摘要:

ObjectiveTo investigate the role of HIV-1 envelope subtypes on disease progression in a rural cohort of Ugandan adults where two major HIV-1 subtypes (A and D) exist.MethodsParticipants of a clinical cohort seen between December 1995 and December 1998 had blood collected for HIV-1 subtyping. These included prevalent cases (people already infected with HIV at the start of the study in 1990) and incident cases (those who seroconverted between 1990 and December 1998). HIV-1 subtyping was carried out by heteroduplex mobility assay and DNA sequencing in the V3envregion. Disease progression was measured by the rate of CD4 lymphocyte count decline, clinical progression for the incident cases as time from seroconversion to AIDS or death, to first CD4 lymphocyte count < 200 × 106/l and to the World Health Organization clinical stage 3. All analyses were adjusted for age and sex.ResultsOne hundred and sixty-four individuals, including 47 prevalent and 117 incident cases, had V3envsubtype data of which 65 (40%) were subtyped as A and 99 as D. In the incident cases, 44 (38%) were subtyped as A and 73 as D. There was a suggestion that for most end-points A had a slower progression than D. The cumulative probability of remaining free from AIDS or death at 6 years post-seroconversion was 0.72 [95% confidence interval (CI), 0.50 to 0.85] for A and 0.58 (95% CI, 0.42 to 0.71) for D, and the adjusted hazard ratio of subtype D compared to A was estimated to be 1.39 (95% CI, 0.66 to 2.94;P= 0.39). The estimated difference in rates of decline in square root CD4 lymphocyte counts was −0.41 per year (95% CI, −0.98 to 0.15;P= 0.15).ConclusionThis study suggests that although subtype A may have a slower progression than D, HIV-1 envelope subtype is not a major factor in determining the progression of HIV-1 disease in a rural population in Uganda.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesTo asses the role of the RNAPII carboxy-terminal domain (CTD) phosphatase FCP1 on HIV-1 Tat-mediated transactivation.DesignConstruction of expression vectors encoding FCP1 phosphatase and analysis of their functions on Tat activity.MethodsBasal and Tat-mediated transactivation of HIV-1 long terminal repeat (LTR)-driven transcription was compared, by transient transfections, in the presence of FCP1 phosphatase. Protein interactions were analysed byin vitrobinding assays.ResultsFCP1 specifically and effectively represses Tat transactivation but not HIV-1 LTR-basal transcription. Protein interaction assays demonstrated that FCP1 specifically and directly binds Tatin vitro.ConclusionThe specific and efficient inhibitory function of FCP1 highlights the important role of this CTD-phosphatase in Tat-mediated transactivation, and it suggests that FCP1 might represent a specific target for modulation of Tat activity in infected cells.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Viral drug susceptibility is associated with virologic response to new treatments. Standardized drug resistance tests are now available, and data from some clinical trials suggest that the use of drug resistance testing may be associated with improved virologic outcome. However, drug resistance testing is complex in terms of performance, interpretation and clinical application.HIV-1 drug resistance testing is used across Europe in patient management, but not in a consistent manner. This is due to differences in the national approaches to treatment, treatment management and reimbursement, as well as availability of tests. National guidelines only exist in some countries. In addition, the laboratory quality assurance and quality control standards are not applied uniformly. The EuroGuidelines Group was established to formulate clinical as well as laboratory guidelines for the use of HIV-1 drug resistance testing that are specific for the European setting. The group is comprised of academic clinicians and virologists, scientist from the industry and representatives of the patient community.The panel of experts will review these guidelines and update them on a yearly basis as new scientific evidence becomes available.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo examine the safety and the immunologic and virologic consequences of corticosteroid use in HIV-1 infection.MethodsA randomized, double-blinded, placebo-controlled trial of corticosteroid administration in 41 patients with advanced HIV-1 infection. Patients had a baseline median CD4 cell count of 131 × 106cells/l at enrollment and 85% had a history of opportunistic infection. All but one of the patients had been taking stable antiretroviral regimen, including a protease inhibitor in 36, for a median duration of 158 days. Patients were randomized to 8 weeks of prednisone 0.5 mg/kg daily or placebo.ResultsNo AIDS-defining events occurred; two patients in each group developed oral candidiasis, and two patients on prednisone developed mild herpes simplex flares. None who developed oral candidiasis or herpes simplex was receiving prophylaxis and each responded promptly to therapy. In the prednisone group, two patients developed hyperglycemia and one diabetic increased insulin requirements. CD4 cell counts and plasma HIV-1 RNA levels did not change, but plasma tumor necrosis factor α levels and CD38+CD8+ cells decreased significantly in those taking prednisone.ConclusionShort-term prednisone administration is well tolerated and reasonably safe in advanced HIV-1 disease and decreases immune activation without effects on HIV-1 RNA levels or CD4 cell counts. These results suggest that, in stable HIV-1 disease, these immune activation markers are more likely consequences of but not inducers of HIV-1 replication.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveLipid disorders associated with the use of protease inhibitors may contribute to the premature development of atherosclerosis. The purpose of the present study was to determine whether the administration of a protease inhibitor-containing regimen to middle-aged (30–50 years) HIV-infected individuals for 6 months or longer is associated with an increased prevalence of atherosclerosis.MethodsHigh-resolution B-mode ultrasound imaging was used to visualize the femoral and carotid arteries of 68 HIV-negative and 168 HIV-infected individuals, including 136 patients who had received protease inhibitors for 26.8 ± 8.9 months (mean ± SD). Atherogenic plaques were defined as a thickening of the intima–media ⩾ 1200 mm.ResultsThe proportion of participants with one or more plaques was higher in the HIV-infected group in comparison with the HIV-negative group (55 versus 38%;P= 0.02), and so was the prevalence of cigarette smoking (61 versus 46%;P= 0.03) and hyperlipidaemia (56 versus 24%;P< 0.001). The presence of plaque was independently associated with age, male gender, plasma low-density lipoprotein cholesterol levels and smoking. In univariate logistic regression analysis, an association was also found with HIV infection. Among HIV-infected subjects protease inhibitor therapy was not associated with the presence of plaque.ConclusionsA large proportion of the middle-aged HIV-infected individuals examined during this study had one or more atherosclerotic plaques within the femoral or carotid arteries. The presence of peripheral atherosclerosis within this population is not associated with the use of protease inhibitors, but rather with ‘classic’ cardiovascular risk factors such as smoking and hyperlipidaemia, which are amenable to interventions.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesThe outcome ofPneumocystis cariniipneumonia (PCP) in HIV-infected infants is poor, and the role of cytomegalovirus (CMV) co-infection in the course and outcome of PCP is unclear. This study describes the prevalence, clinical characteristics, management and changes in survival over time of vertically HIV-infected infants developing PCP and/or CMV infection.MethodsData on children with HIV, born in the UK and Ireland and reported to the National Study of HIV in Pregnancy and Childhood, with PCP and/or CMV were combined with clinical information collected from reporting paediatricians.ResultsBy April 1998, 340 vertically HIV-infected children had been reported, of whom 93 had PCP and/or CMV, as their first AIDS indicator disease; 85 (91%) were infants. Among infants with PCP, 79% were born to mothers not diagnosed as HIV infected, and there was an independent and statistically significant association with breast-feeding, being black African, and developing CMV disease. Median survival after PCP and/or CMV was significantly better in those born between 1993 and 1998 compared with those born before 1993 (P= 0.009), and worse than after other AIDS diagnoses (P= 0.01). Infants with dual infection were more likely to be ventilated (P= 0.003) and receive corticosteroids (P= 0.002) than those with PCP alone.ConclusionAlthough survival from PCP and CMV has improved over time, these remain serious and potentially fatal infections among infants in whom maternal HIV status is not recognized in pregnancy. Breast-feeding increases the risk of combined PCP and CMV infection, which is associated with severe disease.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo determine whether highly active retroviral therapy (HAART) is associated with better neurocognitive outcome over time among HIV-infected women with severely impaired immune function.MethodsA semiannual neurocognitive examination on four tasks was administered: Color Trail Making, Controlled Oral Word Association, Grooved Pegboard and Four-Word Learning. This protocol was initiated in the HIV Epidemiological Research study (HERS) study when a woman's CD4 cell count fell to < 100 × 106cells/l. Immune function (CD4), viral load status and depression severity (CESD) were also assessed semi-annually, along with an interview to determine medication intake and illicit drug use.ResultsHAART was not available to any participant at the time of enrollment (baseline), while 44% reported taking HAART at their most recent visit (mean duration of HAART 36.3 ± 12.6 months). HAART-treated women had improved neurocognitive performance compared with those not treated with HAART. Women taking HAART for 18 months or more showed the strongest neurocognitive performance with improved verbal fluency, psychomotor and executive functions. These functions worsened among women not taking HAART. Substance abuse status, severity of depressive symptoms, age and educational level did not influence the HAART treatment effects on neurocognitive performance. Neurocognitive improvements were strongly associated with the magnitude of CD4 cell count increases.ConclusionsHAART appeared to produce beneficial effect on neurocognitive functioning in HIV-infected women with severely impaired immune systems. Benefits were greatest for women who reported receiving HAART for more than 18 months.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesTo determine the effectiveness of potent antiretroviral therapy in reducing opportunistic infections (OI) as both a presenting event and subsequent to an AIDS-defining event.Design and methodsA total of 543 seroconverters and 1470 men with AIDS were compared for the time to development of OI as the presenting AIDS event and as a subsequent event in the 1984–1989, 1990–1992, 1993–1995, and 1996–1998 periods, when the major treatments were no therapy, monotherapy, combination therapy, and potent antiretroviral therapy, respectively.ResultsThe seroconverters suffered 132 OI and the participants with AIDS had 717 OI. The relative hazard (RH) of OI as the presenting AIDS event declined by 81% in the calendar period when potent antiretroviral therapy was available compared with the monotherapy period. Declines were observed forMycobacterium aviumcomplex, cytomegalovirus disease, and esophageal candidiasis, but were statistically significant only forPneumocystis cariniipneumonia. The RH of OI as a secondary infection dropped by 77% in the last calendar period compared with the monotherapy period. A significant decline was observed for all four OI. Prophylactic drug use did not increase in the era of potent antiretroviral therapy.ConclusionThe hazard of OI in the era of potent antiretroviral therapy has declined dramatically compared with the era of monotherapy, despite the concurrent decrease in the use of prophylactic drugs. Physicians should consider whether it is necessary to include prophylactic drugs as part of the complex drug regimen for patients on potent antiretroviral therapy.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo test thea priorihypothesis that longer duration of ruptured membranes is associated with increased risk of vertical transmission of HIV.DesignThe relationship between duration of ruptured membranes and vertical transmission of HIV was evaluated in an individual patient data meta-analysis.MethodsEligible studies were prospective cohort studies including at least 100 mother–child pairs, from regions where HIV-infected women are counselled not to breastfeed. Analyses were restricted to vaginal deliveries and non-elective Cesarean sections; elective Cesarean section deliveries (those performed before onset of labour and before rupture of membranes) were excluded.ResultsThe primary analysis included 4721 deliveries with duration of ruptured membranes ⩽ 24 h. After adjusting for other factors known to be associated with vertical transmission using logistic regression analysis to assess the strength of the relationship, the risk of vertical HIV transmission increased approximately 2% with an increase of 1 h in the duration of ruptured membranes [adjusted odds ratio, 1.02; 95% confidence interval, 1.01–1.04; for each 1 h increment]. There were no significant interactions of duration of ruptured membranes with study cohort or with any of the covariates, except maternal AIDS. Among women diagnosed with AIDS, the estimated probability of transmission increased from 8% to 31% with duration of ruptured membranes of 2 h and 24 h respectively (P< 0.01).ConclusionsThese results support the importance of duration of ruptured membranes as a risk factor for vertical transmission of HIV and suggest that a diagnosis of AIDS in the mother at the time of delivery may potentiate the effect of duration of ruptured membranes.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesTo evaluate the effect of highly active antiretroviral therapy (HAART) on the sexual behaviour of homosexual men, we conducted (i) an ecological study of time trends in sexual behaviour and sexually transmitted diseases; (ii) a HAART-effect study focused on the practice of unprotected anogenital sex.DesignSubjects were participants in the ongoing Amsterdam Cohort Studies (ACS) among homosexual men, initiated in 1984. Data for (i) represented all ACS visits by HIV-1-positive and -negative participants who entered ACS at or below 30 years of age and were followed until 35 years (n = 1062). Data for (ii) represented all ACS visits of HIV-1-positive men from 1992 to 2000 (n = 365), of whom 84 were HAART recipients with at least 2 months of behavioural follow-up.Results(i) After HAART became generally available in July 1996, unprotected sex was practised more frequently and the incidence of gonorrhoea was higher compared to March 1992–June 1996 among HIV-1-negative and -positive men, respectively. (ii) Among HIV-1-positive men, a higher level of unprotected sex with casual partners was observed after HIV-1 RNA became undetectable and CD4 cell counts increased with the use of HAART. Notably, in individuals who did not receive HAART, high HIV-1-RNA levels (above 105copies/ml) were likewise related to unprotected sex with casual partners.ConclusionData support the need for the reinforcement of safe sex prevention messages among HIV-1-negative men, and our data also provide a lead for redirecting and tailoring current prevention strategies to the needs of HIV-1-positive men.

ISSN:0269-9370    

出版商:OVID    

年代:2001

数据来源: OVID