摘要:

We recently described 102 HIV-1 integrase sequences that were amplified from blood cells or plasma obtained up to 18 years ago from 5 hemophiliacs who later died of AIDS and 5 hemophiliacs subsequently classified as slow or nonprogressors (J Acquir Immune Defic Syndr Hum Retrovirol1998;19:99–110). Although the region of the HIV-1 genome that encodes integrase was highly conserved, none of the deduced protein sequences of the patient-derived enzymes matched that of the clade B consensus or standard laboratory integrases. To test the hypothesis that the activity of HIV-1 integrases prevalent within an infected person contributes to the rate of disease progression, we have now expressed and purified these proteins and compared them in various assays. Most of the 75 unique full-length integrase proteins from the 102 clones were enzymatically active. Comparison of proteins derived from samples obtained soon after infection showed that the specificity and extent of viral DNA processing and the amount of DNA joining (the two biologically relevant activities of integrase) did not differ between the two groups of patients. In addition, the relative usage of alternative nucleophiles for processing and the amount of nonspecific nicking catalyzed by the proteins were indistinguishable between the patient groups. Although the patient-derived enzymes often exhibited different patterns of target site preferences compared with the laboratory integrase, there was no correlation with clinical course. Thus, the activities of HIV-1 integrases prevalent within these infected individuals, at least as reflected by standard assays, did not influence or predict the rate of disease progression.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesTo develop and validate a rapid, genotypic, quantitative AZT resistance assay, and to evaluate the predictive ability of a resistance index.MethodsAZT resistance profiles of paired samples from HIV-infected patients were determined by a ligase chain reaction (LCR) assay. AZT resistance levels and surrogate markers of HIV disease progression (viral load and CD4 counts) were used to compare AZT-naive and AZT-experienced patients. The ability of a “mutant/wild-type HIV-1 quasi-species” index to predict viral load was assessed.ResultsAZT resistance, evident at baseline in both AZT-experienced and AZT-naive patients, increased over 6 months of treatment. The resistance profile of AZT-naive patients differed from that of AZT-experienced patients (p< .05); viral load and CD4 counts were similar. The relative predictive ability (for subsequent viral load) of the resistance index was similar to or higher than that of baseline viral load or CD4 count.ConclusionsThis assay used to detect AZT resistance could be adapted for use with other antiretrovirals. The predictive ability of the proposed resistance index was equal to or surpassed that of viral load and CD4 count, lending further support to the use of resistance assays in selecting drug regimens both before and during antiretroviral therapy.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

