摘要:

ObjectivesTo evaluate the sensitivity and specificity of RNA and DNA polymerase chain reaction (PCR) for early diagnosis of perinatal HIV-1 infection and to investigate early viral dynamics in infected infants.DesignA cohort study of 395 non-breastfed infants born to HIV-infected mothers in a randomized clinical trial of short-course antenatal zidovudine.MethodsInfant venous blood specimens collected at birth, 2 months, and 6 months of age were tested by qualitative DNA and quantitative RNA PCR (Roche Amplicor). To determine sensitivity and specificity of DNA and RNA PCR, results were compared with later DNA PCR results and to antibody results at 18 months. The HIV-1 subtype of the mother's infection was determined by peptide serotyping.ResultsIn the study, 92% of mothers were infected with subtype E. DNA PCR sensitivity was 38% (20 of 53) at birth, and 100% at 2 months (53 of 53) and 6 months (47 of 47). RNA PCR sensitivity was 47% (25 of 53) at birth and 100% (53 of 53) at 2 months. All samples that tested DNA-positive tested RNA-positive. Specificity was 100% for both DNA and RNA testing at all timepoints. For infected infants, the median viral load of RNA-positive specimens was 407,000 copies/ml (5.6 log10) at birth, 3,700,000 copies/ml (6.6 log10) at 2 months, and 1,700,000 copies/ml (6.2 log10) at 6 months. Infant RNA levels at 2 and 6 months did not differ by maternal zidovudine exposure, or RNA level at birth.ConclusionThis RNA PCR assay performed well for diagnosing perinatal HIV subtype E infection, detecting nearly half of infected infants at birth, and 100% at 2 and 6 months, with 100% specificity. Infected infant viral RNA levels were very high at 2 and 6 months, and were unaffected by maternal zidovudine treatment.

ISSN:1525-4135    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveA continual increase in intrapatient HIV-1 heterogeneity is thought to contribute to evasion of host immune response and eventual progression to AIDS. Tuberculosis (TB) is diagnosed both early and late during the course of HIV-1 disease and may increase diversity of HIV-1 quasispecies by activating the HIV-1 immune response and increasing HIV-1 replication. We examined whether HIV-1 heterogeneity is altered in HIV-1–infected individuals with TB.MethodsBlood samples were obtained from 7 HIV-1–infected patients with active TB (HIV/TB patients) and 9 HIV-1–infected patients (HIV patients) in Kampala, Uganda (CD4 counts of 0–650 cells/&mgr;l and HIV loads of 700–750,000 RNA copies/ml). The C2-C3 region of the HIV-1 envelope gene (env) was amplified by nested polymerase chain reaction (PCR) from lysed peripheral blood mononuclear cells (PBMCs) of each patient, and then subject to sequencing, clonal-quasispecies analysis and heteroduplex tracking analysis (HTA).ResultsHTA ofenvDNA fragments showed increased heterogeneity in the HIV/TB individuals compared with the HIV group. Further sequence and HTA analysis on ten individualenvclones for each patient showed significantly greater HIV mutation frequencies in HIV/TB patients than in HIV patients.ConclusionAn increase in HIV-1 heterogeneity may be associated with a TB-mediated increase in HIV-1 replication. However, a diverse HIV-1 quasispecies population in HIV/TB patients as opposed to tight quasispecies clusters in HIV patients suggests a possible dissemination of lung-derived HIV-1 isolates from the TB-affected organ.

