摘要:

Objective:To determine the influence of heterozygosity for the Δ32 mutant CCR-5 allele on HIV-1 disease progression.Design:HIV-1 disease progression and serum viral load were analysed according to the C-C chemokine receptor (CCR)-5 genotype in 412 Caucasian patients (319 men and 93 women) with a known date of seroconversion, who were enrolled in the SEROCO cohort (median follow-up, 74 months).Results:The frequency of heterozygosity for the mutant allele was 17% and did not differ according to sex or risk factor for HIV infection. Heterozygotes were significantly less likely than patients with two functional alleles to have symptomatic primary infection. Their serum viral load was lower during the 6- to 24-month plateau phase after seroconversion. This difference persisted afterwards, although the rate of decline in CD4+ cells was similar. Kaplan-Meier survival curves showed slower progression to clinical AIDS in heterozygotes during the first 7 years following infection (P< 0.02), the two curves tending to join thereafter (overall log-rank test,P= 0.17). However, the interaction term with time did not reach significance in a Cox model. The overall relative risk of progression was 0.67 (95% confidence interval, 0.38–1.18) and was not influenced by adjustment for age at seroconversion or symptomatic primary infection. After adjustment for early viral load the relative risk was 0.83. Pneumocystis carinii pneumonia and toxoplasmosis were less likely to be the first AIDS-defining illness in heterozygotes than in the other patients (0 versus 24.7% of AIDS cases,P= 0.04), despite similar management.Conclusion:Deletion of oneCCR-5gene allele appears to protect against HIV-1 disease progression, mainly during the early years of the infection. Heterozygosity for the deletion leads to persistently lower viral load, and also seems to protect against some opportunistic infections.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Objective:To determine whether, as predicted by predator–prey dynamics, early withdrawal of antiretroviral therapy, i.e., when the number of CD4+ lymphocytes is still elevated, results in an overshoot of HIV-1 viraemia due to infection of increased numbers of available target cells at that time.Design and methods:Five HIV-1-infected individuals were identified who discontinued antiretroviral therapy for various reasons after 8–19 days, and from whom stored serum samples obtained before, during, and shortly after treatment were available for measurement of HIV-1 RNA load. A mathematical model was designed to assess whether increased target cell availability could quantitatively explain the clinical observations.Results:After therapy withdrawal, increases in the HIV-1 RNA load to levels exceeding pretreatment values by log100.6–1.5 copies/ml were observed after 2–17 days in all four of the individuals who had treatment-induced increases in CD4+ cell counts at the time of therapy withdrawal. Increases in viraemia were maximal within a few days, and subsequently seemed to wane until the pretreatment equilibrium between virus and its target cells was attained. Mathematical modelling confirms that these transient increases in viraemia can be explained by increased availability of target cells at the time of therapy withdrawal.Conclusions:Transient rises in HIV-1 viraemia do occur following early therapy withdrawal. These rises especially warrant consideration in short-term antiretroviral regimens for prevention of mother-to-child transmission, as are being studied in developing countries, since they could result in an increased transmission risk during the post-partum period through breast-feeding. This possibility needs to be investigated urgently.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Objective:To detect the expression CXCR4/fusin in human intestinal epithelial cells and to assess its potential role in the pathway of HIV-1 infection mediated by the alternative gp120 receptor galactosylceramide (GalCer).Methods:GalCer+ (HT-29, HT-29/CD4+) and GalCer2− (Caco-2/Cl2, Cl14 and Cl14/CD4+) human intestinal cell lines were analysed for CXCR4/fusin expression using the monoclonal antibody (MAb) 12G5. This MAb was then evaluated for its ability to inhibit HIV-1 infection in permissive cells. HIV-1 infection was measured by detection of p24 antigen, polymerase chain reaction amplification, and cocultivation with CD4+ cells.Results:CXCR4/fusin was detected on the surface of HT-29 and HT-29/CD4+, but not on Caco-2/Cl2, Cl14 and Cl14/CD4+ cells. Ninety per cent of CXCR4/fusin+ HT-29 and HT-29/CD4+ cells co-expressed GalCer. Infection of HT-29 cells by laboratory isolates of HIV-1 was inhibited by both anti-GalCer and anti-CXCR4/fusin MAbs. Expression of CD4 rendered HT-29 cells sensitive to HIV-1(89.6), a macrophage-tropic isolate that does not recognize GalCer. The 12G5 MAb blocked HIV-1 infection of HT-29/CD4+ cells. In contrast, the expression of HIV-1 receptors, i.e., CD4, GalCer or both, into CXCR4/fusin-negative intestinal cells did not confer sensitivity to HIV-1 infection. The resulting receptor-positive cell lines could, however, bind HIV-1, whereas the original cell lines could not.Conclusion:HIV-1 entry into human intestinal cells involves both GalCer and CXCR4/fusin. HIV-1 isolates such as 89.6 that are able to use CXCR4/fusin as coreceptor, but do not bind to GalCer, do not infect these cells. These data raise the possibility that CXCR4/fusin may function as a coreceptor for HIV-1 entry into CD4−/GalCer+ intestinal epithelial cells.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Objective and design:To determine whether the female genital tract contains factors that affect HIV-1 replication. Cervicovaginal lavage (CVL) samples were collected from HIV-1-seropositive and seronegative women and added to cell cultures.Methods:HIV p24 production was used to measure the effects of CVL on replication of HIVMNin a T-cell line, of a primary isolate in peripheral blood mononuclear cells, or on HIV expression by the latently-infected monocytic U1 cell line. The effects of CVL on the HIV long terminal repeat (LTR) were determined in 1G5 T cells by measuring luciferase activity.Results:Increased replication of HIVMNand a primary isolate were observed in T cells cultured with CVL samples from three out of 38 HIV-infected women, one out of four uninfected high-risk women, and none of 12 low-risk women. The CVL factor increased replication by enhancing virus expression via activation of the HIV LTR. The HIV-inducing activity was highly stable to heat but was sensitive to proteases, indicating that the activity was distinct from heat-labile cytokines including tumour necrosis factor-α.Conclusions:This is the first study to show that a factor which can stimulate HIV-1 replication is present at biologically active levels in the reproductive tract of women. This factor could potentially affect sexual or vertical transmission of HIV-1 by altering genital tract virus load or virus expression.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Objective:Kaposi's sarcoma-associated herpesvirus (KSHV), or human herpesvirus 8, has been implicated as the causative agent of Kaposi's sarcoma. Retrospective studies show that the risk of development of Kaposi's sarcoma is significantly lower in AIDS patients who received ganciclovir or phosphonoformic acid (PFA) therapy. Therefore,in vitroantiviral drug sensitivity of KSHV was studied.Methods:The KSHV genome is a latent episome in lymphoma cells such as the BCBL-1 cell line. Lytic KSHV DNA synthesis is induced by the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate in BCBL-1 cells; this system was used to evaluate the effects of antiviral drugs on KSHV DNA synthesis.Results:Linear (lytic) KSHV DNA synthesis and virus secretion was inhibited in BCBL-1 cell cultures by cidofovir (median inhibitory concentration, 0.05 µM), ganciclovir (5.1 µM) and PFA (97 µM), and by aciclovir (75 µM). Prolonged incubation of BCBL-1 cells with antiviral drugs had no effect on episomal KSHV DNA synthesis.Conclusions:The antiviral drug assay developed shows that KSHV is very sensitive to cidofovir, moderately sensitive to ganciclovir and PFA, and weakly sensitive to aciclovir. Therefore, low doses of cidofovir, or high doses of PFA or ganciclovir could suppress clinical reactivation of KSHV. Antiviral drugs did not inhibit episomal virus DNA synthesis, suggesting that the latent form of viral DNA is replicated by host DNA polymerases. Consequently, no benefit can be expected from antiviral drugs in KSHV-positive B-cell lymphomas or during latency.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Objective:To evaluate the predictive value of pp65 antigenaemia quantitative test for cytomegalovirus (CMV) end-organ disease in patients with advanced HIV infection.Design and patients:A prospective study in AIDS patients or HIV-infected subjects with CD4 count < 150 × 106/l or CD4 percentage < 10% was carried out. Patients with a history of CMV disease or positive viraemia or antigenaemia tests, and subjects under anti-herpes suppressive therapy were excluded. Clinical, ophthalmoscopic, biochemical and virological (antigenaemia test) evaluations were performed at baseline and every 1–3 months until the onset of CMV end-organ disease.Setting:Institutional tertiary care centre.Results:Forty-nine patients were evaluable for this study. End-organ disease was observed in 13 patients, 11 with at least one positive test, two with persistently negative assays. Thirteen patients without CMV disease had at least one positive test, whereas 23 always had negative tests. The 12-month Kaplan–Meier estimate of the incidence of CMV disease in our population was 30.9%, and was 75% in antigenaemia-positive subjects. The negative predictive value (NPV) of the test was 92%, and the positive predictive value (PPV) was 45.8%. However, the NPV of quantitative (> 20 cells) antigenaemia assay was 92.1%, and the PPV was 90.9%.Conclusions:The antigenaemia test is a quick, simple and easy to perform assay for diagnosing CMV infection. The NPV is fairly good, as is the PPV when the quantitative method (> 20 positive cells) is used. This test could be used as an alternative to polymerase chain reaction in order to select patients at higher risk of CMV disease who can be treated with pre-emptive anti-CMV therapy.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Objective:Weight loss in HIV-infected patients is extremely common and is associated with increased morbidity and mortality. Decreased testosterone concentrations occur commonly in patients with HIV disease and are associated with weight loss. This study assessed the effect of testosterone therapy on HIV associated weight loss in patients with AIDS.Methods:Forty HIV-seropositive patients with CD4+ counts of < 2 × 105/l and weight loss greater than 5% of usual body weight were randomized in a double-blind manner to receive 200 mg of testosterone cypionate or placebo intramuscularly every 2 weeks for 3 months. Patients were then crossed to receive the alternate treatment for the next 3 months. Outcome variables included weight, skin fold measurement, a quality-of-life questionnaire, Karnofsky score, T-cell subset analysis, complete blood count, routine blood chemistry measurements and free testosterone concentration.Results:Thirty-nine patients entered the study. Of these, 35 completed the first 3-month period (18 on placebo, 17 on testosterone) and 23 completed the whole 6 month trial. Analysis of these 23 patients did not show any significant differences between testosterone and placebo treatment. Analysis of the first 3 months only for the 35 patients who completed it did not show any significant difference between the effects of testosterone and placebo treatment on weight gain. Patients treated with testosterone reported improved overall well-being (P= 0.03) and a trend towards increased muscle strength (P= 0.08). There was no difference between the two groups in terms of side-effects or other effects on hematopoetic, liver, renal or immune function.Conclusions:Treatment with testosterone cypionate compared with placebo did not result in significant weight gain. Testosterone supplementation did appear to produce an improved overall sense of well-being and possibly some increase in muscle strength. This randomized, double-blinded study does not confirm the results of other recent studies which show potential benefits of testosterone and its analogs when used as a treatment for weight loss in HIV-positive patients.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Method:Recombinant human growth hormone (rhGH) is a newly approved treatment for weight loss and wasting in patients with AIDS. We report a male patient with advanced AIDS who developed hypercalcemia 2 weeks after institution of rhGH therapy.Results:Parathyroid hormone, parathyroid hormone-related peptide and 1,25-dihydroxyvitamin D levels were suppressed, suggesting that hypercalcemia was mediated through alternative mechanisms. The hypercalcemia responded to discontinuation of rhGH and a single dose of intravenous pamidronate disodium and has not recurred in 8 months of follow-up.Conclusion:We believe this to be the first reported case of rhGH-induced hypercalcemia in an HIV-infected patient.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Objectives:To describe the spectrum of opportunistic disease in HIV-infected patients admitted to hospital in Abidjan, Côte d'Ivoire, and to describe the level of immunosuppression at which these diseases occur.Design:Cross-sectional study.Setting:In-patient wards of the University Hospital Infectious Diseases Unit.Patients:A total of 250 adult patients recruited by systematic sampling at the point of hospital admission.Main measures:HIV status; CD4 count; diagnoses, confirmed by microbiological/ radiological investigations whenever possible; and outcome of hospitalization (death or discharge).Results:Overall, 79% patients were HIV-positive. The most frequent diagnoses in HIV-positive patients were septicaemia (20%, with non-typhoid salmonellae,Escherichia coliandStreptococcus pneumoniaethe most common organisms), HIV wasting (16%), meningitis (14%), tuberculosis (TB; 13%), isosporiasis (10%), cerebral toxoplasmosis (7%) and bacterial enteritis (7%). Most HIV-positive patients had evidence of severe immunosuppression: 39% had CD4 counts < 50 × 106/l, 17% had 50–99 × 106/l, and 20% had 100–199 × 106/l. In-hospital mortality among HIV-positive patients was 38% compared with 27% among HIV-negative patients [age-adjusted odds ratio (OR), 1.5; 95% confidence interval (CI), 0.7–2.9]. Among HIV-positive patients, the highest case–fatality rates were among patients with meningitis, toxoplasmosis and TB: in a multivariate analysis the strongest independent risk factors for death were an abnormal level of consciousness (OR, 9.3; 95% CI, 3.5–24.6), a haemoglobin concentration below 8 g/dl (OR, 4.2; 95% CI, 1.4–12.8) and age > 40 years (OR, 3.9; 95% CI, 1.5–10.2).Conclusions:Our data show that, as in industrialized countries, most HIV-infected individuals admitted to and dying in hospital in Abidjan are profoundly immunosuppressed. Potentially preventable infections are the main causes of inhospital morbidity and mortality among HIV-infected persons in Abidjan, and the evaluation of appropriate primary prophylactic regimes is a priority.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID