摘要:

Summary:Infectious molecular clones of HTLV-I proviruses have only recently been reported. The long wait for such provirus clones reflects the difficulties inherent in propagating HTLV-I in vitro, and thus a rigorous demonstration of infectivity has awaited improved cell culture systems and sensitive detection techniques for HTLV-I. An intact HTLV-I provirus, originating from an American ATL patient, was subcloned into a plasmid vector and was designated pCS-HTLV. Transient transfections of mammalian cells with pCS-HTLV resulted in the synthesis of viral proteins and mRNAs which were assembled into virions that had physical and morphological characteristics typical of HTLV-I particles. The ability of these virus particles to infect cells, replicate, and produce infectious progeny was demonstrated initially in short term, cell-free infection assays by monitoring the expression of specific viral mRNAs. These studies have been extended in cell culture systems that support continuous virus production. Primary T-lymphocytes have been infected either with cell-free supernatant fluids from, or by coculture with, cells transiently transfected with pCS-HTLV, giving rise to continuous, IL-2-dependent cell lines that have been in culture for >1 year. Furthermore, fetal rhesus lung cells (FRhL) were shown to be permissive for HTLV-I replication and sustained virus expression after infection with pCS-HTLV. Continuous FRhL cell lines now have been established that express various HTLV-I proviruses and mutants. These provirus clones and cell lines provide us with the means to address long-standing questions dealing with the biology of HTLV-I.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:Substantial differences have been described in the response of individual patients to zidovudine (ZDV) therapy, both in the clinical impact and in virus load. Genotypic changes associated with the appearance of drug resistance may also be different or occur at different rates. We have obtained the nucleotide sequence of the RT domain of individual HIV-1 genomes extracted from 10 plasma and peripheral blood mononuclear cell (PBMC) samples donated by two haemophiliac patients before, during, and after long-term ZDV therapy. Although the plasma virus load was similar throughout, the order and timing of appearance of resistance-associated substitutions differed in the two patients. In patient p74, K70R appeared after 4 months, T215Y at 5.5 months, and M41L at 13 months. In p87, K70R also appeared at 4 months, but T215Y and K219Q were not observed until 18 months and M41L not at all. Much greater sequence change overall occurred in p74. The evolution of the viral population in that patient was dominated by the unique appearance of T215Y and subsequently M41L, with all sequences from the last time point being descended by a single path from the pretreatment samples. However, in p87, several different lineages of RT sequences were found to persist throughout treatment. We propose that these differences in outcome may be determined by differences in genetic background at sites other than the five generally considered to be associated with ZDV sensitivity.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:The antibody response to the HIV-1 envelope protein has not been well characterized in patients with AIDS dementia complex (ADC). We evaluated the frequency of antibodies against the HIV-1 envelope in cerebrospinal fluid (CSF) and serum from 21 persons with ADC and 10 symptom-free HIV-1-positive subjects using Western immunoblot with reducing and nonreducing buffer and radioimmunoprecipitation (RIP) analysis. RIP analysis revealed anti-envelope antibodies in all sera tested. Higher anti-envelope levels were observed in CSF than in serum of 12 of 21 ADC patients and only 1 of 10 symptom-free subjects (two-sided Fisher exact test, p < 0.05). All persons with moderate to severe ADC had higher anti-envelope levels in CSF than in sera (p < 0.005). CSF anti-gp120 antibodies were not as readily detected by Western blot analysis even under nonreduced conditions, suggesting that they are directed to conformational epitopes. Higher CSF anti-envelope antibodies appear to be more common in patients with ADC than in symptom-free HIV-1-positive subjects. This antibody pattern may serve as a marker for ADC and its progression.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:We have developed a host range system to measure the mutation frequency of feline immunodeficiency virus (FIV), the feline homologue of human immunodeficiency virus type 1 (HIV-1). When wild-type FIV was grown in the presence of a known mutagen, 5-bromo-2'-deoxyuridine (BUdR), a dose-dependent increase of host range mutants was detected. Using this system, we have evaluated the effects of antiviral drugs upon the mutation frequency of FIV. Subinhibitory concentrations of 3'-azido-3'-deoxythymidine (AZT), the most common antiviral drug used in AIDS chemotherapy, increased the mutation frequency of FIV in a dose-dependent manner. Two other antivirals, 2',3'-dideoxyinosine (ddI) and 2',3'-dideoxycytidine (ddC), did not show this effect.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:Cytomegalovirus (CMV) infection remains a life-threatening infection in patients with HIV disease. A rapid, quantitative diagnostic technique is needed to aid in the diagnosis of CMV disease. This study was undertaken to evaluate the CMV antigenemia test in patients with HIV disease who are at risk for CMV disease. The study included 22 patients who underwent ophthalmologic exams or selected diagnostic techniques in whom CMV cultures and CMV antigenemia tests were performed. All of 11 patients with CMV disease had positive CMV antigenemia assays [range, 48-1,000 positive cells/2 × 105peripheral blood leukocytes (PBL)], and 10 were also CMV viremic. There was no clinical evidence of CMV disease in 11 patients, including seven in whom the CMV antigenemia assay was negative and who remained without evidence of CMV disease after a median follow-up of 159 days. Four patients had low antigenemia levels. Of these four, two subsequently developed CMV retinitis. In conclusion, a positive CMV antigenemia result with ≥48 positive cells/2 × 105PBL correlated with concurrent CMV disease. The CMV antigenemia test appears to be a valuable tool for the rapid diagnosis of CMV disease in HIV-infected individuals.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:The pattern of the development of opportunistic infections (OIs) in HIV-infected patients was evaluated, based on a cohort of 1,530 patients enrolled in two AIDS Clinical Trials Group anti-retroviral studies. We quantified the increase in risk of OIs associated with the occurrence of a previous OI. This assessment was based on the observed event rates of the more common AIDS-defining OIs:Pneumocystis cariniipneumonia (PCP),Mycobacterium aviumcomplex (MAC), cytomegalovirus (CMV), and a systemic mycosis. Additionally, for each OI, we assessed the relative risks associated with a history of prior OIs, changes in CD4 levels, and baseline prognostic factors. We found that the occurrence of each of these OIs increased the risk of subsequent OIs, even after adjusting for the CD4 count. Specifically, the occurrence of PCP significantly increased the risk of MAC and CMV, and somewhat increased the risk of systemic mycoses. Diagnosis with MAC was associated with an increased risk of subsequent CMV, whereas the occurrence of CMV increased the risk of MAC. Finally, once patients were diagnosed with a systemic mycosis, they were at a somewhat increased risk of subsequently developing MAC or CMV. Although current practice for determining the timing and initiation of prophylactic therapies relies chiefly on CD4 count, the occurrence of specific AIDS-defining OIs in patients with HIV infection should also be taken into account in making decisions regarding prophylaxis strategies.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Purpose:To evaluate the impact of missing data due to nonrandom dropout on estimates of the effect of treatment on the CD4 count in a clinical trial of antiretroviral therapy for HIV infected individuals.Methods:The effect of treatment on CD4 counts in a recent study of continued ZDV versus ddI in HIV-infected individuals was estimated from the observed data and after imputing missing CD4 counts for patients who dropped out of the study. Imputation methods studied were (a) carrying forward the last observed CD4 count, (b) predicting missing CD4 counts from regression models, and (c) assuming that CD4 counts of patients who dropped out declined at a rate of 100 cells per year.Results:Of the 245 patients enrolled in the study, 52% completed the planned 48 weeks of follow-up. Patients with lower CD4 counts were more likely to drop out of the study (RR = 1.77; p = 0.0001). Patients receiving ZDV had a greater tendency to drop out than patients receiving ddI (p = 0.07). Mean CD4 counts calculated after imputing missing data were lower than those obtained from the observed data at all follow-up times for both treatment groups. Imputing CD4 counts with regression models yielded higher estimates of the effect of treatment than were obtained using the observed data.Conclusion:Missing outcome data due to dropouts can result in an understimation of the treatment effect and overly optimistic statements about the outcome of participants on both treatment arms due to the selective dropout of participants with lower or decreasing CD4 counts. When there are significant dropout rates in randomized trials, imputation is a useful technique to assess the range of plausible values of the treatment effect.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:We wished to determine the extent to which drugs used to treat HIV disease and its clinical manifestations are prescribed for conditions other than those listed on the U.S. Food and Drug Administration's approved drug label, how such “off-label” use varies by patient characteristics and type of HIV-related medical condition, and the extent to which physicians alter the way they treat HIV-related conditions because of reimbursement problems associated with off-label drug use. We surveyed 1,530 primary care providers for people with HIV disease between February and May 1993. A three-part survey instrument was used to obtain data on the drugs prescribed for the last three patients with HIV disease treated by the provider, the preferred choice of therapy for 32 specific HIV-related conditions, and the extent to which providers faced reimbursement problems regarding the use of drugs for off-label indications. Three drug compendia were used as cited sources of off-label drug uses. In all, 387 (32%) evaluable surveys were returned, yielding data on 1,148 patients. The majority (81%) of patients received at least one drug off-label, and almost half (40%) of all reported drug therapy was off-label. Most off-label drug use was for treatment and prevention of HIV-related opportunistic infections, which frequently represented the community standard of practice (e.g., trimethoprim/sulfamethoxazole for prevention ofPneumocystis cariniipneumonia), or the de facto standard of practice when no licensed therapies were available (e.g., drugs for treatment ofMycobacterium aviumcomplex, MAC). More than 75% of off-label usage was cited in at least one of the three authoritative medical compendia. The use of drugs for off-label indications in HIV care is common and frequently represents community standards of care. Reliance on drug compendia for support of off-label drug use accounts for the majority of such uses, although many legitimate off-label uses may not be included because of compendia publication lag. The prevalence of off-label drug use in routine clinical practice and the development of newer and more costly drugs for treatment of HIV and its medical complications argues for the articulation of an explicit national reimbursement policy for off-label uses of prescription drugs so that medically appropriate therapies will be available to those with insurance in a rational, consistent way.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:To describe the dynamic of HIV-1 prevalence in Italian childbearing women and to estimate the future incidence of pediatric AIDS due to vertical transmission, dried-blood specimens collected from a consecutive sample of newborns in all Italian regions were examined for the presence of anti-HIV-1 antibodies (HIV-Ab) after the routine neonatal screening program was completed. Of 555, 722 blood samples collected and examined for HIV-Ab between 1990 and 1993, 550 (0.099%) were positive. Nationwide, the HIV seroprevalence decreased between 1990 and 1992 (0.124% in 1990, 0.100% in 1991, 0.085% in 1992), and increased, as compared with that in the previous year, in 1993 (0.096%). In an univariate analysis, HIV seroprevalence was positively associated with being born in regions having higher AIDS cumulative incidence and in metropolitan areas, but negatively associated with year of delivery. In a multiple logistic regression analysis, only the AIDS cumulative incidence level of the delivery area and being born in a metropolitan area remained independently associated with HIV seroprevalence. Our results show significant geographical variation in the spread of HIV infection among childbearing women in Italy and provide useful indications to target prevention and care strategies for HIV-infected women and their children and to estimate the potential impact of implementing programs aimed at preventing vertical transmission of HIV infection.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Summary:We wished to identify opportunities for improving the yield of positive HIV test results from federally funded HIV counseling and testing programs. We reviewed client records from 1992 and 1993 for targeting opportunities at the site level based on site type (i.e., family planning clinic) and the seropositivity in the past and at the client level based on the client's history of a past negative test, demographics, and risk history. We studied 1,281,606 records from 1992. The number of tests and opportunities for site-level targeting varied by project area. Seropositivity varied by site type, but the best predictor of seropositivity was seropositivity at that site in the past. Of 1,102 sites with <1% of tests positive in 1992, only five had >3% positive in 1993. Sites with no positive tests in 1992 performed 99,468 tests in 1993, and only 292 (0.3%) were positive. Clients with a past negative test had a slightly lower seropositivity (1.5%) than clients with no previous test (2.0%). In sites with a low (0.1-2.0%) seropositivity, clients with no transmission risk by history were unlikely to be infected (0.8% for black men). However, in sites with high (≥5%) seropositivity, clients without risk were often infected (5.7% for black men). Opportunities for targeting were identified. They vary considerably by project area and testing site. These opportunities for targeting should be considered by sites as AIDS prevention strategies evolve.

ISSN:1077-9450    

出版商:OVID    

年代:1996

数据来源: OVID