Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: ZK856 .18
48,410 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated the effects of plasma HIV RNA, CD4+ T lymphocytes and chemokine receptors CCR5 and CCR2b on HIV disease progression in hemophiliacs. We prospectively observed during follow-up 207 HIV-infected hemophiliacs in the Hemophilia Growth and Development Study. Plasma HIV RNA was measured on cryopreserved plasma from enrollment using the Chiron Corporation bDNA (version 2.0) assay. Genoytpe variants CCR2b-641 and CCR5-delta32 were detected using standard molecular techniques. Those with the mutant allele for CCR2b, and to a lesser extent CCR5, had lower plasma HIV RNA, and higher CD4+ T lymphocytes than did those without these genetic variants. After controlling for the effects of plasma HIV RNA and CD4+ T lymphocytes, those with the CCR2b mutant allele compared with those wild-type, had a trend toward a lower risk of progression to AIDS, adjusted relative hazard of 1.94 (95% confidence interval [CI], 0.9-4.18; p = .092), and AIDS-related death, relative hazard 1.97 (95% CI, 0.98-4.00; p = .059). We conclude that plasma HIV RNA, CD4+ T lymphocytes, and CCR genotypes are correlated, and the protective affect of CCR2b against HIV disease progression is not completely explained by plasma HIV RNA or CD4+ T-lymphocyte number.
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PMID:Effects of plasma HIV RNA, CD4+ T lymphocytes, and the chemokine receptors CCR5 and CCR2b on HIV disease progression in hemophiliacs. Hemophilia Growth and Development Study. 1042 11

HIV surveillance in homosexual men is poor in most countries, as this risk group is difficult to sample. The aim of this study is to test the feasibility of reaching homosexual men for national HIV surveillance using gay community media. In 1989, a questionnaire on general gay issues, with a section on AIDS, was included in a widely sold gay magazine in the Netherlands. Among 17,700 sold copies, 1134 responses were obtained from males (6%). Of these, 669 men (59%) gave their address, of which in turn 84% responded to a questionnaire on risk behaviour in 1990. In 1991/1992, the 669 men were asked to participate in an HIV serosurvey, in which eventually 308 participated with a blood test (46%) and 147 without (total 68%). Participation in the serosurvey with blood test was associated with reporting multiple partners in 1989. Twenty participants were infected (6.5%). In logistic regression analysis, risk factors for infection were recent unprotected receptive anal intercourse with multiple partners (odds ratio (OR): 10.7; 95% confidence interval (CI): (2.18-52.2); one partner 1.17 (0.31-4.48); none 1) and living in Amsterdam (OR: 3.92; 95% CI: (0.99-15.5); urbanised western Netherlands 2.15 (0.57-8.03); elsewhere 1), while a high educational level was protective (OR: 0.29 (0.08-0.96); middle 0.41 (0.11-1.54); low 1). Among those who participated in 1991/1992, risk behaviour increased between 1989 and 1991/1992 (reporting multiple casual partners rose from 55% to 64%; reporting inconsistent condom use with receptive anal sex from 58% to 71%). Using a predictive model which included self-reported serostatus in 1989, the HIV prevalence rate in 1991/1992 among all male responders to the 1989 questionnaire was estimated to be 5.3% (95% CI: 3.1 7.7%). In conclusion, unless initial response is improved, recruitment through a gay magazine may not allow reliable estimates of HIV prevalence in homosexual men. However, it can be useful at the national level for monitoring changes in prevalence and risk behaviour over time, geographical differences and risk factors for infection.
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PMID:Reaching homosexual men for HIV surveillance through a gay magazine. 1044 68