The relationship between HIV-1 replication and hematologic parameters was examined in two separate studies. The first study was a cross-sectional evaluation of 207 untreated patients. In this study, the proportion of patients with hematologic disorders increased with disease progression. There was a significant inverse correlation between HIV-1 plasma viral load and all hematologic values (r = −0.266 to −0.331). The second study was a longitudinal evaluation of patients on combination antiretroviral therapy (HAART) with hematologic alterations before treatment (N= 27 with platelets <150,000/&mgr;l, 24 with hemoglobin <12 g/dl, 36 with neutrophils <2000/&mgr;l and 29 with leukocytes <3000/&mgr;l). Samples were analyzed every 3 months for 2 years. At 2 years, >50% of patients experienced a sustained virologic response, with viral loads <500 RNA copies/ml. Hematologic reconstitution occurred progressively for all blood cell lineages and became statistically significant after the sixth month of therapy (p< .001). Mean values increased from 110 to 180 × 103/&mgr;l for platelets, from 10.7 to 12.3 g/dl for hemoglobin (stabilizing finally at 11.4 g/dl), from 1,260 to 2,240/&mgr;l for neutrophils, and from 2,260 to 3,600/&mgr;l for leukocytes. In conclusion, hematologic disorders are corrected by combination antiretroviral therapy. This suggests a causative role of HIV-1 in hematologic disorders.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo characterize the relationships among highly active antiretroviral therapy (HAART), HIV-1 RNA levels, immune system markers, and clinical outcome in a cohort of HIV-1–infected homosexual men.PatientsA total of 123 men enrolled in the Amsterdam cohort study of HIV-1 infection and AIDS with a documented seroconversion for HIV-1 antibodies and known date of seroconversion were included in this study.MethodsCD4+/CD8+T-cell counts and HIV-1 RNA levels in plasma were measured approximately every 6 months. Dates of starting and stopping antiretroviral therapy were also recorded. The relationship between HIV-1 RNA in plasma, CD4+/CD8+T-cell counts and HAART and their influence on clinical outcome were examined using a graphical chain modeling approach. Generalized estimating equations were used to examine correlations among the three disease markers. Hazards models with time-dependent covariates were used to examine the influence of HAART and the disease markers on progression to AIDS.ResultsHAART was significantly associated with reduced disease progression (relative hazard [RH] of AIDS, 0.20;, 95% confidence interval [CI], 0.05–0.85). The most recent HIV-1 RNA measurement and CD4+T-cell count are independently associated with disease progression (adjusted RH for HIV-1 RNA 1.8 per log10increase; 95% CI, 1.2–2.6,p= .002; adjusted RH for CD4+0.48 per 100 × 106/L increase; 95% CI, 0.40–0.58;p<.001). Depending on these measurements, HAART was no longer significantly associated with AIDS (adjusted RH, 0.81; 95% CI, 0.18–3.6;p= .78).ConclusionsHIV-1 RNA levels in plasma and CD4+T-cell counts are currently considered as effective surrogate markers for the effect of HAART on disease progression in this cohort.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesOur objective was to describe the evolution of adherence to highly active antiretroviral therapy (HAART) over a 20-month period and its relationship with virologic success.MethodsSelf-reported adherence, clinical, and virologic data were collected 4 (M4), 12 (M12), and 20 (M20) months after initiation of a protease inhibitor–containing regimen in the French APROCO cohort. At each visit, patients were classified as nonadherent, moderately, or highly adherent, and HIV plasma RNA was determined.ResultsAmong the 762 patients who were regularly followed until M20, the 436 patients who answered to all questionnaires, including adherence measurement, were selected for the analysis. The proportion of highly adherent patients was 55.7%, 62.2%, and 60.3% at M4, M12, and M20, respectively. A total of 137 patients (31.4%) was “always,” 225 (51.6%) “sometimes,” and 74 (17.0%) “never” “highly adherent” during follow-up. After multiple adjustment for known baseline predictors, virologic success after 20 months of HAART was more likely achieved in patients who were always (odds ratio [OR] 95% confidence interval [CI], 3.02 [1.64–5.58]) or sometimes (OR [95% CI], 2.15 [1.24–3.74]) “highly adherent.”ConclusionAdherence behavior is a dynamic process. Continued adherence was associated with better response to therapy and should be encouraged to reduce the risk of virologic failure.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

HIV infection, even when well controlled, may be associated with important mental health problems. We sought to investigate anxiety, depression, and health-related quality of life using screening measurements in patients with HIV infection and to examine their dependency on biosocial parameters relating to HIV. Prospective clinical, virologic, and immunologic data were obtained in a cross-sectional study within the Swiss HIV Cohort Study. Four self-reported questionnaires were used in 397 HIV-infected individuals. The scores for anxiety and depression were high as measured by the Hospital Anxiety and Depression Scale (HADS) and the State Trait Anxiety Inventory (STAI). Half the population scored <75 on a visual analog scale (VAS) Patients were also affected in their quality of life as measured by the HIV Medical Outcome Study (HIV-MOS). Almost all scores were significantly worse for intravenous drug users compared with other transmission groups. People who were employed, with a higher education or with higher CD4 count tended to score better, whereas those who had been hospitalized within the last 6 months, infected for a longer time, with higher viral load, or loss of weight scored significantly worse. A multivariate analysis showed higher education, being employed, low viral load, female gender, and shorter HIV disease duration to be associated with better scores. This study highlights the importance of mental health assessment regardless of HIV-disease parameters.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

We analyzed the relationship between viral drug resistance and causes of death in 29 HIV-1–infected patients who had been followed in an HIV-outpatient clinic and died in 1999. Six patients (21%) died with plasma HIV-RNA levels <1000 copies/ml. Seven (24%) died with wild-type (WT) virus in plasma, 6 (21%) had reverse transcriptase (RT) mutations only, 10 (34%) had multidrug-resistant (MDR) virus. The causes of death were not differently distributed among these groups; however, 8 of 16 patients (50%) with resistant viruses died of end-organ failure versus 2 of 7 patients (29%) with WT virus. Seventeen of 32 patients (53%) were thought by their physicians to be noncompliant with prescribed therapy. Major resistance mutations to antiretroviral drugs were present in viruses from at least 55% of our HIV-1–infected patients who died in 1999. Nonetheless, deaths also occurred among patients with well-controlled HIV infection and among patients with WT virus in plasma. Infections related to incomplete immune restoration, inability to maintain suppressive antiretroviral drug levels, and end-organ failures all contribute to mortalities in the era of highly active antiretroviral therapy.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

We compared the two commercially available sequencing kits for HIV-1 drug resistance testing, the ViroSeq Genotyping System (Applied Biosystems, Foster City, CA, U.S.A.) and the TRUGENE HIV-1 Genotyping Kit (Visible Genetics, Inc., Toronto, Ontario, Canada), with our in-house genotyping system. Fifteen viral isolates from African patients (6 treated and 9 untreated) covering a panel of HIV-1 subtypes A through J and 7 plasma samples from Belgian and African patients (2 treated and 5 untreated) were tested. All the samples could be amplified and sequenced by the three systems; however, for all systems, alternative amplification/sequencing primers had to be used for some samples belonging to subtype B as well as to other subtypes. The consensus sequence was partially derived from only one strand for the in-house system and for the ViroSeq Genotyping System. The TRUGENE HIV-1 Genotyping Kit scored the highest number of ambiguities, followed by the ViroSeq Genotyping System and the in-house system. For 11 samples, these differences in reporting mixtures affected 14 resistance-related positions, which altered the interpretation toward protease inhibitors for 2 samples when using version 1.2 RetroGram software (Virology Networks, Utrecht, The Netherlands). All three systems were able to sequence diluted samples with a viral load down to 103or 104RNA copies/ml. Our data therefore suggest that the performance of amplification and sequencing primers must be improved to allow fast and reliable resistance testing for all HIV-1 subtypes.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo determine whether adherence with one antiretroviral medication reliably predicts adherence with other antiretroviral medications.DesignCross-sectional repeated-measurement analysis.SettingCohort study enrolling patients from Massachusetts and Rhode Island.PatientsTotal of 454 patients using antiretroviral medications for HIV infection.MethodsFor each antiretroviral medication, we asked patients to report how many days in the last week they had 1) missed a dose of the medication and 2) been off schedule with a dose of the medication. The reliability coefficient was used to compare between-person variance in adherence rates with total variance, which is the sum of between-person and within-person variance.ResultsThe mean age of patients was 42 years; 28% were women and 37% were nonwhite. Sixty-six percent of patients were on three or more antiretroviral medications. Perfect adherence was reported by 42% of patients, and patients reported missing a dose on a mean of 1.5 days per week for each antiretroviral medication currently being taken. The reliability coefficient for days in the last week that the medication was missed was 0.85 (95% confidence interval [CI]: 0.83–0.87), and for days off-schedule in the last week, it was 0.88 (CI: 0.86–0.89).ConclusionsMost of the variability in antiretroviral adherence in this study was accounted for by between-patient differences in overall adherence rather than by within-patient differences in adherence patterns across medications. These data support the theory that when patients skip or are off schedule with doses, they skip or are off schedule with all the antiretroviral medications taken at that time. In the course of exploring patients' adherence issues, clinicians may find it useful to inquire about problematic dosing times. Researchers assessing adherence may not need to separately monitor adherence with each antiretroviral medication in a regimen.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesTo determine trends in HIV infection and risk behaviors among street-recruited self-identified gay and bisexual male injection drug users (IDUs) in San Francisco.MethodsTrends in HIV infection and risk behaviors were calculated for gay/bisexual (n= 1594 interviews) IDUs in 26 semiannual cross sections from 1988 to 2000.ResultsHIV seroprevalence among gay/bisexual IDUs decreased from the range of 35% to 45% in 1988/1989 to 25% in 1996 and then began to increase, reaching 42% in 2000. In contrast, HIV prevalence among heterosexual male IDUs remained stable during the study period. For gay/bisexual IDUs, injection and sex-related HIV risk behaviors declined modestly throughout the study period. As of the last cross section (July 2000), however, over a third of respondents reported recent syringe sharing or unprotected anal sex.ConclusionsGay/bisexual men who inject drugs continue to be at elevated risk for HIV, suggesting that interventions such as amphetamine drug treatment and sexual risk reduction programs targeted at this population are needed.

ISSN:1525-4135    

出版商:OVID    

年代:2001

数据来源: OVID