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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infection with HIV is a problem of growing magnitude among women and children in the United States. During 1991, AIDS will be among the five leading causes of death for women of childbearing age. Over 80% of children with HIV have acquired the infection vertically, and AIDS is now a leading cause of death of children in many urban areas of the United States. Gender and age have important influences on the progression of HIV disease and on the occurrence of complicating illnesses. Zidovudine can slow HIV disease progression, and several regimens of prophylaxis are effective against P. carinii pneumonia, which is the leading cause of death among adults and children with AIDS. Intravenous immunoglobulin may be effective for prevention of serious infections in some children with symptomatic HIV infection. Ultimately, prevention of HIV infection among women and children depends on targeted education and, possibly, the development of medical strategies for interruption of vertical transmission.
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PMID:Impact of human immunodeficiency virus infection on women and infants. 157 10

We have presented a case of HIV-associated thrombocytopenia successfully treated with low dose interferon alfa-2a. Increases in platelet levels were achieved within 1 week without hospitalization or surgery. Further, the patient had no systemic side effects from therapy. Zidovudine alone was ineffective in maintaining noncritical platelet counts. Interferon alfa-2a is a nonimmunosuppressive, nonsurgical therapy that can correct HIV-associated thrombocytopenia without requiring hospitalization.
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PMID:Correction of HIV-associated thrombocytopenia with low doses of interferon alfa. 158 12

3'-Azido-3'-deoxythymidine (AZT) is HIV-inhibitory in human macrophages, which is surprising in view of the low AZT phosphorylation reported in macrophage extracts. To elucidate the mechanism of AZT activation, we studied AZT anabolism as well as catabolism in human lymphocytes and macrophages, and compared it to that of thymidine. Thymidine kinase (TK)-specific activity in mitogen-stimulated lymphocytes was 15 times higher than in macrophages. However, the TK activity per cell was only 1.3 times higher, because of the large macrophage cell volume. Total cellular TK activity, but not specific activity, matched the level of intracellular AZT anabolism. The substrate specificity of TK in macrophages strongly suggests that mitochondrial TK2 was the enzyme phosphorylating thymidine and AZT in these cells, whereas it was cytosolic TK1 in stimulated lymphocytes. In vivo thymidine catabolism was extensive, forming thymine and dihydrothymine. In macrophages more than 95% of the added thymidine (0.5 microM) was degraded within 60 min. AZT, in contrast, was not catabolized, which explains the high AZT nucleotide accumulation, a process opposed only by AZTMP excretion. The lack of catabolism together with phosphorylation by TK2 clarifies how AZT can inhibit human immunodeficiency virus in macrophages. The fact that TK2 and not TK1 phosphorylates AZT in macrophages should have important implications for combination chemotherapy.
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PMID:Thymidine and 3'-azido-3'-deoxythymidine metabolism in human peripheral blood lymphocytes and monocyte-derived macrophages. A study of both anabolic and catabolic pathways. 159 39

In order to study the structure-activity relationships of dioxolane nucleosides as potential anti-HIV agents, various enantiomerically pure dioxolane-pyrimidine nucleosides have been synthesized and evaluated against HIV-1 in human peripheral blood mononuclear cells. The enantiomerically pure key intermediate 8 has been synthesized in nine steps from 1,6-anhydro-D-mannose (1), which was condensed with 5-substituted pyrimidines to obtain various dioxolane-pyrimidine nucleosides. Upon evaluation of these compounds, cytosine derivative 19 was found to exhibit the most potent anti-HIV agent although it is the most toxic. The order of anti-HIV potency was as follows: cytosine (beta-isomer) greater than thymine greater than cytosine (alpha-isomer) greater than 5-chlorouracil greater than 5-bromouracil greater than 5-fluorouracil derivatives. Uracil, 5-methylcytosine, and 5-iodouracil derivatives were found to be inactive. Interestingly, alpha-isomer 20 showed good anti-HIV activity without cytotoxicity. As expected, other alpha-isomers did not exhibit any significant antiviral activity. (-)-Dioxolane-T was 5-fold less effective against AZT-resistant virus than AZT-sensitive virus.
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PMID:Asymmetric synthesis of 1,3-dioxolane-pyrimidine nucleosides and their anti-HIV activity. 159 54

Several laboratories have shown that AZT-resistant variants of HIV-1 can be isolated from patients who have received prolonged therapy with this drug. Our laboratory has now been able to generate HIV-1 variants resistant to both AZT and ddI, in tissue culture, by using step-wise increases in the concentrations of each of these compounds over a 10-week period. This work has been performed by culturing wild-type clinical strains of HIV-1 as well as the HIV-3b laboratory strain of this virus under such conditions. The ID50 values obtained for the resistant viruses thus generated vary between 50-100 times above those of the parental wild-type strains in each case. Furthermore, we have identified several new mutation sites in the HIV-1 pol gene that are responsible for the observed resistance to AZT and ddI. We have not succeeded, however, in generating drug-resistant strains of HIV-1, under conditions in which several compounds or anti-viral agents were simultaneously present during the in vitro selection process. Combinations of drugs which failed to yield drug-resistant variants included AZT plus ddI, AZT plus alpha-interferon, and ddI plus alpha-interferon. These findings indicate that HIV drug resistance is less likely to occur in tissue culture when combinations of drugs are used, and provide rationale for the development of combination clinical trials for treatment of HIV-associated disease.
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PMID:Generation of nucleoside-resistant variants of HIV-1 by in vitro selection in the presence of AZT or DDI but no by combinations. 160 23

