摘要:

Objectives:To describe the uptake of interventions to reduce mother-to-child transmission of HIV infection.Design:Voluntary confidential reporting of HIV infection in pregnancy and childhood; telephone interview with key professionals in all London maternity units.Subjects and setting:HIV-infected pregnant women and children in the United Kingdom and Ireland.Main outcome measures:Trends in breastfeeding, use of zidovudine, mode of delivery and terminations of pregnancy.Results:Between 1990 and 1995, 14 (4%) out of 314 women diagnosed with HIV infection before delivery breastfed compared with 109 (77%) out of 142 diagnosed after delivery. Since 1994, zidovudine use has increased in each 6-month period (14, 39, 67, and 75%; χ2=17.5,P< 0.001), although in 1995 it was the policy of only 48% of London maternity units to offer zidovudine to HIV-infected women. During 1995, 44% of HIV-infected women were delivered by elective Cesarean section. Since 1990, 20% of women first diagnosed in pregnancy were reported to have their pregnancy terminated.Conclusions:Although detection of previously undiagnosed HIV infection in pregnancy remains low in the United Kingdom, and particularly in London, HIV-infected pregnant women who are aware of their status are increasingly active in taking up interventions to reduce transmission to their infants. If all HIV-infected women attending for antenatal care in London consented to testing and took up interventions and termination of pregnancy at the rates observed in this study, the number of vertically infected babies born in London each year could be reduced from an estimated 41 to 13.

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:CD4+ T cells are the main target for HIV. However, the highest HIV antigen concentration in infected subjects accumulates on the cell surface of follicular dendritic cells in the germinal centres of the lymphoid tissue. Germinal centres contain a T-helper cell subset which expresses CD57 molecules. Here we analysed virus replication and viral load in CD57+CD4+ germinal centre T cells and in the CD4+ T cells found mostly outside germinal centres (CD57−CD4+).Methods:Peripheral blood mononuclear cells and lymph-node cells were prepared, stained for CD4 and CD57 and purified by FACS. Defined cell numbers of CD4+CD57+ cells and CD4+CD57− cells were sorted directly into polymerase chain reaction (PCR) tubes by FACS, equipped with an automated cell deposition unit and analysed by PCR to detect proviral DNA. Based on Poisson distribution, the expected level of infection was calculated. Viral replication was determined by amplifying double-spliced, single-spliced, and full-length transcripts of HIV using serially diluted cDNA of the FACS-sorted cells.Results:An up to 10-fold higher frequency of infected cells was found in the CD57+CD4+ germinal centre T cells compared with CD57−CD4+ T cells. Furthermore, active viral replication was detected almost exclusively in the CD57+CD4+ T cells.Conclusions:The CD57+CD4+ germinal centre T cells are one of the sites of HIV infection and replication that may play a pivotal role in the pathogenesis of HIV infection.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Objective:To determine whether two commercial assays for quantification of plasma HIV-1 RNA levels detect different genetic subtypes of HIV-1 with equal efficiency.Design:Blind testing of stored plasma samples from 95 individuals infected with different genetic subtypes of HIV-1 (27 subtype A, 24 B, 18 C, 18 D, two E, two G, two H, and two J). The HIV-1 subtype had previously been determined by direct sequencing of the V3 domain of theenvgene.Methods:One plasma sample from each individual was tested once by the Roche HIV monitor assay and once by the Organon nucleic acid sequence-based amplification (NASBA) HIV-1 RNA quantitative assay, according to the manufacturers' recommendations. Information about CD4+ lymphocyte counts and antiretroviral treatment was available.Results:The results from the two assays were strongly correlated with each other for subtypes B, C and D, but not for subtype A because many samples had RNA levels close to or below the lower detection limit of the assays. Thus, 15 out of 27 (56%) subtype A samples were negative by the HIV monitor assay and 12 (44%) were negative by the NASBA assay. These frequently occurring negative results among subtype-A-infected individuals were not due to better immunological status, more aggressive antiretroviral treatment, or differences in sample storage conditions.Conclusions:The HIV monitor assay and, possibly to slightly lesser degree, the NASBA assay appear unable to accurately quantify HIV-1 RNA levels in plasma samples from many subtype-A-infected individuals. These problems are likely to be due to primer mismatches and they limit the possibility of using these assays for routine monitoring of HIV-1-infected individuals in many parts of the world.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Objectives:To study the temporal relationships between cytomegalovirus (CMV) viral load and specific UL97 mutations in polymorphonuclear leukocytes (PMNL) and plasma samples from a patient with AIDS who developed ganciclovir-resistant CMV retinitis.Methods:Sequential PMNL and plasma samples were analysed for determination of the CMV viral load using non-molecular methods and a quantitative polymerase chain reaction (PCR) assay. Screening of the same samples for the most common mutations conferring ganciclovir resistance was performed using nested PCR and restriction enzyme analysis.Results:At the time of progression of CMV retinitis (after 6 months of ganciclovir), a rapid increase in the CMV DNA load was found in both PMNL and plasma samples. This increase paralleled the emergence of a specific mutation (V594) in the same samples and recovery of ganciclovir-resistant blood isolates. In this patient, however, the only tests that substantially predicted the progression of CMV disease were the quantitative PCR assay using PMNL and to a lesser extent the pp65 antigenemia assay.Conclusions:Quantitative evaluation of the CMV viral load in PMNL using sensitive assays such as PCR appears to be a promising approach for monitoring antiviral therapy in subjects with AIDS. In addition, common mutations conferring ganciclovir resistance can be detected directly in PMNL and plasma samples.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Objectives:To determine the efficacy of isoniazid 300 mg daily for 6 months in the prevention of tuberculosis in HIV-1-infected adults and to determine whether tuberculosis preventive therapy prolongs survival in HIV-1-infected adults.Design and setting:Randomized, double-blind, placebo-controlled trial in Nairobi, Kenya.Subjects:Six hundred and eighty-four HIV-1-infected adults.Main outcome measures:Development of tuberculosis and death.Results:Three hundred and forty-two subjects received isoniazid and 342 received placebo. The median CD4 lymphocyte counts at enrolment were 322 and 346 × 106/l in the isoniazid and placebo groups, respectively. The overall median follow-up from enrolment was 1.83 years (range, 0–3.4 years). The incidence of tuberculosis in the isoniazid group was 4.29 per 100 person-years (PY) of observation [95% confidence interval (CI) 2.78–6.33] and 3.86 per 100 PY of observation (95% CI, 2.45–5.79) in the placebo group, giving an adjusted rate ratio for isoniazid versus placebo of 0.92 (95% CI, 0.49–1.71). The adjusted rate ratio for tuberculosis for isoniazid versus placebo for tuberculin skin test (TST)-positive subjects was 0.60 (95% CI, 0.23–1.60) and for the TST-negative subjects, 1.23 (95% CI, 0.55–2.76). The overall adjusted mortality rate ratio for isoniazid versus placebo was 1.18 (95% CI, 0.79–1.75). Stratifying by TST reactivity gave an adjusted mortality rate ratio in those who were TST-positive of 0.33 (95% CI, 0.09–1.23) and for TST-negative subjects, 1.39 (95% CI, 0.90–2.12).Conclusions:Overall there was no statistically significant protective effect of daily isoniazid for 6 months in the prevention of tuberculosis. In the TST-positive subjects, where reactivation is likely to be the more important pathogenetic mechanism, there was some protection and some reduction in mortality, although this was not statistically significant. The small number of individuals in this subgroup made the power to detect a statistically significant difference in this subgroup low. Other influences that may have diluted the efficacy of isoniazid include a high rate of transmission of new infection and rapid progression to disease or insufficient duration of isoniazid in subjects with relatively advanced immunosuppression. The rate of drug resistance observed in subjects who received isoniazid and subsequently developed tuberculosis was low.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Objective:To perform a cost-effectiveness analysis of strategies to prevent cytomegalovirus (CMV) disease.Method:Markov model and published data.Patients:Hypothetical HIV-infected patients with CD4 cell counts ≤ 50 × 106/l and positive CMV serologies.Interventions:Oral ganciclovir daily versus plasma CMV DNA polymerase chain reaction (PCR) testing every 3 months with oral ganciclovir for patients with positive tests.Outcome measures:The number of CMV disease cases prevented by the interventions, life expectancy, disease-free life expectancy, and the cost to extend life by 1 year.Results:Oral ganciclovir preventive therapy reduces the lifetime number of CMV disease cases by 50 per 1000 cohort, extends life expectancy by 5 days and disease-free life expectancy by 18 days, and costs US$ 1762 517 per year of life extended. Periodic PCR testing reduces the lifetime number of CMV disease cases by eight per 1000 cohort, extends life expectancy by 1 day and disease-free life expectancy by 3 days, and costs US$ 495 158 per year of life extended. The prevention strategies could be acceptably cost effective only under a combination of optimistic assumptions and reduced costs.Conclusions:Oral ganciclovir preventive therapy and periodic plasma testing for CMV PCR with oral ganciclovir for those with positive tests result in small benefits at great cost. They are not cost-effective prevention strategies for persons with advanced HIV infection and positive CMV serologies.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background:Cytomegalovirus (CMV) disease is a major cause of morbidity in patients with HIV infection. Despite treatment, CMV retinitis causes substantial visual loss, especially in patients with CD4 cell counts below 50 × 106/l. Although routine ophthalmological screening of these patients has been recommended, no controlled trials have evaluated how frequently it should be performed. The aim of this study was to assess whether CMV polymerase chain reaction (PCR) results could direct ophthalmological screening to patients at high risk of CMV retinitis.Methods:In a prospective study of HIV-positive patients with CD4 cell counts below 50 × 106/l, CMV viraemia was detected by qualitative PCR of whole blood. Patients who were CMV PCR-viraemic were allocated to monthly virological and ophthalmological follow-up; patients who were PCR-negative received 3-monthly virological and ophthalmological follow-up. CMV viral load was determined in all CMV-positive samples using a quantitative competitive PCR.Results:Nineteen out of 97 patients developed CMV disease over the first 12 months of the study. Sixteen (59%) out of 27 patients who were CMV-positive developed disease compared with three (4%) out of 70 of patients who were PCR-negative (P= 0.0001). A positive CMV PCR result was significantly associated with the development of disease (P= 0.0001), with a relative hazard of 20.15 [95% confidence interval (CI), 5.80–69.98]. Median CMV viral load was significantly higher in those individuals who went on to develop CMV disease (P= 0.02). In PCR-positive patients, each 0.25 log10increase in viral load increased the risk of disease (relative hazard, 1.37; 95% CI, 1.15–1.63;P= 0.0004).Conclusions:CMV PCR predicts the development of CMV disease and can be used to target ophthalmological resources to those patients at highest risk of retinitis. Asymptomatic patients who are PCR-positive represent a high-risk group in whom controlled trials of pre-emptive therapy could be conducted.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Objective:To assess the antiretroviral effect of a combination of zidovudine, didanosine, lamivudine and saquinavir in plasma, peripheral blood mononuclear cells (PBMC) and lymph-node mononuclear cells (LNMC) after 8 weeks.Methods:Ten HIV-1 antiretroviral therapy-naive patients were given a combination of oral zidovudine (200 mg three times daily), oral didanosine (200 twice a day), oral lamivudine (150 mg twice a day) and oral saquinavir (600 mg three times daily). HIV-1 plasma RNA was measured by quantitative reverse transcriptase (RT)-polymerase chain reaction (PCR). Infectious HIV-1 in PBMC and LNMC was measured by a coculture technique. HIV-1 RNA in PBMC and LNMC was quantified by RT-PCR. Proviral DNA titres in PBMC and LNMC were measured by endpoint dilution PCR. CD4 T-cells were analysed by flow cytometry.Results:CD4 cell counts rose in all patients (mean increase of 125 ± 71 CD4 cells × 106/l) and the benefit was greater for patients with fewer than 350 CD4 cells × 106/l (mean increase of 159 ± 74 CD4 cells × 106/l). Plasma HIV-1 RNA decreased exponentially in all patients (mean decrease of 3.1 log10after 8 weeks with a mean half-life of 2.2 ± 0.6 days). HIV-1 RNA showed a decrease of 3.07 log10in PBMC and of 2.1 log10in LNMC. The decrease in plasma HIV-1 RNA was consistently associated with the decrease in LNMC. These data were supported by a concomitant drop of HIV-1 infectious titres in PBMC (mean decrease of 1.41 log10) and in LNMC (mean decrease of 2.54 log).Conclusions:These data show a significant antiretroviral effect of this four-drug combination in blood and lymphoid tissues. However, a greater decrease in HIV-1 RNA was observed in PBMC and in plasma than in lymph node cells.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Objective:To establish a cohort of high-risk individuals suitable for HIV-prevention trials, and to measure changes in sexual behaviour and sexually transmitted disease (STD) incidence after a behavioural intervention.Design:Prospective cohort study in trucking company depots in Mombasa, Kenya.Participants:A total of 556 male HIV-seronegative employees of trucking companies.Interventions:HIV serological testing, individual counselling, condom promotion, STD diagnosis and management.Main outcome measures:Sexual risk behaviour and symptomatic STD incidence.Results:Using time-trend modelling, significant declines in self-reported high-risk sexual behaviour were demonstrated during a 1-year follow-up. The percentage of men reporting any extramarital sex during the 3-month period prior to a follow-up visit decreased from 49% during the first quarter of follow-up to 36% during the last quarter (P< 0.001). The decline in reported female sex worker contact was from 12% to 6% (P= 0.001). Approximately 30% of men reported consistent condom use during extramarital sex and this percentage remained unchanged during the study period. The incidence of STD declined from 34 per 100 person years (PY) during the first quarter to 10 per 100 PY during the last quarter (P= 0.001). Significant reductions in gonorrhoea (15 to five cases per 100 PY,P= 0.04), non-gonococcal urethritis (10 to two cases per 100 PY,P= 0.05), and genital ulcer disease (nine to two cases per 100 PY,P= 0.02) were observed.Conclusions:Among truck company workers who participated in a cohort study in Mombasa, Kenya, there was a significant decrease in sex with high-risk partners, but no change in condom use. The change in heterosexual risk behaviour was accompanied by a significant decrease in incidence of gonorrhoea, non-gonococcal urethritis, and genital ulcer disease.

ISSN:0269-9370    

出版商:OVID    

年代:1997

数据来源: OVID