ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveAn assessment of the impact of one year potent antiretroviral treatment initiated during primary HIV infection on the cell-associated viral burden.Design and methodsProviral HIV-1 DNA was quantified in serial peripheral blood mononuclear cell (PBMC) samples from 19 patients enrolled in the French prospective PRIMO Cohort for whom plasma HIV RNA was suppressed to undetectable levels after one year of triple therapy; that is, plasma HIV-1 RNA was maintained below 200 copies/ml. Results were compared with those observed in 19 patients with chronic HIV-1 infection presenting the same degree of virus suppression after 12 months of treatment.ResultsAt study entry, PRIMO subjects presented heterogeneous levels of proviral HIV-1 DNA: 2–3.92 log10copies/106PBMC and plasma HIV RNA: 2.3–6.5 log10copies/ml. One year of effective highly active antiretroviral therapy (HAART) resulted in a median diminution of proviral DNA of −0.78 log10/106PBMC in PRIMO subjects. The median decline in chronic-phase patients was −0.32 for those who were pre-treated and −0.52 for those previously naive of treatment.ConclusionThe decline in cell-associated HIV DNA observed throughout one year treatment indicated that HAART reduces the proviral HIV-DNA load more effectively when initiated during the primary rather than the chronic phase of HIV infection. These findings therefore tend to lend support to the early initiation of treatment. Nevertheless, heterogeneous baseline values observed for CD4 cell count, plasma HIV RNA and proviral HIV DNA in PRIMO subjects, raise the question of whether treatment should be delayed in some to spare early adverse effects of HAART.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesTo investigate the intracellular accumulation of HIV protease inhibitors (PI) and to assess the effect of active transport on this accumulation.MethodsCEM cells were incubated with a PI for 18 h and the intracellular concentration determined using cell number and radioactivity. The effect of active transport was investigated using cells expressing P-glycoprotein (CEMVBL) and cells expressing multidrug resistance-associated protein 1 (MRP1; CEME1000). Incubations were also carried out at 4°C and in the presence of 2-deoxyglucose plus rotenone to examine the effect of inhibiting active transport.ResultsNelfinavir (NFV) accumulated to the greatest extent (> 80-fold) followed by saquinavir (SQV; ∼ 30-fold), ritonavir (RTV; 3–7-fold) and finally indinavir (IDV; extracellular equivalent to intracellular). In CEMVBLcells there was a significant reduction in the intracellular accumulation of NFV, SQV and RTV and in CEME1000cells there was reduced accumulation of SQV and RTV. Inhibition of active transport processes caused a reduction in SQV and RTV accumulation but had no effect on IDV accumulation in all cell types. NFV accumulation was increased in CEMVBLcells as a result of inhibition of active transport.ConclusionsMarked differences can be detected in the intracellular accumulation of HIV PI drugsin vitro. Both P-glycoprotein and MRP1 may play a role in limiting the intracellular concentration of the PI and active influx mechanisms may contribute to drug accumulation.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesInformation on early HIV-1 infection has come primarily from studies of persons infected with subtype B in North America and Europe; much less is known about other subtypes. The purpose of the present study was to compare the virologic and immunologic parameters following seroconversion among recently-infected persons infected with either of two different HIV-1 subtypes.MethodA prospective cohort study was carried out at methadone treatment clinics administered by the Bangkok Metropolitan Administration, Thailand. A total of 130 HIV-1-infected seroconverters (103 with HIV-1 subtype E and 27 with subtype B) were included in the study. The main outcome measures were serial HIV-1 RNA viral load, natural killer cell percentage, CD4 and CD8 lymphocyte counts since seroconversion.ResultsThe demographic and behavioral characteristics of persons with either subtype were similar. Median RNA viral levels at the earliest time within 3 months of seroconversion were more than three times higher for persons infected with subtype E than subtype B (63 100 versus 18 050 copies/ml,P= 0.001). However, this difference decreased over time such that viral loads were similar at 12, 18, and 24 months following seroconversion. The CD4 and CD8 lymphocyte counts were similar in infections with either subtype during the entire period up to 24 months post-seroconversion.ConclusionsHigher viral loads associated with subtype E may result from inter-subtype biological differences; however, the epidemiological dynamics of transmission in Bangkok may have also contributed to this phenomenon.