ISSN:0269-9370    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0269-9370    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0269-9370    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Objective:HIV-1 particles are enriched with cholesterol; however, the significance of this cholesterol enrichment is unknown. This study examines the structural and functional roles of cholesterol in HIV-1 replication.Methods:Using methyl-β-cyclodextrin (CD) to remove cholesterol from the HIV-1 envelope, buoyant density and infectivity of the cholesterol-deficient HIV-1 particles were compared with the untreated control. The specificity and requirement of cholesterol as an HIV-1-associated lipid were investigated by replenishing cholesterol-deficient HIV-1 with cholesterol, cholestenone (a cholesterol structural analogue) or sphingomyelin (a structurally unrelated yet virion-associated lipid).Results:CD-mediated removal of virion cholesterol increased the buoyant density of virion particles and reduced HIV-1 infectivity.Trans-supplementation of exogenous cholesterol rescued the defects associated with CD-induced cholesterol depletion in HIV-1. However, the restoration of viral infectivity could not be achieved bytrans-supplementation of either cholestenone or sphingomyelin.Conclusion:This study provides the first direct evidence that HIV-1-associated cholesterol is important for the maintenance of virion structure and infectivity. While the buoyant density of cholesterol-defective HIV-1 can be restored by a cholesterol structural analogue, cholestenone, the requirement for cholesterol is essential for HIV-1 infectivity.

ISSN:0269-9370    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Objective:To determine the influence of age on the regeneration rate of naive and memory T cells in the blood of 45 adults on highly active antiretroviral therapy (HAART).Methods:The age of the patients ranged from 25 to 57 years. Naive cells were defined as CD45RA+CD27+. Cells negative for CD45RA and/or CD27 were considered memory type cells.Results:The recovery rates of naive CD4 and CD8 T cells were similar, were negatively correlated with age and were decreasing 5% and 3.6% per year, respectively. In a multivariate regression analysis, only age was significantly correlated with the naive T cell recovery rates. The recovery rate of memory T cells showed no relation to age. The average regeneration rate of naive CD4 T cells during HAART, i.e., 0.34 × 106cells/l per day, is not lower than regeneration rates in HIV-negative adults following cytotoxic chemotherapy or CD4 monoclonal antibody therapy.Conclusion:These observations suggest that the thymus contributes considerably to the regeneration of naive T cells in adults on HAART, and that the impact of HIV infection on naive T cell production is small, or rapidly reversible.

ISSN:0269-9370    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Background:Many HIV-infected men and women have a strong desire for a child. Assisted reproductive technologies (ART) are an option for HIV-serodifferent couples to reduce the risk of HIV transmission from an infected man to the woman. Potential HIV contamination of selected spermatozoa after semen processing is an important issue in this context.Methods:HIV in processed semen obtained in our laboratory since 1995 were analysed. HIV RNA and DNA detection was performed in the selected spermatozoa of 125 men. HIV RNA was analysed in blood and semen plasma as well as HIV DNA in non-sperm cells.Results:HIV RNA and DNA were detected in the selected spermatozoa of eight and two men (6.4% and 1.6%), respectively. HIV RNA was detected with a median load of 5 copies/106spermatozoa. Six of the eight men were untreated, one was taking nucleoside analogue therapy and one was on highly active antiretroviral treatment (HAART). HIV RNA detection was more likely to be positive in selected spermatozoa of men with high seminal plasma viral load. HIV RNA was detected in 26% and 11% of selected spermatozoa fractions when the seminal plasma load was > 10 000 copies/ml and 20–10 000 copies/ml, respectively, but in none when the seminal plasma tested negative.Conclusion:Selected spermatozoa may be positive for HIV RNA detection even in treated patients. Viral validation of processed semen is necessary in ART programmes for serodifferent couples, particularly in men with only partially or poorly controlled HIV infection.

ISSN:0269-9370    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Objective:To evaluate the correlation between host genetic profiles and virological and immunological outcomes among HIV-1-seropositive participants from the Reaching for Excellence in Adolescent Care and Health (REACH) cohort.Methods:HLA class I and chemokine coreceptor (CCR) alleles and haplotypes were resolved in 227 HIV-1-seropositive adolescents (ages 13–18 years; 75% females; 71% African-Americans) and 183 HIV-seronegative individuals, with quarterly follow-up visits between 1996 and 2000. Each HLA and CCR variant with consistent risk and protective effect on HIV-1 pathogenesis was assigned a score of −1 and +1, respectively. All individual markers and genetic scores were analyzed in relation to plasma viral load (VL) and CD4 T lymphocytes during a 6–12-month interval when no antiretroviral therapy was taken.Results:HLA-B*57alone was a strong predictor of VL (P< 0.0001), but composite genetic profiles found in over 50% of patients consistently outperformed the individual component markers in multivariable analyses with or without adjustment for gender, race, age, and membership of clinical patient groups. Adolescents (n = 37) with a favorable combination of VL (< 1000 copies/ml) and CD4 T cell counts (> 450 × 106cells/l) consistently had more positive (+1 to +2) than negative (−1 to −4) HLA and CCR scores compared with those (n = 56) with an unfavorable combination (VL > 16 000 copies/ml and CD4 cells < 450 × 106cells/l) or the remainder (n = 134) of the cohort (overallP< 0.0001).Conclusion:A generalizable genetic scoring algorithm based on seven HLA class I and CCR markers is highly predictive of viremia and immunodeficiency in HIV-1-infected adolescents.