HIV-infected pregnant women have been the focus of considerable research related to biomedical issues of mother-to-child transmission worldwide. However, there have been few reports on the psychological well-being of new mothers with HIV, either in developed or developing countries. As part of a perinatal HIV transmission and family impact study in Bangkok, predictors of psychological scales were evaluated from interview data (N = 129) collected 18-24 months postpartum. Standardised questionnaires were used to assess depressive symptoms and HIV-related worry. Depressive symptomatology and HIV-related worry were common amongst these women. Multivariate logistic regression analysis identified several factors that predicted these psychological outcomes. High depression scores were associated with women who were no longer in a relationship with their partner (odds ratio (OR) 5.72, confidence interval (CI) 2.18-14.97) and who used venting coping strategies (OR 2.15, CI 1.44-3.21). Higher levels of HIV-related worry were associated with women whose babies were HIV-infected (OR 3.51, CI 1.28-10.69), who had not disclosed their HIV status to others (OR 3.05, CI 1.29-7.24) and who reported that their HIV-infection was something about which their family would be ashamed (OR 3.44, CI 1.34-9.77). Based on the current findings, intervention strategies we propose are psychological interventions which address disclosure issues, feelings of shame and coping strategies as well as financial assistance for single mothers. Interventions that require few resources such as group counselling or support merit special consideration.
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PMID:Determinants of depression and HIV-related worry among HIV-positive women who have recently given birth, Bangkok, Thailand. 1045 86

Initial reports have suggested that approximately 10% of patients with HIV-infection develop HIV-associated nephropathy (HIVAN). It has also been predicted that by the end of the decade, HIVAN is likely to become a third leading cause of end-stage renal disease (ESRD) in African-Americans between the ages of 20-64 years. As the morbidity and mortality from HIV-infection has decreased in the last few years, it is possible that prevalence of HIVAN is also changing. We therefore screened HIV-1-infected patients followed in our hospital for HIVAN. A screening urinalysis was performed in 557 HIV-1-infected adult patients between March and May 1998. Of these, 252 were outpatients and 305 were Texas Department of Criminal Justice inmates (TDCJI). Demographic and laboratory data of these patients was obtained from the HIV patients' database. Fifty percent of the patients were African-American, 36.6% were Caucasian and 12. 7% were Hispanic. The mean age of patients was 37 +/- 8 years. Seventy-nine percent of the patients were males and a history of intravenous drug abuse (IVDA) was present in 28%. Twenty-three percent of the patients were concomitantly infected with hepatitis C virus, 4.1% were positive for hepatitis B surface antigen, and rapid plasma reagin test for syphilis was positive in 9.1%. In 38 patients who had more than 100 mg/dl (2+) proteins on screening urinalysis, total urinary proteins were quantitated by collecting 24 h urine specimens. Fifteen of these patients had urinary proteins more than 1.5 g/day (12 patients >3.5 g/24 h and 3 patients >1.5 g/24 h). A renal biopsy was done in 14 of these patients and clinical diagnosis of HIVAN was made in one patient who refused biopsy. Renal biopsies revealed HIVAN [9], diabetic nephropathy [2], membranoproliferative glomerulonephritis [2], Fibrillary glomerulonephritis [1]. All 10 patients (5 TDCJI and 5 outpatients) with HIVAN were African-American. Two of these 10 patients had a history of IVDA and another two were concomitantly infected with hepatitis C virus. The plasma viral load (Pvl) and total CD4 count was not different in patients with or without HIVAN [(Pvl log 10.05 +/- 1.39 vs. 9.9 +/- 2.18 copies/ml, p = 0.78) (CD4: 187 +/- 192 vs. 288 +/- 249 cells/microl, p = 1.17) mean +/- SD]. We conclude that in our HIV-infected population HIVAN exclusively affected African-Americans and the prevalence in them was 3.5%.
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PMID:Is the prevalence of HIV-associated nephropathy decreasing? 1059 59

The FUT2 gene encodes the enzyme alpha (1,2) fucosyltransferase, which determines expression of blood-group antigens on mucosal epithelial cell surfaces and in secretions. Homozygotes for a specific stop mutation in FUT2 (nonsecretors) cannot produce this enzyme and thus are unable to express blood group antigens. Nonsecretor status is associated with a decreased risk of several respiratory viral infections. By use of molecular genotyping, 2 populations of Senegalese women were examined for polymorphisms of the FUT2 gene. Among Senegalese commercial sex workers, absence of FUT2 (nonsecretor genotype) was associated with reduced risk of human immunodeficiency virus (HIV) type 1 infection (odds ratio [OR] adjusted for cervical and vaginal infection, 0.18; 95% confidence interval [CI], 0.04-0.90) and HIV-2 infection (adjusted OR, 0.43; 95% CI, 0.13-1.39), although the latter was not statistically significant. Modification of cell surface carbohydrates at mucosal surfaces determined by the FUT2 gene may underlie the protective association against heterosexual HIV infection.
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PMID:Secretor polymorphism and human immunodeficiency virus infection in Senegalese women. 1066 66

