摘要:

Osteonecrosis has been increasingly associated with HIV disease throughout the 1990s, and the incidence appears to be rising. The hip is most commonly involved and often bilaterally. Although anecodotal reports suggest an association between osteonecrosis and highly active antiretroviral therapy, controlled epidemiologic studies do not support a direct link. Many patients with osteonecrosis have established risk factors, some of which may be related to HIV disease or its therapy, including corticosteroid use and hyperlipidemia. Alcoholism, hypercoagulability, megesterol acetate use, immune reconstitution, and other factors may also contribute. Plain radiographs and magnetic resonance imaging are the cornerstones of diagnosis. Management is dependent on the stage of bone disease and ranges from observation to total joint arthroplasty. Clinicians may help to prevent HIV-associated osteonecrosis by encouraging patients to limit their exposure to the established risk factors for the disease.

ISSN:0269-9370    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background:Tenofovir is a novel nucleotide analogue recommended for use in HIV-1 infected treatment-experienced patients. Recent data suggest an effect on Hepatitis B virus (HBV) replication. We therefore investigated the use of tenofovir in HIV-1 and HBV co-infected individuals.Methods:Twenty HIV-1/HBV co-infected patients with a median of 108 weeks lamivudine experience (range, 0–270 weeks) received tenofovir 245 mg daily in addition to or as part of their combination antiretroviral therapy. Their immunologic parameters and HIV-1 RNA and HBV DNA viral loads were followed over a period of 52 weeks. In addition, their HBV DNA polymerase was sequenced at baseline to measure the frequency of YMDD mutations that are associated with lamivudine resistance.Findings:A significant decrease in HBV DNA viral load (4 × log10) and alanine aminotransferase levels was observed. There were no significant overall differences between the lamivudine-experienced (n = 15) and -naive (n = 5) individuals and tenofovir was well tolerated. Five patients (25%) underwent HBe antigen seroconversion during the study period. Out of the 15 lamivudine-experienced individuals, 10 had YMDD mutations and one had YIDD mutations in HBV DNA.Interpretation:These results indicate that 52 weeks of tenofovir in addition to antiretroviral therapy is active against HBV, and it appears to overcome lamivudine resistance.

ISSN:0269-9370    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Objective:To characterize the subtype C strains of HIV type 1 that circulate in Brazil, especially those originated from the southern part of the country.Design and methods:One hundred and twelve HIV-1-positive subjects had their plasma viral RNA extracted. Protease (PR) and reverse transcriptase (RT) genomic regions were polymerase chain reaction-amplified and sequenced for subtype determination. Subtype C strains were selected and compared to other strains of this subtype from the database, and specific amino acid signature patterns were searched.Results:Brazilian subtype C viruses form a very strong monophyletic group when compared to subtype C viruses from other countries and presented specific signature amino acids. Recombinants between subtype C and B viruses have been documented in areas of co-circulation. The incidence of primary PR and RT inhibitor resistance mutations in drug-naïve subjects was observed. An increasing number of secondary resistance mutations was also seen, some of which are characteristic of subtype C-related sequences.Conclusions:Introduction of subtype C of HIV-1 in Brazil was likely a single event of one or a mixture of similarly related strains. Recombination between subtype C and B viruses is an ongoing process in the country. Primary and secondary drug resistance mutations were observed, although some of the secondary mutations could be associated with subtype C molecular signatures. Subtype-specific polymorphisms of PR and RT sequences found in this subtype C Brazilian variant might influence this emergence and have an impact on HIV treatment and on vaccine development in the country.

