摘要:

ObjectiveThis study examines whether there may be an immune component that protects a relatively rare group of HIV-infected people with very low CD4 cell counts (⩽ 50 × 106/l) who have prolonged asymptomatic periods.Design/methodsThree groups were recruited in Miami: (i) healthy low CD4 cell count patients (HLC; n = 30) who, for 9 months had < 50 × 106CD4 cells/l, were asymptomatic and were not on protease inhibitors during that time; (ii) HIV comparison group (Comp; n = 60) who had CD4 cell counts predominantly 150 × 106to 400 × 106/l and never had AIDS Category C symptoms; this group was also followed for CD4 cell count and viral load change over 6 months; and (iii) healthy community controls (n = 33). The study was replicated at the University of California at Los Angeles (UCLA) with HLC (n = 31) versus HIV-negative laboratory controls (n = 28).ResultsThe HLC patients were significantly higher than the Comp group on natural killer cell cytotoxicity (NKCC) and natural killer cell number (NK#) despite their lower CD4 cell numbers and higher viral loads. In fact, there was no difference between the HLC group and the healthy community control group in NK# or NKCC. The NK findings were replicated at UCLA. A retrospective analysis showing that higher NKCC was related to fewer prior symptoms in the HLC group, and prospective analysis in the Comp group showing that NK# predicted a lower increase in viral load over 6 months further supported the importance of NK# and NKCC.ConclusionsNon-specific cellular immunity may be a factor protecting the health of HIV sero-positive individuals with very low CD4 cell counts.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesTo determine the kinetics and the relationship between the T-cell receptor Vβ (TCRBV) complementary determining region 3 length, the CD4 T-cell count and HIV viral load changes in HIV-1 infected infants treated early with highly active antiretroviral therapy (HAART) during 1 year of follow-up.DesignTwo HIV-1 vertically infected infants, two HIV-1 vertically exposed uninfected and two healthy controls were analysed by spectratyping. Evaluation of viral load, CD4 naive and memory cell counts and a proliferation test were also carried out.MethodsTwenty-six families and subfamilies of the TCR on CD4 and CD8 T cells were analyzed by spectratyping. Flow cytometric analysis on peripheral blood mononuclear cells for CD4CD45Ra, CD4CD45Ro, CD8CD38, proliferation tests and plasma viral load measurements were performed at baseline, 1, 6 and after 12 months of therapy.ResultsHAART induced a marked reduction of viral load in both HIV-1 infected infants and an increase to normal CD4 T-cell count in the symptomatic infant. At baseline the TCRBV family distribution in the majority of CD8 and a few of the CD4 T cells was highly perturbed, with several TCRBV families showing a monoclonal/oligoclonal distribution. During HAART a normalization of the TCR repertoire in both CD8 and CD4 subsets occurred. TCR repertoire normalization was associated with a good virological and immunological response.ConclusionThese results suggest that complete and early virus replication control as a result of early HAART leads to a marked reduction of T-cell oligoclonality and is an essential prerequisite to the development of a polyclonal immune response in HIV-1 infected infants.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveA comparative study of the replication kinetics of different HIV-1 variants (including SIVcpz) was undertaken to determine which viral characteristics were associated with sustained plasma viraemia in chimpanzees.DesignPlasma samples from chimpanzees infected with six different HIV-1 clade B isolates were compared with plasma samples from SIVcpz−ant-infected chimpanzees.MethodsA pan-clade quantitative competitive reverse transcriptase–polymerase chain reaction assay was developed based on conserved primer sequences recognizing M, N and O human lentiviruses as well as different SIVcpzisolates.ResultsImportant differences between early kinetics in the human lentivirus isolates as well as compared with the chimpanzee isolate SIVcpz−antwere observed. R5-dependent non-syncytium-inducing (NSI) isolates (5016, Ba-L, SIVcpz) were found to have relatively higher viral loads than the syncytium-inducing (SI), X4-dependent primary (SF2), T cell-adapted (IIIB) or X4/R5 (Han2, DH12) SI primary isolates.ConclusionInfection of chimpanzees with NSI R5-utilizing isolates correlated with persistent viraemia (approximately 104RNA equivalents/ml) in contrast to transient viraemia observed after infection with SI X4-utilizing isolates.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

BackgroundTreatment for HIV-1 infection is complicated by fat redistribution (lipodystrophy). This is associated with insulin resistance concerning glucose uptake. Our aim was to characterize glucose metabolism more comprehensively in HIV-1-infected patients with lipodystrophy. We assessed glucose disposal and its pathways, glucose production, plasma free fatty acid (FFA) levels, and the degree to which these parameters could be suppressed by insulin.MethodsSix HIV-1-infected men on protease inhibitor-based HAART with lipodystrophy (HIV+LD) were studied. The results were compared with those in six matched healthy male volunteers. Insulin sensitivity was quantified by hyperinsulinemic euglycaemic clamp. Glucose production and uptake were assessed by tracer dilution employing 6,6d2-glucose.ResultsAt post-absorptive insulin concentrations, glucose production was 47% higher in HIV+LD than controls (P= 0.025). During clamp, glucose production was suppressed by 53% in HIV+LD, but by 85% in controls (P= 0.004). Glucose disposal increased in both groups, but by only 27% in HIV+LD versus 201% in controls (P= 0.004). Consequently, insulin-stimulated total glucose disposal was lower in HIV+LD patients (P= 0.006). Non-oxidative glucose disposal as percentage of total disposal did not differ significantly between groups (63% in HIV+LD and 62% in controls). Baseline plasma FFA concentrations were higher (0.60 versus 0.35 mmol/l;P= 0.024), whereas FFA decline during hyperinsulinemia was less (65 versus 85%;P= 0.01) in HIV+LD versus controls .ConclusionsPost-absorptive glucose production is increased in HIV-1-infected patients with lipodystrophy. Moreover, both the ability of insulin to suppress endogenous glucose production and lipolysis, and to stimulate peripheral glucose uptake and its metabolic pathways is reduced, indicating severe resistance concerning multiple effects of insulin.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo characterize predictors and consequences of discontinuing antiretroviral therapy (ART) in terms of CD4 cell count, HIV RNA, and reported side-effects in a large cohort of HIV-infected women.DesignCohort study.MethodsA total of 1058 HIV-infected women initiated potent ART before September 1999. For each 6 month period after October 1996 we determined the proportion of potent ART users who downshifted to non-potent ART and who discontinued all ART. We examined the role of CD4 cell count and HIV RNA with regard to ART discontinuation.ResultsBetween October 1996 and September 1999, 1058 individuals contributed 3362 visits at which potent ART was reported in the previous 6 months. Overall rates of 6 month downshifting and discontinuation were 10.0% and 6.7%. The proportion of individuals discontinuing all ART increased from 2.9% in late 1996 to 9.1% in mid 1999 (P< 0.001). Individuals with high HIV RNA levels were more likely to discontinue (P< 0.05). Compared to those who continued on potent ART, individuals who discontinued experienced large declines (P< 0.001) in CD4 cell counts and were more than three times more likely (P< 0.001) to experience HIV RNA increases. However, over one-third of those discontinuing ART reported side-effects and this subset had smaller CD4 cell count declines as compared to discontinuers not reporting side-effects (P= 0.147).ConclusionsIn a large cohort of HIV-infected women, an increasing proportion of potent ART users discontinued ART over 3 years. Higher HIV RNA levels predicted discontinuation. Immediate immunological/virological deleterious consequences were observed. Side-effects were the most common reason for discontinuation and CD4 cell count declines were larger among those who did not cite side-effects as the reason for discontinuation.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo determine whether differences in adherence to newly initiated antiretroviral therapy exist between subjects who do and do not achieve undetectable plasma viral loads.DesignObservational cohort study monitoring adherence and virological and immunological parameters over the initial 4 months of therapy with nelfinavir. Adherence was measured using the microelectronic monitoring system (MEMS; APREX Corporation, Menlo Park, California, USA).SettingGeneral Clinical Research Center at a tertiary care center.ParticipantsForty-one protease inhibitor-naive subjects with viral loads > 10 000 copies/ml newly starting a regimen including nelfinavir, referred from HIV clinics in Philadelphia.Main outcome measuresThe primary outcome was undetectable viral load (< 50 copies/ml) after 4 months. Secondary measures included changes in viral load and CD4 cell counts. We hypothesized that adherence would be greater in subjects who achieved undetectable viral loads.ResultsAdherence was greater in undetectable subjects, who took a median of 93% of prescribed doses [interquartile range (IQR) 84–96%], whereas detectable subjects took a median of 70% (IQR 46–93%). Adherence correlated with viral load decrease (Spearman's ρ = 0.38,P< 0.01) and CD4 cell count increase (Spearman's ρ = 0.25,P= 0.06). Despite differences between the groups over 4 months of therapy, there were no adherence differences over the first month [undetectables, 95% (IQR 88–98%) versus detectables, 94% (IQR 87–98%),P> 0.50].ConclusionsAdherence is important in determining whether or not individuals achieve suppression with a newly initiated antiretroviral regimen. Adherence begins to wane after the first month of therapy. Therefore, closer assessment of adherence particularly after this first month is important.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo evaluate the impact of immune recovery induced by highly active antiretroviral therapy (HAART) on the survival of AIDS patients with primary central nervous system lymphoma (PCNSL).MethodsIn a multicentric retrospective analysis, 29 HIV-infected patients with histologically confirmed PCNSL were identified. To evaluate median survival, Kaplan–Meier statistics were used. To explore the effects of different variables on survival, a Weibull accelerated failure time regression analysis was performed.ResultsMedian age at manifestation of PCNSL was 39.1 years and median CD4 cell count was 11 × 106cells/l. Seventy per cent of the patients had had a prior AIDS-defining illness. Cranial radiation (CR) was given to 12 out of 29 patients. Six patients were treated with HAART. Survival time of these patients and of the patients treated with CR alone differed significantly from those receiving neither CR nor HAART (median Kaplan–Meier survival estimate: 1093, 132, and 33 days, respectively). In the multivariate regression model, HAART and CR were identified as the only variables independently associated with prolonged survival. HAART versus no HAART and CR versus no CR increased the time to event by a factor of 6.1 (95% confidence interval, 2.4–16.0;P= 0.0002) and 3.1 (95% confidence interval, 1.5–6.3;P= 0.002), respectively. Four out of six patients on HAART showed a marked immune recovery and survived for more than 1.5 years, with two patients still alive.ConclusionData from this cohort indicate that immune recovery induced by HAART leads to dramatic improvement in survival of patients with AIDS-associated PCNSL. These findings may have important implications for future treatment strategies.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo study the impact of chemoprophylaxis for tuberculosis on the survival of HIV-infected patients with a positive tuberculin skin test.DesignProspective observational cohort study.SettingOutpatient clinic of a university hospital, in Rio de Janeiro, Brazil.PatientsTwo-hundred and ninety-seven patients with a positive tuberculin skin test (reaction ⩾ 5mm) who were admitted to the cohort between January 1991 and December 1994. Follow-up ended on September 30, 1998.InterventionThe use of chemoprophylaxis for tuberculosis.Main outcome measuresDeath was the primary outcome variable. The occurrence of tuberculosis