The natural history of human immunodeficiency virus type 1 (HIV-1) viremia and its association with clinical outcomes after seroconversion was characterized in a cohort of homosexual men. HIV-1 RNA was measured by reverse-transcription polymerase chain reaction (RT-PCR) in stored longitudinal plasma samples from 269 seroconverters. Subjects were generally antiretroviral drug naive for the first 3 years after seroconversion. The decline in CD4 lymphocyte counts was strongly associated with initial HIV RNA measurements. Both initial HIV RNA levels and slopes were associated with AIDS-free times. Median slopes were +0.18, +0.09, and -0.01 log10 copies/mL, respectively, for subjects developing AIDS <3, 3-7, and>7 years after seroconversion. In contrast, HIV RNA slopes in the 3 years preceding AIDS and HIV RNA levels at AIDS diagnosis showed little variation according to total AIDS-free time. HIV RNA load at the first HIV-seropositive visit ( approximately 3 months after seroconversion) was highly predictive of AIDS, and subsequent HIV RNA measurements showed even better prognostic discrimination.
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PMID:Natural history of human immunodeficiency virus type 1 viremia after seroconversion and proximal to AIDS in a large cohort of homosexual men. Multicenter AIDS Cohort Study. 1072 May 7

A study was conducted in the Infectious Diseases Hospital, Yangon, for one year from August 1996 to 1997, to assess the extent and the factors related to HIV transmission among sexual partners of HIV/AIDS cases. It was a cross-sectional comparative study on 67 (61 males, 6 females) HIV positive individuals with or without AIDS, and their sexual partners. Separate interviews of index cases and partners were done, and clinical examination and laboratory tests for HIV and sexually transmitted diseases (STDs) were performed. HIV transmission was found in 41.8% of the partners. Male-to-female transmission was 39.3% (n=61) and female to male transmission was 66.7% (n=6), Seven and one half percent of the partners were suffering from AIDS. There were 4 (6.6%) pregnant mothers and 1 (25%) was HIV positive. Though 75% of the partners did not use condoms during their married life, HIV transmission was significantly reduced in the condom users (odds ratio (OR) = 0.18, 95% confidence interval (CI) 0.02-0.98 p = < 0.05). The seropositive men who were less than 30 years of age had greater HIV transmission (OR = 5.67, 95% CI 1.13-36.46). However, socio-demographic factors, number of marital partners and age of first sex partners, duration of marriage, number of sexual relationships between these couples, duration of HIV positivity and AIDS infection, immunological status of the index group and STD positivity among partners had no significant association with the transmission of HIV. This study demonstrated that the transmission of HIV was high among the sexual partners of persons with HIV infection. It also highlighted the requirement of effective counseling and preventive measures against HIV infection among the couples.
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PMID:HIV transmission in sexual partners of persons with HIV/AIDS attending the Infectious Diseases Hospital, Yangon. 1077 88

We evaluated the predictive value of baseline HIV-1 genotypic resistance mutations for failure of a nucleoside reverse transcriptase inhibitor (NRTI) containing therapy. The change in therapy of 88 HIV-1-infected patients was analyzed retrospectively, relating the genotypic resistance profile at baseline to the evolution of viral load and CD4+ T cell counts. Genotypic resistance at baseline and at 6 months was evaluated with the LiPA HIV-1 RT, which detects mutations at codons 41, 69, 70, 74, 184, and 215. At 1 to 3 months after change in therapy, patients without preexisting resistance mutations to the new drug (group S) had a significantly better evolution in viral load (reduction of 0.37 log(10)) compared with patients with known preexisting resistance mutation(s) (group R) (increase of 0.08 log(10)). This difference was particularly striking for patients with the baseline M184V mutation and whose treatment was modified by the addition of lamivudine. After 6 months the median difference in viral load evolution between the two groups increased to 0.61 log(10): the viral load of patients of group S was still 0.18 log(10) below baseline while patients of group R had an increase of 0.43 log(10) in viral load above baseline. Changes in CD4+ T cell counts were not significantly different. The evolution in viral load in HIV-1-infected patients with and without baseline resistance mutation(s) toward a newly added NRTI is significantly different at 1-3 months and at 6 months after changing or adding one NRTI.
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PMID:Baseline HIV type 1 genotypic resistance to a newly added nucleoside analog is predictive of virologic failure of the new therapy. 1077 43