ISSN:0269-9370    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Objective:To test agent and cell-type specificity in insulin resistance induced by prolonged exposure to HIV protease inhibitors (HPI), and to assess its relation to the direct, short-term inhibition of insulin-stimulated glucose uptake.Methods:Following prolonged (18 h) and short (5–10 min) exposure to HPI, insulin-stimulated glucose transport, protein kinase B (PKB) phosphorylation, and GLUT4 translocation were evaluated in 3T3-L1 adipocytes, fibroblasts, L6 myotubes, and L6 cells overexpressing a myc tag on the first exofacial loop of GLUT4 or GLUT1.Results:Prolonged exposure of 3T3-L1 adipocytes to nelfinavir, but not to indinavir or saquinavir, resulted in increased basal lipolysis but decreased insulin-stimulated glucose transport and PKB phosphorylation. In addition, impaired insulin-stimulated glucose uptake and PKB phosphorylation were also observed in the skeletal muscle cell line L6, and in 3T3-L1 fibroblasts. Interestingly, this coincided with increased basal glucose uptake as well as with elevated total-membrane glucose transporter GLUT1 protein content. In contrast to these unique effects of nelfinavir, the mere presence of any of the agents in the 5 min transport assay inhibited insulin-stimulated glucose-uptake activity. This appeared to be caused by direct and specific interaction of the drugs with GLUT4 fully assembled at the plasma membrane, since insulin-stimulated cell-surface exposure of an exofacial myc epitope on GLUT4 was normal.Conclusions:Independent mechanisms for HPI-induced insulin resistance exist: prolonged exposure to nelfinavir interferes with insulin signaling and alters cellular metabolism of adipocytes and muscle cells, whereas a direct inhibitory effect on insulin-stimulated glucose uptake may occurs through specific interaction of HPI with GLUT4.

ISSN:0269-9370    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Objective:Under some circumstances the HIV virus may infect cells that do not express receptors essential to HIV-entry. We hypothesized that platelet- and megakaryocyte-derived microparticles (MP) could play a role in such infections. MP are circular membrane fragments shed from the surface of eukaryotic cells. After adhesion to target cells, MP may transfer membrane-associated proteins to these cells. We found that peripheral blood platelet- (PMP) and megakaryocyte-derived MP (MegaMP) that highly express CXCR4 may transfer this receptor from the surface of platelets or megakaryocytes to the surface of CXCR4-null cells.Design:Since this mechanism could potentially allow CD4+/CXCR4-null cells to become infected by T-tropic HIV, we incubated several human CD4+/CXCR4-null cells such as normal erythroblasts, glioblastomas U87, MAGI and hematopoietic cell lines UT-7, HEL and TF-1 with PMP or MegaMP. We found that these cells became CXCR4+. We next exposed these cells to X4-HIV (IIIB) and evaluated their susceptibility to infection by PCR, ELISA, and morphological analysis.Results:We observed in all instances that after CD4+/CXCR4-null cell lines ‘acquired’ CXCR4 from PMP or MegaMP, they could became infected by X4 HIV.Conclusions:We postulate that both PMP and MegaMP may play a novel and important role in spreading HIV-1 infection by transferring the CXCR4 co-receptor to CD4+/CXCR4-null cells.

ISSN:0269-9370    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Objective:To study the effect of highly active antiretroviral therapy (HAART) with and without hydroxyurea (HU) on changes in plasma viral load (VL) set-point, and on HIV-1-specific responses, after five cycles of structured treatment interruptions (STI).Methods:A group of 20 patients taking HAART for chronic HIV infection with VL < 20 copies/ml were randomized to continue HAART or HAART plus HU for 24 weeks followed by five STI cycles. HU was also stopped in cycles 1–3 but continued in cycles 4 and 5. The number of individuals maintaining a VL set-point < 5000 copies/ml during the fifth interruption were determined.Results:VL remained < 5000 copies/ml in eight out of nine patients in the HU group and in four out of ten patients in the HAART group after a median 48 weeks of follow-up after the fifth interruption (P =0.039). By STI cycle 5, there was a significant increase in the neutralizing activity (NA), in both magnitude and breadth of the total cytotoxic T lymphocyte (CTL) response and in lymphoproliferative response (LPR) from baseline. No significant differences were observed between HAART and HU groups in NA, CTL and LPR at any time-point. There were no differences in the NA titers at any time-point between responder and non-responder patients. There was a trend for higher CTL and LPR levels in responder patients (P =0.10).Conclusions:In this randomized, controlled study of STI with cycles of HAART or HAART plus HU, a lower peak VL rebound and a lower VL set-point was achieved in patients continuing HU while other drugs were discontinued. HU did not blunt anti-HIV-1-specific responses; however, control of VL did not correlate with anti-HIV-1-specific cellular immune responses.