ISSN:0269-9370    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Objectives:An accurate test forMycobacterium tuberculosisinfection is urgently needed. The tuberculin skin test (TST) lacks sensitivity, particularly in HIV-infected individuals, and has poor specificity because of antigenic cross-reactivity with Bacillus Calmette-Guérin (BCG) vaccination. ESAT-6 and CFP-10 are antigens expressed inM. tuberculosis, but not inMycobacterium bovisBCG and most environmental mycobacteria. We investigated whether T cells specific for these antigens could serve as accurate markers ofM. tuberculosisinfection in an area of high tuberculosis and HIV prevalence.Methods:Using the rapid ex-vivo enzyme-linked immunospot (ELISPOT) assay for IFN-γ, we enumerated T cells specific for ESAT-6, CFP-10 and purified protein derivative (PPD) in blood samples from 50 Zambian tuberculosis patients, 75 healthy Zambian adults, and 40 healthy UK residents. TSTs were performed in 49 healthy Zambian adults.Results:All (100%; n = 11) and 90% (n = 39) of HIV-negative and HIV-positive tuberculosis patients, respectively, had detectable ESAT-6- or CFP-10-specific T cells. The ESAT-6/CFP-10-based ELISPOT assay was positive in 37 out of 54 HIV-negative healthy Zambians, suggesting a 69% prevalence of latentM. tuberculosisinfection. Fewer HIV-positive Zambians possessed ESAT-6/CFP-10-specific T cells, but the impact of HIV infection was less on this assay than on the PPD-based ELISPOT or TST.Conclusion:The ESAT-6/CFP-10-based ELISPOT assay detects active tuberculosis in HIV-positive individuals with high sensitivity. It is more specific, and possibly more sensitive, than PPD-based methods of detecting latentM. tuberculosisinfection, and may potentially improve the targeting of isoniazid preventative therapy to HIV-positive individuals with latent tuberculosis infection.

ISSN:0269-9370    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Background:Various drug transporters of the ATP-binding cassette (ABC) family restrict the oral bioavailability and cellular, brain, testis, cerebrospinal fluid and fetal penetration of substrate drugs. MDRI P-glycoprotein (P-gp) has been demonstrated to transport most HIV protease inhibitors (HPI) and to reduce their oral bioavailability and lymphocyte, brain, testis and fetal penetration, possibly resulting in major limiting effects on the therapeutic efficacy of these drugs.Objectives:To investigate whether the ABC transporters MRP1, MRP2, MRP3, MRP5 and breast cancer resistance protein 1 (Bcrp1) are efficient transporters of the HPI saquinavir, ritonavir and indinavir.Methods:Polarized epithelial non-human (canine) cell lines transduced with human or murine complementary DNA (cDNA) for each of the transporters were used to study transepithelial transport of the HPI.Results:MRP2 efficiently transported saquinavir, ritonavir and indinavir and this transport could be enhanced by probenecid. Sulfinpyrazone was also able to enhance MRP2-mediated saquinavir transport. In contrast, MRP1, MRP3, MRP5, or Bcrp1 did not efficiently transport the HPI tested.Conclusions:Human MRP2 actively transports several HPI and could, based on its known and assumed tissue distribution, therefore reduce HPI oral bioavailability. It may also limit brain and fetal penetration of these drugs and increase their hepatobiliary, intestinal and renal clearance. MRP2 function and enhancement of its activity could adversely affect the therapeutic efficacy, including the pharmacological sanctuary penetration, of HPI.In vivoinhibition of MRP2 function might, therefore, improve HIV/AIDS therapy.

ISSN:0269-9370    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Objectives:To describe acute retroviral syndrome and associated primary viraemia in African children infected with HIV-1 through breastfeeding.Design:Matched case–control study performed retrospectively within the ANRS 049 DITRAME project conducted in 1995–1998 in Abidjan, Côte d'Ivoire.Methods:Cases were children infected by HIV-1 postnatally through breastfeeding. All were HIV-1 negative by DNA PCR at least 45 days of age, but positive on a subsequent sample. This period was considered as surrounding the estimated date of postnatal contamination. Signs/symptoms occurring within this period were recorded in cases and compared with those occuring during the same time period in uninfected breastfed children (controls). For cases, plasma specimens were tested for HIV-1 plasma RNA using the branched DNA assay.Results:Of 22 infants infected postnatally (median age at first positive sample, 185 days; range, 87–373 days), 21 (95.5%) exhibited at least one clinical sign, compared with only 27 of the 44 (61.4%) uninfected children (P= 0.003). Three independent factors were associated with primary HIV-1 infection: mononucleosis-like syndrome [odds ratio (OR), 8.3; 95% confidence interval (CI), 1.4–47.8], dermatitis (OR, 6.0; CI, 1.1–31.9), and generalized lymphadenopathy (OR, 26.5; CI, 2.0–348.4). Among cases, initial median plasma HIV-1 RNA viral load was 5.92 log10copies/ml; this declined to 4.96 log1012 months after the first positive viral load.Conclusions:These results may be useful for the recognition of early paediatric cases of postnatal transmission in Africa and could enable targeting of those who should benefit from HIV RNA or DNA testing for primary HIV-1 infection and their subsequent care.

ISSN:0269-9370    

出版商:OVID    

年代:2002

数据来源: OVID