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesThe purpose of the study was to examine the effects of aerobic exercise on physiological fatigue (time on treadmill), dyspnea [rate of perceived exertion (RPE) and forced expiratory volume at 1 s (FEV1)], weight, and body composition in HIV-1-infected adults (200–499 × 106CD4+ cells/l).DesignThe study was a randomized, wait-listed, controlled clinical trial of aerobic exercise in HIV-1-infected adults on signs and symptoms associated with HIV-1 infection or its treatment.MethodsSixty subjects were recruited and randomized to two groups. Experimental subjects completed a 12-week supervised exercise program. Control subjects continued usual activity from baseline to week 12 and were then were enrolled in the exercise program.ResultsAt baseline, the groups were similar in age, weight, body mass index [mean body mass index (BMI) > 27], time since diagnosis, number of symptoms, CD4+ cell count, and number on protease inhibitor therapy (n = 7). Despite disproportionate attrition from the exercise group (38%), exercise subjects were able to remain on the treadmill longer, lost weight, decreased BMI, subcutaneous fat, and abdominal girth when compared to controls. The improvement in weight and body composition occurred without a decrease in kilocalories consumed. Exercise did not seem to have an effect on RPE, a surrogate for dyspnea, and FEV1. There was no significant difference in either the change in CD4+ cell count, percentage or copies of plasma HIV-1 RNA between groups.ConclusionsWe conclude that supervised aerobic exercise training safely decreases fatigue, weight, BMI, subcutaneous fat and abdominal girth (central fat) in HIV-1-infected individuals. It did not appear to have an effect on dyspnea.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

BackgroundOsteopenia has been associated with antiretroviral therapy, particularly with protease inhibitors. Osteopenia in HIV-uninfected men is associated with mitochondrial defects.MethodsBone density was assessed by dual-energy X-ray absorptiometry (DEXA) in 221 HIV-infected men (mean age 43 years) recruited to a lipodystrophy prevalence survey. Additional parameters assessed were demographics, exercise, smoking, type(s) and duration of all antiretroviral therapy, lipodystrophy (overall and by region), CD4 counts, HIV RNA, fasting metabolic parameters (lipid, glycaemic, lactate, liver enzymes, testosterone) and regional body fat and lean mass (DEXA and L4 abdominal computed tomographic scan).ResultsThirty-two patients were drug-naive; 42 were receiving nucleoside analogue reverse transcriptase inhibitors (NRTI) and 147 were receiving these plus protease inhibitors. Osteoporosis (t-score < −2.5 SD below normal) was found in seven (3%) and osteopenia (t-score −1.0 to −2.5 SD) in 44 (22%). No patient had had a fracture since being infected with HIV. The only factors independently associated on logistic regression with osteopenia or osteoporosis were higher lactate levels, even if asymptomatic [odds ratio (OR) 2.39 per 1 mmol/l increase; 95% confidence interval (CI) 1.39–4.11;P= 0.002), and lower weight prior to commencing antiretroviral therapy (OR 1.06 per 1 kg decrease; 95% CI 1.02–1.11;P= 0.006). There was no independent association with any other parameter, including type or duration of antiretroviral therapy and lipodystrophy at any site. Lower total bone mineral density was associated with lower weight prior to commencing antiretroviral therapy whereas lower spinal bone mineral density was associated mostly with higher lactate.ConclusionOsteopenia in HIV-infected men is common, asymptomatic and is associated with asymptomatic NRTI-related lactic acidemia and lower weight pre-antiretroviral therapy.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo assess the characteristics of CD4 and CD8 T cells specific for HIV-1 and cytomegalovirus (CMV) antigens in untreated and treated HIV-1-infected patients.MethodsAntigen-specific T cell frequencies were determined by flow cytometric detection of antigen-induced intracellular cytokines.ResultsIn untreated patients, HIV-1-specific CD4 T cell counts in peripheral blood were less than one tenth of CMV-specific CD4 T cell counts, while the number of specific CD8 T cells was approximately the same for both HIV-1 and CMV. In patients treated with highly active antiretroviral therapy (HAART) for less than 1.5 years, HIV-1-specific CD4and CD8T cell counts were significantly lower than those in untreated patients. Perforin expression in HIV-1-specific CD8 T cells was significantly lower than that in CMV-specific CD8 T cells.ConclusionThese data indicate that HIV-1-specific T cells in HIV-1-infected patients have quantitative and qualitative abnormalities.