ISSN:0269-9370    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Objectives:To determine the levels of residual HIV DNA and RNA in blood and gut reservoirs in aviremic patients, assess correlations among compartmental measurements of HIV burden, and evaluate association with clinical parameters.Design:Cross-sectional analysis of baseline data only, on 40 patients enrolled in phase II study evaluating efficacy of autologous gene-modified CD4+ and CD8+ T cells. All patients were on stable antiretroviral regimen with undetectable plasma HIV RNA (< 50 copies/ml).Methods:Measurements repeatedly performed over 8–12 weeks pre-intervention: blood HIV DNA, analysis of rectal mucosa-associated lymphoid tissue for both HIV RNA and HIV DNA, and quantitative co-culture of HIV from CD8-depleted peripheral blood mononuclear cells (PBMC).Results:Quantifiable levels of HIV detected in compartments despite undetectable levels of plasma HIV RNA: HIV co-culture of PBMC (88%), blood HIV DNA (95%), rectal biopsy HIV DNA (95%), rectal biopsy HIV RNA (65%). A significant correlation existed among various measures of HIV burden (HIV co-culture, blood HIV DNA, rectal biopsy HIV RNA and DNA) but not between assays and clinical parameters [duration of highly active antiretroviral therapy (HAART), type of HAART]. All assays had comparable or less variability than in plasma viral load assays; HIV co-culture had the highest coefficient of variability whereas the blood HIV DNA assay had the lowest and was considered the most reliable assay.Conclusions:The data support safety, feasibility and high compliance of quantifying reservoirs of residual HIV in treated subjects with undetectable plasma HIV RNA. Lack of correlation between levels of HIV in residual reservoirs and duration of HAART suggests treatment-mediated viral suppression alone does not lead to reproducible decay in HIV reservoirs.

ISSN:0269-9370    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Objective:To compare compliance and infant HIV-1 infection risk at 6 weeks with the Thai-CDC and HIVNET-012 antiretroviral regimens in a field setting.Design:Randomized clinical trial.Setting:Tertiary hospital antenatal clinic in Nairobi, Kenya.Participants:HIV-1 infected women referred from primary care clinics.Interventions:Thai-CDC zidovudine regimen or HIVNET-012 nevirapine regimen.Main outcome measures:Women were considered compliant if they used ⩾ 80% of the doses. Infants were tested for HIV-1 at 6 weeks.Results:Seventy women were randomized to Thai-CDC and 69 to HIVNET-012 regimens. More women were compliant with the antenatal (86%) than the intrapartum (44%) Thai-CDC regimen doses (P= 0.001). Ninety-seven per cent took the maternal and 91% gave the infant dose of the HIVNET-012 regimen (P= 0.2). Overall, 41% were compliant with the Thai-CDC regimen and 87% with the HIVNET-012 regimen (P< 0.001). Compliance with the Thai-CDC regimen was associated with partner support of antiretroviral use [odds ratio (OR), 3.0;, 95% confidence interval (CI), 1.0–9.1] and knowledge at recruitment that antiretroviral drugs could prevent infant HIV-1 (OR, 2.9; 95% CI, 1.0–8.1). Compliance with the HIVNET-012 regimen was associated with partner notification (OR, 8.0; 95% CI, 1.5–50) and partner willingness to have HIV-1 testing (OR, 7.5; 95% CI, 1.4–40). There was a trend for a higher risk of transmission with the HIVNET-012 regimen than with the Thai-CDC regimen (22% versus 9%;P= 0.07).Conclusion:Compliance with the Thai-CDC and HIVNET-012 regimens was comparable to that in efficacy trials. Partner involvement, support and education on perinatal HIV-1 prevention may improve compliance and increase the number of infants protected from HIV-1 infection.

