testing with mumps,Candida,and tetanus toxoid antigens were performed on two occasions at a median interval of 74 weeks in 436 HIV-seropositive and 252 seronegative at-risk women; only 10 (2%) HIV-seropositive women were taking highly active antiretroviral therapy at the time of delayed-type hypersensitivity (DTH) testing. Anergy was defined as induration <2 mm to all three antigens.Results:Skin test reactivity at repeat testing was seen in 202 of 233 (87%) HIV-seronegative women who were not anergic at baseline, compared with 10 (53%) of 19 seronegative women who were anergic at baseline (relative risk [RR], 1.7; 95% confidence interval [CI], 1.07-2.5). Anergy at retesting was seen in 108 of 169 (64%) HIV-seropositive women who were previously anergic, compared with 77 of 267 (29%) who were not previously anergic (RR, 2.2; 95% CI, 1.8-2.8). Among initially anergic seropositive women, CD4+lymphocyte counts were lower at both initial and follow-up testing in those who remained anergic than in those who reacted at follow-up (p< .001). The relative risks for anergy at retesting of initially anergic seropositive women, compared with initially reactive seropositive women, were related to CD4+level; 2.5 (95% CI, 1.4-4.3) for CD4+counts < 200 cells/mm3, 2.0 (95% CI, 1.5-1.7) for CD4+counts 200-500 cells/mm3, and 1.6 (95% CI, 0.9-2.8) for CD4+counts >500 cells/mm3.Conclusions:Although anergic HIV-seropositive women may become reactive, cutaneous anergy predicts a higher likelihood of anergy at retesting as well as lower CD4+counts. Stability of anergy is greatest in HIV-seropositive women with low CD4+counts.

ISSN:1077-9450    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objectives:To compare, in a community-based therapeutic setting, the safety, tolerance, and efficacy of combination therapy with recombinant interferon-α2b (rIFN-α2b) and zidovudine (ZDV) to ZDV monotherapy.Design:Open-label, two-armed, randomized study.Patients and Methods:Asymptomatic or minimally symptomatic HIV-infected adults without an AIDS-defining illness, a CD4 count of 200 to 500 cells/μl, and ⩽6 months of prior ZDV therapy received ZDV 100 mg orally five times daily. Patients randomized to rIFN-α2b received 3 million IU subcutaneously three times weekly for 2 weeks and 5 million IU three times weekly thereafter. The groups were compared with respect to adverse events (AEs), dosing modifications, treatment discontinuation, clinical endpoints and changes in CD4 count. A virology substudy compared the treatments with respect to HIV viral load and development of ZDV resistance.Results:Between October, 1991 and January, 1993, 139 patients were randomized to combination therapy and 117 to ZDV alone. Of AEs reported at any grade, fatigue, myalgias, and sweating occurred significantly more often with combination therapy (p< .001). Study subjects receiving combination therapy showed modest but significantly greater weight loss (p= .0001), a significantly higher frequency of any abnormal laboratory test result (p= .002), neutropenia (p= .002), and leukopenia (p= .02), and also required dosage reduction for hematologic toxicity significantly more often (p< .05) than those in the ZDV monotherapy arm. No statistically significant differences were found between the groups with respect to development of specific AIDS-defining events, overall event rate, time to events, or change in performance status or CD4+counts, or percentages or development of ZDV resistance. Viral burden, reflected by serum p24 antigen and quantitative peripheral blood mononuclear cell (PBMC) microcultures, was greater at baseline in the combination therapy group. Baseline SI phenotype predicted progression to AIDS (p= .004, χ2), whereas intermediate susceptibility to ZDV predicted development of ZDV resistance (p< .005, χ2). The annual rate of development of phenotypic resistance to ZDV was 16.8% and was not affected by administration of rIFN-α2b.Conclusions:At the doses and schedule used in this study, the combination of ZDV with rIFN-α2b was not therapeutically superior to ZDV alone and was less well tolerated. The addition of rIFN-α2b to ZDV did not prevent or delay the development of ZDV resistance.

ISSN:1077-9450    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Hepatitis C virus (HCV) has been associated with various lymphoproliferative disorders, and a high prevalence (9%-32%) of chronic HCV infection has been demonstrated among patients with lymphoma. Dual coinfection by HIV and HCV has been demonstrated in ∼40% of certain populations of HIV-infected individuals. Because of this high prevalence of coinfection by HIV and HCV, the known relations between HCV and lymphoproliferative disorders, and the association of HIV and B cell lymphoma, the potential association between chronic HCV and the development of AIDS-related lymphoma was examined. The prevalence of HCV infection in HIV-infected patients with lymphoma was compared with that in patients with AIDS, diagnosed on the basis of an illness other than lymphoma. Risk factors for HCV infection, overall, were also evaluated. Evidence of HCV infection was ascertained by assessing anti-HCV antibodies, and HCV RNA in serum. The study consisted of 99 homosexual/bisexual men with AIDS-related lymphoma, and 43 other AIDS patients. HCV infection was detected in 11 of 99 (11.1%) men with lymphoma, and in 5 of 43 (11.6%) other AIDS patients. Further, in patients with AIDS-related lymphoma, no relation was found between HCV infection and lymphoma histology or site. History of use of injected illicit drugs was associated with a significantly elevated risk of HCV infection in the combined group of lymphoma and other AIDS patients. The current study demonstrates no relation between dual infection by HIV and HCV and subsequent increased risk of lymphoma.

ISSN:1077-9450    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

To assess the kinetics of viral replication and decay in cerebrospinal fluid (CSF), we studied the short-term effects of highly active antiretroviral therapy (HAART) on CSF HIV-1 RNA concentrations. In 15 HIV-positive patients, HIV RNA concentrations were measured in paired CSF and plasma/serum samples. Samples were obtained prior to and 5 to 24 days after initiation or change of HAART. The short-term effects of interruption of HAART were tested in 2 patients. Viral load was measured by the Roche Amplicor assay. During HAART, in 12 of 15 patients a significant reduction of CSF HIV RNA concentration was observed, ranging from 0.55 to 2.77 log10(median, 1.37 log10). This was paralleled by a reduction of blood viremia ranging from 0.12 to 3.0 log10(median, 1.65 log10). The median half-life, as calculated from the slopes of the two time-point measurements, for CSF and blood viral load was 2.66 and 2.36 days, respectively. In 2 patients, CSF viral load remained essentially unchanged despite substantial reduction of plasma viral load. In 1 patient, after interruption of HAART, a rapid increase of HIV RNA in the CSF and blood was seen. No correlation was found between the CSF:blood albumin ratio as a measure of the functional integrity of the blood-CSF barrier and the ratio of CSF:blood RNA concentration, which suggests that no major passive influx of HIV RNA moves from the blood into the CSF compartment. However, a correlation existed between the CSF cell count and the CSF viral load (r = 0.74;p< .003). We conclude that, in most HIV-infected individuals, the decay of viral load in the CSF is similarly rapid as that seen in plasma. The rapid kinetics of virus found in the CSF suggest that it may be produced by rapidly proliferating cells, such as lymphocytes.

ISSN:1077-9450    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objective:Tuberculosis (TB) is the commonest HIV-related opportunistic infection in many developing countries and is thought to be a frequent underlying cause of HIV-associated wasting. We have used reference water dilution methods to examine the body composition changes associated with TB and to assess the severity and pattern of wasting.Methods:The study was conducted at a charitable support house for poor and homeless HIV-infected people in Rio de Janeiro, Brazil. Male patients who were HIV-positive and receiving treatment for active TB (HIVTB+) and HIV-infected controls without TB (HIVTB−) were studied. Total body water (TBW) and extracellular water (ECW) were measured by giving oral doses of deuterium oxide and sodium bromide, respectively, and determining enrichment in plasma after 4 hours. Intracellular water (ICW), body cell mass (BCM), lean body mass (LBM) and fat mass were calculated from these parameters using standard equations.Results:HIVTB+ (n= 11) and HIVTB− (n= 12) groups were similar in age, height, CD4 count and HIV risk factors. HIVTB+ men had significantly lower mean ICW (13.2 versus 16.6 kg;p= .02) and BCM (18.4 versus 23.0 kg;p= .02), a relative expansion of ECW (35.0 versus 30.0 L/kg body weight;p= .04), and small and nonsignificant reductions in total body weight (58.0 versus 62.1 kg;p= .26), LBM (45.5 versus 47.7 kg;p= .33) and fat mass (12.5 versus 14.4 kg;p= .51) compared with HIVTB− controls. BCM in the HIVTB+ group was similar to reference values for severe malnutrition. The relative depletion of BCM appeared excessive in comparison with reference values for uncomplicated starvation.Conclusion:The nutritional status of HIVTB+ patients was significantly worse than HIVTB− patients. Body weight and LBM underestimated the nutritional deficit, and measurement of BCM is therefore necessary to appreciate the extent of malnutrition in such patients. Malnutrition in HIVTB+ patients is severe and may therefore contribute to decreased survival. Hypermetabolism appears to play a role in the wasting process in patients coinfected with HIV and TB.