Duration of the AIDS-free period after HIV-infection and survival time vary to a wide extent. About 50 percent of the patients develop AIDS within 10 years. The most important prognostic factor is the CD4-lymphocyte count. The risk of AIDS increases significantly after CD4-lymphocyte counts drop below 400/microliters. Another prognostic factor is age. In older patients disease progresses more rapidly. AIDS often is preceded by an AIDS-Related-Complex characterized for example by Oral Candidiasis, Hairy Leukoplakia or Zoster of more than one dermatome. AIDS mostly develops 1/2 to 1 year after AIDS-Related-Complex. After AIDS is diagnosed the median survival time is not longer than 1 1/2 years. Single patients live much longer. Prognosis is influenced by the disease defining AIDS. Kaposi's Sarcoma often occurs early in the course of immunodeficiency and median survival is longer than after other opportunistic diseases. Survival also is longer after Pneumocystis Carinii Pneumonia since it is well treatable. A very short survival has been noticed after Non-Hodgkin-Lymphoma. During the last few years survival after HIV-infection and AIDS has been prolonged a little by sufficient prophylaxis of Pneumocystis Carinii Pneumonia which is the most frequent opportunistic disease, by antiretroviral treatment with Zidovudine and by increase of knowledge which makes early diagnosis and treatment of opportunistic diseases possible.
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PMID:[Survival in HIV infection and AIDS]. 162 24

The effect of AZT on serum HIV p24 antigen and endogenous serum alpha interferon levels was studied in AIDS and ARC patients. Following administration of AZT there was a rapid decline in the serum levels of both HIV p24 antigen and alpha interferon. When AZT treatment was interrupted, the levels of both HIV p24 antigen and of interferon rapidly increased. These findings suggest that HIV or some other AZT sensitive microorganism is the inducer of interferon which is characteristically found in the serum of AIDS and symptomatic HIV infected patients. They also suggest that the rapid decline in interferon levels may underlie some of the symptomatic benefit that follows administration of AZT.
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PMID:Modulation of alpha interferon levels by AZT treatment in HIV-seropositive patients. 162 38

Forty-seven HIV-seropositive children were investigated by EEG and evoked potentials (BAEP, SEP). Twenty-three children were symptomatic (P2), 8 seropositive without symptoms (P1), and 16 children were less than 15 months of age (P0). Some of them were investigated at different stages of HIV infection. During the neonatal period, 7 newborns of drug-addicted mothers had seizures and frequent spikes and sharp waves in their EEGs. Among (P2) children 6/23 showed background slowing and 1 had rhythmic theta activity (6 with and 1 without neurological symptoms). In BAEP, bilateral prolonged interpeak latencies (IPL) were found in 1 child with severe AIDS encephalopathy. Side differences greater than or equal to 0.4 ms in IPL were seen in 2 (P2), 1 without and 1 with neurological symptoms. A late onset was seen in 2 (P1) and 4 (P2) children. Median SEPs were normal in 24/26 patients; N20/N13 amplitude ratio was reduced in 2 (P1) patients. EEG and BAEP revealed nonspecific abnormal features in HIV encephalopathy. The the progression of the disease. However, also in the symptomatic group, normal results of EEG and BAEP dominated. SEP in the symptomatic group revealed only normal values. For monitoring the effectiveness of AZT treatment in HIV encephalopathy, EEG seems to be a relevant investigation; for evoked potentials more data and experience are needed.
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PMID:EEG and evoked potentials in HIV-infected children. 162 2

The Michigan Medicaid Program payment records generated in the period 1985-89 by 783 persons were analyzed for services related to human immunodeficiency virus (HIV) infection. Other data from death records and the Michigan AIDS Surveillance Registry were available for a subset of those persons. The average monthly payment in 1989 dollars for HIV-related services was $1,302.57. Services determined to be unrelated to HIV infection accounted for 12.5 percent of the total amount for health care received and another 2.5 percent was questionable. The average monthly expenditure for men was roughly twice that for women. The discrepancy did not exist among persons identified in the AIDS Surveillance Registry. Sex differences ceased to exist when Medicaid eligibility (disability versus Aid to Families with Dependent Children) was controlled for by analysis of variance. There were no significant differences between payments to those infected through male-to-male sexual contact and those infected through intravenous drug use. Payments for HIV treatments rose with age to about 40 years, and declined slightly among older adults. The sharpest rise was for those ages 19-25 years and 26-35 years. Large sex differences existed among those who received zidovudine (AZT), 61.4 percent of the men and 19.1 percent of the women. Controlling for Medicaid eligibility moderated those differences, but they remained statistically significant. Differences in zidovudine usage were not found between men and women in the subset identified in the AIDS Surveillance Registry nor among persons infected through male-to-male sexual contact and intravenous drug use.
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PMID:HIV infection treatment costs under Medicaid in Michigan. 164 44

Novel aryl phosphate derivatives of the anti-HIV nucleoside analogue AZT have been prepared by phosphorochloridate chemistry. These materials are designed to act as membrane-soluble pro-drugs of the bio-active free nucleotides. In vitro evaluation revealed the compounds to have a pronounced, selective antiviral activity, which, in one case, was more potent than the parent nucleoside AZT. The magnitude of the biological effect varied considerably with the nature of the phosphate-blocking group. Moreover, one of the compounds, a phosphoramidate, is particularly active in a cell line restrictive to the activity of AZT, due to poor phosphorylation therein. These data support the suggestion that the phosphate derivatives exert their biological effects via intracellular release of the nucleotide forms.
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PMID:Aryl phosphate derivatives of AZT retain activity against HIV1 in cell lines which are resistant to the action of AZT. 164 82


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