ISSN:0269-9370    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background:Although the incidence ofPneumocystis cariniipneumonia (PCP) has declined, mortality of patients who require intensive care for this disease remains high. Highly active antiretroviral therapy (HAART) might alter the course of PCP either via effects on the immune system or through anti-Pneumocystisactions; however, HAART has not been studied in patients acutely ill with PCP.Objective:To assess the effects of HAART on outcome of patients admitted to the intensive care unit (ICU) with PCP.Design and setting:Retrospective cohort study carried out at a University-affiliated county hospital.Participants:Fifty-eight HIV-infected adults with PCP admitted to an ICU from 1996 to 2001.Measurements:A standardized chart review was performed to collect information on demographic variables, hospital course, and use of antiretroviral therapy. Outcome measured was death while in the ICU or hospital.Results:A total of 20.7% of patients were either receiving HAART or were started on therapy while hospitalized. Mortality in this group was 25%, whereas mortality in those not receiving therapy was 63% (P= 0.03). Multiple logistic regression analyses adjusting for potential confounders showed that HAART started either before or during hospitalization was associated with a lower mortality [odds ratio (OR), 0.14; 95% confidence interval (95% CI), 0.02–0.84;P= 0.03). The need for mechanical ventilation and/or development of a pneumothorax (OR, 20.9; 95% CI, 1.9–227.2;P= 0.01) and delayed ICU admission (OR, 9.7; 95% CI, 2.2–42.1;P= 0.002) were associated with increased mortality.Conclusions:Use of HAART is an independent predictor of decreased mortality in severe PCP and may represent a potential therapy to improve outcome in this disease.

ISSN:0269-9370    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Objective:To evaluate the evolving characteristics of HIV-related Hodgkin's lymphoma (HL) and survival of affected patients since the introduction of highly active antiretroviral therapy (HAART).Design and methods:A retrospective single-institution study was performed over a 15-year follow-up period. For statistical analysis, patients were categorized into a pre-HAART period (1987–1996, n = 61) and a post-HAART period (1997–2001, n = 47).Results:HL characteristics were similar in both groups. The chemotherapy regimens used did not differ significantly, although the MOPP/ABV regimen (mechlorethamine, vincristine, procarbazine substituted by cyclophosphamide since 2000, and prednisone /adriamycin, bleomycin, vinblastin) has progressively replaced the ABVD regimen (adriamycin, bleomycin, vinblastin, dacarbazine). A slight increase in the complete response rate was noted in the post-HAART population (74.5%) versus the pre-HAART population (64.5%), and the probability to relapse was not different between the two groups. Patients diagnosed since 1997 had a higher probability for prolonged survival with a median survival time not reached versus 19 months in the pre-HAART period. The estimate 2-year survival probability was 45% [95% confidence interval (CI), 32.3–57.8% in the pre-HAART period, and 62% (95% CI, 46.7–77.1%) in the post-HAART period (P= 0.03). This decreased mortality was associated with a decrease in AIDS-associated deaths. In the post-HAART period, 12 patients were naive to any antiretroviral therapy and 31 were already on HAART at the time of HL diagnosis. Twenty of them had a plasma HIV-RNA below 500 copies/ml. The response rate and the overall survival were not statistically different in these patients.Conclusions:HL still occurs in patients with HAART-induced HIV suppression. However, overall survival has significantly improved since the introduction of HAART.

ISSN:0269-9370    

出版商:OVID    

年代:2003

数据来源: OVID