was studied as a secondary outcome. Cox regression models were used in these analyses.ResultsThe median follow-up time was 43.6 months. Chemoprophylaxis was used by 128 (43%) of the patients. The use of chemoprophylaxis was associated with a reduction in risk for tuberculosis (hazard ratio, 0.38; 95% confidence interval, 0.14–1.04;P= 0.05). In a regression model adjusted for baseline CD4 cell count, chemoprophylaxis was associated with longer survival (hazard ratio, 0.24; 95% confidence interval, 0.09–0.65;P= 0.002).ConclusionsAnti-tuberculosis chemoprophylaxis was associated with a substantially prolonged survival among purified protein derivative-positive HIV-infected patients in Brazil. These data have important implications for the clinical care of patients with HIV infection in areas of the world with a high prevalence ofMycobacterium tuberculosisinfection.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

BackgroundTreatment of latent infection is needed to protect HIV-infected individuals against tuberculosis. A previous report addressed short-term efficacy of three regimens in HIV-infected adults. We now report on long-term efficacy of the study regimens.MethodsThree daily self-administered regimens were compared in a randomized placebo-controlled trial in 2736 purified protein derivative (PPD)-positive and anergic HIV-infected adults. PPD-positive subjects were treated with isoniazid (INH) for 6 months (6H), INH plus rifampicin for 3 months (3HR), INH plus rifampicin and pyrazinamide for 3 months (3HRZ), or placebo for 6 months. Anergic subjects were randomized to 6H or placebo.Results6H initially protected against tuberculosis in PPD-positive individuals; however, benefit was lost within the first year of treatment. Sustained benefit was observed in persons receiving 3HR and 3HRZ. In a Cox regression analysis, the adjusted relative risk for tuberculosis compared with placebo was 0.67 [95% confidence interval (CI), 0.42–1.07] for 6H, 0.49 (95% CI, 0.29–0.82) for 3HR, and 0.41 (95% CI, 0.22-0.76) for 3HRZ. When the rifampicin-containing regimens were combined, the adjusted relative risk for tuberculosis compared with placebo was 0.46 (95% CI, 0.29–0.71). Among anergic subjects, a modest degree of protection with 6H was present (adjusted relative risk, 0.61; 95% CI, 0.32–1.16). Treatment of latent tuberculosis infection had no effect on mortality.ConclusionSix months of INH provided short-term protection against tuberculosis in PPD-positive HIV-infected adults. Three month regimens including INH plus rifampicin or INH, rifampicin and pyrazinamide provided sustained protection for up to 3 years.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

BackgroundWe have assessed the long-term efficacy and safety of a combination therapy of interferon alpha-2b (IFN) and ribavirin (RBV) for the treatment of severe chronic hepatitis C in co-infected HIV-seropositive patients in an open prospective study.MethodsFifty-one patients were treated for 12 months. Mean baseline CD4 cell count, alanine aminotransferase and aspartate aminotransferase were 412 ± 232 × 106/l, 113 ± 75 IU/l and 111 ± 84 IU/l respectively. The mean Knodell score was 11.5 ± 2.1 with 28 patients (55%) exhibiting histological evidence of active cirrhosis.ResultsFifteen (29%) patients discontinued the treatment prematurely because of adverse events. An end of treatment response (ETR) as defined by the lack of detectable hepatitis C virus (HCV) RNA in plasma at the end of treatment was achieved in 15 patients (29%). A sustained virological response (SVR), defined by the lack of detectable HCV RNA in plasma 6 months after completion of combination therapy, was achieved in 11 patients (21%). The HCV genotype 3a was associated with ETR and SVR (P= 0.002 andP= 0.003, respectively). HCV viraemia at baseline was lower in patients who achieved SVR and ETR than in those who did not (6.7 ± 7.8 versus 24 ± 26.7 × 106genome equivalents/ml,P= 0.03 and 14.3 ± 28.7 versus 22.5 ± 23,P= 0.05, respectively).ConclusionOur results indicate that combination therapy with IFN and RBV is effective in approximately 20% of co-infected patients with severe liver disease.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID