摘要:

Some colonic and neuronal cells which are CD4−but galactosyl ceramide-positive are susceptible to infection with HIV-1. We have previously shown that the T-cell tropic V3 loop of HIV-1 gp120 serves as a primary viral determinant for infectivity of CD4−neuronal cells. However, the nature of the V3 loop of HIV-1 needed for infection and the V3 loop's interaction with coreceptors on colonic epithelial cells have not been fully analyzed. By using HIV-1 molecular clones, we show that the T-cell tropic V3 domain is critical for HIV-1 infection of colonic HT-29 epithelial cells. Because T-cell tropic HIV-1 can use CXCR4 as a coreceptor in T cells, we set out to determine the role of CXCR4 during infection of HT-29 cells. Using reverse transcriptase-polymerase chain reaction (RT-PCR) and immunostaining, we show that these epithelial cells of colonic origin express the chemokine receptor CXCR4. Importantly, antibody against CXCR4 or a neutralizing antibody against HIV-1 gp120 V3 loop blocks T-cell tropic HIV-1 entry into HT-29 cells. These data indicate that the V3 loop of HIV-1 and the chemokine receptor CXCR4 are both critical for HIV-1 infection of colonic HT-29 epithelial cells. An HIV-1 T-tropic virus may be responsible for the infection of human colonic epithelial cells in vivo.

ISSN:1525-4135    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo study phenotypic and genotypic resistance of HIV-2 against nucleoside reverse transcriptase inhibitors (NRTI).MethodsBiologic HIV-2 clones were generated from 3 patients before and after initiation of antiretroviral therapy with zidovudine (AZT) in patient RH2-7, AZT and didanosine (ddI) in patient PH2-1, and after addition of lamivudine (3TC) to AZT monotherapy in patient RH2-5. The sensitivity to NRTI of the virus clones, as defined by the 50% inhibitory concentration (IC50), was determined in vitro. The predicted amino acid sequences of the reverse transcriptase proteins from these clones were determined.ResultsComparing the sensitivity of the biologic HIV-2 clones obtained after start of therapy with those from antiviral naive patients, resistance had developed to AZT (patients RH2-7 and RH2-5) and 3TC (patient PH2-1 and RH2-5). No resistance to AZT was observed in the biologic clone from PH2-1 obtained after start of therapy. The resistant clones from RH2-5 and PH2-1, but not RH2-7, contained amino acid mutations at positions where HIV-1 has been shown to mutate after AZT and 3TC treatment.ConclusionsPhenotypic resistance of HIV-2 to nucleoside analogues, which developed in HIV-2–infected patients treated with NRTIs, was associated with genotypic changes. Some of the mutations at amino acid positions in the HIV-2 reverse transcriptase gene corresponded with those involved in HIV-1 resistance, although no conventional mutations associated with resistance to AZT were observed.

ISSN:1525-4135    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

BackgroundOsteonecrosis (avascular necrosis) has been infrequently reported in HIV-infected patients. It is not known whether HIV itself is an independent risk factor for osteonecrosis.MethodsWe identified 25 patients with osteonecrosis from 1984 to 1999 from a large county teaching hospital and two large practices in Dallas County that specialize in HIV-disease related therapy. A retrospective chart review was performed to evaluate potential risk factors for osteonecrosis. Each case was matched with two controls for HIV positive status and date of osteonecrosis diagnosis.ResultsIn the study, 22 of 25 (88%) case patients had at least one osteonecrosis risk factor compared with 24 of 50 (48%) controls,p= .003. The most common osteonecrosis risk factors were hyperlipidemia (32%), alcoholism (28%), pancreatitis (16%), corticosteroids (12%), and hypercoaguability (12%). Of the cases, 12% were idiopathic. Multiple joints were involved in 72% of cases. Four of the case patients compared with none of the controls received megesterol acetate before the diagnosis of osteonecrosis,p= .01. No significant differences were found between cases and controls with respect to liver function tests, testosterone levels, triglyceride levels, cholesterol levels, or CD4 cell counts. Saquinavir was independently associated with osteonecrosis,p< .05. However, no differences in overall use of protease inhibitors among cases and controls were noted: 79% versus 76%, respectively.ConclusionsThe increased incidence of osteonecrosis in HIV/AIDS may be due to an increased frequency of risk factors previously associated with osteonecrosis such as hyperlipidemia, corticosteroid use, alcohol abuse, and hypercoaguability. Use of protease inhibitors was not independently associated with osteonecrosis.