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo determine the prevalence, course and risk factors for hyperlactatemia in HIV-infected patients.DesignA prospective, longitudinal study of venous lactate concentrations over an 18-month period in 349 participants of the Western Australian HIV Cohort Study.ResultsIn 516 patient-years of observation, two patients experienced severe fulminant lactic acidosis (lactate > 5 mmol/l) and hepatic steatosis attributable to nucleoside analogue reverse transcriptase inhibitors (NRTI). A further five patients with lesser elevations of lactate (2.8–4.1 mmol/l) but with symptoms of nausea or abdominal discomfort and evidence of hepatic steatosis had NRTI therapy revised, with relief of symptoms and a fall in lactate levels. Most remaining patients on highly active antiretroviral therapy (HAART) had mild, chronic, asymptomatic hyperlactatemia, with mean lactate level between 1.5 mmol/l and 3.5 mmol/l most commonly. Longitudinal data was analysed in a non-linear mixed effects growth model which indicated that average lactate levels rose after the start of HAART but tended to stabilise at low-grade elevation, with an average 0.23 mmol/l greater long term level in stavudine users compared with zidovudine users (p < 0.01). A multiple linear regression model showed that the association between stavudine and higher lactate level was not confounded by longer duration of total NRTI exposure. Risk of hyperlactatemia was not significantly associated with use of other NRTIs, protease inhibitors, non-nucleoside analogue reverse transcriptase inhibitors or multiple immunological and virological factors in multivariate analyses.ConclusionsChronic, compensated, asymptomatic hyperlactatemia is common in patients taking HAART. Decompensated, life-threatening lactic acidosis/hepatic steatosis is rare. Treatment with stavudine appears to be the predominant risk factor for development of chronic hyperlactatemia.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesBecause female sex protects against dyslipidaemia and atherosclerosis in normal subjects, we aimed to reveal potential sex differences in metabolic side-effects of a newly initiated highly active antiretroviral therapy (HAART) regimen, and to relate these changes to endothelial cell activation as measured by levels of circulating E-selectin (cE-selectin).DesignProspective longitudinal cohort study.SettingTertiary care centre at a University Hospital.MethodsHIV-seropositive male (n = 27) and female patients (n = 13) with a plasma viral load of ⩾ 10 000 copies/ml and 35 healthy controls were enrolled in the study. All participants were weight stable, free of acute opportunistic infections, and had not taken any protease inhibitors before. Serum levels of lipids, insulin, leptin, and cE-selectin were measured before initiation of HAART, and at 3 and 6 months thereafter.ResultsHAART increased serum levels of triglycerides, leptin, and low-density lipoprotein (LDL) cholesterol; these effects were more distinct in women. Fasting insulin levels and the LDL : high density lipoprotein (HDL) ratio increased only in female HIV-infected patients (P< 0.02 versus men). In contrast, endothelial activation, as measured by cE-selectin, decreased more in men (P< 0.02) than in women. As a consequence, women had higher triglycerides and leptin levels after therapy than did men, and the LDL : HDL ratio and cE-selectin levels, which were initially higher in men, were no longer different between the sexes.ConclusionsMetabolic adverse effects during HAART are more pronounced in women than in men. Hence, female HIV-infected patients seem to loose part of their natural protection from atherosclerosis during antiretroviral therapy.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesTo evaluate prior antiretroviral therapy experience and host characteristics as determinants of immunologic and virologic response to highly active antiretroviral therapy (HAART).MethodsWe studied 397 men from the Multicenter AIDS Cohort Study (MACS) who initiated HAART between October 1995 and March 1999. CD4 cell count and HIV-1 RNA responses to HAART were measured at the first visit following HAART (short-term) and extending from the first visit to approximately 33 months after HAART (long-term). Prior antiretroviral experience was classified into three groups based on antiretroviral therapy use during the 5 years prior to HAART. Age, race and host genetic characteristics also were assessed for their effects on treatment response.ResultsBetter short- and long-term CD4 cell and HIV-1 RNA responses were observed in the treatment-naive users. Intermittently and consistently experienced users did not significantly differ in response. Whereas race did not independently affect response, among those initiating HAART with > 400 × 106CD4 cells/l, younger age and the Δ32CCR5genotype were associated with a better short-term CD4 cell response. There was a suggestion that having the protectiveCCR5genotype also was associated with a better long-term CD4 cell response.ConclusionImmunologic and virologic response to HAART was stronger in individuals who had no prior experience with the antiretroviral therapy agents subsequently included in their initial HAART regimen. Age, level of immune competence and immunogenetics appeared to play a role in the subsequent immune reconstitution following use of highly effective HIV therapy.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID