摘要:

Lion lentivirus (LLV) and puma lentivirus (PLV) exist as highly divergent virus clades among populations of indigenously infected nondomestic felidae. The feline immunodeficiency virus (FIV) is highly divergent from LLV and PLV and is pathogenic for domestic cats. When domestic cats are infected with LLV or PLV, they have immunologically and clinically silent persistent infections. We examined whether LLV or PLV infection might impart resistance to FIV superinfection in vitro by infecting domestic cat lymphoid cells with PLV and assessing resistance of these cells to FIV. We found that infection with FIV was highly restricted by prior established PLV infection. To examine whether this resistance applied in vivo, domestic cats were asymptomatically infected with either LLV or PLV and then challenged with pathogenic FIV. Although all cats became infected with FIV, prior LLV or PLV exposure blunted CD4+cell depletion and suppressed plasma and peripheral blood mononuclear cell FIV loads relative to FIV-challenged controls not infected with LLV or PLV, despite the lack of prechallenge neutralizing antibody activity against FIV. Thus, as compared with naive controls, cats previously infected with LLV or PLV were able to more effectively control FIV infection and resist its immunologic effects, despite the substantial genetic divergence between these lentiviruses—raising the possibility that superinfection may impart resistance to lentivirus infection by heightening innate immune mechanisms.

ISSN:1525-4135    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Amdoxovir ([-]-&bgr;- d -2,6-diaminopurine dioxolane [DAPD]) is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against HIV-1. DAPD is deaminated in vivo by adenosine deaminase to (-)-&bgr;- d -dioxolane guanosine (DXG), a highly active anti-HIV compound. The median 50% effective concentrations (EC50) ± SD (representing antiviral activity against a laboratory-derived HIV-1 isolate) for DAPD and DXG in peripheral blood mononuclear cells were 4.0 ± 2.2 &mgr;mol/L and 0.25 ± 0.17 &mgr;mol/L, respectively. The 50% cytotoxic dose (CC50) of both DAPD and DXG was >500 &mgr;mol/L. Recombinant viruses and clinical isolates of HIV-1 from patients for whom NRTI therapy and/or nonnucleoside reverse transcriptase inhibitor (NNRTI) combination therapies failed remained susceptible to inhibition by DXG (less than fourfold change in EC50). Similar analysis showed that recombinant viruses harboring mutations known to confer resistance to NRTIs (zidovudine, lamivudine, and abacavir) and NNRTIs (efavirenz and nevirapine) as well as the multidrug resistance–associated mutation Q151M and double codon insertions (SS and SG) were also susceptible to inhibition by DXG. Resistance to DXG was observed only in recombinant isolates containing the 65R and 151M double mutations. Phenotypic analysis of a site-directed mutant containing only the 151M mutation demonstrated moderate resistance to DXG (<10-fold change in EC50). We also examined site-directed mutants containing only L74V or K65R, the characteristic resistance mutations for DXG. The L74V mutant remained susceptible to inhibition by DXG, and the K65R mutant demonstrated moderate resistance to DXG.