Clinical benefit of zidovudine alone in the treatment of HIV infection wanes after several years, with decreasing CD4+ cell numbers and increasing HIV RNA in plasma. To develop treatment strategies following prolonged zidovudine treatment, 92 subjects from the AIDS Clinical Trials Group (ACTG) 175 study after a median of 3.6 years of zidovudine monotherapy were randomized to treatment with stavudine or zidovudine and lamivudine. Evaluation of long-term changes, the average of 40- and 48-week HIV plasma RNA, demonstrated that lamivudine and zidovudine provided significantly greater virologic suppression compared with stavudine (mean decrease 0.70 versus 0.18 1og10 copies/ml,p = 0.003). Twenty-nine percent of zidovudine plus lamivudine recipients had HIV RNA levels below 500 copies per milliliter at 48 weeks as compared with 4% of stavudine recipients (p = 0.02). Both regimens significantly increased CD4+ cell numbers, the means of weeks 40 and 48 rose to 49 and 36 CD4+ cells per cubic millimeter among zidovudine plus lamivudine and stavudine recipients, respectively. Treatments were well tolerated and only 3 of 92 subjects died or developed AIDS within 48 weeks. In zidovudine-experienced subjects, addition of lamivudine resulted in significantly decreased plasma HIV RNA levels at 48 weeks compared with treatment with stavudine alone.
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PMID:Virologic and CD4+ cell responses to new nucleoside regimens: switching to stavudine or adding lamivudine after prolonged zidovudine treatment of human immunodeficiency virus infection. ACTG 302 Study Team. AIDS Clinical Trials Group. 1093 17

The purpose of the study was to evaluate the safety and long-term efficacy of an intensive chemotherapy regimen associated with G-CSF in HIV-associated non-Hodgkin's lymphoma (NHL). Fifty two consecutive patients with HIV infection, aggressive NHL and CD4+ cells > or = 100 x 10(6)/l were included. The median CD4 cell count was 276 x 10(6)/l. Nineteen tumors were of the Burkitt's type, 23 were large cells, 7 immunoblastic, and 3 anaplastic. Twenty-five patients had stage IV disease (bone marrow involvement in 7, and central nervous system in 9). Three cycles of ACVBP (doxorubicine, cyclophosphamide, vindesine, bleomycin, prednisolone) were given. A fourth cycle was delivered to patients in partial remission or with initial bulky disease. The induction was followed by three cycles of CVM (cyclophosphamide, etoposide, methotrexate). G-CSF 5 microg/kg was used at each cycle. Results showed that 37 patients (71%) achieved a complete remission. With a median follow-up of 74 months, 8 of them have relapsed. The median survival was 15 months and 34 patients have died (21 with NHL). The 4-year estimate survival was 33.9% (95% CI, 19.8%-47.4%). The Relative Dose-Intensity of the chemotherapy was 85% for doxorubicine and 87% for cyclophosphamide. In a multivariate analysis, homosexual men and patients with ECOG < 2 had a lower risk for death: RR = 0.32 (95% CI, 0.15-0.65) and RR = 0.36 (95% CI, 0.18-0.74), respectively. Achievement of complete remission was strongly associated with survival. In conclusion, it seems that in HIV-infected patients with NHL and a CD4 cell count above 100 x 10(6)/l, high complete remission rate and prolonged survival can be achieved with the intensive LNHIV-91 regimen.
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PMID:Intensive chemotherapy (LNHIV-91 regimen) and G-CSF for HIV associated non-Hodgkin's lymphoma. 1097 87


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