ISSN:1525-4135    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo compare the antiviral activity, effect on CD4 cell count, and tolerability of didanosine (ddI) administered once daily and twice daily in HIV-1–infected patients receiving ddI with stavudine or zidovudine, with or without a protease inhibitor. The study was designed to demonstrate that once-daily dosing of ddI was not inferior to twice-daily dosing.DesignRandomized, open-label, multicenter, two-arm study.Patients and Methods121 HIV-1–infected adults on a stable regimen including ddI (twice daily) during the previous 3 months with a stable viral load <10,000 copies/ml started therapy. Of these, 62 were randomized to switch to a combination that included ddI once daily and 59 to continue with ddI twice daily. The ddI dose was 400 mg/day (250 mg/day if body weight was <60 kg). The primary efficacy analysis compared the time-averaged difference (TAD) between the two treatment regimens in change from baseline log10plasma HIV-1 RNA levels over 24 weeks of therapy, with an equivalence margin between the two treatment groups of <0.5 log10copies/ml.ResultsAt week 24, the mean plasma HIV-1 RNA level had increased by 0.31 and 0.17 log10copies/ml in the ddI once-daily and ddI twice-daily groups, respectively. The time-averaged difference between the two groups in change from baseline plasma HIV-1 RNA levels over 24 weeks was (0.05 log10copies/ml (95% confidence interval, −0.21 to +0.12 log10copies/ml), indicating that the antiviral activity of ddI once daily is similar to that of ddI twice daily. After 24 weeks of treatment, changes from baseline in CD4 cell counts were similar in the two groups. Both regimens were generally well-tolerated.ConclusionsOnce-daily and twice-daily ddI are equally effective at reducing plasma HIV-1 RNA levels when used in a combination regimen with stavudine or zidovudine, with or without a protease inhibitor.

ISSN:1525-4135    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Acute HIV-1 infection (AHI) may present with a clinical picture that represents a diagnostic challenge. We tested the hypothesis that two different routes of infection, that is, sexual versus parenteral, might be associated with a difference in the clinical features of AHI. A prospective cohort of seroconvertors was established in Montréal in private medical clinics and hospitals from February 1996 to May 1999. The prevalence of the symptomatic presentation was almost overlapping within the two groups of newly infected individuals 69% (42 of 61) for men having sex with men (MSM) and 69% (18 of 26) for injection drug users (IDUs;p= .98). Comparison of all types of symptoms and signs as well as their duration was also similar in both groups. Of particular interest, the site of lymph node enlargement was not different despite the estimated sites of intravenous inoculation. Oral and anal ulcers were more frequently observed in MSM than in IDUs (6 versus 0 and 4 versus 1, respectively). Neither the mean CD4+count (514.8 and 414.7 cells/mm3;p= .14) nor the mean viral load (4.45 and 4.70 log copies/ml;p= .40) were different between the two groups at the time of the first study visit. Our study results clearly indicate that health care workers can expect similar clinical presentation of AHI in MSM and in IDUs despite the different routes of infection.

ISSN:1525-4135    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:1525-4135    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo determine the ability of intermediate plasma viral load (pVL) measurements to predict virologic outcome at 52 weeks of follow-up in clinical trials of antiretroviral therapy.MethodsIndividual patient data from three clinical trials (INCAS, AVANTI-2 and AVANTI-3) were combined into a single database. Virologic success was defined to be plasma viral load (pVL) <500 copies/ml at week 52. The sensitivity and specificity of intermediate pVL measurements below the limit of detection, 100, 500, 1000, and 5000 copies/ml to predict virologic success were calculated.ResultsThe sensitivity, specificity, and positive and negative predictive values of a pVL measurement <1000 copies/ml at week 16 to predict virologic outcome at week 52 were 74%, 74%, 48%, and 90%, respectively, for patients on double therapy. For patients on triple therapy, the sensitivity, specificity, and positive and negative predictive values of a pVL measurement <50 copies/ml at week 16 to predict virologic outcome were 68%, 68%, 80%, and 47%, respectively.ConclusionsFor patients receiving double therapy, a poor virologic result at an intermediate week of follow-up is a strong indicator of virologic failure at 52 weeks whereas intermediate virologic success is no guarantee of success at 1 year. For patients on triple therapy, disappointing intermediate results do not preclude virologic success at 1 year and intermediate successes are more likely to be sustained.