ISSN:1525-4135    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The objective of antiretroviral therapy is to obtain an almost complete and durable suppression of viral replication in all compartments to facilitate recovery of the immune system. We assessed the virologic effect in plasma, tonsillar tissue, and cerebrospinal fluid (CSF) in 94 HIV-1–infected patients with CD4 counts >500 × 106cells per liter and viral load >5000 copies/ml randomly assigned to triple antiretroviral therapy (two nucleoside reverse transcriptase inhibitors (NRTIs) plus one protease inhibitor) versus double therapy (two NRTIs). We also analyzed the immunologic recovery in this cohort of patients. Lymphoid tissue and cerebrospinal fluid viral load, development of genotypic resistance, proliferative responses to HIV-1 specific antigens, and other immunophenotypic markers were analyzed. The proportion of patients who achieved a decrease in HIV RNA levels to <200 copies/ml was significantly greater in the triple therapy group than in the two drug groups (p= .0002 for each pair-wise difference). At week 52, tonsillar tissue HIV RNA from 5 patients treated with triple therapy was lower than the limit of detection, whereas the mean ± standard error in patients with double therapy (n= 5) was 5.03 ± 0.34 copies/mg/tissue. In all 10 patients, CSF viral load (VL) was <20 HIV-1 RNA copies/ml at week 52. CSF cell counts and protein levels tended to decrease after 52 weeks of antiretroviral therapy. After 1 year of therapy, 13 of 21 patients (62%) in the double-therapy groups (zidovudine plus lamivudine [n= 9] and stavudine plus lamivudine [n= 12]) had evidence of M184V mutation. None of the 10 samples of patients receiving triple therapy could be amplified because of low HIV RNA levels. The mean increase in CD4 cells at week 52 was greater in the stavudine and lamivudine and indinavir group than in the double-treatment arms (186 versus 67 and 102, respectively;p= .03). In patients treated with triple therapy, the increase in naive T cells (CD4 and CD8) was greater than in patients treated with double therapy. Markers of activation decreased further in patients treated with the regimen that included protease inhibitors. Proliferative responses to HIV-1 p24 antigen were never recovered after double or triple therapy. Our study suggests that even in very early stages of HIV-1 disease only therapy with two NRTIs and one protease inhibitor reduces plasma, lymphoid tissue, and CSF VL to undetectable levels. HIV-1–related immune system abnormalities improved but were still defective after 1 year of antiretroviral therapy.

ISSN:1525-4135    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

SummaryThe aim of this study was to assess the predictive value of HIV RNA levels after 1 month of therapy on the long-term virologic outcome in an unselected general population of HIV-infected patients.DesignAnalysis was conducted retrospectively on an ongoing clinical cohort of HIV-positive patients who were receiving antiretroviral treatment. Data on 575 patients were analyzed.ResultsThe HIV RNA value at 1 month was significantly correlated with the virologic outcome after 12 and 24 months of therapy (R = 0.258 and R = 0.44, respectively). The predictive value of the 1-month viral load was also statistically significant after stratification for baseline CD4 T-cell counts. Prediction was similar in highly compromised patients (CD4 ≤100 cells/&mgr;l; R = 0.426;p= .001) or in patients with a better immunologic status (R = 0.419;p< .0001). It retained validity in patients who were naive or experienced for antiretroviral therapy.ConclusionHIV RNA level after 1 month of therapy is a useful prognostic marker in HIV-infected patients. It predicts long-term virologic and immunologic outcome. A cutoff level of 5000 copies/ml identifies patients most likely to fail current therapy. In these patients, a more aggressive strategy or specific diagnostic interventions to clarify the relative influence of viral resistance and/or subtherapeutic regimens is advised.

ISSN:1525-4135    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The prevalence of oral lesions was assessed in a five-center subset of the Women's Interagency HIV Study (WIHS) and correlated with other features of HIV disease. Oral examinations were performed by dental examiners on 729 women (577 HIV-positive and 152 HIV-negative) during baseline examination. Significant differences between the groups were found for the following oral lesions: pseudomembranous candidiasis, 6.1% and 2.0%, respectively; erythematous candidiasis, 6.41% and 0.7%, respectively; all oral candidiasis, pseudomembranous and/or erythematous, 13.7% and 3.3%, respectively. Hairy leukoplakia was observed in 6.1% of HIV-positive women. No significant differences were found for recurrent aphthous ulcers, herpes simplex lesions, or papillomas. Kaposi's sarcoma was seen in 0.5% of HIV-positive and 0% of HIV-negative women. Using multiple logistic regression models controlling for use of antiretrovirals and antifungals, in HIV-positive women the presence of oral candidiasis was associated with a CD4 count <200 cells/&mgr;l, cigarette smoking, and heroin/methadone use; the presence of hairy leukoplakia was not related to CD4 count but was associated with high viral load. Oral candidiasis and hairy leukoplakia are confirmed as being common features of HIV infection in women and appear to be associated with HIV viral load, immunosuppression, and various other behaviorally determined variables.

ISSN:1525-4135    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveGynecologic disease is common in HIV-infected women. We examine the sociodemographic, clinical, and provider factors associated with the care of women with vaginal symptoms.MethodsWomen enrolled in the HIV Cost and Services Utilization Study (HCSUS), a nationally representative probability sample of HIV-infected adults, were interviewed between January 1996 and April 1997. Women with vaginal symptoms who sought medical attention were asked, “Did your health care provider examine your vaginal area?” Women were also asked if they received medication for their symptoms.ResultsAmong 154 women with vaginal symptoms, 127 sought care for their symptoms. Of those who sought care, 48% saw a gynecologist and 52% sought care from nongynecologists, most often their usual HIV care provider. Women who saw a gynecologist for their symptoms were more likely to have received a pelvic examination (92% versus 76%;p= .06) and vaginal fluid collection (98% versus 88%;p= .06) than those who saw their regular HIV provider. Fifteen percent of women received medication for their symptoms without having a pelvic examination; gynecologists were less likely to prescribe without an examination (8% versus 21%;p= .12).ConclusionGynecologists are more likely to provide adequate care of vaginal symptoms among HIV-infected women than nongynecologists who were HIV care providers. This specialty difference is consistent with quality of care studies for other medical conditions, but the potential gynecologic complications of inadequate evaluation and treatment warrants further investigation.

ISSN:1525-4135    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ContextAccording to recent studies, women have lower plasma HIV RNA concentrations than men. However, these studies did not take into account the duration of HIV infection.ObjectivesTo analyze the relationship between viral load and gender among individuals with known date of seroconversion.SettingSixty infectious disease clinics in Italy.DesignCross-sectional analysis of data collected at enrollment in a cohort study.ParticipantsInjecting drug users and heterosexual contacts naive to antiretroviral therapy at enrollment (245 men; 170 women).Main Outcome MeasuresPlasma HIV RNA concentrations, measured using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) or signal amplification b-DNA assays before antiretroviral therapy.ResultsPlasma HIV RNA concentrations were similar by age and exposure category (p= .80 andp= .39, respectively). Median viral load among women was roughly half that of men (p= .002). The association between viral load and gender remained significant after fitting a two-way analysis of variance (p= .03) and after adjusting for CD4 count, modality of HIV transmission, and age at enrollment in a regression model. Viral load was 0.27 log10copies/ml (95% confidence interval, 0.05–0.40;p= .01) lower in women (i.e., 50% lower in the raw scale).ConclusionsPlasma HIV RNA concentrations were found to be lower among women, even when considering the duration of HIV infection. Compared with men, it is possible women should be given highly aggressive antiretroviral therapy at lower HIV-RNA concentrations.

ISSN:1525-4135    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

BackgroundInjection drug users (IDUs) and their sex partners account for an increasing proportion of new AIDS and HIV cases in the United States, but public debate and policy regarding the effectiveness of various HIV prevention programs for them must cite data from other countries, from non-street-recruited IDUs already in treatment, or other programs, and from infection rates for pathogens other than HIV.MethodsParticipants were recruited from the street at six sites (Baltimore [Maryland], New York [two sites], Chicago [Illinois], San Jose [California], Los Angeles [California], and at a state women's correctional facility [Connecticut]), interviewed with a standard questionnaire, and located and reinterviewed at one or more follow-up visits (mean, 7.8 months later). HIV serostatus and participation in various programs and behaviors that could reduce HIV infection risk were determined at each visit.ResultsIn all, 3773 participants were recruited from the street, and 2306 (61%) were located and interviewed subsequently. Of 3562 initial serum specimens, 520 (14.6%) were HIV-seropositive; at subsequent assessment, 19 people, all from the East Coast and Chicago, had acquired HIV. Not using previously used needles was substantially protective against HIV acquisition (relative risk [RR], 0.29; 95% confidence interval [CI], 0.11–0.80 ) and, in a multivariate model, was significantly associated with use of needle and syringe exchange programs (adjusted odds ratio [ORadj], 2.08; 95% CI, 1.15–3.85). Similarly, reduction of injection frequency was very protective against seroconversion (RR, 0.33; 95% CI, 0.14–0.80), and this behavior was strongly associated with participation in drug treatment programs (ORadj, 3.54; 95% CI, 2.50–5.00). In a separate analysis, only 37.5% of study-participants had sufficient new needles to meet their monthly demand.ConclusionsIn this large multicity study of IDUs in the United States, several HIV prevention strategies appeared to be individually and partially effective; these results indicate the continued need for, and substantial gaps in, effective approaches to preventing HIV infection in drug users.

ISSN:1525-4135    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

We analyzed trends over time and determinants of late diagnosis of HIV infection among people diagnosed with AIDS in 1986 to 1998 in a tertiary care center in Rome, Italy. Information on the date of a first HIV test was collected prospectively, in addition to data routinely collected for AIDS reporting. Patients with AIDS were defined as “late testers” if the time interval between first positive HIV test result and AIDS diagnosis was ≤3 months. Overall, 503 people with AIDS of 1977 included in the analysis (25.4%) were late testers. the proportion of late testers decreased from 62.5% in 1986 to 16% in 1995. Thereafter, this proportion increased to 20.5% in 1996, 33.7% in 1997, and 36.6% in 1998. In multivariate analysis, the following variables were significantly associated with late testing: AIDS diagnosis in years 1986 to 1993 or 1997 to 1998 compared with 1995, male gender, age ≥45 years, men who have sex with men, heterosexual contacts, or having unknown transmission mode compared with intravenous drug users, and being born outside Italy. Since 1996, the overall number of AIDS cases diagnosed at our center began to decrease whereas the number of late-testing AIDS patients did not decrease, resulting in an increasing proportion of late testers during the last 3 years of the study. This findings may reflect the effect of combination antiretroviral therapy in slowing progression to AIDS of HIV-infected persons aware of their status. A relevant number of people still discover their HIV infection late and may therefore miss treatment opportunities. New testing strategies are needed to reach more people who engage in high-risk behaviors, especially those at risk for sexual transmission, and those born outside Italy.

ISSN:1525-4135    

出版商:OVID    

年代:2000

数据来源: OVID