ISSN:1077-9450    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Early in the history of the AIDS epidemic there was clear evidence of differences in the outcomes of HIV infection between injecting drug users and men who have sex with men. There were also some indications that high levels of nonsterile drug injection may increase the progression of HIV infection. Recent epidemiologic studies indicate no differences in rates of progression to AIDS among drug injectors, men who have sex with men, or persons infected through heterosexual contact. In vitro and animal studies suggest that the effects of different psychoactive drugs on HIV infection may be negative, positive, or mixed, and that the effects of a psychoactive drug on immune functioning may differ among acute administration, chronic administration, or cessation of chronic administration. Although the current epidemiologic data do not provide support for the hypothesis that psychoactive drug use will have any important effects on the course of HIV infection, possible interactions between psychoactive drugs and antiviral medications and medication adherence issues among drug users are important areas for AIDS research. Relations between psychoactive drug use, the nervous system, and the immune system are a promising area for basic research.

ISSN:1077-9450    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objective:To compare the rate of HIV disease progression in a sample of polydrug injectors (AIDS Link to Intravenous Experiences [ALIVE] study) with that in a sample of predominantly opiate injectors (Italian Seroconversion Study [ISS]).Design:Prospective cohort studies of HIV-positive individuals whose date of seroconversion (SC) is known with a good degree of precision. The ALIVE study involves a community-based cohort of injection drug users (IDU) in the United States and the ISS reports on a clinic-based cohort of seroconverters in Italy with different exposure modalities to HIV.Methods:Data from the two cohorts were combined. The date of SC was estimated as the midpoint in time between the last negative and the first positive HIV test. Time-to-event (i.e., AIDS or death from an infectious disease) statistical methods were used. Relative hazards (RH) of progression to event were adjusted by age at SC, gender, and year of SC.Results:Of the 1003 IDUs (251 from ALIVE and 752 from ISS), 226 progressed to AIDS, and 146 died after AIDS or from an infectious disease; of these, 10 were without an AIDS diagnosis. The two groups of IDUs differed in terms of age at SC (median, 35 years for ALIVE and 25 years for ISS), proportion of women (24% versus 31%), race (7.6% versus 100% white), and year of seroconversion (i.e., ISS participants seroconverted, on average, earlier than ALIVE participants). Although the univariate analysis suggested possible differences for progression to AIDS, or to death from infectious disease between cohorts, multivariate analyses that adjusted for age showed no significant differences by cohort, gender, race, or time of seroconversion. The median time to AIDS for 25-year-old persons was 12.3 years for ALIVE and 11.8 years for ISS; for 35-year-old persons, it was 8.5 and 8.2 years, respectively. These estimates were similar to those for non-IDUs observed in the ISS and to those from large cohort of homosexual men.Conclusion:Our results confirm the importance of accounting for age when considering the incubation period for HIV infection. Despite differences in drug use characteristics, the similar median times to AIDS, for each age, between the two cohorts of IDUs and between the IDUs and the non-IDUs suggest a negligible effect of injection drug use on HIV progression.

ISSN:1077-9450    

出版商:OVID    

年代:1999

数据来源: OVID