ISSN:1525-4135    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

To study the effect of antiretroviral agents on T-lymphocyte counts in HIV-negative individuals, total counts and CD4+and CD8+lymphocyte counts were measured in health care workers (HCW) who had been occupationally exposed to HIV who were untreated (164 HCW, group A), or had received antiretroviral postexposure prophylaxis (PEP). PEP included zidovudine (150 HCW, group B), zidovudine plus lamivudine (48 HCW, group C), or zidovudine, lamivudine, and indinavir (85 HCW, group D), at standard dosage for a mean of 30, 27, and 27 days of treatment, respectively. Lymphocyte values were collected after a mean of 44 days following exposure in group A, 48 days in group B, and 30 days both in groups C and D. Student'st-, nonparametric Mann-Whitney, and Kruskal-Wallis tests were used for statistical analysis. A slight increase in mean CD4 (range, 4.8%–6.7%) and CD8 (range, 1.4%–9.3%) cells/mm3was observed in each group. Gender, PEP duration, side effects, and follow-up time did not correlate with responses. Data did not vary using CD4 and CD8 percentages. These findings seem to reject any direct effects of antiretroviral agents, independent of retroviral inhibition, on proliferation and redistribution of T lymphocytes, as well as the hypothesized braking of lymphocyte apoptosis. The observed variations could reflect biologic variability.

ISSN:1525-4135    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:1525-4135    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

To ascertain the results of standard ABVD chemotherapy (doxorubicin, bleomycin, vinblastine, dacarbazine) in HIV-infected patients with newly diagnosed Hodgkin's disease (HD), a nonrandomized, prospective, multiinstitutional clinical trial was conducted by the AIDS Clinical Trials Group (ACTG), in HIV-infected patients with Hodgkin's disease. All patients received the standard ABVD regimen, with granulocyte–colony-stimulating factor (G-CSF). Antiretroviral therapy was not used. Between May, 1992 and August, 1996, 21 patients were added to the study and treated. The median CD4 count was 113 cells/mm3, and 29% had a history of a clinical AIDS-defining condition before diagnosis of HD. Systemic “B” symptoms were present in 90% at diagnosis. Stage IV HD was present in 67%, with bone marrow involvement in 12 (57%). Nodular sclerosis HD was present in 38%, with mixed cellular disease in 31%. Among all patients entered and treated, complete remission (CR) was attained in 9 (43%; 90% confidence interval [CI], 24%–63%), whereas partial response occurred in 4 (19%), leading to an overall objective response rate of 62% (90% CI, 42%–79%). Despite routine use of G-CSF, 10 patients (47.6%) experienced life-threatening neutropenia, with absolute neutrophil counts <500 cells/mm3. In all, nine opportunistic infections occurred in 6 patients (29%) during the study or shortly thereafter. Median survival was 1.5 years. Results of this study suggest that alternative treatment strategies should be explored, including use of chemotherapy together with antiretroviral therapy.

ISSN:1525-4135    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Longitudinal data were analyzed to determine changes in willingness to participate in HIV vaccine efficacy trials and knowledge of vaccine trial concepts among populations at high risk of HIV-1 infection. Gay men (MSM), male and female injection drug users, and non-injecting women at heterosexual risk were recruited (n= 4892). Follow-up visits occurred every 6 months up to 18 months. Willingness was significantly lower at follow-up visits compared with at baseline. Knowledge levels increased for all study populations. Problematic concepts were possible effects of the vaccine on the immune system and lack of knowledge about efficacy of a vaccine before the start of a trial. For concepts concerning safety, blinding, and guarantees of future participation in trials, MSM men had significant increases in knowledge, but little to no change occurred for the other populations. An increase in knowledge was associated with becoming not willing, particularly among MSM with low knowledge levels. At least half of high-risk participants were consistently willing to participate in future vaccine efficacy trials and with basic vaccine education, knowledge levels increased. Continued educational efforts at the community and individual level are needed to address certain vaccine trial concepts and to increase knowledge levels in all potential study populations.

ISSN:1525-4135    

出版商:OVID    

年代:2000

数据来源: OVID