ISSN:1525-4135    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

BackgroundCross-sectional and retrospective surveys suggest that nucleoside reverse transcriptase inhibitors (NRTIs) contribute to the metabolic and morphologic alterations observed in patients on antiretroviral therapy (ART).ObjectivesTo assess the risk of developing body habitus changes (BHCs) and metabolic abnormalities in protease inhibitor (PI)-naive HIV-1–infected patients treated with two NRTIs, and the risk associated with each of these drugs.DesignProspective cohort study.Patients and MethodsThe BHCs occurring in 335 patients treated with two NRTIs were evaluated every 3 months. The laboratory tests included determination of CD4 cell counts and the measurement of HIV RNA, serum glucose, cholesterol, and triglyceride levels. Cox proportional hazard models were used to describe the factors associated with the development of BHCs.ResultsDuring a median exposure of 747.5 days, 46 patients (13.7%) developed BHCs: nine fat accumulation alone, 12 fat loss alone, and 25 combined fat loss and accumulation in different body regions. Fat loss alone occurred after a significantly longer median duration of treatment than the other two forms (p= .004). The risk of developing any BHC was significantly higher in female patients (p< .0001). Fat loss was the prevalent alteration in males. Hypertriglyceridemia was observed in 76 patients (22.7%), hypercholesterolemia in 35 (10.5%), and hyperglycemia in 48 (14.3%). The adjusted risk of developing hypertriglyceridemia was higher in the stavudine-treated patients (p= .04) and in those who had previously received ART (p= .02). The only independent factor associated with the development of hypercholesterolemia was to be ART experienced at baseline (p= .02), whereas age was associated with the development of hyperglycemia (p= .0096).ConclusionsTreatment with NRTIs may be responsible for the same morphologic alterations as those observed in patients treated with PIs. Moreover, altered triglyceride levels are also frequently observed. The different timing of presentation and gender distribution of BHCs suggest that multiple pathogenetic mechanisms are involved.

ISSN:1525-4135    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

BackgroundMetabolic disturbances and fat maldistribution are main features of the antiretroviral-related lipodystrophy syndrome (LDS). Different phenotypes of fat distribution abnormalities can be observed: fat loss, fat accumulation, or a mixed pattern. In patients with predominant loss of fat, the roles of leptin, lipids, and glucose homeostasis disturbances have not yet been clearly established.MethodsThe study comprised 34 HIV-infected male patients receiving antiretroviral treatment that included protease inhibitors. A lipoatrophic phenotype, defined as fat loss in face or extremities, both normal weight and waist:hip ratio, and absence of fat accumulation elsewhere, was present in all cases. Fat distribution disturbances were confirmed by abdominal and midthigh computed tomography–calculated adipose tissue content. Fasting plasma glucose, insulin, proinsulin, total leptin, testosterone, and lipid profiles were measured. After 2 hours, 75-g oral glucose tolerance test (OGTT), glucose, insulin, and proinsulin levels were also obtained. Insulin resistance was calculated using the homeostasis model assesment for insulin resistance (HOMA-r) method. Both healthy study subjects (n= 385) and antiretroviral-naive HIV-positive patients (n= 13) were used as controls.ResultsOf these LDS patients, 5.8% showed diagnostic criteria for diabetes and 17.8% for impaired glucose tolerance. A lipid pattern characterized by high total cholesterol and high low density lipoprotein (LDL) plasma levels, hypertriglyceridemia, and normal high density lipoprotein (HDL) levels was observed. Fasting insulin and 2-hour post OGTT insulin levels, and insulin resistance index were significantly higher in LDS patients than in antiretroviral-naive HIV-positive patients. Plasma leptin levels were significantly lower in lipoatrophic patients than in healthy control individuals. Patients with LDS presented with significant midthigh fat reduction and visceral fat accumulation compared with findings in antiretroviral-naive HIV-positive patients. A significant correlation was found between plasma leptin levels and midthigh fat content.ConclusionPeripheral fat loss in extremities in LDS patients with lipoatrophic phenotype is also associated with low plasma leptin levels, visceral fat accumulation, and metabolic disturbances related to an increased cardiovascular risk. In LDS patients, plasma leptin levels could be a marker of subcutaneous adipose tissue content.

ISSN:1525-4135    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

To evaluate the occurrence of hepatotoxicity in patients during antiretroviral therapy (ART) that contains protease inhibitors and the role of hepatitis viruses in its development, we performed a retrospective study including 1325 HIV-infected patients treated with ART for at least 6 months. Presence or absence of hepatitis viruses, alanine aminotransferase (ALT), total bilirubin, CD4 cell count, and plasma HIV RNA levels were evaluated. Hepatotoxicity developed in a few study subjects without coinfection, whereas it was significantly higher in coinfected patients. Univariate logistic regression analysis showed that viral hepatitis coinfections are independent risk factors for hepatotoxicity. After 6 months of treatment, ritonavir was associated with higher rates of severe hepatotoxicity in the coinfected group; in fact, ritonavir seems to be the most strongly hepatotoxic agent among coinfected patients. After 12 months of therapy, hepatotoxicity occurred more frequently in patients with hepatitis C virus who did not respond to antiretroviral therapy (ART), whereas patients who did respond to ART showed decreased ALT levels. Hepatotoxicity is not exclusively an effect of drug toxicity, and the presence of hepatitis coinfection is an independent risk factor. Moreover, chronic hepatotoxicity mainly occurs in patients who did not respond to therapy. Conversely, patients who did respond to ART seemed to show improvement of chronic liver infection.

ISSN:1525-4135    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The relationship of immunity toHistoplasma capsulatumand CD4 count in HIV-1–infected patients is unknown. Samples of blood from people with HIV infection and from HIV-negative volunteers were assessed for immune responsiveness to the histoplasmin antigen using proliferation and interferon-&ggr; production as indicators of immunity. Results of histoplasmin skin tests, lymphoproliferative responses (LPR), and interferon-&ggr; production were positive in 9 of 20 (45%) HIV-negative controls, and in vitro measurements agreed highly with skin test reactivity. Among HIV-1–infected patients with recent histoplasmosis, skin test results were positive in none, LPR results were positive in 14%, and interferon-&ggr; production in 18%. Among HIV-1–infected patients with CD4 counts between 200 and 500 cells/mm3, LPR was positive in 8% and interferon-&ggr; production in 33%, and among those with CD4 counts >500 cells/mm3, LPR was positive in 31% and interferon-&ggr; production in 46%. In conclusion, immune responsiveness toH. capsulatumwas depressed in HIV-1–infected persons with CD4 counts between 200 and 500 cells/mm3, but approached normal in those with CD4 counts >500 cells/mm3.

ISSN:1525-4135    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

BackgroundAnemia is common in HIV infection, particularly in advanced disease states. We wished to determine how highly active antiretroviral therapy (HAART) and other factors affected the level of hemoglobin in HIV infection.MethodsWe analyzed data from 905 patients receiving care at Johns Hopkins in Baltimore, Maryland after July 1, 1996. Analyses were done of hemoglobin levels obtained at baseline and during 1 year of follow-up in patients who received and did not receive a HAART regimen. Use of HAART and other demographic and clinical factors were examined.ResultsEleven percent of patients had a hemoglobin count <10 g/dL, 27% had a hemoglobin count 10 to 12 g/dL, and 21% had a hemoglobin count of >14 g/dL at baseline before HAART was started. During 1 year of follow-up, use of HAART was associated with a hemoglobin levels >14 g/dL in 42% of patients, irrespective of use of zidovudine as part of HAART regimen, compared with 31% of patients who did not use HAART. In multivariate analysis, use of HAART was strongly associated with not having anemia during 1 year of follow-up, adjusting for patient gender, race, injection drug use history, baseline CD4 and HIV-1 RNA levels, and anemia treatments.ConclusionsHAART is an effective treatment of the anemia of HIV infection. Patients who continue to have symptomatic anemia while receiving HAART may need additional intervention.

ISSN:1525-4135    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

In most studies, people who have not responded virologically to a protease inhibitor (PI)-containing regimen have tended to experience poor virologic responses to subsequent regimens. We describe the 2-year viral load, CD4 count, and clinical outcome of a multidrug regimen used in 60 people who had not responded virologically to a PI-containing regimen. At baseline, median CD4 count was 126/mm3(nadir 30/mm3) and median viral load was 320,000 copies/mL. A median of five antiretroviral drugs had previously been used, of which a median of two were PIs. Of these patients, 16% had previously used another nonnucleoside reverse transcriptase inhibitor besides efavirenz. The multidrug regimen (median 5 drugs) started most commonly included efavirenz (100%), at least one PI (92%, usually indinavir/ritonavir), didanosine (78%), and hydroxyurea (74%). At year 2, 5 patients had died and 5 had no measure available. Nine patients developed a new AIDS event and 10 patients were known to have stopped all antiretroviral therapy. Thirty-one patients (52% of the whole group, 72% of those remaining on therapy with viral load value available) had viral load <50 copies/mL. Thus, a substantial proportion of patients who had failed to respond virologically to PI-containing regimens can achieve profound and sustained virologic suppression with a multidrug regimen.

ISSN:1525-4135    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Epidemic HIV-1 infections were first recognized in Thailand in 1988 but increased dramatically in the 1990s primarily as a result of sexual transmission. The Ministry of Public Health instituted programs, including condom promotion during commercial sex, and health education to prevent HIV transmission. We assessed the HIV infection prevalence and risk behaviors among eight cohorts of 21-year-old randomly selected male military conscripts in northern Thailand between 1991 and 1998 to evaluate temporal trends in HIV infection and risk behavior. The prevalence of HIV was 11.4% to 11.9% in 1991 through 1993 and progressively fell to 2.4% in 1998. The men reported progressive decreases in commercial sex from 80% in 1991 to 38% in 1998, increases in condom use for commercial sex to greater than 95% in 1998, and decreases in lifetime history of a sexually transmitted infection from 42% in 1991 to 4.4% in 1997. There was an increasing proportion of men who reported a history of injecting illicit drugs, however, which involved 1.0% of the men in 1991 but 4.2% in 1997. The population attributable risk of drug use for HIV infection increased in recent years; the proportion of HIV-positive men with a history of drug use increased from 1.0% in 1991 to 25.8% in 1998. The public health program to prevent the sexual transmission of HIV in Thailand continues to be highly successful. Nevertheless, injection drug use has emerged as an important risk behavior and is maintaining endemic HIV transmission in Thailand.

ISSN:1525-4135    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectivesTo evaluate factors associated with use of HIV specialist care by women, and to determine whether medical indications for therapy validate lower rates of antiretroviral use in women not using HIV specialty care.DesignCross-sectional analysis of the 1998 interview from the HIV Epidemiology Research Study (HERS) cohort.MethodsData from 273 HIV-infected women in the HERS were analyzed by multiple logistic regression to calculate predictors of the use of HIV specialist care providers. Variables included study site, age, education, insurance status, income, substance abuse, depression, AIDS diagnosis, CD4+lymphocyte count, and HIV-1 viral load. In addition, medical indications for therapy and medical advice to begin antiretroviral therapy were assessed.ResultsOf 273 women, 222 (81%) used HIV specialists and 51 (19%) did not. Having health insurance, not being an injection drug user, and being depressed were predictive of using HIV specialist care (allp≤.05). Although medical indications for therapy in the two groups were comparable, the rate of highly active antiretroviral therapy (HAART) use was significantly higher in women using HIV specialist care (27%) compared with those not using HIV specialists (7.8%). Women using HIV specialists received significantly more advice to begin antiretroviral therapy (ART) in the 6 months prior to the interview compared with those not using specialists (relative risk, 2.4; 95% CI = 1.3–4.6).ConclusionsHaving insurance, not being an injection drug user, and being depressed all increased the likelihood of women receiving HIV specialty care, which, in turn, increased the likelihood of receiving recommended therapies. The level of HAART use (23%) and any ART use (47%) in these HIV-infected women was disturbingly low. Despite comparable medical indications, fewer women obtaining care from other than HIV specialists received HAART. These data indicate substantial gaps in access to HIV specialist care and thereby to currently recommended antiretroviral treatment.

ISSN:1525-4135    

出版商:OVID    

年代:2002

数据来源: OVID